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The effects of VI-28 (a Yang-invigorating Chinese herbal formula) treatment on the renal mitochondrial antioxidant system and susceptibility to gentamicin-induced nephrotoxicity were investigated in rats. VI-28 treatment (80 or 240 mg/kg/day x 12) enhanced the renal mitochondrial antioxidant system, as indicated by dose-dependent increases in the level/activities of reduced glutathione, Mn-superoxide dismutase, Se-glutathione peroxidase and glutathione S-transferases. VI-28 treatment protected against nephrotoxicity induced by gentamicin administration (100 mg/kg/day x 8) and the nephroprotection was associated with an enhancement in the renal mitochondrial antioxidant system. In conclusion, VI-28 treatment enhanced the renal mitochondrial antioxidant system, thereby protecting against gentamicin nephrotoxicity. Copyright (c) 2007 John Wiley & Sons, Ltd.

The effects of VI-28 (a Yang-invigorating Chinese herbal formula) treatment on the renal mitochondrial antioxidant system and susceptibility to gentamicin-induced nephrotoxicity were investigated in rats. VI-28 treatment (80 or 240 mg/kg/day x 12) enhanced the renal mitochondrial antioxidant system, as indicated by dose-dependent increases in the level/activities of reduced glutathione, Mn-superoxide dismutase, Se-glutathione peroxidase and glutathione S-transferases. VI-28 treatment protected against nephrotoxicity induced by gentamicin administration (100 mg/kg/day x 8) and the nephroprotection was associated with an enhancement in the renal mitochondrial antioxidant system. In conclusion, VI-28 treatment enhanced the renal mitochondrial antioxidant system, thereby protecting against gentamicin nephrotoxicity. Copyright (c) 2007 John Wiley & Sons, Ltd.

In order to investigate the pharmacological basis of `Yang-invigorating' action, the effect of oral treatment with the methanolic extract of `Yang-invigorating' herbs on ATP-generation capacity was examined, using heart homogenates prepared from herb-pretreated mice. Tonifying (i.e., health-promoting) herbs of other functional categories were also included for comparison. The results indicated that `Yang-invigorating' Chinese tonifying herbs could invariably enhance myocardial ATP-generation capacity, with the extent of stimulation varying among the herbs. In contrast, `Yin-nourishing' herbs either did not stimulate or even decreased myocardial ATP-generation capacity. While `Qi-invigorating' herbs produced variable effects on myocardial ATP-generation capacity, most of the `blood-enriching' herbs did not cause any significant changes. The results obtained from studies using myocardial mitochondrial fractions isolated from herb-pretreated mice suggest that `Yang-invigorating' herbs might speed up ATP generation by increasing mitochondrial electron transport. The ensemble of results has provided evidence for the first time to support the pharmacological basis of `Yang invigoration' in Chinese medicine. (c) 2006 Elsevier GmbH. All rights reserved.

In order to investigate the pharmacological basis of `Yang-invigorating' action, the effect of oral treatment with the methanolic extract of `Yang-invigorating' herbs on ATP-generation capacity was examined, using heart homogenates prepared from herb-pretreated mice. Tonifying (i.e., health-promoting) herbs of other functional categories were also included for comparison. The results indicated that `Yang-invigorating' Chinese tonifying herbs could invariably enhance myocardial ATP-generation capacity, with the extent of stimulation varying among the herbs. In contrast, `Yin-nourishing' herbs either did not stimulate or even decreased myocardial ATP-generation capacity. While `Qi-invigorating' herbs produced variable effects on myocardial ATP-generation capacity, most of the `blood-enriching' herbs did not cause any significant changes. The results obtained from studies using myocardial mitochondrial fractions isolated from herb-pretreated mice suggest that `Yang-invigorating' herbs might speed up ATP generation by increasing mitochondrial electron transport. The ensemble of results has provided evidence for the first time to support the pharmacological basis of `Yang invigoration' in Chinese medicine. (c) 2006 Elsevier GmbH. All rights reserved.

In order to investigate the pharmacological basis of `Yang-invigorating' action, the effect of oral treatment with the methanolic extract of `Yang-invigorating' herbs on ATP-generation capacity was examined, using heart homogenates prepared from herb-pretreated mice. Tonifying (i.e., health-promoting) herbs of other functional categories were also included for comparison. The results indicated that `Yang-invigorating' Chinese tonifying herbs could invariably enhance myocardial ATP-generation capacity, with the extent of stimulation varying among the herbs. In contrast, `Yin-nourishing' herbs either did not stimulate or even decreased myocardial ATP-generation capacity. While `Qi-invigorating' herbs produced variable effects on myocardial ATP-generation capacity, most of the `blood-enriching' herbs did not cause any significant changes. The results obtained from studies using myocardial mitochondrial fractions isolated from herb-pretreated mice suggest that `Yang-invigorating' herbs might speed up ATP generation by increasing mitochondrial electron transport. The ensemble of results has provided evidence for the first time to support the pharmacological basis of `Yang invigoration' in Chinese medicine. (c) 2006 Elsevier GmbH. All rights reserved.

