摘要:ObjectiveTo observe the effect of Buyang Huanwutang in treating diabetic peripheral neuropathy (DPN) by inhibiting pyroptosis through AMP-activated protein kinase (AMPK)/UNC-51-like kinase 1 (ULK1) mitophagy pathway.MethodSixty male SPF SD rats (6-7 weeks old) were used in animal experiments and numbered according to their body mass. They were then randomly divided into four groups by computer: normal group, model group, α-lipoic acid group(60 mg·kg-1), and Buyang Huanwutang group(15 g·kg-1), with 15 rats in each group. The diabetic model was established by injection of streptozocin (STZ). After successful modeling, the α-lipoic acid group and the Buyang Huanwutang group were given corresponding drugs, and the normal group and the model group were given normal saline. Sensory nerve conduction velocity (SNCV) and paw withdrawal threshold (PWT) were measured at the end of administration for 12 weeks. Immunohistochemistry and Western blot were used to detect the expression of phosphorylated AMP activated protein kinase (p-AMPK), phosphorylated UNC-51-like kinase 1 (p-ULK1), protein involved in microtubule-associated protein 1 light chain 3 (LC3), selective autophagy receptors (p62/SQSTM1), Beclin1, NOD receptor protein structure domain-related proteins 3 (NLRP3), Caspase-1 (Caspase-1), and interleukin-1 beta (IL-1β) in dorsal root ganglia (DRG). Immunofluorescence was used to detect the expression of the N-terminal gasdermin D (N-GSDMD).ResultCompared with those in the normal group, rats in the model group had increased fasting blood glucose (P<0.01) and significantly reduced SNCV, PWT (P<0.01), LC3Ⅱ/LC3Ⅰ, Beclin1, p-AMPK/AMPK, and p-ULK1/ULK1 (P<0.01). In addition, p62, NLRP3, N-GSDMD/GSDMD, IL-1β, and cleaved Caspase-1/Caspase-1 were significantly increased (P<0.01). Compared with those in the model group, SNCV and PWT were increased (P<0.01) in each administration group, and LC3Ⅱ/LC3Ⅰ, Beclin1, p-AMPK/AMPK, and p-ULK1/ULK1 were significantly increased (P<0.05, P<0.01). p62, N-GSDMD/GSDMD, cleaved Caspase-1/Caspase-1, NLRP3, and IL-1β decreased (P<0.05, P<0.01). Compared with the α-lipoic acid group, the Buyang Huanwutang group had significantly increased SNCV, PWT (P<0.05), LC3Ⅱ/LC3Ⅰ, and p-ULK1/ULK1 (P<0.05) and significantly decreased NLRP3 and N-GSDMD/GSDMD (P<0.05).ConclusionBuyang Huanwutang regulates mitophagy and inhibits pyroptosis through the AMPK/ULK1 pathway to prevent and treat DPN, and its therapeutic effect may be better than α-lipoic acid.
摘要:ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan (AMD) developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor (OX1R)/phosphatidylinositol-specific phospholipase Cβ-1 (PLCβ-1)/protein kinase Cα (PKCα)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway.MethodSixty SPF-grade SD rats were randomized into blank, model, suvorexant (30 mg·kg-1·d-1), and low-, medium-, and high-dose (4.55, 9.09, 18.09 g·kg-1·d-1, respectively) AMD groups, with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine (PCPA) and administrated with corresponding drugs by gavage, and the blank group received an equal volume of normal saline. The general condition, body mass, and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin(HE)staining and Masson staining. The expression of gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), epinephrine (EPI), norepinephrine (NE), and acetylcholine (ACh) in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate (Glu) expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1, Per2, Cry1, Cry2, Bmal1, and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR, respectively.ResultCompared with the blank group, the modeling decreased the body mass (P<0.05, P<0.01) and caused mania and disturbed resting rhythms (P<0.01), hepatic muscle fiber fracture, and edema with inflammatory cell infiltration. In addition, the modeling decreased the GABA, 5-HT, EPI, NE, and ACh content, increased Glu content (P<0.01), down-regulated the mRNA levels of Per1, Per2, Cry1, and Cry2 (P<0.01), up-regulated the mRNA levels of Bmal1 and Bmal2 (P<0.01), and promoted the expression of OX1R, PLCβ-1, PKCα, and ERK1/2 at both protein and mRNA levels (P<0.01). Compared with the model group, suvorexant and AMD increased the body mass (P<0.05, P<0.01), alleviated the mania, and increased the resting time and frequency (P<0.05, P<0.01). Moreover, the medications elevated the levels of GABA, 5-HT, EPI, NE, and ACh, lowered the Glu level, up-regulated the mRNA levels of Per1, Per2, Cry1, and Cry2 (P<0.05, P<0.01), down-regulated the mRNA levels of Bmal1 and Bmal2, and inhibited the expression of OX1R, PLCβ-1, PKCα, and ERK1/2 at both mRNA and protein levels (P<0.05, P<0.01).ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway, and high-dose AMD demonstrated the strongest effect.
摘要:ObjectiveTo investigate the molecular mechanism by which Si Junzitang in intervening in the development of hepatocellular carcinoma (HCC) by regulating the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of nuclear factor kappa-B (NF-κB) p65 in the paracancerous tissues.MethodThe orthotopic liver cancer mouse model was established. Twenty-four C57BL/6 mice were randomly divided into four groups: Normal group, model group, Si Junzitang low-dose group (10 g·kg-1), and Si Junzitang high-dose group (25 g·kg-1), with 6 mice in each group. The O-GlcNAcylation level and phosphorylation modification level of p65 in the paracancerous tissues were detected using Western blot. The O-GlcNAcylation of p65 was assessed using immunoprecipitation (IP). The mRNA expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) in the paracancerous tissues was detected using real-time quantitative polymerase chain reaction (Real-time PCR). The tumor number, liver weight, locomotor activity, grip strength, and Qi status of the mice were observed and analyzed.ResultCompared with the normal group, the model group showed a significant decrease in O-GlcNAcylation in the paracancerous tissues (P<0.01), a significant decrease in p65 O-GlcNAcylation (P<0.01), a significant increase in p65 phosphorylation (P<0.01), significantly elevated mRNA levels of cytokines IL-6, TNF-α, TGF-β1, VEGFA, MMP-2, and MMP-9 (P<0.01), significantly increased liver weight (P<0.01), significantly declined grip strength, number of grid crossings, and number of vertical stand-ups (P<0.01), and significantly dwindled Qi status (P<0.01). Compared with model group, the Si Junzitang low-dose and high-dose groups showed significantly increased levels of O-GlcNAcylation in the paracancerous tissues (P<0.05, P<0.01), significantly upregulated p65 O-GlcNAcylation levels (P<0.05, P<0.01), and significantly decreased p65 phosphorylation levels (P<0.01). In the Si Junzitang low-dose group, the mRNA levels of IL-6, TGF-β1, and VEGFA significantly decreased (P<0.05, P<0.01). In the Si Junzitang high-dose group, the mRNA levels of IL-6, TNF-α, TGF-β1, VEGFA, MMP-2, and MMP-9 significantly decreased (P<0.01), the number of tumors larger than 3 mm in diameter significantly decreased (P<0.01), and liver weight significantly decreased (P<0.05). Additionally, grip strength, number of grid crossings, and number of vertical stand-ups significantly increased (P<0.05, P<0.01), along with a significant increase in qi status (P<0.01).ConclusionSi Junzitang can inhibit the progression of orthotopic HCC in mice, which may be achieved by increasing the O-GlcNAcylation level in the paracancerous tissues, enhancing the O-GlcNAcylation of p65, inhibiting the phosphorylation modification of p65, and ultimately suppressing the expression of downstream IL-6, TNF-α, TGF-β1, VEGFA, MMP-2, and MMP-9.
摘要:ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling pathway.MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment, and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model, irbesartan (25 mg·kg-1), and high-, medium-, low-dose (33.8, 16.9, 8.45 g·kg-1) Zhenwutang groups (n=15) and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed, and the traditional Chinese medicine (TCM) syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency, fasting blood glucose (FBG), and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels, respectively, of Nrf2, HO-1, glutamate-cysteine ligase catalytic subunit (GCLC), and GPX4 in the renal tissue of mice in each group.ResultCompared with the blank group, the modeling increased the TCM syndrome score (P<0.05), elevated the estradiol (E2) and FBG levels (P<0.05), lowered the testosterone (T), triiodothyronine (T3), and tetraiodothyronine (T4) levels (P<0.05), and weakened the renal function (P<0.05). In addition, the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening, decreased the catalase (CAT) activity, total antioxidant capacity (T-AOC), and glutathione (GSH) content (P<0.05), increased the malondialdehyde (MDA) content (P<0.05), and down-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). Compared with the model group, high and medium doses of Zhenwutang decreased the TCM syndrome score and E2 content (P<0.05), increased the T, T3, and T4 content (P<0.05), improved the renal function (P<0.05), alleviated the pathological changes in the renal tissue, increased CAT, T-AOC, and GSH (P<0.05), reduced MDA (P<0.05), and up-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05).ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.
