Abstract：ObjectiveTo explore the effect of Chaishao Liujuntang on Hedgehog signaling pathway in rats with chronic atrophic gastritis （CAG） of liver depression and spleen deficiency.MethodWistar rats were randomized into normal group and modeling group. CAG with the liver depression and spleen deficiency syndrome was induced in rats in the modeling group with a compound method. After modeling， they were classified into the model group， vitacoenzyme group， Chaishao Liujuntang group， GDC-0449 （blocker） group， and Chaishao Liujuntang + GDC-0449 group. Normal group and model group were given （ig） normal saline. Vitacoenzyme and Chaishao Liujuntang group received （ig） corresponding drugs at 240 mg·kg-1·d-1 and 5.1 g·kg-1·d-1， respectively， and GDC-0449 group was treated （ip） with GDC-0449 at 50 mg·kg-1·d-1. For the Chaishao Liujuntang + GDC-0449 group， rats received GDC-0449 （ip） at 50 mg·kg-1·d-1 and Chaishao Liujuntang （ig） at 5.1 g·kg-1·d-1. The administration lasted 4 weeks. The pathological morphology of rat gastric mucosa was observed based on hematoxylin-eosin （HE） staining. mRNA and protein expression of sonic hedgehog （Shh）， 12th transmembrane receptor Patched1 （Ptch1）， and glioma-associated oncogene homolog 1 （Gli1） in gastric mucosa tissues was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot. Content of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA）.ResultCompared with normal group， the model group demonstrated decrease in gland cells， glandular atrophy， large lumen volume， plasma cell infiltration， intestinal metaplasia， decrease in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa （P<0.01）， and rise of serum IL-1β and TNF-α content （P<0.01）. Compared with model group， vitacoenzyme group and Chaishao Liujuntang group showed ordered cells， alleviation of gland atrophy， and no obvious inflammatory infiltration， and GDC-0499 group and Chaishao Liujuntang + GDC-0449 showed no significant improvement. Significant rise in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa tissues of vitacoenzyme group and Chaishao Liujuntang group （P<0.01）， no significant difference in serum IL-1β content and significant decrease in TNF-α content in vitacoenzyme group （P<0.01）， significant reduction in content of serum IL-1β and TNF-α in Chaishao Liujuntang group （P<0.05， P<0.01） were observed compared with those in the model group. The mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa and the content of serum IL-1β and TNF-α were insignificantly different between the GDC-0449 group and Chaishao Liujuntang + GDC-0449 group.ConclusionChaishao Liujuntang can effectively improve the pathological state of gastric mucosa in CAG rats with liver depression and spleen deficiency， which may be related to the activation of Hedgehog signaling pathway and the decrease of IL-1β and TNF-α content.
Abstract：ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease （AD） under the guidance of the theory of "interior-exterior relationship between heart and small intestine".MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 （Aβ1-42）. The rats were then randomly divided into the blank group， sham-operated group， model group， low-， medium-， and high-dose （5.6， 11.2，22.4 g·kg-1·d-1） Qishengwan groups， and donepezil （0.46 mg·kg-1·d-1） group. After medication for 28 successive days， the spatial memory ability of rats was observed in water maze test， and the levels of Aβ1-42， nuclear transcription factor-κB （NF-κB）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in the hippocampus were analyzed by enzyme-linked immunosorbent assay （ELISA）. Additionally， the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora.ResultCompared with the blank group and sham-operated group， the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings （P<0.05， P<0.01） and elevated Aβ1-42 content in the hippocampus （P<0.01） and central inflammatory factors NF-κB， TNF-α， and IL-6 （P<0.05， P<0.01）. Compared with the model group， Qishengwan at each dose significantly alleviated the impaired spatial memory function （P<0.05， P<0.01）， improved the deposition of Aβ1-42 in the hippocampus of rats （P<0.05， P<0.01）， and reduced the expression of central nervous system inflammatory factors （P<0.05， P<0.01）， thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased （P<0.01）， while that of Escherichia-Shigella was reduced （P<0.05， P<0.01）. Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae.ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats， which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae， the attenuation of the central neuroinflammatory response， and the reduction of central Aβ1-42 deposition.
Abstract：ObjectiveTo explore the pharmacodynamic effect of gramine on 2，4-dinitrochlorobenzene （DNCB）-induced atopic dermatitis （AD） in mice and its potential mechanism.MethodThe mice were divided into the normal control group， model group， dexamethasone （0.05 g·kg-1） group， and high- and low-dose （0.12，0.06 g·kg-1） gramine groups. Mice in all groups except for the normal control group were stimulated with DNCB， followed by medication 13 d later. The changes in skin lesions were then observed， and the skin thickness， moisture content， and transepidermal water loss （TWEL） in each group were measured. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining， and the effects of drugs on CD4+/CD8+T-cell ratio in the spleen were detected by flow cytometry. The levels of immunoglobulin E （IgE）， interleukin （IL）-4， and IL-6 in serum were detected by enzyme-linked immunosorbent assay （ELISA）， and the changes in serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （CRE） by microplate method. The mRNA expression levels of inflammatory cytokines γ-interferon（IFN-γ）， IL-13， IL-17， IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in skin lesions were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of nuclear transcription factor -κB (NF-κB) and NF-κB inhibitory protein α (IκBα) in skin lesions by Western blot.ResultCompared with the normal control group， the model group showed skin edema， erythema， scab， scratch， and lymphocyte and neutrophil infiltration， decreased skin moisture content， as well as increased skin thickness， TWEL （P<0.01）， spleen index， CD4+/CD8+ T-cell ratio in the spleen （P<0.05）， mRNA expression of IFN-γ， IL-13， IL-17， IL-1β， IL-6， and TNF-α in the skin lesions （P<0.05）， serum contents of IgE， IL-4， and IL-6 （P<0.05）， and protein expression of IκBα and NF-κB in skin lesions （P<0.05）. Compared with the model group， dexamethasone and gramine at different doses alleviated skin erythema， scale， scab， and inflammatory cell infiltration， elevated skin moisture content， inhibited skin thickening and TWEL， and decreased spleen index， CD4+/CD8+T-cell ratio in the spleen， mRNA expression of inflammatory factors in the skin lesions， serum contents of IgE and inflammatory factors， and protein expression of IκBα and NF-κB in skin lesions， especially in the dexamethasone group and the high- dose gramine group（P<0.05，P<0.01）.ConclusionGramine can inhibit the expression of related inflammatory factors and regulate the immune function of AD mice via the IκBα/NF-κB pathway， enabling it become a potential drug for treating AD.
