Abstract：［Background］ In order to implement the spirit of the National Conference on Traditional Chinese Medicine （TCM）， and the Opinions on Promoting the Inheritance， Innovation and Development of TCM， regularly review and summarize the research achievements of TCM， dynamically present the trajectory and trend of TCM academic research and innovation achievements， and give full play to the academic leading role of academic organizations， China Association of Chinese Medicine organized the selection of the top 10 academic progress of TCM in 2021. In the forefront of world science and technology， economic main battlefield and the national major requirements and the needs of the people′s life and health， taking the new rules， new discoveries， new methods， new products and new theories with originality， breakthrough and leadership in the field of basic research and applied basic research of TCM as the inclusion criteria， the top 10 academic progress of TCM in 2021 has been determined through working procedures of dynamic collection， first trial， review and final instance.
Keywords：traditional Chinese medicine （TCM）;academic progress;acupuncture;emotional disease;herbgenomics;international standard;dispensing granules
Abstract：ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway.MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa.ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）.ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.
Keywords：allergic rhinitis;Xiao Qinglongtang;T helper cell type 2 （Th2）;interleukin-33 （IL-33）;suppression of tumorigenicity 2 （ST2）
Abstract：ObjectiveTo explore the intervention effect and mechanism of Buzhong Yiqiwan （BZYQ） on colitis mice.MethodSixty-four C57BL/6 mice were randomly divided into 2 weeks blank group， 2 weeks model group， 2 weeks high-dose BZYQ （12 g·kg-1） group， 2 weeks low-dose BZYQ （6 g·kg-1） group， 4 weeks blank group， 4 weeks model group， 4 weeks high-dose BZYQ （12 g·kg-1） group， and 4 weeks low-dose BZYQ （6 g·kg-1） group. The colitis model was induced in mice by feeding 3% dextran sodium sulfate （DSS） for 7 days. The mice received BZYQ （12 and 6 g·kg-1） by gavage on the 8th day after modeling， once per day， and sacrificed on the 2nd and 4th weeks， correspondingly. The colon length and weight of mice in each group were measured. Hematoxylin-eosin （HE） staining was used for pathological observation and colonic mucosal inflammation was scored. The mRNA and protein expression of NOD-like receptor thermoprotein domain 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and cysteinyl aspartate-specific protease-1 （Caspase-1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of inflammatory cytokines， such as interleukin （IL）-1β， IL-18， and IL-33 in colonic tissues.ResultCompared with the 2 weeks blank group， the 2 weeks model group showed shortened colon length， increased colon weight （P<0.05）， loss of epithelial cells， destruction of gland structure， infiltration of a large number of inflammatory cells in mucosa and submucosa， local crypt abscess， and increase in mucosal inflammation score （P<0.01） as revealed by light microscopy， elevated levels of IL-1β， IL-18， and IL-33 in colonic tissues （P<0.05）， and increased mRNA and protein expression of NLRP3， ASC， and Caspase-1 （P<0.05）. The intervention of BZYQ （12 g·kg-1） restored colon length， alleviated mucosal injury （P<0.05）， down-regulated the content of IL-18 （P<0.05）， reduced the mRNA expression of NLRP3 and ASC as well as the protein expression of ASC and Caspase-1 compared with the conditions in the 2 weeks model group. Compared with the 4 weeks blank group， the 4 weeks model group showed decreased colon length， increased colon weight （P<0.05）， decreased glands in the mucosal layer， expansion of glandular cavity， atrophy of crypt， local connective tissue hyperplasia and lymphocyte infiltration， increased inflammation score （P<0.01） as revealed by the light microscopy， increased expression of IL-1β， IL-18， and IL-33 （P<0.05）， and elevated mRNA and expression of NLRP3 inflammasome complex （P<0.05）. Compared with the conditions in the 4 weeks model group， the intervention of BZYQ （12 and 6 g·kg-1） could improve colon length and weight （P<0.05）， and the intervention of BZYQ （12 g·kg-1） could also improve the inflammation score of the colon （P<0.05）. Different from the acute stage， the intervention of BZYQ （12 and 6 g·kg-1） increased the content of IL-33 in the intestinal mucosa and up-regulated the mRNA and protein expression of NLRP3 inflammasome complexes ASC and Caspase-1 （P<0.05）.ConclusionBZYQ can relieve the injury of colitis induced by DSS in mice. The mechanism is related to the regulation of intestinal immune response mediated by NLRP3 inflammasome， and it has different regulatory effects in acute and chronic inflammation stages.
Abstract：ObjectiveTo observe the effects of Fuzitang （FZT） on the proliferation of MH7A cells， the human rheumatoid arthritis synovial fibroblasts， and the expression of miR-155 and explore its anti-rheumatoid arthritis mechanism.MethodMH7A cells were cultured in vitro and divided into a blank group， high- （25 g·L-1） and low-dose （12.5 g·L-1） FZT groups， and a positive drug group （hydroxychloroquine， 0.006 25 g·L-1）. The cell proliferation was detected by cell counting kit-8（CCK-8） method， and the change in the MH7A cell cycle was detected by flow cytometry. The mRNA expression of miR-155 and its downstream genes， including SH2 domain-containing inositol 5-phosphatase-1（SHIP-1）， protein kinase B 3（Akt3）， and mammalian target of rapamycin（mTOR）， was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of phosphatidylinositol 3-kinase （PI3K）， Akt3， and mTOR was detected by Western blot.ResultFZT in vitro in a concentration of 6.25 g·L-1 above could inhibit the proliferation of MH7A cells in the significant dose- and time-effect manner. Compared with the blank group， the FZT groups showed increased proportions of cells in the G2/M phase （P<0.05）， and the high-dose FZT group showed a decreased proportion of cells in the G0/G1 phase （P<0.05）. The arresting effect of FZT on the cell cycle was in a significant dose-effect manner. Compared with the blank group， the FZT groups showed down-regulated miR-155 and mTOR mRNA expression （P<0.05）， and the high-dose FZT group showed up-regulated SHIP1 mRNA expression and down-regulated Akt3 mRNA expression （P<0.05）. Compared with the blank group， the FZT groups showed reduced protein expression of PI3K， Akt3， and mTOR （P<0.05）.ConclusionFZT can significantly inhibit the proliferation of MH7A cells， and the mechanism is related to the promotion of the expression of SHIP-1 and down-regulation of the gene expression of the PI3K/Akt3/mTOR signaling pathway by down-regulating the expression of miR-155.
Keywords：Fuzitang;rheumatoid arthritis;MH7A cells;miR-155;SH2 domain-containing inositol 5-phosphatase-1（SHIP-1）;phosphatidylinositol 3-kinase （PI3K）/protein kinase B 3 （Akt3）/mammalian target of rapamycin （mTOR） signaling pathway
Abstract：ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway.MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D1. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D1， β-catenin nuclear import was explored by immunofluorescence assay.ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD1 were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD1 were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells.ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.