摘要:ObjectiveTo observe the effects of Danggui Buxuetang on the mitochondrial fission and apoptosis of podocytes in the rat model of diabetic kidney disease (DKD) and to explore the protective effect and mechanism of Danggui Buxuetang on DKD rats.MethodSD rats were randomized into a modeling group (n=65, fed with a high-sugar and high-fat diet) and a normal group (n=10, fed with a normal diet). After 6 weeks, the modeled rats were injected intraperitoneally with streptozotocin (STZ) for the modeling of type 2 diabetes mellitus (T2DM). Sixty T2DM rats were randomized into model, irbesartan (0.014 g·kg-1), and low-, medium-, and high-dose (0.36, 0.72, 1.44 g·kg-1, respectively) Danggui Buxuetang groups and administrated with corresponding drugs by gavage for 16 weeks. The levels of fasting blood glucose (FBG) and 24 h urinary protein (24 h UTP) were determined at the end of the 16th week. The pathological changes of the renal tissue were observed by hematoxylin-eosin and Masson staining. The mitochondrial ultrastructure of rat podocytes was observed by transmission electron microscopy. The level of reactive oxygen species (ROS) in the renal tissue of rats was measured by the fluorescent probe labeling of dihydroethidium (DHE). The apoptosis of renal cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The expression levels of Synaptopodin, Podocin, and cleaved caspase-3 in renal podocytes were detected by the immunohistochemical method (IHC). Western blot was employed to determine the protein levels of A-kinase anchoring protein 1 (AKAP1), phosphorylated dynamin-related protein 1 (p-Drp1), mitofusin-2 (Mfn2), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax).ResultCompared with the control group, the model group showed elevated levels of FBG and 24 h UTP, mesangial hyperplasia, basement membrane thickening, mitochondrial swelling, mitochondrial crista breakage and disorder, and increased ROS and TUNEL-positive cells. In addition, the model group showcased down-regulated expression of Synaptopodin and Podocin, increased expression of cleaved Caspase-3, up-regulated protein levels of AKAP1 and p-Drp1 , and down-regulated protein levels of Mfn2 and Bcl-2/Bax (P<0.01). Compared with the model group, high-dose Danggui Buxuetang lowered the levels of FBG and 24 h UTP, alleviated the pathological injuries of the renal tissue and the mitochondrial injury of podocytes, decreased ROS and TUNEL-positive cells, promoted the expression of Synaptopodin and Podocin, inhibited the expression of cleaved Caspase-3, down-regulated the protein levels of AKAP1 and p-Drp1, and up-regulated the protein levels of Mfn2 and Bcl-2/Bax (P<0.05, P<0.01).ConclusionDanggui Buxuetang may inhibit mitochondrial fission and apoptosis of podocytes and reduce urine protein by regulating the AKAP1/Drp1 pathway, thereby delaying the progression of DKD.
摘要:ObjectiveTo investigate the effect of icariin (ICA)-mediated vitamin D system on peripheral blood dendritic cells (DCs) and helper T cells 17 (Th17)/regulatory T cells (Treg) balance in myocardial remodeling model of Dahl salt-sensitive rats.MethodFifty SPF Dahl salt-sensitive rats were divided into model group, vitamin D group (3×10-5 mg·kg-1·d-1), and high-, medium-, and low-dose ICA groups (120, 60, 30 mg·kg-1·d-1), and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling, the normal group and the model group were given an equal volume of ultrapure water by gavage, and other groups were continuously administrated for six weeks. Cardiac echocardiography, hematoxylin-eosin (HE) staining, and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25(OH)D3, B-type N-terminal pro-brain natriuretic peptide (NT-ProBNP), interleukin (IL)-17, transforming growth factor (TGF)-β1, IL-12, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor (VDR),1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) in peripheral blood DCs of rats.ResultCompared with the control group, the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly, and the arrangement of myocardial fibers was disordered. The levels of serum 25(OH)D3 and IL-10 were significantly decreased, and the levels of serum IL-17, TGF-β1, IL-6, IL-12, and NT-ProBNP were significantly increased (P<0.05). The costimulatory molecules CD40, CD80, CD86, and MHC-Ⅱ were highly expressed in the peripheral blood DCs, and the expression of CD11 and CD11b was lower (P<0.05). The proportion of Th17 cells in the peripheral blood was significantly increased, and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased (P<0.05). The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased, and the mRNA and protein expressions of CYP27B1 and VDR decreased (P<0.05). Compared with the model group, the arrangement of myocardial fibers in each drug administration group was relatively regular, and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP, IL-17, TGF-β1, IL-6, and IL-12 and increase the level of serum 25(OH)D3 and IL-10 (P<0.05). The expression of costimulatory molecules CD40, CD80, CD86, and MHC-Ⅱ in the peripheral blood DCs of rats was decreased, and the expression of CD11 and CD11b molecules was increased (P<0.05). The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells (P<0.05). It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 (P<0.05).ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.
关键词:icariin;vitamin D;helper T cells (Th17)/regulatory T cells (Treg);dendritic cells;myocardial remodeling
SUN Qiyue, LI Shuran, GAO Shuangrong, GUO Shanshan, GENG Zihan, BAO Lei, ZHAO Ronghua, ZHANG Jingsheng, PANG Bo, XU Yingli, ZHANG Yu, CAO Shan, WANG Yaxin, CUI Xiaolan, HAN Bing, SUN Jing
摘要:ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment.MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK).ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats.ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.
关键词:Lutongning granules;trigeminal neuralgia;anti-inflammation;analgesia;improvement of nerve injury
摘要:ObjectiveTo investigate the effect of Yiqi Tongxin formula (YQTM) on liver inflammation in apolipoprotein E-∕- (ApoE-∕-) mice by regulating the nuclear transcription factor-κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway.MethodForty ApoE-∕- mice were randomly divided into a model group, an atorvastatin group (positive drug group), and low-, medium-, and high-dose YQTM groups (0.39, 0.78, 1.56 g·kg-1). Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks, oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin (HE) staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in mouse serum, as well as total cholesterol (TC) and triglyceride (TG) in the liver. Interleukin-1β (IL-1β) and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB, NF-κB inhibitory protein (IκB), IκB kinase β (IKKβ), phosphorylated NF-κB (p-NF-κB), phosphorylated IκB (p-IκB), phosphorylated IKK β (p-IKKβ), NLRP3, and Caspase-1 in the livers of mice.ResultCompared with the blank group, the model group showed severe aortic lipidosis, and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles(P<0.01). The serum levels of TG, TC, LDL-C, AST, and ALT were significantly elevated in the mice(P<0.01). TG and TC levels were elevated in the liver(P<0.01). The levels of IL-1β and IL-18 in liver tissue, as well as the protein expression levels of NF-κB, IκB, IKKβ, p-NF-κB, p-IκB, p-IKKβ, NLRP3, and Caspase-1 in the liver were significantly elevated(P<0.01). Compared with the model group, the aortic arch plaques of mice in each YQTM group were attenuated, and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated(P<0.05,P<0.01). The serum levels of TG, TC, LDL-C, AST, and ALT were significantly reduced(P<0.05,P<0.01). TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue, as well as protein expression levels of NF-κB, IκB, IKKβ, p-NF-κB, p-IκB, p-IKKβ, NLRP3, and Caspase-1 in the liver were significantly reduced(P<0.05,P<0.01).ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.
