lignans and Hepatitis

Acanthopanax senticosus (Rupr. et Maxim) Harms (Araliaceae), also called Siberian Ginseng, Eleutherococcus senticosus, and Ciwujia in Chinese, is a widely used traditional Chinese herb that could invigorate qi, strengthen the spleen, and nourish kidney in the theory of Traditional Chinese Medicine. With high medicinal value, Acanthopanax senticosus (AS, thereafter) is popularly used as an "adaptogen" like Panax ginseng. In recent decades, a great number of chemical, pharmacological, and clinical studies on AS have been carried out worldwide. Several kinds of chemical compounds have been reported, including triterpenoid saponins, lignans, coumarins, and flavones, among which, phenolic compounds such as syringin and eleutheroside E, were considered to be the most active components. Considerable pharmacological experiments both in vitro and in vivo have persuasively demonstrated that AS possessed anti-stress, antiulcer, anti-irradiation, anticancer, anti-inflammatory and hepatoprotective activities, etc. The present review is an up-to-date and comprehensive analysis of the botany, chemistry, pharmacology, toxicity and clinical trials of AS.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bone and Bones; Botany; Coumarins; Eleutherococcus; Enzyme Inhibitors; Fatigue; Flavones; Hepatitis; Humans; Hypoglycemic Agents; Immunologic Factors; Lignans; Neuroprotective Agents; Nitrites; Oils, Volatile; Plant Extracts; Polysaccharides; Radiation-Protective Agents; Saponins; Triterpenes

The traditional Chinese medicine Forsythiae Fructus is the dried fruit of Forsythia suspensa (Thunb.) Vahl. It is commonly used to clear heat and detoxify, reduce swelling and disperse knot, and evacuate wind and heat.. Inflammation is involved in liver fibrosis. Phillygenin (PHI) is a kind of lignans extracted and separated from Forsythiae Fructus, which has been reported to have a good anti-inflammatory effect. Therefore, we aimed to explore whether PHI has a therapeutic effect on liver fibrosis caused by inflammation.. Firstly, the induction of the LX2 cells inflammatory model and fibrosis model by LPS with different concentrations were studied. Then, high, medium and low doses PHI was given for intervention therapy. The secretion of IL-6, IL-1β and TNF-α inflammatory factors were detected by ELISA kit, and the expression of collagen I and α-SMA was detected by Western blot and RT-qPCR. The possible mechanism of PHI on TLR4/MyD88/NF-κB signal pathway was studied by computer-aided drug design software and the results were further verified by Western blot and RT-qPCR experiments.. The results showed that LPS could promote the expression of IL-6, IL-1β and TNF-α and the expression of collagen I and α-SMA, indicating that LPS could induce inflammation and fibrosis in LX2 cells. PHI could inhibit LX2 cell activation and fibrotic cytokine expression by inhibiting LPS-induced pro-inflammatory reaction. Molecular docking results showed that PHI could successfully dock with TLR4, MyD88, IKKβ, p65, IκBα, and TAK1 proteins. Subsequently, Western blot and qPCR results further proved that PHI could inhibit the proteins expression in TLR4/MyD88/NF-κB signal pathway which were consistent with the molecular docking results.. PHI can inhibit LPS-induced pro-inflammatory reaction and LX2 cell activation through TLR4/MyD88/NF-κB signaling pathway, thereby inhibiting liver fibrosis.

Topics: Actins; Anti-Inflammatory Agents; Cell Line; Collagen Type I; Hepatic Stellate Cells; Hepatitis; Humans; Interleukin-1beta; Interleukin-6; Lignans; Lipopolysaccharides; Liver Cirrhosis; Myeloid Differentiation Factor 88; NF-kappa B; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

As a phenylpropanoid and dibenzylbutyrolactone lignan present in medical plants, such as those used in traditional Chinese herbal medicine, including Arctium lappa (Niubang), arctigenin exhibits antimicrobial, anti-inflammatory, and anticancer activities. In this study, we investigated the protective role of arctigenin in Concanavalin A (ConA)-induced acute hepatitis in mice. Arctigenin remarkably reduced the congestion and necroinflammation of livers, and improved hepatic function (ALT and AST) in ConA-induced acute hepatitis in vivo. The infiltration of CD4 T, NKT and macrophages into the livers was found to be reduced with arctigenin treatment. Arctigenin suppressed ConA-induced T lymphocyte proliferations that might have resulted from enhanced IL-10 production by macrophages and CD4 T cells. These results suggested that arctigenin could be a powerful drug candidate for acute hepatitis through immune suppression.

