摘要:ObjectiveTo observe the impact of Xiao Xianxiongtang on 5-fluorouracil (5-FU)-induced myocardial fibrosis and the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway in mice and explore its potential mechanism in suppressing 5-FU-induced cardiotoxicity.MethodOne hundred SPF-grade male ICR mice were randomly divided into normal control group, model group, and Xiao Xianxiongtang groups with low-, medium-, and high-doses (8.3, 16.6, and 33.2 g·kg-1), with 20 mice in each group. Except for the normal control group, all other groups were injected intraperitoneally with 5-FU (30 mg·kg-1) for seven consecutive days to establish a myocardial injury model. During the modeling process, the mice in the low-, medium-, and high-dose Xiao Xianxiongtang groups were administered the corresponding doses of Xiao Xianxiongtang by gavage. The normal control group and the model group were given equal volumes of normal saline for seven consecutive days. Left ventricular internal dimension at end-diastole (LVIDd), left ventricular internal dimension at end-systole (LVIDs), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) were measured by color Doppler echocardiography. Histopathological changes in myocardial tissues were observed through hematoxylin-eosin (HE) and Masson staining. The protein expression of alpha-smooth muscle actin (α-SMA) was detected by immunohistochemistry. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of HIF-1α and VEGF were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of HIF-1α, VEGF, collagen Ⅰ (ColⅠ), and collagen Ⅲ (Col Ⅲ) were detected by Western blot.ResultCompared with the normal control group, the model group exhibited significantly increased LVIDd and LVIDs (P<0.01), decreased LVEF and LVFS (P<0.01), and pathological changes such as obvious disarray of myocardial tissue, inflammatory cell infiltration, and interstitial fibrosis. The collagen volume fraction% (CVF%) was significantly increased (P<0.01). Additionally, there were significant elevations in the protein expression of α-SMA, ColⅠ, and Col Ⅲ (P<0.01), as well as increased levels of MDA (P<0.01) and decreased levels of SOD (P<0.01). Furthermore, the mRNA and protein expression levels of HIF-1α and VEGF were significantly upregulated (P<0.01). Compared with the results in the model group, the LVIDd and LVIDs were significantly reduced in the medium-dose and high-dose Xiao Xianxiongtang groups (P<0.05, P<0.01), while the LVEF and LVFS were significantly increased (P<0.05, P<0.01). In addition, the myocardial tissue damage, inflammatory cell infiltration, and myocardial fibrosis were significantly alleviated in all Xiao Xianxiongtang groups. The CVF% was significantly decreased in all Xiao Xianxiongtang dose groups (P<0.05, P<0.01). Furthermore, the protein expression of α-SMA, ColⅠ, and Col Ⅲ was significantly decreased in the medium-and high-dose Xiao Xianxiongtang groups (P<0.01). The MDA levels were significantly reduced (P<0.01), while the SOD levels were significantly elevated (P<0.01). Additionally, the mRNA and protein expression levels of HIF-1α and VEGF were significantly downregulated in these groups (P<0.05, P<0.01).ConclusionThe above results indicate that Xiao Xianxiongtang can attenuate 5-FU-induced oxidative stress injury in the myocardium of mice, inhibit myocardial fibrosis, improve cardiac function, and mitigate the cardiac toxicity of 5-FU. This effect may be related to its regulation of the HIF-1α/VEGF signaling pathway.
摘要:ObjectiveTo observe the effect of Danggui Buxuetang on the endoplasmic reticulum stress (ERS) of high glucose-stimulated mouse podocyte cells MPC5 via the protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcript factor 4 (ATF4)/CCAAT enhancer-binding protein homologous protein (CHOP) pathway and the expression B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved Caspase-3 and to elucidate the specific mechanism and targets of Danggui Buxuetang in regulating podocyte apoptosis by cell experiments.MethodAfter the preparation of drug-containing serum and screening of the optimal intervention concentration, the mouse podocyte cells MPC5 were classified into five groups: normal control (NG), high glucose (HG), blank serum control (KB, HG+10% blank serum), Danggui Buxuetang-containing serum (DBT, HG+10% drug-containing serum), and ERS inhibitor (4-PBA, HG+2.5 mmol·L-1 4-PBA). The podocytes in the NG and HG groups were cultured with the complete media containing 5.5 mmol·L-1 and 30 mmol·L-1 glucose, respectively. Each group was treated with the corresponding drug for 48 h, and then the cells were collected. The expression of glucose-regulated protein 78 (GRP78), p-PERK, ATF4, CHOP, podocin, and synaptopodin was detected by immunofluorescence. DNA damage was examined by the terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. The proteins of podocytes were extracted, and the protein levels of GRP78, PERK, p-PERK, eukaryotic initiation factor 2α (eIF2α), p-eIF2α, ATF4, CHOP, Bcl-2, Bax, and cleaved Caspase-3 were determined by Western blot.ResultCompared with the NG group, the HG group showed increased fluorescence intensities of GRP78, p-PERK, ATF4, and CHOP, weakened fluorescence intensities of podocin and synaptopodin, increased TUNEL-positive nuclei of podocytes, up-regulated protein levels of GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and cleaved Caspase-3, and down-regulated protein level of Bcl-2 (P<0.01). Compared with the HG group, the DBT and 4-PBA groups presented weakened fluorescence intensities of GRP78, p-PERK, ATF4, and CHOP, enhanced fluorescence intensities of podocin and synaptopodin, reduced TUNEL-positive nuclei of podocytes, reduced nucleus damage, down-regulated protein levels of GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and cleaved Caspase-3, and up-regulated protein level of Bcl-2 (P<0.01). There was no significant difference in the above results between the HG and KB groups.ConclusionThe Danggui Buxuetang-containing serum could inhibit the apoptosis of podocytes by antagonizing the activation of the PERK/ATF4/CHOP signaling pathway to protect podocytes.
摘要:ObjectiveTo observe the effect of Huangjingwan (CHP) on hippocampal autophagy in the mice model of learning and memory impairments induced by D-galactose combined with scopolamine and decipher the underlying mechanism.MethodNinety 8-week-old male Kunming mice were randomized into the normal, model, donepezil (0.65 mg·kg-1), and low-, medium-, and high-dose (1.25, 2.5, 7.5 g·kg-1, respectively) CHP groups. The mice in other groups except the normal group were subcutaneously injected with 0.14 g·kg-1 D-galactose once daily for the first 3 weeks and then intraperitoneally injected with 2 mg·kg-1 scopolamine once daily for the next 2 weeks to induce learning and memory impairments and simulating Alzheimer's disease (AD). One week after modeling, mice were administrated with corresponding drugs by gavage once daily for 4 consecutive weeks. The learning and memory abilities of mice in all groups were examined by Morris water maze, and the hippocampal neural structure was observed by Nissl staining. The mRNA levels of mammalian target of rapamycin (mTOR), Beclin-1, and p62 in the hippocampus of mice were determined by real-time fluorescence quantitative polymerase chain reaction. The protein levels of mTOR, Beclin-1, microtubule-associated protein light chain 3 Ⅱ (LC3Ⅱ), microtubule-associated protein light chain 3 Ⅰ (LC3Ⅰ), and p62 in the hippocampus of mice were measured by Western blot. The positive expression of Beclin-1 in the hippocampus of mice was detected by immunohistochemistry.ResultCompared with the normal group, the model group showed obvious dementia, poor learning and memory, disarrangement of hippocampal neural structure, and reduced number of neurons (P<0.01). In addition, the modeling down-regulated the mRNA and protein levels of mTOR and Beclin-1, decreased the protein ratio of LC3Ⅱ/LC3Ⅰ, and up-regulated the mRNA and protein levels of p62 (P<0.01). Compared with the model group, donepezil and CHP alleviated dementia, improved the learning and memory performance, mitigated the disarrangement of hippocampal neural structure, and increased the number of neurons (P<0.05, P<0.01). Furthermore, donepezil and CHP up-regulated the mRNA and protein levels of mTOR and Beclin-1, increased the protein ratio of LC3Ⅱ/LC3Ⅰ, and down-regulated the mRNA and protein levels of p62 (P<0.05, P<0.01).ConclusionCHP promotes hippocampal autophagy to treat AD by activating the mTOR signaling pathway.
关键词:Huangjingwan;Alzheimer's disease;learning and memory impairments;autophagy;mammalian target of rapamycin (mTOR) signaling pathway
摘要:ObjectiveTo evaluate the protective effect of Shengmaisan (SMS) on doxorubicin (DOX)-induced cardiotoxicity in rats and investigate the mechanism of SMS in regulating the mitochondrial function in cardiotoxic rats.MethodSixty SD rats were randomized into blank (normal saline), model (DOX), low-, medium-, and high-dose (1.81, 3.62, 7.24 g·kg-1) SMS, and dexrazoxane (25 mg·kg-1) groups. The rat model of cardiotoxicity was established by intraperitoneal injection of DOX at a dose of 2.5 mg·kg-1 for 6 consecutive times (a cumulative dose of 15 mg·kg-1). Drugs were administered concurrently during modeling, once a day for three weeks. The body weights of the rats were recorded at the time of each injection of DOX. Traditional Chinese medicine (TCM) syndrome score was assessed and the cardiac function was evaluated by echocardiography after the last administration. After rats were anesthetized, the heart tissue samples were collected. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and creatine kinase-MB (CK-MB) in the serum. The pathological changes and fibrosis in the myocardial tissue were examined by hematoxylin-eosin and Masson staining, respectively. Fluorescent staining was employed to determine the mitochondrial membrane potential. The mRNA and protein levels of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase 1 (PDK1) were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively.ResultCompared with the blank group, the DOX group showed reduced body weight (P<0.01) and appearance of dry hair and slow movement, which were manifested as an increase in the TCM syndrome score (P<0.01). The modeling decreased the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01), increased the left ventricular end-systolic diameter (LVIDs) (P<0.01), led to disarrangement of the myocardial tissue, aggravated cardiac fibrosis, elevated the serum levels of CK, LDH, AST, and CK-MB (P<0.01), reduced mitochondrial membrane potential, and up-regulated the mRNA and protein levels of HK2, PDK1, and LDHA in the myocardial tissue (P<0.05, P<0.01). Compared with the DOX group, high-dose SMS alleviated the DOX-induced weight loss and decreased the TCM syndrome score (P<0.05). The low-, medium-, and high-dose SMS increased LVEF and LVFS, reduced LVIDs (P<0.01), and improved the cardiac function. The medium- and high-dose SMS alleviated myocardial injury and myocardial fibrosis, lowered the levels of CK, LDH, AST, and CK-MB in the serum, and increased mitochondrial membrane potential (P<0.01). In addition, SMA recovered the DOX-induced aberrant mRNA and protein levels of HK2, LDHA, and PDK1 (P<0.05, P<0.01).ConclusionSMS may exert a protective effect against DOX-induced cardiotoxicity by regulating the mitochondrial function.
