Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.

Objective:To investigate the impact and clinical outcomes of intraoperative prone-position lumbar anteroposterior (AP) fluoroscopy under anesthesia on the selection of the lowest instrumented vertebra (LIV) in the patients with adolescent idiopathic scoliosis (AIS) plus structural lumbar curves.Methods:A retrospective analysis was conducted of the clinical data of 35 patients (29 females and 6 males) with AIS who had undergone surgical posterior correction and fusion at Scoliosis Center, The Third Affiliated Hospital, Sun Yat-sen University between January 2020 and October 2023. The mean age was (17.9±5.7) years. Lenke's classification: 6 cases of type 3, 12 cases of type 4, 7 cases of type 5 and 10 cases of type 6. Preoperatively, all patients underwent standing AP and lateral radiographs of the full-length spine, left and right bending radiographs of the spine, and full-spine CT. Intraoperatively, all patients underwent prone-position lumbar AP fluoroscopy under anesthesia. The criteria for LIV selection were: (1) it should be the most cephalad vertebra touched by the central sacral vertical line (CSVL); (2) its rotation should be ≤ grade Ⅱ by the Nash-Moe classification; (3) its tilt angle should be <25°. The preoperative and postoperative LIV rotation angles were compared, and the number of lumbar fusions was compared between preoperative planning and actual surgery. Comparisons were also made between preoperation, postoperation and the final follow-up, examining Cobb angle of the major curve, Cobb angle of the minor curve, LIV inclination, coronal balance distance (CBD), sagittal vertical axis (SVA), and distance between CSVL and LIV (CSVL-LIV). The correction rates of the major curve and the minor curve, and change in LIV inclination were compared between postoperation and the final follow-up.Results:The patients were followed for (18.0±3.0) months. The LIV rotation decreased from 8.34°±4.95° preoperatively to 5.03°±2.99° postoperatively. The intraoperative fluoroscopy reduced at least one segment fusion for 57.1% (20/35) of the patients so that the number of lumbar fusions decreased significantly from 4.2±0.7 in preoperative planning to 3.6±0.8 after actual surgery ( P<0.05). The Cobb angles of the major and minor curves, LIV inclination, and CSVL-LIV at postoperation and the final follow-up were significantly lower than the preoperative values ( P<0.05), but there were no significant differences between the final follow-up and postoperation in the Cobb angle of the major cure, Cobb angle of the minor curve, or LIV inclination ( P>0.05). None of the patients required surgical revision for distal junctional complications. Conclusions:In the surgical treatment of AIS patients with structural lumbar curves, compared to the preoperative X-rays using the same criteria, intraoperative prone-position lumbar AP fluoroscopy under anesthesia can not only be a safe and effective method for LIV selection but also effectively reduce the number of lumbar fusions to preserve more lumbar mobility.

Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.

Objective:To investigate the impact and clinical outcomes of intraoperative prone-position lumbar anteroposterior (AP) fluoroscopy under anesthesia on the selection of the lowest instrumented vertebra (LIV) in the patients with adolescent idiopathic scoliosis (AIS) plus structural lumbar curves.Methods:A retrospective analysis was conducted of the clinical data of 35 patients (29 females and 6 males) with AIS who had undergone surgical posterior correction and fusion at Scoliosis Center, The Third Affiliated Hospital, Sun Yat-sen University between January 2020 and October 2023. The mean age was (17.9±5.7) years. Lenke's classification: 6 cases of type 3, 12 cases of type 4, 7 cases of type 5 and 10 cases of type 6. Preoperatively, all patients underwent standing AP and lateral radiographs of the full-length spine, left and right bending radiographs of the spine, and full-spine CT. Intraoperatively, all patients underwent prone-position lumbar AP fluoroscopy under anesthesia. The criteria for LIV selection were: (1) it should be the most cephalad vertebra touched by the central sacral vertical line (CSVL); (2) its rotation should be ≤ grade Ⅱ by the Nash-Moe classification; (3) its tilt angle should be <25°. The preoperative and postoperative LIV rotation angles were compared, and the number of lumbar fusions was compared between preoperative planning and actual surgery. Comparisons were also made between preoperation, postoperation and the final follow-up, examining Cobb angle of the major curve, Cobb angle of the minor curve, LIV inclination, coronal balance distance (CBD), sagittal vertical axis (SVA), and distance between CSVL and LIV (CSVL-LIV). The correction rates of the major curve and the minor curve, and change in LIV inclination were compared between postoperation and the final follow-up.Results:The patients were followed for (18.0±3.0) months. The LIV rotation decreased from 8.34°±4.95° preoperatively to 5.03°±2.99° postoperatively. The intraoperative fluoroscopy reduced at least one segment fusion for 57.1% (20/35) of the patients so that the number of lumbar fusions decreased significantly from 4.2±0.7 in preoperative planning to 3.6±0.8 after actual surgery ( P<0.05). The Cobb angles of the major and minor curves, LIV inclination, and CSVL-LIV at postoperation and the final follow-up were significantly lower than the preoperative values ( P<0.05), but there were no significant differences between the final follow-up and postoperation in the Cobb angle of the major cure, Cobb angle of the minor curve, or LIV inclination ( P>0.05). None of the patients required surgical revision for distal junctional complications. Conclusions:In the surgical treatment of AIS patients with structural lumbar curves, compared to the preoperative X-rays using the same criteria, intraoperative prone-position lumbar AP fluoroscopy under anesthesia can not only be a safe and effective method for LIV selection but also effectively reduce the number of lumbar fusions to preserve more lumbar mobility.

ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus （T2DM） rats based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） axis. MethodSix ZDF （fa/+） rats were as assigned to the blank group， and 30 ZDF （fa/fa） rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling， the rats were randomly divided into the model group， metformin group （0.18 g·kg^-1）， and low， medium， and high dose groups of modified Dahuang Huanglian Xiexintang （0.54， 1.08， 2.16 g·kg^-1）， with six rats in each group. After 12 weeks of drug intervention， the body mass， liver mass， fasting blood glucose （FBG）， and oral glucose tolerance test （OGTT） levels were measured. Serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， low-density lipoprotein cholesterol （LDL）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the activity of superoxide dismutase （SOD）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， and the level of malondialdehyde （MDA） in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group， the model group showed a significant increase in body mass， liver mass， and liver index （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight， liver mass， and liver index （P<0.01）. Compared with the normal group， the model group showed significantly increased TC， TG， and LDL levels （P<0.01）， and significantly decreased HDL levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels （P<0.01）， and significantly reduced TG levels （P<0.05）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels （P<0.05）. The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels （P<0.05）. Compared with the normal group， the model group showed significantly increased ALT and AST activities （P<0.01）. Compared with the model group， all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities （P<0.05） and significantly reduced AST activities （P<0.01）. Compared with normal group， the model group showed significantly increased FBG at all time points （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8， 10， 12 weeks. The OGTT results showed that compared with the normal group， the model group had significantly increased blood glucose at all time points （P<0.01）. Compared with the model group， the metformin group showed significantly reduced blood glucose at all time points （P<0.01）， and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90， 120 min （P<0.01）. HE pathology showed clear and regular liver cell structure in the normal group， while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang， with fewer necrotic cells. Compared with the normal group， the model group showed significantly reduced SOD and GSH-Px levels （P<0.01）， and significantly increased ROS and MDA levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels （P<0.01）， and significantly reduced MDA levels （P<0.01）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels （P<0.05）. Compared with the normal group， the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels （P<0.05）. Immunohistochemistry showed that compared with the normal group， the model group had significantly reduced positive expression of Nrf2 and HO-1 （P<0.05）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1， with a significant increase in brown-yellow granules around the cell nucleus （P<0.05）. Western blot results showed that compared with the normal group， the model group had significantly reduced protein expression of Nrf2 and HO-1 （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 （P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.

ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus （T2DM） model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups： Model group， metformin group （0.18 g·kg^-1）， and high， medium， and low dose groups of modified Dahuang Huanglian Xiexintang （2.16， 1.08， 0.54 g·kg^-1）， with eight rats in each group. Additionally， eight ZDF （fa/+） rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg^-1， with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose （FBG） was regularly measured. After 12 weeks of intervention， the body weight， epididymal fat weight， and serum levels of glucose （GLU）， glycated serum protein （GSP）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy （TEM） was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α （HIF-1α）， Bcl-2/adenovirus E1B 19 kDa interacting protein 3 （BNIP3）， microtubule-associated protein 1 light chain 3B （LC3B）， p62/SQSTM1， uncoupling protein 1 （UCP1）， iodothyronine deiodinase 2 （Dio2）， and PR domain containing 16 （Prdm16） in epididymal fat. Western blot was used to detect the protein expression of HIF-1α， BNIP3， LC3B， p62， and UCP1 in epididymal fat. ResultCompared with the normal group， the model group showed pathological changes in epididymal fat， with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight， epididymal fat weight， FBG， GLU， GSP， TC， TG， and LDL-C levels （P<0.01）， significantly decreased HDL-C levels （P<0.01）， significantly elevated mRNA and protein expression of HIF-1α， BNIP3， and LC3B （P<0.01）， significantly reduced mRNA and protein expression of p62 and UCP1 （P<0.01）， and significantly reduced mRNA expression of Dio2 and Prdm16 （P<0.01）. Compared with the model group， all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology， clear cristae， uniform matrix， and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight （P<0.01）. The epididymal fat index was reduced in all intervention groups （P<0.05）， and FBG was lowered in all intervention groups （P<0.01）.Serum GSP， GLU， TG， and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.01）， and HDL-C levels were significantly increased in all intervention groups （P<0.05， P<0.01）. The mRNA and protein expression of HIF-1α， BNIP3， and LC3B were significantly reduced， and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The mRNA and protein expression of p62， Dio2， and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway， thereby improving glucose and lipid metabolism in obese T2DM rats.

