Abstract:ObjectiveTo observe the effect of Xiaoyaosan on the expression of RAS homologous gene family member A (RhoA) and Rho-related coiled protein kinase 1 and 2 (ROCK1 and ROCK2) in gastric tissues of rats with liver depression and spleen deficiency syndrome and to explore its mechanism of regulating gastrointestinal motility in rats with liver depression and spleen deficiency syndrome.MethodSeventy-two male SD rats were randomly divided into 6 group, namely the normal group, the model group, the fluoxetine group (0.001 8 g·kg-1), the Xiaoyaosan high (16.7 g·kg-1), medium (8.35 g·kg-1) and low-dose (4.175 g·kg-1) group, with 12 rats in each group. In addition to the normal group, the rats in other groups were used to establish the model of liver depression and spleen deficiency syndrome by chronic restraint stress. At the same time, the rats in the normal group and the model group were given normal saline (10 mL·kg-1), and the rats in each drug group were given corresponding doses of drugs once a day for 21 d. After modeling, the gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The mRNA and protein expressions of RhoA, ROCK1, and ROCK2 in gastric tissues were detected by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot.ResultAs compared with the normal group, the gastric emptying rate, intestinal propulsion rate, and the mRNA and protein expressions of RhoA, ROCK1, and ROCK2 in gastric tissues in the model group were lower (P<0.05, P<0.01). The abnormal changes in the above indexes in the Xiaoyaosan high, medium, and low-dose groups were all improved in varying degrees as compared with the model group (P<0.05, P<0.01).ConclusionXiaoyaosan improves gastrointestinal motility in rats with liver depression and spleen deficiency syndrome, which may be related to the up-regulation of the RhoA/ROCK signal pathway in gastric tissues.
Keywords:Xiaoyaosan;liver depression and spleen deficiency syndrome;stomach;RAS homologous gene family member A (RhoA)/Rho-related coiled protein kinase (ROCK)
Abstract:ObjectiveTo study the effect of Huangqintang on intestinal T helper cells(Th)17/regulatory T cells(Treg) and Th1/Th2 balance in experimental ulcerative colitis (UC) mice.MethodSixty male C57BL/6J mice were randomly divided into normal group, model group, sulfasalazine group (0.2 g·kg-1), and Huangqintang low-dose, medium-dose and high-dose groups (4.55,9.1,18.2 g·kg-1, respectively) according to body weight. Except for the normal group, all mice were given 2.5% dextran sodium sulfate (DSS, added to free drinking water) for 5 days to induce UC. After 7 days of continuous intragastric administration, the mice were sacrificed and the mesenteric lymph nodes (MLNs) and colon tissues were collected. The Th17/Treg and Th1/Th2 cell ratios in MLNs of mice were measured by flow cytometry. Interleukin-2 (IL-2), interleukin-17A (IL-17A), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10) and other cytokines in colon tissues were detected by flow cytometric microsphere-based assay. The colon tissues samples were sectioned, and immunohistochemical method was used to detect the expression levels of T-box transcription factor (T-bet), GATA binding protein 3 (GATA-3), IL-17A and forkhead box P3 (FoxP3) in colon tissues. The content of transforming growth factor-β (TGF-β) in colon tissue of mice was determined by enzyme-linked immunosorbent assay (ELISA).ResultCompared with the normal group, the number of Th1 and Th17 cells in the model group was significantly increased, while the number of Th2 and Treg cells was significantly decreased, and Th1/Th2 and Th17/Treg were significantly increased (P<0.05, P<0.01). The expressions of T-bet, GATA-3, IL-17A and FoxP3 in colon tissues of mice were significantly increased (P<0.05, P<0.01), and the contents of cytokines IL-2, IL-17A, IL-6, TNF-α and IFN-γ were significantly increased. The contents of IL-4, TGF-β and IL-10 were significantly decreased (P<0.05, P<0.01). Compared with the model group, the imbalance of Th1/Th2 and Th17/Treg cells was reversed in each dose group of Huangqin decoction (P<0.01). The expressions of T-bet and GATA-3 in colon of mice were significantly decreased in low-dose, medium-dose and high-dose groups of Huangqintang (P<0.05, P<0.01), and the expression of IL-17A was significantly decreased in high-dose and low-dose groups of Huangqintang (P<0.01). The contents of cytokines IL-2, IL-17A, IFN-γ, IL-6 and TNF-α were significantly decreased in the high-dose and medium-dose groups of Huangqintang, and the contents of TGF-β and IL-10 were significantly increased in the high-dose group of Huangqintang (P<0.05, P<0.01).ConclusionHuangqintang could reduce colonic inflammation and improve colonic tissue damage in UC mice, possibly by regulating Th17/Treg and Th1/Th2 balance and related cytokines levels, and the release level of pro-inflammatory cytokines.
Keywords:Huangqintang;ulcerative colitis;T helper cells(Th)17/regulatory T cells(Treg) and Th1/Th2 balance
Abstract:ObjectiveTo observe the effect of Shenghuitang on serum levels of neurotransmitters in the mouse model of Alzheimer's disease (AD) and explore the mechanism of Shenghuitang in mitigating the cognitive impairment and circadian rhythm disturbance of AD.MethodTwenty-seven APP/PS1 dementia mice were randomly assigned into a model group, a donepezil (0.92×10-4 g·kg-1·d-1) group, and a Shenghuitang (13.5 g·kg-1·d-1) group. Another nine wild-type C57BL/6JNju mice was set as the control group. The mice were administrated with corresponding drugs by gavage and the control and model groups were given the same volume of pure water. Every group was continuously treated for 4 weeks. The cognitive function and circadian rhythm of mice were evaluated by Morris water maze test and open field test. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to determine the expression levels of acetylcholine (ACh), choline acetyltransferase (ChAT), norepinephrine (NE), epinephrine (E), glutamate (Glu), 5-hydroxyindoleacetic acid (5-HIAA), and dopamine (DA) in the serum.ResultCompared with the control group, the modeling increased the escape latency, swimming distance, time of first arrival on the platform, activity time of light environment, activity time of dark environment, and total activity time (P<0.01), while it decreased the number of crossing the platform and the swimming time in the target quadrant (P<0.01). Compared with the model group, donepezil and Shenghuitang decreased the escape latency, swimming distance, time of first arrival on the platform, activity time of light environment, activity time of dark environment and total activity time (P<0.05, P<0.01), while they increased the number of crossing the platform and the swimming time in the target quadrant (P<0.05, P<0.01). Compared with the control group, the modeling down-regulated the expression levels of ACh and ChAT in the serum (P<0.01). Compared with the model group, donepezil and Shenghuitang up-regulated the expression levels of ACh and ChAT in the serum (P<0.05, P<0.01). Compared with the control group, the modeling up-regulated the expression level of Glu in the serum (P<0.01) and down-regulated the expression levels of NE, 5-HIAA, and DA (P<0.01). Compared with the model group, Shenghuitang down-regulated the expression level of Glu (P<0.05) and up-regulated the expression levels of NE, 5-HIAA, and DA (P<0.05, P<0.01). The expression levels of NE, Glu, 5-HIAA, and DA in the donepezil group did not change significantly compared with those in the model group. The expression level of E showed no significant difference among different groups.ConclusionShenghuitang may ameliorate the cognitive impairment and circadian rhythm disturbance of AD mice by regulating the levels of neurotransmitters in the serum.
Keywords:Alzheimer's disease;Shenghuitang;neurotransmitter;learning and memory;circadian rhythm
Abstract:ObjectiveTo investigate the therapeutic effect of Gexia Zhuyutang on rats with endometriosis (EMT) with Qi stagnation and blood stasis syndrome and its mechanism.MethodSix female unpregnant healthy SD rats of SPF grade were randomly selected as a blank group. The rest were treated with the compound factor method to induce EMT with Qi stagnation and blood stasis syndrome in rats. After successful modeling, 30 rats from 36 rats were randomly divided into a model group, a medroxyprogesterone (0.416 mg·kg-1) group, and low, medium, and high-dose Gexia Zhuyutang groups (4.063, 8.125, 16.25 g·kg-1), with 6 rats in each group. Each group was given corresponding drugs, once a day for 4 consecutive weeks. The effect of Gexia Zhuyutang on rats with EMT was observed by the pathological changes and the volume of ectopic foci. The endometrial tissues of each group were taken for hematoxylin-eosin (HE) staining to observe histopathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of interleukin (IL)-10 and IL-6 in the serum supernatant of each group. Immunohistochemistry (IHC) was used to determine the protein expressions of nuclear factor kappa B (NF-κB), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and Bcl-2 related X protein (Bax) in the tissues of rats in each group. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to determine the mRNA expressions of NF-κB, MMP-9, VEGF, and Bax.ResultAfter treatment, the volume of ectopic foci in the low, medium, and high-dose Gexia Zhuyutang groups and the medroxyprogesterone group was significantly reduced. The pathological observation under the microscope showed that the endometrial structure of rats in the sham-operated group and the blank group was intact, glands and mesenchymal cells grew well, glandular epithelial cells were arranged tightly and neatly, the cytoplasm was abundant and highly columnar, the interstitial cells were evenly distributed, and the blood vessels were abundant and spindle-shaped. Compared with the blank group and the sham-operated group, the model group was dominated by columnar epithelium and cubic epithelium. In the model group, ectopic endometrial epithelial cells were short columnar, some were pseudo-lamellar, the cell morphology was incomplete, the number of interstitial cells and glands was reduced, some glands were round, and degenerative dysplasia was formed. Compared with the blank group, the serum content of IL-10 in the model group was decreased (P<0.05), and the content of IL-6 was increased (P<0.05). The model group increased the protein expressions of NF-κB, VEGF, and MMP-9 (P<0.05) and decreased the protein expression of Bax in eutopic and ectopic endometrial tissues. Compared with the model group, the serum content of IL-10 in the medium and high-dose Gexia Zhuyutang groups was increased (P<0.05), and the content of IL-6 was decreased (P<0.05). The protein expressions of NF-κB, VEGF, and MMP-9 in eutopic and ectopic endometrial tissues of rats in the low, medium, and high-dose Gexia Zhuyutang were decreased (P<0.05), and the protein expression of Bax was increased (P<0.05). Compared with the ectopic endometrium of the model group, the mRNA expressions of NF-κB, MMP-9, and VEGF in the ectopic endometrium of the medium and high-dose Gexia Zhuyutang groups were decreased (P<0.05), and the mRNA expression of Bax was increased (P<0.05).ConclusionGexia Zhuyutang has the effect of inhibiting the invasion of ectopic foci in rats with EMT with Qi stagnation and blood stasis syndrome, and its mechanism may be related to the intervention of immunosuppression mediated by overactivation of the NF-κB signaling pathway, the improvement of the inflammatory response, and the blocking of microvascular regeneration function.