Abstract：ObjectiveTo investigate the immunomodulatory mechanism of Kangxian Yixin prescription （KYP） on autoimmune injury mice and its relationship with the T helper 17 （Th17）/regulatory T cell （Treg） balance.MethodSixty healthy 8-week-old male BALBc mice were randomly divided into a normal group and an experimental group at a ratio of 1∶5. On the 0th， 7th， and 28th days， 0.2 mL of porcine cardiac myosin emulsion （containing 0.1 mg of porcine cardiac myosin） was subcutaneously injected into the groin， armpit， and back of the mice in the experimental group to induce an animal model of myocardial immune injury. Mice with myocardial immune injury were randomly divided into a model group （Model）， a KYP group （20.4 g·kg-1·d-1， ig）， and a valsartan group （12 mg·kg-1·d-1， ig）. Mice in the control group and the model group received the same amount of normal saline by gavage. After four weeks of intervention， the heart tissues were collected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect pathological damage in heart tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of type B-type natriuretic peptide （BNP）， anti-cardiac antibody， interleukin-17 （IL-17）， and interleukin-10 （IL-10） in the serum of mice， and the expression levels of Th17 cells and Tregs in the spleen were detected by flow cytometry. The protein expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X （Bax） in heart tissues was detected by Western blot， and the mRNA expression of retinoid-related orphan receptor gamma t （RORγt） and forkhead box P3 （FoxP3） in the spleen was detected by quantitative real-time polymerase chain reaction （Real-time PCR）.ResultCompared with the control group， the model group showed worsened pathological damage in heart tissues， elevated serum levels of BNP， anti-myocardial antibody， and IL-17， decreased serum expression of IL-10 （P<0.05）， increased expression of Th17 cells and reduced expression of Tregs in spleen tissues （P<0.05）， increased protein expression of Bax， diminished Bcl-2 protein expression， elevated Bax/Bcl-2 ratio， up-regulated mRNA expression of RORγt， dwindled mRNA expression of FoxP3， and elevated ratio of RORγt/FoxP3 （P<0.05）. Compared with the model group， the KYP group and the valsartan group displayed relieved pathological damage in heart tissues， decreased serum expression of BNP， anti-myocardial antibody， and IL-17， increased serum expression of IL-10 （P<0.05）， reduced expression of Th17 cells and increased Tregs in spleen tissues （P<0.05）， dwindled protein expression of Bax and elevated protein expression of Bcl-2in heart tissues （P<0.05）， diminished Bax/Bcl-2 ratio， reduced mRNA expression of RORγt， up-regulated FoxP3， and down-regulated ratio of RORγt/FoxP3 （P<0.05）.ConclusionKYP may improve myocardial immune damage by regulating the Th17/Treg cell balance.
Abstract：ObjectiveTo establish an evaluation method for mitochondrial energy metabolism with Seahorse analyzer and investigate the protective effect of Yiqi Jiedu prescriptions （YQ） on mitochondria in rat adrenal pheochromocytoma （PC12） cells against hypoxia injury.MethodThe PC12 cell injury model was induced in vitro using hypoxic chambers. Five groups were set up， ie， a control group， a model group （model）， high- （25 µmol·L-1）， medium- （5 µmol·L-1） and low-dose （1 µmol·L-1） YQ groups， and a positive drug trimetazidine （TMZ） group， with three replicate wells in each group. The experiment was repeated three times. The established method for energy metabolism analysis was used to assay the activity of mitochondrial complex in cells and screen the optimal dosing concentration. Subsequently， the YQ group and modified YQ groups were set up， and the aerobic respiration and glycolysis function were assayed by the Seahorse analyzer. According to the non-mitochondrial oxygen consumption， proton leakage， basal respiration， maximum respiration， ATP production， and potentially improved respiration， the effects of modified YQ groups on the aerobic respiration of mitochondria damaged by hypoxia were evaluated by principal component analysis （PCA） and variable importance in projection （VIP）. The expression of cytochrome C， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） was detected by Western blot.ResultCompared with the groups of other concentrations， the optimal dosing concentration of carbonyl cyanide-4 （trifluoromethoxy）phenylhydrazone （FCCP） was 2 µmol·L-1. Compared with the model group， the medium-dose YQ group showed enhanced mitochondrial complex activity （P<0.05）. The YQ groups were superior to the model group in improvement （P<0.01）. The combination of ginsenoside and geniposide showed the optimal effect among the modified YQ groups （P<0.01）. VIP analysis revealed that for the improvement of mitochondrial respiratory function， the contribution of geniposide in YQ was the greatest. Compared with the model group， the high-dose YQ group displayed reduced leakage of mitochondrial cytochrome C （P<0.01）， decreased expression of Bax protein （P<0.01）， and increased expression of Bcl-2 protein （P<0.05， P<0.01）.ConclusionA cellular， high-throughput quantitative evaluation method for mitochondrial energy metabolism was established， which demonstrated that YQ could significantly improve the impaired mitochondrial energy metabolism in PC12 cells damaged by hypoxia， and the underlying mechanism might be related to the protection against mitochondrial apoptosis.
Keywords：Yiqi Jiedu prescriptions;combination;Seahorse;mitochondrial energy metabolism;hypoxia model
Abstract：ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway.MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E2 （PGE2） were detected by enzyme-linked immunosorbent assay （ELISA）.ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE2 contents （P<0.05， P<0.01）.ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.
Abstract：ObjectiveTo investigate the effect of modified Xiaoyaosan on central dopamine transporter （DAT）/protein kinase C （PKC）-dependent signaling pathway in hyperprolactinemia （HPRL） rats.MethodHPRL rat model was established by chronic combined stress combined with intraperitoneal injection of metoclopramide. Ninety-six rats were randomly divided into six groups， namely， the blank group， model group， western medicine （bromocriptine， 0.001 g·kg-1·d-1） group， and high-， medium-， and low-dose （60， 30， 15 g·kg-1·d-1） modified Xiaoyaosan groups. After 14 days of administration， the serum prolactin （PRL） content was detected by enzyme-linked immunosorbent assay， the expression of tyrosine hydroxylase （TH） in rat hypothalamus by immunohistochemistry， and the protein expression of DAT and PKC in hypothalamus by Western blot.ResultCompared with the blank group， the model group exhibited significantly increased PRL and DAT （P<0.01）， but decreased TH and PKC （P<0.01）. Compared with the model group， bromocriptine and modified Xiaoyaosan at the medium dose significantly lowered the content of PRL （P<0.01）. The modified Xiaoyaosan at the medium and high doses elevated the expression of TH （P<0.05， P<0.01）. The expression levels of PKC in the medium- and low-dose modified Xiaoyaosan groups and the western medicine group were significantly increased （P<0.01）， while the DAT expression levels in the high-， medium-， and low-dose modified Xiaoyaosan groups and the western medicine group were decreased （P<0.01）.ConclusionThe modified Xiaoyaosan is able to up-regulate the expression of TH and down-regulate the level of DAT through PKC-dependent signaling pathway， thereby regulating the PRL.
Keywords：hyperprolactinemia （HPRL）;liver-soothing and spleen-invigorating method;dopamine transporter （DAT）;mechanism of action
Abstract：ObjectiveTo observe the effects of modified Chaihu Shugansan（CHSG） and its disassembled formulas on angiotensin-converting enzyme 2 （ACE2）-angiotensin （Ⅰ-Ⅶ） ［Ang （Ⅰ-Ⅶ）］-mitochondrial assembly receptor （MasR） axis in hyperlipidemic rats with myocardial ischemia and depression， and to explore the underlying mechanism of its prevention and treatment of myocardial ischemia and depression.MethodA total of 108 male SD rats were randomly divided into a normal group， a model group， a modified CHSG group （11.7 g·kg-1）， a Quyu Huatan disassembled formula group （4.05 g·kg-1）， a Shugan Xingqi disassembled formula group （3.15 g·kg-1）， a Jianpi Yangxue disassembled formula group （4.5 g·kg-1）， a fluoxetine group （0.001 8 g·kg-1）， a trimetazidine group （0.005 4 g·kg-1）， and a simvastatin group （0.001 8 g·kg-1）， with 12 rats in each group. The hyperlipidemia model with myocardial ischemia and depression was induced with a high-fat diet combined with injection of isoproterenol （ISO） and chronic unpredictable mild stress （CUMS） in rats in the model group and groups with drug intervention for eight weeks. The rats in each group with drug intervention were treated correspondingly by gavage from the first day of modeling， while those in the normal group and the model group received the same amount of normal saline. The behavioral changes of rats in each group were observed by open field test and forced swimming test. Left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） were measured by echocardiography. The serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected by the enzyme-labeled apparatus. Hematoxylin-eosin （HE） staining was used to observe the histomorphological changes of the heart. The serum levels of angiotensin Ⅱ （AngⅡ）， ACE2， and Ang（Ⅰ-Ⅶ） were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of ACE2 and MasR in the hippocampus and the heart was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot.ResultCompared with the normal group， the model group showed reduced movement time， distance， and average speed in the central area of the open field （P<0.01）， prolonged immobility time of rats in the forced swimming test （P<0.01）， decreased LVFS and LVEF （P<0.01）， inflammatory exudation and disorderly arranged fiber in heart tissues， elevated serum levels of TC， LDL-C， AngⅡ， ACE2 and Ang（Ⅰ-Ⅶ）， diminished HDL-C （P<0.01）， dwindled mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and up-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Compared with the model group， the modified CHSG group displayed increased movement time， distance， and average speed in the center area of the open field （P<0.01）， shortened immobility time in the forced swimming test （P<0.01）， increased LVFS and LVEF （P<0.01）， relieved heart injury， reduced serum levels of TC， LDL-C， AngⅡ， ACE2， and Ang（Ⅰ-Ⅶ）， elevated level of HDL-C （P<0.01）， up-regulated mRNA and protein expression of ACE2 in the hippocampus and the heart and MasR in the hippocampus， and down-regulated mRNA and protein expression of MasR in the heart （P<0.01）. Each disassembled formula could improve the above indexes to a certain extent （P<0.05， P<0.01）， but the effect of the whole formula was optimal.ConclusionThe modified CHSG and its disassembled formulas have the effects of resisting depression， improving myocardial injury， and reducing blood lipid. Due to the synergistic effects of stasis-resolving/phlegm-eliminating drugs， liver-smoothing/Qi-moving drugs， and spleen-tonifying/blood-nourishing drugs in the formula， the modified CHSG is superior to each disassembled formula in efficacy. Its mechanism may be related to the activation of the ACE2-Ang （Ⅰ-Ⅶ）-MasR axis.
