Cardioprotective effect of Justicia gendarussa on doxorubicin induced toxicity in mice.

Justicia gendarussa Burm.f, belonging to the family Acanthaceae, is widely used for various ailments traditionally. Antioxidant, anti-arthritic, anti-inflammatory, analgesic, anticancerous, properties of the plant have been widely reported. The present study analyzed the cardioprotective effect of J. gendarussa on doxorubicin (DOX) induced toxicity in mice. Ethanolic extract of J. gendarussa was administered orally for 7 consecutive days. The alterations in oxido-reduction status, biochemical and histopathological parameters were analyzed in heart tissue. DOX increased superoxide dismutase (SOD) and catalase activities to 3.4 ± 0.5 and 3.68 ± 1 from their normal values 2.43 ± 0.8 and 2.72 ± 0.88, respectively. The increased activities of both the enzymes were found reduced to 3.12 ± 0.24 and 3.41 ± 0.65 by the treatment of the extract. Similarly, DOX elevated glutathione peroxidase (GPx) activity to 44.6 ± 3.71 from the normal level 32.33 ± 3.41. DOX decreased the glutathione (GSH) level to 15.66 ± 2.51 from the normal values 31.66 ± 4.05. Upon treatment, GPx activity and GHS level found restored. The increased lipid peroxidation 2.53 ± 0.25 of DOX was also decreased to 2.0 ± 0.34 by the extract. Histopathology observations substantiate the protective effect of J. gendarussa extract. In conclusion, DOX-induced disturbance of oxido-reduction status and histopathology of heart attenuated closer to the normal indicating the protective effect of J. gendarussa against DOX-induced toxicity in cardiomyocytes.

Root Bark Extract of Oroxylum indicum Vent. Inhibits Solid and Ascites Tumors and Prevents the Development of DMBA-Induced Skin Papilloma Formation.

Oroxylum indicum is a traditionally used plant in Ayurvedic and folk medicines. The plant is useful for the management of gastrointestinal diseases as well as skin diseases. In the present study, we analyzed the antitumor potential of O. indicum in Dalton's lymphoma ascites tumor cells (DLA) and Ehrlich ascites carcinoma (EAC)-induced solid and ascites tumors. Further, the potential of O. indicum extract (OIM) on skin papilloma induction by dimethyl benz(a) anthracene (DMBA) and croton oil was evaluated. The chemical composition of the extract was analyzed using UPLC-Q-TOF-MS. The predominant compounds present in the extract were demethoxycentaureidin 7-O-rutinoside, isorhamnetin-3-O-rutinoside, baicalein-7-O-glucuronide, 5,6,7-trihydroxyflavone, 3-Hydroxy-3',4',5'-trimethoxyflavone, 5,7-dihydroxy-3-(4-methoxyphenyl) chromen-4-one, and 4'-Hydroxy-5,7-dimethoxyflavanone. Treatment with high-dose OIM enhanced the percentage of survival in ascites tumor-bearing mice by 34.97%. Likewise, high and low doses of OIM reduced the tumor volume in mice by 61.84% and 54.21%, respectively. Further, the skin papilloma formation was brought down by the administration of low- and high-dose groups of OIM (by 67.51% and 75.63%). Overall, the study concludes that the Oroxylum indicum root bark extract is a potentially active antitumor and anticancer agent.

Desmodium gyrans dc modulates lipid trafficking in cultured macrophages and improves functional high-density lipoprotein in male wistar rats.