摘要:ObjectiveTo investigate the impact of icariin (ICA) on autophagy in glucocorticoid-induced bone microvascular endothelial cells (BMECs) mediated by the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.MethodBMECs were isolated and cultured from femoral heads obtained during total hip arthroplasty and identified using immunofluorescence staining. The experimental cells were divided into four groups: A control group, a glucocorticoid group (100 mg·L-1 hydrocortisone), an ICA group (100 mg·L-1 hydrocortisone+6.7×10-3 mg·L-1 ICA), and a Rapamycin group (100 mg·L-1 hydrocortisone+6.7×10-3 mg·L-1 ICA+1 mg·L-1 rapamycin). Autophagy in BMECs was induced using 100 mg·L-1 hydrocortisone. LC3 fluorescence staining was used to observe the peak of autophagy at different time points. Western blot analysis was employed to analyze the expression of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins in each group. Electron microscopy was used to observe autophagosomes and autolysosomes in the cells.ResultHydrocortisone at 100 mg·L-1 induced autophagy in BMECs, reaching a peak at around 5 hours, which then declined with further intervention. Compared to the control group, the glucocorticoid group showed cell membrane damage, disordered organelle arrangement, and a large number of autophagosomes and autolysosomes. Compared to the glucocorticoid group, the ICA group had more intact cell membranes, sparser organelle arrangement, and fewer autophagosomes and autolysosomes. Compared to the ICA group, the Rapamycin group showed cell membrane damage, disordered organelle arrangement, and more autophagosomes and autolysosomes. Compared to the control group, the glucocorticoid group had significantly increased expression of light chain 3B (LC3B), Atg4B, and p62 (P<0.01). Compared to the glucocorticoid group, the ICA group showed significantly decreased expression of LC3B, Atg4B, p62, and Beclin-1 (P<0.01). Compared to the ICA group, the Rapamycin group had significantly increased expression of Atg4B and p62 (P<0.01). Compared to the control group, the glucocorticoid group had significantly decreased expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR (P<0.01). Compared to the glucocorticoid group, the ICA group showed significantly increased expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR (P<0.01). Compared to the ICA group, the Rapamycin group had significantly decreased expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR (P<0.01). Ubiquitination levels were significantly decreased in the glucocorticoid group compared to the control group (P<0.01). Compared to the glucocorticoid group, ubiquitination levels were significantly increased in the ICA group (P<0.01), and significantly decreased in the Rapamycin group compared to the ICA group (P<0.01).ConclusionThe glucocorticoid-induced autophagy in BMECs is time-dependent. ICA inhibits glucocorticoid-induced autophagy in BMECs, and this effect may be related to the regulation of the PI3K/Akt/mTOR pathway.
关键词:icariin;steroid-osteonecrosis of the femoral head;bone microvascular endothelial cells;autophagy;phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway
摘要:ObjectiveTo observe the effects of Jianpi Bushen Huoxue prescription (JPBSHX) on rat brain microvascular endothelial cells (RBMECs) based on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway, aiming to provide a theoretical basis for the treatment of ischemic stroke.MethodTwelve 8-week-old male SPF-grade SD rats were selected. Eight of them were randomly chosen and given 3.25 g·mL-1 JPBSHX solution by gavage at a dose of 10 mL·kg-1 for 5 consecutive days to prepare the medicated serum, which was then preserved for later use. The remaining four rats were given the same volume of normal saline. Follow-up operations were the same as those of the above eight rats. Normal rat serum was collected and stored for later use. RBMECs were revived, cultured, passaged, and randomly divided into five groups: normal group (20% normal rat serum+80% high glucose DMEM), model group (hypoxia-reoxygenation injury) (20% normal rat serum+80% glucose-free DMEM), medicated serum group (20% JPBSHX-medicated serum+80% glucose-free DMEM), medicated serum+HIF-1α inhibitor group (20% JPBSHX-medicated serum+HIF-1α inhibitor 1 mg +80% glucose-free DMEM), and medicated serum+VEGF inhibitor group (20% JPBSHX-medicated serum +VEGF inhibitor 1 mg+80% glucose-free DMEM). The relative protein expression levels of Claudin-1 and Claudin-5 in RBMECs, the expression levels of HIF-1α and VEGF in RBMEC culture supernatants, the repair ability of RBMECs, and the number of nodes, microvessels, and their lengths after 72 h of culture were observed in each group.ResultAfter 24 h of reoxygenation, the scratch healing rate in the model group was significantly lower than in the normal group (P<0.01). Compared with the result in the model group, the scratch healing rates significantly improved in the medicated serum group, medicated serum+HIF-1α inhibitor group, and medicated serum+VEGF inhibitor group (P<0.05). However, the healing rates in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group were significantly lower than that in the medicated serum group (P<0.05). The number of nodes, microvessels, and total length of microvessels in the model group were significantly lower than those in the normal group (P<0.01). These indicators significantly improved in the medicated serum group, medicated serum+HIF-1α inhibitor group, and medicated serum+VEGF inhibitor group compared with those in the model group (P<0.05), but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group compared with those in medicated serum group (P<0.05). The relative expression levels of Claudin-1 and Claudin-5 proteins were significantly lower in the model group than in the normal group (P<0.01). These levels were significantly higher in medicated serum group, medicated serum+HIF-1α inhibitor group, and medicated serum+VEGF inhibitor group than those in the model group (P<0.05), but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group than those in the medicated serum group (P<0.05). The expression levels of HIF-1α and VEGF in the RBMEC culture supernatants were significantly lower in the model group than those in the normal group (P<0.01). These levels were significantly higher in the medicated serum group, medicated serum+HIF-1α inhibitor group, and medicated serum+VEGF inhibitor group than those in the model group (P<0.05), but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group than those in the medicated serum group (P<0.05).ConclusionJPBSHX can promote the proliferation, migration, and angiogenesis, such as tubule formation, of RBMECs damaged by hypoxia-reoxygenation injury, and this effect may be achieved through the regulation of the HIF-1α/VEGF signaling pathway.
摘要:ObjectiveTo explore the mechanism of Qidi Tangshen prescription (QDTS) in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy (DN).MethodUsing network pharmacology methods, we collected the chemical components and targets of QDTS, as well as the targets related to DN. Subsequently, we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model, QDTS (3.34 g·kg-1), and losartan capsules (10.29 mg·kg-1) groups, and db/m mice served as the normal group. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and the urinary albumin excretion rate (UAER) and renal pathological changes were measured and observed. The expression levels of protein kinase B1 (Akt1), hypoxia-inducible factor-1 alpha (HIF-1α), phosphorylated B-cell lymphoma-extra-large (p-Bcl-xl), as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein p62 (p62), and autophagy-related gene 6 homolog (Beclin1), were determined. Furthermore, mouse podocytes were divided into the normal glucose (5.5 mmol·L-1), high glucose (35 mmol·L-1), DMSO (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder) groups. After 48 h of intervention, the protein levels of Akt1, HIF-1α, p-Bcl-xl, LC3, p62, and Beclin1 in podocytes were measured.ResultQDTS had 34 active components acting on 143 targets in the treatment of DN, and 55 targets were related to autophagy, in which Akt1, HIF-1α, and Bcl-xl were the key targets. Compared with the normal group, mice in the model group exhibited significantly increased UAER, glomerular hypertrophy, deposition of blue collagen fibers, thickening of the glomerular basement membrane, and noticeable fusion of podocyte foot processes in some segments. Furthermore, the modeling up-regulated the protein levels of p-Akt1, HIF-1α, and p62 and down-regulating the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). Compared with the model group, QDTS and losartan decreased UAER (P<0.05) and alleviated the pathological damage in the renal tissue. Moreover, QDTS and losartan down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in the renal tissue (P<0.05). In comparison to the normal glucose group, the high glucose group displayed up-regulated protein levels of p-Akt1, HIF-1α, and p62 and down-regulated protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05). Compared with the high glucose group, QDTS down-regulated the protein levels of p-Akt1, HIF-1α, and p62 and up-regulated the protein levels of p-Bcl-xl, LC3, and Beclin1 in podocytes (P<0.05).ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway, thereby enhancing podocyte autophagy.