The practice of traditional Chinese medicine (TCM) always emphasizes the prevention of diseases and delaying the onset of senility. In this regard, the maintenance of a balance of Yin and Yang-two opposing components involved in life activities as exemplified by the antagonistic action of the sympathetic and parasympathetic nervous systems-is essential in achieving a healthy condition. Previous studies have shown that long-term treatment with a Yang-invigorating Chinese herbal formula (VI-28) could increase red cell CuZn-superoxide dismutase (SOD) activity in male human subjects. In the present study, we examined the effects of chronic VI-28 treatment (80 and 240 mg/kg/day for 30 days) on red cell CuZn-SOD activity as well as mitochondrial functional ability and antioxidant components in various tissues of male and female rats. The results indicated that VI-28 treatment increased red cell CuZn-SOD activity as well as mitochondrial ATP generation capacity, reduced glutathione and a-tocopherol levels, and Mn-SOD activity in brain, heart, liver, and skeletal muscle tissues in both male and female rats to varying extents. The VI-28-induced increase in mitochondrial antioxidant capacity in various tissues was evidenced by the significant reduction in the extent of reactive oxygen species generation assessed by in vitro measurement. The red cell CuZn-SOD activities correlated positively with tissue mitochondrial antioxidant component levels/activity. The beneficial effect of VI-28 treatment on mitochondrial functional ability and antioxidant capacity may have clinical implications in the prevention of age-related diseases.

The practice of traditional Chinese medicine (TCM) always emphasizes the prevention of diseases and delaying the onset of senility. In this regard, the maintenance of a balance of Yin and Yang-two opposing components involved in life activities as exemplified by the antagonistic action of the sympathetic and parasympathetic nervous systems-is essential in achieving a healthy condition. Previous studies have shown that long-term treatment with a Yang-invigorating Chinese herbal formula (VI-28) could increase red cell CuZn-superoxide dismutase (SOD) activity in male human subjects. In the present study, we examined the effects of chronic VI-28 treatment (80 and 240 mg/kg/day for 30 days) on red cell CuZn-SOD activity as well as mitochondrial functional ability and antioxidant components in various tissues of male and female rats. The results indicated that VI-28 treatment increased red cell CuZn-SOD activity as well as mitochondrial ATP generation capacity, reduced glutathione and a-tocopherol levels, and Mn-SOD activity in brain, heart, liver, and skeletal muscle tissues in both male and female rats to varying extents. The VI-28-induced increase in mitochondrial antioxidant capacity in various tissues was evidenced by the significant reduction in the extent of reactive oxygen species generation assessed by in vitro measurement. The red cell CuZn-SOD activities correlated positively with tissue mitochondrial antioxidant component levels/activity. The beneficial effect of VI-28 treatment on mitochondrial functional ability and antioxidant capacity may have clinical implications in the prevention of age-related diseases.

The practice of traditional Chinese medicine (TCM) always emphasizes the prevention of diseases and delaying the onset of senility. In this regard, the maintenance of a balance of Yin and Yang-two opposing components involved in life activities as exemplified by the antagonistic action of the sympathetic and parasympathetic nervous systems-is essential in achieving a healthy condition. Previous studies have shown that long-term treatment with a Yang-invigorating Chinese herbal formula (VI-28) could increase red cell CuZn-superoxide dismutase (SOD) activity in male human subjects. In the present study, we examined the effects of chronic VI-28 treatment (80 and 240 mg/kg/day for 30 days) on red cell CuZn-SOD activity as well as mitochondrial functional ability and antioxidant components in various tissues of male and female rats. The results indicated that VI-28 treatment increased red cell CuZn-SOD activity as well as mitochondrial ATP generation capacity, reduced glutathione and a-tocopherol levels, and Mn-SOD activity in brain, heart, liver, and skeletal muscle tissues in both male and female rats to varying extents. The VI-28-induced increase in mitochondrial antioxidant capacity in various tissues was evidenced by the significant reduction in the extent of reactive oxygen species generation assessed by in vitro measurement. The red cell CuZn-SOD activities correlated positively with tissue mitochondrial antioxidant component levels/activity. The beneficial effect of VI-28 treatment on mitochondrial functional ability and antioxidant capacity may have clinical implications in the prevention of age-related diseases.

In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may reflect a corresponding change in antioxidant status of peripheral tissues. Copyright (C) 2004 John Wiley Sons, Ltd.

Cordyceps sinensis (Berk.) Sacc. (Cordyceps), a popular Chinese tonifying herb, was revered for being both `Yin-nourishing' and `Yang-invigorating' in Chinese medicine. In order to establish the pharmacological basis for the `Yin-nourishing' and `Yang-invigorating' action of Cordyceps, the effects of wild and cultured Cordyceps on concanavalin A (Con A)-stimulated splenocytes, an in vitro bioassay for `Yin-nourishment', and myocardial ATP generation capacity, an ex vivo bioassay for `Yang-invigoration', were investigated in mice. The results indicated that methanolic extracts of wild and cultured Cordyceps enhanced both the Con A-stimulated splenocyte proliferation in vitro and myocardial mitochondrial ATP generation ex vivo in mice, with no significant difference in potency of action between the two types of Cordyceps. While the immuno-potentiating effect was associated with the increase in interleukin II production, the stimulation of myocardial ATP generation was paralleled by an enhancement in mitochondrial electron transport. When compared with typical `Yin' and `Yang' tonifying Chinese herbs, Cordyceps was found to possess both, `Yin-nourishing' and `Yang-invigorating' activities, with a lower potency in both modes of action. The pharmacological characterization of Cordyceps by means of contemporary bioassays is consistent with the time-honored clinical observation from Chinese herbalists. (C) 2004 Elsevier Inc. All rights reserved.