Abstract：ObjectiveTo investigate the effect of Yiqi Jiedu prescription-containing serum on the proliferation of medullary thymic epithelial cells （mTEC） and regulatory T （Treg） cells in myasthenia gravis （MG） patients with thymus hyperplasia.MethodAccording to serological methods，35 SD rats were adaptively fed for one week and randomized into the low-，medium-， and high-dose Yiqi Jiedu prescription groups，control group， and prednisone group，with seven rats in each group， which were then gavaged with the corresponding drugs for one week for preparing the drug-containing serum. The effect of Yiqi Jiedu prescription-containing serum at different concentrations on the proliferation of mTEC and Treg cells were determined by cell counting kit-8 （CCK-8） assay. Besides， the effect of mTEC and Yiqi Jiedu prescription-containing serum on Treg cell proliferation were observed through co-culture.ResultThymocytes were cultured for a period of time. Their mean positive rate revealed by flow cytometry using mTEC characteristic marker Ulex europaeus agglutinin Ⅰ （UEAI） was 92.54%. Treg cells were sorted by magnetic beads. The purity of Treg cells after repeated magnetic bead sorting was as high as 92%. mTEC and Treg cells showed high positive expression rates，and their cell purity met the requirements of subsequent experiments. When the concentration of Yiqi Jiedu prescription-containing serum was 2.5%-15%，it exhibited an inhibitory effect against mTEC and Treg cells. When the concentration was equal to or greater than 20%，it promoted cell proliferation，which was further enhanced with the extension of action time. The results after 48 h of culture showed that compared with the control group，prednisone and low-dose Yiqi Jiedu prescription had no significant effect on the proliferation of these two kinds of cells，but the medium- and high-dose Yiqi Jiedu prescription remarkably reduced their proliferation inhibition rate （P<0.01）. After co-culture with mTEC， the control group was not significantly different from the prednisone group and the low-dose Yiqi Jiedu prescription-containing serum group in the proliferation of Treg cells，while the medium- and high-dose Yiqi Jiedu prescription-containing serum groups significantly lowered the proliferation inhibition rate （P<0.01）.ConclusionYiqi Jiedu prescription-containing serum affects the proliferation of mTEC and Treg cells in MG patients with thymus hyperplasia. Compared with the solely cultured Treg cells isolated from MG patients，the Treg cells co-cultured with mTEC exhibit enhanced proliferation in MG patients，suggesting that mTEC can regulate the proliferation of Treg cells. This effect becomes more obvious after the intervention with Yiqi Jiedu prescription-containing serum，indicating that intervention effect of Yiqi Jiedu prescription on Treg cells can be produced during its treatment of mTEC， which may be one of the mechanisms of Yiqi Jiedu prescription-containing serum in alleviating MG.
Abstract：ObjectiveTo observe the effect of asiaticoside （AC） on the expression of T helper 17 （Th17） cells and regulatory T （Treg） cells in DBA/1 mice with collagen-induced arthritis （CIA）.MethodMale SPF DBA/1 mice were randomized into six groups according to body weight： control group， CIA group， methotrexate group （MTX group， ip， 0.5 mg·kg-1）， and AC low-， medium-， and high-dose groups （ig， 5， 15， 45 mg·kg-1， respectively）. Modeling was performed in rats other than the control group. To be specific， they were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21st day. Administration began on the day of the second immunization， once a day for 28 days. On the 49th day， related tissues were collected. Then， hematoxylin-eosin （HE） staining was performed to observe the pathological changes of the joints. Immunohistochemical method was used to detect the expression of interleukin-17 （IL-17） and forkhead box protein-3 （FoxP3）， the markers of Th17 and Treg cells， respectively， immunofluorescence double staining the expression of IL-17 and FoxP3 in CD4+T cells of mouse joint tissue， and flow cytometry the proportions of Th17 and Treg cells in mouse lymph nodes.ResultCompared with the control group， CIA group demonstrated joint disorder， damage of articular cartilage and bone， severe bone erosion （P<0.01）， increase in stained CD4 and IL-17 and the integral absorbance （IA） （P<0.01）， decrease in stained FoxP3 and the IA （P<0.01）， rise of Th17/Treg ratio （P<0.01）， elevation of Th17 expression in mouse lymph nodes （P<0.01）， and reduction in Treg expression （P<0.01）. Compared with CIA group， MTX group and three AC groups showed normal joints， alleviated bone erosion and damage， intact and smooth joint surface， and decrease in stained IL-17 and IA （P<0.05， P<0.01）， and MTX group and AC medium-dose and high-dose groups registered decrease in stained CD4 and IA （P<0.01） and reduction in Th17/Treg ratio （P<0.05， P<0.01）. Moreover， AC medium-dose and high-dose groups showed rise in stained FoxP3 and IA （P<0.05， P<0.01）. In the lymph nodes of mice， decrease in expression of Th17 cells （P<0.05， P<0.01） and the increase in expression of Treg cells （P<0.05， P<0.01） were observed in all the three AC group.ConclusionAC can regulate Th17/Treg balance by inhibiting the expression of Th17 cells and promoting the expression of Treg cells in CIA mice.
Keywords：asiaticoside;collagen-induced arthritis;DBA/1 mice;T helper 17 （Th17） cell;regulatory T （Treg） cell
Abstract：ObjectiveTo study the effect-enhancing and toxicity-reducing activities of astragalus polysaccharide injection （APS） on U14 cervical cancer in model mice receiving X-ray treatment.MethodU14 mouse cervical cancer cells were cultured in vitro and injected into the right forelimb armpit of Kunming mice for constructing a subcutaneous tumor-bearing model of cervical cancer. The tumor-bearing mice were randomly divided into the model group， X-ray intervention（IR， 6 Gy） group， APS （10 mL·kg-1·d-1） group， and IR + APS group. Following the observation of the state， body mass， and food intake of mice in each group， the volume of the tumor was measured. The tumor cell cycle and apoptosis were determined by flow cytometry. The protein and mRNA expression levels of apoptosis-related proteins p53， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cleaved cysteine-dependent aspartate-directed protease-3 （Caspase-3） in tumor tissues were assayed by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）.ResultThe comparison with the model group showed that mice in the IR group had poor mental status and reduced mobility. The IR group and IR + APS group exhibited reduced food intake and body mass since the 8th d （P<0.05， P<0.01） and narrowed tumor volume since the 9th d （P<0.01）. In the IR group， the proportion of cells in the G1 phase was increased， while the proportion of those in the S phase was decreased （P<0.01）. In the IR + APS group， the proportion of cells in the G1 phase rose， whereas the proportion of those in the G2 and S phases cells declined （P<0.05， P<0.01）. The apoptotic rates in both the IR group and IR + APS group were elevated significantly （P<0.01）. Compared with the model group， the IR group and IR + APS group displayed up-regulated cleaved Caspase-3 and Bax protein and mRNA expression in tumor tissues， but down-regulated Bcl-2 and p53 protein and mRNA expression （P<0.05， P<0.01）. Compared with the IR group， the mice in the IR + APS group had better mobility and hair， normal body mass， and increased food intake （P<0.05）. The tumor volume in the IR + APS group was reduced （P<0.05）. The proportion of cells in the G2 phase was reduced， but the proportion of those in the S phase was raised （P<0.05）. The apoptosis rate was increased （P<0.05）. The apoptosis-related protein Bax protein expression in the tumor tissue was up-regulated， while the protein expression levels of Bcl-2 and p53 were down-regulated （P<0.05， P<0.01）.ConclusionAPS maintains the life state of U14 cervical cancer model mice treated with X-ray and promotes tumor cell apoptosis， thus enhancing the efficiency and reducing toxicity.