摘要:ObjectiveTo observe the clinical efficacy and safety of Tinglu Yixin prescription in the treatment of patients with heart failure with preserved ejection fraction (HFpEF) combined with diabetes (syndromes of Qi and Yin deficiency and water retention and blood stasis) from taste-based compatibility and descending adverse Qi with bitter and pungent medicinals.MethodA total of 108 HFpEF patients with diabetes (syndromes of Qi and Yin deficiency and water retention and blood stasis) treated in the Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from May 2022 to March 2023 were enrolled in this study and randomized into an observation group (54 patients) and a control group (54 patients). Both groups received conventional Western medicine treatment according to the guide recommendations for chronic heart failure and diabetes, and the observation group additionally received Tinglu Yixin prescription. The treatment course for both groups was 12 weeks. The New York Heart Association (NYHA) grading of cardiac function, left ventricular end diastolic diameter (LVEDD), left atrium diameter (LAD), the ratio of early diastolic maximum mitral flow velocity (E) to early diastolic mitral annular motion velocity (e') (E/e'), N-terminal pro-B-type natriuretic peptide (NT-proBNP), hemoglobin A1c (HbA1c), 6-minute walking test (6MWT), Minnesota Living with Heart Failure Questionnaire, traditional Chinese medicine (TCM) syndrome scores, and safety indicators were determined before and after treatment.ResultFinally, 104 patients were included for analysis, including 52 patients in the observation group and 52 patients in the control group. After treatment, 35 and 47 patients in the control and observation groups showed improved cardiac function, which indicated the total response rates of 67.3% and 90.4%, respectively. The total response rate regarding the cardiac function in the observation group was higher than that in the control group (χ2=2.754, P<0.05). The observation group outperformed the control group in reducing LVEDD and LAD (P<0.05), decreasing the E/e' ratio (P<0.05), lowering the NT-proBNP and HbA1c levels (P<0.05), and recovering the 6MWT and Minnesota quality of life score TCM syndrome scores (P<0.05). None of the safety indicators in the two groups showed abnormal values before and after treatment, and no serious adverse reaction was observed.ConclusionTinglu Yixin prescription can improve the heart function, exercise tolerance, and quality of life, lower the HbA1c level, and alleviate the TCM syndrome in the patients with HFpEF combined with diabetes (syndrome of qi and yin deficiency and water stagnation and blood stasis).
关键词:heart failure with preserved ejection fraction;type 2 diabetes mellitus;Qi and Yin deficiency, water stagnation and blood stasis;Tinglu Yixin decoction;clinical effect
摘要:ObjectiveTo observe the clinical efficacy and safety of modified Banxia Xiexintang in treating simple obesity in children with the syndrome of stomach hyperactivity and spleen stagnation.MethodA randomized, double-blind, placebo-controlled study was conducted, in which 78 children with simple obesity due to stomach hyperactivity and spleen stagnation were randomized into an observation group (39 cases) and a control group (39 cases). On the basis of diet and exercise intervention, the observation group received modified Banxia Xiexintang and the control group received placebo. The two groups were compared in terms of the therapeutic effect regarding TCM symptoms, body mass index (BMI), waist circumference, hip circumference, obesity, and visual analogue scale of appetite after 2 months of treatment, and the treatment safety was observed.ResultAfter treatment, the response rate in the observation group was 88.89% (32/36), which was higher than that (77.14%, 27/35) in the control group (Z=-2.301, P<0.05). After 2 months of treatment, the body weight, BMI, waist circumference, hip circumference, and obesity decreased in both groups (P<0.05,P<0.01). The TCM symptom scores and visual analogue scale scores of appetite in the observation group declined (P<0.05). The control group showed decreased scores of TCM symptoms except gluttony and overeating (P<0.05), declined scores of desire to eat, hunger, and willingness to eat declined (P<0.05), and no significant change in the score of fullness before and after treatment. Compared with the control group, the observation group showed decreased total score of TCM symptoms, scores of primary and secondary TCM symptoms, body weight, BMI, waist circumference, hip circumference, obesity, and scores of desire to eat, hunger, and willingness to eat (P<0.05) and no significant difference in the score of fullness after treatment. No adverse reaction related to the drug application was observed during the treatment period.ConclusionModified Banxia Xiexintang can reduce the body weight, BMI, waist circumference, hip circumference, and obesity, improve the body shape, alleviate the symptoms, and enhance the therapeutic effect and compliance of children with simple obesity, being safe in clinical application.
关键词:simple obesity in children;modified Banxia Xiexintang;syndrome of stomach hyperactivity and spleen stagnation;randomized controlled study
摘要:ObjectiveTo evaluate the clinical efficacy and safety of traditional Chinese medicine (TCM) suppository combined with Yishen Tongluo Qingkang decoction in the treatment of immune infertility.MethodA total of 116 patients meeting the inclusion criteria of this study were randomly divided into an observation group (58 cases) and a control group (58 cases). The observation group was treated with TCM suppository combined with Yishen Tongluo Qingkang decoction,and the control group was treated with prednisone acetate tablets. Both groups were treated for 12 weeks and followed up six months after treatment. Semen samples of the patients were collected before and after treatment,and the pregnancy status of their spouses,negative conversion rate of seminal plasma anti-sperm antibody (AsAb),sperm concentration,motility,percentage of forward motile sperm,sperm acrosin activity, and incidence of adverse reactions were compared between the two groups.ResultA total of 104 patients completed the study,including 53 cases in the observation group and 51 cases in the control group. Before treatment,the baseline data of the two groups were balanced. After treatment,the total effective rate of the observation group was 92.45%,which was higher than that of the control group (76.47%)(P<0.05),and the negative conversion rate of AsAb in the observation group was higher than that in the control group,but the difference was not statistically significant. After treatment,the sperm motility, percentage of forward motile sperm, and sperm acrosin activity increased in the two groups(P<0.05),and the sperm concentration in the observation group increased (P<0.05). There was no significant difference in sperm concentration in the control group. After treatment,the sperm concentration,motility,percentage of forward motile sperm, and acrosin activity in the observation group were better than those in the control group (P<0.05). During the trial,the incidence of adverse reactions in the observation group was lower than that in the control group (P<0.05).ConclusionTCM suppository combined with Yishen Tongluo Qingkang decoction can significantly increase the negative conversion rate of AsAb and improve the quality of semen in patients with immune infertility.
关键词:immune infertility;Yishen Tongluo Qingkang decoction;traditional Chinese medicine suppository;anti-sperm antibody;prednisone acetate
摘要:ObjectiveTo comprehensively evaluate the clinical value of Feilike mixture and provide a basis for the allocation of medical resources, rational drug use, and hospital procurement and supply of Chinese patent medicines.MethodWith the data from available studies and provided by drug manufacturers, the methods of evidence-based medicine, pharmacoeconomics, and health technology assessment were employed to construct a multi-criteria decision-making analysis framework from the "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine (TCM). The clinical evidence and value evaluation software of Chinese patent medicine, CSCv2.0, was used to comprehensively evaluate the clinical value of Feilike mixture.ResultBased on the existing clinical evidence, the following results were obtained. ① Safety: Multi-sources of evidence showed that Feilike mixture had little known risk and sufficient evidence, with the safety rated as grade A, which indicated good safety. ② Effectiveness: The systematic review and Meta-analysis showed that Feilike mixture combined with conventional Western medicine in the treatment of bronchitis shortened the time to disappearance of cough compared with conventional Western medicine alone, with the evidence rated as grade B by the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) system, which indicated high effectiveness. ③ Economy: From the perspective of health system, Feilike mixture combined with conventional Western medicine was more economical than conventional Western medicine alone, and the quality evaluation of pharmacoeconomics rated the economy as grade B. ④ Innovation: Feilike mixture combined with conventional Western medicine improved the clinical treatment effect and had innovation advantages compared with similar drugs. From the aspects of cultivation, identification of medicinal materials, and production, the sufficient supply and safety of medicinal materials can be ensured for Feilike mixture. This medicine was rated as grade B in terms of the medicinal material quality, preparation technology, and patents, which indicated good innovation. ⑤ Suitability: According to the results of the questionnaire survey, the usage of Feilike mixture was easy to be mastered and accepted by doctors and nurses, without special administration time, complex personalized treatment, and special technical and management requirements. It is convenient for patients to use, with convenient supply and storage, and weak influences of policy, publicity, and drug information. Therefore, the suitability of Feilike mixture was rated as grade B. ⑥ Accessibility: Among the similar Chinese patent medicines, Feilike mixture had a moderate price, high production capacity, wide sales coverage, wide coverage of hospitals, sustainable supply of medicinal materials, and low costs of treatment for acute bronchitis, with the accessibility rated as grade A. ⑦ TCM characteristics: Feilike mixture is composed of Scutellariae Radix, Peucedani Radix, Stemonae Radix, Gentianae Rhodanthae Herba, Scleromitrion diffusum, Firmiana platanifolia Radix, and Aster ageratoides, with reasonable compatibility. This formula is derived from the medical experience of Miao ethnic group, with rich experience in human use and the TCM characteristics rated as grade B. According to the evaluation results in the "6+1" dimensions, Feilike mixture was evaluated as class B, with a high clinical value.ConclusionAccording to the existing clinical evidence, compared with conventional Western medicine alone, Feilike mixture combined with conventional Western medicine demonstrates a high clinical value and prominent TCM characteristics in the treatment of acute bronchitis with phlegm-heat invading lung. It is suggested that it should be translated into the basic clinical drug management policy results according to the conditions.