The `Yin-Yang' theory is an ancient Chinese philosophy that underlies the practice of traditional Chinese medicine. Although Yang-tonic herbs tend to boost body function possibly through enhancing the mitochondrial oxidative processes, the Yin property (i.e. antioxidant potential) of these herbs can also play a role in safeguarding mitochondrial ATP generation. The pharmacological basis of `Yang-invigoration' by Chinese tonic herbs might be due primarily to the enhancement of mitochondrial ATP generation.

The `Yin-Yang' theory is an ancient Chinese philosophy that underlies the practice of traditional Chinese medicine. Although Yang-tonic herbs tend to boost body function possibly through enhancing the mitochondrial oxidative processes, the Yin property (i.e. antioxidant potential) of these herbs can also play a role in safeguarding mitochondrial ATP generation. The pharmacological basis of `Yang-invigoration' by Chinese tonic herbs might be due primarily to the enhancement of mitochondrial ATP generation.

The `Yin-Yang' theory is an ancient Chinese philosophy that underlies the practice of traditional Chinese medicine. Although Yang-tonic herbs tend to boost body function possibly through enhancing the mitochondrial oxidative processes, the Yin property (i.e. antioxidant potential) of these herbs can also play a role in safeguarding mitochondrial ATP generation. The pharmacological basis of `Yang-invigoration' by Chinese tonic herbs might be due primarily to the enhancement of mitochondrial ATP generation.

Cordyceps sinensis (Berk.) Sacc. (Cordyceps), a popular Chinese tonifying herb, was revered for being both `Yin-nourishing' and `Yang-invigorating' in Chinese medicine. In order to establish the pharmacological basis for the `Yin-nourishing' and `Yang-invigorating' action of Cordyceps, the effects of wild and cultured Cordyceps on concanavalin A (Con A)-stimulated splenocytes, an in vitro bioassay for `Yin-nourishment', and myocardial ATP generation capacity, an ex vivo bioassay for `Yang-invigoration', were investigated in mice. The results indicated that methanolic extracts of wild and cultured Cordyceps enhanced both the Con A-stimulated splenocyte proliferation in vitro and myocardial mitochondrial ATP generation ex vivo in mice, with no significant difference in potency of action between the two types of Cordyceps. While the immuno-potentiating effect was associated with the increase in interleukin II production, the stimulation of myocardial ATP generation was paralleled by an enhancement in mitochondrial electron transport. When compared with typical `Yin' and `Yang' tonifying Chinese herbs, Cordyceps was found to possess both, `Yin-nourishing' and `Yang-invigorating' activities, with a lower potency in both modes of action. The pharmacological characterization of Cordyceps by means of contemporary bioassays is consistent with the time-honored clinical observation from Chinese herbalists. (C) 2004 Elsevier Inc. All rights reserved.

In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may reflect a corresponding change in antioxidant status of peripheral tissues. Copyright (C) 2004 John Wiley Sons, Ltd.

In the present study, the hepatoprotective effect of metformin (Met), a dimethylbiguanide anti-hyperglycemic, was examined in a mouse model of liver damage induced by chronic repeated administration of carbon tetrachloride (CCl4) (5 mul/kg, twice a week for 12 weeks). Met, when given orally in drinking water at an estimated daily dose of 25 or 50 mg /kg for 10 weeks starting 2 weeks after CCl4 challenge, protected against CCl4 hepatotoxicity. The results indicate that the hepatoprotection afforded by Met treatment at a dose of 25 mg/kg against CCl4 toxicity may at least in part be mediated by the enhancement of mitochondrial glutathione redox status.

In this study, the time course of schisandrin B- (Sch B-) induced changes in hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (HSP) 25/70 induction was examined to study their differential roles in the hepatoprotection afforded by Sch B pretreatment against carbon tetrachloride (CCl4) toxicity in mice. Dimethyl diphenyl bicarboxylate (DDB), a nonhepatoprotective analog of Sch B, was also included for comparison. The results indicate that Sch B treatment (2 mmol/kg) produced maximum enhancement in hepatic mtGAS and increases in both hepatic HSP 25 and HSP 70 levels at 24 It after dosing. While the extent of hepatoprotection afforded by Sch B pretreatment against CCl4 was found to correlate inversely with the elapsed time postdosing, the protective effect was associated with the ability to sustain mtGAS and/or HSP 70 levels in a CCl4-intoxicated condition. On the other hand, DDB (2 mmol/kg) treatment, which did not sustain mtGAS and HSP 70 level, could not protect against CCl4 toxicity. Abolition of the Sch B-mediated enhancement of mtGAS by buthionine sulfoximine/phorone did not completely abrogate the hepatoprotective action of Sch B. The results indicate that Sch B pretreatment independently enhances mtGAS and induces HSP 25/70 production, particularly under conditions of oxidative stress, thereby protecting against CCl4 hepatotoxicity. (C) 2003 Elsevier Inc.