Keywords:Gexia Zhuyutang;endometriosis;nuclear factor kappa B (NF-κB) signaling pathway;inflammatory response;immunosuppression;microvascular regeneration
Abstract:ObjectiveTo observe the effect of Simiaowan on the intestinal ATP-binding cassette superfamily G (White) member 2 (ABCG2) expression and the intestinal uric acid excretion in hyperuricemia rats.MethodA total of 48 SD male rats were randomized into the normal, model, benzbromarone (4.7 mg·kg-1), and high-, medium-, low-dose Simiaowan groups (2 260.6, 1 130.3, 565.2 mg·kg-1, respectively), with 8 rats in each group. Potassium oxonate and hypoxanthine was employed to induce hyperuricemia in rats (21 days). On the 8th day, administration began (once a day for 14 days). Rats were killed on the 21st day, and serum uric acid, serum creatinine, blood urea nitrogen, and intestinal uric acid were detected. The protein expression of ABCG2 in the small intestine was detected by Western blot. The ABCG2 protein expression and localization in intestinal tissues were determined by immunohistochemistry. The ABCG2 mRNA expression in small intestine was measured by quantitative real-time PCR.ResultThe levels of serum uric acid, serum creatinine, and blood urea nitrogen in the model group were higher than those in the normal group (P<0.01). Low level of serum uric acid in the three Simiaowan groups and benzbromarone group (P<0.01), high level of intestinal uric acid in medium-dose and low-dose Simiaowan groups (P<0.05, P<0.01), high level of serum creatinine in benzbromarone group (P<0.01), and low level of blood urea nitrogen in low-dose Simiaowan group (P<0.05) were observed as compared with those in the model group. Serum uric acid showed insignificant difference between the low-dose Simiaowan group and benzbromarone group. The expression of ABCG2 protein in the model group was lower than that in the normal group (P<0.05). The expression of ABCG2 protein in the medium-dose and low-dose Simiaowan groups (P<0.05, P<0.01), the high-dose Simiaowan group, and benzbromarone group increased as compared with that in the model group. ABCG2 mRNA expression was insignificantly different between the model group and the normal group, while the expression in the medium-dose and low-dose Simiaowan groups was higher than that in the model group (P<0.05). ABCG2 protein was mainly distributed in intestinal villi, and ABCG2 protein expression demonstrated no significant difference between the model group and the normal group. The ABCG2 protein expression in the three Simiaowan groups increased as compared with that in the model group (P<0.05).ConclusionSimiaowan can significantly reduce the serum uric acid level in hyperuricemia rats. Particularly, the low-dose Simiaowan shows similar efficacy to benzbromarone in lowering uric acid and protects renal function. The mechanism is the likelihood that it up-regulates intestinal ABCG2 expression to promote intestinal excretion of uric acid.
Keywords:Simiaowan;hyperuricemia;intestinal uric acid;ATP-binding cassette superfamily G (White) member 2 (ABCG2)
Abstract:ObjectiveTo explore the mechanism of Chaihu Guizhitang (CHGZT) in alleviating neuropathic abdominal pain induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats with chronic pancreatitis (CP).MethodFifty male SD rats were randomly assigned into five groups: sham operation, CP model, and low-, medium-, and high-dose (4, 8, and 16 g·kg-1, respectively) CHGZT groups. In the sham operation group, the abdomen was closed after the pancreas was gently stirred. The rat model of CP was established by retrograde injection of 2% TNBS-10% ethanol into the pancreatic duct. The oral administration of CHGZT started 4 weeks after modeling and lasted for 2 weeks. Pain threshold was measured by Von Frey fibers 6 weeks after surgery. Hematoxylin-eosin (HE) staining was employed to reveal the chronic inflammation and fibrosis of the pancreatic tissue. Immunohistochemmistry (IHC) was employed to detect the expression of PGP9.5 (a marker of pancreatic nerves) and reveal the inflammatory changes around the nerves. IHC and immunofluorescence (IF) were used to determine the location of ionized calcium-binding adaptor molecule-1 (Iba-1, microglia marker) and purinergic receptor P2X7 (P2RX7) and the co-expression of P2RX7 and Iba-1 in the thoracic spinal dorsal horn.ResultCompared with the sham operation group, the modeling increased the scores of pancreatic gland atrophy, inflammatory infiltration, and fibrosis (P<0.01), the abdominal pain response under different force values (P<0.05, P<0.01), and the score of peripancreatic inflammation. Moreover, the modeling up-regulated the expression of Iba-1 and P2RX7 in the thoracic spinal dorsal horn (P<0.01). Compared with the model group, the high- and medium-dose CHGZT lowered the scores of pancreatic gland atrophy, inflammatory infiltration, and fibrosis, the abdominal pain response, and the score of peripancreatic inflammation (P<0.05, P<0.01). The high-, medium-, and low-dose CHGZT all down-regulated the expression of Iba-1 and P2RX7 (P<0.01).ConclusionCHGZT can significantly relieve abdominal pain in CP rat by suppressing the inflammation around nerves in the pancreas and the P2RX7 activation of microglia in the spinal dorsal horn.
Abstract:Qingweisan is one of the classical prescriptions commonly used in the treatment of oral diseases. By means of Bibliometrics, the authors collected the ancient books on Qingweisan and sifted out 411 valid data, involving 116 classics of traditional Chinese medicine. The historical origin, drug composition, indications, principle of composition, dosage,and preparation of Qingweisan were statistically analyzed, and it was found that the prescription originated from the Treatise on Spleen and Stomach(《脾胃论》) by LI Dongyuan and is composed of Rehmanniae Radix, Angelica Sinensis, Cortex Moutan, Coptidis Rhizoma and Cimicifugae Rhizoma, with the functions of clearing stomach, purging fire, cooling blood and dispersing depression. And Qingweisan was mainly used to treat toothache, headache, and preference for cold and aversion to heat caused by "excessive heat in yang brightness meridian". There were 352 indications recorded, most of which followed LI Dongyuan's theory and the expanded indications reached 70 kinds. Specifically, toothache (132) was the most, accounting for 22.49% of the total indications, followed by headache (60, 10.22%). In addition, Qingweisan was widely used in modern clinical practice for multiple system diseases, among which oral system (197) was dominant, accounting for 72.69%, followed by skin system (28, 10.33%) and digestive system (27, 9.96%). Although the indications were wide, the pathogenesis always belonged to "upward attack of stomach fire". Through the excavation and statistical analysis of the ancient books on Qingweisan and its modern clinical application, the authors aimed to provide a more scientific reference for the research and application of classical famous prescriptions.
