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Abstract: Ethnopharmacological relevance: Tripterygium wilfordii HOOK F (TWHF) is a traditional Chinese medicine used in the treatment of various autoimmune diseases and inflammatory disorders including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and skin diseases. Triptolide (TP) is one of the main active ingredients of this traditional Chinese medicine. MC002 is a novel semi-synthetic derivate of TP which is highly water soluble, acts as a prodrug and is converted to TP in vivo. Aim of this study: A sensitive, rapid method for the simultaneous determination of TP and its chemo-unstable prodrug MC002 in dog blood was developed and validated using electrospray ionization (ESI) liquid chromatography–tandem mass spectrometry (LC–MS/MS). Using this method, a pharmacokinetic study of MC002 and TP following an intravenous drip infusion of 0.2mg/kg MC002 in dogs was performed. Materials and methods: Chemo-degradation of the prodrug in blood samples was inhibited by the addition of a small amount of sodium fluoride solution before using liquid–liquid extraction with ethyl acetate. The concentrations of MC002 and TP in dog blood were determined using the LC–MS/MS method. Results: The quantitative method showed good precision and stability and is suitable for the assay of biological samples. The pharmacokinetic study showed that the elimination of MC002 was faster than that of TP, and the concentrations and AUC0−t values of TP were higher than MC002. MC002 can rapidly convert to TP in vivo. Conclusions: This validated method was successfully applied in a pharmacokinetic study of MC002 following an intravenous drip infusion in dogs. With the development of this new prodrug of TP as a promising anti-cancer drug, this method is suitable for its further analysis in clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Tripterygium wilfordii HOOK F (TWHF) is a traditional Chinese medicine used in the treatment of various autoimmune diseases and inflammatory disorders including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and skin diseases. Triptolide (TP) is one of the main active ingredients of this traditional Chinese medicine. MC002 is a novel semi-synthetic derivate of TP which is highly water soluble, acts as a prodrug and is converted to TP in vivo. Aim of this study: A sensitive, rapid method for the simultaneous determination of TP and its chemo-unstable prodrug MC002 in dog blood was developed and validated using electrospray ionization (ESI) liquid chromatography–tandem mass spectrometry (LC–MS/MS). Using this method, a pharmacokinetic study of MC002 and TP following an intravenous drip infusion of 0.2mg/kg MC002 in dogs was performed. Materials and methods: Chemo-degradation of the prodrug in blood samples was inhibited by the addition of a small amount of sodium fluoride solution before using liquid–liquid extraction with ethyl acetate. The concentrations of MC002 and TP in dog blood were determined using the LC–MS/MS method. Results: The quantitative method showed good precision and stability and is suitable for the assay of biological samples. The pharmacokinetic study showed that the elimination of MC002 was faster than that of TP, and the concentrations and AUC0−t values of TP were higher than MC002. MC002 can rapidly convert to TP in vivo. Conclusions: This validated method was successfully applied in a pharmacokinetic study of MC002 following an intravenous drip infusion in dogs. With the development of this new prodrug of TP as a promising anti-cancer drug, this method is suitable for its further analysis in clinical studies. [Copyright &y& Elsevier]

Abstract: Aim of study: To investigate action mechanism of Yi Guan Jian Decoction on cirrhosis induced by CCl4 in rats. Material and methods: CCl4 (3mL/kg) for the first time and then olive oil CCl4 solution 50% (2mL/kg) was administered hypodermically to rats twice each week for 12 weeks. At the end of 8th week, rats were randomly divided into CCl4 control group (n =10), Yi Guan Jian Decoction group (n =9) and Xiao Chai Hu Decoction group (n =9). Yi Guan Jian Decoction and Xiao Chai Hu Decoction were oral administrated per day respectively for 4 weeks, concomitantly continued CCl4 administration. At 12th weekend, the rats were sacrificed for sampling and detection of liver function, histological changes of liver tissue, liver tissue hydroxyproline content and expression of α-SMA, CD68, MMP-13, TIMP-1, TIMP-2, Caspase-12, HGFα, MMP-2, MMP-9 and hepatocyte apoptotic index. Results and conclusions: (1) Compared with that of normal rats, expression of α-SMA, CD68 and TIMP-1 in liver tissue of 8 week model group rats increases significantly (P <0.01), moreover further increased in the 12 week of model group. However, MMP-13, HGFα, TIMP-2 content decreases gradually and the statistical difference is seen between each time point (P <0.01). Activity of MMP-2, MMP-9, content of Caspase-12 and hepatocyte apoptotic index increased gradually at 4th, 8th, 12th week. (2) Compared to that of the same time point model group, activity of MMP-9 and contents of MMP-13, TIMP-2 and HGFα in Yi Guan Jian Decoction group improves significantly (P < 0.01), and activity of MMP-2 and contents of α-SMA, TIMP-1, Caspase-12 and hepatocyte apoptotic index decreases significantly (P < 0.01). This work suggests that Yi Guan Jian Decoction exerts significant therapeutic effect on CCl4-induced cirrhosis in rats, through mechanism of inhibiting hepatocytes apoptosis and hepatic stellate cells activation, and regulating the function of Kupffer cell. Ethnopharmacological relevance: This study investigates the mechanism of Yi Guan Jian against cirrhosis from aspect of heptocytes apoptosis and hepatic stellate cells activation. It suggest that although of unknown bioactive ingredients, mechanism of traditional Chinese medicine recipe against cirrhosis can be disclosed and of profound significance. [Copyright &y& Elsevier]

Huai hua san (HHS) is a traditional Chinese herbal formula which is firstly documented in the ancient Chinese classic medical work "Pu Ji Ben Shi Fang" in 1132 AD. It has been widely used in the treatment of lower gastrointestinal disorders such as acute colitis and hematochezia for more than 800 years. However, scientific evidence of the efficacy and the exact mechanism of HHS against colitis has not yet been reported. The aim of this study is to investigate the potential effects of HHS in the alleviation of dextran sulphate sodium (DSS)-induced colitis and the alteration of colonic microbiota composition and structure. HHS solution was orally administrated to 5% DSS-challenged rats once a day for 8 days. Colitis clinical symptoms of colitis were collected, together with colonic mucosal damage assessed at histomorphometric and ultrastructural levels. The protein levels of inflammatory mediators TNF-α and CRP were detected by ELISA. The colonic vascular permeability was evaluated by Evans blue extravasation. Meanwhile, The effects of the HHS therapy on the colonic microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Daily oral administration of HHS markedly alleviated DSS-induced colitis, as evidenced by decreased colitis disease activity index (DAI) score, reduced colonic inflammation and normalization of colonic vascular hyperpermeability. Moreover, the 16S rRNA gene sequencing analysis demonstrated that HHS treatment during colitis prevented the colitis-associated