In the present study, the hepatoprotective effect of metformin (Met), a dimethylbiguanide anti-hyperglycemic, was examined in a mouse model of liver damage induced by chronic repeated administration of carbon tetrachloride (CCl4) (5 mul/kg, twice a week for 12 weeks). Met, when given orally in drinking water at an estimated daily dose of 25 or 50 mg /kg for 10 weeks starting 2 weeks after CCl4 challenge, protected against CCl4 hepatotoxicity. The results indicate that the hepatoprotection afforded by Met treatment at a dose of 25 mg/kg against CCl4 toxicity may at least in part be mediated by the enhancement of mitochondrial glutathione redox status.

In this study, the time course of schisandrin B- (Sch B-) induced changes in hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (HSP) 25/70 induction was examined to study their differential roles in the hepatoprotection afforded by Sch B pretreatment against carbon tetrachloride (CCl4) toxicity in mice. Dimethyl diphenyl bicarboxylate (DDB), a nonhepatoprotective analog of Sch B, was also included for comparison. The results indicate that Sch B treatment (2 mmol/kg) produced maximum enhancement in hepatic mtGAS and increases in both hepatic HSP 25 and HSP 70 levels at 24 It after dosing. While the extent of hepatoprotection afforded by Sch B pretreatment against CCl4 was found to correlate inversely with the elapsed time postdosing, the protective effect was associated with the ability to sustain mtGAS and/or HSP 70 levels in a CCl4-intoxicated condition. On the other hand, DDB (2 mmol/kg) treatment, which did not sustain mtGAS and HSP 70 level, could not protect against CCl4 toxicity. Abolition of the Sch B-mediated enhancement of mtGAS by buthionine sulfoximine/phorone did not completely abrogate the hepatoprotective action of Sch B. The results indicate that Sch B pretreatment independently enhances mtGAS and induces HSP 25/70 production, particularly under conditions of oxidative stress, thereby protecting against CCl4 hepatotoxicity. (C) 2003 Elsevier Inc.

In the present study, the hepatoprotective effect of metformin (Met), a dimethylbiguanide anti-hyperglycemic, was examined in a mouse model of liver damage induced by chronic repeated administration of carbon tetrachloride (CCl4) (5 mul/kg, twice a week for 12 weeks). Met, when given orally in drinking water at an estimated daily dose of 25 or 50 mg /kg for 10 weeks starting 2 weeks after CCl4 challenge, protected against CCl4 hepatotoxicity. The results indicate that the hepatoprotection afforded by Met treatment at a dose of 25 mg/kg against CCl4 toxicity may at least in part be mediated by the enhancement of mitochondrial glutathione redox status.

In this study, the time course of schisandrin B- (Sch B-) induced changes in hepatic mitochondrial glutathione antioxidant status (mtGAS) and heat shock protein (HSP) 25/70 induction was examined to study their differential roles in the hepatoprotection afforded by Sch B pretreatment against carbon tetrachloride (CCl4) toxicity in mice. Dimethyl diphenyl bicarboxylate (DDB), a nonhepatoprotective analog of Sch B, was also included for comparison. The results indicate that Sch B treatment (2 mmol/kg) produced maximum enhancement in hepatic mtGAS and increases in both hepatic HSP 25 and HSP 70 levels at 24 It after dosing. While the extent of hepatoprotection afforded by Sch B pretreatment against CCl4 was found to correlate inversely with the elapsed time postdosing, the protective effect was associated with the ability to sustain mtGAS and/or HSP 70 levels in a CCl4-intoxicated condition. On the other hand, DDB (2 mmol/kg) treatment, which did not sustain mtGAS and HSP 70 level, could not protect against CCl4 toxicity. Abolition of the Sch B-mediated enhancement of mtGAS by buthionine sulfoximine/phorone did not completely abrogate the hepatoprotective action of Sch B. The results indicate that Sch B pretreatment independently enhances mtGAS and induces HSP 25/70 production, particularly under conditions of oxidative stress, thereby protecting against CCl4 hepatotoxicity. (C) 2003 Elsevier Inc.

Two enantiomers of schisandrin B (Sch B), an active ingredient isolated from the fruit of Schisandra chinensis, were chirally separated. Pretreating mice with ()Sch B or ()Sch B at a daily oral dose of 1 mmol/kg for 3 days protected against carbon tetrachloride (CCl4) hepatotoxicity, as evidenced by highly significant decreases in plasma alanine aminotransferases activity and hepatic malondialdehyde level. The hepatoprotection afforded by pretreatment with the enantiomers was associated with increases in hepatic glutathione S-transferases and glutathione reductase (GRD) activities as well as mitochondrial reduced glutathione (GSH) level. However, only the (+)Sch B pretreated animals showed a reduction in the extent of CCl4-induced inhibition of hepatic Se-glutathione peroxidase activity. In addition, ()Sch B pretreatment produced a more potent stimulatory effect on hepatic GRD activity and mitochondrial GSH level in CCl4-treated mice. The differential ability between (+)Sch B and (-)Sch B in enhancing hepatic glutathione antioxidant system in CCl4-intoxicated mice may implicate the presence of a chiral-/stereo-specific intracellular target for mediating the antioxidant action of Sch B.