Keywords：Shenbai Jiedu prescription;colorectal cancer;cell proliferation;phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway;β-catenin nuclear import
Abstract：ObjectiveTo observe the behavioral and pain threshold alterations， as well as the changes in indexes related to depression and pain in the serum and central system in mice stressed by maternal separation and chronic neuropathic pain， and explore the underlying mechanism of Wenyang prescription （WY）， Jieyu prescription （JY）， and Wenyang Jieyu prescription （WYJY） in improving depression and pain sensitivity.MethodThe birth date of mice was recorded as PD0. After birth， the mice were divided into a blank group and an experimental group. The neonatal mice in the experimental group underwent maternal separation in PD5-14 at 8 h·d-1. After ablactation， the mice were divided into a maternal separation group， a WY group （Erxian decoction， 5.84 g·kg-1）， a JY group （Xiaoyaosan， 12.00 g·kg-1）， a WYJY group （16.68 g·kg-1）， and a fluoxetine group （2.60 mg·kg-1）， with 15 mice in each group. Meanwhile， 15 male mice of the same age without maternal separation were assigned to the normal control group. Mice in the blank group and the maternal separation group were fed on a regular chow diet in PD21-PD90， while the remaining groups were fed on the corresponding drugs. In PD91， sciatic nerve ligation was performed to induce a model of maternal separation and chronic neuropathic pain. The open field test was used to observe the depression-like behaviors of mice in each group， and the mechanical and temperature pain thresholds were measured to detect the pain sensitivity of mice in each group. The serum levels of corticosterone （CORT）， substance P， and β-endorphin （β-EP） were determined by enzyme-linked immunosorbent assay （ELISA）， and the expression of the glucocorticoid receptor （GR） in the amygdala and β-EP protein in the hypothalamus was detected by immunohistochemistry. The mRNA expression levels of amygdala GR gene （Nr3c1）， FK506 binding protein 5 gene （FKBP5）， metabolic glutamate receptor 5 gene （GRM5）， and brain-derived neurotrophic factor （BDNF） were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）.ResultCompared with the blank group， the maternal separation group showed reduced stay time and total distance traveled in the 5-min open field test （P<0.01）， reduced mechanical pain threshold （P<0.01）， increased serum CORT and β-EP （P<0.01）， declining FKBP5 mRNA expression （P<0.01）， and increased hypothalamic β-EP expression （P<0.05）. Compared with the maternal separation group， the groups with drug intervention showed prolonged stay time （P<0.05， P<0.01） and up-regulated pain thresholds to different degrees. The total distance traveled in the 5-min open field test increased in the WY group， the WYJY group， and the fluoxetine group （P<0.05， P<0.01）. The JY group showed decreased serum CORT （P<0.01）， reduced β-EP ， and increased BDNF mRNA （P<0.01）. Nr3c1 and GRM5 mRNA decreased in the WY group （P<0.05， P<0.01）. The WYJY group showed decreased serum CORT （P<0.05）and decreased Nr3c1， GRM5， and BDNF mRNA （P<0.05， P<0.01）. The levels of β-EP expression were elevated to different degrees in the groups with drug intervention， but the differences were not significant. The levels of GR expression in the WY group， the JY group， and the WYJY group increased （P<0.05）.ConclusionWYJY can inhibit central pain sensitization and regulate hypothalamic-pituitary-adrenal gland （HPA） axis function by enhancing the expression of GR in the amygdala and inhibiting neuroplasticity and excitability in the amygdala to relieve depression-like behaviors and improve somatic hyperalgesia.
Abstract：ObjectiveTo preliminarily explore the mechanism of Shufeng Tongluo prescription （SFTLP） in inhibiting airway inflammation in asthma mice by affecting the expression levels of eotaxin in the serum， CC type chemokine receptor 3 （CCR3）， and extracellular signal-regulated kinase （ERK） phosphorylation in lung tissues.MethodSeventy C57BL/6 mice were randomly divided into a blank group， a model group， low-， medium-， and high-dose SFTLP groups （7.75， 15.5， 30 g·kg-1）， a pertussis toxin （PTX） group， a CCR3 inhibitor （SB328437） group， a phosphoinositide 3-kinase （PI3K） inhibitor （LY294002） group， a p38 protein kinase antagonist inhibitor （SB203580） group， and an ERK inhibitor （PD98059） group. The asthma model was induced in mice by intraperitoneal injection of ovalbumin （OVA） and aluminum hydroxide ［Al（OH）3］ combined with OVA atomization （0.2 mL for all）. After modeling， hematoxylin-eosin staining （HE staining） was used to observe the inflammatory infiltration of lung tissues in mice. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of eotaxin ［CC chemokine ligand （CCL） 11 and CCL24） in each group. Western blot was used to detect the levels of ERK phosphorylation and CCR3 in lung tissues.ResultCompared with the blank group， the model group showed obvious bronchial constriction， lumen stenosis， damaged alveolar structure， massive inflammatory cell infiltration in lung tissues， mucous plug in the bronchus， edema in the submucosal tissues of the trachea， increased folds， increased serum levels of CCL11 and CCL24 （P<0.01）， and increased expression of CCR3 protein in lung tissues （P<0.05）. The ERK levels in lung tissues of the model group and the PTX group increased （P<0.05）. The level of p-ERK in lung tissues of the model group and the low-dose SFTLP group increased （P<0.05）. As revealed by pathological results， compared with the model group， the high-dose SFTLP group showed relieved lung lesions. The high-dose SFTLP group and the SB328437 group showed reduced CCL11 content （P<0.05）. The low- and high-dose SFTLP group， the PTX group， the SB203580 group， the PD98059 group， and the SB328437 group showed decreased CCR3 protein expression in lung tissues （P<0.05）. The high-dose SFTLP group and the PD98059 group showed reduced p-ERK level （P<0.05）. The PD98059 group showed reduced ERK level （P<0.05）.ConclusionSFTLP can inhibit airway inflammation in asthma， and the mechanism may be related to the inhibition of eosinophil activation by down-regulating CCR3 and CCL11 expression and ERK phosphorylation.
Abstract：ObjectiveTo explore the effects of phillygenin （PHI） on the inflammation in L02 cells induced by lipopolysaccharide （LPS） and adenosine triphosphate （ATP） and the expression of purinergic 2X7 receptor （P2X7R）， NOD-like receptor family pyrin domain containing 3 （NLRP3）， and nuclear factor kappa B （NF-κB） expression.MethodIn this study， the inflammation model was induced in L02 cells by 100 μg·L-1 LPS treatment for 24 h and 5 mmoL·L-1 ATP treatment for 5 h. The cells in the PHI groups were cultured with PHI （100， 50， 25 mg·L-1） for 6 h in the LPS treatment period， followed by LPS treatment for another 18 h. After ATP treatment for 5 h， the mRNA and protein expression of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， P2X7R， NLRP3， Caspase-1 precursor （pro-Caspase-1）， cleaved Caspase-1， NF-κB， and NF-κB inhibitor protein α （IκBα） in L02 cells was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. Molecular docking was used to predict whether P2X7R could bind to PHI， and DCFH-DA was employed to detect the accumulation of reactive oxygen species （ROS） in cells. P2X7R was silenced by small interfering ribonucleic acid （siRNA）， and then the mRNA expression of IL-1β， IL-18， P2X7R， NLRP3， Caspase-1， NF-κB， and IκBα was detected by Real-time PCR.ResultReal-time PCR and Western blot showed that compared with the normal group， the model group showed increased expression of IL-1β and IL-18 （P<0.05）， and compared with the model group， the PHI groups showed down-regulated IL-1β， IL-18 mRNA and protein expression （P<0.05）. Molecular docking suggested a good binding effect of PHI to P2X7R. Real-time PCR and Western blot analysis showed that the expression of P2X7R in the model group was significantly up-regulated compared with that in the normal group （P<0.05）， and compared with the model group， the PHI groups showed down-regulated mRNA and protein expression of P2X7R （P<0.05）. DCFH-DA results showed that compared with the normal group， the model group showed increased content of ROS （P<0.05）， and compared with the model group， the PHI groups decreased the accumulation of ROS （P<0.05）. As demonstrated by Real-time PCR and Western blot， compared with the normal group， the model group showed increased expression of NLRP3 inflammasome and NF-κB （P<0.05）， and compared with the model group， the PHI groups significantly decreased the mRNA and protein expression of NLRP3 and cleaved Caspase-1， and up-regulated the mRNA and protein expression of NF-κB and IκBα （P<0.05）. Real-time PCR analysis showed that compared with the results in the model group， after silencing P2X7R by siRNA， the mRNA expression of IL-1β， IL-18， P2X7R， NLRP3， Caspase-1， NF-κB， and IκBα was decreased （P<0.05）. PHI exerted the same effect， and the mRNA expression was further reduced after the combination of them.ConclusionPHI is presumed to suppress the expression of the NLRP3/NF-κB signaling pathway by down-regulating upstream P2X7R to alleviate the LPS/ATP-induced inflammation in L02 cells， suggesting that P2X7R may be the target of PHI against inflammation.