alteration of colonic microbial community at operational taxonomic unit level, together with the DSS-induced colonic microbiota dysbiosis at taxonomic levels. In addition, HHS therapy reduced colitis-associated high increased ratio of Bacteroidetes to Firmicutes to a normal level. HHS could attenuate ulcerative colitis and ameliorate gut microbial dysbiosis. Image 1 [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine has great potential and advantages in the treatment of liver fibrosis, with Fuzheng Huayu formula (FZHY) serving as a prime example due to its remarkable efficacy in delaying and reversing liver fibrosis while simultaneously improving clinical symptoms for patients. Aim of the review: In this paper, we present a comprehensive review of recent studies on the therapeutic potential of FZHY and its components/ingredients in the treatment of liver fibrosis and cirrhosis, with the aim of providing insights for future research endeavors. A comprehensive literature search was conducted on FZHY, TCM319, traditional Chinese medicine 319, liver fibrosis and cirrhosis using multiple internationally recognized databases including PubMed, Embase, Springer, Web of science, SciVerse ScienceDirect, Clinical Trails. Gov, CNKI, Wanfang, and VIP. FZHY is widely used clinically for liver fibrosis and cirrhosis caused by various chronic liver diseases, with the effects of improving serum liver function, liver pathological histology, serological indices related to liver fibrosis, decreasing liver stiffness values and portal hypertension, as well as reducing the incidence of hepatocellular carcinoma and morbidity/mortality in patients with cirrhosis. Numerous in vivo and in vitro experiments have demonstrated that FZHY possesses anti-fibrotic effects by inhibiting hepatic stellate cell activation, reducing inflammation, protecting hepatocytes, inhibiting hepatic sinusoidal capillarization and angiogenesis, promoting extracellular matrix degradation, and facilitating liver regeneration. In recent years, there has been a growing focus on investigating the primary active components/ingredients of FZHY, and significant strides have been made in comprehending their synergistic mechanisms that enhance efficacy. FZHY is a safe and effective drug for treating liver fibrosis. Future research on FZHY should focus on its active components/ingredients and their synergistic effects, as well as the development of modern cocktail drugs based on its components/ingredients. This will facilitate a more comprehensive understanding of the molecular mechanisms and targets of FZHY in treating liver fibrosis, thereby further guide clinical applications and drug development. [Display omitted] • A comprehensive summary of recent clinical trials of FZHY in treating liver fibrosis and cirrhosis. • To review the findings on the anti-hepatic fibrotic mechanisms of FZHY. • The effective combinations of components/ingredients of FZHY against hepatic fibrosis were reviewed for the first time. [ABSTRACT FROM AUTHOR]

Erzhu Jiedu Recipe (EZJDR) is a formula of traditional Chinese medicine (TCM) for treating hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). However, its effective components and the mechanism of action remain unclear. To explain how the active compounds of EZJDR suppress the growth of hepatoma cells. UHPLC-Q-Exactive Orbitrap HRMS was used to identify the chemical constituents of EZJDR and their distribution in the serum and liver of mice. Together with experimental investigations, network pharmacology unraveled the molecular mechanism of components of EZJDR underlying the inhibited Hep3B cells. A total of 138 compounds which can be divided into 18 kinds of components (such as sesquiterpenoids, diterpenoids, anthraquinones, flavonoids and so on) were found in the aqueous extract of EZJDR. Of these components, the tricyclic-diterpenoids exhibited a highest exposure in the serum (74.5%) and liver (94.7%) of mice. The network pharmacology revealed that multiple components of EZJDR interacted with key node genes involved in apoptosis, proliferation, migration and metabolism through various signaling pathways, including ligand binding and protein phosphorylation. In vitro experiments demonstrated that 6 tricyclic-diterpenoids, 2 anthraquinones and 1 flavonoid inhibited the viability of Hep3B cells, with IC 50 values ranging from 3.81 μM to 37.72 μM. Dihydrotanshinone I had the most potent bioactivity, arresting the S phase of cell cycle and inducing apoptosis. This compound changed the expression of proteins, including Bad, Bax, Bcl-2, Bal-x, caspase3 and catalase, which were associated with mitochondria-mediated apoptotic pathways. Moreover, dihydrotanshinone I increased the levels of p21 proteins, but decreased the phosphorylated p53, suggesting accumulation of p53 protein prevented cell cycle progression of Hep3B cells with damaged DNA. These results suggested that multiple components of EZJDR—diterpenoid, anthraquinone and flavonoid—could be the effective material for the treatment of HBV-HCC. This research provided valuable insights into the molecular mechanism of action underlying the therapeutic effects of EZJDR. [Display omitted] • A total of 138 compounds of EZJDR, and 48 absorbed in the liver and serum of mice were identified. • The diterpenoid, flavonoid and anthraquinone components showed effective suppression of growth of human hepatoma cells. • Network pharmacology unraveled the complexity of action mechanism of EZJDR, involving multiple biological processes. • These potential compounds displayed anti-cancer activity by inducing apoptosis and arresting cell cycle. • Dihydrotanshinine I induced Hep3B cell death involved caspase-dependent apoptosis and p53 pathways. [ABSTRACT FROM AUTHOR]

Chronic liver diseases mainly include chronic viral liver disease, metabolic liver disease, cholestatic liver disease (CLD), autoimmune liver disease, and liver fibrosis or cirrhosis. Notably, the compound formulas of traditional Chinese medicine (TCM) is effective for chronic liver diseases in clinical trials and basic research in vivo , which provide evidence of chronic liver disease treatment with integrated TCM and traditional Western medicine. This paper aims to provide a comprehensive review of the compound formulas of TCM for treating different chronic liver diseases to elucidate the composition, main curative effects, and mechanisms of these formulas and research methods. Different keywords related to chronic liver diseases and keywords related to the compound formulas of TCM were used to search the literature. PubMed, Scopus, Web of Science, and CNKI were searched to screen out original articles about the compound formulas of TCM related to the treatment of chronic liver diseases, mainly including clinical trials and basic in vivo research related to Chinese patent drugs, classic prescriptions, proven prescriptions, and hospital preparations. We excluded review articles, meta-analysis articles, in vitro experiments, articles about TCM monomers, articles about single-medicine extracts, and articles with incomplete or uncertain description of prescription composition. Plant names were checked with MPNS (http://mpns.kew.org). In this review, the clinical efficacy and mechanism of compound formulas of TCM were summarized for the treatment of chronic viral hepatitis, nonalcoholic fatty liver disease, CLD, and liver fibrosis or cirrhosis developed from these diseases and other chronic liver diseases. For each clinical trial and basic research in vivo , this review provides a detailed record of the specific composition of the compound formulas of TCM, type of clinical research, modeling method of animal experiments, grouping methods, medication administration, main efficacy, and mechanisms. The general development process of chronic liver disease can be summarized as chronic hepatitis, liver fibrosis or cirrhosis, and hepatocellular carcinoma. The compound formulas of TCM have some applications in these stages of chronic liver diseases. Owing to the continuous progress of medical technology, the benefits of the compound formulas of TCM in the treatment of chronic liver diseases are constantly changing and developing. [Display omitted] • Review on the progress of compound formulas of TCM in the treatment of chronic liver disease from 1997 to 2023. • Focused on the compound formulas of TCM for HBV, NAFLD, CLD, hepatic fibrosis, etc. • Summarized the research scheme and results of compound formulas of TCM intervention in chronic liver disease. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. Aim of the study: The present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running. Materials and methods: Seventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13mg/kg/d doge, KXS treatment at 175mg/kg/d, 350mg/kg/d and 700mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA. Results: CFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment. Conclusions: The results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Kai-Xin-San (KXS) is a famous traditional Chinese medicine (TCM) formula. It has been used in the treatment of diseases including neurasthenia, Alzheimer''s disease and neurosis. Aim of the study: To provide information on the potential toxicity of KXS, we evaluated the acute and subchronic toxicity in rodents. Materials and methods: In acute study, a single administration of KXS was given orally to mice at doses ranging from 19.67 to 60.04g/kg. In the sub-chronic oral toxicity study, KXS was administered to rats at 0, 1, 3 and 9g/kg for 13 weeks. Moreover, 30 days of post treatment (withdrawal study) was conducted. Mortalities, clinical signs, body weight changes, food and water consumption, haematological and biochemical parameters, gross findings and organ weights were monitored during the study period. Results: In the sub-chronic study in rats, daily oral administration of KXS at the dose of 9g/kg/day result in significant increase in WBC, lymphocyte, alkaline phosphatase, blood sugar and significant decrease in bodyweight, serum Cre, CK and CHO at the last week of treatment. Recovery except for the body weight was observed after 30 days of post treatment. Conclusions: KXS is relatively safe for oral medication. The LD50 of KXS was over 32.59g/kg for mice. The no-observed-adverse-effect-level (NOAEL) was considered to be 19.67g/kg/day for rats. [Copyright &y& Elsevier]

Qingre Huashi (QRHS) formula is an empirical prescription for the treatment of Gan-Dan-Shi-Re syndrome (GDSR) syndrome in traditional Chinese medicine (TCM). GDSR is one of the typical TCM syndromes in chronic hepatitis B (CHB). However, little is known about the mechanism of the QRHS formula in treating CHB patients with GDSR. The biological basis of GDSR also remains largely unknown. Aim of the study : GDSR mostly occurs in the acute and early stages of chronic liver disease. Effectively alleviating GDSR stalls disease development and benefits patients. The purpose of this study was to explore the molecular basis of GDSR in CHB and then study the mechanism of the QRHS formula treating GDSR using transcriptomics and metabolomics. The transcriptome and metabolome of CHB patients with GDSR syndrome were detected using RNA microarray combined with ultra-high performance liquid chromatography/mass spectrometry and information mining. The potential biomarkers were identified from differentially expressed genes and metabolites, and the metabolic pathway was analyzed. We also investigated the callback of metabolic biomarkers after treatment with the QRHS formula, an empirical prescription for the treatment of GDSR syndrome. RT-PCR analysis was carried out in an independent patient cohort of CHB for validation. Four candidate genes— GPT2 , HK2 , DDIT3 , and HIF1A —and 14 candidate metabolic biomarkers, including L-alpha-aminobutyric acid, selenomethionine, and fructose 1,6-bisphosphate, were identified and validated. All four transcripts of GPT2 , HK2 , DDIT3 , and HIF1A were significantly differentially expressed between the GDSR and non-GDSR groups through independent microarray data and RT-PCR. After treatment with the QRHS formula, the clinical indexes and TCM syndrome were significantly improved, and the 14 disturbed biomarkers were obviously corrected. Three metabolic pathways were confirmed to be perturbed in CHB GDSR patients: alanine, aspartate, and glutamate metabolism, arginine biosynthesis, and aminoacyl-tRNA biosynthesis. Using integrated transcriptomic and targeted metabolomic methods, we identified the potential biomarkers and dysregulated metabolic pathways in CHB patients with GDSR syndrome, which was alleviated by the QRHS formula treatment. These results may provide the mechanism of metabolic dysregulation in GDSR syndrome as well as that underlying the curative effect of the QRHS formula. [Display omitted] [ABSTRACT FROM AUTHOR]

Cholestatic Liver Fibrosis (CLF) is a hepatobiliary disease that typically arises as a late-stage complication of cholestasis, which can have multiple underlying causes. There are no satisfactory chemical or biological drugs for CLF. Total Astragalus saponins (TAS) are considered to be the main active constituents of the traditional Chinese herb Astragali Radix (AR), which has the obvious improvement effects for treating CLF. However, the mechanism of anti-CLF effects of TAS is still unclear. The present study was undertaken to investigate the therapeutic effects of TAS against bile duct ligation (BDL) and 3, 5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) -induced CLF models and to reveal the potential mechanism to support its clinic use with scientific evidence. In this study, BDL-induced CLF rats were treated with TAS (20 mg/kg, 40 mg/kg) and DDC-induced CLF mice were treated with 56 mg/kg TAS. The therapeutic effects of TAS on extrahepatic and intrahepatic CLF models were evaluated by serum biochemical analysis, liver histopathology and hydroxyproline (Hyp). Thirty-nine individual bile acids (BAs) in serum and liver were quantified by using UHPLC-Q-Exactive Orbitrap HRMS. qRT-PCR, Western blot and immunohistochemistry analysis were used to measure the expression of liver fibrosis and ductular reaction markers, inflammatory factors and BAs related metabolic transporters, along with nuclear receptor farnesoid X receptor (FXR). The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBiL), direct bilirubin (DBiL) and contents of liver Hyp were dose-dependently improved after treatment for TAS in BDL and DDC- induced CLF models. And the increased levels of ALT and AST were significantly improved by total extract from Astragali radix (ASE) in BDL model. The liver fibrosis and ductular reaction markers, α-smooth muscle actin (α-SMA) and cytokeratin 19 (CK19), were significantly ameliorated in TAS group. And the liver expression of inflammatory factors: interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were significantly decreased after TAS treatment. In addition, TAS significantly ameliorated taurine-conjugated BAs (tau-BAs) levels, particularly α-TMCA, β-TMCA and TCA contents in serum and liver, which correlated with induced expressions of hepatic FXR and BAs secretion transporters. Furthermore, TAS significantly improved short heterodimer partner (SHP), cholesterol 7α-hydroxylase (Cyp7a1), Na+ taurocholate cotransport peptide (NTCP) and bile-salt export pump (BSEP) mRNA and protein expression. TAS exerted a hepatoprotective effect against CLF by ameliorating liver injury, inflammation and restoring the altered tau-BAs metabolism to produce a positive regulatory effect on FXR-related receptors and transporters. [Display omitted] • TAS improve cholestatic liver fibrosis in BDL and DDC models. • TAS regulate tau-BAs contents, especially α-TMCA, β-TMCA and TCA. • FXR signaling pathways are critical for the treatment of TAS in CLF. [ABSTRACT FROM AUTHOR]