Keywords:classical famous prescriptions;Qingweisan;ancient books of traditional Chinese medicine(TCM);textual research;historical evolution;clinical application
Abstract:ObjectiveTo explore the compatibility advantage of Scutellariae Radix-Coptidis Rhizoma in the prevention and treatment of neuroinflammation, and to elucidate the action characteristics and mechanism of the compatibility advantage based on Toll like receptor (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappaB (NF-κB) pathway.MethodRepresentative mouse microglia cells (BV2) in vitro were selected and divided into 8 groups: control group, model group, Scutellariae Radix-Coptidis Rhizoma group, Piracetam group, Scutellariae Radix group and Coptidis Rhizoma group. The BV2 cell inflammatory model was established by lipopolysaccharide (LPS), and the cell activity was detected by cell counting kit-8 (CCK-8). Cell morphology was observed under bright field. The production and release of pro-inflammatory factors in BV2 cells were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay, and the mRNA expressions of TLR4, MyD88 and NF-κB were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The nuclear translocation of NF-κB p65 was detected by immunofluorescence, and TLR4 signal transduction inhibitor (CLI-095) and NF-κB inhibitor (PDTC) were used to confirm the anti-neuroinflammation targets of Scutellariae Radix-Coptidis Rhizoma.ResultCompared with the conditions in the control group, most cells in LPS-induced model group were activated, and the contents of IL-6, TNF-α and IL-1β in culture medium and cells and the mRNA expressions of TLR4, MyD88, NF-κB p50 and NF-κB p65 were increased (P<0.01), with obvious nuclear entry of NF-κB p65. Compared with the conditions in the model group, BV2 cell morphology was mostly recovered after pretreatment in Scutellariae Radix-Coptidis Rhizoma and Piracetam groups, and the levels of IL-6, TNF-α and IL-1β and the mRNA expressions of TLR4, MyD88, NF-κB p50 and NF-κB p65 were decreased (P<0.05, P<0.01), with NF-κB p65 mostly observed in cytoplasm. Compared with the conditions in the model group, cell morphology was slightly recovered in Scutellariae Radix group and Coptidis Rhizoma group, and the levels of pro-inflammatory factors and mRNA expressions of TLR4, MyD88, NF-κB p50 and NF-κB p65 were reduced. In terms of inhibitory effect on pro-inflammatory factors, Scutellariae Radix group and Coptidis Rhizoma group were lower than Scutellariae Radix-Coptidis Rhizoma group (P<0.05). Compared with the model group, the "Scutellariae Radix-Coptidis Rhizoma+CLI-095" group and "Scutellariae Radix-Coptidis Rhizoma+PDTC" group had lowered mRNA expressions of TLR4, MyD88, NF-κB p50 and NF-κB p65 (P<0.05, P<0.01), and the transfer of NF-κB p65 into nucleus was obviously inhibited.ConclusionThe anti-neuroinflammation effect of Scutellariae Radix-Coptidis Rhizoma was significantly better than Scutellariae Radix or Coptidis Rhizom alone, and the anti-neuroinflammation advantage was closely related to the inhibition of activation of TLR4/MyD88/NF-κB signaling pathway in microglial cells. It was confirmed that TLR4, MyD88 and NF-κB were potential targets for Scutellariae Radix-Coptidis Rhizoma to exert the compatibility advantage.
Abstract:ObjectiveTo investigate the effect of Shouwuwan on apoptosis of hippocampal neurons in D-galactose-induced aging rats through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway.MethodFifty male SD rats of SPF grade were randomly divided into normal group, model group, vitamin E group, and Shouwuwan medium- and high-dose groups. Except the normal group, the other four groups were given D-galactose (120 mg·kg-1) to prepare aging model. Additionally, Shouwuwan was used to intervene in the Shouwuwan medium- and high-dose groups (1.08 and 2.16 g·kg-1, respectively), and vitamin E group (0.018 g·kg-1) was given vitamin E by gavage. After 6 weeks of modeling, the whole brain and hippocampal tissue were taken and the morphological changes of hippocampal neurons were observed by Nissl staining. The apoptosis of hippocampal cells was detected by in situ end labeling [TdT-mediated dUTP nick-end labeling (TUNEL)]. The protein expression levels of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, Caspase-3, forkhead box protein O3a (FoxO3a), p-FoxO3a, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by Western blot. Real-time fluorescence quantitative PCR (Real-time PCR) was performed to determine the mRNA expression level of FoxO3a in hippocampus.ResultCompared with the conditions in the normal group, the apoptotic cells of hippocampal neurons in the model group were significantly increased, and the apoptosis index was elevated (P<0.01). Nissl staining of the hippocampal CA1 region showed that hippocampal neurons were lost and sparse, and the number of Nissl bodies was reduced, with pyknosis and deep staining. The relative protein expression of p-PI3K, p-Akt, Caspase-3 and Bax, p-PI3K/PI3K ratio and p-Akt/Akt ratio were all increased (P<0.01), while the relative protein expression of FoxO3a, p-FoxO3a and Bcl-2, and p-FoxO3a/FoxO3a ratio were decreased (P<0.01). The mRNA expression of FoxO3a was lowered (P<0.01). Compared with the conditions in the model group, after treatment with Shouwuwan, the apoptotic cells were markedly reduced, and the apoptosis index of each treatment group was decreased (P<0.01). Nissl staining of the hippocampal CA1 region demonstrated that the loss of neurons in each treatment group was improved, and Nissl bodies were increased and densely arranged. There was no statistically significant difference in the relative protein expression of PI3K and Akt in each group. In Shouwuwan medium- and high-dose groups, the relative protein expression of p-PI3K, p-Akt, Caspase-3 and Bax, p-PI3K/PI3K ratio and p-Akt/Akt ratio were decreased, while the relative protein expression of FoxO3a andp-FoxO3a, and Bcl-2, and p-FoxO3a/FoxO3a ratio were increased (P<0.01). The mRNA expression of FoxO3a was up-regulated (P<0.01).ConclusionShouwuwan could improve the structure of hippocampal neurons, inhibit PI3K/Akt signal pathway, down-regulate Caspase-3 and Bax, activate FoxO3a, and up-regulate Bcl-2 and Bcl-2/Bax ratio, to reduce neuronal apoptosis.
Keywords:brain aging;Shouwuwan;neuronal apoptosis;phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway;forkhead box protein O3a (FoxO3a)
Abstract:ObjectiveTo study the effect of total flavone of Litchi Semen (TFL) on proliferation, apoptosis, migration, and invasion of hepatoma cells HepG2.MethodMethyl thiazolyl tetrazolium colorimetric (MTT) assay was used to detect the effect of different-dose TFL and cisplatin on the proliferation of HepG2 cells. TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect the effects of low, medium, and high-dose (70, 140, 210 mg·L-1) of TFL and cisplatin (60 mg·L-1) on the apoptosis of HepG2 cells, thus selecting the optimal dose of TFL for the follow-up experiment. HepG2 cells were divided into a blank group, a TFL group (140 mg·L-1), a TFL+XL019 group (140 mg·L-1 TFL+0.5 μmol·L-1 XL019), and a TFL+TPI-1 group (140 mg·L-1 TFL+1 μmol·L-1 TPI-1). The effect of TFL on migration and invasion of HepG2 cells were examined by wound healing test and Transwell invasion assay, and the effect of TFL on the expression of epithelial-mesenchymal transition (EMT) marker in HepG2 cells were examined by cell immunofluorescence assay. Western blot was used to detect the expression of key proteins in Janus kinase 2(JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway after the intervention by TFL.ResultMTT assay showed that the proliferation of HepG2 cells was significantly inhibited by TFL and cisplatin at 24 and 48 h as compared with blank group (P<0.01), and the half maximal inhibitory concentration (IC50) of TFL on HepG2 cells was (136.7±2.40) mg·L-1 at 24 h and (106.8±1.11) mg·L-1 at 48 h. The IC50 of cisplatin on HepG2 cells was (58.48±2.04) mg·L-1 at 24 h and (5.15±0.56) mg·L-1 at 48 h. The results of TUNEL assay showed that TFL induced apoptosis of HepG2 cells. The optimal dose of TFL was 140 mg·L-1. The results of wound healing test showed that compared with the blank group, the TFL group, TFL+XL019 group, and the TFL+TPI-1 group significantly inhibited the migration of HepG2 cells (P<0.05, P<0.01). As compared with the TFL group, the inhibitory effect of the TFL+XL019 Group was significantly increased (P<0.05), while that of the TFL+TPI-1 group was significantly decreased (P<0.01). The Transwell invasion assay showed that compared with the blank group, the TFL group, TFL+XL019 group, and the TFL+TPI-1 group significantly inhibited the invasion of HepG2 cells (P<0.01). As compared with the TFL group, the inhibitory effect of the TFL+XL019 group was significantly increased (P<0.05), while that of the TFL+TPI-1 group was significantly decreased (P<0.01). The results of immunofluorescence showed the intervention of TFL up-regulated the expression of E-cadherin, and down-regulated the expression of Vimentin in HepG2 cells, which was stronger in the TFL+XL019 group and weaker in the TFL+TPI-1 group. The results of Western blot showed that compared with the blank group, the TFL group, TFL+XL019 group, and the TFL+TPI-1 group did not affect the expression of JAK2 or STAT3 protein, but significantly decreased the expression levels of phosphorylatied (p)-JAK2 and p-STAT3 (P<0.05, P<0.01). As compared with the TFL group, the expression levels of p-JAK2 and p-STAT3 in the TFL+XL019 group were significantly decreased (P<0.01), while those in the TFL+TPI-1 group were significantly increased (P<0.01). Compared with the blank group, the TFL group significantly increased the expression level of Src-homology domain 2 containing protein tyrosine phosphatase-1(SHP-1) with sh2 domain (P<0.01).ConclusionTFL has the effects of inhibiting the proliferation, promoting apoptosis of HepG2 cells, and reversing the EMT process of HepG2 cells to reduce the migration and invasion, which are presumably related to the activation of SHP-1 by TFL to block JAK/STAT3 signaling pathway.