Keywords：phillygenin;purinergic 2X7 receptor （P2X7R）;L02 cell;NOD-like receptor family pyrin domain containing 3 （NLRP3） inflammasome;nuclear factor kappa B （NF-κB）
Abstract：ObjectiveThe effect of modified Shengjiangsan on immunoglobulin A （IgA） nephropathy was observed. The microRNA-148b （miRNA-148b）， interleukin 6 （IL-6）， core 1 beta 1，3-galactosyltransferase （C1GALT1）， molecular chaperone Cosmc （core1β3-Gal-T-specific molecular chaperone C1GALT1C1）， and galactose-deficient IgA1 （Gd-IGA1） in serum and kidney tissues of IgA nephropathy rats were detected to explore the underlying mechanism. The result is expected to lay a scientific basis for clinical application of modified Shengjiangsan in the treatment of IgA nephropathy.MethodA total of 42 SPF male SD rats were randomized into the normal group （8rats） and modeling group （34 rats） with the random number table method. After one week of adaptive feeding， rats for modeling were given bovine serum albumin （BSA， gavage）， lipopolysaccharide （LPS， injection into tail vein）， carbon tetrachloride （CCl4， subcutaneous injection）， and castor oil to induce IgA nephropathy. After modeling， two rats were randomly selected to test the modeling outcome. Then the model rats were classified into the model group， low-dose Chinese medicine group （modified Shengjiangsan，6.27 g·kg-1）， high-dose Chinese medicine group （modified Shengjiangsan，12.54 g·kg-1）， and benazepril group （10 mg·kg-1） with the random number table method， 8 in each group. The administration （gavage， once a day） lasted 4 weeks. The 24-h urinary total protein （24 h-UTP） was detected at the end of the 1st， 9th， and 13th week of the experiment. At the 14th week， after anesthesia， femoral artery blood was collected and centrifugated. The supernatant was collected to detect albumin （ALB）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The expression levels of IL-6 and Gd-IGA1 were determined by enzyme-linked immunosorbent assay （ELISA）. Based on hematoxylin-eosin （HE）/Masson/periodic Schiff-methenamine silver （PASM） staining， the pathological changes of renal tissues were observed. Ultrastructural changes of glomeruli were observed by transmission electron microscopy. The expression of miRNA-148b， IL-6， C1GALT1， and C1GALT1C1 was detected by immunohistochemistry. The mesangial area of the glomeruli was observed by immunofluorescence. Real-time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of mirNA-148b， IL-6， C1GALT1， and C1GALT1C1， and Western blot was used to detect the protein levels of IL-6， C1GALT1， and C1GALT1C1.ResultCompared with normal group， the model group showed increase in the content of 24 h-UTP， SCr， ALT， IL-6， and GD-IGA1 （P<0.05）， decrease in ALB content （P<0.05）. Moreover， rats in the model group demonstrated hyperplasia of glomerular mesangial cells， thickening of mesangial area， podocyte foot process effacement， and a large number of granular IgA immune complex in the mesangial area. In addition， the model group showed increase in the expression of IL-6 in mesangial area and podocytes， decrease in the expression of C1GALT1 and C1GALT1C1 in mesangial area and podocytes， enhanced expression of IL-6 mRNA and miRNA-148b （P<0.01）， weakened expression of C1GALT1 mRNA and C1GALT1C1 mRNA （P<0.01）， rise of IL-6 protein expression （P<0.01）， and reduction in the protein expression of C1GALT1 and C1GALT1C1 （P<0.01）. Compared with the model group， modified Shengjiangsan decreased the content of 24 h-UTP， SCr， ALT， IL-6， and Gd-IGA1 （P<0.05） and increased the content of ALB （P<0.05， P<0.01）. Moreover， with the treatment of this Chinese medicine， the pathological damage was significantly alleviated and the deposition of IgA immune complex in basement membrane was reduced. The expression of IL-6 in the mesangial area and podocytes of rats was decreased， and the expression of C1GALT1 and C1GALT1C1 in the mesangial area and podocytes of rats was increased. Moreover， the expression of IL-6 mRNA and miRNA-148b was decreased （P<0.01）， and the expression of C1GALT1 mRNA and C1GALT1C1 mRNA was increased （P<0.01）. The protein expression of IL-6 was decreased （P<0.05， P<0.01）， and the protein expression of C1GALT1 and C1GALT1C1 was enhanced （P<0.05， P<0.01）. The Chinese medicine group showed obvious dose-effect trend.ConclusionModified Shengjiangsan may reduce the expression of miRNA-148b and IL-6 in serum and kidney tissue of IgA nephropathy rats， restore the expression of C1GALT1 and C1GALT1C1， and decrease the generation of Gd-IGA1， so as to reduce renal pathological damage and proteinuria， protect the kidney protection， and finally delay the disease progression. Moreover， the effect is enhanced with the rise of dose.
Abstract：ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice.MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg-1）， a DIO + high-dose tripterine group （1.0 mg·kg-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg-1）， and a COM + high-dose tripterine group （1.0 mg·kg-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes.ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells.ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.
Abstract：ObjectiveTo investigate the mechanism of quercetin in regulating chondrocyte extracellular matrix metabolism and inflammatory response in knee osteoarthritis （KOA） from the perspective of autophagy.MethodChondrocytes were extracted and cultured， and the primary cells were identified by immunofluorescence staining with collagen Ⅱ. The chondrocytes induced by lipopolysaccharide （LPS） were divided into a control group （without any treatment）， a model group （10 mg·L-1 LPS treatment for 48 h）， and low-， medium-， and high-dose quercetin group （10 mg·L-1 LPS treatment for 48 h combined with 50， 100， and 150 mmol·L-1 quercetin for 24 h）. The inhibitory effects of LPS （2.5， 5， 7.5， 10， 12.5 mg·L-1） on the proliferation of chondrocytes for different periods （24， 48， 72 h） were detected by cell counting kit-8 （CCK-8）. The effects of quercetin （50， 100， 150， 200 mmol·L-1） on the LPS-induced proliferation of chondrocytes for different periods （12， 24， and 48 h） were investigated. The expression of microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） and ubiquitin-binding protein p62 was detected by Western blot. LPS-induced chondrocytes were treated with 3-methyladenine （3-MA）. The resultant cells were divided into a control group （without any treatment）， a model group （10 mg·L-1 LPS）， a quercetin group （model group + 100 mmol·L-1 quercetin）， a 3-MA group （model group + 100 μmol·L-1 3-MA）， and a 3-MA + quercetin group （model group + 100 μmol·L-1 3-MA + 100 mmol·L-1 quercetin， specifically， LPS for 48 h， 3-MA for 2 h， and then quercetin for 24 h）. The content of interleukin （IL）-1β and tumor necrosis factor （TNF）-α was determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of matrix metalloproteinase 13 （MMP-13） and tissue inhibitor of metalloproteinase 1 （TIMP1） was detected by Western blot.ResultCollagen Ⅱ immunofluorescence staining showed that the extracted cells were consistent with the characteristics of chondrocytes. As revealed by CCK-8， the optimum concentration of LPS was 10 mg·L-1 with an action time of 48 h， and the optimum concentration of quercetin was 100 mmol·L-1 with an action time of 24 h. Western blot results showed that compared with the control group， the model group showed decreased expression of LC3Ⅱ （P<0.01） and increased expression of p62 （P<0.01）. The expression of LC3Ⅱ in the quercetin groups was higher than that in the control group （P<0.01）， especially in the medium-dose quercetin group. The p62 expression in the quercetin groups was lower than that in the control group （P<0.01）， especially in the medium-dose quercetin group. Compared with the control group， the model group showed increased expression of MMP-13 （P<0.05） and decreased expression of TIMP1 （P<0.01）. Compared with the model group， the quercetin groups and the 3-MA + quercetin group showed decreased expression of MMP-13 （P<0.05， P<0.01）， especially the quercetin groups， and increased expression of TIMP1 （P<0.01）， especially the quercetin groups. Morphological changes in chondrocytes under the inverted microscope showed that quercetin could restore the morphology of damaged chondrocytes. CCK-8 showed that compared with the control group， the model group showed inhibited chondrocyte proliferation （P<0.01）， and compared with the model group， the quercetin groups and the 3-MA + quercetin group showed promoted chondrocyte proliferation （P<0.01）， especially the quercetin groups. ELISA results showed that IL-1β and TNF-α levels in the model group were higher than those in the control group （P<0.01）， and the levels of IL-1β and TNF-α in the quercetin groups and the 3-MA + quercetin group were lower than those in the model group （P<0.05， P<0.01）， and the decrease in the quercetin groups was the most significant.ConclusionQuercetin can promote LPS-induced chondrocyte proliferation， regulate chondrocyte extracellular matrix synthesis and metabolic balance， inhibit the inflammatory response， and restore chondrocyte function. The mechanism may be related to the activation of autophagy by quercetin.