关键词:Shengmaisan;doxorubicin;cardiotoxicity;mitochondrial function
摘要:ObjectiveTo explore the mechanism of Xiaoyaosan in regulating apoptosis in the hippocampus of the mouse model of lipopolysaccharide (LPS)-induced depressive-like behavior.MethodAfter adaptive feeding, C57BL/6J mice were randomized into the following groups: control, model, minocycline (intraperitoneal injection, 50 mg·kg-1), fluoxetine (gavage, 2.6 mg·kg-1), and low-, medium-, and high-dose (gavage, 6.012 5, 12.025, and 24.050 g·kg-1, respectively) Xiaoyaosan. After 14 days of drug administration, 2 mg·kg-1 LPS was injected intraperitoneally for modeling. The sucrose preference test and tail suspension test were carried out to examine the depressive-like behavior in mice. High performance liquid chromatography was used to determine the content of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus. Enzyme-linked immunosorbent assay was employed to measure the serum levels of tumor necrosis factor (TNF)-α. Immunohistochemistry was employed to detect the positive expression of ionized calcium binding adaptor molecule 1 (Iba1). The mRNA levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), B-cell lymphoma-xl (Bcl-xl), and Caspase-3 were determined by Real-time PCR. The Wes system was used to determine the protein levels of Bax and Bcl-2 in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) was employed to observe the apoptosis of hippocampal neurons in mice.ResultCompared with the control group, the model group showed reduced sucrose consumption rate (P<0.01), elevated TNF-α level in the serum and up-regulated mRNA level of TNF-α in the hippocampus (P<0.01), lowered levels of 5-HT and DA in the hippocampus (P<0.05, P<0.01), increased expression of Iba-1 (P<0.05), up-regulated mRNA and protein levels of Bax, and down-regulated mRNA and protein levels of Bcl-2 (P<0.01). Compared with the model group, fluoxetine, minocycline, and medium-dose Xiaoyaosan increased the sucrose consumption rate and reduced the immobility time in the tail suspension test (P<0.05, P<0.01). Minocycline and Xiaoyaosan elevated the levels of 5-HT and DA in the hippocampus (P<0.05, P<0.01). In addition, the drug administration lowered the level of TNF-α in the serum, down-regulated the mRNA level of TNF-α, reduced the expression of Iba-1, down-regulated the mRNA and protein levels of Bax, and reduced neuronal apoptosis (P<0.05, P<0.01).ConclusionXiaoyaosan can ameliorate the LPS-induced depressive-like behavior of C57 mice by inhibiting neuroinflammation and reducing neuronal apoptosis in the hippocampus.
摘要:ObjectiveTo observe the effects of Bushen Zhuangjin decoction (BSZJ) on bone metabolism, bone mineral density (BMD), bone trabecular microstructure, and osteoprotegerin/receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B (OPG/RANKL/RANK) signaling pathway in ovariectomized rats and explore the action of mechanism of BSZJ against osteoporosis.MethodThirty-two female SD rats were randomly divided into a sham-operated group (SHAM), an ovariectomized group (OVX), an alendronate group (ALN, 7.35 g·kg-1), and a BSZJ group (3.2 g·kg-1). Corresponding drugs were given by gavage 12 weeks after ovarian removal, and the process lasted for 12 weeks. Serum and bone specimens were collected after 12 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum procollagen Ⅰ N-terminal propeptide (PINP) and C-telopeptide of type Ⅰ collagen (CTX-Ⅰ). Biomechanics of rat tibia was tested by a three-point bending test. BMD of lumbar vertebrae and bone trabecular microstructure were analyzed by micro-computed tomography (Micro-CT), including bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation/spacing (Tb.Sp), and structure model index (SMI). Hematoxylin-eosin (HE) and Masson staining were used to analyze trabecular and collagen changes in lumbar vertebrae. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA expression of OPG, RANKL, and RANK in lumbar vertebrae. Protein expression of OPG, RANKL, and RANK in lumbar vertebrae was determined by Western blot.ResultSerum PINP and CTX-Ⅰ were significantly increased in the OVX group compared with the SHAM group (P<0.05). Serum CTX-Ⅰ was significantly reduced in the ALN and BSZJ groups compared with the OVX group (P<0.05). Tibial fracture load was significantly lower in the OVX group compared with the SHAM group (P<0.05). Fracture Load was increased in the ALN and BSZJ groups compared with the OVX group. Compared with those in the SHAM group, BMD, BV/TV, Tb.Th, and Tb.N in lumbar vertebrae were significantly lower, and Tb.Sp and SMI were significantly higher in the OVX group (P<0.05). Compared with those in the OVX group, BMD, BV/TV, and Tb.N in lumbar vertebrae were significantly increased, and Tb.Sp and SMI were significantly decreased in the BSZJ group (P<0.05). Compared with that in the SHAM group, the structure of bone trabeculae in the OVX group was disorganized, and the distance between trabeculae was increased. Collagen fibers were thinned and had poor continuity. Compared with that in the OVX group, the trabecular structure of lumbar vertebrae was relatively intact in the BSZJ group, with smaller distances between the trabeculae and thick collagen fibers. Compared with that in the SHAM group, the mRNA and protein expression of OPG in lumbar vertebrae was significantly lower, and the mRNA and protein expression of RANKL and RANK was significantly higher in the OVX group (P<0.05). Compared with that in the OVX group, the mRNA and protein expression of OPG were significantly increased, and the mRNA and protein expression of RANKL and RANK were significantly decreased in the BSZJ group (P<0.05).ConclusionBSZJ can regulate bone metabolism and exert anti-osteoporosis effects in ovariectomized rats. The potential mechanism of action is related to the regulation of the OPG/RANKL/RANK signaling pathway.
关键词:osteoporosis;Bushen Zhuangjin decoction (BSZJ);ovariectomized rats;osteoprotegerin/receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B (OPG/RANKL/RANK) signaling pathway
摘要:ObjectiveTo explore the mechanism of Jisheng Shenqi pills in ameliorating chronic kidney disease (CKD) by observing the effects of this formula on the cyclic adenosine monophosphate (cAMP)/aquaporin 2 (AQP2)/NOD-like receptor protein 3 (NLRP3) signaling pathway and related inflammatory mediators in the rat model of CKD.MethodSixty SPF-grade male SD rats were randomized into a blank group (n=15) and a modeling group (n=45). The rat model of CKD was established by gavage with adenine for 28 days. The modeled rats were randomized into a model group and high-, medium-, and low-dose (1.2, 0.6, 0.3 g·kg-1·d-1, respectively) Jisheng Shenqi pills groups. Rats were administrated with corresponding drugs or pure water (blank group and model group) by gavage for 28 days. On days 14 and 28, the 24 h urine output was collected from rats for measurement of the 24 h urine protein. After the last administration, rats were anesthetized and samples were collected. The biochemical methods were employed to determine the serum levels of creatinine (SCr) and blood urea nitrogen (BUN) in rats. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of AQP2, arginine vasopressin (AVP), cAMP, and interleukin-1β (IL-1β) in the renal tissue. Western blot was employed to determine the expression levels of NLRP3 and AQP2 in the renal tissue. Hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff staining (PAS) were employed to observe the pathological changes in the renal tissue.ResultCompared with the blank group, the model group showcased decreased body weight and 24 h urine output, increased 24 h urine protein, kidney wet weight, and kidney-to-body weight ratio (P<0.01), elevated levels of SCr and BUN in the serum and IL-1β in the renal tissue (P<0.05, P<0.01), lowered levels of AVP, cAMP, and AQP2 in the renal tissue (P<0.01), up-regulated expression of NLRP3 (P<0.01), and down-regulated expression of AQP2 (P<0.01) in the renal tissue. In addition, the modeling led to severe pathological damage to the renal tissue. Compared with the model group, Jisheng Shenqi pills improved the mental status of rats, increased the body weight and 24 h urine output, decreased the 24 h urine protein, kidney wet weight, and kidney-to-body weight ratio (P<0.05, P<0.01), lowered the serum levels of SCr and BUN (P<0.05, P<0.01), elevated the levels of AVP, cAMP, and AQP2 in the renal tissue (P<0.01), down-regulated the expression levels of IL-1β and NLRP3 (P<0.05, P<0.01), and up-regulated the expression level of AQP2 (P<0.01) in the renal tissue. Moreover, Jisheng Shenqi pills alleviated the pathological injury in the renal tissue.ConclusionJisheng Shenqi pills may regulate the cAMP/AQP2/NLRP3 signaling pathway to reduce the release of inflammatory mediators, improve the kidney function, and alleviate the pathological injury, thus playing a role in the prevention and treatment of CKD.