OBJECTIVE: High-density lipoprotein (HDL) cholesterol-mediated atherosclerotic plaque regression has gained wide therapeutic attention. The whole plant methanolic extract of the medicinal plant Desmodium gyrans Methanolic Extract (DGM) has shown to mitigate hyperlipidemia in high fat- and-cholesterol fed rats and rabbits with significant HDL enhancing property. The study aimed to assess the functionality and mechanistic basis of HDL promoting effect of DGM. MATERIALS AND METHODS: Macrophage cholesterol efflux and foam cell formation assays were performed in THP-1 macrophages. Male Wistar rats were given DGM extract over 1 month and assessed the serum HDL, Apolipoprotein A1 (Apo-A1), and paraoxonase activity. Quantitative Polymerase chain reaction was carried out to assess the expression level of Apo-A1, SR-B1 (Scavenger receptor B1), and Cholesteryl ester transfer protein (CETP) on cDNA of HepG2 cells exposed to DGM. RESULTS: Pretreatment of DGM inhibited uptake of oxidized lipids and enhanced the lipid efflux by THP-1-derived macrophages. Oral administration of DGM (100 and 250 mg/kg) progressively enhanced the serum HDL, Apo-A1 level, and associated paraoxonase activity in normal male Wistar rats. In support to this, DGM exposed HepG2 cells documented dose-dependent increase in the expression of SR-B1 and Apo-A1 mRNA, while reduced the CETP expression. CONCLUSION: Overall the results indicated that DGM modulates lipid trafficking and possesses functional HDL enhancing potential through increased Apo-A1 levels and paraoxonase activity. Further, reduced CETP expression and increased expression of SR-B1 suggest the reverse cholesterol transport promoting role of DGM.

Oroxylum indicum root bark extract prevents doxorubicin-induced cardiac damage by restoring redox balance.

BACKGROUND: Oroxylum indicum Vent., a Dasamula plant used in Ayurveda possesses antioxidant properties. OBJECTIVES: To evaluate the cardioprotective effect of 70% methanolic extract of O. indicum Vent. root bark (OIM) against doxorubicin induced cardiomyopathy in female Sprague Dawley rats. MATERIALS AND METHODS: Cardiotoxicity was induced by intra-peritoneal injection of doxorubicin 30 mg/kg body weight (b.w.) for 4 consecutive days after a ten-day pre-treatment of animals with OIM at 200 mg/kg b.w. and 400 mg/kg b.w (p.o.). Drug treatment continued up to day 14. Probucol, orally administered at a dose of 20 mg/kg b.w. served as standard. ECG was recorded. The animals were sacrificed on day 15 and comparative analysis of serum marker levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), tissue antioxidant status based on Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), reduced Glutathione (GSH) and lipid peroxidation (LPO) was carried out. Histopathological examination was carried out using hematoxylin-eosin staining. RESULTS: ECG records of OIM treated animals showed normal pattern, in comparison to the control with ST depression and arrhythmia in cardiogram. Tissue antioxidant profile (SOD, GSH and GPx) was significantly (p < 0.01) elevated in the cardiac tissue of treated group in dose-dependent manner; lipid peroxidation level was found to decrease with treatment. Comparative analysis of serum markers - CPK, LDH, SGOT and SGPT - among untreated control, standard and extract treated groups revealed that OIM extract at 400 mg/kg b.w. dose significantly reduced the levels (p < 0.01). Histological analysis revealed normal myocardial architecture in OIM treated groups. HPTLC fingerprint of OIM revealed 8 bands and detected the presence of chrysin, apigenin and quercetin. CONCLUSION: O. indicum root bark shows marked cardio-protective activity, possibly due to the presence of antioxidant compounds acting synergistically.

Partially Purified Aqueous Fraction of Desmodium gyrans DC Improves Reverse Cholesterol Transport and Lipoprotein Metabolism in Wistar Rats Fed with High Fat Diet.

Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-density lipoprotein (HDL) mimetics as well as agents that augment the functional HDL and RCT pathways are under intense exploration. Desmodium gyrans (Fabacea) has been shown to have hypolipidemic efficacy, with an HDL-enhancing property. In this study, a chromatographically purified active fraction of D. gyrans (DGMAF) significantly decreased the serum and lipid profiles as well as lipotoxicity in liver in Wistar rats fed with high-fat diet (HFD). Except for the marginal deposition of liver lipids, all other organs showed no weight gain due to lipid accumulation. A lower level of lipid peroxidation and a reduced atherogenic index suggests the hypolipidemic efficacy of DGMAF, which was comparatively higher than clinically used atorvastatin. Furthermore, the DGMAF-treated animals had enhanced levels of HDL, associated ApoA-1, and paraoxonase activity. The mRNA levels of ApoA-1 and SR-B1 were upregulated, and cholesteryl ester transfer protein (CETP) was downregulated. Overall, the results of this study indicate that D. gyrans augments the RCT pathway and improves the lipid metabolism in rats fed an HFD.

Kingiodendron pinnatum, a pharmacologically effective alternative for Saraca asoca in an Ayurvedic preparation, Asokarishta.

Saraca asoca (Fabaceae) is a prime ingredient in Asokarishta, a well-known Ayurvedic preparation for gynecological ailments. Due to scarcity, adulteration or substitution of related raw drugs is a common practice in its preparation. The bark of Kingiodendron pinnatum (Roxb. ex DC.) Harms, morphologically similar to S. asoca (Asoka) is a widely used substitute. The present study aimed to evaluate the pharmacological effectiveness of K. pinnatum as an alternative for S. asoca in Asokarishta by determining the inhibitory effect of estrogen induced uterus endometrial thickening in immature female rats. Arishta was prepared using S. asoca and with the substitute, K. pinnatum as per Ayurvedic Pharmacopeia. Uterus endometrial thickening was induced by the administration of estradiol (20 µg/kg b. wt, i.p) to 8-day-old rats for 5 alternate days. On day 16, following estradiol administration, the serum estrogen level was found elevated to 156.5 ± 8 pg/ml from the normal value 32.4 ± 5 pg/ml and consequently increased the thickness of uterus endometrium from 16.7 ± 1.4 to 75.2 ± 15.3 µm. Upon oral administration of 400 µl/kg b. wt Asokarishta (ASA) and Arishta made with K. pinnatum (AKP), the thickening was reduced to 42.5 ± 12.7 and 47.1 ± 10.5 µm and the estrogen level diminished to 102.6 ± 10 and 97.3 ± 8 pg/ml, respectively. Arishta also reduced the chronic/acute inflammations in mice and improved the antioxidant status of rats. No toxic symptom was observed in the animals by the treatment of Arishta. The study supports the use of K. pinnatum as an alternative to S. asoca in Asokarishta and gives a scientific validation for Asokarishta in gynecological ailments.

Inhibition of Dimethylbenz(a)anthracene (DMBA) - Croton Oil-Induced Mouse Skin Tumorigenesis by Gmelina arborea with Potential Anti-Inflammatory Activity.

In traditional Indian medicine, the plant Gmelina arborea Linn. (GA) is described to have the ability to relieve edema. The present study evaluates the anticancer property of GA stem bark against 7,12-dimethylbenz(a) anthracene (DMBA)-croton oil-induced skin tumorigenesis along with the evaluation of anti-inflammatory activity. The observed inhibition of inflammation in carrageenan-induced (41.8%) and formalin-induced (34.07%) models may be due to inhibition of prostaglandins (PGs). Skin papilloma was induced by a single topical application of DMBA (470 nmol/200 µL acetone), followed by repeated application of croton oil (1% in 200 µL acetone). Low-concentration GA (GALC; 5% in 200 µL distilled water) and high-concentration GA (GAHC; 10% in 200 µL distilled water) were applied topically 30 min before croton oil application. The GALC and GAHC groups showed 85.7% and 57.14% tumor incidence, respectively. The number of papillomas per mouse was observed to be significantly (p ≤ 0.01) reduced in the treated groups. The onset of papilloma development was delayed considerably from 6 (control) to 12 wk (GAHC). Thus, results from the study give insights into the anticancer efficacy of Gmelina arborea, which may be due to prevention of inflammation-mediated tumor promotion by inhibiting PGs.