Abstract：ObjectiveTo investigate the effect of betulinic acid （BA） on apoptosis and autophagy of human colorectal cancer SW620 cells and the regulatory role of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway.MethodCell viability was detected by methyl thiazolyl tetrazolium （MTT） colorimetry to determine the optimal administration time and dosage for subsequent experiments. Four groups were designed， including blank group and low-， medium-， and high-dose BA groups. Hematoxylin-eosin （HE） staining was conducted for the observation of SW620 cell morphology， and annexin-V/propidium iodide double staining for the determination of apoptosis rate in SW620 cells. Hoechst33258 staining and MDC staining were used for the observation of apoptosis and autophagy， respectively. Western blotting was employed to determine the protein levels of B-cell lymphoma/leukemia-2（Bcl-2）-associated X protein （Bax）， aspartate proteolytic enzyme-9 （Caspase-9）， activated aspartate proteolytic enzyme-3 （cleaved Caspase-3）， microtubule-associated protein 1 light chain 3 （LC3）， the mammalian homolog of yeast Atg6 （Beclin-1）， p62， phosphorylated PI3K （p-PI3K）， phosphorylated Akt （p-Akt）， and phosphorylated mTOR （p-mTOR） in SW620 cells.ResultBA inhibited the activity of SW620， HT29， and HCT116 cells in a concentration- and time-dependent manner. The cells treated with BA for 48 h had lower viability than those treated for 24 h （P<0.05， P<0.01）. The half maximal inhibitory concentration (IC50） value of BA at the time point of 48 h was also lower than that at the time point of 24 h （P<0.01）， and that for SW620 cells was the minimum. BA induced the apoptosis in a concentration-dependent manner and increased the autophagosomes. Compared with the blank group， BA increased the apoptosis rate （P<0.01）， up-regulated the protein levels of Bax， Caspase-9， cleaved Caspase-3， and LC3 Ⅱ （P<0.05， P<0.01）， and down-regulated the protein levels of p62， p-Akt， p-PI3K， and p-mTOR （P<0.01）. Additionally， medium- and high-dose BA up-regulated the protein level of beclin-1 （P<0.01）.ConclusionBA may inhibit the activity of SW620 cells by hindering the PI3K/Akt/mTOR signaling pathway to induce cell apoptosis and autophagy.
Keywords：betulinic acid （BA）;phosphatidylinositol-3 kinase/ protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway;colorectal cancer cell;SW620;apoptosis;autophagy
Abstract：ObjectiveTo observe the clinical efficacy and safety of traditional Chinese medicine （TCM） external therapeutic protocol of enriching pus for tissue growth （EPTG） in the treatment of Wagner 2-3 diabetic foot ulcer.MethodThe randomized controlled trial （RCT） design was adopted. Patients receiving basic treatment were divided into the EPTG group and the control group （debridement and change of nano-silver medical antibacterial dressing）. Ulcer healing rate， ulcer area， ulcer depth， TCM symptom score， visual analogue scale（VAS）， transcutaneous partial pressure of oxygen， wound blood flow， inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）］， growth factors ［vascular endothelial growth factor （VEGF）， transforming growth factor-β1 （TGF-β1）， and fibroblast growth factor-β （FGF-β）］， adverse events， and outcome events of the two groups before and after treatment were observed.ResultCompared with the conditions before treatment， the ulcer healing rate， ulcer area， ulcer depth， TCM symptom score， VAS score， transcutaneous partial pressure of oxygen， wound blood flow， CRP， IL-6， TNF-α， VEGF， TGF-β1， and FGF-β were significantly improved （P<0.01）. In terms of the improvement in the ulcer healing rate， ulcer area， ulcer depth， VAS score， transcutaneous partial pressure of oxygen， wound blood flow， CRP， IL-6， TNF-α， VEGF， TGF-β1， and FGF-β， the EPTG group was superior to the control group （P<0.01）. There were no statistically significant differences in adverse events and outcome events between the two groups.ConclusionThe TCM external therapeutic protocol of EPTG is safe and effective in the treatment of Wagner 2-3 diabetic foot ulcer. It can greatly reduce the area and depth of diabetic foot ulcer， improve the ulcer healing rate and TCM symptom score， relieve the pain of patients， and improve the microcirculatory blood supply in the local ulcer. Its mechanism of action may be related to the reduction of the local inflammatory response of the wound and the improvement of the proliferation of fibroblasts and vascular endothelial cells.
Keywords：enriching pus for tissue growth;Zizhu ointment;diabetic foot;diabetic ulcer;Wagner 2-3;etraditional Chinese medicine external treatment
Abstract：ObjectiveTo study the efficacy of Aclasta combined with Liuwei Dihuangwan on osteoporosis and the effect on quality of life.MethodA total of 126 patients with osteoporosis who were treated in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from September 2019 to September 2020 were classified into the observation group and the control group with the randomized double-blind method. The observation group consisted of 60 patients （26 males and 34 females） with the age of 59-85 years old ［mean： （72.0 ± 6.5） years old］. The control group was composed of 66 patients （31 males and 35 females）， with the age of 62-82 years old ［mean： （73.0±8.2） years old］. The control group was treated with Aclasta， and the observation group Aclasta combined with Liuwei Dihuangwan. After treatment， the effective rate of each group was calculated. Bone mineral density （BMD） was measured in both groups before and after treatment， and serological parameters calcium （Ca）， total 25 （OH） vitamin D3 （VITD-T）， osteocalcin （OC）， serum alkaline phosphatase （ALP）， parathyroid hormone （PTH）， β-collagen special sequence （β-CTX）， and total procollagen 1 N-terminal propeptide （T-P1NP） were also measured. Visual Analogue Scale （VAS） score， Japanese Orthopaedic Association （JOA） score， and Oswestry Disability Index （ODI） score were evaluated. On this basis， the effect was compared between the two groups.ResultThe indexes were insignificantly different between the two groups before treatment. After 6 months of treatment， the two groups showed decrease in VAS score and ODI score （P<0.01）， increase in JOA score （P<0.01）， BMD of lumbar spine and hip joint， elevation of Ca， VITD-T， OC， ALP， and PTH （P<0.05， P<0.01）， and decrease of β-CTX （P<0.01） as compared with before treatment. The level of T-P1NP dropped in the observation group after treatment （P<0.01）.After treatment， the total effective rate of the observation group was 88.3% （53/60）， as compared with the 74.2% （49/66） in the control group （χ2=4.047， P<0.05）. Moreover， after treatment， the observation group demonstrated higher levels of BMD， Ca， VITD-T， OC， and PTH （P<0.05）， lower levels of T-P1NP （P<0.05）， lower VAS score （P<0.01）， and higher JOA score （P<0.05） than the control group， but the ODI score was insignificantly different from that in the control group.ConclusionAclasta combined with Liuwei Dihuangwan is effective on osteoporosis， without increasing the incidence of adverse reactions. In addition， the combination can alleviate pain and improve the quality of life of osteoporosis patients.
Keywords：Aclasta;Liuwei Dihuangwan;osteoporosis;bone mineral density
Abstract：ObjectiveTo observe the variation in content of vascular endothelial growth factor （VEGF） in patients with Alzheimer's disease （AD） and to investigate efficacy of Yangxue Qingnao granule on AD and the effect on VEGF.MethodA total of 60 patients with cognitive impairment ［30 of AD and 30 of amnestic mild cognitive impairment （aMCI）］ were selected， and another 30 healthy people with Montreal Cognitive Assessment （MoCA）≥26 and age， gender， and complications insignificantly different from the patients were included as healthy control. The venous blood of aMCI group， AD group， and the healthy control group was collected at the enrollment to measure the level of serum VEGF. Then， the aMCI and AD patients were randomized into the observation group and the control group， with 30 patients in each group. The control group was given Donepezil Hydrochloride （5 mg·d-1）， while the observation group received Donepezil Hydrochloride （5 mg·d-1） and Yangxue Qingnao granule. MoCA was used to evaluate the severity of cognitive impairment. After the treatment for 6 months， the clinical efficacy and adverse reactions of the two groups were compared， and the serum VEGF levels were detected again by enzyme-linked immunosorbent assay （ELISA）.ResultThe serum content of VEGF in AD patients was significantly lower than that in aMCI patients and healthy people （P<0.05）. Serum VEGF levels in aMCI patients were significantly decreased compared with those in healthy people （P<0.05）. After treatment for 6 months， the serum VEGF level in the observation group was significantly higher than that before treatment， and was higher than that in the control group （P<0.05）. MoCA scores in the observation group were higher than those in control group （P<0.05）. The incidence of adverse reactions was insignificantly different between both groups.ConclusionThe serum levels of VEGF significantly decreased in aMCI and AD patients， suggesting that angiogenesis might be involved in the pathophysiological process of AD and correlated with the early stage of AD. Yangxue Qingnao granule， as a safe adjuvant therapy， showed ideal effect on aMCI and AD， as manifested by the improvement of cognitive function. The mechanism is the likelihood that it can elevate the expression of angiogenic factors such as VEGF， promote angiogenesis， and then improve the microcirculation of cortex.