摘要:ObjectiveTo investigate the molecular mechanism by which Shengyang Yiweitang inhibits podocyte injury and apoptosis in rats with membranous nephropathy based on Helper T cell (Th) 1/Th2 immune balance.MethodForty SD rats were used to establish a rat model of membranous nephropathy via tail vein injection of sheep anti-rat kidney brush border antibody (Fx1A) serum. Successfully modeled rats were divided into the following three groups: Low-dose Shengyang Yiweitang, high-dose Shengyang Yiweitang, and benazepril hydrochloride group, with 10 healthy rats being assigned to the normal control group. Each group received corresponding drugs via gavage once daily for six weeks. Before the end of the intervention, the Coomassie Brilliant Blue method was used to measure 24-hour urine protein content. After the intervention, blood was drawn from the abdominal aorta under anesthesia, and serum levels of creatinine (Crea), blood urea (UREA), and total cholesterol (TC) were measured using an automatic biochemical analyzer. Immunofluorescence staining was used to observe immunoglobulin G (IgG) and complement C3 deposition in kidney tissues. Immunohistochemistry (IHC) was performed to detect the expression levels of podocyte markers synaptopodin, nephrin, and podocalyxin in kidney tissues. Western blot was used to detect the expression levels of synaptopodin, nephrin, podocalyxin, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2-associated X protein (Bax), γ-interferon(IFN-γ), interleukin-4 (IL-4), T-cell-specific transcription factor (T-bet), and GATA binding protein 3 (GATA-3) in kidney tissues.ResultCompared with the normal control group, the model group showed significantly higher serum TC levels (P<0.05), significantly higher 24-hour urine protein levels (P<0.01), and significant deposition of C3 and IgG in kidney tissues. The semi-quantitative immunohistochemical expression of podocyte markers synaptopodin, nephrin, and podocalyxin was significantly lower (P<0.05). Western blot revealed significantly lower expression levels of synaptopodin, nephrin, and podocalyxin proteins (P<0.05), significantly higher expression levels of Bax and Bad proteins (P<0.05), and significantly lower expression levels of Bcl-2 protein (P<0.05). Additionally, IL-4 and GATA-3 protein levels were significantly higher (P<0.05), while IFN-γ and T-bet protein levels were significantly lower (P<0.05). Compared with the model group, the treatment groups showed significantly lower TC levels (P<0.05) and significantly lower 24-hour urine protein levels (P<0.01). The deposition of IgG and C3 was significantly reduced, and the semi-quantitative immunohistochemical expression of podocyte markers synaptopodin, nephrin, and podocalyxin was significantly increased (P<0.05). The expression levels of synaptopodin, nephrin, and podocalyxin proteins were significantly higher (P<0.05), while the expression levels of Bax and Bad proteins were significantly lower (P<0.05), and Bcl-2 protein expression was significantly higher (P<0.05). Moreover, IL-4 and GATA-3 protein levels were significantly lower (P<0.05), and IFN-γ and T-bet protein levels were significantly higher (P<0.05).ConclusionShengyang Yiweitang may alleviate podocyte injury and alleviate kidney injury in rats with membranous nephropathy by modulating the Th1/Th2 immune balance, thereby reducing podocyte apoptosis.
摘要:ObjectiveTo investigate the effect of the modified application of Sargassum and Glycyrrhizae Radix et Rhizoma combination that was two times the dose of the high limit in the Pharmacopoeia of the People's Republic of China 2020 in Haizao Yuhutang (HYT) on the goiter and tumor suppressor protein (p53), cell cycle-dependent protein kinase inhibitor (p21), and p53/p21/Caspase-3 signaling pathway.MethodA total of 128 Wistar rats were randomly divided into blank group, model group, euthyrox group (20 μg·kg-1), HYT group (12.06 g·kg-1), group without Sargassum (9.90 g·kg-1), group without Glycyrrhizae Radix et Rhizoma (10.26 g·kg-1), group without Sargassum and Glycyrrhizae Radix et Rhizoma (8.10 g·kg-1), and group with Sargassum and Glycyrrhizae Radix et Rhizoma (3.96 g·kg-1), with 16 rats in each group. All groups, except for the blank group, were given PTU to replicate the pathology model of goiter, with euthyrox as the positive drug, and the other groups were given the corresponding medicinal solution. The sample was collected 12 hours after the last administration. The morphology of the thyroid in each group was observed, and the thyroid coefficients of rats in each group were calculated. The levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were detected in the serum of the rats in each group. The pathological changes in the thyroid were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expressions of p53, p21, and p38 mitogen-activated protein kinase (p38 MAPK), Cyclin D1, and Caspase-3 in thyroid tissue. Western blot was used to detect the protein expression of p53, p21, and Caspase-3 in apoptosis-related signaling pathways in thyroid tissue.ResultCompared with the blank group, the thyroid coefficient of the model group was significantly higher (P<0.01), and the levels of T3, T4, FT3, and FT4 were all reduced (P<0.01). The level of TSH was increased (P<0.01), and the pathological morphology of thyroid tissue changed significantly (P<0.05). The mRNA expression of p53, p21, Cyclin D1, and Caspase-3 were all reduced (P<0.05). Compared with the model group, the thyroid coefficient of the whole prescription group was significantly reduced (P<0.01), and the levels of T3, T4, FT3, and FT4 all increased (P<0.05). The level of TSH decreased (P<0.01), and the pathological morphology of the thyroid tissue was significantly restored (P<0.05). The mRNA expression of p53, p21, Cyclin D1, and Caspase-3 increased (P<0.05), and the protein expression of p53, p21, and Caspase-3 increased (P<0.05).ConclusionUnder the condition of two times the dose of the high limit in the Pharmacopoeia of the People's Republic of China 2020, the modified application of Sargassum and Glycyrrhizae Radix et Rhizoma combination in HYT had obvious effects in improving thyroid coefficient, thyroid hormones, and thyroid tissue morphology of the model rats with goiter, and the mechanism of its action might be related to the elevation of the relevant expression of p53, p21, and Caspase-3, thus promoting the apoptosis.
关键词:Haizao Yuhutang;eighteen incompatibilities;model rats with goiter;apoptosis;p53;p21;Caspase-3
摘要:ObjectiveTo explore the mechanism of Culuan Heji in improving oxidative stress and apoptosis in rats with follicular maldevelopment (FM) by regulating the adenylate activated protein kinase/mammalian target protein of rapamycin/hypoxia-inducing-factor-1/vascular endothelial growth factor (AMPK/mTOR/HIF-1/VEGF) pathway.MethodA total of 48 female SD rats were randomly divided into a normal group (eight rats) and a modeling group (40 rats). The rats in the modeling group were given continuous instillation of tripterygium wirelli polyside suspension (75 mg·kg-1) for 30 days for modeling. After modeling, the rats were randomly divided into model group, clomiphene group (4.5 mg·kg-1), and low-, medium-, and high-dose groups of Culuan Heji (8.1, 16.2, 32.4 g·kg-1), with eight rats in each group. The groups were administered the corresponding drugs, and the normal group and the model group were injected with the same volume of sterilized water. The intervention lasted for 14 days. The changes in the estrous cycle of rats in each group were detected by Pap staining. Ovarian histopathology and follicle count were observed by hematoxylin-eosin (HE) staining. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined by enzyme-related immunosorbent assay (ELISA). The contents of reactive oxygen species (ROS) and superoxide dismutase (SOD) in ovarian tissue were detected by chemical fluorescence. The apoptosis rate of ovarian granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The expression of B-cell lymphoma-2 protein (Bcl-2) associated X protein (Bax) and Bcl-2 in ovarian tissue was detected by immunohistochemistry. Real-time fluorescence quantitative PCR (Real-time PCR) and Western blot were used to detect AMPK/mTOR/HIF-1/VEGF mRNA and protein expressions in ovarian tissue.ResultCompared with that in the normal group, the estrous cycle of rats in the model group was disturbed, and secondary and mature follicles were decreased. Atretic follicles were increased, and FSH and LH contents, ROS content, Bax expression, apoptosis rate of ovarian granulosa cells, and AMPK mRNA and protein expressions were significantly increased (P<0.01). E2 content, SOD content, Bcl-2 expression, mTOR, HIF-1, and VEGF mRNA and protein expressions were significantly decreased (P<0.01). Compared with those in the model group, secondary follicles and mature follicles increased in the clomiphene group and medium- and high-dose groups of Culuan Heji. Atretic follicles significantly decreased, and FSH and LH contents, ROS content, Bax expression, apoptosis, and AMPK mRNA and protein expressions decreased (P<0.05, P<0.01). E2 content, SOD content, Bcl-2 expression, mTOR, HIF-1, and VEGF mRNA and protein expressions were all increased (P<0.05, P<0.01).ConclusionCuluan Heji may inhibit oxidative stress by regulating the AMPK/mTOR/HIF-1/VEGF pathway to reduce granulosa cell apoptosis, promote normal follicle development and maturation, reduce follicle atresia, protect ovarian function, and thus play a therapeutic role in FM.
关键词:follicular maldevelopment;Culuan Heji;oxidative stress;apoptosis;adenylate activated protein kinase/mammalian target of rapamycin/hypoxia-inducible factor-1/vascular endothelial growth factor (AMPK/mTOR/HIF-1/VEGF) pathway
摘要:ObjectiveTo observe the clinical efficacy and safety of Qingke Pingchuan granules in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) due to phlegm-heat obstructing lung.MethodOne hundred patients with the syndrome of phlegm-heat obstructing lung during acute exacerbation of COPD were selected and assigned into a treatment group (50 cases) and a control group (50 cases) according to the random number table. The treatment group was treated with Qingke Pingchuan granules combined with conventional western medicine, and the control group was treated with conventional western medicine. The treatment course was 14 days in both groups, and the follow-up lasted for 1 month. Before and after the treatment, the traditional Chinese medicine (TCM) symptom score, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale core, 6-minute walk distance (6MWD), and C-reactive protein (CRP) level were determined. In addition, the TCM symptom score, CAT score, and mMRC score were recorded one month after treatment in the follow-up.ResultThe general information of the patients showed no significant difference between the two groups. The treatment group had higher comprehensive treatment efficacy than the control group, as demonstrated by the lower scores of cough, wheezing, shortness of breath, sputum volume, sputum color, sputum texture, irritability, tongue coating, and pulse manifestation and lower total TCM symptom score (P<0.05). The treatment group outperformed the control group in terms of the total CAT score and scores of symptoms, such as cough, expectoration, and chest tightness (P<0.05). The treatment group had lower mMRC scale score than the control group (P<0.05), and there was no significant difference in 6MWD or CRP level between the two groups. The follow-up results showed that compared with the control group, the treatment group showcased reductions in cough, wheezing, sputum volume, chest tightness, and total TCM symptom scores (P<0.05), total CAT score and the scores of cough, expectoration, and chest tightness (P<0.05), and mMRC scale score (P<0.05). During the treatment period, serious adverse reactions occurred in neither group, which indicated high safety.ConclusionQingke Pingchuan granules can mitigate the symptoms of cough, expectoration, and chest tightness and improve the quality of life of the patients with the syndrome of phlegm-heat obstructing lung during the acute exacerbation of COPD, with a long-lasting pharmacological effect and high safety, being worthy to be promoted in clinical practice.
