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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]

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]