Radical scavenging and gastroprotective activity of methanolic extract of Gmelina arborea stem bark.

BACKGROUND: Gmelina arborea (GA) is widely used in traditional medicine for treating a number of ailments including gastrointestinal tract disorders. OBJECTIVE: To evaluate the gastroprotective effect of GA stem bark against ethanol-induced gastric ulcer in Wistar rats. MATERIALS AND METHODS: All animals were fasted for 36 h and received GA extract 250 and 500 mg/kg body weight (bw), 1 h before the administration of ethanol. The animals received ranitidine 50 mg/kg bw which served as the standard. The rats were sacrificed after 4 h. Then, the injuries to the gastric mucosa were estimated through gross evaluation of ulcer lesions and histology. The antioxidant parameters such as level of lipid peroxidation, superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx) in gastric tissue were also determined. RESULTS: GA treatment at a dose of 500 mg/kg bw offered 91.98% inhibition of ulcer formation, which is higher than that of ranitidine. The ethanol treatment extensively increased lipid peroxidation and it was significantly (P < 0.01) reduced in GA-treated group that eventually helped to prevent free radical accumulation. The GA enhanced the gastric mucosal antioxidant system, as indicated by a dose-dependent increase in the level/activities of GSH, GPx, and SOD. GA also attenuated the severity of histological signs of cell damage. Further, GA extract showed in-vitro 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity with IC50 value of 124.39 µg/ml. CONCLUSION: The results indicate that the gastroprotective effect of GA is probably related to its antioxidant activities that protect gastric mucosa against oxidative damage and antilipid peroxidative activity that maintain membrane integrity.

Development of an Anti-Atherosclerotic Polyherbal Formulation: GSTC3.

A polyherbal formulation consisting of different proportions of Commiphora mukul (Hook ex Stocks) Eng., Salacia reticulata Wight, Terminalia arjuna (Roxb.) Wight & Arn, and Curcuma longa Linn extracts was tested for free-radical scavenging and anti-lipid peroxidative effects on serum and platelets in vitro. The most active formulation (GSTC3) was evaluated for its hypolipidemic potential on a high-fat, high-cholesterol diet (HFD) fed to male Wistar rats for a period of 45 days. At a dose of 100 mg/kg body weight, GSTC3 decreased serum total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and phospholipids similar to standard atorvastatin while maintaining high-density lipoprotein (HDL) at normal levels. Significantly lower levels of thiobarbituric acid-reactive substances (TBARS) were observed in both the liver and sera of rats treated with GSTC3. Although the phospholipid levels in liver remained unchanged, lower values of LDL, VLDL, and atherogenic index of plasma as well as higher HMG-CoA/ mevalonate ratios suggested a significant hypolipidemic effect for GSTC3, possibly by partial inhibition of HMG-CoA reductase activity. The histopathological analysis of liver tissue did not reveal lipid accumulation or indicate tissue damage. Overall, the results of this study suggest the hypolipidemic and anti-atherogenic efficacy of a nontoxic herbal formulation.

Cyperus rotundus L. prevents non-steroidal anti-inflammatory drug-induced gastric mucosal damage by inhibiting oxidative stress.