关键词:acute exacerbation of chronic obstructive pulmonary disease;syndrome of phlegm-heat obstructing lung;Qingke Pingchuan granules;clinical efficacy;clinical randomized controlled trial
摘要:Latent wind is either congenital or acquired. The former is related to constitution, and the latter can be classified into internal wind and external wind. As a latent pathogen, latent wind has both the pathogenic characteristics of latent pathogen and the onset pattern of wind pathogen. The deficiency of healthy Qi is a necessary condition for the formation of latent wind. External pathogen, emotional and dietary disorders, and fatigue are the common causes for the onset of latent wind, and heat stagnation damaging Yin is the inevitable outcome. The internal accumulation of latent wind and the contraction with external pathogen lead to the abnormal movement of Qi and the disorder of triple energizer, affecting the metabolism of Qi, blood, and body fluid. The intertwining of wind, phlegm, fire, and stasis becomes a cause for the lingering of latent wind. We suggest that the treatment of latent wind should follow principle of reinforcing healthy Qi to consolidate the body and ventilating wind to expel pathogen. According to the different pathogenic factors, the methods of dispersing cold, clearing heat, detoxifying, moisturizing dryness, nourishing Yin, softening liver, invigorating spleen, and replenishing kidney can be adopted. According to the nature and attribute of latent wind and the different pathogenic factors associated with latent wind, the pathogeneses of latent wind can be summarized into three types: external pathogen invasion, triple energizer disorder, and healthy Qi deficiency. According to different pathogenic factors, external pathogen invasion can be divided into wind-cold attacking lung, wind-heat invading lung, intense wind-fire, wind-dryness damaging lung, and lung-heat damaging Yin. According to the different locations in Zang-fu organs, triple energizer disorder is divided into internal stirring of liver wind, disorder of upper energizer, internal accumulation of latent wind in spleen, dysfunction of middle energizer in transportation, internal accumulation of wind in kidney, and dysfunction of lower energizer in assisting. According to the natural endowment, healthy Qi deficiency is classified into the third category. Different formulas are used to treat the patients with different syndromes. Fully understanding the theory of latent wind helps to explain the combination of external and internal pathogens, repeated attacks, and lingering of pulmonary diseases. Elaborating on the pathogenesis, treatment principle, and syndrome differentiation of latent wind enlightens the clinical treatment of pulmonary diseases.
关键词:internal accumulation of latent wind;internal wind;external wind;ventilating wind to expel pathogen;pulmonary diseases
摘要:ObjectiveTo investigate the establishment and evaluation of a rat model of cough variant asthma (CVA, syndrome of latent wind damaging Yin).MethodSixty rats were randomized into Blank, CVA + latent wind damaging Yin, CVA, budesonide, and Sangmei Zhike granules, with 12 rats in each group. The rats in other groups except the blank group were sensitized by intraperitoneal injection of ovalbumin and aluminum hydroxide + atomization inhalation of ovalbumin and aluminum hydroxide. The rats in the groups of CVA + latent wind damaging Yin, budesonide, and Sangmei Zhike granules were then placed in a draught and administrated with thyroxine tablets (0.15 g·kg-1) by gavage to induce latent wind damaging Yin. Days 1-15 of the experiment constituted the modeling stage while days 16-29 served as the verification stage. On day 16, the rats in the budesonide group received atomization inhalation of the drug (0.5 g·L-1), and those in the Sangmei Zhike granules group were administrated with the granules (4.19 g·kg-1) by gavage once a day for 14 days. On days 1, 8, and 15, the body mass, water intake, anal temperature, and temperatures in the precordium and paw center were compared among the blank, CVA + latent wind damaging Yin, and CVA groups. On day 28, the body mass, water intake, anal temperature, and temperatures in the precordium and paw center were compared among five groups. On day 29, cough sensitivity was assessed based on the number of capsaicin (1 × 10-4 mol·L-1)-induced coughs within 2 min. On day 30, the pulmonary function indexes and the serum levels of inflammatory mediators [interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, and total immunoglobulin E (IgE)], cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) were determined. Hematoxylin-eosin staining was employed to observe the pathological damage in the lung. Real-time PCR was carried out to determine the relative expression levels of cAMP, IL-4, IL-5, and IL-13 in the lung tissue.ResultOn day 15, compared with the blank and CVA groups, the CVA + latent wind damaging Yin group showcased a decrease in body mass and increases in water intake, anal temperature, and temperatures of the precordium and paw center (P<0.05). On day 28, compared with the CVA + latent wind damaging Yin group, the budesonide and Sangmei Zhike granules groups presented reduced water intake and declined anal temperature and temperatures of precordium and paw center (P<0.05). Compared with the budesonide group, the Sangmei Zhike granules group had a reduction in temperatures of precordium and paw center of the left and right hindlimbs. There was statistical significance (P<0.05). Compared with blank group, the cough times within 2 min in CVA + latent wind damaging Yin and CVA groups increased (P<0.05). Compared with CVA + latent wind damaging Yin group, the Sangmei Zhike granules group showed decreased coughs (P<0.05). Compared with the blank group, the forced vital capacity (FVC) in the CVA + latent wind damaging Yin and CVA groups decreased (P<0.05). Compared with CVA + latent wind damaging Yin group, the FVC in the Sangmei Zhike granules group increased (P<0.05). Compared with the blank group, the CVA + latent wind damaging Yin and CVA groups presented elevated serum levels of total IgE, IL-4, and IL-13 (P<0.05), and the CVA + latent wind damaging Yin group showcased elevated cAMP level and lowered cGMP and IFN-γ levels (P<0.05). Compared with the CVA + latent wind damaging Yin group, the Sangmei Zhike granules group presented lowered IgE, IL-4, IL-13, and cAMP levels and elevated cGMP and IFN-γ levels (P<0.05). Compared with budesonide group, the Sangmei Zhike granules group showcased a reduction in IL-13 level (P<0.05). The lung tissue in CVA + latent wind damaging Yin and CVA groups was severely damaged, while budesonide and Sangmei Zhike granules alleviated bronchial mucosa damage, necrosis and exfoliation of airway epithelial cells, inflammatory cell infiltration, and gland hyperplasia. Compared with the blank group, CVA + latent wind damaging Yin group showed downregulated relative expression of IL-4 (P<0.05). Compared with CVA + latent wind damaging Yin group, the relative expression of IL-4 in budesonide and Sangmei Zhike granules group were upregulated (P<0.05).ConclusionThe CVA model prepared by intraperitoneal injection with ovalbumin and aluminum hydroxide + atomization inhalation with ovalbumin and aluminum hydroxide + wind blowing + gavage with thyroxine tablets presented the syndrome of latent wind damaging Yin.
关键词:cough variant asthma;latent wind damaging Yin;animal model;evaluation of syndromes by prescriptions;combination of disease and syndrome
摘要:ObjectiveA cross-sectional study was conducted to analyze the constitution distribution characteristics of patients with allergic asthma, aiming to provide a basis for the regulation of constitution and the treatment of allergic asthma.MethodThe patients with allergic asthma treated in the outpatient clinic from December 2021 to September 2023 were selected. The clinical data of the patients were collected by a questionnaire survey. The composite constitution distribution characteristics of the patients and the correlations of constitution with gender, age, body mass index (BMI), comorbid allergic diseases, history of allergy, family history, keeping pets, and fractional exhaled nitric oxide (FeNO) in the patients with special constitution were analyzed.ResultA total of 252 patients with allergic asthma were included in this study, with a male-to-female ratio of 1∶1.5, and the proportion of young people was the highest. The proportion of special constitution alone was the highest, and the proportions of other constitutions combined with special constitution followed the order of Yang deficiency, Qi deficiency, Qi depression, phlegm dampness, dampness heat, Yin deficiency, and blood stasis. There were 58 patients with special constitution combined with one other constitution, of which Yang deficiency accounted for the highest proportion. There were 38 patients with special constitution combined with two other constitutions, of which Qi deficiency + Yang deficiency was the most common. Among the patients, 116, 48, and 117 patients were overweight or obese, had a family history of allergic diseases, and had a history of allergy, respectively. Seventy patients kept pets, and there was a correlation between keeping pets and allergy to cat and dog hair (P<0.05). Other allergic diseases complicated with allergic asthma occurred in 202 patients, being dominated by allergic rhinitis, urticaria, and eczema. There were 177 patients with eosinophilic airway inflammation. The patients with allergic asthma mainly presented the syndromes of wind asthma (134, 53.17%), heat asthma (51, 20.24%), cold asthma (32, 12.7%), deficiency asthma (15, 5.95%), Qi depression asthma (14, 5.56%), and blood stasis asthma (6, 2.38%). The results of binary logistic regression suggested that women were more likely have Yang deficiency and Qi depression than men. Older patients were less likely to present phlegm dampness and dampness heat. BMI was positively correlated with phlegm dampness and negatively correlated with Yang deficiency (P<0.05).ConclusionThe patients with allergic asthma mainly present special constitution and wind asthma syndrome. The combination of special constitution and other constitutions (commonly Qi deficiency and Yang deficiency) leads to repeated attacks of allergic asthma. The incidence of allergic asthma is higher in women and young people, and women are more likely to have Yang-deficiency or Qi-deficiency constitution. Obesity may be a risk factor for allergic asthma. Obese people are more likely to have phlegm-dampness and dampness-heat constitutions. Pet contact and allergic rhinitis may lead to poor control of allergic asthma.