摘要:The complex chemical composition and limited research ideas of traditional Chinese medicine (TCM) have led to the unclear material basis and mechanism of the medicinal effects, which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study, we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore, a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM, thus promoting the modern research and the innovative development of TCM.
关键词:structure-activity omics;Qizhi Weitong granules;anti-inflammatory and analgesic;structure;target
摘要:ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics.MethodOn the basis of the previous in vitro screening study, we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge, the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids, a study of structure-activity omics was carried out to summarize the rules of their connection.ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo, involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain, and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction (PPI) and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine, and the core targets were prostaglandin endoperoxide synthase 2 (PTGS2), glutamate receptor metabotropic 5 (GRM5), estrogen receptor 1 (ESR1), solute carrier family 6 member 4 (SLC6A4), and fusion oncoproteins (FOS). According to the differences of mother nucleus, the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories, including protoberberine, berberine, and aporphine, which had high binding affinities with PTGS2, GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine, appropriate substituents with hydroxyl, alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine, the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues, which greatly improves the binding affinity.ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma, and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.
关键词:Corydalis Rhizoma;alkaloid;structure-activity omics;molecular docking;anti-inflammatory and analgesic
摘要:ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics.MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and Search Tool for Recurring Instances of Neighbouring Genes (STRING). The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets.ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E2 (PGE2) in the mouse model, showcasing a significant inhibitory effect on the inflammatory pain caused by PGE2. Nine components and 39 targets of saikosaponins, as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out, and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction (PPI) analysis showed that the main active components of Bupleurum Radix were saikosaponins a, b1, b2, b3, c, d, e, f, and v, and the key targets were fms-related receptor tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and signal transducer and activator of transcription 3 (STAT3). Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks, including 6 docks with scores of 5-6 and 18 docks with scores above 6.ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo, providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.
关键词:anti-inflammatory and analgesic;saikosaponins;structure-activity omics;molecular docking;protein-protein interaction (PPI)
摘要:ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach.MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team, an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Online Mendelian Inheritance in Man (OMIM), and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges, the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets.ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium (DSS)-induced colitis in mice, which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β)(P<0.05). Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis, 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores, prostaglandin-endoperoxide synthase 2(PTGS2) and mitogen-activated protein kinase 3(MAPK3) were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets.ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.
关键词:Aurantii Fructus;flavonoid;anti-inflammatory and analgesic;structure-activity omics;molecular docking
摘要:ObjectiveTo analyze the correlation between 11 small molecule active components and 1 protein component of characteristic processed products with porcine cardiac blood and other products of Salviae Miltiorrhizae Radix et Rhizoma(SMRR) from Menghe medical school and anti-cerebral ischemic oxidative damage, and to identify its key component markers of characteristic processed products with porcine cardiac blood for anti-cerebral ischemic oxidative damage.MethodHigh performance liquid chromatography(HPLC) was established to simultaneously determine the contents of 11 active ingredients in SMRR and its processed products[processed with porcine cardiac blood, porcine blood, wine and transferrin(Tf) in porcine cardiac blood], and the content of Tf in different processed products of SMRR was detected by enzyme-linked immunosorbent assay(ELISA). Furthermore, A zebrafish ischemic stroke model was constructed to evaluate the effects of different processed products of SMRR on the behavioral trajectory of cerebral ischemic zebrafish, the neuronal damage of transgenic zebrafish Tg(elavl3:eGFP) brain, as well as the levels of malondialdehyde(MDA) and superoxide dismutase(SOD) in the brain tissues. The hippocampal neurons oxygen-glucose deprivation/reoxygenation(OGD/R)-induced ischemia-hypoxia model was constructed to evaluate the effects of different processed products of SMRR on oxidative damage of neuronal cells by taking lactate dehydrogenase(LDH), reactive oxygen species(ROS), MDA and SOD as indexes. Finally, principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and Spearman correlation analysis were used to analyze the 11 small molecule active components and 1 protein component with efficacy indicators, in order to screen the key components of the characteristic processed products with porcine cardiac blood for cerebral ischemic oxidative damage.ResultCompared with the raw products, the contents of water-soluble and fat-soluble components in processed products of SMRR increased to different degrees, while the content of salvianolic acid A decreased. Compared with the wine-processed products, the contents of salvianolic acid B, danshensu, rosmarinic acid and other components in the porcine cardiac blood-processed products, porcine blood-processed products, Tf-processed products were increased, while the content of salvianolic acid A was decreased. ELISA results showed that there was no significant difference in Tf content between the porcine cardiac blood-processed products, porcine blood-processed products, Tf-processed products. Pharmacological results showed that different processed products of SMRR could improve the behavioral deficits, brain neuronal injury and oxidative stress after ischemic stroke in zebrafish, and the effect of the porcine cardiac blood-processed products was most pronounced. PCA results showed that salvianolic acid B, salvianolic acid A, rosmarinic acid, lithospermic acid, danshensu, tanshinone ⅡA, caffeic acid, cryptotanshinone and tanshinone Ⅰ were the main contributing components of SMRR and its processed products. And the results of correlation analysis showed that the contents of cryptotanshinone, rosmarinic acid, caffeic acid, dihydrotanshinone Ⅰ, salvianolic acid B, tanshinone ⅡA and tanshinone Ⅰ were negatively correlated with MDA level in zebrafish brain tissue, while the contents of lithospermic acid, protocatechuic aldehyde, rosmarinic acid, dihydrotanshinone Ⅰ, salvianolic acid B and Tf were positively correlated with SOD level, and the contents of rosmarinic acid, caffeic acid, dihydrotanshinone Ⅰ, salvianolic acid B, tanshinone ⅡA, tanshinone Ⅰ, danshensu, Tf were positively correlated with neuronal fluorescence intensity in the zebrafish brain. And the contents of lithospermic acid, protocatechuic aldehyde, rosmarinic acid, dihydrotanshinone Ⅰ, salvianolic acid B, tanshinone ⅡA and Tf were negatively correlated with LDH, ROS and MDA levels and positively correlated with SOD level.ConclusionThere are differences in the anti-ischemic oxidative damage effects of SMRR and its different processed products, among which the porcine cardiac blood-processed products has the strongest effect on improving oxidative damage, which may be related to the content changes of salvianolic acid B, danshensu, rosmarinic acid and other components. This study can provide a basis for clarifying the quality markers of SMRR processed with porcine cardiac blood for cerebral ischemia and elucidating its processing mechanism.
关键词:characteristic processing of Menghe medical school;Salviae Miltiorrhizae Radix et Rhizoma processed with porcine cardiac blood;high performance liquid chromatography(HPLC);quantitative analysis;cerebral ischemia;oxidative damage;transferrin(Tf)
摘要:ObjectiveTo explore the potential mechanism of different processed products of Baiyaojian and its compound Xiangmei pills in rats with ulcerative colitis(UC) by comparing the pharmacodynamic and metabolomic differences.MethodEighty SD rats were acclimatized and kept for 3 d, and randomly divided into 8 groups[blank group, model group, mesalazine group(0.4 g·kg-1), Baiyaojian group(1.89 g·kg-1), stir-fried Baiyaojian group(1.89 g·kg-1), carbonized Baiyaojian group(1.89 g·kg-1), and Xiangmei pills low and high dose groups(1.89, 5.67 g·kg-1)], with 10 rats in each group. Rats in the blank group were administered physiological saline by gavage, and rats in the remaining 7 groups were orally administered 5% dextran sodium sulfate(DSS) solution daily for 8 consecutive days to induce UC model. After successful modeling, each dosing group was given the corresponding dose of drug solution by gavage, and the blank and model groups were given equal amounts of saline by gavage, and the drug was administered continuously for 8 d. Then serum levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-10 and IL-1β were measured by enzyme-linked immunosorbent assay(ELISA), hematoxylin-eosin(HE) staining was used to observe the histopathological changes of colon tissue, the proportion of T helper 17 cells(Th17) and regulatory T cells(Treg) in the peripheral blood of rats in each group was detected by flow cytometry. The endogenous metabolites in serum of rats were detected by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the differential metabolites were characterized by combining principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), and were analyzed according to the variable importance in the projection(VIP) value>1.0 and P<0.05, and potential metabolic pathways were analyzed according to Human Metabolome Database(HMDB).ResultCompared with the blank group, the colon tissue of the model group was congested and the mucosa was ulcerated, the colon length was significantly reduced(P<0.01) and the quality was significantly increased(P<0.05), the proportion of Th17/Treg in the peripheral blood and the serum levels of TNF-α, IL-6 and IL-1β were significantly increased, while the IL-10 expression wassignificantly reduced(P<0.05, P<0.01). Compared with the model group, the colon tissue of UC rats in each treatment group was improved with scattered ulcers, reduced inflammatory cell infiltration, significantly increased colon length, and significantly decreased mass(P<0.05), the proportion of Th17/Treg in the peripheral blood decreased, the expression of TNF-α,IL-6 and IL-1β was significantly reduced(P<0.05, P<0.01), while the IL-10 expression was significantly increased(P<0.01). The therapeutic effect of different administration groups on UC was in the order of high dose group of Xiangmei pills>low dose group of Xiangmei pills>carbonized Baiyaojian group>stir-fried Baiyaojian group>Baiyaojian group. And a total of 26 differential metabolites were screened in the metabolomics results. Compared with the blank group, 14 differential metabolites were up-regulated and 5 metabolites were down-regulated in the model group, and 14, 9, 14, 12 and 17 metabolites could be recalled in the Baiyaojian group, stir-fried Baiyaojian group, carbonized Baiyaojian group, Xiangmei pills low and high dose groups. The main metabolic pathways involved were citrate cycle pathway, pantothenic acid and coenzyme A biosynthesis pathway, aromatic hydrocarbon receptor(AhR) signaling pathway, glycolysis/gluconeogenesis pathway.ConclusionThe therapeutic effect of Baiyaojian on UC is significantly improved after charcoal stir-frying, and the efficacy is more prominent when combined with Angelicae Dahuricae Radix and Mume Fructus Carbonisata, which can provide a basis for the development of Baiyaojian compound preparations.