Type 2 diabetes mellitus （T2DM） is based on insulin resistance （IR） and insulin secretion deficiency， with the specific mechanisms still unclear. Current research involves mechanisms such as glycolipid toxicity， inflammatory response， oxidative stress damage， and mitochondrial dysfunction. Modern traditional Chinese medicine （TCM） scholars have named it "blood glucose collateral disease" based on the clinical characteristics and natural progression of T2DM. This condition is primarily manifested as abnormal blood sugar levels in the early stages， and as the disease progresses， it gradually causes widespread damage to the body's veins and collaterals， ultimately leading to lesions in vessels and collaterals. Among these， "spleen heat" （obesity type） is the most common clinical type of T2DM. The concept of "internal heat-induced elimination" runs through both the onset and complications of T2DM， with internal heat being a key factor in its pathogenesis. The clinical application of Dahuang Huanglian Xiexintang and its modifications has achieved significant therapeutic effects. This paper reviews the origins and treatment characteristics of Dahuang Huanglian Xiexintang， along with clinical application research and experimental studies related to T2DM treatment， involving mechanisms for regulating glucose and lipid metabolism disorders， improving IR， modulating inflammatory responses， combating oxidative stress damage， regulating autophagy-related signaling pathways， modulating intestinal flora， inhibiting pyroptosis， and alleviating endoplasmic reticulum stress， with the purpose to provide direction for further research on the prevention and treatment of T2DM and its related complications， to offer reference for developing Dahuang Huanglian Xiexintang as a rapid hypoglycemic Chinese patent medicine for obese T2DM， and to better guide the clinical promotion of this drug.

Objective To summarize and analyze the"Qiangzhi"drugs in Shennong's Classic of the Materia Medica,and to explore the effect and mechanism of improving memory impairment.Methods To screen the drugs with the effect of"Qiangzhi"in Shennong's Classic of the Materia Medica,and summarize their properties and tastes.By searching the common action targets of"Qiangzhi"traditional Chinese medicine through network pharmacology,it is speculated that it may be the basis for playing the role of"Qiangzhi".Animal experiments were carried out,and 80 mice were divided into blank group,model group,Radix Aucklandiae group,Radix Polygalae group,Eucommiae Cortex group,Rubi Fructus group,Euryale Semen group,Fructus Xanthii group,Epimedium group(0.06 g·d1)and Pilose Antler group(0.018 g·d1),with 8 mice in each group,and the corresponding dosage was given by gavage for 30 days.From the 23th day,scopolamine(2 mg·kg-1)was injected intraperitoneally in all groups except the blank group.On the 31th day,the platform test and water maze test were carried out on the mice in each group.After the experiment,the mice were killed and the materials were taken.The damage of neurons in the cortex and hippocampus of the mice was observed by LFB staining.According to the results of network pharmacology,Use ELISA kit to detect prostaglandin endoperoxide synthase 2(COX-2),monoamine oxidase A(MAOA),serotonin(5-HT),serotonin receptor 2A(5-HT2AR),acetylcholine(Ach),acetylcholinesterase(AchE),adenosine receptor A2a(A2aR)and adenosine receptor A1(A1R)in hippocampus of mice.Western blot was used to detect the expression of nuclear transcription factor-κB(NF-κB)and 5-HT transporter(SERT)in hippocampus of mice.Results There are eight kinds of drugs for"Qiangzhi"in Shennong's Classic of the Materia Medica,including Radix Aucklandiae,Cortex et Radix Polygalae,Eucommiae Cortex,Rubi Fructus,Euryale Semen,Fructus Xanthii,Herba Epimedii,and Cornu Cervi Pantotrichum.The main drugs are pungent and sweet,and the main drugs are warm,and most of them belong to the kidney meridian.According to the network pharmacology analysis,their common targets are COX-2,MAOA,5-HT2AR,AchE,A2aR,A1R.In the behavioral experiment,compared with the model mice,the latency of jumping off the platform was significantly increased,the number of jumping off the platform was significantly reduced,and the latency of water maze was significantly shortened(P＜0.05 or P＜0.01),and the mice in each Qiangzhi drug group were obviously more familiar with the swimming route.The results of LFB staining showed that each Qiangzhi drug could reduce the neuronal damage in cortex and hippocampus of mice.The results of ELISA showed that compared with the model group,the contents of COX-2,Ach,AchE,MAOA,A1R,A2aR in the hippocampus of mice in each Qiangzhi drug group were significantly decreased(P＜0.05 or P＜0.01),while the contents of 5-HT and 5-HT2AR were significantly increased(P＜0.01).Western blot method was used to detect the contents of NF-κB and SERT in hippocampus of mice in each"Qiangzhi"drug group,which was significantly lower than that in model group.Conclusion Eight"Qiangzhi"drugs all have the effect of improving memory impairment in different degrees.The mechanism of their"Qiangzhi"effect and improving memory impairment may be related to various ways,such as inhibiting NF-κB/COX-2 inflammatory pathway,reducing 5-HT hydrolysis and increasing 5-HT2A receptor content,stabilizing the contents of Ach and AchE,and reducing the contents of adenosine A1 and A2a receptors.