关键词:allergic asthma;characteristics of constitution;special constitution;composite constitution;clinical data
摘要:ObjectiveTo analyze the factors affecting the therapeutic effect on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the patients with the syndrome of phlegm-heat obstructing lung.MethodThe general information (gender, age, history of smoking and alcohol, and duration of COPD) of 100 AECOPD patients was collected. In addition, the data of laboratory test results, past medical history, modified Medical Research Council (mMRC) scale score, COPD assessment test (CAT) score, six-minute walk distance (6MWD), traditional Chinese medicine (TCM) symptom scores, whether or not taking traditional Chinese medicine, and the date of disease onset were collected. The independent samples t-test, χ2 test or univariate Logistic regression analysis was performed to analyze the data, and multivariate Logistic regression analysis was employed to determine the main factors affecting the therapeutic effect.ResultA total of 100 patients were enrolled in this study, including 47 patients in the significant remission group and 53 patients in the non-significant remission group. The two groups showed differences in age, body mass index (BMI), red blood cell count (RBC), haemoglobin, blood urea nitrogen (BUN), mMRC scale score, taking traditional Chinese medicine, and onset season (P<0.05). In addition, there were significant differences in terms of the domination in circuit by element Qi, dominant Qi, and join of subordinate Qi to dominant Qi between the two groups (P<0.05). The disease in the significant remission group mainly occurred in spring and summer. Multivariate Logistic regression showed that there were differences in the BMI, BUN, taking traditional Chinese medicine, and dominant Qi being lesser Yin and sovereign fire (relative to reverting Yin and wind-wood) between the two groups (P<0.05).ConclusionIncreasing the BMI, lowering the BUN level, and taking traditional Chinese medicine can improve the therapeutic effect, which is better when the dominant Qi is lesser Yin and sovereign fire relative to reverting Yin and wind-wood.
关键词:acute exacerbation of chronic obstructive pulmonary disease;syndrome of phlegm-heat obstructing lung;Qingke Pingchuan granules;retrospective study;five circuits and six Qi
摘要:ObjectiveTo evaluate the safety and effectiveness of Rujietai capsules in the treatment of breast hyperplasia (syndrome of liver depression and Qi stagnation and syndrome of phlegm coagulation and blood stasis) under the condition of widespread use, and to provide data support for guiding clinical drug use and completing re-registration.MethodA multicenter, open, single-arm clinical trial was conducted. A total of 2 406 patients with breast hyperplasia (syndrome of liver depression and Qi stagnation and syndrome of phlegm coagulation and blood stasis) treated in 38 experimental centers were included. They were treated by oral administration with Rujietai Capsules (4 capsules once, 3 times a day). The drug was generally taken on the fifth day of the menstrual cycle for 21 consecutive days, and 3 menstrual cycles were taken as a course of treatment. The safety was evaluated based on vital signs, physical and laboratory examinations, and adverse events before and after treatment. The changes of breast pain, breast lumps, and TCM symptoms were observed and recorded to evaluate the effectiveness of the drug.ResultAfter treatment for 3 menstrual cycles, Rujietai capsules reduced breast pain and tenderness in the patients with breast hyperplasia (syndrome of liver depression and Qi stagnation and syndrome of phlegm coagulation and blood stasis) and decreased the average maximum pain score by (2.20±1.63) points. After treatment for 3 menstrual cycles, the average relief rate of breast pain was 54.9%(1 275/2 322), and the average pain relief rate in the first 7 days of menstruation was 61.5%.(1 427/2 322) The average reduction rate in breast tenderness was 42.3%(1 005/2 374). Palpated breast lumps showcased a significantly reduced distribution range, with the disappearance rate of 19.5%(463/2 374) and the average reduction of 57.6%. In addition, Rujietai capsules alleviated TCM symptoms such as chest and hypochondriac distension or pain, irritability, insomnia, dreaminess, dysphoria, bitter mouth, abdominal pain during menstruation, and low menstrual volume. The total response rate in terms of TCM syndrome was 79.4%, and the clinical benefit was significant. No serious adverse reaction occurred during the trial.ConclusionRujietai capsules can alleviate the pain and TCM syndrome and improve the vital signs of the patients with breast hyperplasia, demonstrating definite effect and high safety in the context of wide application.
关键词:Rujietai Capsules;breast hyperplasia;multi-center;clinical trials;real world clinical study
摘要:ObjectiveTo investigate the clinical efficacy of Zhengqing Fengtongning tablets (Sinomenine, SIN) in treating active rheumatoid arthritis (RA) in the patients with the syndrome of wind-cold-dampness impediment and whether the regimen of Zhengqing Fengtongning tablets combined with methotrexate can be used in clinical practice.MethodA total of 159 RA patients were recruited from the rheumatology and immunology departments of 7 hospitals and randomized into three groups (n=53): SIN (3 tablets/time, 3 times/d), methotrexate tablets (MTX, 4 tablets/time, 1 time/week), SIN+MTX (3 tablets/time, 3 times/d + 4 tablets/time, 1 time/week). The clinical efficacy was evaluated at baseline and after 12 weeks of intervention, with the primary efficacy index being the proportion of patients achieving an American College of Rheumatology (ACR) 20 response after 12 weeks. The mitigation of clinical symptoms such as morning stiffness, joint tenderness, and swollen joint count was recorded, and immune inflammation indexes [erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and rheumatoid factor (RF)] were monitored. The disease activity was assessed based on the visual analogue scale (VAS) score and disease activity based on 28 joints (DAS28) score. The traditional Chinese medicine (TCM) symptom scores were recorded to assess the patients' quality of life.ResultAmong the 159 patients, 150 (94.3%) completed the 12-week treatment. The ACR20 response rates in the MTX and SIN group were 60.78% and 61.22%, respectively, which were lower than that (70%) in the SIN+MTX group. The treatment regimens in all the three groups reduced ESR, CRP, DAS28, and VAS, and the SIN+MTX group had lower VAS score than the SIN and MTX groups (P<0.05). Notably, the reductions in TCM symptom scores were more significant in the SIN group than in the MTX and SIN+MTX groups (P<0.05). The erythrocyte count and haemoglobin in the SIN group increased after treatment (P<0.05). During the treatment period, the incidence of adverse reactions was 6.0% in the MTX group, 2.04% in the SIN group, and 3.92% in the SIN+MTX group. The incidence in the MTX group was slightly higher and the combination of SIN+MTX did not increase the risk of adverse reactions.ConclusionZhengqing Fengtongning tablets can reduce the immune inflammation indexes and TCM symptom scores, slow down the disease progression, and improve the quality of life of RA patients. The results suggest that Zhengqing Fengtongning tablets can effectively inhibit the immune inflammation in RA patients, with the efficacy comparable to that of MTX. The combination of SIN+MTX may serve as a therapeutic option for the patients with active RA.
摘要:ObjectiveTo evaluate the clinical efficacy and decipher the potential mechanism of Yunpi Huazhuo prescription in regulating copper homeostasis of Wilson's disease (WD) and thus provide evidence for the clinical application of this prescription.MethodSixty patients with WD treated in the First Affiliated Hospital of Anhui University of Chinese Medicine from January to December in 2023 and meeting the inclusion criteria were enrolled in this study and assigned into an observation group (30 cases) and a control group (30 cases). The control group was treated with the routine therapy for copper excretion and liver protection, and the observation group with Yunpi Huazhuo prescription in addition to routine therapy. The treatment lasted for four courses (32 days). The serum levels of non-ceruloplasmin-bound copper, ceruloplasmin, copper, copper oxidase, and ratio of copper to zine, 24-hour urinary copper excretion, 24-hour urinary zinc excretion, ratio of 24-hour urinary copper excretion to zinc excretion, and traditional Chinese medicine (TCM) syndrome score were determined before and after treatment, and the response rate was calculated for both groups. Furthermore, network pharmacology and molecular docking were employed to construct the "disease-Yunpi Huazhuo prescription-active ingredients-core targets" network, which was visualized by PyMOL, on the basis of which the potential treatment mechanism of Yunpi Huazhuo Prescription was explored.Result① The treatment in both groups decreased the TCM syndrome scores (P<0.05), and the decrease in the observation group was larger than that in the control group (P<0.05). The total response rate in the observation group was 66.67% (20/30), which was higher than that (40.00%, 12/30) in the control group (χ2=4.286, P<0.05). The treatment in both groups elevated the 24-hour urinary copper excretion and lowered the serum levels of non-ceruloplasmin-bound copper and ratio of 24-hour urinary copper excretion to zine excretion (P<0.05), and the changes were larger in the observation group than in the control group (P<0.05). The serum levels of copper (P<0.01) and ceruloplasmin (P<0.05) declined in both groups after treatment, and the observation group had lower serum level of copper than the control group after treatment (P<0.05). There was no significant change in the serum level of copper oxidase, ratio of serum copper to zine or 24-hour urinary zinc excretion in the two groups after treatment. ②There were 83 active ingredients in Yunpi Huazhuo prescription, which shared 341 common targets with copper homeostasis in WD. The active ingredients included quercetin, isorhamnetin, and sitosterol and the core targets included protein kinase B1 (Akt1), tumor necrosis factor (TNF), and Caspase-3.The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses predicted nuclear factor kappa B signaling pathway, sirtuin signaling pathway, pathway in cancer, and lipid and atherosclerosis pathway were significantly enriched. Molecular docking results showed strong binding affinity between key active ingredients and core targets.ConclusionYunpi Huazhuo prescription could significantly reduce the TCM syndrome score and improve the clinical efficacy in treating for WD. It may regulate the copper homeostasis of WD by acting on multiple key targets and signaling pathways.