关键词:Baiyaojian(Chinese gall leaven);ulcerative colitis;serum metabolomics;flow cytometry;T helper 17 cells(Th17);regulatory T cells(Treg);inflammatory factors;ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS)
摘要:ObjectiveTo explore the improving effects and its synergistic mechanism of Olibanum before and after processing with vinegar on glycodesoxycholic acid(GDCA) intervention in mice with ulcerative colitis(UC) based on the perspective of intestinal flora.MethodC57BL/6J male mice were randomly divided into the normal group, model group, GDCA group, Olibanum group(1.5 g·kg-1) and vinegar-processed Olibanum(1.5 g·kg-1) group, with 6 mice in each group. Mice in the normal group drank water freely, and mice in the other groups were given 2% dextran sulfate sodium(DSS) periodically to establish a UC mouse model. During the modeling, GDCA group, Olibanum group and vinegar-processed Olibanum group were intervened by intraperitoneally injection of GDCA(0.05 g·kg-1). From the 13th day after modeling, Olibanum group and vinegar-processed Olibanum group were given the corresponding doses of drugs by gavage, once a day, for 36 d. During this period, the body mass of mice was recorded and the disease activity index(DAI) was assessed. On day 48, faeces were collected for 16S rRNA and metagenomic sequencing to analyse changes in intestinal flora. On the 49th day, hematoxylin-eosion(HE) staining was used to observe the colon histological lesions, enzyme-linked immunosorbent assay(ELISA) was used to determine serum levels of tumour necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6, and Spearman correlation analysis was used to explore the correlation between differential bacterial species and inflammatory factor levels.ResultCompared with the normal group, the model group showed a significant decrease in body weight(P<0.01), a significant increase in DAI(P<0.05), and a significant increase in TNF-α, IL-1β and IL-6 levels(P<0.01), and there was partial infiltration of inflammatory cells in the colon. Compared with the model group, mice in the GDCA group showed a significant decrease in body weight, a significant increase in DAI and levels of TNF-α, IL-1β and IL-6(P<0.01), and severe disruption of colonic crypt structure, extensive infiltration of inflammatory cells, and a significant decrease in goblet cells. Compared with the GDCA group, both the Olibanum and vinegar-processed Olibanum groups showed a significant recovery in body weight, a significant decrease in DAI and levels of TNF-α, IL-6 and IL-1β(P<0.05, P<0.01), and the modulating effect of vinegar-processed Olibanum was significantly better than that of Olibanum. Alpha diversity showed that Chao1 index of UC mice significantly increased(P<0.01) and Shannon index decreased significantly(P<0.05) in UC mice after GDCA intervention. Beta diversity showed that the microbial community structure of the 5 groups had significant changes, Olibanum and vinegar-processed Olibanum could modulate the changes in the structure of the intestinal flora in UC mice after GDCA intervention. Microbial sequencing results indicated that, compared with the normal group, the Firmicutes/Bacteroidetes ratio in the model group was significantly higher(P<0.05), and the relative abundance of 3 genera and 5 species of flora changed significantly(P<0.05, P<0.01). Compared with the model group, the Firmicutes/Bacteroidetes ratio in the GDCA group was significantly higher(P<0.05), the relative abundance of 7 pathogenic bacterial genera and four species was significantly increased(P<0.05, P<0.01), and the relative abundance of three beneficial bacterial genera and Bacteroides_intestinalis was significantly decreased(P<0.05, P<0.01). Olibanum group and vinegar-processed Olibanum group could modulate the Firmicutes/Bacteroidetes ratio, the relative abundance of pathogenic bacteria and beneficial bacteria, and the vinegar-processed Olibanum group was significantly superior to Olibanum group in terms of modulating the Firmicutes/Bacteroidetes ratio, the relative abundance of the three genera and five species of bacteria(P<0.01, P<0.05). Correlation analysis showed that the relative abundance of Bacteroides_intestinalis was negatively correlated with the levels of TNF-α, IL-6 and IL-1β, the relative abundance of Prevotella_sp_CAG873, Bacteroides_sp_CAG927, Bacteroidales_bacterium_52_46 and Bacteroidales_bacterium was positively correlated with TNF-α, IL-6 and IL-1β levels.ConclusionGDCA can exacerbate UC colonic inflammation, and Olibanum and vinegar-processed Olibanum have an ameliorative effect on GDCA-mediated UC, with the vinegar-processed Olibanum showing a stronger ameliorative effect, the mechanism may be related to the regulation the abundance and structure of intestinal beneficial and pathogenic bacteria, and the reduction of inflammatory factor levels.
关键词:Olibanum;processing with vinegar;ulcerative colitis;conjugated bile acids;glycodesoxycholic acid;intestinal flora;synergistic mechanism
摘要:ObjectiveRoot rot is one of the most serious diseases in the cultivation and production of Atractylodes lancea. Trichoderma spp. are effective in the biocontrol of root rot without causing environmental pollution. This study aims to isolate and study a Trichoderma strain capable preventing and controlling root rot from the rhizosphere of A. lancea and to solve the problem of disease prevention and control in the planting and production of A. lancea.MethodTrichoderma T2204 was isolated by the dilution-coating method and identified by ITS sequencing. The inhibitory activities of T2204 and its volatiles against two pathogenic fungal strains were examined by dual-culture and co-culture experiments. The biocontrol potential of T2204 on root rot of A. lancea and the effect of T2204 on the accumulation of medicinal compounds in the rhizosphere of A. lancea were investigated by pot experiments and GC-MS, respectively. In addition, the optimal medium, photoperiod, temperature, pH, and carbon and nitrogen sources for the culture of T2204 were explored.ResultThe Trichoderma isolate T2204 was identified as T. citrinoviride and had direct inhibitory effects on two highly pathogenic strains causing root rot. In the dual-culture experiments with the two pathogenic strains, T2204 showcased the inhibition rates of 77.90% and 76.80%, respectively. In the co-culture experiments with the two pathogenic strains, the volatile organic compounds produced by T2204 showed the inhibition rates of 57.11% and 81.11%, respectively. The pot experiments showed that the survival rate of A. lancea seedlings infected by root rot reached 100% after inoculation with T2204 and was only 50% in the case without inoculation of T2204. After 150 days of cultivation, the dry weight and atractylodin content of the rhizome of A. lancea plants treated with T2204 increased by 32% (P<0.05) and 11%, respectively, compared with the untreated group. The optimal conditions for the growth of T2204 were PDA or PSA medium, photoperiod of 12 h dark/12 h light, 25-30 °C, pH 5-6, carbon sources of glucose, D-fructose, soluble starch, and maltose, and the nitrogen sources of ammonium sulfate and ammonium dihydrogen phosphate. The optimal conditions for the sporulation of T2204 were PSA or CMA medium, photoperiod of 12 h dark/12 h light, 20-30 °C, pH 8, carbon source of sucrose, and nitrogen source of sodium nitrate.ConclusionT2204 could improve the growth and root rot resistance of A. lancea and promote the accumulation of medicinal compounds. The findings laid a foundation for the industrialized production and application of T2204 in the production of A. lancea in the future.
