OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE^-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg^-1） and simvastatin group （0.002 g·kg^-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）. MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg^-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg^-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L^-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot. ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）. ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.

ObjectiveTo investigate the mechanism and effect of Qingfei Paidu decoction on transient receptor potential vanilloid-1/Transient receptor potential ankyrin1 （TRPV1/TRPA1） based on heat-sensitive channel and inflammatory response. MethodAccording to body weight， 80 8-week-old C57BL/6 mice were randomly divided into the normal group， model group， dexamethasone group （5 mg·kg^-1）， and low-dose， medium-dose， and high-dose groups of Qingfei Paidu decoction （14.865， 29.73， 59.46 g·kg^-1）， with 12 mice in each group. In addition to the normal group， the other groups were administered 20 μL （1×10^-3 g·kg^-1） to each mouse by airway infusion to establish the acute lung injury （ALI） model. In the administration group， the drug was given 1 h after modeling and again after an interval of 24 h. The lung tissue was taken 36 h after modeling. Double lung wet/dry weight ratio（W/D）， hematoxylin-eosin （HE） staining， enzyme-linked immunosorbent assay （ELISA）， and Western blot were used to observe and detect the pathological changes of lung tissue， expression levels of inflammatory cytokine tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）， and expressions of TRPV1 and TRPA1 proteins in heat-sensitive channel， nuclear factor kappa-B （NF-κB）， inhibitor of NF-κB （IκBα） in inflammatory pathway， and phosphorylated proteins. The phosphorylated protein/total protein ratio was calculated. ResultCompared with that in the normal group， the lung tissue of mice in the model group was seriously damaged， and pulmonary capillary permeability increased. Alveolar capillary congestion and dilation destroyed the complete structure of the alveolar， and the alveolar wall thickened. A large number of inflammatory cells and red blood cells were infiltrated， and pulmonary edema was significantly aggravated. The expressions of TNF-α， IL-6， TRPV1， TRPA1， phosphorylated NF-κB p65/NF-κB p65， and phosphorylated IκBα/IκBα were significantly increased （P<0.01）， and the whole lung W/D was significantly increased （P<0.01）. Compared with the model group， the dexamethasone group and low-dose， medium-dose， and high-dose groups of Qingfei Paidu decoction could significantly improve pulmonary edema. TNF-α， IL-6， TRPV1， TRPA1， lung tissue NF-κB p65， and IκBα phosphorylated protein/total protein ratio decreased significantly （P<0.05， P<0.01）. The whole lung W/D also decreased significantly （P<0.05， P<0.01）. ConclusionQingfei Paidu decoction has anti-inflammatory and protective effects on LPS-ALI mice， which can effectively reduce inflammation， induce diuresis， and alleviate edema. Its mechanism may be related to the regulation of the expression of TRPA1 and TRPV1 and the inhibition of the activation of the NF-κB pathway.

Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.

ObjectiveTo observe the therapeutic effect and underlying mechanism of Linggui Zhugantang on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice. MethodSeventy-two 7-week-old C57BL/6 mice of SPF grade were randomly divided into a normal group， a model group， a dexamethasone group （5 mg·kg^-1）， and high-， medium-， and low-dose Linggui Zhugantang groups （9.36， 4.68，2.34 g·kg^-1）， with 12 mice in each group. Except for the normal group， the remaining groups underwent intranasal instillation of LPS （50 μg per mouse） for the induction of the ALI model. The treatment groups received oral administration for 7 days prior to modeling. After 12 hours of modeling， mouse lung tissues were taken to measure the wet/dry weight ratio （W/D）. Hematoxylin-eosin （HE） staining was performed to observe the pathological morphological changes in lung tissues. Bronchoalveolar lavage fluid （BALF） was collected for total cell count using a cell counter， and Wright-Giemsa staining was conducted to classify and quantify inflammatory cells （neutrophils and macrophages）. Enzyme-linked immunosorbent assay （ELISA） was used to determine the expression levels of inflammatory cytokines tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in BALF. Western blot analysis was performed to detect the expression of nuclear factor-κB （NF-κB） inhibitory protein α （IκBα）， NF-κB p65， and their phosphorylated proteins， and the ratio of phosphorylated protein/total protein was calculated. ResultCompared with the normal group， the model group exhibited severe lung tissue damage， disrupted alveolar structure， thickened alveolar walls， infiltration of extensive inflammatory cells and red blood cells， and significantly aggravated lung edema （P<0.01）. The total cell count， inflammatory cell count， expression levels of IL-6， and TNF-α in BALF， as well as NF-κB p65 and phosphorylated IκBα in lung tissues， were significantly upregulated in the model group （P<0.01）. Compared with the model group， high-， medium-， and low-dose Linggui Zhugantang groups， as well as the dexamethasone group， showed improved lung injury， reduced lung edema （P<0.01）， downregulated total cell count， neutrophil count， expression levels of IL-6 and TNF-α in BALF， and NF-κB p65 and phosphorylated IκBα in lung tissues （P<0.01）， and reduced macrophage count （P<0.05）. ConclusionLinggui Zhugantang has anti-inflammatory and protective effects on LPS-induced ALI in mice， effectively reducing inflammation and promoting diuresis and edema elimination. Its mechanism may be related to the inhibition of NF-κB pathway activation.

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B₂ （TXB₂）， prostacyclin I₂（PGI₂） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.