Glehnia littoralis Fr. Schmidtex Miq. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. G. littoralis has the effects of treating the lungs with heat, nourishing yin and blood, and acting as an expectorant. Traditional Chinese medicine (TCM) prescriptions containing G. littoralis have various clinical applications, such as clearing heat, relieving coughs, treating hepatic fibrosis, resolving phlegm, and treating esophagitis. This paper aims to provide a comprehensive and productive review of G. littoralis , mainly including traditional application, ethnopharmacology, chemical composition, pharmacological activities, and quality control. Literature search was conducted through the Web of Science, ScienceDirect, Springer Link, PubMed, Baidu Scholar, CNKI, and WanFang DATA by using the keywords " Glehnia littoralis ", "Radix Glehniae", "Bei Shashen", "Clinical application", "Chemical composition", "Quality control" and "pharmacological action". In addition, information was collected from relevant ancient books, reviews, and documents (1980–2022). G. littoralis is a traditional Chinese herbal medicine with great clinical value and rich resources. More than 186 components, including coumarins, lignans, polyacetylenes, organic acids, flavonoids, and terpenoids, have been isolated and identified from G. littoralis. The pharmacological activities of more than half of these chemicals are yet unknown. Polyacetylenes and coumarins are the most important bioactive compounds responsible for pharmacological activities, such as antiproliferative, anti-oxidation, anti-inflammatory, antibacterial, antitussive, immune regulation and analgesic. In this study, the progress in chemical analysis of G. littoralis , including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), gas chromatography–mass spectrometry (MS), and HPLC–MS, were summarized. In this paper reviewed the previous literature regarding ethnopharmacological, phytochemical, pharmacological, and quality evaluation of the processing of G. littoralis was reviewed, providing potential reference information for future investigation and clinical applications. However, research on the relationship between chemical constituents and traditional uses of G. littoralis is lacking, and the comprehensive pharmacological effects and mechanisms of G. littoralis require further detailed exploration. In addition, an efficient method for chemical profiling is still unavailable to obtain potent bioactive markers for quality control. Perfect quality standards, which are also the basis for further drug development of G. littoralis , are urgently needed to ensure its quality and clinical application. [Display omitted] • Glehnia littoralis is a widely utilized in Asian countries as herbal medicines. • This review updates the phytochemistry and pharmacological of G. littoralis. • Few systematic review of G. littoralis is available in the preceding literature. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy remains one of the most drug-resistant focal epilepsy, leading to enormous healthcare burden. Among traditional herb medicine, some ingredients have the potential to treat seizure and alleviate the neuronal excitoxicity. The dried rhizome of Gastrodia elata Blume has been used to treat convulsive disorder, dizziness, dementia and migraine in eastern Asia. To determine whether gastrodin, an active ingredient of Gastrodia elata Blume, can reduce lithium-pilocarpine induced seizure severity and neuronal excitotoxicity and explore the underlying mechanism. We divided the Sprague-Dawley rats into an experimental group (gastrodin group) and a control group (Dimethyl sulfoxide, vehicle group) and performed the behavioral analysis and electroencephalography to determine the effect of gastrodin on the seizure severity induced by lithium-pilocarpine injection. Nissl-stained histopathology elucidated the degree of rat hippocampal neuronal damage as markers of acute and subacute neuronal excitotoxicity. Besides, the Western blotting of dissected hippocampus was carried out to demonstrate the protein expression involving GABAergic transmission and metabolic pathway. Gastrodin reduced the acute seizure severity in lithium-pilocarpine-induced seizure model. In electroencephalography recording, gastrodin exerted inhibitory action on epileptiform discharge. Compared with control group, gastrodin exhibited neuroprotective effect against seizure related hippocampal neuronal damage at acute and subacute stages. The Western blotting showed that gastrodin reversed the degradation of GABA A receptor after pilocarpine-induced seizures. In the experimental seizure model, gastrodin showed anti-seizure and neuroprotective abilities. Enhancing the expression of GABA A receptor plays an important role in its antiepileptic mechanism. The results offer a new insight of developing new antiepileptic drugs from traditional Chinese medicine. Image 1 • Gastrodin alleviated the acute seizure severity and epileptiform discharge in lithium-pilocarpine model. • Gastrodin showed neuroprotective effect against the seizure related hippocampal neuronal damage. • The treatment of gastrodin reversed the degradation of GABA A receptor after pilocarpine-induced seizures. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a global prevalent chronic autoimmune inflammatory disease and acceptable safety drugs are lack for its treatment. The rhizomes of Souliea vaginata (Maxim) Franch (SV) possess anti-inflammatory functions and are used as substitution of Coptis chinensis Franch. SV is also traditional Chinese medicine and Tibetan medicine for the treatment of conjunctivitis, enteritis and rheumatic. For searching complementary and alternative anti-RA drugs, it is necessary to characterize the potential anti-arthritic activity of SV and underlying mechanism involved. The aim of the study was to test the chemical compositions, evaluate the anti-arthritic effects and underlying mechanisms of SV. The chemical compositions of SV were analyzed using liquid chromatography-ion trap-time of flight tandem mass spectrometry (LCMS-IT-TOF). From day 11 to day 31, SV (0.5, 1.0 and 1.5 g/kg body weight) and Tripterygium glycosidorum (TG, 10 mg/kg body weight) were administered orally to the CIA model rats once a day. Thickness of paw and body weights were measured once every two days from day 1 to day 31. Histopathological changes were measured using hematoxylin-eosin (HE) staining. Effects of SV on the levels of IL-2, TNF-α, IFN-γ, IL-4 and IL-10 in serum of CIA rats were measured by enzyme-linked immunosorbent assay (ELISA) kits. CD3+, CD4+, CD8+ and CD4+CD25+ T cells populations were measured using flow cytometric analysis. To evaluate the possible hepatotoxicity and nephrotoxicity, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea (UREA) and creatinine (CREA) in CIA rats were also tested using blood auto analyzer. 