关键词:Wilson's disease;traditional Chinese medicine;Yunpi Huazhuo prescription;copper homeostasis;clinical efficacy;mechanism
摘要:ObjectiveThe rat models of depression established in three different ways were evaluated by comparing the depressive state, and the differences of metabolites in brain, liver and kidney tissues, in order to provide a reference for the preparation of animal models of depression and the standardized diagnosis, treatment and research of depression.MethodForty healthy male rats were randomly divided into blank group(K group), chronic unpredictable group(GY group), kidney deficiency depression group(SM group) and spleen deficiency depression group(PM group). K group was reared normally, GY group was modeled by chronic unpredictable mild stimulation(CUMS) in combination with solitary rearing, and SM group was modeled by CUMS combined with subcutaneous injection of hydrocortisone(25 mg·kg-1) and solitary rearing, group PM was modeled by CUMS combined with intraperitoneal injection of rifampicin (0.5 mg·kg-1), and the modeling period lasted for 4 weeks in all groups. Behavioral experiments were used to evaluate the degree of depression, the levels of 5-hydroxytryptamine(5-HT) and norepinephrine(NE) in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA). The metabolomics of brain, liver and kidney tissues of rats in each group were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), and principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed to screen the differential metabolites by variable importance in the projection(VIP) value>1, and pathway enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes(KEGG) database.ResultThe behavioral results showed that compared with the group K, the sugar water consumption rate of the three model groups was significantly decreased(P<0.01). In the forced swimming test, the rest time increased significantly and the climbing times decreased significantly(P<0.01). In the open field experiment, the movement distance decreased, the corner activity time and the rest time increased(P<0.05, P<0.01), the central area activity time of GY and SM groups was significantly decreased(P<0.01), but the central area activity time of PM group was significantly increased(P<0.05). In the social interaction test, the contact time with Stranger1 was significantly decreased(P<0.01), the contact times with Familiar and Stranger2 were significantly decreased(P<0.05, P<0.01). In the Morris water maze test, the escape latency increased significantly, while the escape platform retention time, platform quadrant entry times and platform crossing times decreased significantly(P<0.01). The levels of 5-HT and NE in serum were significantly decreased(P<0.05, P<0.01). The metabolomics results showed that the brain, liver and kidney tissues of rats in the three model groups were significantly separated from those of the K group, in which there was no intersection of the differential metabolites and pathways in the brain tissues of the three model groups, and the common metabolite in the brain tissues of rats in the GY group and the SM group was only O-ureido-L-serine, and there were 5 common differential metabolites in the GY and PM groups. There were 12 different metabolites common to the 3 groups in liver tissue, and the biosynthesis of steroid hormones was a common metabolic pathway, and kidney tissue had a total of 9 different metabolites common to all 3 groups, and the D-amino acid metabolic pathway was a common metabolic pathway.ConclusionAll 3 methods can construct a stable rat model of depression, in which the method of combined drug intervention can significantly reduce the cycle of model construction, and at the same time can construct a depression model in line with the characteristics of Chinese medicine evidence. And the metabolomics of brain, liver and kidney tissues of rats in the three depression models shows obvious differences, and there are opposite trends of liver and kidney differential metabolites in rats with kidney-deficiency and spleen-deficiency depression models, which can provide an experimental basis for the study of depression in traditional Chinese medicine.
关键词:depression;traditional Chinese medicine syndrome model;metabolomics;differential metabolites;model evaluation;hydrocortisone;reserpine;ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)
摘要:ObjectiveTo evaluate the tolerance of healthy subjects to Fuqi Gubengao, and to explore the pharmacokinetics of its major active components and the potential mechanisms in treating syndrome of deficiency of kidney Yang.MethodA Single-center, randomized, double-blind, continuous administration, placebo-controlled trial was designed. A total of 24 healthy subjects were enrolled in 2 dosage groups(75 g and 100 g), with each group consisting of 12 participants randomized in a ratio of 2∶1 to either the experimental and placebo groups, and each group was given the drug or the placebo at the dose for 14 d, the physical signs of subjects were recorded for safety assessment. Biological samples were collected at the specified time points according to the trial protocol. The concentrations of 6 aconite alkaloids(aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypacoitine) in the biological samples were determined using ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS), and pharmacokinetic parameters were calculated by non-compartment model. The relative contents of endogenous metabolites in plasma and urine samples were measured by UPLC-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed by EZinfo 3.0 software, differential metabolites were screened with variable importance in the projection(VIP) value>1 and P<0.05, and pathway enrichment analysis was conducted using MetaboAnalyst 6.0 platform.ResultIn the safety evaluation, no trend of significant increase in adverse events with increasing dose was observed. Pharmacokinetic results showed that the plasma concentrations of aconitine, mesaconitine and hypaconitine were mostly below the limit of quantification, and 71% of the plasma concentration of benzoylaconine was below the limit of quantification after the initial administration. The plasma concentration of benzoylmesaconine in the 75 g and 100 g groups reached steady state after 12 d of continuous administration, and compared with the first administration, the concentration and overall exposure in the body increased after the last administration, but there was no safety-related drug accumulation. Forty-five differential metabolites induced by Fuqi Gubengao were identified in the plasma samples, including 11 acylcarnitines, 10 fatty acids, 4 amino acids, and 20 lipids, enriched in pathways such as α-linolenic and linoleic acid metabolism, branched-chain fatty acid oxidation, phenylalanine and tyrosine metabolism, and fatty acid biosynthesis. Twenty-two differential metabolites were identified in the urine, mainly including 7 amino acids and their metabolites, 7 nucleic acids and their metabolites, 2 carnitines, and 6 others, enriched in pathways such as tryptophan metabolism, pantothenic acid and coenzyme A(CoA) biosynthesis, β-alanine metabolism, and sphingolipid metabolism.ConclusionFuqi Gubengao shows good clinical safety and tolerability at the tested doses, its mechanism in treating kidney Yang deficiency may be related to enhancing adrenal function, promoting fat breakdown and oxidation, and enhancing energy metabolism in the body.
摘要:ObjectiveTo analyze the differences in volatile components and odors of Inulae Flos from different regions, providing reference for improving the quality evaluation method of this herb.MethodA total of 20 batches of Inulae Flos samples were collected from four production areas of Dezhou(Shandong), Pingyi(Shandong), Anyang(Henan) and Hebei, and the odor information of each sample was identified by PEN electronic nose, and principal component analysis(PCA) and analysis of variance with multiple comparisons were used to identify the differences in odors of the samples among different regions. Headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to identify and quantify the volatile components of samples from different regions, and PCA and partial least squares-discriminant analysis(PLS-DA) were employed to analyze the differences in volatile components of the samples among different regions. According to the principle of variable importance in the projection(VIP) value>1 and P<0.05, the volatile differential components of Inulae Flos from different regions were screened. After that, PCA correlation analysis and Person correlation analysis were applied to explore the correlation between volatile differential compounds and electronic nose sensors with their origin, as well as the correlation between electronic nose sensors and volatile differential compounds.ResultThe difference in odor is mainly reflected in W1W, W2W and W5S sensors, and the PCA results of electronic nose data indicated that they could be better differentiated the samples of Inulae Flos from Hebei. A total of 48 volatile components were detected by HS-GC-MS, mainly including aldehydes, olefins, carboxylic acids, aromatics and alcohols. Meanwhile, the results of PCA and PLS-DA showed that there were significant differences among different regions, and 19 differential compounds were screened out, among which the relative content of n-hexanal was the highest. The correlation analysis between volatile differential compounds and production areas obtained 15 characteristic components for distinguishing production areas. The correlation analysis between electronic nose sensors and production areas showed that W1W had the strongest correlation with Hebei, which could be used as a significant indicator for distinguishing Hebei from other production areas. W2W and W5S had a strong correlation with Dezhou and Anyang. Person correlation analysis between W1W, W2W and W5S sensors and differential compounds indicated that the material basis for odor generation was furfural, 2-pentylfuran, hexanal, linalool, and 3-methyl-1-glutaraldehyde, which were could be used as the main odorants to distinguish different production areas.ConclusionThis study is able to better differentiate the different regions of Inulae Flos by HS-GC-MS and electronic nose technology, the screened 15 volatile differential compounds and 5 odorants can provide a reference for interpretation of odor characteristics and quality evaluation research of Inulae Flos.
关键词:Inulae Flos;volatile components;electronic nose;headspace gas chromatography-mass spectrometry(HS-GC-MS);producing area;odor material basis;quality evaluation
摘要:ObjectiveTo establish a method for the determination of 14 components in Liuwei Dihuangwan and set up a scoring system to evaluate the samples from different manufacturers.MethodUltra performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was established for the quantification of 14 components(allantoin, gallic acid, rehmannioside D and so on) in 109 batches of Liuwei Dihuangwan from 12 manufacturers and 4 dosage forms. At the same time, morroniside, loganin and paeonol were quantified according to the methods under the content detection item of Liuwei Dihuangwan in the 2020 edition of Chinese Pharmacopoeia, and the content distributions were investigated on the basis of different dosage forms and manufacturers. Each component(except 5-hydroxymethylfurfural) was assigned a value according to the ranking of its content, the attribution and monarch, minister, assistant and guide of the medicinal flavors. The samples from each manufacturer were evaluated by the system established above.ResultThe established method for the determination of 14 components in Liuwei Dihuangwan showed good linear relationship within their concentration ranges, good specificity, repeatability, durability and accuracy. The evaluation results showed that the quality of basically all batches from large honeyed pill manufacturers including Shanxi B and Guangdong E were excellent, while almost all scores were below 70 including large honeyed pill manufacture Guangxi D, water-honeyed pill manufacture Yunnan I, small honeyed pill manufacture Hunan J and watered pill manufacture Jilin K. Heat maps displayed that contents of components attributed to Rehmanniae Radix Praeparata, Alismatis Rhizoma, wine-steamed Corni Fructus, Poria in large honeyed pill manufacturer Shanxi B, components attributed to Alismatis Rhizoma, Rehmanniae Radix Praeparata in manufacturer Guangdong E were much higher than others. The scores of components belonged to Rehmanniae Radix Praeparata and Alismatis Rhizoma in manufacture Hunan J and Guangxi D were low, suggesting that these two manufactures should pay attention to the quality of the two crude drugs. Manufacture Yunnan I samples had low contents of components in Rehmanniae Radix Praeparata and Moutan Cortex, and devoted Moutan Cortex was also analyzed to be sulphur fumed.ConclusionThe established quantitative analysis method and evaluation system of Liuwei Dihuangwan can distinguish the quality of the manufacturers' samples intuitively and systematically, suggesting that manufacturers should pay attention to the medicinal flavors that are not monitored for content in the current edition of Chinese Pharmacopoeia, especially Rehmanniae Radix Praeparata and Alismatis Rhizoma, and need to pay attention to the sulfur fumigation of Moutan Cortex.