Keywords：cervical cancer;X-ray;astragalus polysaccharide injection （APS）;enhancing efficiency and reducing toxicity
Abstract：ObjectiveTo investigate the effects of gallic acid （GA） on human colon cancer HCT-116 and Caco-2 cell activities， intracellular Janus kinase （JAK）/signal transducer and activator of transcription factor （STAT） signaling pathway， and the expression of anti-apoptotic protein B-cell lymphoma-2 （Bcl-2） and pro-apoptotic protein B-cell lymphoma-2-associated X protein （Bax）， so as to explore its underlying molecular mechanism.MethodFollowing the classification of cells into GA group， blank group， and 5-fluorouracil （5-FU， 0.05 g·L-1） group， the HCT-116 and Caco-2 cells were treated with GA （0.02， 0.05， 0.1， 0.15， 0.2 g·L-1） for 12， 24， 48， and 72 h， respectively， and the cell proliferation inhibition rats were determined by cell counting kit-8 （CCK-8） assay to select the GA concentration that effectively inhibited proliferation. The colony formation ability was detected by crystal violet staining and the migration of cells by scratch test. The level of reactive oxygen species （ROS） was measured using a fluorescent probe （DCFH-DA）. The expression of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in cell supernatant were determined using the enzyme-linked immunosorbent assay （ELISA） kits. The expression levels of JAK2， phosphorylated （p）-JAK2， STAT3， p-STAT3， Bcl-2， and Bax were assayed by Western blot.ResultCCK-8 assay showed that after 12， 24， 48， and 72 h of treatment， GA （0.02， 0.05， 0.1， 0.15， 0.2 g·L-1） inhibited the proliferation of HCT-116 and Caco-2 cells in a dose- and time-dependent manner， and the inhibition rates were higher than those in the blank control group. Compared with the 5-FU group， GA （0.2 g·L-1） enhanced the inhibition of cell proliferation in a time-dependent manner. Compared with the blank control group， GA （0.1， 0.15， and 0.2 g·L-1） significantly decreased the number of cell colonies （P<0.01）， increased the inhibition rate of cell colony formation （P<0.01）， diminished the scratch healing rate （P<0.05， P<0.01）， elevated the fluorescence intensity of intracellular ROS （P<0.01）， and down-regulated the expression of IL-6 and TNF-α in the supernatant （P<0.01） in a dose-dependent manner. Compared with the 5-FU group， GA （0.2 g·L-1） decreased the scratch healing rate （P<0.01）， enhanced the fluorescence intensity of intracellular ROS （P<0.01）， and down-regulated the levels of IL-6 and TNF-α in cell supernatant （P<0.01）. According to Western blot analysis， compared with the blank control group， GA （0.1， 0.15， 0.2 g·L-1） obviously lowered the expression of p-JAK2， p-STAT3， Bcl-2， p-JAK2/JAK2， p-STAT3/STAT3， and Bcl-2/Bax （P<0.01） and raised Bax protein expression （P<0.05， P<0.01） in a dose-dependent manner. Compared with the 5-FU group， GA （0.2 g·L-1） down-regulated the expression of p-JAK2， p-STAT3， Bcl-2， p-JAK2/JAK2， p-STAT3/STAT3， and Bcl-2/Bax （P<0.05， P<0.01） and up-regulated the expression of Bax protein （P<0.05， P<0.01）.ConclusionGA significantly inhibits the proliferation of HCT-116 and Caco-2 cells， which may be related to the increased accumulation of intracellular ROS， down-regulation of inflammatory factors IL-6 and TNF-α， p-JAK2 and p-STAT3 protein expression in JAK/STAT signaling pathway， and Bcl-2， and up-regulation of Bax.
Keywords：gallic acid （GA）;colorectal cancer;Janus kinase （JAK）;signal transducer and activator of transcription （STAT）;B-cell lymphoma-2 （Bcl-2）;B-cell lymphoma-2 associated X protein （Bax）
Abstract：ObjectiveTo investigate the effects of hirsutine on proliferation， apoptosis， metastasis， and invasion of human cervical cancer Ca Ski cells and its action mechanism.MethodThe cell proliferation was determined by cell counting kit-8 （CCK-8） assay and the cell apoptosis by Hoechst 33258 staining and flow cytometry. The mRNA expression levels of B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and p53 were detected by real-time fluorescence quantitative polymerase chain reaction. The scratch test was conducted to detect the cell mobility， followed by the detection of cell invasion ability using a Transwell chamber. The contents of fibronectin （FN）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9） were measured by enzyme linked immunosorbent assay （ELISA）， and their protein expression levels were assayed by Western blot.ResultCompared with the control group， hirsutine inhibited the proliferation of Ca Ski cells in a dose- and time-dependent manner. The apoptosis rates and Bax and p53 mRNA expression levels in the 8.0， 16.0， 32.0 μmol·L-1 hirsutine groups rose （P<0.05， P<0.01）， while the Bcl-2 mRNA expression and phosphorylated Src （p-Src） and phosphorylated signal transducer and activator of transcription factor 3 （STAT3） protein expression declined （P<0.05， P<0.01）. Compared with the control group， the 1.0， 2.0， 4.0 μmol·L-1 hirsutine groups exhibited lowered cell mobility， number of transmembrane cells， FN， MMP-2 and MMP-9 contents， and hypoxia inducible factor-1α （HIF-1α）， Vimentin， and N-cadherin protein expression （P<0.05， P<0.01）， but elevated E-cadherin protein expression （P<0.01）.ConclusionHirsutine inhibits the proliferation， metastasis， and invasion of human cervical cancer Ca Ski cells and induces their apoptosis， which may be related to its regulation of Src/STAT3 and HIF-1α/epithelial mesenchymal transformation （EMT） signaling pathways.
