Antioxidant activity of tannoid principles of Emblica officinalis (amla) in chronic stress induced changes in rat brain

Effect of tannoid principles emblicanin A, emblicanin B, punigluconin, and pedunculagin of E. officinalis was assessed on chronic unpredictable footshock-induced stress-induced perturbations in oxidative free radical scavanging enzymes in rat brain frontal cortex and striatum. Chronic stress, administered over a period of 21 days, induced significant increase in rat brain frontal cortical and striatal superoxide dismutase (SOD) activity, concomitant with significant reduction in catalase (CAT) and glutathione peroxidase (GPX) activity. The changes in the enzyme activities was accompanied by an increase in lipid peroxidation, in terms of augmented thiobarbituric acid-reactive products. Administration of Emblica tannoids (10 and 20 mg, po) for 21 days, concomitant with the stress procedure, induced a dose-related alteration in the stress effects. Thus, a tendency towards normalization of the activities of SOD, CAT and GPX was noted in both the brain areas, together, with reduction in lipid peroxidation. The results indicate that the reported antistress rasayana activity of E. officinalis may be, at least partly due to its tendency to normalize stress-induced perturbations in oxidative free radical scavenging activity, in view of the postulate that several stress-induced diseases, including the process of aging, may be related to accumulation of oxidative free radicals in different tissues.     

Antioxidant activity of active tannoid principles of Emblica officinalis (amla).

The antioxidant activity of tannoid active principles of E. officinalis consisting of emblicanin A (37%), emblicanin B (33%), punigluconin (12%) and pedunculagin (14%), was investigated on the basis of their effects on rat brain frontal cortical and striatal concentrations of the oxidative free radical scavenging enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and lipid peroxidation, in terms of thiobarbituric acid-reactive products. The results were compared with effects induced by deprenyl, a selective monoamine oxidase (MAO) B inhibitor with well documented antioxidant activity. The active tannoids of E. officinalis (EOT), administered in the doses of 5 and 10 mg/kg, i.p., and deprenyl (2 mg/kg, i.p.), induced an increase in both frontal cortical and striatal SOD, CAT and GPX activity, with concomitant decrease in lipid peroxidation in these brain areas when administered once daily for 7 days. Acute single administration of EOT and deprenyl had insignificant effects. The results also indicate that the antioxidant activity of E. officinalis may reside in the tannoids of the fruits of the plant, which have vitamin C-like properties, rather than vitamin C itself.     

Reduction of hexachlorocyclohexane-induced oxidative stress and cytotoxicity in rat liver by Emblica officinalis gaertn

The effect of prefeeding of dehydrated E. officinalis (amla) powder at 5 and 10% levels on hexachlorocyclohexane (HCH)-induced changes in multicomponent antioxidant system and lipid peroxides in rat liver was studied. HCH induced significant elevation in hepatic malondialdehyde, conjugated dienes and hydroperoxides. The prefeeding of amla at 10% level could decrease the formation of these lipid peroxides significantly. The HCH abuse resulted in a significant reduction in hepatic glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G-6-PDH) and superoxide dismutase (SOD) activities with an elevation in the activities of glutathione peroxidase and gamma-glutamyl transpeptidase (GGT). On the other hand, the HCH-induced impairment in hepatic catalase, G-6-PDH and SOD activities were modulated by amla at the 10% level of intake. Prefeeding of amla at 5 and 10% levels appeared to reduce the HCH-induced raise in renal GGT activity. The results show the elevation of hepatic antioxidant system and reduction of cytotoxic products as a result of prefeeding of amla, which were otherwise affected by the HCH administration.     

Effect of bioactive tannoid principles of Emblica officinalis on ischemia-reperfusion-induced oxidative stress in rat heart.

The tannoid principles of the fruits of Emblica officinalis have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin-A (37%) and -B (33%) enriched fraction of fresh juice of Emblica fruits (EOT) was investigated for antioxidant activity against ischemia-reperfusion (IRI)-induced oxidative stress in rat heart. Vitamin E (VE) was used as the standard antioxidant agent. IRI was induced in isolated rat heart by perfusing it with modified Kreb-Hensleitt's solution for 5 min, followed by a period of ischemia (stoppage of perfusion) for 10 min and then restoring the perfusion (reperfusion) for 15 min. IRI induced a significant decrease in the activities of cardiac superoxide dismutase, catalase and glutathione peroxidase, with a concomitant increase in lipid peroxidation. These IRI-induced effects were prevented by the administration of EOT (50 and 100 mg/kg body wt.) and VE (200 mg/kg body wt.) given orally twice daily for 14 days prior to the sacrifice of the animals and initiation of the perfusion experiments. The study confirms the antioxidant effect of E. officinalis and indicates that the fruits of the plant may have a cardioprotective effect.     

Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress

Background

Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. It has been suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. The aim of present study was to determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C could improve the biochemical and histological abnormalities associated with diet-induced NASH in rats.

Methods

NASH was induced in male N-Mary rats by feeding a methionine - choline deficient (MCD) diet. The rats were fed either normal chow or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly divided into four groups of six: the NASH group that received MCD diet, the EUK-8 group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK-8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage for eight weeks.

Results

Treatment of MCD-fed rats with salens reduced the sera aminotransferases, cholesterol, low density lipoprotein contents, the extent of lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis, ballooning degeneration and inflammation in liver of MCD-fed rats.

Conclusion

Antioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced biochemical and histological abnormalities, pointing out that antioxidant strategy could be beneficial in treatment of NASH.     

Effect of Emblica officinalis (Gaertn) on CCl4 induced hepatic toxicity and DNA synthesis in Wistar rats

A single dose of CCl4 (1 ml/kg body weight, po in corn oil) increased the levels of SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase), LDH (lactate dehydrogenase), glutathione-S-transferase and depletion in reduced glutathione, glutathione peroxidase and glutathione reductase. It also caused enhancement in the levels of lipid peroxidation (LPO) and DNA synthesis. There was also pathological deterioration of hepatic tissue as evident from multivacuolated hepatocytes containing fat globules around central vein. The pretreatment of E. officinalis for 7 consecutive days showed a profound pathological protection to liver cell as depicted by univacuolated hepatocytes. Pretreatment with E. officinalis at doses of 100 and 200 mg/kg body weight, prior to CCl4 intoxication showed significant reduction in the levels of SGOT, SGPT, LDH, glutathione-S-transferase, LPO and DNA synthesis. There was also increase in reduced glutathione, glutathione peroxidase and glutathione reductase. The results suggest that E. officinalis inhibits hepatic toxicity in Wistar rats.     

Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats

BACKGROUNDChromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats.METHODSGC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively.RESULTSTwenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H₂O₂) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers.CONCLUSIONConclusively, REO had a potential antioxidant capacity in ameliorating K₂Cr₂O₇-induced nephrotoxicity, especially in the protection group.     

Amelioration of salt-induced oxidative stress in eggplant by application of 24-epibrassinolide

The effects of exogenous 24-epibrassinolide (EBR) on the growth, oxidative damage, antioxidant system and ion contents in eggplant (Solanum melongena L.) seedlings under salt stress were investigated. Eggplant seedlings were exposed to 90 mM NaCl with 0, 0.025, 0.05, 0.10 and 0.20 mg dm⁻³ EBR for 10 d. EBR, especially at concentration 0.05 mg dm⁻³, alleviated growth suppression caused by NaCl stress, decreased electrolyte leakage, superoxide production and content of malondialdehyde and H₂O₂ in NaCl-treated plants. EBR also increased activities of superoxide dismutase, guaiacol peroxidase, catalase and ascorbate peroxidase and the contents of ascorbic acid and reduced glutathione. Furthermore, we also found that Na⁺, Cl⁻ contents were decreased, K⁺, Ca²⁺ contents and K⁺/Na⁺, Ca²⁺/Na⁺ ratios were increased in the presence of EBR under salt stress.     

Modulation of acute cadmium toxicity by Emblica officinalis fruit in rat

The efficacy of Emblica officinalis in modifying the acute cytotoxicity of cadmium in male rats was evaluated. Oral administration of Emblica fruit juice (500 mg/kg, b.w.) for 8 days followed by a single toxic dose of Cd as CdCl2 (3 mg/kg,b.w. ip), considerably reduced the mortality in rats as well as prevented to some extent the cadmium induced histopathological damage in testis, liver and kidneys. Biochemical investigation also revealed reduced levels of Cd induced serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and gamma glutamyltranspeptidase. The enhanced levels of Cd and lipid peroxidation in liver, kidney, and testes and metallothionein and total sulphydryl in liver and kidney by Cd were significantly reduced by Emblica pretreatment. These results suggest cytoprotective potential of Emblica fruit in acute cadmium toxicity which could be due to its multiple role in biological system.     

Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid

Cinnamic acid (C9H8O2), is a major constituent of the oriental Ayurvedic plant Cinnamomum cassia (Family: Lauraceae). This phenolic acid has been reported to possess various pharmacological properties of which its antioxidant activity is a prime one. Therefore it is rational to hypothesize that it may ameliorate myelosuppression and oxidative stress induced by cyclophosphamide, a widely used chemotherapeutic agent. Commercial cyclophosphamide, Endoxan, was administered intraperitoneally to Swiss albino mice (50mg/kg) pretreated with 15, 30 and 60mg/kg doses of cinnamic acid orally at alternate days for 15days. Cinnamic acid pre-treatment was found to reduce cyclophosphamide induced hypocellularity in the bone marrow and spleen. This recovery was also reflected in the peripheral blood count. Amelioration of hypocellularity could be correlated with the modulation of cell cycle phase distribution. Cinnamic acid pre-treatment reduced bone marrow and hepatic oxidative stress as evident by lipid peroxidation and activity assays of antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. The present study indicates that cinnamic acid pretreatment has protective influence on the myelosuppression and oxidative stress induced by cyclophosphamide. This investigation is an attempt and is the first of its kind to establish cinnamic acid as an agent whose consumption provides protection to normal cells from the toxic effects of a widely used anti-cancer drug.     

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.     

Role of oxidative stress in the pathogenesis of alcohol-induced liver disease

Abstract

Chronic alcohol consumption is a well-known risk factor for liver disease, which represents a major cause of morbidity and mortality worldwide. The pathological process of alcohol-induced liver disease is characterized by a broad spectrum of morphological changes ranging from steatosis with minimal injury to more advanced liver damage, including steato-hepatitis and fibrosis/cirrhosis. Experimental and clinical studies increasingly show that the oxidative damage induced by ethanol contribute in many ways to the pathogenesis of alcohol hepatotoxicity. This article describes the contribution of oxidative mechanisms to liver damage by alcohol.     

Effect of bioactive tannoid principles of Emblica officinalis on iron-induced hepatic toxicity in rats.

The tannoid principles of the fruits of the plant Emblica officinalis Gaertn comprising of emblicanin A. emblicanin B, punigluconin and pedunculagin, have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin A (37%) and B (33%) enriched fraction of fresh juice of Emblica fruits (EOT), administered prophylactically (10, 20 and 50 mg/kg, p.o.) for 10 consecutive day, was found to inhibit acute iron overload (30 mg/kg, i.p.) hepatic lipid peroxidation and the increase of serum levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, used as markers of the induced hepatic dysfunction. A similar effect was produced by silymarin (20 mg/kg, p.o.), an antioxidant hepatoprotective agent. The results support the use of Emblica fruits for hepatoprotection in Ayurveda.     

Modulation of carbon tetrachloride-induced oxidative stress by dietary fat in rats(open star)

Oxidative stress is believed to be involved in the pathophysiology of a number of chronic diseases including atherosclerosis, diabetes, and cataracts and to accelerate the aging process. The aim of this study was to elucidate the role of various dietary fats in the in vivo modulation of CCl(4) induced oxidative stress using rat as a model. Rats were raised on diets enriched with saturated (Beef Tallow), n-9 (Sunola oil), n-6 (Safflower oil) or n-3 (Flaxseed oil) fatty acids and exposed to elevated oxidative stress by administration of CCl(4.) Plasma concentration of 8-iso-PGF(2alpha), antioxidant micronutrients and antioxidant enzymes were measured to examine changes to oxidative stress subsequent to the administration of CCl(4). The fatty acid profiles of plasma and RBC membranes reflected the fats fed in the different diets. CCl(4) administration had no significant effect on fatty acid composition of plasma or RBC lipids. Plasma 8-iso-PGF(2alpha) concentrations were elevated by CCl(4) administration regardless of the dietary fat fed. Within the induced oxidative groups the 8-iso-PGF(2alpha) concentrations were highest in Safflower oil followed by Sunola oil, Tallow and finally Flaxseed oil. Induction of oxidative stress by CCl(4) administration was associated with a significant reduction in Vitamin A content reaching a significantly lower concentration (P <0.05) in the Tallow and Flaxseed oil groups. Vitamin E concentrations were significantly lower (p = 0.01) in the Safflower oil and the Flaxseed oil than in the Tallow diet group following CCl(4) administration. Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSHPx) activities were not affected by dietary fat manipulation. The results of this study indicate that dietary fat can modulate lipid peroxidation and antioxidant defenses when exposed to a pro-oxidant challenge.     

Depression by a green tea extract of alcohol-induced oxidative stress and lipogenesis in rat liver

We determined the effects of a green tea extract with 36% alcohol on the blood alcohol content, oxidative stress, lipogenesis, inflammation and liver function of female Wistar rats. Tea alcohol significantly decreased the O??, H?O? and HOCl amounts via catechins and not caffeine. Thirty days of alcohol gavage improved the level of reactive oxygen species (ROS) in the liver, bile and blood, increased the 4-hydroxynonenal-protein adducts, Kupffer cell infiltration and lipid accumulation in the liver, and elevated the plasma alanine aminotransferase level. A western blot analysis showed reduced expression of the oxidative enzymes (CYP2E1 and NADPH oxidase p47phox protein) and lipogenic enzymes (SREBP-1c and fatty acid synthase) in the alcohol-treated liver. Tea alcohol significantly attenuated these elevated parameters. We conclude that the green tea extract in alcohol efficiently reduced the amounts of O??, H?O? and HOCl primarily due to the catechin content, and not caffeine. The developed tea liquor attenuated alcohol-induced oxidative injury and lipogenesis in the liver by the synergetic action of catechins and caffeine.     