BACKGROUND: Since centuries, Cyperus rotundus L. has been used against gastric ailments in traditional Indian medicine, especially in Ayurveda and Siddha. Therefore, it is very obvious that this plant will have a greater potential to treat gastric ulcers. For this reason, in this study, we mainly focused on the ulcer-preventive role of C. rotundus in rats treated with non-steroidal anti-inflammatory drugs. METHODS: Seventy percent methanolic extract of the plant was prepared and fed to 36-h fasted rats. Ulcer was induced in these rats by single oral administration of aspirin (400 mg/kg) 1 h after the administration of the plant extract. After 4 h, the rats were sacrificed, ulcer index was calculated, and antioxidant activity of the extract in gastric mucosa was evaluated by determining the levels of superoxide dismutase, glutathione, glutathione peroxidase, and tissue lipid peroxidation. RESULTS: Oral administration of different doses of C. rotundus rhizome methanolic extract (CME; 250 mg/kg and 500 mg/kg) significantly inhibited aspirin-induced gastric ulceration in animals in a dose-dependent manner (49.32% and 53.15%, respectively), which was also comparable with the standard gastric ulcer drug ranitidine. Administration of CME also significantly increased the activity of superoxide dismutase, cellular glutathione and glutathione peroxidase, and inhibited the lipid peroxidation in the gastric mucosa of ulcerated animals in a dose-dependent manner. CONCLUSIONS: Our results showed that C. rotundus extract has the capacity to significantly inhibit aspirin-induced gastric ulcers through an antioxidant defense mechanism. This study warrants further examination of this plant for its gastroprotective activities.

Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

BACKGROUND: Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. METHODS: Endometrial thickening was induced by intraperitoneal injection of estradiol (20 µg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. RESULTS: Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. CONCLUSIONS: Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

Short-term effect of G-400, polyherbal formulation in the management of hyperglycemia and hyperlipidemia conditions in patients with type 2 diabetes mellitus.

OBJECTIVE: Salacia oblonga, Tinospora cordifolia, Emblica offinalis Gaertn, Curcuma longa and Gymnema sylvestre are Ayurvedic medicinal plants reported to lower plasma glucose levels in animal models. To our knowledge, however, no clinical validations of those extracts for efficacy have been. The aim of this study was to evaluate the effect of polyherbal combination in patients with type 2 diabetes mellitus. METHODS: We screened 250 patients enrolled in a diabetes mellitus screening camp held at District Ayurvedic Hospital, Kottayam, Kerala, India. Of these, 89 patients diagnosed with type 2 diabetes mellitus and 50 healthy volunteers of similar age group were included in the study. Patients were treated with a polyherbal combination drug namely G-400 (1000 mg/d) for 8 wk with a follow-up of 2wk interval. RESULTS: Fasting and postprandial blood glucose levels measured after 8 wk of G-400 treatment in patients were significantly lower. Indeed diabetic rats showed similar protection with G-400 administration. Furthermore, glycosylated hemoglobin, serum total cholesterol, both high- and low-density lipoprotein cholesterol, and triglycerides showed a significant improvement in G-400-administered patients. Toxicologic profile of the drug was assessed by analyzing the enzyme activities of alkaline phosphatase and alanine aminotransferase along with the concentration of blood urea nitrogen and creatinine in blood and found insignificant change compared with control. CONCLUSION: Short-term supplementation of G-400 not only attenuates the hyperglycemia, but also acts as hypolipidemic agent in patients with diabetes. Further study should be done for the long-term effect of the drug in larger populations.

Antitumor activities of an anthraquinone fraction isolated from in vitro cultures of Ophiorrhiza rugosa var decumbens.

The biological effects of the anthraquinone fraction (AQf) isolated from in vitro cultures of Ophiorrhiza rugosa Wall. var decumbens (Rubiaceae) were evaluated. AQf showed differential activity on reactive oxygen species; it mediated the generation of superoxide radical and inhibited hydroxyl radical and lipid peroxidation. No considerable nitric oxide scavenging activity was observed for AQf. The AQf induced 50% cytotoxicity in Ehrlich ascites carcinoma and Dalton's lymphoma ascites at concentrations of 130 and 60 µg/mL, respectively. It effectively reduced the inflammation induced by carrageenan in mice. An AQf concentration of 200 mg/kg body weight reduced solid tumor progression in mice. It also prolonged the life span of ascites tumor-bearing mice compared with control mice.

Antioxidant effects of ethyl acetate extract of Desmodium gangeticum root on myocardial ischemia reperfusion injury in rat hearts.