Abstract：ObjectiveTo evaluate the clinical efficacy of sequential syndrome differentiation of Yiqi Huayu Qingre prescription （YHQ） in the treatment of refractory nephrotic syndrome in children.MethodA total of 112 children with refractory nephrotic syndrome were randomly divided into an observation group （57 cases） and a control group（55 cases）. The children in the control group were treated with prednisone tablets combined with tacrolimus，and those in the observation group were treated with YHQ by sequential syndrome differentiation on the basis of the control group. The total effective rates of the two groups after treatment were observed. The 24-hour urinary total protein（24 h UTP），plasma albumin（ALB），cholesterol（CHO），triglycerides（TG）， and traditional Chinese medicine quality of life scale scores before treatment and after four weeks，eight weeks，16 weeks，24 weeks，32 weeks，40 weeks，and 52 weeks in the two groups were recorded. The total course of treatment and the total accumulation of hormones were compared among the children with reduced or no hormone treatment till 52 weeks during treatment.ResultThe total effective rate in the observation group was higher （Z=-2.052，P<0.05）. The observation group had lower 24 h UTP and higher ALB at each follow-up time point than the control group（P<0.05，P<0.01）. At four weeks，eight weeks，and 16 weeks of treatment，there was no statistically significant difference in CHO between the observation group and the control group，and the observation group was lower than the control group in CHO at the rest of the time points （P<0.05，P<0.01）. For TG， the observation group was not significantly different from the control group at four weeks，eight weeks，16 weeks，and 40 weeks of treatment，but lower at 24，32，and 52 weeks （P<0.05，P<0.01）. The total treatment course of hormones in the observation group was shorter（P<0.01）， with less total accumulation（P<0.01）. At different follow-up time points，the total score of traditional Chinese medicine quality of life scale in the observation group was superior to that in the control group（P<0.05，P<0.01），and the scores of the observation group in the four dimensions （physiological function，independent factor，social factor，and psychological factor） after treatment were higher than those in the control group（P<0.05，P<0.01）.ConclusionYHQ under sequential syndrome differentiation has a definite clinical effect in treating children with refractory nephrotic syndrome. It has advantages in shortening the total course of hormone treatment and reducing the total accumulation of hormones，and can improve the quality of life of children with refractory nephrotic syndrome.
Keywords：refractory nephrotic syndrome;traditional Chinese medicine quality of life scale;Yiqi Huayu Qingre prescription;children;sequential syndrome differentiation
Abstract：ObjectiveTo evaluate the clinical efficacy and safety of Yangxin Dawayimicol honey ointment （YDHO） in the treatment of insomnia with the syndrome of Qi stagnation and blood stasis.MethodEighty insomnia patients who met the inclusion criteria in the Department of Encephalopathy of the Third Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to October 2020 were randomly divided into an experimental group （48 cases） and a control group （32 cases）. The experimental group was treated with YDHO + Xuefu Zhuyu capsule simulators，and the control group was treated with Xuefu Zhuyu capsules + YDHO simulators for eight weeks. The changes in Pittsburgh sleep quality index（PSQI）score，traditional Chinese medicine （TCM） syndrome score，insomnia severity index （ISI），neurotransmitter indexes ［γ-aminobutyric acid（GABA），glutamic acid（Glu），and 5-hydroxy tryptamine（5-HT）］，serum inflammatory indexes ［interleukin-6（IL-6）and interleukin-10（IL-10）］， and safety index of the two groups were compared.ResultThe total effective rate was 97.83%（45/46） in the experimental group， higher than 68.75%（22/32） in the control group（Z=-4.292，P<0.01）. The experimental group was superior to the control group in PSQI score，ISI score，TCM syndrome score， and sleep duration（P<0.05）. The curative effects were equivalent between the two groups in shortening the time to fall asleep. The experimental group showed increased serum content of GABA，5-HT， and IL-10 and reduced content of Glu and IL-6，with few adverse reactions （P<0.05）.ConclusionYDHO is effective，safe， and reliable in the treatment of insomnia with Qi stagnation and blood stasis syndrome.
Keywords：Yangxin Dawayimicol Honey Ointment;insomnia;Qi stagnation and blood stasis syndrome;clinical study
Abstract：ObjectiveA feedforward control model for dry granulation of polysaccharide components was established to guide the adjustment and optimization of critical process parameters （CPPs） in the design space， so as to reduce the impact of fluctuations in raw materials properties on the quality of medicines.MethodTaking Astragali Radix extract powder as the model drug， the design space of dry granulation CPPs was determined by Box-Behnken design. Astragali Radix mixed powder with different powder properties were prepared by mixture design， the variance inflation factor （VIF） was used to diagnose the multicollinearity of the powder properties， and principal component analysis （PCA） was used to extract the characteristic data of the model. Radial basis function neural network （RBFNN） was used to establish a feedforward control model for reflecting the relationship between the powder properties of polysaccharide components， dry granulation CPPs and one-time molding rate.ResultThe design space for dry granulation CPPs of polysaccharide components was 16-35 Hz for feeding speed， 10-23 Hz for roller speed， and 10-46 kg·cm-2 for roller pressure. The established RBFNN feedforward control model had a good predictive effect on the one-time molding rate of dry granulation of polysaccharide components， which could be used to guide the adjustment and optimization of CPPs in the design space， the relative error was 0.38%-6.73%， and the average relative error was 3.42%.ConclusionThe established feedforward control model can well reflect the relationship between the powder properties of the polysaccharide components， the dry granulation CPPs and the one-time molding rate of the granules， which can be used to guide the adjustment and optimization of CPPs in the design space， reduce the impact of material property fluctuation on product quality， and provide ideas for promoting the quality of traditional Chinese medicine from passive control to active control.
Keywords：quality by design （QbD）;dry granulation;principal component analysis （PCA）;radial basis function neural network （RBFNN）;polysaccharide components of Astragali Radix;powder properties;critical quality attribute （CQA）
Abstract：ObjectiveTo establish an integrated method of fingerprint qualitative， multi-component quantitative analysis and chemometrics， and to evaluate the quality attributes and differences of Aurantii Fructus from different production areas and origins.MethodAnalysis was performed on COSMOSIL 5C18-MS-Ⅱ column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile-0.2% phosphoric acid solution for gradient elution （0-4 min， 19%A； 4-5 min， 19%-21%A； 5-18 min， 21%A； 18-19 min， 21%-28%A； 19-27 min， 28%A； 27-28 min， 28%-40%A； 28-36 min， 40%A； 36-37 min， 40%-50%A； 37-42 min， 50%-60%A； 42-46 min， 60%-95%A； 46-55 min， 95%-100%A）， the flow rate was 1 mL·min-1， the column temperature was 30 ℃， the detection wavelength was set at 320 nm， and the injection volume was 10 μL. High performance liquid chromatography （HPLC） fingerprints of Aurantii Fructus from different production areas and origins were established. Then， the quality of 26 batches of samples was evaluated by cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA）. A method for the determination of 12 components was developed and verified， and a thermal map-based CA of Aurantii Fructus from different production areas and origins was carried out based on the content difference of samples.ResultThe fingerprint and determination methods were well verified. The similarity of HPLC fingerprint of 12 batches of Aurantii Fructus was 0.85-0.996， 20 common peaks were calibrated and 14 of them were assigned. The resolution and linear relationship of 12 components in quantitative analysis were good. The recovery rates were 99.2%-101.0% with RSD≤2.0%. The results of CA， PCA and OPLS-DA indicated that the differentiation of Aurantii Fructus in different production areas was great， and there were differences among different cultivars.ConclusionThe qualitative analysis of fingerprint and quantitative analysis of multiple indexes based on the same chromatographic analysis conditions are convenient， accurate and reliable， and combined with chemometrics， the identification and quality analysis of Aurantii Fructus from different production areas and origins can be realized， which can provide reference for quality control and evaluation of Aurantii Fructus.
