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Liver and gut communicates with each other through metabolites and the gut-liver axis plays a crucial role in lipid metabolism. Enterohepatic bile acid circulation is an important constitution of gut-liver axis. Farnesoid X receptor (FXR)，a bile acid mediated nuclear receptor, is promising therapeutic targets for the non-alcoholic fatty liver disease (NAFLD). More and more studies have confirmed the effects of Angelica sinensis polysaccharide (ASP) on liver protection and lipid regulation. However, little attention has been paid to the role of ASP on the gut-liver axis, which is crucial to clarify how ASP play a role in liver protection after oral administration. In vivo and in vitro models of NAFLD were established to examine the effect of ASP on hepatic fat accumulation. Our results showed that ASP could alleviate liver fat accumulation. However, the expression of FXR was not changed when ASP directly acting on hepatocytes, while ASP could change the expression of FXR in liver and intestine of mice after oral administration. In addition, our results showed that ASP could promote the excretion of bile acids, thereby increasing cholesterol metabolism. Our research provided a new concept for the mechanism of ASP regulating liver lipid metabolism and exerting liver protection.

Yu Gan Long (YGL) is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor (TGF-β) in the previous study. But the mechanisms associated with platelet-derived growth factor (PDGF)-BB remain obscure. In this study, we further investigated the mechanism of YGL reducing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV (Col IV), type HI precollagen (PCHI), hyaluronuc acid (HA) and laminin (LN), which are implicated in liver fibrosis. Also, YGL reduced the α-smooth muscle actin (α-SMA) expression, which acts as the indicator of liver fibrosis. Furthermore, YGL decreased the serum levels of hepatic stellate cell (HSC) mitogen PDGF-BB and inflammation cytokines, including TNF-α, IL-1β, IL-6. Markers involved in liver fibrosis, such as Ras, p-Raf-1, p-ERK1/2, p-JNK, p-P38, p-PI3K, p-AKT, p-JAKl, p-STAT3 were downregulated significantly after treatment with YGL. Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production, and suppressing Ras/ERK, PI3K/AKT, and JAK1/STAT3 signaling pathways, which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.

In Uygur medicine, Huganbuzure granule (HBG) is one of the classical prescriptions for liver protection. However, its role in immune liver injury remains unknown. This study evaluates the effect of HBG on concanavalin-A- (ConA-) induced immune liver injury and investigates its protective underlying mechanism. BALB/c mice were randomly divided into five groups (n = 24 mice per group): control, ConA, 1.6 g/kg HBG + ConA, 3.2 g/kg HBG + ConA, and 6 mg/kg prednisolone + ConA. HBG was intragastrically administrated once daily for ten consecutive days, prior to ConA (20 mg/kg) injection. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), superoxide dismutase (SOD), and malondialdehyde (MDA) in mouse serum were measured after ConA injection. Moreover, liver-related mRNA levels were evaluated by qPCR. The detection of liver-related proteins was assessed by immunohistochemistry and western blot analysis. Compared with the ConA group, HBG reduced the mRNA expression of IL-17A and IFN-γ and the protein expression of T-bet and ROR-γt. In addition, HBG increased the mRNA expression of IL-4 and TGF-β and protein expression of GATA3 and Foxp3, indicating that HBG regulated the balance of Th1/Th2 and Th17/Treg. Furthermore, HBG alleviated immune liver injury by reducing oxidative stress, inhibiting apoptosis, and decreasing the expression of p-JNK, p-ERK, p-p38, p-JAK1, p-STAT1, p-STAT3, and IRF1. Our data suggested that HBG attenuated ConA-induced immune liver injury by regulating the immune balance and inhibiting JAK1/STATs/IRF1 signaling, thereby reducing apoptosis induced by JNK activation. The findings indicate that HBG may be a promising drug for immune liver injury.

Poria cocos (Schw.) Wolf (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. It has a very good therapeutic effect for functional dyspepsia (FD). However, the material basis and mechanism of PC on FD were not reported.To investigate the function and potential mechanisms of PC including its three extracts (triterpenoid, PCT; water-soluble polysaccharide, PCWP; acidic polysaccharide, PCAP) on FD.The study explored the therapeutic effect of PC and its three extracts on FD in rats for the first time and discussed its mechanisms based on brain-gut peptides, immunity and repair of the gastrointestinal mucosa.The chemical components of PC extracts were analyzed and quantified using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and gel permeation chromatography coupled with size exclusion chromatography (GPC/SEC). The FD rat models were established using weight-loaded forced swimming and alternate-day fasting for 42 days. After 14 days of treatment, the effect and mechanisms were investigated using ELISA, histopathology, immunohistochemistry as well as Western blot.Seventy-seven triterpenoids in PCT were identified. PCWP was primarily composed of component A (Mw: 3.831 × 10PC extracts showed therapeutic effects on FD rats, and the mechanism of action involved multiple pathways. PCAP, which is often discarded in traditional applications, was effective. Our study provides new ideas for the application and development of PC extracts.

Yu Gan Long (YGL) is a Chinese traditional herbal medicine that has been used in the treatment of liver fibrosis for many years in clinical practice. However, its anti-hepatofibrotic mechanism has not been studied yet. In this study, the effect and mechanism of YGL in reducing liver fibrosis was demonstrated in vivo. Our results showed that liver fibrosis biomarkers collagen IV (Col IV), type III precollagen (PCIII), hyaluronuc acid (HA) and laminin (LN), were increased after CCl4 treatment and decreased by YGL. Among the liver fibrosis indicators, α-smooth muscle actin (α-SMA) was decreased by YGL in the CCl4-treated rats, while MMP2 and MMP9 was upregulated followed by TIMP1 downregulation. Proteins involved in liver fibrosis such as p-Smad2, p-Smad3 and Smad4 were down-regulated, while Smad7 protein was up-regulated by YGL after CCl4-induced liver damage. YGL also suppressed the increase of TGF-β1, TNF-α, IL-1β, IL-6, IL-4 and IL-17 A induced by CCl4 treatment, while promoted IFN-γ expression. Finally, the transcription factors ROR-γt and GATA3 were decreased, while T-bet was increased after YGL treatment. These results suggested that YGL attenuated CCl4-induced hepatic fibrosis by accelerating the extracellular matrix degradation, blocking the TGF-β1/Smad signaling pathway and modulating the balance among IL-4, IL-17 A and IFN-γ, demonstrating YGL protective effect and its potential mechanisms in treating liver fibrosis.

Depression is a severe and recurrent mental disease and contributes to the global disease burden. However, there are limited effective treatments for depression. This study evaluated the effect of a compound Gaoziban tablet (CGZBT) on depression and explored its potential mechanisms that underlie its action in rats.

Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.