Two enantiomers of schisandrin B (Sch B), an active ingredient isolated from the fruit of Schisandra chinensis, were chirally separated. Pretreating mice with ()Sch B or ()Sch B at a daily oral dose of 1 mmol/kg for 3 days protected against carbon tetrachloride (CCl4) hepatotoxicity, as evidenced by highly significant decreases in plasma alanine aminotransferases activity and hepatic malondialdehyde level. The hepatoprotection afforded by pretreatment with the enantiomers was associated with increases in hepatic glutathione S-transferases and glutathione reductase (GRD) activities as well as mitochondrial reduced glutathione (GSH) level. However, only the (+)Sch B pretreated animals showed a reduction in the extent of CCl4-induced inhibition of hepatic Se-glutathione peroxidase activity. In addition, ()Sch B pretreatment produced a more potent stimulatory effect on hepatic GRD activity and mitochondrial GSH level in CCl4-treated mice. The differential ability between (+)Sch B and (-)Sch B in enhancing hepatic glutathione antioxidant system in CCl4-intoxicated mice may implicate the presence of a chiral-/stereo-specific intracellular target for mediating the antioxidant action of Sch B.

Two enantiomers of schisandrin B (Sch B), an active ingredient isolated from the fruit of Schisandra chinensis, were chirally separated. Pretreating mice with ()Sch B or ()Sch B at a daily oral dose of 1 mmol/kg for 3 days protected against carbon tetrachloride (CCl4) hepatotoxicity, as evidenced by highly significant decreases in plasma alanine aminotransferases activity and hepatic malondialdehyde level. The hepatoprotection afforded by pretreatment with the enantiomers was associated with increases in hepatic glutathione S-transferases and glutathione reductase (GRD) activities as well as mitochondrial reduced glutathione (GSH) level. However, only the (+)Sch B pretreated animals showed a reduction in the extent of CCl4-induced inhibition of hepatic Se-glutathione peroxidase activity. In addition, ()Sch B pretreatment produced a more potent stimulatory effect on hepatic GRD activity and mitochondrial GSH level in CCl4-treated mice. The differential ability between (+)Sch B and (-)Sch B in enhancing hepatic glutathione antioxidant system in CCl4-intoxicated mice may implicate the presence of a chiral-/stereo-specific intracellular target for mediating the antioxidant action of Sch B.

The in vivo antioxidant mechanism of Sheng Mai San (SMS), a compound formulation in traditional Chinese medicine comprising Panax ginseng, Schisandra chinensis and Ophiopogon japonicus, was investigated using a rat model of CCl4 hepatotoxicity. SMS-crude extract and its aqueous or chloroform fraction were found to protect against CCl4-induced hepatotoxicity. The hepatoprotection afforded by SMS or its fraction pretreatment was associated with an enhanced hepatic glutathione (GSH) status, as indicated by increases in hepatic GSH levels and glucose-6-phosphate dehydrogenase activities, as well as a decrease in susceptibility of hepatic homogenates to peroxide-induced GSH depletion. These results suggest that the in vivo antioxidant mechanism of SMS may involve the facilitation of hepatic GSH regeneration under increased oxidative stress conditions.

The in vivo antioxidant mechanism of Sheng Mai San (SMS), a compound formulation in traditional Chinese medicine comprising Panax ginseng, Schisandra chinensis and Ophiopogon japonicus, was investigated using a rat model of CCl4 hepatotoxicity. SMS-crude extract and its aqueous or chloroform fraction were found to protect against CCl4-induced hepatotoxicity. The hepatoprotection afforded by SMS or its fraction pretreatment was associated with an enhanced hepatic glutathione (GSH) status, as indicated by increases in hepatic GSH levels and glucose-6-phosphate dehydrogenase activities, as well as a decrease in susceptibility of hepatic homogenates to peroxide-induced GSH depletion. These results suggest that the in vivo antioxidant mechanism of SMS may involve the facilitation of hepatic GSH regeneration under increased oxidative stress conditions.

The in vivo antioxidant mechanism of Sheng Mai San (SMS), a compound formulation in traditional Chinese medicine comprising Panax ginseng, Schisandra chinensis and Ophiopogon japonicus, was investigated using a rat model of CCl4 hepatotoxicity. SMS-crude extract and its aqueous or chloroform fraction were found to protect against CCl4-induced hepatotoxicity. The hepatoprotection afforded by SMS or its fraction pretreatment was associated with an enhanced hepatic glutathione (GSH) status, as indicated by increases in hepatic GSH levels and glucose-6-phosphate dehydrogenase activities, as well as a decrease in susceptibility of hepatic homogenates to peroxide-induced GSH depletion. These results suggest that the in vivo antioxidant mechanism of SMS may involve the facilitation of hepatic GSH regeneration under increased oxidative stress conditions.

