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Schisandra (Schisandra chinensis) and Detox / cleansing: evidence and sources
inferred from hepatoprotective action
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Schisandra chinensis Turcz. (Baill.) fruits, their extracts, and bioactive compounds are used in alternative medicine as adaptogens and ergogens protecting against numerous neurological, cardiovascular, gastrointestinal, liver, and skin disorders. S. chinensis fruit extracts and their active compounds are potent antioxidants and mitoprotectors exerting anti-inflammatory, antiviral, anticancer, and anti-aging effects. S. chinensis polyphenolic compounds-flavonoids, phenolic acids and the major constituents dibenzocyclooctadiene lignans are responsible for the S. chinensis antioxidant activities. This review will focus on the direct and indirect antioxidant effects of S. chinensis fruit extract and its bioactive compounds in the cells during normal and pathological conditions.
Ethnopharmacological relevance Schisandra chinensis (called bei-wuweizi in Chinese, S. chinensis) and Schisandra sphenanthera (called nan-wuweizi in Chinese, S. sphenanthera) are two highly similar plants in the Magnoliaceae family. Their dried ripe fruits are commonly used as traditional Chinese medicine in the treatment of coughs, palpitation, spermatorrhea, and insomnia. They also are traditionally used as tonics in Russia, Japan, and Korea. Aim of the review S. chinensis and S. sphenanthera are similar in appearance, traditional applications, ingredient compositions, and therapeutic effects. This review, therefore, aims to provide a systematic insight into the botanical background, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicology of S. chinensis and S. sphenanthera, and to explore and present the similarities and differences between S. chinensis and S. sphenanthera. Materials and methods A comprehensive literature search regarding S. chinensis and S. sphenanthera was collected by using electronic databases including PubMed, SciFinder, Science Direct, Web of Science, CNKI, and the online ethnobotanical database. Results In the 2020 Edition of Chinese Pharmacopoeia (ChP), there were 100 prescriptions containing S. chinensis, while only 11 contained S. sphenanthera. Totally, 306 and 238 compounds have been isolated and identified from S. chinensis and S. sphenanthera, respectively. Among these compounds, lignans, triterpenoids, essential oils, phenolic acid, flavonoids, phytosterols are the major composition. Through investigation of pharmacological activities, S. chinensis and S. sphenanthera have similar therapeutic effects including hepatoprotection, neuroprotection, cardioprotection, anticancer, antioxidation, anti-inflammation, and hypoglycemic effect. Besides, S. chinensis turns out to have more effects including reproductive regulation and immunomodulatory, antimicrobial, antitussive and antiasthmatic, anti-fatigue, antiarthritic, and bone remodeling effects. Both S. chinensis and S. sphenanthera have inhibitory effects on CYP3A and P-gp, which can mediate metabolism or efflux of substrates, and therefore interact with many drugs. Conclusions S. chinensis and S. sphenanthera have great similarities. Dibenzocyclooctadiene lignans are regarded to contribute to most of the bioactivities. Schisandrin A-C, schisandrol A-B, and schisantherin A, existing in both S. chinensis and S. sphenanthera but differing in the amount, are the main active components, which may contribute to the similarities and differences. Study corresponding to the traditional use is needed to reveal the deep connotation of the use of S. chinensis and S. sphenanthera as traditional Chinese medicine. In addition, a joint study of S. chinensis and S. sphenanthera can better show the difference between them, which can provide a reference for clinical application. It is worth mentioning that the inhibition of S. chinensis and S. sphenanthera on CYP3A and P-gp may lead to undesirable drug-drug interactions.
2 sources supporting Schisandra for Detox / cleansing. Includes scientific publications, books, monographs and traditional-use references.