关键词:Liuwei Dihuangwan;liquid chromatography-mass spectrometry;characteristic components;Rehmanniae Radix Praeparata;wine-steamed Corni Fructus;processing of traditional Chinese medicine;evaluation system
摘要:As one of the malignant gynecological malignant tumors, ovarian cancer has atypical early symptoms and a high rate of metastasis and recurrence, making it a significant threat to women's health. Traditional Chinese medicine (TCM) believes that the balance of Yin and Yang guides the dynamic transformation of functions and substances in the body, achieving normal distribution of Qi, blood, and body fluids, and coordinating the strength and vitality of muscles and organs. Conversely, the imbalance of Yin and Yang, with the accumulation of Qi and blood in the uterus, can lead to ovarian cancer. With the progress on modern research, it has been found that autophagy, a process involving metabolic and energy changes within the body, also exhibits dynamic attributes of Yin and Yang. Inhibition of autophagy corresponds to "Yang decline and Yin excess", promoting the formation of ovarian cancer, while activation of autophagy corresponds to "Yang growth and Yin flourishing", driving the development of ovarian cancer. Tumor body autophagy imbalance, characterized by "Yin-Yang autophagy disorder", is associated with ovarian cancer recurrence and drug resistance, suggesting a high correlation between the pathogenesis of ovarian cancer and the pathological states of Yin and Yang. Therefore, based on the explanation of the related mechanisms of ovarian cancer and autophagy from Yin and Yang theory in TCM, this paper took the main contradictions of different stages of ovarian cancer as the starting point, and put forward the prevention and treatment principles for each stage: initially "nourishing the source of fire" to activate autophagy and "eliminate yin obstruction", then "attacking the toxic knot" to inhibit autophagy and "unblock yang stagnation", and finally "balancing Yin and Yang" to control autophagy and "slow the disease progression". It emphasized dynamically regulating Yin and Yang, harmonizing autophagy, treating both healthy and pathogenic Qi, and adapting reinforcing and expelling therapies, further preforming treatment along with variations and syndromes. The article suggested clinical methods and theoretical bases for integrating TCM and Western medicine in treating ovarian cancer, aiming to expand new ideas for its prevention and treatment and promote the modernization of TCM theories and diagnostic processes.
摘要:Depression is a common complication of diabetes mellitus, with the incidence growing year by year. The circular motion theory is a dialectical thought put forward by PENG Ziyi from the holistic view of man and the universe, and it expounds the pathogenesis and treatment of various diseases. This paper expounds the pathogenesis of diabetes mellitus complicated with depression from the circular motion theory, and demonstrates the theoretical and clinical basis of Sinisan in the treatment of this disease. This paper proposes that the axis damage and disorder of ascending and descending is the core mechanism of diabetes mellitus complicated with depression, and discusses the meaning of Sinisan in mediating the axis and ascending and descending the four dimensions. With circular motion as a bridge, this paper innovatively links the biological rhythm abnormalities, hypothalamic-pituitary-adrenal (HPA) axis imbalance, oxidative stress, and inflammatory response in modern medical research with the traditional Chinese medicine (TCM) connotation of diabetes mellitus complicated with depression. The experience of using Sinisan is summarized from TCM clinical practice, and the evidence of Sinisan in the treatment of diabetes mellitus complicated with depression was supplemented based on modern basic research. From the perspective of TCM and modern biology, this paper enriches the circular motion theory, elaborates on the mechanism of diabetes mellitus complicated with depression, expands the connotation of Sinisan, and suggests that follow-up research should focus on basic research to provide complete and clear evidence for interpretation.
关键词:diabetes mellitus;depression;Sinisan;circular motion;modern experimental research
摘要:In order to implement the spirit of the 20th National Congress of the Communist Party of China, and the Opinions on Promoting the Inheritance, Innovation and Development of Traditional Chinese Medicine(TCM), to regularly summarize the research results of TCM, to present the academic progress of TCM dynamically, and to give full play to the academic leadership of academic groups, the China Association of Chinese Medicine had organized the selection of the top 10 academic progress of TCM in 2023. The selection work adhered to the "four orientations", eliminated the "four only", highlighted the solution of clinical problems, answered scientific questions, led the development of the industry, reflected the exploratory and forward-looking, innovative and breakthrough, focused on new laws, new discoveries, new methods, new products, new theories in the field of basic research and applied basic research in TCM. After dynamic collection, preliminary examination, review and final judgment, the top 10 academic progress of TCM in 2023 were determined, including clinical studies have made important breakthroughs or achievements in the treatment of acute ST-segment elevation myocardial infarction(STEMI) by Tongxinluo, acupuncture treatment of refractory diseases such as chronic spontaneous urticaria and pregnancy vomiting, and Xuesaitong soft capsules to improve neurological function in patients with ischemic stroke. The mechanism of Huashi Baidusan, Pien Tze Huang, astragaloside Ⅳ, capsaicin was revealed. The application of technologies and methods such as spatial metabolomics, network medicine, multi-dimensional nucleic acid data resource platform of TCM, multi-unit transmission and information fusion provided new ideas for the research of TCM. The scientific system of TCM supervision was initially constructed and applied.
关键词:traditional Chinese medicine(TCM);academic progress;acute myocardial infarction;spontaneous urticaria;pregnancy vomiting;acupuncture;intestinal flora;spatial metabolomics
摘要:Celastrol (CEL) is a natural pentacyclic triterpenoid extracted and isolated from the traditional Chinese medicine (TCM) Tripterygium wilfordii in China. Modern pharmacological research has demonstrated that CEL has multiple pharmacological activities such as immunomodulation, anti-inflammation, anti-tumor, anti-fibrosis, and anti-virus, and it can protect cardiovascular and cerebrovascular systems and nervous systems, with good in vivo safety. In recent years, CEL has received much attention in anti-inflammatory and anti-tumor research due to its advantages of fewer adverse reactions, high efficiency, broad spectrum, multiple targets, and low drug resistance. CEL exhibits broad-spectrum pharmacological activity against multiple inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis, as well as a wide range of tumors such as liver cancer, lung cancer, breast cancer, and glioma by inhibiting the activation of various signaling pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear transcription factor -κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK). However, CEL has low content, poor solubility, low bioavailability, and high metabolic rate in plants, which have limited its clinical application. To address the above issues, researchers have investigated its total synthesis, structural modification, and development of nanomedicines. The authors have searched literature reports on CEL in China and abroad in the past five years and reviewed its total synthesis, in vivo metabolic transformation, pharmacological activity, and mechanism of action, so as to provide a theoretical basis for clarifying the mechanism of action of pharmacological activity of CEL and laying a foundation for the comprehensive development and future clinical applications of CEL.
关键词:celastrol;total synthesis;pharmacological activity;mechanism of action
摘要:This article reviews the immunological progress in 2022 by searching the papers published in academic journals. Focuses were put on the main achievements in innate immunity and activation of inflammasomes, T cell immune response and immunotherapy, recognition, regulation, and memory of B cells, immunodepletion, immunological mechanism of novel coronavirus pneumonia (COVID-19), and prevention and treatment of COVID-19 with traditional Chinese medicine. Interdisciplinary and technological integration have become a powerful force driving the development of immunology. With the development and application of high-throughput sequencing and screening technology, full spectrum flow cytometry, gene editing technology, protein engineering technology, and AI combined biotechnology, researchers are able to deeply explore the immune response characteristics, patterns, intrinsic mechanisms, and targets of natural and adaptive immunity, in order to find effective treatment methods and develop vaccines and drugs for indications. In 2022, immunology will make remarkable achievements in basic theory and application transformation, but also face greater challenges. The constant variation of novel coronavirus and its immune escape characteristics will continue to perplex and endanger human society. How to improve the effectiveness and safety of immunotherapy for tumor and autoimmune diseases, as well as the basic research of natural immunity and adaptive immunity still needs to be further understood.
关键词:novel coronavirus pneumonia (COVID-19);severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2);traditional Chinese medicine;immune regulation;innate immunity;immunodepletion
摘要:Si Junzitang is a classic traditional Chinese medicine (TCM) formula consists of Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma. With the effects of tonifying Qi and invigorating spleen, it is mainly used to treat the patients with spleen and stomach deficiency. In modern clinical practice, this prescription is employed in the prevention and treatment of digestive tract tumors, including colorectal cancer (CRC) and gastric cancer. The main active components of Si Junzitang include ginsenosides Rg3, Rb1, Rh1, and Rh2, atractylodes lactones Ⅰ and Ⅲ, pachymic acid, and glycyrrhizic acid. Clinical studies have shown that Si Junzitang can prevent and treat precancerous lesions, reduce the toxicity and enhance the efficacy of radiotherapy and chemotherapy, improve the quality of life, and prolong the survival time. Si Junzitang is widely used in the whole treatment course of CRC, while its mechanism remains to be systematically elucidated. This article summarizes relevant articles published in the past 10 years and obtains the following findings. Si Junzitang and its active components can prevent the transformation of inflammation into cancer by inhibiting intestinal inflammation. They can control tumor growth by regulating signaling pathways such as protein 53 (p53), Wnt, and nuclear factor-kappa B (NF-κB). They can inhibit tumor metastasis by regulating Wnt/β-catenin and Hippo signaling pathways. In addition, they can inhibit the proliferation, invasion, and migration of tumor cells by negatively regulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways. Meanwhile, they can promote the apoptosis of tumor cells by activating apoptotic proteins such as Bax and Caspase-9 and reverse drug resistance in chemotherapy and targeted therapy by downregulating the expression of drug resistance genes. Si Junzitang and its active components can restore the activities of cluster of differentiation 8+ thymic cells (CD8+ T cells), macrophages, and natural killers in the tumor microenvironment to enhance anti-tumor immunity. Moreover, they can alleviate the symptoms of cachexia, such as weight loss and muscle atrophy, by upregulating the expression of Kruppel like factor 4 (KLF4), thereby prolonging the survival time of tumor-bearing mice. Finally, this article discusses the current shortcomings in clinical and basic research and prospects promising research directions such as the interaction between Si Junzitang and intestinal microbiota, aiming to provide a reference for the development and clinical application of new, efficient, and low-toxic drugs for CRC in the future.