Abstract：ObjectiveIn order to explore the changes of chemical constituents in Plantaginis Semen before and after stir-frying， ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MSE） was used to rapidly identify and semi-quantitatively analyze the differential components in Plantaginis Semen processed at different stir-frying time.MethodWaters ACQUITY UPLC BEH C18 column （2.1 mm×100 mm， 1.8 μm） was employed with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-1 min， 5%-10%B； 1-2 min， 10%-15%B； 2-10 min， 15%-20%B； 10-12 min， 20%-40%B； 12-13 min， 40%-100%B； 13-14 min， 100%-5%B； 14-15 min， 5%B）， the flow rate was 0.3 mL·min-1， the column temperature was 40 ℃， and the injection volume was 3 μL. Electrospray ionization （ESI） was applied for mass spectrometric analysis under positive and negative ion modes， and the scanning range was m/z 50-1 500. MarkerLynx 4.1 software was used to find the differential compounds， and the intensity of each ion peak in samples with different stir-frying time was compared to study the content variations of these compounds.ResultA total of 20 components with potential significant differences were found， among which 17 were identified and 3 were unknown， mainly including phenylethanoid glycosides， iridoid glycosides， alkaloids and others. After processing， the peak intensities of 7 compounds， such as sucrose， geniposidic acid， verbascoside and plantagoguanidinic acid A， in Plantaginis Semen decreased. The peak intensities of orobanchoside， dianthoside and plantain D increased first and then decreased during the stir-frying process. The peak intensities of 10 compounds （decaffeoylacteoside， calceolarioside A， isoacteoside， etc.） increased， and 9 of them were newly generated components.ConclusionThe content and composition of the chemical components in Plantaginis Semen changed significantly after stir-frying， which may be related to the reduction of laxative effect and the enhancement of antidiarrheal and diuretic activities of Plantaginis Semen after stir-frying.
Abstract：ObjectiveTo study the correlation between the apparent color， comprehensive sweetness and the content of main components in the preparation of Rehmanniae Radix Praeparata processed with Amomi Fructus and Citri Reticulatae Pericarpium， so as to lay a foundation for revealing the processing principle of Rehmanniae Radix.MethodThe color of Rehmanniae Radix Praeparata sample powder was measured by automatic colorimeter， the contents of 14 active components in samples with different heating time points were determined by high performance liquid chromatography， including 7 glycosides of catalpol， rehmannia glycoside D， leonurine glycoside， 5-hydroxymethyl furfural， verbascoside， isoacteoside and hesperidin， and 7 carbohydrates of D-fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose）， and the mobile phase was acetonitrile-water for gradient elution. The comprehensive sweetness difference of sample was calculated by the sweetness of saccharides， SPSS 21.0 was used to analyze the relationship between the color， comprehensive sweetness and the main component contents in the processing of Rehmanniae Radix Praeparata processed with Amomi Fructus and Citri Reticulatae Pericarpium， the quality comprehensive evaluation index of Rehmanniae Radix Praeparata by triangular area method was established.ResultDuring the processing， the color value of the powder increased， and the apparent color of the sample became darker. the content determination results showed that the content of glycosides decreased， monosaccharides and comprehensive sweetness increased with the increase of heating time. The results of correlation analysis showed that chromaticity value， comprehensive sweetness were significant negatively correlated with the content of iridoid glycosides （P<0.01）， the chromaticity value was significant positively correlated with the contents of furaldehyde derivatives， phenylethanoid glycosides， flavonoids and comprehensive sweetness was significant positively correlated with the contents of furaldehyde derivatives， phenylethanoid glycosides （P<0.01）， and the comprehensive sweetness was positively correlated with the content of flavonoids （P<0.05）. After 52 h of processing， the comprehensive evaluation index of samples reached 0.99.ConclusionThe overall trend of cluster analysis of powder chromaticity value of Rehmanniae Radix Praeparata is basically consistent with that of naked eyes， the comprehensive quality evaluation of Rehmanniae Radix Praeparata processed with Amomi Fructus and Citri Reticulatae Pericarpium can be carried out by combining the three indexes of powder chromaticity value， comprehensive sweetness and glycosides content.
Abstract：Tibetan medicine is an important part of traditional Chinese medicine with a long history，complete theories and rich contents. As the core of the sustainable development of Tibetan medicine，the reserve of Tibetan medicine is an important strategic resource of the country. The Stainless Crystal Minrror：A Tibetan Materia Medica is based on the classic book Crystal Pearl Materia Medica. Combined with modern Tibetan medicine，it has collected and introduced more than 1 430 Tibetan medicines and equipped with more than 1 200 colorful pictures of medicinal materials，which has important reference value for the research of Tibetan medicines and the establishment of quality standards. This paper starts from three perspectives of "data analysis-plant distribution-Tibetan medicine classification". Based on The Stainless Crystal Minrror：A Tibetan Materia Medica，the database of plant Tibetan medicine was constructed and analyzed statistically，and the correlation between regional distribution，medicinal parts，altitude and medicinal properties of plant Tibetan medicine was explored. The results showed that The Stainless Crystal Minrror：A Tibetan Materia Medica contained 711 plant medicines，involving 127 families and 368 genera. Angiosperms accounted for 94.1%，among which compositae had 34 genera and 74 species，occupying the first place. There are 10 medicinal parts of plant Tibetan medicine，of which 327 species （44.9%） use whole grass.The average altitude of Tibetan medicine is 3 500 m，among which 81.0% grow above 3 000 m.There is a relationship between altitude and medicinal parts and taste Classification of Tibetan medicines is usually based on the classification of the general drug name，Tibetan name，primitive and family. The analysis of plant medicine resource varieties in The Stainless Crystal Minrror：A Tibetan Materia Medica is beneficial to the effective utilization of Tibetan medicine plant resources.
Abstract：ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019（COVID-19） based on the differences of syndromes and traditional Chinese medicine（TCM） treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases.MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system （HIS） of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas.ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai，dominated by young and middle-aged males，had clinical symptoms of fever， abnormal sweating，and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat， with manifest cold， dampness， and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness， accompanied by draining depressed heat. The core Chinese medicines used are Poria，Armeniacae Semen Amarum，Gypsum Fibrosum，Citri Reticulatae Pericarpium，and Pogostemonis Herba. By contrast，the 105 patients in Ruili， dominated by young females， had atypical clinical symptoms， and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach， with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen， resolving dampness， and dispersing Qi with light drugs. The core Chinese medicines used are Poria，Atractylodis Macrocephalae Rhizoma，Glycyrrhizae Radix et Rhizoma，Coicis Semen，Platycodonis Radix，Lonicerae Japonicae Flos， and Pogostemonis Herba.ConclusionThe differences in clinical characteristics， TCM syndromes， and medication of COVID-19 patients from the two places may result from different regions，population characteristics， and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.
Keywords：corona virus disease 2019（COVID-19）;traditional Chinese medicine（TCM）;treatment of disease in accordance with three conditions;unexpected acute infectious diseases
Abstract：Wuzhuyu Tang （WZYT）， a classical traditional Chinese medicine （TCM） formula， was first recorded in Treatise on Cold Damage by the prestigious physician ZHANG Zhong-jing in the Eastern Han Dynasty， and included in Catalogue of Ancient Classical Formulas （First Batch）. WZYT is composed of four medcinals： Euodiae Fructus， Ginseng Radix et Rhizoma， Zingiberis Rhizoma Recens， and Jujubae Fructus， which has the effects of warming the middle and tonifying deficiency， dissipating cold and descending adverse qi. Based on data mining， this paper analyzes the modern clinical research literature on WZYT， which is expected to lay a basis for clarifying the "disease-symptom-prescription-medicinal" relationship of WZYT， as well as its modern clinical indications and clinical dosage. With the search term "Wuzhuyu Tang"， 253 complete medical records were retrieved from CNKI， VIP， and Wanfang （2000-2020）， involving 292 TCM prescriptions. Microsoft Excel 2019 was employed to establish the medical record database and the main clinical indications were statistically analyzed. Moreover， the syndromes， incidence law， and medication regularity were summed up. The result indicates WZYT has a wide range of modern clinical applications， mainly including the treatment of headache， dizziness， vomiting， diarrhea， dysmenorrhea， morning sickness， and other diseases， and the "deficiency， cold， and reversal" symptoms， mainly manifested as nausea and vomiting， headache， fatigue and lack of strength， reversal cold of hands and feet， poor appetite， gloomy complexion， dizziness， aversion to wind and cold， abdominal pain， sloppy diarrhea， abdominal distension， poor sleep， pale tongue， white coating， and deep thread wiry pulse. These diseases and symptoms mainly occur in women and middle-aged people. In most cases， medicinals are added or subtracted according to the symptoms， and the common doses of Euodiae Fructus， Zingiberis Rhizoma Recens， Codonopsis Radix or Ginseng Radix et Rhizoma， and Jujubae Fructus in the original prescription are 6-15 g， 10-15 g， 10-15 g or 9-12 g， and 4-6， respectively. The added medicinals are in the descending order of Pinelliae Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhize Radix et Rhizoma， and Chuanxiong Rhizoma according to the frequency.