Mechanistic basis
This use is associated with the plant's hepatoprotective (liver support) action. Further evidence for that pharmacology:
Aim Schisandra chinensis is a well-known traditional Chinese medicine used mainly as a recipe for hepatoprotection. Modern researches have revealed that the hepatoprotection is related to its lignans and crude polysaccharide. In this study, we examined the effect and mechanism of Schisandra chinensis acidic polysaccharide (SCAP) on the liver injury induced by ethanol. Main methods SCAP was extracted with water extraction and ethanol precipitation. Liver injury models of both mice and HepG2 cells were produced by ethanol. The liver index, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum of the mice and cell culture supernatant were examined; HE staining was performed for observing pathological changes of liver. The malondialdehyde (MDA) level and superoxide dismutase (SOD) activities in serum, liver tissue and HepG2 cells, and triglyceride (TG) content in liver tissue were tested. Western blot was conducted to determine cytochrome P450 2E1 (CYP2E1) expression in liver tissue of mice and HepG2 cells. Key findings SCAP significantly reduced serial AST and ALT levels in the injuried liver and HepG2 cells induced by ethanol and also decreased TG level in the liver tissue. SCAP also obviously improved the hepatopathological changes and decreased MDA level as well as increased SOD activities in the serum, liver tissue and HepG2 cells induced by ethanol. Furthermore, Western blot analysis indicated that SCAP significantly inhibited the upregulation of CYP2E1 protein. Significance SCAP has a protective effect on ethanol-induced liver injury in mice and cells, and the mechanism underlying may be via inhibiting the expression of CYP2E1 protein and then alleviating oxidative stress injury induced by ethanol.
Fruit of Schisandra chinensis Turcz. (Baill.) (S. chinensis) is a traditional herbal medicine widely used in China, Korea, and many other east Asian countries. At present, S. chinensis commonly forms Chinese medicinal formulae with other herbal medicines to treat liver disease and neurological disease in clinical. Modern researches indicated that lignans were the main active ingredients of S. chinensis with high content and novel dibenzocyclooctadiene skeletal structure, exhibited considerable antioxidant, anti-inflammatory, and neuroprotective properties. Additionally, some of these lignans also showed certain potentials in anti-cancer, anti-fibrosis, and other effects. In the current review, we summarize literature reported lignans from S. chinensis in the past five years, and highlight the molecular mechanisms of lignans in exerting their biological functions. Also, we point out some deficiencies of existing researches and discuss the future direction of lignans study.
Ethnopharmacological relevance Schisandra chinensis is used as a traditional Chinese medicine to treat a variety of diseases. Schisandra chinensis lignans (SCL) are one of the most active components extracted from Schisandrae chinensis fructus, exhibit a broad array of pharmacological properties, especially anti-inflammatory and hepatic lipid-lowering effects, suggesting SCL may have potential anti-nonalcoholic steatohepatitis (NASH) ability. However, the therapeutic efficacy of SCL against NASH and the underlying mechanism of this action remains unclear. Aim of the study In the current study, we aimed to investigate the anti-NASH action of SCL and explore the underlying mechanism in vitro and in vivo. We also assess the involvement of the gut-liver axis in the anti-NASH effects of SCL. Methods Palmitic acid (PA)-treated HepG2 cells, mouse primary hepatocytes (MPHs) and methionine-choline deficient (MCD) diet-fed mice were selected as NASH models. ORO staining and qRT-PCR were performed to assess hepatic steatosis and inflammatory responses, respectively. Masson's trichrome staining was used to detect the liver fibrosis. Protein expression was detected by Western blotting or immunohistochemistry. The changes of gut microbiota were analyzed using 16S rDNA sequencing in mice. The levels of metabolites in liver and feces were measured by metabolomics. Results The results showed that SCL treatment alleviated steatosis and inflammation in palmitic acid (PA)-treated HepG2 cells and mouse primary hepatocytes (MPHs). SCL treatment suppressed the phosphorylation of key components involved in NF-κB signaling and enhanced the expression of fatty acid oxidation (FAO)-related enzymes (e.g. CPT1, HMGCS2, and ACOX1) in PA-treated HepG2 cells. SCL could ameliorate hepatic steatosis and inflammation in NASH mice. SCL also ameliorated intestinal barrier injury and restructured the gut microbiota in NASH mice. SCL also modulated hepatic and colonic bile acid metabolism via FXR signaling. Conclusion These findings indicate that SCL treatment ameliorates hepatic inflammation and steatosis in NASH mice, potentially though to the suppression of NF-κB signaling and the promotion of fatty acid β-oxidation. Moreover, SCL could restore gut microbiota-mediated bile acid homeostasis via activation of FXR/FGF15 signaling. Our study presents a pharmacological rationale for using SCL in the management of NASH.