Abstract：ObjectiveAlmond， which is bitter in taste， contains traces of toxic substances. For the sake of the safety of prescriptions containing this medicinal material， the processing method of "soaking in boiling water" was selected. Moreover， through literature research and network pharmacology， the characteristic index of this medicinal material was determined. On this basis， a method was established for the determination of amygdalin in Qingfei Paidu Granules （QFPD） and the transfer rate of it in the processing of this prescription was monitored， aiming at improving the quality control system of QFPD.MethodThe high performance liquid chromatography conditions are as follows： YMC Triart C18 column （4.6 mm × 150 mm， 5 µm）， mobile phase of methanol-water with flow of 1.0 mL·min-1， column temperature of 35 ℃， and detection wavelength of 210 nm.ResultThe linear curve fitted well and the average recovery of amygdalin was 97.74% with RSD of 4.3%. The transfer rates of amygdalin from the medicinal material to the extract， from extract to concentrate， and from concentrate to granules were investigated with this method. The result showed that the average transfer rate from the medicinal material to the granules was （60±3.91）%. The comparison of transfer rate between the processes suggesting that the extraction of the medicinal material might be the key part influencing the prescription preparation.ConclusionThe method is simple， sensitive， reproducible， stable， and accurate， and the index is reasonable. Thus， the method can be used for the quality control of QFPD and determination of transfer rate of components in the preparation of QFPD. This study further improves the quality control standard of almond in QFPD， which can serve as a reference for the clinical application of QFPD.
Abstract：ObjectiveBy comparing the difference of volatile components of the decoction pieces before and after being processed by braising method of Jianchangbang and steaming method included in the 2020 edition of Chinese Pharmacopoeia， the influence of processing methods on the flavor formation of Polygoni Multiflori Radix （PMR） was compared.MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components of 30 batches of PMR samples from 3 origins with 3 processing methods. The GC was performed under programmed temperature （starting temperature of 40 ℃， rising to 150 ℃ at 5 ℃·min-1， and then rising to 195 ℃ at 10 ℃·min-1） with high purity helium as carrier gas and the split ratio of 10∶1. Mass spectrometry conditions were electron impact ion source （EI） and the detection range of m/z 50-650， the peak area normalization method was used to calculate the relative mass fraction of each component. The chromaticity values of different processed products were measured by a precision colorimeter， the relationship between chromaticity values and relative contents of volatile components was investigated by OriginPro 2021， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed on the sample data by SIMCA14.1. The differential components of different processed products of PMR were screened according to the principle of variable importance in the projection （VIP） value>1.5， and the material basis of different odor formation of PMR and its processed products was explored.ResultA total of 59 volatile components were identified， among which 34 were raw products， 33 were braised products， and 27 were steamed products. PCA and OPLS-DA results showed that there were significant differences between the three， but there was no significant difference between samples from different origins of the same processing method. Color parameters of a*， b*， E*ab had no significant correlation with contents of volatile components， while L* was negatively correlated with contents of 2-methyl-2-butenal， 2-methyltetrahydrofuran-3-one and 2，3-dihydro-3，5-dihydroxy-6-methyl-4（H）-pyran-4-one （P<0.05）. The contents of pungent odor components such as caproic acid， nonanoic acid and synthetic camphor decreased after processing， while the contents of sweet flavor components such as 2-methyl-2-butenal， furfural and 5-hydroxymethylfurfural increased after processing， and the contents of furfural， 5-methyl-2-furanmethanol， 5-hydroxymethylfurfural and other aroma components in the braised products were significantly higher than that in the steamed products.ConclusionHS-GC-MS can quickly identify the volatile substance basis that causes the different odors of PMR and its processed products. The effect of processing methods on the odor is greater than that of origin. There is a significant correlation between the color parameter of L* and contents of volatile components， the "raw" taste of PMR may be related to volatile components such as caproic acid， pelargonic acid and synthetic camphor， the "flavor" after processing may be related to the increase of the contents of 2-methyl-2-butenal， furfural， 5-hydroxymethylfurfural， methyl maltol and furfuryl alcohol.
Keywords：Polygoni Multiflori Radix;headspace-gas chromatography-mass spectrometry （HS-GC-MS）;braising method;volatile components;chromaticity values;processing of traditional Chinese medicine
Abstract：ObjectiveTo investigate the quality of Ligustri Lucidi Fructus in the market， and the moisture， extract， determination of Zhuyao and Douchi Ligustri Lucidi Fructus were compared to increase the utilization rate of Ligustri Lucidi Fructus.MethodThe properties， moisture， total ash， alcohol-soluble extract content and thin layer chromatography （TLC） identification were determined by the methods of Ligustri Lucidi Fructus included in the 2020 edition of Chinese Pharmacopoeia， and high performance liquid chromatography （HPLC） fingerprint and determination of specnuezhenide and salidroside were established with the mobile phase of 0.2% phosphoric acid aqueous solution （A）-acetonitrile （B） （0-70 min， 92%-65%A） for gradient elution， and the detection wavelength of 220 nm at 0-14 min and 225 nm at 14-70 min. The two different characters of Ligustri Lucidi Fructus were comprehensively compared by the above indicators.ResultExcept for one batch which did not meet the requirements due to the quality of harvesting， the other 12 batches of samples all met the requirements of the 2020 edition of Chinese Pharmacopoeia， but there were two different characters. Comparing the two different characters of Ligustri Lucidi Fructus， it is found that the moisture， total ash， extract， salidroside and specnuezhenide contents of Zhuyao samples were 2.22%-5.19%， 3.91%-4.49%， 32.56%-40.95%， 0.073%-0.170% and 1.45%-4.14%， and these values of Douchi samples were 3.57%-5.61%， 3.65%-4.44%， 41.31%-46.70%， 0.041%-0.067% and 3.01%-4.20%， respectively.ConclusionThe contents of extract and specnuezhenide of Douchi Ligustri Lucidi Fructus are mostly higher than those of Zhuyao Ligustri Lucidi Fructus， while the content of salidroside is lower than that of Zhuyao samples， and there are no significant differences in moisture， TLC identification and total ash content. Based on the above research， if the main purpose is to extract salidroside， it is recommended to choose Zhuyao Ligustri Lucidi Fructus. If the main purpose is to use Ligustri Lucidi Fructus as medicine， it is recommended to choose Douchi Ligustri Lucidi Fructus.
Abstract：Objetive： To investigate the mechanism of antidepressant effect of verbascoside based on high-throughput sequencing technology （RNA-Seq），and to explore the possible targets and signaling pathways.MethodsForty C57BL/6 mice were randomly divided into control group，model group，fluoxetine group and verbascoside group，10 mice in each group. Except for the control group，all the other three groups were constructed with chronic unpredictable mild stimulation （CUMS） combined with solitary feeding for four weeks. Control group，fluoxetine group and verbascoside group were administered by gavage once daily for three weeks during the second week of modeling. The mice were assessed by sugar-water preference test，forced swimming test，open field test，elevated cross maze test，and water maze test. Enzyme linked immunosorbent assay（ELISA） was performed to detect the levels of major neurotransmitters and inflammatory factors in mice serum，and mRNA high-throughput sequencing was performed in the nucleus accumben and colon to screen differentially expressed genes and perform pathway enrichment analysis. Real-time polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression of Gad，Slc32a1（VGAT） and brain-derived neurotrophic factor (BDNF） in nucleus accumbens.ResultCompared with the control group，the anxiety and depression-like behaviors in the model group increased，while the learning and memory ability decreased significantly. The content of neurotransmitter in serum decreased significantly. The content of pro-inflammatory factors increased significantly. The mRNA expression of Gad and Slc32a1（VGAT） in nucleus accumbens decreased significantly，while that of BDNF increased significantly. Compared with the model group，the anxiety and depression-like behavior of mice in verbascoside group was significantly relieved. The neurotransmitter content increased significantly，and the pro-inflammatory factors decreased significantly. The mRNA expression of Gad and Slc32a1（VGAT） in nucleus accumbens increased significantly，while that of BDNF decreased significantly.A total of 48 differentially expressed genes in nucleus accumbens and 43 differentially expressed genes in colon were screened by high-throughput sequencing. Differential genes in nucleus accumbens mainly focus on neuroactive ligand-receptor interaction， γ-aminobutyric acid（GABA）ergic synapse，synaptic vesicle cycle and other pathways. Colonic differential genes are mainly concentrated in GABAergic synapses，synaptic vesicle circulation，cyclic adenosine monophosphate（cAMP） signal pathway and other signal pathways. Compared with the control group，the mRNA expression of Gad and Slc32a1（VGAT） in nucleus accumbens of model group decreased significantly，while the mRNA expression of BDNF increased significantly.ConclusionVerbascoside has significant antidepressant effects. Its antidepressant effect may be related to the increase of monoamine neurotransmitters，the decrease of pro-inflammatory factors and the restoration of neurotransmitter homeostasis by increasing GABA，and it mainly acts through the signaling pathways such as neuroactive ligand-receptor interaction，GABAergic synapses，synaptic vesicle cycle and cAMP signaling pathway.