Keywords:total flavone of Litchi Semen;Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway;invasion;migration;HepG2;epithelial-mesenchymal transition(EMT)
Abstract:ObjectiveTo observe the effect of Guben Jiedu prescription (GBJ) on the epithelial-mesenchymal transition (EMT) of lung cancer A549 cells and to explore the mechanism based on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.MethodThe GBJ-medicated serum was prepared. Cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay to screen the optimal doses of GBJ-medicated serum for further experiment. A549 cells were classified into normal serum group, low-, medium-, and high-dose GBJ-medicated serum groups (2.5%, 5%, and 10% GBJ-medicated serum), PI3K/Akt pathway activator SC79 group, and high-dose GBJ-medicated serum + SC79 group. Cell migration ability was measured by wound-healing assay. The protein expression of E-cadherin, N-cadherin, vimentin, Akt, phosphorylated Akt (p-Akt), glycogen synthase kinase-3β (GSK-3β), and phosphorylated GSK-3β (p-GSK-3β) was detected by Western blotting, and the mRNA expression of N-cadherin and vimentin by Real-time PCR.ResultCompared with the normal serum, GBJ-medicated serum (2.5%, 5%, 10%, 20%, 40%) decreased the viability of A549 cells (P<0.05), and 10%, 5%, 2.5% GBJ-medicated serum was respectively selected for the follow-up experiment. The migration ability of cells in the high-, medium-, and low-dose GBJ-medicated serum groups was lower than that in the normal serum group. The expression of N-cadherin mRNA and Vimentin mRNA in A549 cells in the three GBJ-medicated serum groups was significantly lower than that in the normal serum group (P<0.01). The protein expression of E-cadherin was higher in the high- and medium-dose GBJ-medicated serum groups than in the normal serum group (P<0.01). The three GBJ-medicated serum groups showed lower protein expression of N-cadherin, vimentin, p-Akt, and p-GSK-3β (P<0.01) and lower expression of p-Akt/Akt, p-GSK-3β/GSK-3β (P<0.05, P<0.01) than normal serum group. Compared with the SC79 group, the high-dose GBJ-medicated serum group demonstrated high protein expression of E-cadherin (P<0.01) and low expression of N-cadherin, vimentin, p-Akt, p-GSK-3β, and p-Akt/Akt, p-GSK-3β/GSK-3β (P<0.01). Compared with the high-dose GBJ-medicated serum group, high-dose GBJ-medicated serum + SC79 group showed low protein expression of E-cadherin (P<0.01) and high protein expression of N-cadherin, vimentin, p-Akt, p-GSK-3β, p-Akt/Akt, and p-GSK-3β/GSK-3β (P<0.01).ConclusionGBJ can inhibit the migration and EMT of lung cancer A549 cells by regulating the PI3K/Akt signaling pathway.
Abstract:ObjectiveTo observe the effect of Didang Xianxiong decoction on the ultrastructure of myocardium and the expression of connective tissue growth factor (CTGF) and low-density lipoprotein receptor-related protein (LRP) in diabetic rats.MethodThe diabetic rat model was established by the intraperitoneal injection of high-dose streptozotocin (55 mg·kg-1) and the rats were further fed for 3 weeks. Forty model rats were randomly assigned into model group, a Xiao Xianxiongtang (4.05 g·kg-1·d-1) group, Xuefu Zhuyutang (6.30 g·kg-1·d-1) group, Didang Xianxiong decoction (8.10 g·kg-1·d-1) group, and alagebrium chloride (ALT-711, 3 mg·kg-1·d-1) group, with 8 rats in each group. Ten normal healthy rats were randomly selected as the blank group. The corresponding drugs were administrated by gavage, and the blank group and the model group were given distilled water at a dose of 10 mL·kg-1·d-1 for 8 weeks. The myocardial tissue was collected from the rats under anesthesia at the end of the 8th week for pathological examination. The expression of CTGF and its receptor LRP in the myocardial tissue was detected by immunohistochemistry and Western blot.ResultCompared with the blank group, the modeling led to obvious ultrastructural damage of the myocardium, up-regulated the expression of CTGF (P<0.01), and did not significantly change the expression of LRP. Compared with the model group, the drugs alleviated the damage in myocardium ultrastructure, down-regulated the expression of CTGF (P<0.01), and did not significantly change the expression of LRP. Moreover, Didang Xianxiong decoction showed better performance than Xiao Xianxiongtang and Xuefu Zhuyutang (P<0.01).ConclusionDidang Xianxiong decoction may protect myocardial tissue by down-regulating the high expression of CTGF in myocardial tissue of diabetic rats, thereby delaying myocardial fibrosis. The results indicate that the therapy of treating both phlegm and blood stasis has better performance than the simple method of resolving phlegm or stasis.
Abstract:ObjectiveTo study the mechanism of Mahuang Xixin Fuzitang (MXFT) against migraine.MethodTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SiwssTargetPrediction and other databases were used to screen the active components and action targets of MXFT as well as migraine-related targets. The potential protein-protein interaction (PPI) network diagram was plotted for the intersection targets of MXFT and migraine using STRING 11.5. Metascape was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of potential intersection targets. The component-target-pathway network of MXFT was constructed by Cytoscape 3.7.1 to screen core targets with high degree value. Finally, the binding strength between core target and its mapping components was verified by molecular docking, and the core targets with desirable docking results were verified by animal experiments in vivo. Forty eight SD rats were selected, and except the blank group, the other rats were subcutaneously injected with nitroglycerin to prepare the migraine rat model. The modeled rats were randomly divided into model group, positive drug group and MXFT high-, medium- and low-dose groups. The positive drug group was given zolmitriptan tablets, and the MXFT high-, medium- and low-dose groups were given high, medium and low doses of MXFT, respectively. The changes of behavior and pain threshold of rats in each group were observed every other day after modeling. The levels of calcitonin gene-related peptide (CGRP), extracellular signal-regulated kinase 2 (ERK2) and c-fos proto-oncogene (FOS) protein in plasma were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical technique and Western blot were employed to determine the levels of extracellular signal-regulated kinase 1/2 (ERK1/2, also known as MAPK1/3) and protein kinase B 1 (Akt1), protein kinase C α (PRKCA) in trigeminal nerve of SD rats.ResultThe network pharmacology showed that the core targets of MXFT in the treatment of migraine were MAPK1, MAPK3, Akt1, PRKCA, etc., mainly involving neuroactive ligand-receptor interaction signaling pathway, calcium signaling pathway, MAPK signaling pathway, etc. The molecular docking demonstrated that MAPK1, MAPK3, Akt1, PRKCA, PRKCB and PRKCG had good binding ability with their mapping components. The animal experiments indicated that compared with the conditions in the blank group, the number of head scratching in the model group was increased (P<0.01), and the pain threshold was decreased (P<0.01). Compared with the conditions in the model group, the number of head scratching in each administration group was reduced (P<0.01), and the pain threshold was increased (P<0.01). In addition, the levels of CGRP, ERK2 and FOS proteins in plasma, and Akt1, ERK1/2 and PRKCA proteins in trigeminal ganglion of the model group were higher than those of the blank group (P<0.05, P<0.01). The levels of CGRP, ERK2 and FOS proteins in plasma and Akt1, ERK1/2 and PRKCA proteins in trigeminal ganglion of each administration group were lower than those of the model group (P<0.05, P<0.01).ConclusionMXFT had multi-component, multi-target and multi-pathway characteristics in the treatment of migraine, and the mechanism might be related to inhibiting vasodilation, reducing the release of inflammatory factors and inhibiting neuronal hyperactivity.
Abstract:ObjectiveTo analyze the pharmacodynamic material basis of Hippophae Folium in the treatment of hyperlipidemia by network pharmacology and experimental verification.MethodThe hyperlipidemic HepG2 cell model induced by oleic and palmitic acid (molar ratio 2∶1) was established. The optimal concentration of Hippophae Folium containing serum was determined by cell counting kit (CCK)-8 method. The cells were intervened by the medicated serum, and oil red O staining was used to determine the success of the model. The contents of total cholesterol (TC) and triglyceride (TG) were determined by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of action was analyzed by network pharmacology, and molecular docking was performed to detect the binding ability of the potential targets.ResultCCK-8 assay showed that 10% medicated serum was the optimal concentration for cell growth. Oil red O staining proved that the hyperlipidemic cell model induced by oleic and palmitic acid has been built. After treatment with medicated serum, the contents of TG and TC decreased, indicating that Hippophae Folium had a good therapeutic effect on hyperlipidemia. Network pharmacology revealed that the core targets of Hippophae Folium in the treatment of hyperlipidemia were albumin (ALB), peroxisome proliferative activated receptor γ (PPARγ) and matrix metalloprotein(MMP)-9, involving 755 biological processes, 73 molecular functions and 3 cellular components. By Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis, it was found PPAR, hypoxia inducible factor(HIF)-1, AMP-activated protein kinase(AMPK) and other signal pathways were involved in the treatment of hyperlipidemia by Hippophae Folium.ConclusionHippophae Folium containing serum (10%) could reduce lipid accumulation and intracellular TG and TC levels in hyperlipidemic cell model, and its mechanism of action might be realized by activating PPAR signal pathway.