Abstract：ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology.MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin.ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H2O2-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）.ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.
Keywords：Cervi Cornu Pantotrichum;osteoarthritis;network pharmacology;mechanism of action;signaling pathway;oxidative stress;inflammation
Abstract：ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology.MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information （NCBI）， and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed. Finally， AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them.ResultA total of 29 important chemical components in the prescription were screened out， including β-sitosterol， sesamin， and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved， such as protein kinase B1 （Akt1）， epidermal growth factor receptor （EGFR）， hypoxia inducible factor-1A （HIF-1A）， proto-oncogene tyrosine-protein kinase （SRC）， and matrix metalloproteinase-9 （MMP-9）. Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism， nucleic acid transcription， and metabolic enzyme pathway， and 28 key KEGG pathways， including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1.ConclusionKanglao granule improved the sterilization level and immune response through multi-component， multi-target， and multi-pathway interactions， thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.
Abstract：Evidence and value：impact on DEcisionMaking （EVIDEM） framework was developed by EVIDEM collaboration. Its core is the combination of multiple criteria decision analysis （MCDA） model and standardized health technology assessment （HTA） report， which aims to evaluate the overall value of medical interventions. It has been tested and implemented in the real-world evaluation environments. After more than 10 years of development， EVIDEM framework has been updated to version 10， and the relevant operation manuals have been published. More than 40 countries have joined the collaboration and more than 20 countries have carried out relevant studies. The framework is constructed with patients， population and sustainability as the overall goals， combing the evidence and value， forming a relatively complete decision-making framework system composed of 2 levels， 7 dimensions and 20 criteria. The two levels include normative universal criteria and contextual criteria. The normative universal criteria， namely EVIDEM core model， is the quantitative evaluation， consisting of 5 dimensions and 13 criteria. Contextual criteria， namely contextual tools， are qualitative evaluation， consisting of 2 dimensions and 7 criteria. The specific operation steps of EVIDEM framework include selecting and constructing criteria， assigning weights， integrating and evaluating evidence， quantitative and qualitative evaluation of value， comprehensive value estimation and ranking based on value estimation. EVIDEM framework is applicable to disease diagnosis， treatment， management and other fields. Its application scope includes medical insurance reimbursement， clinical practice decision-making， drug selection and so on， which can provide a method for more systematic， transparent and scientific healthcare decision-making. At present， the framework has been introduced into the field of traditional Chinese medicine and can provide a scientific and feasible evaluation tool and methodology system for the clinical comprehensive evaluation of Chinese patent medicine.
Keywords：evidence and value;evidence and value：impact on DEcisionMaking （EVIDEM）;multiple criteria decision analysis （MCDA）;health technology assessment （HTA）;healthcare decision making;Chinese patent medicine;clinical comprehensive evaluation
Abstract：Major depressive disorder （MDD） is an affective disorder characterized by significant and long-lasting depression， hypoactivity， and thinking and cognitive retardation. Some patients may conduct self-hram or suicide and have delusion， hallucination， and other mental symptoms. MDD is believed to be correlated with brain and heart， but there is no complete theory or mechanism fully explaining the pathogenesis of MDD. Traditional Chinese medicine （TCM） holds that the brain and heart dominate the formation of and change in mind， and MDD falls into the category of mental disease. It is mainly diagnosed as depression， visceral agitation， or Lily disease. Triple energizer is a key zang-fu organ that governs Qi transformation. There has always been some controversy about its anatomical structure. In recent years， important progress has been made in the research on the substantive structure of triple energizer. It is found that the structure and function of triple energizer are highly consistent to those of "mesenchyme"， a fluid space supported by a complex network of collagen fibers and widely distributed throughout the body. Different from known tissues and organs， it is a large organ responsible for information communication， material exchange， and energy metabolism. The triple energizer is partially contained in the structure of brain and heart and connects with the brain and heart， thus forming a "brain-heart-triple energizer" system with close physiological and pathological connections. With the association of "brain-heart-triple energizer" as the basis and Qi transformation as the core link， this paper elucidated the pathogenesis of MD and put forward that MDD resulted from "brain and heart Yang deficiency and Qi depression due to triple energizer obstruction"， so as to improve TCM understanding of the pathogenesis of MDD and perfect the TCM theories of encephalopathy and triple energizer.
Abstract：The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.
Keywords：restraining excessiveness to acquire harmony;diabetic macroangiopathy;endothelial dysfunction;pathogenesis;treatment principles
Abstract：Based on the clinical characteristics of multiple sclerosis （MS） in traditional Chinese medicine （TCM） and western medicine and literature analysis， this paper aims to formulate the diagnostic criteria of TCM and western medicine for MS. Moreover， the modeling methods of experimental autoimmune encephalomyelitis （EAE）， animals for the modeling， and characteristics of the models were analyzed and summarized， and the consistency between the EAE models and the diagnostic criteria of TCM and western medicine was evaluated. The results showed that animal models had low consistency with the clinical characteristics in TCM （highest consistency 68%） and western medicine （highest consistency 60%）. Pathological models account for the majority of animal models for MS research， but there is a lack of intuitive performance indicators. Thus， it is difficult to comprehensively evaluate the models. The mental state， limb numbness， lack of strength， loss of muscle tone， tremor， and balance disorders of the mice are among the diagnostic criteria in western medicine. In TCM diagnostic criteria， the major symptoms which are reflected in animal behavior， such as physical fatigue， lack of strength， mental fatigue， distinclination to talk， and weak heavy numb limbs， are consistent with the western diagnostic criteria. The minor symptoms， including mental decline， bitter taste in mouth， frequent and urgent urination， fecal incontinence， and aggravated fever， are not well reflected in the models. According to TCM， MS is caused by deficiency of kidney essence and external contraction of pathogen， but no index is available for evaluating the external contraction of pathogen in existing animal models. The key to experimental research on MS is to establish an appropriate animal model based on the clinical pathogenesis and characteristics. However， there is a lack of MS animal model with TCM characteristics for syndrome classification. Therefore， renewed efforts should be made to prepare animal models with both TCM and western medicine characteristics that can be used in both basic experiments and clinical research.
Keywords：multiple sclerosis;traditional Chinese medicine（TCM）and western medicine;clinical syndrome characteristics;animal model
Abstract：Recurrent genital herpes is a sexually transmitted disease induced by herpes simplex virus（HSV）， mainly manifested as erythema， papules， vesicles， erosion， and exudation on the skin and mucosal membranes of the genital and anal area， accompanied by burning pain， or tingling. Factors leading to its recurrence are overworking， fever， alcohol consumption， infection， sexual activity， etc. At least 1 in 10 of the 15-49-year-old population are infected with herpes simplex virus-2. There is currently no available method to completely remove the herpes simplex virus and prevent its recurrence， and recurrence seriously affects the quality of life and psychological health of patients. According to the theory of traditional Chinese medicine （TCM）， the recurrence of genital herpes is mostly related to wind， dampness， heat， yin deficiency of liver and kidney， internal injuries due to emotional disorder， and dietary preference. TCM has advantages in reducing its recurrence rate. The lower energizer is closely related to skin diseases， and "lower energizer resembles drainage". Thus， the lower energizer is closely related to water and damp metabolism. Recurrent genital herpes occurs in the lower energizer and belongs to lower energizer diseases， and the fluid metabolism and qi movement in lower energizer are closely related to the occurrence of the disease. Based on thought of "lower energizer resembling drainage" and the clinical characteristics of recurrent genital herpes， this paper considered malfunction of lower energizer as its pathogenesis. Thus， smoothing the lower energizer according to the prevailing circumstances is particularly important and the treatment principle should be dispersing the pathogen from lower energizer without damaging yin. Zhulingtang （Treatise on Cold Damage and Miscellaneous Diseases） cures the difficulty in urination and thirst with desire to drink by smoothing the lower energizer. Thus， Zhulingtang was selected to treat recurrent genital herpes. This study is expected to provide a new idea for its clinical diagnosis and treatment.