Abstract：ObjectiveTo explore the application law of compound prescriptions containing Coptidis Rhizoma to diabetes and its complications based on data mining.MethodA total of 288 records on formulas containing Coptidis Rhizoma in the treatment of diabetes and its complications and the corresponding syndromes and symptoms were retrieved from the medical records of modern physicians， with 218 on the treatment of diabetes and 70 on the treatment of diabetes complications. The Traditional Chinese Medicine Inheritance Computing Platform （V3.0） was used or data mining on the compositions of the formulas. Moreover， it was employed for the frequency statistics， formula analysis， symptom analysis， association rules analysis， network visualization， and cluster analysis.ResultThe 218 formulas containing Coptidis Rhizoma for the treatment of diabetes involved 190 Chinese medicinals. A total of 12 syndromes showed the occurrence frequency ≥ 6， and the one with the highest frequency was deficiency of both qi and yin， followed by the syndrome of excessive heat in lung and stomach， syndrome of Yin deficiency and effulgent fire， and syndrome of excessive heat and fluid consumption. The dose of Coptidis Rhizoma for the treatment of diabetes ranged from 1.5-30 g， and the most frequently used doses were 10， 6， and 5 g. The medicinal was frequently applied for the traditional Chinese medicine symptoms of dry stool， dry mouth and tongue， and swift digestion with rapid hungering. Moreover， 26 core medicinal pairs， 17 association rules， 3 diagrams on medicinal relationship， and 3 core combinations were yielded. The 70 formulas containing Coptidis Rhizoma for the treatment of diabetes complications involved 184 Chinese medicinals， and the top 3 complications were diabetic nephropathy， diabetic peripheral neuropathy， and diabetic gastroenteropathy. The dose of Coptidis Rhizoma in the treatment of diabetes complications fell in the range of 2-15 g， and 10， 6， and 5 g were most frequently used.ConclusionFormulas containing Coptidis Rhizoma for the treatment of diabetes and its complications mainly target the syndrome of dampness-heat transforming into fire and the syndrome of excessive heat damaging yin. This study can serve as a reference for standard use of Coptidis Rhizoma in the prevention and treatment of diabetes and its complications.
Keywords：Coptidis Rhizoma;diabetes;data mining;medication rules;Traditional Chinese Medicine Inheritance Computing Platform （V3.0）
Abstract：ObjectiveTo explore the effective components， targets， and mechanism of Houttuynia cordata against lung cancer by means of systems pharmacology and further to provide a reference for the further development and clinical application of this medicinal.MethodChemical components of H. cordata were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the active components were screened based on oral bioavailability （OB） and drug-likeness （DL）. Then the potential targets were predicted， followed by enrichment analysis. Finally， sodium houttuyfonate （SH） was selected for verifying the anti-tumor mechanism. Cell counting kit-8 （CCK-8） assay was used to evaluate the effect of SH on the in vitro proliferation of two lung cancer cell lines： A549 and LLC， and the regulation of tumor-related proteins by SH was verified by Western blot.ResultA total of 7 active compounds and 352 targets of the active components were screened out. According to the enrichment analysis of targets， H. cordata had potential therapeutic effects on cancer. SH had inhibitory effect on both A549 and LLC. Western blot results showed that G1/S-specific Cyclin D1， E1 and cyclin-dependent kinase （CDK）2， CDK4 all tended to be down-regulated， and Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） also changed significantly.ConclusionH. cordata has the potential anti-tumor effects by arresting the tumor cells in the G1 phase through the JAK2/STAT3 pathway.
Abstract：Primary liver cancer is one of the common tumors in China， which seriously endangers human health. With the advancement in medical science and technology， some achievements have been made in the clinical treatment of liver cancer， but there is an urgent need to find a safe and effective solution for patients with advanced liver cancer. As a unique therapy in China， traditional Chinese medicine （TCM） has the characteristics of multiple targets and multiple pathways and plays a certain role in the treatment of malignancies. The present study aimed to clarify the mechanism of action of "dispelling pathogens" in the treatment of liver cancer through literature research. In TCM etiology and pathogenesis， deficient healthy Qi and exuberance of pathogenic Qi， such as phlegm， blood stasis， and toxins， lead to the development of liver cancer. The treatment should follow the principles of reinforcing healthy Qi and eliminating pathogens. It has been generally believed that tumor cell is the "pathogenic factor" and the immune function serves as the "healthy Qi". In the treatment of malignancies and the regulation of the immune function of patients， it is often advocated to reinforce healthy Qi to eliminate the accumulation. With the continuous updating of knowledge on tumors and tumor microenvironment， it is also recognized that there are "healthy Qi" and "pathogenic Qi" in the immune microenvironment of tumors. For example， the immune cells and immune factors that inhibit tumor growth can be classified as "healthy Qi" with TCM attributes， while those promoting tumor growth can be classified as "pathogenic Qi". Additionally， as proved by clinical data and experimental research， the elimination methods represented by "activating blood， resolving phlegm， and removing toxins" in the treatment of liver cancer can combat tumor cells and also regulate the "healthy Qi" and "pathogenic Qi" in the immune microenvironment of liver cancer to achieve the balance of Yin and Yang. Based on this， the present study reviewed from the TCM theory and the mechanisms of western medicine to provide theoretical support for the TCM treatment of malignancies by elimination methods and some ideas for TCM in tumor resistance.
Keywords：liver cancer;tumor immune microenvironment;traditional Chinese medicine;eliminating pathogens;activating blood， resolving phlegm， and removing toxins
Abstract：Oligozoospermia and asthenospermia are common causes of clinical male infertility. The number of patients increases year by year and shows a younger trend. Its etiology is complex， the mechanism and unclear pathogenesis and rely on empirical therapy. Therefore， it is necessary for exploring the pathogenesis and developing corresponding drugs to establish reasonable animal models. By comparing different animal model making methods， this paper provides ideas for constructing a more standardized animal model of oligoasthenospermia. At the moment， a lot of molding methods for oligoasthenospermia are available. Combined with the animal experimental articles of oligoasthenospermia in recent years， this study described the modeling with adenine， ornidazole， tripterygium glycoside， hydrocortisone， cyclophosphamide， busulfan， paclitaxel， heat stress， ionizing radiation， high-fat diet， and gene knockout， respectively， and compared the modeling methods in terms of the time， indexes， animal line， and model evaluation. Thereby， the advantages and disadvantages of different models of oligoasthenospermia were summarized， and finds that the existing animal models of oligoasthenospermia still have many shortcomings that need to be further improved. The selection， standardization and innovation of animal models need to be solved urgently， and the coincidence between animal models and clinical patients' traditional Chinese medicine syndromes is not coincident. In view of the existing problems， we should further explore how to build a modeling method in line with clinical characteristics and syndrome types， select the compound model method of integrated traditional Chinese and Western medicine， copy the model closer to the law of disease development and in line with traditional Chinese medicine syndrome， and provide animal experimental support for exploring the mechanism of disease， developing characteristic drugs and guiding clinical medication.
Abstract：The most common manifestations of inflammatory bowel disease （IBD） are Crohn's disease and ulcerative colitis， and the global incidence of IBD is on the rise. Traditional Chinese medicine （TCM） is advantageous in the treatment of IBD. IBD， with TCM names based on clinical symptoms， mostly belongs to recurrent dysentery， long dysentery， diarrhea， dysentery， bowel， and other categories. In TCM pathogenesis of IBD， spleen deficiency and exuberant dampness predominate in the whole course of the disease. Since the lung is associated with the large intestine and the lung Qi and spleen Qi are interconnected， the lung Qi and spleen Qi are deficient and the dampness and heat accumulate internally， which caused collateral obstruction by stagnant blood and the development of IBD. From the perspective of "associating lung with large intestine"，it is believed that the main mechanism of IBD is the Qi imbalance and abnormal metabolism of fluids in the lung and the intestine，and the nutrient-Yin injury of the lung and the intestine. According to the chronic， recurrent， and diffuse pathogenesis characteristics and main clinical manifestations of IBD， IBD is closely related to the lung and the intestine. In terms of therapeutic principles， IBD can be treated by tonifying the spleen and replenishing the lung， which highlights the treatment of the intestine from the lung. To be specific， in time of tonifying the spleen and removing dampness， the intestine is regulated by tonifying the spleen and replenishing the lung. Shenling Baizhusan， a commonly used classical prescription for IBD， is mainly potent in replenishing Qi， invigorating the spleen， draining dampness， checking diarrhea， and especially "reinforcing earth to generate metal". It can enhance the function of the lung through "reinforcing earth to generate metal"， which in turn regulates the intestine and promote the improvement of IBD. The present study clarified the mechanism of Shenling Baizhusan in regulating the intestine by tonifying the spleen and replenishing the lung. On the basis of modern research， its therapeutic effect on IBD was achieved through multiple links， such as regulation of the level of inflammatory factors， immunoregulation， barrier function improvement via mucosal repair， and intestinal flora. The findings of this study are expected to provide new ideas for the regulation of the lung-spleen-large intestine axis in the syndrome differentiation and treatment of IBD and subsequent experimental research.