Keywords:Hippophae Folium;hyperlipidemia;mechanism of action;molecular docking
Abstract:ObjectiveTo observe the curative effect of Lishui Xiaogu plaster combined with liver disease therapeutic apparatus on the treatment of refractory ascites due to hepatitis B cirrhosis.MethodA total of 120 cases of refractory ascites due to hepatitis B cirrhosis were randomly divided into a control group and an observation group, with 60 cases in each group. The control group was treated with conventional western medicine and DSG-Ⅲ liver disease therapeutic apparatus, and the observation group was externally applied with Lishui Xiaogu plaster in the liver area and abdomen based on the control group. After 4 weeks of continuous treatment, the weight, abdominal circumference, 24-hour urine volume, the quantitative score of clinical symptoms, liver function, serum endothelin-1 (ET-1), nitric oxide (NO), and interferon-γ (IFN-γ) before and after treatment were observed in the patients of two groups.ResultAfter 4 weeks of treatment, the total effective rate of the observation group was 87.72% (50/57), higher than 67.9% (38/56) in the control group (P<0.05) (χ2=6.411, P<0.05). The changes in abdominal circumference, body weight, and 24-hour urine volume in the two groups were better than those before treatment (P<0.05). In terms of traditional Chinese medicine (TCM) clinical symptom scores, there was no significant difference in the symptoms of appetite, fatigue, sleep, and yellowing of the body and eyes in the control group before and after treatment, and other indexes in the two groups were better than those before treatment (P<0.05). The observation group was better than the control group in improving symptoms such as abdominal distension, hypochondriac pain, appetite, fatigue, and lower limb edema (P<0.05), but there was no significant difference between the two groups in improving sleep and yellowing of the body and eyes. In the experiment, the total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin/globulin ratio (AGR), ET-1, NO, and IFN-γ in the two groups were all better than those before treatment (P<0.05). Except that there was no significant difference between the two groups of TBIL, other indexes in the observation group were better than those in the control group (P<0.05). In terms of portal vein hemodynamics, the portal vein diameter (DPV), the maximum blood flow velocity (Vmax), and portal vein blood flow (Q) in the two groups improved after treatment, and the DPV, Vmax, and Q in the observation group were better than those in the control group (P<0.05).ConclusionExternal application of Lishui Xiaogu plaster combined with liver disease therapeutic apparatus significantly improves the effective rate of refractory ascites due to hepatitis B cirrhosis, and its mechanism is presumedly related to the decreasing of serum NO and ET-1 levels, the increasing of serum IFN-γ level, and the improvement of portal hemodynamics.
Keywords:hepatitis B cirrhosis;refractory ascites;Lishui Xiaogu plaster;Chinese medicine external application;liver disease therapeutic apparatus
Abstract:ObjectiveTo observe the clinical efficacy of modified Bufei Huangqitang combined with acupuncture on moderate-to-severe allergic rhinitis due to deficiency and cold in lung and kidney.MethodA total of 130 patients were divided into a control group (65 cases) and an observation group (65 cases) according to a random number table. The patients in the control group were treated with cetirizine hydrochloride tablets (10 mg per night) combined with mometasone furoate nasal spray (one press on each side,once a day),and those in the observation group were treated with acupuncture (once a day) combined with modified Bufei Huangqitang(1/2 dose each time,twice a day) for 15 days. The rhinoconjunctivitis quality of life questionnaire (RQLQ),total nasal symptom score (TNSS),nasal airway resistance (NAR),and traditional Chinese medicine (TCM) syndrome score of allergic rhinitis with deficiency and cold in lung and kidney syndrome were observed before and after treatment in two groups. The neuropeptide Y (NPY),vasoactive intestinal peptide (VIP),substance P (SP) in nasal secretions, and immune inflammatory markers [eosinophil (EOS),eotaxin (EOT),immunoglobulin E (IgE),and interleukin-33 (IL-33)] in serum were detected. Adverse reactions of the two groups were observed during the study period.ResultThe total effective rate was 96.9% (63/65) in the observation group, higher than 81.5% (53/65) in the control group (χ2=7.943,P<0.05). After treatment,the RQLQ,TNSS,NAR, and TCM syndrome scores in the observation group were lower than those in the control group (P<0.05). The nasal secretions NPY in the observation group was higher than that in the control group (P<0.05),while VIP and SP in the observation group were lower than those in the control group (P<0.05). The serum EOS,IgE, and IL-33 in the observation group were lower than those in the control group (P<0.05), while the serum EOT in the observation group was higher than those in the control group (P<0.05). Adverse reactions occurred in two cases in the control group and one case in the observation group. The incidence of adverse reactions had no statistical significance between the two groups.ConclusionAcupuncture combined with modified Bufei huangqitang can significantly relieve the clinical symptoms of moderate-to-severe allergic rhinitis due to deficiency and cold in lung and kidney and improve the serum immune inflammatory markers, with good safety.
Keywords:acupuncture;Bufei Huangqitang;allergic rhinitis;deficiency and cold in lung and kidney syndrome
Abstract:ObjectiveTo observe the clinical effect of Tianma Goutengyin combined with acupuncture on adult patients with tic disorder of ascendant liver-yang hyperactivity.MethodThe 64 adult patients with tic disorder of ascendant liver-yang hyperactivity who were treated in the outpatients and inpatients of the 989th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from January 2019 to December 2020 were selected and classified into the control group (32 cases) and the treatment group (32 cases) with the random number table method. The control group took oral western medicine Duloxetine Hydrochloride Enteric Capsules, and the treatment group was treated by Tianma Goutengyin and acupuncture. The treatment lasted 8 weeks for both groups and the efficacy was observed.ResultThe traditional Chinese medicine (TCM) syndrome score, Yale Global Tic Severity Scale (YGTSS) score, total bile acid (TBA), triglyceride (TG), and partial pressure of carbon dioxide (PaCO2) were significantly lower, and the Na+ concentration and partial pressure of oxygen (PaO2) were significantly higher than those before treatment in both groups (P<0.05). After treatment, the TCM syndrome score, YGTSS score, and TBA were significantly lower, and and the Na+ concentration and PaO2 were significantly higher than in the treatment group than in the control group (P<0.05). The efficacy on TG and PaCO2 was similar in the two groups. The total clinical effective rate of the treatment group was 90.6% (29/32), as compared with the 64.5% (20/31) of the control group (χ2=6.210, P<0.05). The incidence of clinical adverse reactions in the treatment group was 12.5% (4/32) in comparison with the 35.5% (11/31) in the control group (χ2=4.585, P<0.05). The recurrence rate in the treatment group (9.4%, 3/32) was lower than that (32.3%, 10/31) in the control group (χ2=5.035, P<0.05).ConclusionThe combination of Tianma Goutengyin and acupuncture can remarkably alleviate the clinical symptoms of adult tic disorder patients with ascendant hyperactivity of liver yang, reduce TBA, TG and PaCO2, and increase the concentration of Na+ and PaO2. Patients treated with the combination show small adverse reactions and low recurrence rate.
Keywords:Tianma Goutengyin;acupuncture;ascendant hyperactivity of liver yang;tic disorder;clinical efficacy
Abstract:ObjectiveTo explore the dynamic evolution law of syndrome elements in different stages of chronic obstructive pulmonary disease (COPD).MethodThe clinical questionnaire of COPD was formulated,and the clinical data of 303 patients with COPD in the acute exacerbation stage,risk window stage,and stable stage in the First Affiliated Hospital of Henan University of Chinese Medicine from June 2019 to December 2020 were dynamically collected. The Clinical Investigation and Research Database on the Evolution of Syndrome Elements of COPD was established,with syndrome elements as nodes and complex relationships between syndrome elements and syndrome elements in different stages as edges. With the help of Pycharm (JetBrains PyCharm Edition 2018.2.3) development tool,python programming was used to preprocess the data and perform complex network modeling. The complex network of different stages of COPD was constructed to analyze the evolution law of syndrome factors in different stages.ResultA total of 303 patients with COPD were included and finished. Eleven syndrome elements were extracted in the acute exacerbation stage,10 syndrome elements were extracted in the risk window stage,and 8 syndrome elements were extracted in the stable stage. According to the complex network centrality and edge weight of disease syndrome elements,it was found that the core nodes of disease syndrome elements in the network from the acute exacerbation stage to the stable stage were phlegm,heat,and Qi deficiency,Qi deficiency,phlegm,and dampness,and Qi deficiency,Yin deficiency,and blood stasis.ConclusionFrom the acute exacerbation stage to the stable stage,the disease syndrome elements change from excess to deficiency,and phlegm heat gradually changes into phlegm dampness,and gradually weakens or disappears. Qi deficiency runs through the whole process of the disease and turns into both qi and yin deficiency with blood stasis.
Keywords:chronic obstructive pulmonary disease;complex network;syndrome elements;evolution law
Abstract:ObjectiveTo analyze the changes of volatile organic compounds (VOCs) and bacterial community characteristics in rhizosphere soil during the growth of Rehmanniae Radix, as well as the relationship between VOCs and bacterial community structure, so as to lay the foundation for the evaluation of the characteristics of continuous cropping soil and the regulation of continuous cropping soil microorganisms.MethodThe rhizosphere soil during the three main growth periods of Rehmanniae Radix in July, August and October was used as the research object. Gas chromatography-mass spectrometry (GC-MS) was used to determine the relative contents of VOCs in ethyl acetate and dichloromethane parts in rhizosphere soil. The characteristics of rhizosphere bacterial community structure was determined by high-throughput sequencing, SPSS 24, SIMCA 14.1 and other software were used to analyze the differences of VOCs and bacterial community structure in rhizosphere soil of the three periods, and the main VOCs and iconic bacteria that caused the differences were screened, and the correlation between VOCs and bacterial community structure was analyzed.ResultThere were differences in VOCs in different parts of rhizosphere soil during the three growth stages of Rehmanniae Radix. Among them, and the main VOCs that cause differences were dioctyl isophthalate, 2-octyl-1-dodecanol and 2-ethylhexyl p-toluic acid in the ethyl acetate part, and 1,3-benzenedicarboxylic acid, di (2-propylpentyl) phthalate and 2-ethylhexyl p-toluenecarboxylic acid in the dichloromethane part. From the seedling stage to the end of tuber enlargement of Rehmanniae Radix, the relative abundance of dominant bacteria such as Actinobacteria, Firmicutes and Chloroflexi in the rhizosphere soil was gradually decreased, and there were unique bacterial communities in rhizosphere soil of each growth stage. Correlation analysis showed that the VOCs in rhizosphere soil of Rehmanniae Radix had an impact on the rhizosphere bacterial community structure, especially the components of esters and alcohols.ConclusionDuring the growth of Rehmanniae Radix, the characteristics of rhizosphere soil are mainly manifested in the content changes of main VOCs such as esters and alcohols and the gradual decrease of the abundance of the main beneficial bacteria, and the VOCs in rhizosphere soil play a certain role in shaping the structure of bacterial community.
