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Clinical Studies
Schisandra is an adaptogen for increasing resistance to disease and stress, energy and increasing physical performance and endurance. Schisandra is believed to improve liver function and may also have a liver protective effect. Schisandra may increase cognition, concentration, coordination and endurance. Schisandra is used also for depression, irritability and memory loss, for improving energy, preventing premature aging, increasing lifespan, for premenstrual syndrome (PMS), stimulating the immune system, speeding recovery after surgery, protecting against radiation, preventing infection, improving adrenal health and energizing RNA-DNA to rebuild cells. It is reported to have antioxidant and anti-inflammatory properties. Other reported properties of various Schisandra lignans include anticonvulsant, antidepressant, anti-fatigue, tranquilizing, respiratory stimulant and platelet activating factor (PAF) inhibition.
Published Clinical Studiescl top
Triterpenoids from Schisandra henryi with cytotoxic effect on Leukemia and Hela cells in vitro.1
Chen YG, Wu ZC, Lv YP, Gui SH, Wen J, Liao XR, Yuan LM, Halaweish F.
Department of Chemistry, Yunnan Normal University, Kunming 650092, China. ygchen48@hotmail.com
Four known lanostane triterpenoids, schiprolactone A (1), schisanlactone B (2), nigranoic acid (3) and schisandronic acid (4) were isolated from the stems of Schisandra henryi for the first time. Their structures were characterized by IR, MS and NMR techniques. Compounds 1, 2 and 4 showed moderate cytotoxic activity against Leukemia cells in vitro. Cytotoxic activity of compounds 1-4 showed IC50 of 0.0097, 0.01, 0.097 and 0.0099 micromol/mL respectively toward Leukemia cells and IC50 of 0.097, 0.1, 0.097 and 0.099 micromol/mL toward Hela cells respectively. It is the first report that these compounds possess cytotoxic activity on Leukemia and Hela cells.
PMID: 14661856 [PubMed - in process]
The mechanism of retinol-induced irritation and its application to anti-irritant development.2
Kim BH, Lee YS, Kang KS.
Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Despite many beneficial effects on dermatological applications, retinol and its derivatives cause severe local irritation manifested as mild erythema and stratum corneum peeling of the skin. It is hypothesized that cytokines may be important inflammatory mediators in retinoid-induced dermatitis. The present study was designed to determine cytokine mediators and thereby, to screen potential anti-irritants in retinoid-induced inflammation. The changes in mRNA expression of inflammation-related cytokines including mouse analogue of human monocyte chemoattractant protein-1 (MCP-1) (JE), mouse analogue of human interleukin-8 (IL-8) (KC), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-12p40, IL-6, IL-10, Eotaxin were determined in mouse epidermal cells treated by 2% retinol using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The up-regulated mRNA level was confirmed with protein levels in culture supernatants from human epidermal keratinocytes, melanocytes, and fibroblasts treated with 10 microM retinol or retinoic acid. As results, retinoid-induced inflammation was mainly mediated through MCP-1 and IL-8 as evidenced by increased levels of mRNA expression and protein secretion. The potential anti-irritant substances including beta-sitosterol, Magnoliae flos, beta-glycyrrhetinic acid, SC-glucan, Ginko extract, Raspberry extract, Schisandra extract, Cola extract, Enna complex or Vegetol red grapevine extract were evaluated for their inhibitory effects on retinol-induced cytokine (MCP-1 and IL-8) secretion in vitro cultured human fibroblasts. Furthermore, in vivo efficacy tests for the retinol-induced irritancy were performed using Draize skin irritation test in the rabbit and human patch test. Most of the substances that reduced the secretion of MCP-1 and IL-8 in vitro cultured fibroblasts, showed a good inhibition against the retinol-induced irritation in the rabbit and human patch test. In conclusion, the present study demonstrated that among proinflammatory cytokines, MCP-1 and IL-8 mainly mediated retinol-induced skin irritation, and that inhibition of production of these cytokines can be applied as good markers to screen the anti-irritants against the retinol-induced irritation.
PMID: 14615068 [PubMed - indexed for MEDLINE]
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Role of component herbs in antioxidant activity of shengmai san--a traditional Chinese medicine formula preventing cerebral oxidative damage in rat.
Ichikawa H, Wang X, Konishi T.
Department of Radiochemistry--Biophysics and Functional Food Science, Niigata University of Pharmacy and Applied Life Sciences, Japan.