关键词:Atractylodes lancea;Trichoderma citrinoviride;root rot;biocontrol;growth-promoting effect;promotion of secondary metabolism
摘要:Hepatic ascites is one of the common and difficult complications in the decompensated stage of liver cirrhosis, and its incidence is increasing. In clinical practice, the prognosis of patients with hepatic ascites after surgery is worse, and the disease is recurrent. Traditional Chinese medicine (TCM) has certain advantages in treating hepatic ascites. However, there is no uniform standard for the preparation of animal models of hepatic ascites in accordance with TCM evidence. Therefore, this paper summarized the literature on animal models of hepatic ascites and analyzed the existing animal models of hepatic ascites based on the clinical diagnostic criteria of hepatic ascites in TCM and western medicine. The results show that the commonly used modeling methods for hepatic ascites mainly include the single-factor method, composite factor induction method, surgical method, and immunization method. Most of them are guided by western medicine theories, and their pathogenic mechanisms are mostly consistent with those of western medicine and are different from TCM evidence. Therefore, it is suggested that TCM intervening factors should be imposed in the process of model preparation, so as to prepare an animal model of hepatic ascites that meets the clinical evidence characteristics of TCM and western medicine.
摘要:The theory of "linkage between spleen and small intestine" has been put forward by doctors as early as the Ming dynasty. In traditional Chinese medicine, the spleen and small intestine cooperate and work together physiologically, and they are also closely related and interact with each other pathologically. The spleen governs transportation and transformation, which involves the function of the small intestine in transforming water and grain. The small intestine, governing the receiving and transformation of substances, depends on the normal transportation of the spleen. At the same time, it provides guarantee for the spleen to transform Qi and generate blood as well as ascend lucidity and descend turbidity. The dysfunction of spleen in transportation is closely related to the dysfunction of small intestine. The stability of intestinal microecology necessitates the normal functioning of the spleen. When the original balance of intestinal flora is disturbed, the spleen functioning will be affected. This study explored the pathogenesis and treatment of diabetes based on the physiological functions of the spleen and small intestine and the Western medicine targets of "nutrients-intestinal flora". According to modern medicine, nutrients are essential to maintain the normal physiological activities of the human body. Proper intake of nutrients can affect the absorption and metabolism of the human body for nutrients by regulating the composition and function of intestinal flora, so as to prevent the occurrence of diabetes. The imbalance of intestinal flora which harbors rich microorganisms may lead to the disturbance of energy metabolism and the dysfunction of the immune system, eventually leading to diabetes. As a metabolic disease, diabetes is closely related to the imbalance of intestinal flora and nutrient intake. Based on the theory of "linkage between spleen and small intestine", this paper discusses the relationship between spleen and small intestine. Furthermore, this paper discusses the correlation between "spleen-small intestine" and "nutrients-intestinal flora" by reviewing the latest progress in modern medicine and clinical research, aiming to provide a theoretical basis and new ideas for the clinical prevention and treatment of type 2 diabetes mellitus.
关键词:linkage between spleen and small intestine;nutrients;intestinal flora;type 2 diabetes mellitus;traditional Chinese medicine
摘要:Chronic bronchitis (CB) is a common respiratory system disease that is classified as a lung disease in traditional Chinese medicine (TCM) and is closely related to lung dysfunction. Lung Yang is the Yang Qi of the lungs,which drives the physiological activities within the lungs. It has physiological functions such as warming the lung system,regulating lung fluid,and dispersing the protective Yang. It can be distributed on the surface of the airway's Yin skin through sweat pores in the form of airflow and fluid,playing a protective and nourishing role. If the protective Yang fails to guard the Yin skin or if the lung fluid cannot nourish the Yin skin,the structural integrity of the airway's Yin skin may be compromised. This may weaken lung Yang's functions, such as clearing phlegm turbidity,dispersing lung fluid,and resisting external pathogens. Consequently, the retention of phlegm turbidity,insufficient nourishment of the Yin skin,and invasion by external pathogens all damage the lung Yang,burn the lung fluid,and exacerbate the pathological state of Yin skin unprotected,forming a vicious cycle that ultimately results in lung Yang asthenia and then the onset of CB. Based on the intrinsic connection between "Yin skin unprotected" and "lung Yang asthenia",this paper interprets the etiology and pathogenesis of CB. It proposes that "Yin skin unprotected" in the airway is the basic cause of CB and "lung Yang asthenia" caused by "Yin skin unprotected" is the core pathogenesis of CB. By integrating micro differentiation indicators with macro differentiation syndromes, the study explores its modern biological basis. Guided by the theory of "warming the lung Yang and protecting the Yin skin" and based on modern pharmacology research,this study further explores the scientific connotation of single TCM and compound formulations for treating TCM by warming the lung Yang and protecting the Yin skin. Furthermore, it proposes methods for dispelling pathogenic factors and protecting the Yin skin during the acute exacerbation phase,as well as nourishing and warming lung Yang during the remission phase,in order to provide new ideas for the early prevention and treatment of TCM.
关键词:chronic bronchitis;Yin skin unprotected;lung Yang asthenia;warm lung Yang;protect Yin skin
LIU Yingke, CUI Hong, YANG Jian, WANG Junhong, WU Liqun, JI Xiaohua, AN Bing, LIU Xiaomei, WAN Weilin, WANG Hong, ZHOU Gaojun, ZHANG Wen, QIU Liyi, GUO Kai, ZHANG Xiaoxiao
摘要:The traditional Chinese medicine (TCM) in pediatric care has a long history,proven efficacy,and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases,enhancing diagnostic and treatment levels,inheriting TCM knowledge,promoting the integration of TCM and Western medicine,and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not,excelling at what others have,being special in what others excel at,and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems,including respiratory,digestive,endocrine,psychological,and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon,such as upper respiratory tract infections,coughs,pneumonia,allergic rhinitis,bronchial asthma,atopic dermatitis,functional dyspepsia,functional constipation,enuresis,marginal short stature,simple obesity,attention deficit hyperactivity disorder,and tic disorders.The overall advantages were reflected in three aspects:First,the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases,making the treatment methodical and precise.Second,most traditional Chinese herbs are natural and have strong safety profiles.Third,TCM treatment methods are abundant,especially the external treatment methods,which are widely used in pediatrics,highly accepted by parents,and have definite efficacy,as well as good safety and compliance.
关键词:pediatric traditional Chinese Medicine;superior disease categories;traditional Chinese medicine treatment;expert guidelines and recommendations
摘要:Hepatocellular carcinoma (HCC) is a common tumor in the digestive tract, the formation mechanism of which remains to be fully elucidated. Although surgery, radiation, chemotherapy, targeted therapy, and immunotherapy have achieved significant results in the treatment of HCC, these methods are accompanied by a considerable number of adverse reactions and complications. In recent years, Chinese medicine has shown remarkable efficacy in the treatment of HCC, and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine, which exerts therapeutic effects via multiple components and multiple targets. However, the pathogenesis of HCC is exceptionally complex and not fully understood, which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Hedgehog, Wnt/β-catenin, nuclear factor-κB (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and transforming growth factor-β (TGF-β)/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis, inhibiting cell proliferation and migration, and blocking the cell cycle via the above pathways. However, the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets, new perspectives, and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.
摘要:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by incompletely reversible airflow limitation that progresses over time. Its recurrent and incurable nature imposes a significant health burden on patients. The pathogenesis of COPD is complex and has not been fully elucidated. Currently, Western medicine is commonly used in clinical treatment, which often yield suboptimal results and may lead to adverse reactions and drug resistance. Therefore, finding an effective and safe treatment method is a crucial focus in medical research. With the ongoing advancement in disease research, many scholars have discovered that traditional Chinese medicine (TCM) can target various signaling pathways such as nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), neurogenic locus notch homolog protein (Notch), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), transforming growth factor-β (TGF-β)/Smad, secreted glycoprotein (Wnt), Hippo, and nuclear factor erythroid 2-related factor 2 (Nrf2). By influencing these pathways, TCM can affect airway mucus secretion, inhibit inflammation and oxidative stress, alleviate airway and microvascular remodeling, and regulate apoptosis and autophagy, ultimately reducing disease symptoms and improving lung function. TCM has thousands of years of clinical practice experience in treating COPD, demonstrating significant efficacy. Therefore, delving deeply into this from a cellular and molecular perspective can provide a reliable theoretical basis for the clinical application of TCM in treating COPD. However, systematic summaries of how TCM regulates COPD-related signaling pathways are scarce. This article aimed to extensively review and summarize recent literature in China and abroad on interventions of TCM monomers or compound prescriptions in COPD, identifying multiple related pathways to provide new insights for future clinical formulation and experimental research. Integrating basic TCM theories with modern pharmacological research mechanisms can jointly propel the development of TCM in the prevention and treatment of COPD.