BACKGROUND: This study aims to evaluate the antioxidant potential of the ethyl acetate extract of Desmodium gangeticum root for cardioprotection from ischemia reperfusion-induced oxidative stress. METHODS: The in vitro antioxidant potential of the extract was in terms of hydroxyl radical scavenging activity, lipid peroxide scavenging activity, nitric oxide scavenging activity and diphenylpicrylhydrazyl radical scavenging activity. The in vivo antioxidant potential of the extract was assessed in an isolated rat heart model. RESULTS: Free radicals were scavenged by the extract in a concentration-dependent manner within the range of the given concentrations in all models. Administration of the ethyl acetate extract of Desmodium gangeticum root (100 mg per kg body weight) before global ischemia caused a significant improvement of cardiac function and a decrease in the release of lactate dehydrogenase in coronary effluent, as well as the level of malondialdehyde in myocardial tissues. CONCLUSION: The ethyl acetate extract of Desmodium gangeticum root protects the myocardium against ischemia-reperfusion-induced damage in rats. The effects of the extract may be related to the inhibition of lipid peroxidation.

Comparative phytochemical and biological analysis to detect the genuineness of substitutes of the plant Moovila in drug preparations.

Pseudarthria viscida is the preferred source of the raw drug Salaparni in Ayurvedic system of medicine, especially in the preparation of Dasamoolarishtam. Due to its scarcity, other trifoliate leguminous plants, particularly the species of Desmodium and Uraria are used as substitutes. The phytochemical and biological properties of these plants were analyzed to sort out the genuineness of the substitutes. Qualitative as well as quantitative chemical profiles obtained for P. viscida showed similarity to U. rufescens. In vitro antioxidant and in vivo gastroprotective assays carried out to determine the biological properties of the extracts revealed that the acetone extract of P. viscida inhibited the formation of hydroxyl, superoxide, nitric oxide radicals, and lipid peroxidation. The oral administration of P. viscida extract significantly reduced ethanol-induced gastric ulceration in mice. Even though more or less the same chemical profile was obtained for P. viscida and U. rufescens, only P. viscida exhibited significant biological properties.

Apoptosis induction of Centella asiatica on human breast cancer cells.

The present study evaluated the ability of methanolic extract of Centella asiatica (Linn) Urban (Umbelliferae) to induce apoptosis in different cancer cell lines. MCF-7 cells emerged as the most sensitive cell line for in vitro growth inhibitory activity. C. asiatica extract induced apoptosis in MCF-7 cells as indicated by nuclear condensation, increased annexin staining, loss of mitochondrial membrane potential and induction of DNA breaks identified by TUNEL reactivity. It is possible that the use of C. asiatica extract as a component in herbal medicines could be justifiable.

Protective effect of Cyclea peltata Lam on cisplatin-induced nephrotoxicity and oxidative damage.

The aim of the present investigation was to evaluate the protective effect of a 70% methanolic leaf extract of Cyclea peltata Lam on cisplatin-induced renal toxicity. The concentration of creatinine, urea, sodium, and potassium in serum and levels of malonyldyaldehyde (MDA), glutathione (GSH), as well as gluathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities were determined in kidney tissue. The marked cisplatin-induced renal damage, characterized by a significant increase in creatinine and urea levels, decreased in extract-treated group, whereas sodium and potassium levels did not change significantly. C. peltata Lam extract significantly changed the increased MDA level and decreased GSH levels found in rats treated with cisplatin alone. The reduced activities of GSH-Px, SOD, and CAT in groups treated with cisplatin alone were significantly increased by the extract. The protective effect was greater in the post-treated than in the pre-treated group of animals. The results indicate that the post-treatment of C. peltata Lam extract might effectively ameliorate the oxidative stress parameters observed in cisplatin induced renal toxicity and could be used as a natural antioxidant against cisplatin-induced oxidative stress.