Traditional Chinese medicine (TCM) is an attractive model for studying antioxidant-based composite therapy. We previously reported that Shengmai San (SMS), a TCM formulation for treating cardiac disorders, inhibited cerebral oxidative damage in rats when evaluated by both glutathione peroxidase (GPX) activity loss and thiobarbituric acid reactive substance (TBARS) formation after forebrain ischemia-reperfusion. In the present study, we further examined the preventive effect of SMS and related decoctions composed of three component herbs (Panax ginseng, Ophiopogon japonicus and Schisandra chinensis) against oxidative brain injury to rationalize the complex formulation of SMS. Schisandra chinensis itself and decoctions containing it all inhibited TBARS formation in vivo. In contrast, Ophiopogon japonicus itself and formulations containing it had little effect on TBARS formation. GPX activity loss in vivo, on the other hand, was completely prevented only by SMS and Ophiopogon japonicus itself. A comparison of the in vitro antioxidant potential of SMS and related decoctions and in vivo effectiveness in preventing cerebral oxidative damage revealed that all the in vitro antioxidant indices examined here essentially correlated well with inhibition of TBARS formation in vivo. DPPH quenching and crocin bleaching activities showed particularly good correlation, and then, superoxide scavenging activity followed. However, none of them correlated with the inhibition of GPX activity loss in vivo. The role of each component herb is also discussed for the SMS effect.
PMID: 14587874 [PubMed - in process]
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Small scale rat hepatocyte primary culture with applications for screening hepatoprotective substances.
Nakagiri R, Oda H, Kamiya T.
Kyowa Hakko Kogyo Co., Ltd., Tsukuba Research Laboratories, 2 Miyukigaoka, Tsukuba-shi, Ibaraki 305-0841, Japan. ryuusuke.nakagiri@kyowa.co.jp
Isolated hepatocytes are known to maintain their physiological functions for over a week when cultured on Matrigel, artificially reconstituted from basement membrane components. Although this culture technique has been frequently used in research on hepatocyte functions, there has been a limitation on its application for small scale experiments due to some technical problems. By using micro-culture plates with 96 round-bottom wells, we succeeded in coating the wells uniformly with Matrigel. When the cultured hepatocytes were treated with either 10 mM, 15 mM, or 20 mM of acetaminophen or 1 mM, 10 mM, or 20 mM of D-galactosamine, the viability of the hepatocytes became 91.1%, 75.3%, 64.7%, and 79.0%, 43.8%, 26.2% of the non-treated control at 48 hours, respectively. Fractionated extracts of Glycyrrhiza glabra L. and Schisandra chinensis Baillon inhibited the action of acetaminophen or D-galactosamine in this model. From these results, we concluded that the microculture system presented here is capable of maintaining the in vivo characteristics of hepatocytes and is suitable for the screening of hepatoprotective substances.
PMID: 12951493 [PubMed - in process]
Herbal preparations as a source of hepatoprotective agents.5
Ram VJ.
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.
Mono- and polyherbal preparations with potent antihepatotoxic activity in various liver disorders, made from traditionally used herbs with proven efficacy, have been described. More than 700 mono- and polyherbal preparations in the form of decoction, tincture, tablets and capsules from more than 100 plants are in clinical use. Some of the herbs--such as Silybum marianum, Picrorhiza kurroa, Andrographis paniculata and Glycyrrhizae radix--are very common in most of the polyherbal preparations. This review covers the preparations of widely used herbs such as S. marianum, Schisandra chinensis, Phyllanthus amarus, P. kurroa, A. paniculata, G. radix, Lycium chinense and Cochlospermum tinctorium as hepatoprotectants and includes the mode of action of these preparations. Some polyherbal preparations such as Livex, HD-03, Hepatomed and Hepatoguard with proven efficacy are also described in this review. (c) 2001 Prous Science. All rights reserved.
PMID: 12813598 [PubMed]
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Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice.
Pan SY, Han YF, Carlier PR, Pang YP, Mak DH, Lam BY, Ko KM.
Department of Biochemistry, Hong Kong University of Science & Technology, China.
Intragastric administration (100-200 micromol/kg) of tacrine (THA) or bis(7)-THA could cause an acute and dose-dependent increase in plasma alanine aminotransferases activity in mice at 6 h after the drug administration. The increase in plasma enzyme activity was associated with an increase in hepatic malondialdehyde level, an indirect index of oxidative tissue damage. Pretreating mice with schisandrin B (Sch B), an active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 0.125-0.5 mmol/kg for 3 days protected against the THA/bis(7)-THA induced hepatic oxidative damage in a dose-dependent manner. Sch B treatment (0.025-0.5 mmol/kg/day x 5) also enhanced the passive avoidance-response in mice as assessed by the step-through task experiment. The ensemble of results suggests that Sch B may be useful for reducing the potential hepatotoxicity of THA/bis(7)-THA in anti-Alzheimer's therapy.