Objective To summarize and analyze the"Qiangzhi"drugs in Shennong's Classic of the Materia Medica,and to explore the effect and mechanism of improving memory impairment.Methods To screen the drugs with the effect of"Qiangzhi"in Shennong's Classic of the Materia Medica,and summarize their properties and tastes.By searching the common action targets of"Qiangzhi"traditional Chinese medicine through network pharmacology,it is speculated that it may be the basis for playing the role of"Qiangzhi".Animal experiments were carried out,and 80 mice were divided into blank group,model group,Radix Aucklandiae group,Radix Polygalae group,Eucommiae Cortex group,Rubi Fructus group,Euryale Semen group,Fructus Xanthii group,Epimedium group(0.06 g·d1)and Pilose Antler group(0.018 g·d1),with 8 mice in each group,and the corresponding dosage was given by gavage for 30 days.From the 23th day,scopolamine(2 mg·kg-1)was injected intraperitoneally in all groups except the blank group.On the 31th day,the platform test and water maze test were carried out on the mice in each group.After the experiment,the mice were killed and the materials were taken.The damage of neurons in the cortex and hippocampus of the mice was observed by LFB staining.According to the results of network pharmacology,Use ELISA kit to detect prostaglandin endoperoxide synthase 2(COX-2),monoamine oxidase A(MAOA),serotonin(5-HT),serotonin receptor 2A(5-HT2AR),acetylcholine(Ach),acetylcholinesterase(AchE),adenosine receptor A2a(A2aR)and adenosine receptor A1(A1R)in hippocampus of mice.Western blot was used to detect the expression of nuclear transcription factor-κB(NF-κB)and 5-HT transporter(SERT)in hippocampus of mice.Results There are eight kinds of drugs for"Qiangzhi"in Shennong's Classic of the Materia Medica,including Radix Aucklandiae,Cortex et Radix Polygalae,Eucommiae Cortex,Rubi Fructus,Euryale Semen,Fructus Xanthii,Herba Epimedii,and Cornu Cervi Pantotrichum.The main drugs are pungent and sweet,and the main drugs are warm,and most of them belong to the kidney meridian.According to the network pharmacology analysis,their common targets are COX-2,MAOA,5-HT2AR,AchE,A2aR,A1R.In the behavioral experiment,compared with the model mice,the latency of jumping off the platform was significantly increased,the number of jumping off the platform was significantly reduced,and the latency of water maze was significantly shortened(P＜0.05 or P＜0.01),and the mice in each Qiangzhi drug group were obviously more familiar with the swimming route.The results of LFB staining showed that each Qiangzhi drug could reduce the neuronal damage in cortex and hippocampus of mice.The results of ELISA showed that compared with the model group,the contents of COX-2,Ach,AchE,MAOA,A1R,A2aR in the hippocampus of mice in each Qiangzhi drug group were significantly decreased(P＜0.05 or P＜0.01),while the contents of 5-HT and 5-HT2AR were significantly increased(P＜0.01).Western blot method was used to detect the contents of NF-κB and SERT in hippocampus of mice in each"Qiangzhi"drug group,which was significantly lower than that in model group.Conclusion Eight"Qiangzhi"drugs all have the effect of improving memory impairment in different degrees.The mechanism of their"Qiangzhi"effect and improving memory impairment may be related to various ways,such as inhibiting NF-κB/COX-2 inflammatory pathway,reducing 5-HT hydrolysis and increasing 5-HT2A receptor content,stabilizing the contents of Ach and AchE,and reducing the contents of adenosine A1 and A2a receptors.

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg^-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg^-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg^-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.