Topics: Acute Disease; Animals; CD4-Positive T-Lymphocytes; Concanavalin A; Furans; Hepatitis; Inflammation; Inflammation Mediators; Interleukin-10; Lignans; Liver; Macrophages; Male; Mice; Mice, Inbred BALB C; Natural Killer T-Cells; Protective Agents; RAW 264.7 Cells

Concanavalin A-induced autoimmune hepatitis is a well-established experimental model for immune-mediated liver injury. It has been widely used in the therapeutic studies of immune hepatitis. The in-depth analysis of dysregulated proteins from comparative proteomic results indicated that the activation of immune system resulted in the deregulation of autophagy. Follow-up studies validated that some immune related proteins, including Stat1, Pkr, Atg7, and Adrm1, were indeed upregulated. The accumulations of LC3B-II and p62 were confirmed by immunohistochemistry and Western blot analyses. Arctigenin pretreatment significantly alleviated the liver injury, as evidenced by biochemical and histopathological investigations, whose protective effects were comparable with Prednisone acetate and Cyclosporin A. Arctigenin pretreatment decreased the levels of IL-6 and IFN-γ, but increased the ones of IL-10. Next, the quantitative proteomic analysis demonstrated that ARC pretreatment suppressed the activation of immune system through the inhibition of IFN-γ signaling, when it downregulated the protein expressions of Stat1, P-Stat1, Pkr, P-Pkr, Bnip3, Beclin1, Atg7, LC3B, Adrm1, and p62. Meanwhile, Arctigenin pretreatment also reduced the gene expressions of Stat1, Pkr, and Atg7. These results suggested that Arctigenin alleviated autophagy as well as apoptosis through inhibiting IFN-γ/IL-6/Stat1 pathway and IL-6/Bnip3 pathway. In summary, the comparative proteomic analysis revealed that the activation of immune system led to Concanavalin A-induced hepatitis. Both autophagy and apoptosis had important clinical implications for the treatment of immune hepatitis. Arctigenin might exert great therapeutic potential in immune-mediated liver injury.

Topics: Animals; Apoptosis; Autophagy; Biomarkers; Concanavalin A; Cytokines; Disease Models, Animal; Female; Furans; Hepatitis; Immune System; Immunohistochemistry; Inflammation Mediators; Lignans; Mice; Proteomics

The role of inflammation and oxidative stress is critical during onset of metabolic disorders and this has been sufficiently established in literature. In the present study, we evaluated the effects of sesamol and sesamin, two important bioactive molecules present in sesame oil, on the generation of inflammatory and oxidative stress factors in LPS injected rats. Sesamol and sesamin lowered LPS induced expression of cPLA

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Arachidonate 5-Lipoxygenase; Benzodioxoles; Biomarkers; Dietary Supplements; Dioxoles; Glutathione Transferase; Hepatitis; Inflammation Mediators; Leukotriene Antagonists; Leukotrienes; Lignans; Lipid Peroxidation; Lipopolysaccharides; Liver; Male; Oxidative Stress; Phenols; Phospholipases A2, Cytosolic; Rats, Wistar; Receptors, Leukotriene B4; Sesame Oil

The effects of wuweizisu C, a lignan component of schizandra fruits, on liver injuries induced by carbon tetrachloride (CCl4), d-galactosamine and dl-ethionine were investigated by means of serum-biochemical and histopathological examinations in rats. Pretreatment or combined administration of wuweizisu C dose-dependently reduced the elevation of serum transaminase activity and histological changes such as fatty degeneration, cell necrosis, inflammatory cell infiltration, etc., which were caused by the single administration of 1 ml/kg, p.o., or the repeated administration of 0.2 ml/kg, s.c., daily for 4 days of CCl4, respectively. The effects of wuweizisu C on the liver injuries induced by a low dose (200 mg/kg, i.p.) and a high dose (400 mg/kg, i.p.) of d-galactosamine were compared with those of uridine. Wuweizisu C significantly lowered the rise of serum transaminase activity after the administration of a low dose of d-galactosamine in the serum-biochemical analysis. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by both doses of d-galactosamine in the histopathological examination. On the other hand, uridine markedly repaired the serum-biochemical and histopathological changes after the administrations of both doses of d-galactosamine. Also wuweizisu C cured the liver injury by the repeated administration of 150 mg/kg, i.p., daily for 4 days of d-galactosamine. After the repeated administration of 250 mg/kg, s.c., daily for 4 days of ethionine, liver cell atrophy, diffuse fatty degeneration and decrease of serum triglyceride were observed, but not cell necrosis. Wuweizisu C dose-dependently inhibited fatty degeneration and decrease of serum triglyceride. These findings suggest that wuweizisu C can be protective and/or therapeutic on hepatocellular phenomena such as cell necrosis, fatty degeneration, inflammatory cell infiltration, etc., in human hepatitis.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cyclooctanes; Ethionine; Fatty Liver; Galactosamine; Hepatitis; Lignans; Liver Diseases; Male; Plant Extracts; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Inbred Strains

This paper reports the total synthesis of (+/-) schizandrin, C, namely 5,6,7,8-tetrahydro-1, 12-dimethoxy-2, 3, 10, 11-bismethylenedioxy-6, 7-cis-dimethyldibenzo (a, c) cyclooctene (12B), a new active SGPT lowering principle isolated from the Chinese medical plant Schizandra chinensis, and its 6, 7-trans-dimethyl isomer (16B). We also synthesized two more isomers, namely 5, 6, 7, 8-tetrahydro-3, 10-dimethoxy-1, 2, 11, 12-bismethylenedioxy-6, and 7-cis-(and trans-) dimethyldibenzo (a, c) cyclooctene (12A and 16A). The NMR, UV and mass spectra of these four isomers are discussed. IR (in chloroform), UV, NMR and MS of synthetic schizandrin C (12B) are identical with those of the natural compound.

Topics: Animals; Cyclooctanes; Hepatitis; Humans; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Plants, Medicinal; Polycyclic Compounds; Spectrophotometry, Ultraviolet