PMID: 11914957 [PubMed - indexed for MEDLINE]
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Improvement of phase I drug metabolism with Schisandra chinensis against CCl4 hepatotoxicity in a rat model.
Zhu M, Yeung RY, Lin KF, Li RC.
Department of Pharmacy, Chinese University of Hong Kong, Hong Kong.
The seed extract of Schisandra chinensis was investigated in the rat for its restorative or therapeutic effect on Phase I hepatic drug metabolism following intoxication by carbon tetrachloride (CCl4). Male Sprague Dawley rats (220-250 g) were divided into two sets, one included rats with or without CCl4 intoxication, the other included CCl4 intoxicated rats with or without treatment of Schisandra extract. With the treatment regimen, rats received four oral doses of Schisandra (160 mg/kg) or the same volume of water at 8, 24, 32 and 48 h after CCl4 intoxication. A single oral dose (80 mg/kg) of antipyrine, a conventional probe for oxidative drug metabolism, was then administered. The levels of liver serum transaminases and cytochrome P450 were measured and the pharmacokinetics of antipyrine were assessed using a non-compartmental approach via WinNonlin. In comparison to the rats without CCl4 intoxication (t1/2: 2.2 +/- 0.9 h; Cl/F: 0.30 +/- 0.01 L/h/Kg; P450: 0.611 +/- 0.190 nmol/mg protein), CCl4 administration significantly decreased elimination (t1/2: 12.0 +/- 3.9 h) and oral clearance (Cl/F: 0.049 +/- 0.018 L/h/kg) of antipyrine, and markedly reduced the content of P450 (0.075 +/- 0.011 nmol/mg protein). Data obtained from intoxicated animals treated by Schisandra extract, compared to those without treatment, showed significant (p < 0.05) improvement in the t1/2 (4.45 +/- 1.7 h) and Cl/F (0.096 +/- 0.018 ml/h) estimates of antipyrine and a 2-3 fold increase in P450 level (0.190 +/- 0.072 nmol/mg protein). Findings in this study suggest that the seed extract of Schisandra appeared to be a promising agent for the improvement of Phase I oxidative metabolism in the liver damaged by CCl4.
PMID: 10985077 [PubMed - indexed for MEDLINE]
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Structure-activity relationships of lignans from Schisandra chinensis as platelet activating factor antagonists.
Lee IS, Jung KY, Oh SR, Park SH, Ahn KS, Lee HK.
Biotechnology Research Division, Korea Research Institute of Bioscience and Biotechnology, Taejon.
We studied the structure-activity relationships of lignans from Schisandra chinensis and their derivatives as platelet activating factor (PAF) antagonists. Strong activity was shown in lignans without an ester group at C-6, a hydroxyl group at C-7 or a methylene dioxy moiety and with an R-biphenyl configuration. 6(7)-Dehydroschisandrol A, a derivative of schisandrol A, showed the highest activity (IC50, 2.1x10(-6) M) in this study.
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Effect of a lignan-enriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity.
Ko KM, Ip SP, Poon MK, Wu SS, Che CT, Ng KH, Kong YC.
Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon.
The effect of a lignan-enriched extract of the fruits of Schisandra chinensis (FS) on hepatic glutathione (GSH) status was examined in both control and carbon tetrachloride (CCl4)-treated rats. FS treatment caused a dose-dependent enhancement in hepatic GSH status, as evidenced by significant increases in hepatic GSH level and activities of hepatic glucose-6-phosphate and glutathione reductase (GRD), as well as a decreased susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion. The beneficial effect of FS treatment on hepatic GSH status became more evident after CCl4 challenge. Pretreating rats with FS extract at increasing daily doses ranged from 0.2 to 3.2 g/kg for 3 days caused a dose-dependent protection against the CCl4-induced impairment in hepatic GSH status. The enhancement in hepatic GSH status was associated with corresponding decreases in tissue malondialdehyde levels and plasma alanine aminotransferases activities, indicating a significant reduction in the extent of oxidative hepatocellular damage. Our results indicate that the molecular mechanism of hepatoprotection afforded by FS pretreatment may involve the facilitation of GSH regeneration via the GRD-catalyzed and NADPH-mediated reaction.
PMID: 7753920 [PubMed - indexed for MEDLINE]