Keywords：inflammatory bowel disease;Shenling Baizhusan;reinforcing earth to generate metal;associating lung with large intestine
Abstract：The basic pathological change of diabetic macroangiopathy is atherosclerosis， and the metabolism legacy effect of hyperglycemia will cause continuous damage to the large vessels. Oxidative stress is a common mechanism for diabetes and its chronic complications and it is also the basis of the metabolism legacy effect which keeps damaging the large vessels. Anti-oxidant therapy can delay the course of diabetic macroangiopathy. According to the theory of traditional Chinese medicine （TCM）， the pathogenicity of hidden pathogen is concealing， lingering， and refractory. On the basis of the syndrome and treatment of collateral diseases， vessel-collateral theory， and hidden pathogen theory of TCM， the pathological changes of diabetic macroangiopathy are summarized as pathogen concealment-accumulation of sugar and lipids leading to phlegm and blood stasis-accumulation of toxins-damage to vessels and collaterals-hardening vessels. The core pathogenesis is the hidden pathogen damaging the collaterals， and the basic pathological change is vessel hardening. The toxins of sugar， lipid， phlegm， and stasis are the pathological products and the key to be treated. According to this theory， the medicinal materials with the functions of activating blood to dredging collaterals， resolving phlegm to clearing collaterals， Promoting qi to unblocking collaterals and removing toxins to shunting collaterals can be selected for prescription. These medicinal materials can inhibit the generation of reactive oxygen species， affect the oxidase activity， and enhance the antioxidant capacity， thereby regulating the oxidative stress response， protecting the vascular endothelial function， reducing the damage of the large blood vessels， and slowing down the progression of the disease. Such therapy is of great significance in clinical practice and research， providing a new idea for the prevention and treatment of diabetic macroangiopathy.
Abstract：After more than 100 years of development， spray drying technology has become more mature and widely used， and it is of great importance in the field of traditional Chinese medicine （TCM）. TCM powders prepared by spray drying is the raw material of dispensing granules， and the powder properties have an important influence on subsequent molding process and product quality. As a new form of TCM， dispensing granules have been included in the management category of TCM decoction pieces， indicating a broader application market， and a consensus has also been reached on the importance of TCM powder research. Based on this， the author summarized the application progress of spray drying in the study of TCM powders， including the factors affecting spray drying process， such as liquid properties， process parameters and equipment factors， as well as the application of computational fluid dynamics （CFD） and thermodynamic model in spray drying process simulation. Moreover， some commonly used pharmaceutical excipients for the modification of TCM powders were also introduced such as maltodextrin， microcrystalline cellulose and povidone. In addition， spray drying technology can also be used as a preparation technology for new drug delivery systems such as microcapsules and solid dispersions. Through the summary of this paper， the author suggests that the future research direction of spray drying of TCM can be carried out from the aspects of application rule of the coprocessing auxiliary materials based on the "unification of medicines and excipients"， the "structure-property" relationship of spray-dried powders and the application of computer simulation and design， so as to further enrich the application of spray drying in the field of TCM powders.
Keywords：spray drying;quality by design （QbD）;physical characterization;powder modification;pharmaceutical excipients;computational fluid dynamics （CFD）;unification of medicines and excipients
Abstract：Bronchial asthma is a common heterogeneous chronic inflammatory disorder of airways characterized by airway hyperreactivity， mucus hypersecretion， and airflow obstruction. The incidence of asthma has been on the rise worldwide， and about 45.7 million adults in China suffer from asthma. Asthma is considered a costly disease， resulting in a significant economic and social burden. microRNAs （miRNAs） are long noncoding RNAs that regulate gene expression. They play a role in asthma through their activity in multiple immune and non-immune cell subsets. They impact multiple facets of critical cell function including cell survival， proliferation， and differentiation， which in turn induce the occurrence of airway spasm， mucus hypersecretion， and asthma symptoms. Traditional Chinese medicine has a long history in the treatment of asthma. Over the past a few decades， a growing number of herbs have proven effective in treating asthma in clinical trials or asthma inflammation in animal models. Chinese medicine has the features of multiple components and multiple targets. Evidence suggests that Chinese medicine and components of Chinese medicine can regulate immune homeostasis， improve airway inflammation and airway remodeling by modulating microRNA expression for asthma treatment. However， there is a lack of systematic and detailed reviews on the regulation of asthma-related microRNA expression by Chinese medicine. The article aims to review the correlation between microRNAs and asthma in animal experiments and clinical trials in recent years， as well as the mechanism of microRNA regulation by Chinese medicine in the treatment of asthma， with the intention of providing a reference for basic research and clinical application.
Abstract：Alzheimer's disease（AD） is an irreversible neurodegenerative disease with clinical manifestations such as memory impairment， aphasia， impaired visuospatial skills， executive function impairment， and personality changes. AD has brought a heavy burden to the family and society due to its unrevealed pathogenesis and the lack of therapeutic approaches. Saponins， a group of oligoglycosides whose aglycones are triterpenes or spirosteroids， are divided into triterpene saponins and steroidal saponins， which have a variety of biological activities. At present， there is no systematic review on the anti-AD effect of saponins. According to the literature published in recent years， the authors summarized the studies of saponins in improving AD based on animal experiments. The results indicated that saponins enhanced learning ability and improved cognitive impairment by inhibiting amyloid β-protein （Aβ） cascade activity， suppressing microtubule-associated protein （tau） hyperphosphorylation， inhibiting neuronal oxidative stress， inhibiting inflammatory factors， regulating apoptosis， inhibiting cholinergic neuronal degeneration， promoting mitochondrial autophagy， regulating intestinal flora， and enhancing energy metabolism， which in turn improved the pathological state of AD animal models. The therapeutic effects of different saponins on AD are different. The present study discussed the effect of different aglycones and sugar chains on the anti-AD activity based on saponins and anti-AD effect to provide new ideas and a theoretical basis for the development and utilization of saponins.
Abstract：Rheumatoid arthritis （RA） is a common autoimmune disease. Excessive hyperplasia of synovial tissues and osteoclastic bone absorption are two main causes of bone and joint destruction in RA. Synovial fibroblasts in RA （RA-FLS） are important cells in the synovial tissues of RA. The changes in their growth characteristics and inhibition of apoptosis lead to the proliferation of synovial tissues， stimulate inflammatory reactions， damage joint structure， and result in joint dysfunction. Therefore， regulating abnormal proliferation and promoting apoptosis of RA-FLS can interfere with the pathogenesis of RA. At present， there are many studies on the effect of Chinese medicine and its monomer components on the excessive proliferation and apoptosis of RA-FLS. The present study reviewed the effect of RA-FLS in RA and the intervention of Chinese medicinal monomers and compounds by regulating RA-FLS. The results showed that monomer components mainly included terpenoids， flavonoids， alkaloids， and anthraquinones. Despite different types， they can effectively intervene in RA through different approaches. For instance， they can prevent bone and cartilage injury by inhibiting the secretion of inflammatory cytokines and inhibiting the generation of chondrocytes and osteoclasts. They can achieve apoptosis by up-regulating the pro-apoptotic genes B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific protease （Caspase） in the Fas/FasL， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription protein （STAT）， and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathways， and down-regulating the anti-apoptotic genes Bcl-xl and Bcl-2. They can also inhibit the proliferation of RA-FLS by inhibiting the protein expression of microtubule-associated protein 1 light chain 3Ⅱ（LC3Ⅱ）/LC3Ⅰ and Beclin-1. Although their molecular mechanisms of action and targets are different， they all exert corresponding roles. The above research results provide a scientific basis for elucidating the multi-component and multi-target characteristics of Chinese medicine in the treatment of RA.