34 compounds were identified from SV based on LCMS-IT-TOF, and triterpenoids are major anti-arthritic compositions. SV significantly relieved CIA rats' paw swelling without obvious influence on the body weight growth. SV decreased the serum levels of IL-2, TNF-α and IFN-γ in CIA rat, and increased the serum levels of IL-4 and IL-10. SV significantly increased and decreased the percentages of CD4+ and CD8+, with no significant effects on CD3+ in lymphocytes of CIA model rats. Moreover, SV simultaneously decreased thymus and spleen indexes and no hepatotoxicity and nephrotoxicity was observed after short-term treatment. These findings suggest that SV possesses preventive and therapeutic effect on RA by modulating the inflammatory cytokines, T-lymphocyte, thymus and spleen indexes and shows no hepatotoxicity and nephrotoxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Depression is a major mental disorder and it is currently recognized as the second-leading cause of disability worldwide. However, the therapeutic effect of antidepressants remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely used for centuries, including commonly-used complementary and alternative medical therapies for depression. Recent clinical trials have been carried out to assess the efficacy and safety of TCM, and to explore the mechanisms of action in relation to the treatment of depression. To summarize frequently used TCM decoctions and Chinese patent medicines (CPM) for treating depression, review their clinical therapeutic effects in treating depressive disorders, consider their possible mechanisms, and characterize the relationships between their efficacy and mechanisms. We performed a computerized literature search using the electronic databases such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases, with the keywords "depression", "traditional Chinese medicine decoction", "Chinese patent medicine", "application", "mechanism", and their combinations, from January 1, 2000 to August 8, 2022 (inclusive). A total of 51 papers were identified. We reviewed studies on six each TCM decoctions and CPMs, which demonstrated their significant clinical efficacy for treating depression and examined their mechanisms of action. The anti-depressive effects were related to: 1) increased monoamine neurotransmitter levels, 2) inhibiting hyperactivity of the hypothalamic-pituitary-adrenal axis, 3) regulating hippocampal neurons and neurotrophic factors, 4) regulating immune cytokines, 5) counteracting excitatory amino acid toxicity, and 6) regulating microbe-gut-brain axis function. TCM plays an increasingly important role in the management of depression by enhancing the therapeutic effects and alleviating the side effects of antidepressant chemicals. [Display omitted] • Traditional Chinese medical formulas with antidepressant effect have been confirmed. • TCM has the advantage of multi-target antidepressant effects. • The combination of TCM and Western medicine can improve the efficacy and reduce side effects. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Huangqi decoction (HQD) is a well-known traditional Chinese herbal formulation, It is an effective treatment for consumptive disease and chronic liver diseases. It consists of Radix Astragali ( Astragalus membranceus ( Fisch. ) Bge. Root, Huangqi ) and Radix Glycyrrhizae ( Glycyrrhiza uralensis Fisch ., root and rhizome, Gancao ). Total astragalus saponins (AST) is a main component of Radix Astragali and glycyrrhizic acid(GA) is a main component of Radix Glycyrrhizae. Our primary results showed that the combination of AST and GA had an obvious synergistic effect in reducing liver collagen deposition and decreasing serum alanine aminotransferase (ALT) activity in dimethylnitrosamine (DMN)-induced liver fibrosis. Aim of the study Through in vivo and in vitro experiments, we aimed at investigating the key anti-fibrosis signal pathway TGF-β1/Smads to further explore the synergistic mechanism of AST and GA. Material and methods Two hepatic fibrosis animal models, bile duct ligation-induced (BDL) and DMN-induced, were utilized. Rats were treated orally with AST, GA or AST/GA, with the effects evaluated via liver histopathology, hydroxyproline (Hyp) levels, and α-SMA expression. In the hepatic stellate cell line JS-1, cells were treated with AST/GA for 24 h, followed by a cell viability assessment using Cell Counting Kit-8(CCK-8) and Real-time PCR and Western blot analysis of α-SMA, ColⅠ and TGF-β1/Smads signaling pathway related components. Results The AST/GA combination attenuated liver tissue inflammation, collagen deposition, Hyp levels, and α-SMA expression in both BDL-and DMN-stimulated hepatic fibrosis rats. In vitro results showed that the AST/GA combination significantly inhibited JS-1 cell viability, significantly suppressed α-SMA, ColⅠ, TGF-β1, Smad2 and Smad3 mRNA and protein expression, as well reduced p-Smad2/3. Compared with AST or GA treatment alone, the AST/GA combination significantly reduced Smad3 mRNA expression levels and TGF-β1, Smad3, and p-Smad2/3 protein levels. Conclusions AST and GA synergistically alleviated both BDL-and DMN-induced hepatic fibrosis via TGF-β1/Smads signaling pathway inhibition in hepatic stellate cells. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Huangqi Decoction (HQD), a classical traditional Chinese medicine (TCM) formula, is used to treating liver injury in China. The aim of the study is to investigate mechanisms of HQD against dimethylnitrosamine (DMN)-induced liver fibrosis underlying metabolic profiles of bile acids. Materials and methods DMN-induced liver fibrosis rats were administrated HQD and its compounds, astragalosides (AS), glycyrrhizic acid (GA) and their combination. The anti-fibrosis effects were evaluated and targeted metabolomics by UPLC-MS was used to examine whether HQD had an influence on bile acid metabolism. The levels of mRNAs associated with bile acid metabolism were expressed by RT-PCR. Chenodeoxycholic acid (CDCA)-induced hepatic stellate cells (HSCs) proliferation and activation were examined using MTS assay and Western blot. Results Histopathological changes and serum liver function in HQD group had significant improvements ( P <0.01). Concentrations of free bile acids and taurine conjugates were significantly increased in DMN group ( P <0.05). HQD and its compounds restored the increased bile acids to normal levels, and HQD was more effected on parts of bile acids. Furthermore, the levels of mRNAs related bile acid synthesis and reabsorption such as CYP7A1, CYP8B1, CYP27A1, OATP2, OATP3, OATP4 and NTCP were significantly down-regulated in DMN group ( P <0.05), mRNAs related excretion such as MRP3 and BESP were up-regulated ( P <0.01), and CYP7A1, CYP8B1, OAT P 3, OATP4, NTCP and MRP3 restored to normal levels by HQD treatment. Moreover, CDCA-induced HSCs proliferation and activation were weaken by HQD ( P <0.05) with down-regulated α-SMA, TGF-β1, p-Smad2 and p-Smad3 expressions. Conclusions HQD alleviated DMN-induced liver fibrosis with a better effect than its compounds, which may be involved in the regulation of bile acid metabolism enzyme. Moreover, HQD may inhibit CDCA-induced HSCs proliferation and activation. [ABSTRACT FROM AUTHOR]