Abstract:ObjectiveTo study the constituents migrating to blood of Qingyan formula by serum pharmacochemistry, and investigate the binding energy between these constituents and estrogen receptor (ER), so as to confirm the pharmacodynamic material basis of Qingyan formula in rats.MethodUltra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry (UPLC-Q-Orbitrap-MS) was used to determine the constituents migrating to blood of Qingyan formula in rats by comparing the fingerprint differences of 70% ethanol extract of Qingyan formula, 70% ethanol extract of each single drug in this formula, blank serum and serum after administration of 70% ethanol extract of Qingyan formula, according to the retention time, relative molecular weight and the primary and secondary ion fragments provided by MS. Mobile phase was 0.1% formic acid aqueous solution (A)-acetonitrile(B) for gradient elution (0-5 min, 2%-20%B; 5-10 min; 20%-50%B; 10-15 min, 50%-80%B; 15-25 min, 80%-95%B; 25-26 min, 95%-2%B; 26-30 min, 2%B), the flow rate was 0.3 mL·min-1 and the injection volume was 5 μL, electrospray ionization was used with detection range of m/z 150-2 000, positive and negative ion scanning modes. Molecular docking technology was used to characterize the binding energy of constituents migrating to blood with ERα and ERβ, and to confirm the material basis of this formula.ResultAfter oral administration of Qingyan formula, 30 components were detected in serum, of which 9 were prototype components and 21 were metabolites. Nine prototype components were identified as monotropein, asperuloside, verbascoside, β-ecdysone, allantoin, deacetyl asperuloside acid, echinacoside, betaine and caffeic acid, 21 metabolites mainly included organic acids, amino acids, cholines and so on. The binding energies of the above 9 prototype components with ERα were -6.7, -8.9, -6.0, -5.7, -5.3, -4.9, -7.3, -3.3, -6.3 kcal·mol-1 (1 kcal≈4 184 J), and the binding energies of them with ERβ were -6.6, -7.2, -7.7, 8.0, -7.4, -5.5, -6.9, -3.6, -6.4 kcal·mol-1, respectively.ConclusionThese nine prototype components into blood are the active ingredients of Qingyan formula that play estrogen-like role in the body, which can provide experimental basis for the formulation of quality standards and subsequent research and development of Qingyan formula.
Keywords:Qingyan formula;serum pharmacochemistry;molecular docking;prototype components;fingerprint;estrogen receptor (ER);ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry (UPLC-Q-Orbitrap-MS)
Abstract:ObjectiveTo find the different metabolites of Schisandrae Chinensis Fructus fresh fruits dried in different ways by proton nuclear magnetic resonance (1H-NMR) metabonomics technology, and to explore the possible effect of green removing on its metabolic profile.MethodFifteen samples of Schisandrae Chinensis Fructus fresh fruits were used, and each 3 samples was divided into one group. The samples were processed by five methods, including drying, drying in the sun, microwave, blanching and steaming. These samples were extracted with 50% methanol and analyzed by 1H-NMR. Combined with multivariate statistical analysis, the differences of the metabolic profile between green removing samples and dried samples, sun-dried samples were compared.ResultA total of 27 chemical components were identified by 1H-NMR and Chenomx database, mainly including amino acids, alkaloids, carbohydrates and organic acids. These metabolites were mainly involved in the energy metabolism of fruit postharvest physiology. The results of multivariate statistical analysis showed that there were significant differences among the 5 groups. The dried and sun-dried samples were used as the controls, 17 differential metabolites (asparagine, citric acid, glucose, sucrose, choline glycerophosphate, trigonelline, alanine, lysine, glycerol, leucine, isoleucine, valine, uridine, threonine, methionine, phenylalanine and fructose) were screened by variable importance in the projection (VIP) value and S-plot. One-way ANOVA was used for comparison between groups, the results showed that compared with dried and sun-dried samples, the contents of sucrose and choline glycerophosphate increased significantly (P<0.05, P<0.01) in samples treated with green removing, but the contents of valine, leucine, isoleucine, threonine, phenylalanine and methionine decreased significantly (P<0.01), the content of asparagine increased significantly (P<0.05, P<0.01) in samples treated by microwave, while the contents of trigonelline and uridine decreased significantly (P<0.01) in samples treated by blanching.ConclusionThe consumption, decomposition and/or transformation of active ingredients may be inhibited by interfering with its energy metabolism after the green removing of Schisandrae Chinensis Fructus fresh fruits.
Abstract:ObjectiveIn the previous stage,our research group isolated Pseudomonas ZL8 from Polyporus umbellatus, which has a broad-spectrum inhibitory effect on plant pathogenic fungi such as Fusarium oxysporum of Salvia miltiorrhiza and promotes plant growth. On this basis, this study optimized the fermentation medium and conditions of Pseudomonas ZL8,to improve the number of bacteria in the fermentation broth per unit volume, and provide a basis for the development and application of this strain.MethodThe growth curve of strain ZL8 in LB culture medium was determined and its growth law in liquid medium was clarified. With the number of live bacteria in the fermentation broth of strain ZL8, the dry weight of the bacteria and the A600 value of the broth as detection indicators, single factor investigation was carried out on different nitrogen sources,carbon sources and inorganic salts to determine the optimal medium components. Additionally, orthogonal test was conducted to optimize the component ratio to screen the optimal fermentation medium. Similarly, single factor investigation and orthogonal test were also carried out in four aspects: inoculation amount,culture temperature,time and rotating speed to obtain the optimal culture conditions.ResultThe optimal medium for liquid fermentation of strain ZL8 was peptone 15 g·L-1, glucose 7.5 g·L-1, and potassium chloride 10 g·L-1. After 48 h of fermentation,the number of viable bacteria in the fermentation liquid could reach 8.93×109 cfu·mL-1,3.93 times that of LB liquid medium (P<0.01). The optimal fermentation conditions were as follows: inoculation amount 3%, temperature 28 ℃, time 72 h,and rotating speed 220 r·min-1, and the number of viable bacteria in the fermentation broth could reach 6.37×1010 cfu·mL-1.ConclusionCompared with LB culture medium and the initial fermentation conditions,the optimized culture medium and conditions could effectively increase the bacterial volume of strain ZL8 per unit volume and prolong the stable growth of the strain, with low medium cost, which provided a theoretical basis for the efficient fermentation and application of Pseudomonas ZL8.
Keywords:Pseudomonas ZL8;endophytic fungus of Polyporus umbellatus;biocontrol bacteria;optimization of culture medium;optimization of fermentation conditions
Abstract:Objective and MethodChemical components in four varieties of Moringa Folium (MF); traditional Indian YD, modified species of Indian species PKM1, modified species of PKM1 species PKM2, and red river No.1 variety HH) were qualitatively analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography mass spectrometry(GC-MS), and potential mechanism and material basis of MF in the treatment of constipation were revealed based on network pharmacology.ResultData of accurate relative molecular mass and fragment ions in primary and secondary mass spectra in both positive and negative ion modes were acquired by UPLC-Q-TOF-MS, and then 20 nonvolatile components were identified from the four varieties by comparison with references and consulting literature reports. Nineteen volatile components were identified by comparing mass spectrometry information and that in NIST (version 1.7) based on GC-MS, and 674 chemical component targets were predicted using SwissTargetPrediction and SEA after integration and duplicate elimination. A total of 1 086 constipation-related targets were predicted using GeneCards. With Venny, 88 intersection targets were obtained by mapping chemical component targets and disease targets and venny diagram was drawn. STRING and Cytoscape were used to plot protein-protein interaction(PPI) network diagram. Gene ontology(GO) function analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis were completed through Metascape, which indicated that MF treated constipation mainly via thyroid hormone signaling pathway, advanced glycation end products/receptor for advanced glycation end products(AGE/RAGE) signaling pathway, and cancer signaling pathway. Additionally, the "component-target-pathway" map was plotted by Cytoscape, which predicted that the key components of MF in the treatment of constipation were adenosine, astragalin, geranylacetone, 2-methyloctan-3-one, palmitic acid and oleamide. Also, we inferred that the core targets might be prostaglandin-endoperoxide synthase 2(PTGS2), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), alpha 2A adrenergic receptor(ADRA2A), and interleukin (IL)-6, which distributed in multiple tissues such as colon, small intestine, and rectum.ConclusionThis study clarified the volatile and non-volatile divisions in four varieties of MF comprehensively, and explained that MF treated constipation by reducing inflammatory state and promoting intestinal movement and secretion of intestinal fluid, which provided reference for further quality evaluation and clinical research of MF.