Keywords：rheumatoid arthritis（RA）;synovial fibroblasts in RA;Chinese medicine;research progress
Abstract：With serious environmental problems and the aging of population， the incidence of cancers worldwide has increased dramatically. For modern medicine， cancer is an incurable malignant disease with a high metastasis rate and strong cell proliferation and invasion ability. At present， clinical anti-cancer therapies mainly include chemotherapy and radiotherapy， but most chemotherapy drugs can cause serious side effects. Therefore， Chinese medicine with high safety has been widely used in anti-cancer treatment， which can inhibit the proliferation of cancer cells， improve the quality of life， and prolong life. Ligustrazine is a pyrazine alkaloid isolated and purified from Chuanxiong Rhizoma， which has pharmacological effects， such as anti-fibrosis， anti-oxidation， and anti-tumor. In recent years， ligustrazine， as an index active component of Chuanxiong Rhizoma alkaloids， has gradually become one of the hot spots in clinical medical research due to its pharmacological actions， and its anti-tumor effect has attracted more attention from researchers. The present study mainly investigated the anti-cancer effect of ligustrazine from the induction of tumor cell apoptosis and autophagy， inhibition of cell proliferation and migration， reversal of multidrug resistance of cancer cells， and inhibition of angiogenesis， and the anti-tumor efficacy was observed in various malignancies such as gastric cancer， lung cancer， rectal cancer， bladder cancer， breast cancer， and ovarian cancer. In addition， ligustrazine can be combined with cisplatin， paclitaxel， podophyllotoxin， chalcone， curcumin， and other drugs to exert an anti-tumor effect. This study conducted a literature review based on the anti-tumor mechanism of ligustrazine to provide a reference for the treatment of clinical malignancies.
Abstract：Shexiang Baoxin pills （SBP） are prescribed based on Suhexiang Pills derived from the Formulary of the Bureau of Taiping People's Welfare Pharmacy （《太平惠民和剂局方》） in the Song Dynasty. As the classic Chinese patent medicine in warming and dredging with aromatics， SBP have been widely used in clinical treatment for 30 years by virtue of their unique efficacy in coronary atherosclerotic heart disease （CHD）. Angiogenesis is a biological process in which the body activates angiogenesis-related factors in the body to act on endothelial cells under local vascular injury， tumor growth， local inflammation， and other stimuli to promote the proliferation， migration， and infiltration of endothelial cells， and form new sprouting or non-sprouting blood vessels. As a new strategy for ischemic diseases such as CHD， therapeutic angiogenesis is of great significance in the prevention and treatment of CHD in promoting angiogenesis of ischemic myocardium and establishing effective collateral circulation. However， for the atherosclerotic plaque and tumor， angiogenesis promotion is a risk factor for accelerating the disease progression. Therefore， safe and effective regulation of ischemic myocardial angiogenesis has become the focus of the current prevention and treatment of CHD. Studies in recent years have shown that SBP can intervene in angiogenesis with multiple pathways and targets， which can exert therapeutic angiogenesis effect on CHD and also inhibit atherosclerotic plaque and tumor angiogenesis to varying degrees. This study reviewed the experimental and clinical trials on the regulatory effect of SBPs on angiogenesis in CHD to provide references for the research on Chinese medicine intervention in angiogenesis of CHD.
Abstract：Multidrug resistance （MDR） has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells， the innate drug-resistant cells， are generally insensitive to radiotherapy and chemotherapy. Moreover， as the early symptoms of hepatocellular carcinoma are atypical， most patients are diagnosed at the advanced stage， with short survival period and high recurrence rate. Thus， the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma （PHC） treatment. Therefore， it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors， the mechanisms of compound Chinese medicine prescriptions， Chinese medicine injections， and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports， the mechanisms can be summarized as increasing intracellular drug concentration， influencing changes in enzyme activity， inducing apoptosis， reversing abnormalities in cellular signaling pathways， and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways， thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells. Therefore， exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However， there are few experimental types and adverse effects available. Thus， the multi-mechanism and multi-target experiments and clinical research should be carried out in the future.
Abstract：As a traditional Chinese medicinal material， Citri Sarcodactylis Fructus is often used as medicine after steaming to reduce its pungency and give full play to its medicinal effects. By consulting the relevant literature， this paper intends to sort out the related researches on the processing history， modern processing standard records， flavor and meridian tropism， efficacy， processing and taking methods， processing technology， chemical composition， pharmacological effects and quality analysis of Citri Sarcodactylis Fructus. It is found that the processing methods of Citri Sarcodactylis Fructus in the past dynasties are mainly roasting， distilled into dew， aging， frying， salting and steaming， of which steaming is the most common. In modern times， steaming is mainly used in Guangdong and Sichuan. The descriptions of flavor and meridian tropism and efficacy of Citri Sarcodactylis Fructus in the past dynasties are basically consistent with the modern descriptions. Its taste is pungent， bitter and acidic， and it is warm in nature. It belongs to the liver， spleen， stomach and lung meridians. Citri Sarcodactylis Fructus contains volatile oil， flavonoids and their glycosides， coumarins and limonins and other compounds. In recent years， high performance liquid chromatography （HPLC）， gas chromatography-mass spectrometry （GC-MS） and ultra performance liquid chromatography-mass spectrometry （UPLC-MS） and other methods are commonly used for the chemical composition analysis. Citri Sarcodactylis Fructus has the activities of relieving cough， reducing phlegm， relieving asthma， anti-inflammation， anti-bacteria and anti-oxidation， etc. After processing， its volatile and non-volatile components， and pharmacological effects all have a certain change. However， the current research on processing of Citri Sarcodactylis Fructus is not in-depth enough. It is necessary to further analyze the material basis of steaming to reduce dryness， explore its dryness medicinal substances and dryness-effect quantitative correlation， so as to clarify its processing mechanism， and provide basis for the subsequent processing research， resource development and comprehensive application of Citri Sarcodactylis Fructus in the future.
Abstract：Glycyrrizae Radix et Rhizoma has high medicinal value and is widely used in compatibility. It is used most frequently in the compatibility of Chinese medicine prescriptions，and is known as ''Guolao''（national medicine） and "master of all medicines". The characteristic active ingredients are mainly liquitin，glycyrrizic acid，glycyrrizin，and licochalcone. In different compatibilities，based on traditional and modern pharmacological theories，the corresponding effect of Glycyrrizae Radix et Rhizoma are brought into play through different mechanisms. Based on the traditional pharmacology of Glycyrrizae Radix et Rhizoma for tonifying spleen，replenishing Qi，clearing heat，removing toxin，dispelling phlegm，relieving cough and pain，and harmonizing various medicines，this paper used herbal authentication to analyze its compatibility application and mechanism. It was found that Glycyrrizae Radix et Rhizoma played corresponding effect in compatibilities through "tonification"，"harmonization"，and "regulation". For example，Glycyrrizae Radix et Rhizoma was combined with tonics including Ginseng Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma to tonify the five Zang-organs through its strong tonifying effect，combined with Paeoniae Radix Alba and Aconiti Lateralis Radix Praeparata to relieve emergencies and pains through harmonizing medicine power and properties，and combined with Rhei Radix et Rhizoma and Natrii Sulfas to reduce medicine intensity through regulating medicine properties and body characteristics. The application law and mechanism of the modern pharmacological compatibility of Glycyrrizae Radix et Rhizoma were analyzed by data mining and network pharmacology. It was found that the modern clinical formula was often compatible with Glycyrrizae Radix et Rhizoma for anti-inflammation，cardiovascular and cerebrovascular protection，anti-virus，and anti-tumor，Ephedrae Herba and Scutellariae Radix for anti-inflammation，Bambusae Caulis in Taenias，Salviae Miltiorrhizae Radix et Rhizoma，and Aurantii Fructus Immaturus for cardiovascular and cerebrovascular protection，and Ophiopogonis Radix and Chuanxiong Rhizoma for nerves protection. Meanwhile，the important targets of the characteristic ingredients were protein kinase B1 （Akt1），interleukin-6 （IL-6），tumor necrosis factor （TNF），and epidermal growth factor receptor （EGFR）. The important characteristic pathways such as tyrosine kinase inhibitor resistance pathway and cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG） signal pathway played the role of cardiovascular and cerebrovascular protection，and proteoglycan pathway in cancer played a neuroprotective role. This study is expected to provide references for the rational compatibility and application of Glycyrrizae Radix et Rhizoma，as well as the compatibility application of Chinese medicine prescriptions.
Keywords：Glycyrrizae Radix et Rhizoma;compatibility;pharmacological effect;chemical composition;clinical application;mechanism;herbal authentication;data mining;network pharmacology