Antiviral therapy can alleviate liver fibrosis in chronic hepatitis B, but it has a limited effect on advanced liver fibrosis/cirrhosis. Traditional Chinese medicine (TCM), particularly FuZheng HuaYu (FZHY) tablet, appears to have an antifibrotic effect, but its improving resolution of hepatitis b virus (HBV) -associated advanced fibrosis and experienced anti-viral treatment has not been investigated. To observe the safety and efficacy of adjunctive FZHY on the HBV-associated cirrhosis patients who received 2 years of entecavir but still with advanced fibrosis. An open-label, multicentre, single arm trial. 251 patients were included and treated with TCM consisted of FZHY tablets 1.6 g and granules, three times a day in addition to entecavir 0.5 mg daily for an additional 48 weeks. Primary outcome was regression of fibrosis (the proportion of patients with a 1-point decrease in the Ishak liver fibrosis score from baseline to week 48). Fibrosis regression occurred in 94 of 184 patients with paired liver biopsy (51.09%, 95% CI: 43.9～58.0). In 132 compensated cirrhosis patients (Ishak score ≥5), 56.06% (74/132, 95% CI: 47.5～64.2) showed fibrosis regression and reached the goal of 54% (15% more than entecavir mono-therapy). 10 patients occurred adverse reaction, most of them were mild, and all recovered or achieved remission. The combination therapy of FZHY, TCM granules and ETV could regress the liver fibrosis in the patients with HBV cirrhosis, who experienced 2 years of ETV treatment, and it is safe and well tolerated. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People׳s Welfare Pharmacy in the Song Dynasty (AD1078). It consists of Radix Astragali ( Astragalus membranceus (Fisch.) Bge. Root, Huangqi) and Radix Glycyrrhizae ( Glycyrrhiza uralensis Fisch., root and rhizome, Gancao), and it is an effective recipe that is usually used to treat consumptive disease and chronic liver diseases. Astragaloside (AS) is a main component of Radix Astragali had an effect similar to the Huangqi decoction on hepatic fibrosis. Aim of the study Cholestasis is associated with a number of chronic liver diseases and Notch signaling has been demonstrated to be involved in ductular reaction. Previous studies have shown that AS can prevent the progression of cholestatic liver fibrosis, however, whether AS affects the Notch signaling pathway is unclear. Materials and methods Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. At first weekend, the rats were randomly divided into a model group (BDL), an AS group, and a Sorafenib positive control group (SORA) and treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, -4, Jagged 1 (JAG1), Delta-like (DLL)-1, -3, -4, Hes1, Numb and RBP-Jκ. Activation of the Wnt signaling pathway was evaluated by analyzing expressions of Wnt-4, -5a, -5b, Frizzled (Fzd)-2, -3, -6 and β-catenin. Results (1) Compared with the BDL group, AS significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs. In addition, AS significantly decreased the protein and mRNA expressions of TGF-β1 and α-SMA. In contrast, AS significantly enhanced expression of the Smad 7 protein. AS also reduced biliary epithelial cell proliferation, and reduced the mRNA and protein expressions of CK7, CK8, CK18, CK19, OV6, Sox9 and EpCAM. (2) The mRNA and protein expressions of Notch-2, -3, -4 and JAG1 were significantly reduced in the AS compared to the BDL group. In contrast, the mRNA and protein level of Numb was clearly enhanced after AS treatment. Conclusion AS may prevent biliary liver fibrosis via inhibition of the Notch signaling pathway, thereby inhibiting the abnormal proliferation of biliary epithelial cells. Results indicate that AS may be a potential therapeutic drug for cholestatic liver disease. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Yinchenzhufu decoction (YCZFD) is a classical Chinese herbal formula and has been used to treat severe jaundice in chronic liver injuries since the Qing Dynasty (18th century CE). To identify the components absorbed into the blood in YCZFD and explore their pharmacokinetic profile for understanding the effective ingredients of YCZFD. Materials and methods: After rats were given YCZFD by intragastric administration, the plasma was processed by precipitation of protein. The compounds in YCZFD extract and the plasma were identified by using high-resolution mass spectrometry with a database-directed strategy. The pharmacokinetics of multiple compounds from YCZFD in rat plasma was studied by using the established UPLC-MS/MS method. Results: Forty compounds in YCZFD extract and 21 prototype compounds with 11 metabolites in rat plasma were detected after oral administration. The pharmacokinetic parameters of glycyrrhizic acid, glycyrrhetic acid, cinnamic acid, ononin, atractylenolide III, and liquiritin from YCZFD were obtained in rats. Conclusions: The identified constituents and the pharmacokinetic features of YCZFD are helpful for understanding the material bases of its therapeutic effects. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. Material and methods: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4) in C57BL/6 mice for 6 weeks. From week 4 to week 6, the CCl4-injected mice were randomly divided into three groups, followed by oral administration of Sorafenib, XFZY and water for 3 weeks. Biochemical parameters, hydroxyproline (Hyp) content and histological changes of the liver were determined. The expressions of alpha smooth muscle actin (α-SMA), collagen I, CD31 and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and western blot. The protein expressions of VEGFR-2, hypoxia inducing factor (HIF)-1α, asymmetric dimethylarginine (ADMA) and dimethylarginine hydrolase (DDAH) 1 were determined by western blot. The mRNA levels of α-SMA, VEGF and HIF-1α were measured by RT-PCR. Results: Both Sorafenib and XFZY improved biochemical parameters of the liver fibrosis mice. A significant reduction in Hyp content was found in the XFZY-treated mice as well as the Sorafenib-treated mice. Changes in histopathology showed that Sorafenib and XFZY decreased inflammatory and fibrotic stages of the liver in fibrosis mice. Compared to CCl4 model group, Sorafenib and XFZY decreased α-SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1α and ADMA, and increased the expression of DDAH1. Conclusion: XFZY inhibits liver fibrosis not only through inhibiting collagen deposition but also through an antiangiogenic effect on the fibrotic liver. Moreover, the antiangiogenic mechanism of XFZY involves alleviating hypoxia and protecting liver sinusoidal endothelial cell function. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Ding-Zhi-Xiao-Wan (DZ, also known as Kai-Xin-San) is a famous traditional Chinese medicine used for the treatment of emotional disease. Previously, we have found that in a variety of animal models of depression (such as tail suspension model, model of chronic fatigue and forced swimming model) DZ demonstrated significant antidepressant behavior and promoted the production of 5-hydroxytryptamine (5-HT). However, the mechanisms of 5-HT regulation are still unclear. Therefore, the current study is designed to further investigate the antidepressant effect of DZ by observing its influence on 5-HT synthesis, metabolism, transport and other key links, so as to clarify the molecular mechanism of its 5-HT regulation. Materials and methods: Solitary rising combined with the chronic unpredictable mild stress (CMS) was used to establish the rat model of depression. The rats were given DZ for 3 weeks, the behavior change and the following items in hippocampus and prefrontal cortex were detected simultaneously: 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC), monoamine oxidase (MAO) and 5-HT transporter (5-HTT) were observed. Results: Our results showed that treatment with the DZ significantly improved the behavior and simultaneously increased the 5-HT level in the hippocampus, prefrontal cortex tissues and hippocampus extracellular of depressive rats. In future studies revealed that DZ could significantly increase the protein and mRNA expression of the key enzymes TPH during the 5-HT synthesis process in the hippocampus and prefrontal cortex of the depressed rats, and suppress the expression of 5-HTT protein and mRNA at the same time. But it had no effects on MAO-A and MAO-B activities. Conclusion: We believe that antidepressant effect of DZ is caused by the increase of 5-HT synthesis and reduction of 5-HT re-uptake, and eventually increase the content of 5-HT in the brain and the synaptic gaps. [Copyright &y& Elsevier]

Kaixinsan (KXS) decoction, as an herbal formula, was used to treat the diseases, such as insomnia, amnesia, emotional disorders in ancient china. It has been demonstrated to be active in various animal models resembling human depression with multitarget effects. However, effective verification on the clinical application of KXS is still lacking. Supplements in this knowledge field are urgently needed. This very first study evaluated the efficacy and tolerability of ShenZhiLing (SZL) tablets (KXS preparation), compared with fluoxetine (FLX, positive comparator), in patients with mild to moderate depressive disorder. In this randomized, double-blind, parallel-group study, 156 patients with mild to moderate depression without taken any antidepressants in the past 6 months or 4 continuous weeks were randomized to receive either 3.2 g/d SZL plus 20 mg/d FLX placebo (SZL group) or 20 mg/d FLX plus 3.2 g/d SZL placebo (FLX group), for 8 weeks. Their clinical presentations and some metabolic indexes were assessed during the 8 weeks' visiting period. Patients in SZL group showed a statistically significant improvement after 8 weeks of treatment in HAM-D17 score (18.79±2.09 to 4.43±4.71, p<0.001) and self-rating depression scale (SDS) score (58.49±8.89 to 39.84±12.09, p<0.001), but not in N-back total respond time (1145.55±608.26 to 1128.47±387.49, p>0.05). In addition, no significant difference at 8 weeks of treatment was found between SZL and FLX groups in SDS score (39.84±12.09 vs. 36.63±12.44) and N-back respond time (1128.47±387.49 vs. 1089.43±352.08) as well as reduction of HAM-D17 score (14.79±4.88 vs. 15.24±4.29) (p>0.05 for all). However, the serum APOB, APOC3 and ALB levels and LDL-C/HDL-C ratio decreased significantly in patients after SZL treatment, while only APOB/APOA1 ratio decreased significantly in FLX group. Other metabolic indexes did not alter significantly after treated with SZL or FLX. The efficacy and safety profile of SZL are comparable to that of fluoxetine in patients with mild to moderate depression. The beneficial effect of SZL is probably associated with improvement of lipid metabolic balance. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Kai Xin San (KXS) is a traditional Chinese herbal prescription for the treatment of depression-like disorders, anxiety, and impairment in learning and memory, however, there is very little scientific data concerning the efficacy of this. Aim of the study: The present study aimed to investigate the antidepressant potential of Kai Xin San and its possible mechanisms. Materials and methods: Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of KXS. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis, akinesia and hypothermia and 5-HTP induced head-twitch response in mice. The contents of monoamine neurotransmitters including epinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) in mice brain were determined by Elisa. Spontaneous motor activities of mice and rotarod test were performed to find whether KXS has excitatory or inhibitory actions on the central nervous system. Results: The results showed that intragastric administration of KXS at 175, 350, 700, 1400mg/kg/day or fluoxetine at 28mg/kg/day for 3 days significantly reduced the duration of immobility in TST and FST, while it showed no effect on the spontaneous motor activity and rotarod performance in mice. However, the effect was not dose-dependent. The pre-treatment with KXS or fluoxetine for 3 days could elevate the contents of NE, 5-HT and DA in mice brain significantly. When the mice were treated with KXS (350mg/kg, p.o) or desipramine (30mg/kg, p.o) for 7 days, both of them could antagonize reserpine-induced ptosis, akinesia and hypothermia. The KXS (350mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20min when KXS at dosages of 175, 350, 700 and 1400mg/kg/day were performed per os (p.o.) during a 1-day, 3-day or 7-day period. Conclusions: Our results suggested that KXS exerts antidepressant-like effect. A possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role. [Copyright &y& Elsevier]

Aims: Qindan-capsule (QC) is a prescription of traditional Chinese medicine for the treatment of hypertension. We investigated the effect and mechanism of QC-containing serum on proliferation of aortal adventitial fibroblasts (AFs) and composition of extracellular matrix (ECM). We also tested whether the Smad3 signaling pathway is activated in the progress. Materials and methods: AFs were cultured by tissue explant in vitro. The proliferation of AFs induced by transforming growth factor β1 (TGF-β1) and affected by QC-containing serum with high or low dose was detected by MTT. The protein and mRNA expressions of Smad3 and Procollagen I were observed by Western blot and Real-time PCR respectively. Results: Western blot and Real-time PCR revealed that after being activated by TGF-β1 for 24h, the expressions of Smad3, Pho-Smad3 and Procollagen I were all higher than those in the control group. But these functions were inhibited, to some extent in different doses, by QC-containing serum. So that the proliferation of AFs which was evaluated by MTT. Conclusions: The results suggested QC-containing serum has significantly improved proliferation of AFs and composition of extracellular matrix. TGF-β1/Smad3 signaling pathway may be involved in the mechanism. [Copyright &y& Elsevier]