Keywords:Moringa Folium;network pharmacology;constipation;ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS);gas chromatography mass spectrometry(GC-MS)
Abstract:Relativity between prescription and syndrome is a theory of clinical syndrome differentiation by exploring the inherent laws between prescriptions and diseases, and it is also a unique syndrome differentiation thoughts, which is the core and essence of syndrome differentiation and treatment. Relativity between prescription and syndrome was initially recorded in Treatise on Febrile Diseases(《伤寒论》). Prescriptions include empirical prescription, classic prescription, and current prescription. Syndrome is symptom, but also pathogenesis. Relativity between prescription and syndrome means that the prescription corresponds to pathogenesis. The disease manifests itself differently in different patients, meanwhile the symptom changes at different stages. Therefore, simply applying the original classic prescription cannot better reflect the syndrome differentiation principle of “changing treatment with syndromes”, nor does it solve complex clinical problems. Mastering the principle of relativity between prescription and syndrome can improve the accuracy of the syndrome differentiation and understand the constant changes, thus grasping the core and essence of the syndrome differentiation. The classic prescription and its syndrome have the most fixed relationship, so that the classic prescription can be used as a typical representative to explore the relativity between prescription and syndrome. Based on Treatise on Febrile Diseases, this paper summarized the relativity between prescription and syndrome into nine principles, including using medical classics to classify syndromes, using prescriptions to classify syndromes, focusing on the main syndromes, changing prescriptions when the main syndromes change, changing medicines with syndrome changing, modifying prescriptions according to syndromes, changing dosage according to syndromes, syndrome differentiation according to pulse, and syndrome differentiation according to time. Through analyzing the content in Treatise on Febrile Diseases, this paper described the application of the nine principles to explore the scientific connotation and improve the accuracy of syndrome differentiation, thereby expanding the range of classic prescription applications and providing references for the flexibly application of classic prescriptions and improvement of clinical efficacy.
Keywords:relativity between prescription and syndrome;principle;Treatise on Febrile Diseases;classic prescriptions;theoretical discussion
Abstract:With high incidence and lethality rate and certain disability rate, tumor has become a major global public health threat. It has been verified that the occurrence and development of tumor are resulted from the synergy of environment, heredity, and gene mutation, involving the abnormal activation or inhibition of a variety of related pathways such as oxidative stress, inflammation, autophagy, and mesenchymal transition of cells. Among them, the excessive activation of inflammatory signaling pathway is one of the main mechanisms of carcinogenesis and tumor progression, which enhances the proliferation, chemoradiotherapy resistance, invasion, and metastasis of cancer cells. At the moment, the correlation between long-term chronic uncontrollable inflammation and "inflammation-cancer transformation" has been widely recognized. Therefore, it is of great significance for the prevention and treatment, diagnosis, and prognosis evaluation of tumor to clarify the role of inflammation in the incidence of tumor. Blockers or activators have been developed to target the corresponding inflammatory pathways. However, tumor is accompanied by the abnormality of multiple inflammatory pathways, especially the advanced tumor with metastasis of cancer cells, and thus the efficacy of single pathway-targeting agents is non-ideal. Chinese medicine, featuring multiple components and multiple targets, can remarkably control the inflammatory response, delay tumor progression, enhance the sensitivity of tumor cells to radiotherapy and chemotherapy, and reduce postoperative infection and the adverse reactions caused by radiotherapy and chemotherapy, thereby exerting the anti-cancer effect. Nevertheless, a few reports on the anti-tumor effect of Chinese medicine from the perspective of inflammation are available. Therefore, this paper mainly expounds the influence of inflammation on the occurrence and development of tumor and summarizes the research on the intervention of tumor by Chinese medicine through inflammatory pathway, which is expected to provide a new mindset for the prevention and treatment of tumor.
Abstract:Platform method is a modeling method that forces experimental animals to stand on the platforms for a long time without rest by taking advantage of the rodent's fear of water. The application time and node of platform method in model construction can be adjusted according to the needs of different types of animal models. At present, the research hotspot of platform method focuses on constructing animal models of sleep deprivation, anxiety and depression and other mental diseases as well as fatigue. In recent years, with the development of the modernization of traditional Chinese medicine (TCM), this method has been gradually applied to the study of TCM syndrome model and TCM disease and syndrome combination model with "heart","liver" and "spleen" as the centers. Due to the extensive application of platform method and the diversity of modeling diseases, there is still a lack of systematic discussion on this method as the core. This paper systematically summarized the research in China and abroad and explored the application of platform method in animal models of human diseases from three dimensions: its development process, current application and problems and future development. In addition, through the analysis of the research hotspots on sleep deprivation, mental diseases, fatigue, TCM syndrome model and TCM disease and syndrome combination model,the ideas and specific applications of platform method in construction of various animal models were discussed. This paper was expected to provide reference for researchers and promote further exploration and research of this modeling method.
Keywords:platform technique;modified multiple platform method (MMPM);traditional Chinese medicine (TCM) disease and syndrome combination;fatigue;sleep deprivation;depression;anxiety;mania
Abstract:Atherosclerosis (AS) is a chronic multifactorial vascular disease and a major pathological basis of cardiovascular diseases. It mainly occurs in the middle-aged and elderly and causes high mortality. Apoptosis is a form of spontaneous programmed death. Under pathological conditions, the apoptosis of vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and macrophages is the key factor of the occurrence and development of AS. The apoptosis of VECs may be an early event that promotes the formation and progression of AS lesions, while the subsequent apoptosis of VSMCs and macrophages accelerates the formation of AS unstable plaques and plays a key role in the late stage of AS. Therefore, apoptosis may provide a new target for the treatment of AS. Increasing evidence has demonstrated that Chinese medicine plays a positive role in the treatment of AS by regulating apoptosis factors and apoptosis-associated signaling pathways. However, the studies about the treatment of AS with Chinese medicine from apoptosis have not been systematically reviewed. Therefore, we reviewed the relevant literature and systematically summarized the molecular mechanisms of apoptosis. Specifically, we focused on mitochondrial apoptosis pathway, death receptor apoptosis pathway, endoplasmic reticulum stress apoptosis pathway and explored the role of apoptosis in AS. Further, we reviewed the progress in the role and mechanism of Chinese medicine in regulating apoptosis against AS, aiming to provide a theoretical basis for the treatment of AS and the development of drugs.
Keywords:apoptosis;vascular endothelial cells;vascular smooth muscle cells;macrophages;atherosclerosis;Chinese medicine
Abstract:Malignancies are diseases resulting from an imbalance of cell growth and proliferation, endangering human health and life. Currently, there is no clinically effective treatment for tumors. Tumor cells may alter cell adhesion and tumor cell migration and movement by degrading the extracellular matrix, generating vascular factors, affecting epithelial-mesenchymal transformation, or altering the tumor microenvironment. The mechanisms which lead to multidrug resistance (MDR) are the regulation of membrane proteins, apoptosis-regulated gene expression, enzyme-mediated multidrug resistance, DNA damage repair, and epithelial-stromal transformation, resulting in ineffective treatment of tumors. Therefore, the search for natural, safe, and effective chemosensitizers has become a critical part in tumor research. Due to the increasing use of Chinese medicine in cancer treatment, researchers have conducted more extensive studies on its monomers and compounds. In addition, the mechanisms of Chinese medicine in inhibiting tumor invasion and metastasis and reversing drug resistance are gradually unraveled. The monomers and compounds of Chinese medicine may inhibit tumor invasion, metastasis, and drug resistance by enhancing the sensitivity of chemotherapy drugs and adjuvant properties. Furthermore, they can also improve the tolerance of patients to chemotherapy drugs, relieve side effects of chemotherapy, reduce the chance of recurrence, and prolong the life of patients. The development of traditional Chinese medicine plays an important role in reducing tumor recurrence and metastasis, reversing drug resistance, prolonging the prognosis of cancer patients, improving their quality of life, and prolonging their survival time. Currently, various types of Chinese medicines have been proven to be capable of reducing tumor invasion and metastasis, and reversing drug resistance. The present article reviewed development and findings of Chinese medicine as an anti-tumor invasion, anti-metastasis, and anti-tumor resistance therapy in recent years, in order to provide ideas for future research on anti-tumor effect of active components in Chinese medicine.
