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Ethnopharmacological relevance Diosbulbin B (DB) is the main hepatotoxic compound distributed in Dioscorea bulbifera L., which is widely used for the treatment of cancer and thyroid disorders in Asia. Scutellarin (SC) is the main compound in medicinal herb Scutellaria barbata D. Don, which is usually combined with Dioscorea bulbifera used for cancer therapy in clinic. Aim of the study This study aims to investigate the protection of SC against the liver injury induced by DB and its engaged mechanism. In addition, the anti-tumor effect of DB and SC is further observed in vivo . Materials and methods The protection of SC against DB-induced liver injury was evaluated by detecting serum alanine/aspartate aminotransferases (ALT/AST) and alkaline phosphatase (ALP) activities, and further liver histological observation. The inflammatory response was assessed by detecting liver myeloperoxidase (MPO) activity, and serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon-γ (IFN-γ). Western-blot analysis was used to detect the protein expression. The oxidative liver injury was evaluated by detecting liver malondialdehyde (MDA) and glutathione (GSH) contents, and glutathione peroxidase (GPx) enzymatic activity. In vivo anti-tumor activity was analyzed in S180 tumor-bearing mice. Results SC significantly decreased the increased serum ALT/AST, and ALP activities induced by DB. Liver histological observation evidenced the protection of SC against DB-induced liver injury. SC obviously reduced the increased liver MPO activity and the number of MPO-positive staining cells induced by DB. SC also reversed the decreased expression of inhibitor of κB (IκB) and the translocation of nuclear factor κB (NF-κB) p65 from cytoplasm to nucleus induced by DB. In addition, SC significantly abrogated the increased serum levels of TNF-α, IL-6, and IFN-γ induced by DB. SC decreased the increased liver MDA content induced by DB significantly, and it also increased liver GSH level. The decreased GPx protein expression and its enzymatic activity induced by DB were both obviously reversed after SC treatment. The results in S180 tumor-bearing mice showed that SC combined with DB significantly inhibited tumor growth in vivo . Conclusions Our results demonstrate that SC prevents DB-induced liver injury by attenuating NF-κB-mediated hepatic inflammation and ameliorating liver oxidative stress injury. Meanwhile, DB plus SC has significant anti-tumor activity in vivo . This study indicates the potential combination of DB with SC for the treatment of cancer in clinic. [ABSTRACT FROM AUTHOR]

Natural bear bile powder (NBBP) is a traditional Chinese medicine used for treating liver dysfunction. Cultured bear bile powder (CBBP), which is produced using biotransformation of chicken bile, acts as an appropriate substitute for NBBP when treating cholestatic liver injury. To investigate the molecular mechanisms underlying the hepatoprotective effects of CBBP in an α-naphthylisothiocyanate (ANIT)-induced cholestatic mouse model. Cholestatic mice were pretreated with CBBP or NBBP via oral gavage once a day for two weeks. Their blood biochemistry and liver histopathology were then evaluated using standard protocols. Western blot analyses, real-time polymerase chain reaction, and immunohistochemistry were used to evaluate changes in the protein levels and gene expression profiles of factors associated with hepatic inflammation and apoptosis in cholestatic mice. CBBP significantly decreased the serum indices of liver injury, and ameliorated neutrophil infiltration and hepatocyte necrosis within liver tissue of cholestatic mice. Expression of the inflammatory factors, such as tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule 1, was significantly reduced in CBBP-treated cholestatic mice. Moreover, proteins involved in the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B (TLR4/Myd88/NF-κB) signaling pathway, such as CD14, TLR4, Myd88, and NF-κB, that were increased in cholestatic mice, were downregulated by CBBP. Meanwhile, increased expression of the apoptosis-related proteins, caspase-3 and Bax, in cholestatic mice was reversed by CBBP treatment. CBBP treatment alleviates ANIT-induced cholestasis and liver injury by reducing hepatocyte inflammation and apoptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Fengshi Gutong (FSGT) capsule, a traditional Chinese medicine formula, has effects including warming meridians and dispersing cold, and relieving pain by dredging collaterals. FSGT is generally used for the treatment of rheumatoid arthritis (RA) in clinic in China. This study aims to investigate the alleviation provided by FSGT capsule on RA in vivo and the engaged mechanism. The collagen-induced arthritis (CIA) mouse model was used to evaluate the alleviation of FSGT capsule on RA in vivo. Network pharmacology was used to find the potential involved molecular targets. Western-blot, Real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were conducted. Wound healing assay was performed in human umbilical vein endothelial cells (HUVECs). FSGT capsule (300, 900 mg/kg) alleviated RA in CIA mice with no obvious side effects. The results from network pharmacology showed that the top 6 molecular targets involved in the FSGT-provided alleviation on RA were interleukin 6 (IL-6), tumor necrosis factor α (TNFα), C-C motif chemokine 2 (CCL2), vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), interleukin 1β (IL-1β), and these results imply the critical participation of inhibiting inflammation or angiogenesis. Next, FSGT capsule decreased the elevated serum contents of rheumatoid factor (RF) and VEGF, and some pro-inflammatory cytokines like TNFα and IL-6. Moreover, FSGT capsule also reduced the elevated protein expression of ICAM1, IL-1β and phosphorylated protein kinase B (Akt) in synovium from CIA mice. Further in vitro results showed that totally 13 compounds from FSGT reduced the enhanced IL-1β and inducible nitric oxide synthase (iNOS) mRNA expression in RAW264.7 macrophages stimulated by lipopolysaccharide (LPS). Meanwhile, 7 compounds from FSGT decreased the VEGF-induced HUVEC migration. Among those compounds, benzoylhypaconine (BHA), pseudoephedrine hydrochloride (PSE), glycyrrhetnic acid (GA), isoliquiritigenin (ISL), quercetin (QUER) and kaempferol (KAE) were found to inhibit both inflammation and angiogenesis in vitro. FSGT capsule ameliorates RA in CIA mice by reducing inflammation, abrogating angiogenesis and relieving pain. Some compounds in FSGT, including BHA, GA, PSE, ISL, QUER and KAE, reduced both inflammation and angiogenesis in vitro , which suggests that those compounds may contribute to the FSGT capsule-provided alleviation on RA. [Display omitted] • FSGT capsule alleviates RA in CIA mice with no obvious side effects. • Network pharmacology analysis implies the inhibition of inflammation and angiogenesis provided by FSGT capsule. • FSGT capsule reduces the elevated expression of some pro-inflammatory and pro-angiogenic molecules in CIA mice. • PI3K-Akt signal pathway is involved in the FSGT-provided alleviation on RA. • Total 6 compounds in FSGT reduces both inflammation and angiogenesis in vitro. [ABSTRACT FROM AUTHOR]

Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. Aim of the study: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α. Image 1 • Sweroside ameliorates the HFD-induce body weight gain, hepatic steatosis and serum lipid levels in DIO mice. • Sweroside improves glucose homeostasis and insulin sensitivity in DIO mice. • Sweroside attenuates HFD-induced hepatic inflammation in DIO mice. • Sweroside improves obesity with fatty liver by regulating the lipid metabolism and inflammatory responses. • The effect of sweroside in regulating inflammatory response and lipid metabolism is closely related with PPAR-α. [ABSTRACT FROM AUTHOR]