关键词:chronic obstructive pulmonary disease;signaling pathways;traditional Chinese medicine;research progress
摘要:Gegen Qinliantang is a representative prescription for dual releasing of exterior and interior and treating diarrhea with fever in the Treatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》). This prescription consists of Puerariae Lobatae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The combination of the four herbal medicines has the ability to clear both the exterior and the interior, thereby halting diarrhea and clearing heat. According to the idea of treating different diseases with the same method, Gegen Qinliantang is used in clinical practice to treat type 2 diabetes mellitus (T2DM), which demonstrates positive outcomes. T2DM is a chronic metabolic disease characterized by elevated blood glucose levels. The etiology and pathogenesis of T2DM are complex, mainly related to heredity, lifestyle, environment, diet and other factors. Clinical observations and experimental studies have shown that Gegen Qinliantang and its effective ingredients have significant effects of preventing and treating T2DM. Clinically, Gegen Qinliantang is often applied with modification, or in combination with Western drugs, demonstrating better therapeutic effects than Western drugs alone. Clinical practice has confirmed that Gegen Qinliantang can effectively alleviate the clinical symptoms, reduce the occurrence of complications, and alleviate gastrointestinal adverse reactions in T2DM patients. Experimental studies have demonstrated that Gegen Qinliantang can ameliorate insulin resistance and boost pancreatic function by regulating the insulin and inflammation signaling pathways, alleviating oxidative stress, and modulating gut microbiota to treat T2DM. Nevertheless, more thorough studies remain to be carried out to decipher the mechanism of Gegen Qinliantang in ameliorating insulin resistance in T2DM. To provide theoretical and data references for the subsequent in-depth research on the mechanism of Gegen Qinliantang in treating T2DM and the prevention and treatment of this disease, this article systematically reviews the clinical and experimental research progress of Gegen Qinliantang in ameliorating insulin resistance in T2DM.
摘要:Yuhuanglian is one of the representative processed products to change the medicinal properties of Coptidis Rhizoma, which was first published in Hanshi Yitong. Its processing method is to mix Evodiae Fructus juice with Coptidis Rhizoma with stir-frying for drying, that is, Coptidis Rhizoma processed with Evodiae Fructus juice can reduce the bitterness and cold properties on the basis of retaining the effect of purging fire and detoxification, so that Yuhuanglian is cold but not stagnant, which can clear dampness-heat in Qifen, and is effective in treating the liver-qi invading stomach, vomiting and swallowing acid. As a representative variety of processing with medicine juice, Yuhuanglian is included in the 2020 edition of Chinese Pharmacopoeia and local processing standards, and its processing technology research and optimization has been attracting much attention. Modern studies have shown that Yuhuanglian not only contains berberine, jatrorrhizine, palmatine and other components, but also contains evodiamine, rutaecarpine, limonin and other components from Evodiae Fructus, which have anti-inflammatory, antibacterial, anti-tumor and other pharmacological activities. This paper collated and summarized the related research reports of Yuhuanglian in the past 20 years from the perspectives of processing history, efficacy and medicinal properties, quality evaluation and clinical application, and found that the processing methods and standards of Yuhuanglian were quite different in different provinces and cities, mainly involving the preparation and dosage of Evodiae Fructus juice and the criteria for the processing end point. In addition, the changes in the major components of Yuhuanglian before and after processing varied greatly among different studies, presumably related to the different processes and quality standards, this paper summarized the processing history, technology, pharmacodynamics, quality evaluation and clinical application of Yuhuanglian, in order to provide reference for improving its quality evaluation system.
关键词:Yuhuanglian;neutralizing bias of drugs with opposite property drugs;processing specification;quality evaluation;efficacy and properties;clinical application;characteristic components
摘要:Bone is a dynamic tissue undergoing continuous regeneration and reconstruction, and its metabolic activities are mainly regulated by bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. In addition, a variety of cells such as adipocytes, inflammatory cells, endothelial cells, and nerve cells can affect bone metabolism by changing the bone marrow microenvironment. The incidence of bone metabolic diseases caused by bone metabolism disorders is increasing with aging of the population. At present, the clinical treatment of bone metabolic diseases has the disadvantages of long cycle, high cost and many side effects. Therefore, there is an urgent need for safe and effective prevention and treatment drugs. Corylin is an isoflavonoid extracted from Psoraleae Fructus, which has a variety of pharmacological effects such as anti-inflammatory, anti-oxidation, anti-tumor, anti-atherosclerosis, attenuating obesity and improving insulin resistance. Studies have shown that corylin not only exerts osteoprotective effects by promoting osteoblast differentiation and inhibiting osteoclast differentiation, but also plays a positive role in bone metabolism by regulating lipid metabolism, inflammatory response, angiogenesis and anti-aging. The current review overviews the effects and mechanisms of corylin on regulating bone metabolism directly or indirectly, hoping to open up a new perspective for the prevention and treatment of osteoporosis, fracture, osteoarthritis and other related diseases.
摘要:Attention deficit hyperactivity disorder (ADHD), also known as hyperactivity disorder in children, is a behavioral disorder commonly found in children, particularly preschool-aged children. This disorder can lead to cognitive impairment, learning difficulties, conduct disorders, and other mental health issues, severely impacting the quality of life for affected children. Moreover, the global prevalence of ADHD continues to rise. Establishing an animal model that closely aligns with clinical symptoms and the pathogenesis of the disease is crucial for advancing research on the prevention and treatment of ADHD. In recent years, research on animal models of ADHD has rapidly developed. Researchers have developed nearly 20 animal models from genetic and environmental perspectives. However, most of these models are still in the exploratory stage, and there is insufficient research to thoroughly investigate their pathogenesis, core characteristics, and drug effects. The spontaneously hypertensive rat (SHR) is currently the most commonly used animal model for ADHD because of its excellent face validity and developmental stage that better corresponds to childhood. In addition, dopamine transporter (DAT) knockout mice, LPHN3 knockout rats, and neonatal rat hypoxia models have also shown good face validity. Some researchers have injected SHRs with daily doses of levothyroxine sodium, which not only induces typical ADHD symptoms in the rats but also exhibits signs of Yin deficiency and Yang hyperactivity, which successfully simulates the Yin deficiency and Yang hyperactivity syndrome type of ADHD, providing a new approach for constructing and evaluating ADHD animal models that combine both traditional Chinese and western medicine. This article reviewed ADHD animal models reported in China and abroad over the past decade, summarized rodent models of ADHD into three major categories: genetic models, chemically induced models, and environmentally induced models, and analyzed each category to provide a reference for selecting and exploring appropriate models for experimental ADHD research.
摘要:Prostate cancer (PCa) is one of the most common malignant tumors in the male genitourinary system. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is a carcinogenic pathway responsible for the migration, proliferation, and drug resistance of various cancers. In recent years, as the research on the pathogenesis of PCa is deepening, the role of the PI3K/Akt signaling pathway in the development of PCa has attracted much attention. Traditional Chinese medicine, comprehensively regulating multiple components, targets, and pathways, has shown great potential in the treatment of PCa. This article reviews the research progress of traditional Chinese medicine targeting the PI3K/Akt signaling pathway in the treatment of PCa and discusses the expression of the PI3K/Akt signaling pathway in PCa, which involves inhibiting apoptosis of PCa cells, promoting the cell cycle, invasion, and migration of PCa cells, promoting tumor tissue angiogenesis, and mediating the androgen receptor. Additionally, it summarizes the single Chinese medicines that target and regulate this pathway, including Hedyotis diffusa, Taxus chinensis, Bovisc Alculus, and Atractylodis Macrocephalae Rhizoma. The active ingredients of these Chinese medicines mainly include flavonoids, alkaloids, terpenes, polyphenols, lignans, and other compounds. The Chinese medicine compound prescriptions targeting the PI3K/Akt pathway mainly include Wenshen Sanjie prescription, Jianspi Lishi Huayu prescription, Yishen Tonglongtang, Qilan prescription, Xihuangwan, and modified Shenqi Dihuangtang. This review is expected to provide a scientific basis for deeply understanding the pathogenesis of PCa and identifying potential therapeutic targets, as well as to provide new ideas for clinical research and drug development for PCa.
关键词:prostate cancer;phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt);signaling pathway;traditional Chinese medicine;research progress