A comparative study on the beneficial effects of garlic (Allium sativum Linn), amla (Emblica Officinalis Gaertn)and onion (Allium cepa Linn) on the hyperlipidemia induced by butter fat and beef fat in rats

Three months feeding of butter fat (BUF) and beef (BF) separately as components of diet at a level of 21% by weight for albino rats, significantly raised their serum and tissue lipids, lipid peroxidation and activities of certain enzymes. BUF was found to be more atherogenic than BF. On incorporation of 5% garlic, amla or onion separately in the above diets, each of them ameliorated the deleterious effects of the animal fats. A higher hyperlipidemic effect of BUF as compared to that of BF may be due to the fact that the ratio of unsaturated to saturated fats is lower for the former (0.56) than for the latter (0.75) and also that the former is richer in cholesterol content than the latter. The order of the curative effects of the vegetables are garlic>amla>onion. The better hypolipidemic effects and correction of elevated levels of certain enzymes shown by garlic and amla may be due to the facts that they contain comparatively better active principles than that found in onions.     

Amelioration of adriamycin-induced cardiotoxicity by Salsola kali aqueous extract is mediated by lowering oxidative stress

Abstract

Objectives

To assess the cardioprotective effect of the Salsola kali aqueous extract against adriamycin (ADR)-induced cardiotoxicity in male Swiss albino mice.

Methods

The aqueous extract of S. kali was phytochemically screened by traditional methods for different classes and further evaluated for antioxidant activity in vitro. In vivo, cardioprotective evaluation of the extract was designed to have four groups of mice: (1) control group (distilled water, orally; normal saline, intraperitoneally (i.p.)); (2) ADR group (15 mg/kg, i.p.); (3) aqueous S. kali extract (200 mg/kg, orally); and (4) ADR + S. kali group. ADR (5 mg/kg) was injected three times over 2 weeks while S. kali was orally administered daily for 3 weeks (1 week before and 2 weeks during ADR treatment). Cardioprotective properties were assessed using biochemical and histopathological approaches.

Results

ADR caused a significant increase in serum enzymes (lactate dehydrogenase, creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase). Myocardial levels of malondialdehyde, nitric oxide, and reduced glutathione, as well as the activities of superoxide dismutase and catalase increased while the activities of glutathione peroxidase and glutathione S-transferase declined. Histopathological examination of heart sections revealed that ADR caused myofibrils loss, necrosis and cytoplasmic vacuolization.

Discussion

Pretreatment with S. kali aqueous extract normalized serum and antioxidant enzymes minimized lipid peroxidation and cardiac damage. These results have suggested that the extract has antioxidant activity, indicating that the mechanism of cardioprotection during ADR treatment is mediated by lowering oxidative stress.     

Amelioration of age-dependent increase in oxidative stress markers in male mice by extract of Potentilla fulgens

Objective: To investigate the effect of Potentilla fulgens extract on lipid peroxidation and antioxidant status in male mice as a function of age.

Methods: Eighteen-month-old Swiss albino male mice were administered the dichloromethane-methanol extract of P. fulgens (250?mg/kg b.w.) on alternate days via intraperitoneal route for a period of 14 days. Lipid peroxidation and activities of catalase (CAT) and glutathione peroxidase (GPx1) in liver and kidney were measured and serum oxygen radical absorbance capacity (ORAC) assay was estimated. Phytochemical analysis of P. fulgens extract using high performance thin layer chromatography (HPTLC) was carried out with gallic acid, quercetin, catechin, and epicatechin as markers.

Results: Significant increase in level of thiobarbituric acid-reactive substances (TBARS), decreased GPx1, and CAT activities as well as reduction in ORAC were observed in 18-month-old mice as compared to that of 2-month-old mice. Treatment with P. fulgens extract significantly lowered TBARS level, ameliorated CAT, and GPx1 activities in liver and kidney and improved serum ORAC in aging mice. HPTLC studies revealed well resolved bands of P. fulgens extract containing epicatechin and catechin.

Discussion: This study showed that P. fulgens is a potent antioxidative agent, which can emerge as a promising candidate in alleviating the age-associated oxidative stress and related diseases.