Aim: To investigate the mechanism of action of Fuzheng Huayu recipe (FZHY) and vitamin E (Vit E) against renal interstitial fibrosis related to transforming growth factor-beta1 (TGF-β1) mediated tubular epithelial-to-mesenchymal transition. Materials and methods: Renal interstitial fibrosis was induced by administration of HgCl2 at a dose of 8mg/kg body weight once a day for 9 weeks. Rats were randomly divided into four groups: normal, model, FZHY, and Vit E group. Rats in the latter two groups were treated with the FZHY recipe and Vit E respectively. HK-2 cells were treated with TGF-β1 for 24h, followed by incubation with either SB-431542 (a potent and specific inhibitor of TβR-I kinase) or FZHY drug-containing serum for another 24h. Hyp content in rat kidney tissue was assayed with Jamall''s method and collagen deposition in kidney was visualized using Masson stain. Protein expression of TGF-β1, TβR-I, Smad2, p-Smad2, Smad3, and p-Smad3 was analyzed by Western blotting. Protein expression and the location of Smad3 in kidney was assayed by immunohistochemistry, E-cadherin, cytokeratin 18 (CK-18), α-SMA and TGF-β1 by immunofluorescent stain. Results: FZHY and Vit E inhibited renal collagen deposition and reduced Hyp content significantly. They upregulated E-cadherin protein expression and down-regulated the protein expression of α-SMA, TGF-β1, p-Smad2, p-Smad3, and TβR-I. Lastly, they inhibited the nuclear translocation of Smad3 in fibrotic kidney tissue. FZHY drug-containing serum significantly upregulated the expression of CK-18 and down-regulated the expression of α-SMA, TβR-I, p-Smad2/3 in TGF-β1 stimulated HK-2 cells. Conclusion: The mechanism of action of FZHY and Vit E against renal interstitial fibrosis is related to the reversal of tubular EMT induced by TGF-β1. [Copyright &y& Elsevier]

Cholestasis caused by bile secretion and excretion disorders is a serious manifestation of liver disease. With limited treatment methods, it affects millions of people worldwide. Huangqi decoction (HQD), an effective traditional Chinese medicine, is used to treat chronic cholestatic liver diseases. However, the action mechanisms of it were not fully elucidated. We aim to investigate the therapeutic effect of HQD, and its active component, astragalosides, against α-naphthylisothiocyanate (ANIT)-induced cholestasis in rats based on targeted metabolomics analysis and revel the potential mechanism. The therapeutic effect of HQD and astragalosides on ANIT-induced cholestasis model rats were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The levels of bile acids (BAs) and free fatty acids (FFAs) in serum and liver tissues were measured by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQMS). qRT-PCR and Western blot analysis were used to measure the expression of nuclear hormone receptor, membrane receptor and BA transporter protein in cholestatic rats before and after HQD and astragalosides treatment. The obtained data showed that the administration of ANIT caused obvious cholestasis with significantly increased intrahepatic retention of hydrophobic BAs and altered FFAs, which were consistent with the liver histopathological and serum biochemical findings. HQD and astragalosides treatment were able to attenuate ANIT-induced BAs and FFAs perturbation, ameliorate the impaired liver function, histopathological ductular reaction, and lipid peroxidation damage by ANIT. Elevated mRNA and protein expression of transporters related to BA metabolism and genes related to lipogenesis and lipid oxidation metabolism in cholestasis were attenuated or normalized by HQD and astragalosides treatment. Intervention by ANIT can significantly change the homeostasis of BAs and FFAs. HQD and astragalosides exerted a hepatoprotective effect against cholestatic liver injury by restoring the altered BA and FFA metabolism through the improvement of BA transporter, nucleus hormone receptor, and membrane receptor. Image 1 [ABSTRACT FROM AUTHOR]

Gut microbiome dysbiosis is closely associated with cholestatic liver disease. Huangqi decoction (HQD), a traditional herbal formula, has protection against cholestatic liver injury. However, the effect of HQD on gut microbiome remains unknown. To investigate the effect of HQD on 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) induced cholestatic liver injury and its effect on the gut microbiome profiles. Mice with DDC-induced cholestatic liver injury were treated with low and high doses of HQD for 8 weeks. Fecal samples were analyzed by 16 S ribosomal DNA sequencing. Barrier function as well as intestinal and hepatic inflammation was analyzed by real-time PCR and western blotting. HQD treatment ameliorated the DDC-induced liver injury and collagen deposition around hepatic bile ducts. Moreover, decreased diversity, reduced richness, and abnormal composition of intestinal microbiota of cholestatic mice were remarkably attenuated by HQD supplementation. Differences in bacterial abundance, including levels of Prevotellaceae_NK3B31_group , Alistipes , and Gordonibacter , were increased in DDC-induced mice, as compared with control mice, and were decreased after HQD treatment. Moreover, intestinal dysbiosis promoted disruption of the intestinal barrier in cholestatic mice. However, HQD treatment alleviated intestinal barrier dysfunction. Importantly, increased hepatic expression of pro-inflammatory factors and the NLRP3 inflammasome, which have a positive correlation with differential bacteria, were characteristics found in DDC-induced cholestatic mice that were alleviated upon treatment with HQD. HQD treatment alleviated gut microbiota dysbiosis, ameliorated the intestinal barrier dysfunction, inhibited liver inflammation, and protected against DDC-induced cholestatic liver injury. Image 1 [ABSTRACT FROM AUTHOR]

In this study, in order to explore potential depressive biomarkers and potential regulatory targets of KXS on depression, we assessed the effects of Kai-Xin-San (KXS) on lipid metabolism in depressed patients (DPs) and rats exposed to chronic and unpredictable mild stress (CUMS). Serum samples were collected from DPs, DPs with 8 weeks of KXS treatment (KXS) and healthy controls (HCs), and non-targeted lipidomics was used to analyze the effect of KXS on serum lipid metabolites in DPs. Based on UPLC-Q-TOF/MS technology, differential metabolites were validated in a large sample size. The potential regulatory network of KXS was analyzed by bioinformatic analysis, and the expressions of proteins in serum were verified using western boltting analysis. Moreover, effects of KXS on serum lipid and lipid metabolism-related hormone levels in CUMS rats were detected by enzyme-linked immunosorbent assay and enzymatic method. We validated that the levels of six serum lipid metabolites (N-Desmethylcitalopram (HMDB14021), PC(14:1(9Z)/24:0) (HMDB07926), PC(P-18:1(11Z)/20:0) (HMDB11281), PC(O-18:0/20:4(8Z,11Z,14Z,17Z)) (HMDB13420), PC(16:0/P-18:0) (HMDB07995) and PC(16:0/P-18:1(11Z)) (HMDB07996)) between HC/DP groups and between DP/KXS groups were significantly different. Among these six metabolites, HMDB07995, HMDB07996, HMDB13420 and HMDB11281 were highly sensitive and specific for depression and KXS treatment by receiver operating characteristic (ROC) curve analysis. matrix metalloproteinases (MMPs) including MMP2 and MMP9, apolipoproteins (Apo) including APOA1 and APOC1 were up-regulated and apolipoproteins (Apo) including APOB, APOD and APOE, phospholipid transfer protein (PLTP), Paraoxonase 1 (PON1) were down-regulated in DPs, and KXS treatment could reverse these changes. In CUMS rats, KXS could increase the open-field score, sucrose preference and body weight, and reduce immobility time. Furthermore, KXS increased the serum levels of the above-mentioned six metabolites, reduced serum total cholesterol (TCH), triglyceride (TG) and free fatty acid (FFA) levels and increased the serum high-density lipoprotein cholesterol (HDL-C) level in CUMS rats. In addition, leptin and ghrelin were down-regulated by KXS. The results suggested that KXS exerted antidepressant effects by regulating the signaling pathways involved in lipid metabolism disorders. The lipid metabolites might be potential biomarkers of depression and possible targets for KXS-based treatment of depression. Image 1 [ABSTRACT FROM AUTHOR]