We have demonstrated that pretreatment with a lignan-enriched extract of Fructus schisandrae (FS) protected against physical exercise-induced muscle damage in rats. The muscle protection afforded by FS pretreatment was associated with a significant enhancement in hepatic antioxidant status, as assessed by hepatic glutathione (GSH) and malondialdehyde (MDA) levels. Pretreating rats with α-tocopherol acetate, though decreasing the MDA level in skeletal muscle, did not protect against exercise-induced muscle damage or improve hepatic antioxidant status in exercised rats. The results indicate that the protective effect of FS pretreatment on physical exercise-induced muscle damage may result from the enhancement of hepatic GSH status, thereby providing sufficient GSH for effective antioxidant protection of skeletal muscle during exercise. © 1996 by John Wiley & Sons, Ltd.

We have demonstrated the presence of both in vivo and in vitro antioxidant activities in the crude water-extract of the root of Polygonum multiflorum Thunb. (PMC), as indicated by its ability to protect against CCl4-induced hepatotoxicity in rats and to scavenge ferri-heme oxidants generated in an in vitro system. Activity directed fractionation of the PMC indicated that the antioxidant components were contained in the ethylacetate fraction. (C) 1997 by John Wiley & Sons, Ltd.

We have demonstrated the presence of both in vivo and in vitro antioxidant activities in the crude water-extract of the root of Polygonum multiflorum Thunb. (PMC), as indicated by its ability to protect against CCl4-induced hepatotoxicity in rats and to scavenge ferri-heme oxidants generated in an in vitro system. Activity directed fractionation of the PMC indicated that the antioxidant components were contained in the ethylacetate fraction. (C) 1997 by John Wiley & Sons, Ltd.

We have demonstrated the presence of both in vivo and in vitro antioxidant activities in the crude water-extract of the root of Polygonum multiflorum Thunb. (PMC), as indicated by its ability to protect against CCl4-induced hepatotoxicity in rats and to scavenge ferri-heme oxidants generated in an in vitro system. Activity directed fractionation of the PMC indicated that the antioxidant components were contained in the ethylacetate fraction. (C) 1997 by John Wiley & Sons, Ltd.

Effects of Schisandrin B (Sch B) and alpha-tocopherol (alpha-TOC) on ferric chloride (Fe3+) induced oxidation of erythrocyte membrane lipids in vitro and carbon tetrachloride (CCl4) induced lipid peroxidation in vivo were examined. While alpha-TOC could produce prooxidant and antioxidant effect on Fe3+-induced lipid peroxidation, Sch B only inhibited the peroxidation reaction. Pretreatment with alpha-TOC (3 mmol/kg/day x 3) did not protect against CCl4-induced lipid peroxidation and hepatocellular damage in mice, whereas Sch B pretreatment (0.3 mmol/3.0 mmol/kg/day x 3) produced a dose-dependent protective effect on the CCl4-induced hepatotoxicity. The ensemble of results suggests that the ability of Sch B to inhibit lipid peroxidation, while in the absence of pro-oxidant activity, may at least in part contribute to its hepatoprotective action.

Treatment of rats with a lignan-enriched extract of the fruit of Schisandra chinensis could enhance hepatic antioxidant/detoxification system, as indicated by increases in hepatic reduced glutathione (GSH) level as well as hepatic glutathione reductase and glutathione S-transferase activities. The hepatoprotective action was evident after aflatoxin beta(1) or cadmium chloride (Cd) challenge. Schisandra chinensis pretreatment protected against aflatoxin B-1- or Cd-induced hepatocellular damage in rats. However, pretreating rats with alpha-tocopherol acetate (vitamin E) did not protect against hepatic damage induced by both toxins. Results from the present as well as our previous studies demonstrate that the hepatoprotection afforded by Schisandra chiensis pretreatment is not hepatotoxin specific. Schisandra chinensis seems to be more effective than vitamin E in protecting against aflatoxin B-1 and Cd toxicity. The mechanism of hepatoprotection afforded by Schisandra chinensis pretreatment may involve facilitation of both antioxidant and detoxification processes in the liver.

We have demonstrated that pretreatment with a lignan-enriched extract of Fructus schisandrae (FS) protected against physical exercise-induced muscle damage in rats. The muscle protection afforded by FS pretreatment was associated with a significant enhancement in hepatic antioxidant status, as assessed by hepatic glutathione (GSH) and malondialdehyde (MDA) levels. Pretreating rats with alpha-tocopherol acetate, though decreasing the MDA level in skeletal muscle, did not protect against exercise-induced muscle damage or improve hepatic antioxidant status in exercised rats. The results indicate that the protective effect of FS pretreatment on physical exercise-induced muscle damage may result from the enhancement of hepatic GSH status, thereby providing sufficient GSH for effective antioxidant protection of skeletal muscle during exercise.

Effects of Sheng Mai San (SMS), a traditional Chinese medicine used for the treatment of coronary heart disease, and the lignan-enriched extract of Fructus Schisandrae (FS), an antioxidant component of SMS, were examined in an in vivo model of myocardial infarction and an ex vivo model of myocardial ischemia-reperfusion injury in rats. Pretreatment with SMS (12 g/kg/day x 3, p.o.) or FS extract (0.8 g/kg/day x 3, p.o.) was found to protect against the isoproterenol-induced myocardial injury in rats and the ischemia-reperfusion injury in isolated perfused hearts prepared from the pretreated animals. Pretreatment with alpha-tocopherol (0.8 g/kg/day x 3, p.o.) produced similar beneficial effect on the myocardium. The myocardial protection afforded by SMS pretreatment is likely, at least in part, mediated by the FS-derived antioxidant activity.