Keywords：recurrent genital herpes;lower-jiao resembling drainage;prevailing circumstances;induce drainage of the evil from lower-jiao;Zhulingtang
Abstract：Macrophages are natural immune cells with strong plasticity. The polarization of macrophages mainly responds to stimuli in the microenvironment by changing their phenotype and related functions. In recent years， studies have found that the polarization of macrophages is involved in the occurrence and development of various diseases such as bone arthritis， skin diseases， diabetes， coronary heart disease， breast cancer， colorectal cancer， and lung cancer， especially the metastasis of malignancies and drug resistance， through multiple signaling pathways， including nuclear factor kappa-B（NF-κB）， c-Jun N-terminal kinase（JNK）， protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， signal transducer and activator of transcription 6 （STAT6）， Wnt/β-catenin， and mammalian target of rapamycin （mTOR） and regulatory factors， such as granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin （IL）-4， IL-10， transforming growth factor （TGF）-β， tumor necrosis factor（TNF）-α， and interferon-γ（IFN-γ）. Chinese medicine is also pivotal in the prevention and treatment of malignancies. In recent years， therefore， the specific anti-tumor mechanism of Chinese medicine and its active ingredients has become a research hotspot. The tumor microenvironment is crucial to the occurrence and development of tumors. The polarization of tumor-associated macrophages is involved in the proliferation， apoptosis， and metastasis of tumor cells. Therefore， targeted regulation of the polarization of tumor-associated macrophages is a potential target for clinical treatment of malignancies. Based on the research articles published in the past three years， this article reviewed macrophage polarization and the anti-tumor mechanism of Chinese medicine from four perspectives， i.e.， macrophage polarization， related pathways and regulatory factors of macrophage polarization， macrophage polarization and breast cancer， colorectal cancer， and lung cancer， and macrophage polarization and anti-tumor effects of Chinese medicine， active ingredients of Chinese medicine， and self-formulated prescriptions/classic prescriptions. This study is expected to provide certain ideas for the clinical treatment， basic research， and development of new Chinese medicine in the treatment of tumors.
Abstract：Seborrheic alopecia is a chronic dermatological disease caused by multiple factors. It occurs frequently in young and middle-aged men aged 20-30 years. The main clinical manifestations are greasy hair， itching， excessive dandruff， receding hairline， sparse hair on the top of the head， and progressive hair loss in the frontotemporal area. Seborrheic alopecia is not fatal， but it affects the appearance of patients， seriously harming their self-esteem and bringing great psychological distress to them. The Wnt/β-catenin signaling pathway widely exists in multicellular eukaryotes and is a basic growth regulatory pathway which regulates cell proliferation and differentiation， maintains stem cells activity and organ homeostasis， and affects cell migration. At present， it has been reported in China and abroad that Wnt/β-catenin signaling pathway is closely related to the occurrence and development of seborrheic alopecia and the action mechanism of drugs. Traditional Chinese medicine （TCM） has multi-component， multi-target， and multi-pathway advantages， and it can promote the formation of hair follicle laminae， the proliferation and differentiation of hair follicle stem cells， and the periodic changes in hair follicles by regulating the Wnt/β-catenin signaling pathway， thereby alleviating seborrheic alopecia. This article reviewed the relationship of Wnt/β-catenin signaling pathway and its key target protein factors with seborrheic alopecia to clarify the important role of Wnt/β-catenin signaling pathway in seborrheic alopecia. At the same time， the TCM that targeted the Wnt/β-catenin signaling pathway to relieve seborrheic alopecia were summarized， so as to provide reference for the treatment of seborrheic alopecia and further development of new drugs.
Keywords：Wnt/β-catenin signaling pathway;seborrheic alopecia;traditional Chinese medicine （TCM）;action mechanism
Abstract：Esophageal carcinoma is one of the malignant tumors with a high mortality rate， accounting for nearly 570，000 cancer deaths worldwide annually， and this number is increasing year by year. In recent years， despite the continuous improvement of treatment programs for esophageal carcinoma， the overall five-year survival rate of esophageal carcinoma is still less than 20% due to the development of drug resistance and the tolerance of patients during the treatment process. Tumor microenvironment （TME） is composed of various cells and related components with tumor cells as the core and featured by hypoxia， acidosis， chronic inflammation and immunosuppression， which plays an important role in the progression of tumors. Studies have found that tumor-associated fibroblasts， tumor-associated macrophages， myeloid-derived suppressor cells and regulatory T cells in TME can promote the proliferation， migration， invasion， and lymph node metastasis of cancer cells by secreting cytokines and activating pro-inflammatory pathways， and promote cancer progression by inducing the drug resistance of cancer cells and evading immunosuppression. Because cancer-associated cells in TME are genetically more stable than cancer cells， have fewer mutations and have lower chance of drug resistance， targeting cancer-associated cells in TME by regulating TME is a new research direction of cancer therapy. Traditional Chinese medicine has the advantages of multi-component and multi-target. It can participate in the regulation of TME through multiple ways， reduce the number of cancer-associated cells in TME， inhibit crosstalk between TME and cancer cells， and restore immune cell function. It is an important source for the regulation of TME and the research and development of drugs targeting cancer-associated cells in TME. In this paper， the role of cancer-associated cells in the TME of esophageal cancer and the current application of traditional Chinese medicine targeting cancer-associated cells in TME are reviewed， so as to provide reference for the research and development of TME targeted drugs for esophageal carcinoma.
Abstract：In the greying society， pension burden and high incidence of geriatric diseases have hindered social and economic development to a certain extent. Aging is a biological process involving multiple organs and factors， which leads to the occurrence of a variety of diseases. The occurrence of aging is related to a variety of signal pathways， such as nutrient sensing signal pathway and intracellular stress signal pathway， which attracts the interest of scholars in anti-aging drugs and poses a challenge to the development of such drugs. The anti-tumor， hypoglycemic， hypolipidemic， antioxidant， and antiviral activities of Chinese medicinal polysaccharides have been gradually confirmed， and they also have significant advantages in anti-aging. Thus， they are potential candidates for the development of anti-aging drugs. It has been verified that Chinese medicinal polysaccharides exert the anti-aging effect through a variety of mechanisms. To be specific， through dietary restriction， they promote the expression of longevity genes silencing information regulator 1 （Sirt1） and forkhead box O （FoxO） transcription factor， enhance the sensitivity to insulin， activate Sirt1 deacetylase or inhibit insulin/IGF-1 signaling （IIS） and mammalian target of rapamycin （mTOR） signal pathway， thereby exerting the anti-aging effect. In addition， they can inhibit the production of reactive oxygen species （ROS） and the release of pro-inflammatory mediators， enhance anti-inflammatory and antioxidant capacity， and regulate the immunity to inhibit inflammation and aging. Moreover， they can also inhibit apoptosis and delay aging through p53-mediated pathway. Despite the extensive research on anti-aging effect of Chinese medicinal polysaccharides， and the diverse effects and ideal efficacy of the polysaccharides， the anti-aging mechanism has not been systematically reviewed. Therefore， this paper summarizes the relevant literature in PubMed and CNKI and systematically expounds the aging-related signal pathways regulated by Chinese medicinal polysaccharides， which is expected to provide a reference for researchers and clinical workers.
Keywords：anti-aging;Chinese medicinal polysaccharides;nutrient sensing signal pathway;intracellular stress signal pathway