摘要:Cardio-cerebrovascular diseases are neurological and circulatory system diseases that damage the target organs such as the heart, brain, and blood vessels, with complex pathogenesis and high disability and mortality. Banxia Baizhu Tianmatang, first recorded in the Medical Insights written by Cheng Guopeng in the Qing dynasty, is composed of Gastrodiae Rhizoma, Pinellia Rhizome, Poria, Citri Exocarpium Rubrum, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus. With the effects of extinguishing wind, resolving phlegm, invigorating spleen, and resolving dampness, this prescription is often used to treat wind-phlegm symptoms. Clinical studies have confirmed that the application of modified Banxia Baizhu Tianmatang, or combined with western medicine, acupuncture, and massage, can treat cardio-cerebrovascular diseases such as ischemic stroke, coronary atherosclerotic heart disease, hypertension, hyperlipidemia, carotid atherosclerosis, migraine, and posterior circulation ischemic vertigo. Basic studies have found that its pharmacological mechanism may be related to regulating neurotransmitters, blood-brain barrier permeability, and intracranial circulation, restoring neurological function, protecting vascular endothelium, improving lipid metabolism disorders, hemorheology, and insulin resistance, reducing blood pressure, blocking renin-angiotensin-aldosterone system, and inhibiting oxidative stress and inflammatory response. This article reviewed the clinical research and mechanism research on Banxia Baizhu Tianmatang in the treatment of cardio-cerebrovascular diseases, so as to provide a theoretical basis for the clinical application of Banxia Baizhu Tianmatang.
摘要:Aquaporins (AQPs) playing a crucial role in maintaining the body fluid balance, energy metabolism, cell signaling, cell migration, and cell proliferation are closely associated with diseases. The dysfunction of AQPs is linked to cardiovascular diseases. The research on the regulation and functions of AQPs not only gives new insights into the diagnosis and prognosis of cardiovascular diseases but also promotes the development of therapeutic strategies. By reviewing the recent research findings, this article briefs the localization and expression of AQPs in the cardiovascular system of mammals and summarizes the physiological and pathological roles and regulatory mechanisms of AQP1, AQP4, AQP7, AQP9, and AQP2 associated with cardiovascular diseases in the cardiovascular tissue. From the perspective of integrating traditional Chinese medicine (TCM) with western medicine, the article explores the correlation between AQPs and the body fluid metabolism in TCM, providing a modern biological interpretation for TCM theories, contributing to a deeper scientific understanding of TCM, and offering possible molecular mechanisms for explaining the specific functions of Zang-fu organs in TCM. Furthermore, this article summarizes the research progress of TCM compound prescriptions/single Chinese medicines targeting AQP-related signaling pathways and discusses the regulation of AQP expression by TCM in the treatment of cardiovascular diseases. The review provides molecular evidence for the modern research and application of TCM and emphasizes the regulatory mechanisms of TCM targeting AQPs in the treatment of cardiovascular diseases. It offers potential molecular targets and a basis for the clinical application of TCM in treating the diseases of body fluid metabolism imbalance. Integrating TCM theory with modern biology provides a new direction for the future research.
关键词:aquaporins (AQPs);traditional Chinese medicine;cardiovascular diseases;body fluid metabolism balance;heart failure
摘要:Salvia genus is a common ethnic medicinal resource, and the various types of traditional Chinese medicine (TCM) belonging to the Salvia genus have a long history of being used for the treatment of diseases. They are widely used and have high medicinal value, making them valuable for research and development. To the 78 species of Salvia plants in China, 32 species are used by 18 ethnic minorities, and they have pharmacological effects of anti-cancer, analgesia, anti-inflammation, anti-radiation, liver protection, anti-cardiovascular disease, hypoglycemic effect, oxidation resistance, anti-pathogenic microorganisms, anti-fibrosis, hemostasis, kidney protection, anti-Alzheimer's disease, immune regulation, and anti-gout. The main active substance bases are phenolic acid, flavonoids, terpenoids, and polysaccharides. However, despite the rich medicinal value and material basis of the medicinal resources of the Salvia genus, there are still certain problems in research and application. The research on some Salvia plants in this genus of ethnic medicinal resources is still weak, and its medicinal mechanism and clinical application value need to be further explored and verified. In addition, since there are many varieties of Salvia genus, with different chemical constituents, structural types, and biological activities, the quality of Salvia plants is different, and thus the research on its quality standard needs to be further improved. Therefore, the systematic research and exploitation of the ethnic medicinal resources of the Salvia genus are important. In this study, the medicinal resources, chemical constituents, pharmacological activity, and quality of the plants in this genus were systematically sorted out and analyzed, so as to provide a reference for the in-depth research and rational development of the ethnic medicinal resources of this genus.
摘要:Uterine aging is an important factor contributing to uterine-related diseases and affecting fertility. However, uterine aging has rarely been explored at present. Functionally, uterine aging is associated with endometrial hormonal abnormalities, reduced endometrial tolerance, and impaired uterine metamorphosis. Structurally, uterine aging is associated with altered uterine morphology, diminished contractility of the myometrium, and decreased uterine vascular functions, and uterine aging induces a negative feedback regulation of multiple molecular mechanism pathways, including immune abnormalities mediated by macrophages and uNK cells and inflammatory factor-mediated pathological inflammatory response. With the promulgation of the three-child policy, the willingness of elderly women to have children has increased, and the problem of reduced fertility in elderly women caused by uterine aging has become prominent, but the specific pathogenesis of uterine aging, as well as its prevention and treatment strategies, have rarely been reported. In recent years, there has been more and more research on traditional Chinese medicine to alleviate uterine aging by regulating reproductive endocrine levels, autoimmunity, and oxidative stress damage through multiple levels and pathways. Many randomized controlled trials have proved the clinical efficacy of traditional Chinese medicine to alleviate uterine aging. This paper reviewed the functions, structural changes, and molecular mechanisms of the aging uterus and summarized the mechanism of traditional Chinese medicine to alleviate uterine aging and the progress of randomized controlled trials, so as to clarify the current status of the research and its shortcomings and provide a reference for the improvement of fertility and pregnancy outcome of elderly women.
关键词:uterine aging;elderly parturient women;infertility;traditional Chinese medicine
摘要:Adenomyosis (AM) is one of the most common and refractory gynecological diseases in the clinic. It has the characteristics of complicated pathogenesis and a long course. Currently,there is no standard unified treatment plan for AM,and individual treatment plans are usually formulated according to the different symptoms and demands of patients. However,due to the long treatment cycle of AM,easy recurrence, and difficult eradication,patients' compliance is not good during treatment. Through multi-channel,multi-link, and multi-target treatment of AM,traditional Chinese medicine (TCM) has the advantages of significant clinical efficacy,few adverse reactions, and low recurrence rate,and it has been accepted by the majority of patients. At present,the literature mainly focuses on the summary of the experience of famous TCM practitioners,the improvement of clinical symptoms of AM, as well as the enhancement of clinical efficacy of TCM,and the research reports on the mechanism of TCM in the treatment of AM are insufficient. Therefore,this paper reviewed relevant literature in China and abroad and summarized the mechanism of action of active ingredients of TCM,TCM pairs,TCM compounds, and external therapy of TCM in the treatment of AM. It mainly included inhibition of the proliferation,migration, and invasion of ectopic endometrial cells in AM,induction of apoptosis,blocking of cell cycle,anti-endometrial fibrosis,regulation of mitochondrial autophagy,inhibition of angiogenesis,regulation of estrogen-effecting factors,regulation of immune imbalance, and improvement of inflammatory response,involving multiple signaling pathways and related molecules. This paper reviewed the research progress on the mechanism of action of TCM in the treatment of AM,so as to provide some references for the clinical treatment and experimental research of TCM in the future.
关键词:adenomyosis;traditional Chinese medicine;mechanism of action;experimental research;research progress
摘要:Brain glioma is one of the malignant tumors with the highest mortality rate in the world,but its pathogenesis is not yet clear. Although surgery,radiotherapy,chemotherapy,immunotherapy,and electric field therapy have achieved good clinical efficacy in treating brain gliomas,these treatment methods have problems such as high adverse reactions,as well as heavy economic and psychological burdens on patients. In recent years,traditional Chinese medicine (TCM) has become a highlight in tumor treatment due to its multi-component,multi-target,and multi-pathway characteristics. Its low adverse reactions can complement the advantages of Western medicine in treatment. Multiple studies have shown that active ingredients of TCM monomers and compound formulas can reshape the tumor microenvironment (TME),inhibit the proliferation,invasion,migration,and angiogenesis of brain glioma cells,and promote apoptosis and autophagy of brain glioma cells,thereby delaying the process of brain glioma development and achieving therapeutic effects on brain glioma. In recent years,there have been many research achievements related to this topic,and the existing summary literature is not fully included and lacks systematic organization. Therefore,this study investigated the correlation between TME and brain glioma,aiming to systematically summarize the relevant mechanisms of TCM intervention in the treatment of brain glioma, provide new targets,perspectives,and ideas for the treatment of brain glioma,and promote the modernization of TCM.
关键词:tumor microenvironment;brain glioma;traditional Chinese medicine;molecular mechanisms;research progress