Sheng-Mai-San (SMS), a traditional Chinese formulation used for the treatment of coronary heart disease, is comprised of Radix Ginseng, Fructus Schisandrae and Radix Ophiopogonis. Pretreatment with a lignan-enriched SMS (17 g/kg/day x 3, p.o.) was found effective in protection against isoproterenol-induced myocardial injury in rats, and in ischemia-reperfusion injury in isolated perfused hearts prepared from pretreated animals. Results obtained from pretreatment studies using extracts prepared by mixing various combinations of the three component herbs indicate that the major myocardial protective component in SMS is the lignan-enriched extract of Fructus Schisandrae.

Changes in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats for a period of 15 weeks were examined. Total glutathione level was significantly increased in kidney tissue, but were slightly decreased and increased in liver and heart tissues, respectively. The small changes in total glutathione level in the liver and heart, though not statistically significant, were associated with reciprocal alterations in the activity of gamma-glutamylcysteine synthetase (GCS). While the GCS activity was not changed in kidney tissue, the activity of gamma-glutathione peroxidase was significantly increased in kidney tissue. Insulin treatment could completely or partly normalize almost all of these changes induced by diabetes. However, the decrease in hepatic glutathione S-transferases activity in diabetic rats was not reversed by the insulin treatment. The ensemble of results suggests that the diabetes-induced alterations in tissue glutathione antioxidant system may possibly reflect an inter-organ antioxidant response to a generalized increase in tissue oxidative stress associated with diabetes.

We have demonstrated that pretreatment with a lignan-enriched extract of Fructus schisandrae (FS) protected against physical exercise-induced muscle damage in rats. The muscle protection afforded by FS pretreatment was associated with a significant enhancement in hepatic antioxidant status, as assessed by hepatic glutathione (GSH) and malondialdehyde (MDA) levels. Pretreating rats with alpha-tocopherol acetate, though decreasing the MDA level in skeletal muscle, did not protect against exercise-induced muscle damage or improve hepatic antioxidant status in exercised rats. The results indicate that the protective effect of FS pretreatment on physical exercise-induced muscle damage may result from the enhancement of hepatic GSH status, thereby providing sufficient GSH for effective antioxidant protection of skeletal muscle during exercise.

Sheng-Mai-San (SMS), a traditional Chinese formulation used for the treatment of coronary heart disease, is comprised of Radix Ginseng, Fructus Schisandrae and Radix Ophiopogonis. Pretreatment with a lignan-enriched SMS (17 g/kg/day x 3, p.o.) was found effective in protection against isoproterenol-induced myocardial injury in rats, and in ischemia-reperfusion injury in isolated perfused hearts prepared from pretreated animals. Results obtained from pretreatment studies using extracts prepared by mixing various combinations of the three component herbs indicate that the major myocardial protective component in SMS is the lignan-enriched extract of Fructus Schisandrae.

Effects of Sheng Mai San (SMS), a traditional Chinese medicine used for the treatment of coronary heart disease, and the lignan-enriched extract of Fructus Schisandrae (FS), an antioxidant component of SMS, were examined in an in vivo model of myocardial infarction and an ex vivo model of myocardial ischemia-reperfusion injury in rats. Pretreatment with SMS (12 g/kg/day x 3, p.o.) or FS extract (0.8 g/kg/day x 3, p.o.) was found to protect against the isoproterenol-induced myocardial injury in rats and the ischemia-reperfusion injury in isolated perfused hearts prepared from the pretreated animals. Pretreatment with alpha-tocopherol (0.8 g/kg/day x 3, p.o.) produced similar beneficial effect on the myocardium. The myocardial protection afforded by SMS pretreatment is likely, at least in part, mediated by the FS-derived antioxidant activity.

Changes in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats for a period of 15 weeks were examined. Total glutathione level was significantly increased in kidney tissue, but were slightly decreased and increased in liver and heart tissues, respectively. The small changes in total glutathione level in the liver and heart, though not statistically significant, were associated with reciprocal alterations in the activity of gamma-glutamylcysteine synthetase (GCS). While the GCS activity was not changed in kidney tissue, the activity of gamma-glutathione peroxidase was significantly increased in kidney tissue. Insulin treatment could completely or partly normalize almost all of these changes induced by diabetes. However, the decrease in hepatic glutathione S-transferases activity in diabetic rats was not reversed by the insulin treatment. The ensemble of results suggests that the diabetes-induced alterations in tissue glutathione antioxidant system may possibly reflect an inter-organ antioxidant response to a generalized increase in tissue oxidative stress associated with diabetes.

Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B), an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl4) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1,3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl4-treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.

