Schisandrin B Enhances Cerebral Mitochondrial Antioxidant Status and Structural Integrity, and Protects against Cerebral Ischemia/Reperfusion Injury in Rats

Abstract

Schisandrin B (Sch B) is the most abundant, active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis (FS), a traditional Chinese herb clinically used for the treatment of viral and chemical hepatitis. 1)A recent study from our laboratory has demonstrated that long-term treatment with Sch B was able to enhance mitochondrial antioxidant status and the resistance to Ca 2ϩ -induced mitochondrial permeability transition (PT) in an ageindependent manner in various rat organs including the heart and brain.2) The Sch B-induced enhancement of mitochondrial protective parameters in the heart was associated with the protection against myocardial ischemia/reperfusion (I/R) injury in both young and middle-aged rats.2) Given that the maintenance of mitochondrial antioxidant status and structural integrity is crucial for cell survival, 3) Sch B has been proposed to be used as a universal cell protectant against tissue damage caused by endogenous and exogenous oxidants. 2)While the protection of Sch B against I/R injury has been demonstrated in the heart, 2,4) it is still unclear whether Sch B treatment can produce any beneficial effect on cerebral I/R injury.In the present study, we investigated the effect of longterm treatment with Sch B on cerebral I/R injury in rats. To elucidate the biochemical mechanism involved in the cerebroprotection against I/R injury, cerebral mitochondrial antioxidant status as well as mitochondrial structural integrity were assessed in control and Sch B-treated rats, without or with I/R challenge. MATERIALS AND METHODS ChemicalsReduced glutathione (GSH), oxidized glutathione, glutathione reductase, cytochrome c, a-tocopherol (a-TOC), cyclosporin A (Cs A) and 2,3,5-triphenyl tetrazolium chloride (TTC) were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). All other chemicals were of analytical grade. Solvents used for HPLC were of HPLC grade.Herbal Material Dried FS was imported from mainland China. It was authenticated and supplied by a commercial dealer (Lee Hoong Kee Ltd.) in Hong Kong. Sch B was purified from the petroleum ether extract of FS, with the purity being higher than 95% as determined by HPLC analysis. 5)Animal Care Adult female Sprague-Dawley rats (8-10 weeks; 200-250 g) were maintained under a 12-h dark/light cycle at about 22°C, and allowed food and water ad libitum. Experimental protocols were approved by the Research Practice Committee at the Hong Kong University of Science & Technology.Drug Treatment Animals were randomly divided into groups, with five animals in each. In the Sch B treatment groups, rats were intragastrically administered with Sch B (dissolved/suspended in olive oil) at a daily dose of 1, 10 or 30 mg/kg from day 1 to day 15 of the experiment. This dosage regimen was found to be effective in protecting against myocardial ischemia/reperfusion injury in rats.2) Sch B-untreated animals received the vehicle (i.e. olive oil) only. The rat model of cerebral I/R injury was modified from that of Ischikawa and Konishi.6) Phenobarbita...

Prooxidant-Induced Glutathione Antioxidant Response <i>in Vitro</i> and <i>in Vivo</i>: A Comparative Study between Schisandrin B and Curcumin

“…1) Our laboratory has shown that the induction of glutathione antioxidant response is essential to confer cellular/tissue protection against various oxidant-induced injuries. [2][3][4][5][6] Daily consumption of antioxidants, such as ascorbic acid and α-tocopherol, has been recommended for enhancing cellular antioxidant defense capacity. However, results obtained from epidemiological studies as well as clinical trials have failed to demonstrate the beneficial effects of antioxidant intake.…”

The α-iso-cubebenol compound isolated from Schisandra chinensis induces p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells

“…The aforementioned ligands contribute to the hepatic regeneration process via the induction of mRNA transcription for hepatocyte growth factor, as well as the stimulation of hepatocyte proliferation and increased blood flow to the liver. Additionally, in an effort to improve regenerative capacity via reduced glutation and the synthesis of hepatic glucogen, the addition of these lignans induces increases in the levels of mitochondrial hepatic glutation and mitochondrial reductase glutation activity (31,32). However, relatively few functional studies have been conducted to investigate in detail whether the novel lignans isolated from S. chinensis influence cell death of the hepatocellular carcinoma cells in vitro.…”

Analysis of lignans in Schisandra chinensis and rat plasma by high‐performance liquid chromatography diode‐array detection, time‐of‐flight mass spectrometry and quadrupole ion trap mass spectrometry

“…For example, gomisin G and schisantherin A were a group of isomers with the same molecular weight (MW) of 536.2125 at peaks 9 and 12, and gomisin E, gomisin F and schisantherin B were a group of isomers with MW 514.2203 at peaks 11, 13 and 14. Although the two groups of isomers have different molecular formulae (C 30 H 32 O 9 for gomisin G and schisantherin A, and C 28 H 34 O 9 for gomisin E, gomisin L 1 and schisantherin B), the same ion (m/z 537) was present in the mass spectrum, which cannot be distinguished to within 5 ppm error only according to accurate mass measurement by TOFMS. However, other adduct ions at m/z 537 and 559 were present in the mass spectra of peaks 9 and 12, which can be tentatively inferred as the [MþH] þ ion at m/z 537.…”

“…They have different pharmacological actions, such as schisandrin B has crucial antioxidant and antiinflammatory actions. [8][9][10] However, most of these components were isolated from the concentrated extract of large amounts of herbals, and their effectiveness cannot be explained clearly because the amount of an individual compound isolated is so small that no effective method is available to detect its efficacy. For this reason, it is not clear which components play a bioactive role in the pharmacological actions of S. chinensis.…”