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Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus.

ABSTRACT: In the dimethylnitrosamine (DMN)-induced hepatic fibrosis Wistar rat model, the mycelium extract of Phellinus linteus (PLE) (20 mg/Kg) displayed significant protection against hepatic fibrosis. The present investigation characterized eleven new ionone derivatives, phellinulins D?N (4?14), from the P. linteus mycelium extract and the relative stereochemical structures were constructed according to the spectroscopic and spectrometric analytical results. Some purified compounds were examined for their inhibitory effects on activated rat hepatic stellate cells (HSCs) and several isolates did exhibit significant protection. The results indicated that the mycelium of P. linteus could be explored as a hepatoprotective drug or healthy food candidate in the near future.

SUBMITTER: Huang SC

PROVIDER: S-EPMC6099599 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus.

Huang Shiow-Chyn SC Wang Pei-Wen PW Kuo Ping-Chung PC Hung Hsin-Yi HY Pan Tai-Long TL

Molecules (Basel, Switzerland) 20180712 7

In the dimethylnitrosamine (DMN)-induced hepatic fibrosis Wistar rat model, the mycelium extract of Phellinus linteus (PLE) (20 mg/Kg) displayed significant protection against hepatic fibrosis. The present investigation characterized eleven new ionone derivatives, phellinulins D⁻N (4⁻14), from the P. linteus mycelium extract and the relative stereochemical structures were constructed according to the spectroscopic and spectrometric analytical results. Some purified co ...[more]

PMID: 30002357

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Project description:BackgroundComplementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism.MethodsThe immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4(+) T cells by real time PCR and ELSIA.ResultsTreatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-?) and chemokines (CCL17 and CCL22) involved in AD development.ConclusionsOur study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease.

Project description:The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be approximately about 25.24% of the population worldwide. NAFLD is a complex syndrome and is characterized by a simple benign hepatocyte steatosis to more severe steatohepatitis in the liver pathology. Phellinus linteus (PL) is traditionally used as a hepatoprotective supplement. Styrylpyrone-enriched extract (SPEE) obtained from the PL mycelia has been shown to have potential inhibition effects on high-fat- and high-fructose-diet-induced NAFLD. In the continuous study, we aimed to explore the inhibitory effects of SPEE on free fatty acid mixture O/P [oleic acid (OA): palmitic acid (PA); 2:1, molar ratio]-induced lipid accumulation in HepG2 cells. Results showed that SPEE presented the highest free radical scavenging ability on DPPH and ABTS, and reducing power on ferric ions, better than that of partitions obtained from n-hexane, n-butanol and distilled water. In free-fatty-acid-induced lipid accumulation in HepG2 cells, SPEE showed an inhibition effect on O/P-induced lipid accumulation of 27% at a dosage of 500 μg/mL. As compared to the O/P induction group, the antioxidant activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced by 73%, 67% and 35%, respectively, in the SPEE group. In addition, the inflammatory factors (TNF-α, IL-6 and IL-1β) were significantly down-regulated by the SPEE treatment. The expressions of anti-adipogenic genes involved in hepatic lipid metabolism of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were enhanced in the SPEE supplemented HepG2 cells. In the protein expression study, p-AMPK, SIRT1 and PGC1-α were significantly increased to 121, 72 and 62%, respectively, after the treatment of SPEE. Conclusively, the styrylpyrone-enriched extract SPEE can ameliorate lipid accumulation and decrease inflammation and oxidative stress through the activation of SIRT1/AMPK/PGC1-α pathways.

Project description:OBJECTIVE:To provide a hazard prioritisation for reported chemical constituents of cigarette smoke using toxicological risk assessment principles and assumptions. The purpose is to inform prevention efforts using harm reduction. DATA SOURCES:International Agency for Research on Cancer Monographs; California and US Environmental Protection Agency cancer potency factors (CPFs) and reference exposure levels; scientific journals and government reports from the USA, Canada, and New Zealand. STUDY SELECTION:This was an inclusive review of studies reporting yields of cigarette smoke constituents using standard ISO methods. DATA EXTRACTION:Where possible, the midpoint of reported ranges of yields was used. DATA SYNTHESIS:Data on 158 compounds in cigarette smoke were found. Of these, 45 were known or suspected human carcinogens. Cancer potency factors were available for 40 of these compounds and reference exposure levels (RELs) for non-cancer effects were found for 17. A cancer risk index (CRI) was calculated by multiplying yield levels with CPFs. A non-cancer risk index (NCRI) was calculated by dividing yield levels with RELs. Gas phase constituents dominate both CRI and NCRI for cigarette smoke. The contribution of 1,3-butadiene (BDE) to CRI was more than twice that of the next highest contributing carcinogen (acrylonitrile) using potencies from the State of California EPA. Using those potencies from the USEPA, BDE ranked third behind arsenic and acetaldehyde. A comparison of CRI estimates with estimates of smoking related cancer deaths in the USA showed that the CRI underestimates the observed cancer rates by about fivefold using ISO yields in the exposure estimate. CONCLUSIONS:The application of toxicological risk assessment methods to cigarette smoke provides a plausible and objective framework for the prioritisation of carcinogens and other toxicant hazards in cigarette smoke. However, this framework does not enable the prediction of actual cancer risk for a number of reasons that are discussed. Further, the lack of toxicology data on cardiovascular end points for specific chemicals makes the use of this framework less useful for cardiovascular toxicity. The bases for these priorities need to be constantly re-evaluated as new toxicology information emerges.

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Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus.

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Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus.

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