Treatment of rats with a lignan-enriched extract of the fruit of Schisandra chinensis could enhance hepatic antioxidant/detoxification system, as indicated by increases in hepatic reduced glutathione (GSH) level as well as hepatic glutathione reductase and glutathione S-transferase activities. The hepatoprotective action was evident after aflatoxin beta(1) or cadmium chloride (Cd) challenge. Schisandra chinensis pretreatment protected against aflatoxin B-1- or Cd-induced hepatocellular damage in rats. However, pretreating rats with alpha-tocopherol acetate (vitamin E) did not protect against hepatic damage induced by both toxins. Results from the present as well as our previous studies demonstrate that the hepatoprotection afforded by Schisandra chiensis pretreatment is not hepatotoxin specific. Schisandra chinensis seems to be more effective than vitamin E in protecting against aflatoxin B-1 and Cd toxicity. The mechanism of hepatoprotection afforded by Schisandra chinensis pretreatment may involve facilitation of both antioxidant and detoxification processes in the liver.

We have demonstrated that pretreatment with a lignan-enriched extract of Fructus schisandrae (FS) protected against physical exercise-induced muscle damage in rats. The muscle protection afforded by FS pretreatment was associated with a significant enhancement in hepatic antioxidant status, as assessed by hepatic glutathione (GSH) and malondialdehyde (MDA) levels. Pretreating rats with alpha-tocopherol acetate, though decreasing the MDA level in skeletal muscle, did not protect against exercise-induced muscle damage or improve hepatic antioxidant status in exercised rats. The results indicate that the protective effect of FS pretreatment on physical exercise-induced muscle damage may result from the enhancement of hepatic GSH status, thereby providing sufficient GSH for effective antioxidant protection of skeletal muscle during exercise.

Treatment of rats with a lignan-enriched extract of the fruit of Schisandra chinensis could enhance hepatic antioxidant/detoxification system, as indicated by increases in hepatic reduced glutathione (GSH) level as well as hepatic glutathione reductase and glutathione S-transferase activities. The hepatoprotective action was evident after aflatoxin beta(1) or cadmium chloride (Cd) challenge. Schisandra chinensis pretreatment protected against aflatoxin B-1- or Cd-induced hepatocellular damage in rats. However, pretreating rats with alpha-tocopherol acetate (vitamin E) did not protect against hepatic damage induced by both toxins. Results from the present as well as our previous studies demonstrate that the hepatoprotection afforded by Schisandra chiensis pretreatment is not hepatotoxin specific. Schisandra chinensis seems to be more effective than vitamin E in protecting against aflatoxin B-1 and Cd toxicity. The mechanism of hepatoprotection afforded by Schisandra chinensis pretreatment may involve facilitation of both antioxidant and detoxification processes in the liver.

Sheng-Mai-San (SMS), a traditional Chinese formulation used for the treatment of coronary heart disease, is comprised of Radix Ginseng, Fructus Schisandrae and Radix Ophiopogonis. Pretreatment with a lignan-enriched SMS (17 g/kg/day x 3, p.o.) was found effective in protection against isoproterenol-induced myocardial injury in rats, and in ischemia-reperfusion injury in isolated perfused hearts prepared from pretreated animals. Results obtained from pretreatment studies using extracts prepared by mixing various combinations of the three component herbs indicate that the major myocardial protective component in SMS is the lignan-enriched extract of Fructus Schisandrae.

Effects of Sheng Mai San (SMS), a traditional Chinese medicine used for the treatment of coronary heart disease, and the lignan-enriched extract of Fructus Schisandrae (FS), an antioxidant component of SMS, were examined in an in vivo model of myocardial infarction and an ex vivo model of myocardial ischemia-reperfusion injury in rats. Pretreatment with SMS (12 g/kg/day x 3, p.o.) or FS extract (0.8 g/kg/day x 3, p.o.) was found to protect against the isoproterenol-induced myocardial injury in rats and the ischemia-reperfusion injury in isolated perfused hearts prepared from the pretreated animals. Pretreatment with alpha-tocopherol (0.8 g/kg/day x 3, p.o.) produced similar beneficial effect on the myocardium. The myocardial protection afforded by SMS pretreatment is likely, at least in part, mediated by the FS-derived antioxidant activity.

Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B), an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl4) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1,3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl4-treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.

Changes in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats for a period of 15 weeks were examined. Total glutathione level was significantly increased in kidney tissue, but were slightly decreased and increased in liver and heart tissues, respectively. The small changes in total glutathione level in the liver and heart, though not statistically significant, were associated with reciprocal alterations in the activity of gamma-glutamylcysteine synthetase (GCS). While the GCS activity was not changed in kidney tissue, the activity of gamma-glutathione peroxidase was significantly increased in kidney tissue. Insulin treatment could completely or partly normalize almost all of these changes induced by diabetes. However, the decrease in hepatic glutathione S-transferases activity in diabetic rats was not reversed by the insulin treatment. The ensemble of results suggests that the diabetes-induced alterations in tissue glutathione antioxidant system may possibly reflect an inter-organ antioxidant response to a generalized increase in tissue oxidative stress associated with diabetes.

Exposure of liver homogenates to an in vitro tert-butyl hydroperoxide challenge can be used as a means for measuring the reduced glutathione regeneration capacity (GRC) of hepatic tissues. Pretreatment of rats with a lignan-enriched extract of Fructus Schisandrae (FS) caused a moderate enhancement of hepatic GRC in control rats, but the GRC enhancing effect of FS pretreatment on hepatic tissues was greatly exaggerated after CCl4 challenge. This in vitro bioassay can be used for investigating the hepatic GRC promoting action of orally active agents.