Keywords:Chinese medicine;tumor;invasion and metastasis;multidrug resistance;mechanism of action
Abstract:The massive accumulation of β-amyloid (Aβ) in the brain is believed to be the first pathological mechanism of Alzheimer's disease (AD), and the accumulation is mainly resulted from the overproduction and dysfunction in the clearance. Extensive and in-depth research has been carried out on AD. In addition to the drugs which are commonly used in clinical settings to improve cognitive function, Aβ monoclonal antibody aducanumab (Aduhelm) has been successfully marketed in the US, which may delay the progress of AD. Thus, it is a potential method for the treatment of AD to target Aβ, but it is expensive, with many adverse reactions and contraindications, which hinders the clinical promotion. Traditional Chinese medicine, featuring multiple components, multiple targets, multiple pathways, and high safety, can regulate the level of Aβ deposition in the brain, alleviate neurotoxicity, and prevent and treat AD by inhibiting the production and aggregation of Aβ and promoting the clearance in the brain. Berberine, gallic acid, osthole, scutellaria barbata flavonoids, Huannao Yicong decoction and Ditantang can promote α-secretase and inhibit the activity and expression of β- and γ-secretase, thus reducing production of Aβ. Baicalein, aloe-emodin, gallic acid, and curcumin can suppress the aggregation of Aβ, promote its depolymerization, and reduce the toxic effect of Aβ on nerve cells by interacting with the hydrophobic structure of Aβ and the H bond, salt bridge, and β-sheet that mediate the aggregation of Aβ. Curcumin and resveratrol can promote the expression of triggering receptor 2 in bone marrow cells of microglia and the migration and phagocytosis of Aβ in microglia. Bilobalide, Kaixinsan and curcumin can up-regulate the expression of encephalin-degrading enzyme and insulin degrading enzyme to promote Aβ degradation, and geniposide, dihydrotanshinone, dihydroartemisinin, and curcumin can degrade Aβ in cells by activating normal autophagy or inhibiting abnormal autophagy. Cycloastragenol, Danggui Shaoyaosan, Yizhi Fangdai formula and Linggui Zhugan decoction can promote the outflow of Aβ and inhibit the inflow of Aβ by improving the integrity and permeability of the blood-brain barrier (BBB). Yizhi Fangdai formula and Xueshuantong can promote the polarization of aquaporin 4(AQP4), allow Aβ to be cleared through the lymphatic system, and reduce the aggregation of Aβ in the brain, thereby relieving or preventing nerve cell damage and improving cognitive function. The above summary aims to provide more sufficient evidence and ideas for the clinical treatment of AD with traditional Chinese medicine.
Abstract:Chinese materia medica is the material basis of the development of traditional Chinese medicine, but the rapid growth of the demand for Chinese materia medica resources and environmental deterioration make a large number of wild medicine resources endangered. At present, artificial cultivation of Chinese medicinal materials is the main way to alleviate the contradiction between supply and demand in the market, but the production and quality of medicinal materials are seriously affected by the lack of process control, specialization and fine management in medicinal plant cultivation. Early prediction and evaluation of the growth, yield, diseases and insect pests of medicinal plants is an important technical means to guarantee the yield and quality of Chinese medicinal materials, and effective and non-destructive process monitoring technology is the prerequisite for realizing the modernization of Chinese medicine agriculture. With the advantages of rapid, non-destructive and accurate detection, hyperspectral remote sensing has been widely used in recent years for plant growth information extraction and yield assessment, as well as monitoring crop growth and response to adversity stress, becoming an important technical tool for precision agricultural production such as quality monitoring and pest and disease prevention. Therefore, combined with hyperspectral data processing and analysis methods, the application of hyperspectral remote sensing technology in monitoring plant physiological characteristics, environmental stress, resource investigation and quality inspection of medicinal materials is systematically reviewed, and combined with the characteristics of medicinal plants, the application prospect of hyperspectral remote sensing technology in improving the monitoring ability of production process of Chinese medicinal materials, realizing real-time dynamic monitoring of medicinal materials cultivation, developing early diagnosis technology of pests and diseases for nondestructive detection, and establishing quality traceability of high-quality Chinese medicinal materials is discussed, in order to solve the related problems in precision cultivation of Chinese medicine agriculture by hyperspectral remote sensing technology, and provide new ideas and solutions for the sustainable utilization of Chinese medicine resources and the development of intelligent Chinese medicine agriculture.
Keywords:hyperspectral remote sensing;medicinal plant;non-destructive detection;dynamic monitoring;stress;pest and disease prevention and control;artificial intelligence (AI)
Abstract:Type 2 diabetes mellitus (T2DM),as a chronic disease with an increasing prevalence,has greatly affected the quality of life of patients, and aroused widespread concern in society. Previous studies have shown that inflammation is closely related to the occurrence and development of T2DM. The role of inflammatory response and its signaling pathway in the pathogenesis of T2DM has become a research hotspot,and the intervention of inflammatory response to control the progression of T2DM has become a new approach for treatment. With the deepening in the research field of traditional Chinese medicine (TCM),the generation of inflammation is attributed to turbid phlegm and blood stasis, whose mutual transformation results in the impairment of body functions. However,the monomers and compounds of Chinese medicine in the treatment of T2DM based on inflammatory signaling pathways are advantageous in multiple targets,multiple pathways, and few side effects,which can significantly relieve the symptoms of T2DM. In recent years,there has been an increasing number of studies on TCM intervention in T2DM. The present article elaborated the understanding of the relationship between T2DM and inflammation in TCM and the seven signaling pathways related to the regulation of inflammation in T2DM by TCM, including nuclear transcription factor-κB (NF-κB) signaling pathway,mitogen-activated protein kinase (MAPK)-dependent signaling pathway,phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway,protein kinase C (PKC) signaling pathway,adenosine 5′-monophosphate (AMP)-activated kinase (AMPK) signaling pathway,Wnt signaling pathway,and transforming growth factor-β (TGF-β) signaling pathway.
Keywords:type 2 diabetes mellitus;inflammatory response;inflammatory signaling pathway;traditional Chinese medicine
Abstract:Endometriosis(EMs) is a common chronic inflammatory gynecological disease,affecting about 5%-10% of women of childbearing age worldwide,and has always been a major challenge in clinical treatment. Huposan, derived from the Experiential Prescriptions for Universal Relief (《普济本事方》), has the effects of moving qi, activating blood,expelling blood stasis, and relieving pain. It is often used to treat EMs clinically and has achieved good curative effect. The relevant studies on the treatment of EMs by Huposan were retrieved from databases, such as CNKI,PubMed,Wanfang Data, and VIP for summarizing the mechanisms of action and clinical application of Huposan in the treatment of EMs, aiming to provide ideas and references for the basic research and clinical application of Huposan. As revealed by basic experiments,Huposan could exert therapeutic effects on EMs through resisting cell adhesion by reducing intercellular adhesion molecule 1(ICAM-1)content,decreasing concentrations of matrix metalloproteinase(MMP)-2 and MMP-9 against ectopic endometrial invasion,inhibiting vascular endothelial growth factor(VEGF)expression for antiangiogenesis,inhibiting the expression of tumor necrosis factor-α(TNF-α), interleukin (IL)-6, and IL-1,reversing helper T cell(Th)1/Th2 balance shifts to regulate the body's immune mechanism,and reducing the serum levels of nitric oxide(NO)and nitric oxide synthase(NOS). In clinic practice,Huposan has the effects of reducing ectopic lesions,relieving pain symptoms,reducing serum carbohydrate antigen 125(CA125)content,improving hormone levels,regulating endocrine and immune factors,and reducing postoperative recurrence rate. Huposan plays a therapeutic role in EMs through multiple targets and mechanisms,which is worthy of further exploration and clinical promotion.
Abstract:Ischemic stroke, an acute cerebrovascular disease caused by sudden arterial occlusion, is characterized by high morbidity, high mortality, and high disability rate. It is a major cause of the occurrence and death of neurologic diseases in the world. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is a classic pathway for cellular metabolism, growth, and apoptosis. In recent years, Chinese medicine has played an important role in the treatment of ischemic stroke because of the small side effects and wide range of targets and has received extensive attention. The compound prescriptions and extracts of Chinese medicines can treat diseases via multiple targets and pathways. Researchers have extensively studied the occurrence and development of ischemic stroke and the pathophysiological mechanism of drug intervention in the treatment of ischemic stroke and have demonstrated that PI3K/Akt signaling pathway plays a key role in this process. The PI3K/Akt signaling pathway is involved in the occurrence and development of ischemic stroke by regulating pathophysiological processes such as inflammation, oxidative stress response, apoptosis, and autophagy, in which Chinese medicines play a regulatory role. This paper reviews the relationship between PI3K/Akt signaling pathway and ischemic stroke and the mechanism of Chinese medicine in treating ischemic stroke by regulating PI3K/Akt signaling pathway, aiming to provide a new theoretical basis for the clinical treatment of stroke.
Keywords:phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway;Chinese medicine;ischemic stroke;mechanism of action
Abstract:Cell pyroptosis is a programmed death of inflammatory cells. Many members of the gasdermin family (the effector protein family that forms pores) participate in the pathological process of a variety of diseases, such as cancer, myocardial ischemia, renal injury, and osteoarthritis, mainly by activating cysteine aspartate-specific protease (Caspase) for polymerization and shear. Cell pyroptosis has bidirectional regulation. Induction of pyroptosis can promote cell clearance under pathological conditions (such as cancer and tumor cells), but long-term induction of pyroptosis can lead to abnormal lipid and related vitamin metabolism in vivo. Regulating the balance between cell pyroptosis and proliferation is an important target for traditional Chinese medicine (TCM) treatment of diseases. The Yin-Yang theory runs through the whole process of TCM diagnosis and treatment, which is used to explain the physiological and pathological changes of human body and guide the theory, diagnosis and treatment of diseases and health care. The balance between cell proliferation and pyroptosis is essentially the embodiment of Yin-Yang balance at the cellular level, and the theory of Yin-Yang spontaneous harmonization dominates the balance. TCM intervention on cell pyroptosis is mainly reflected in promoting and inhibiting cell pyroptosis, which has the same significance as Yin-Yang regulation. Based on this theory, this paper revealed the relationship between TCM inhibiting and promoting cell pyroptosis through the Yin-Yang theory, to provide theoretical support for the modernization of the Yin-Yang theory and new goals for the diagnosis and treatment of diseases.
Keywords:cell pyroptosis;traditional Chinese medicine;Yin-Yang theory;Yin-Yang regulation;cysteine aspartate-specific protease (Caspase);gasdermin family