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.

Boswellia serrata Extract Containing 30% 3-Acetyl-11-Keto-Boswellic Acid Attenuates Inflammatory Mediators and Preserves Extracellular Matrix in Collagen-Induced Arthritis.

Boswellia serrata extracts have been traditionally employed for the treatment of inflammatory diseases. In the present study, we have evaluated the mechanism of activity of Boswellin Super® FJ (BSE), a standardized extract of B. serrata containing not less than 30% 3-acetyl-11-keto-ß-boswellic acid along with other ß-boswellic acids. The in vitro anti-inflammatory activities were carried out in RAW 264.7 macrophages or human peripheral blood mononuclear cells stimulated with bacterial lipopolysaccharides (LPS) and treated with 1.25-5µg/ml BSE. The anti-arthritic activity of the extract was evaluated in a rat model of collagen-induced arthritis. BSE at 40 and 80mg/kg and celecoxib 10mg/kg were orally dosed for 21days. BSE showed significant (p<0.05) inhibition of inflammation (TNF-α, IL-6, nitric oxide, and COX-2 secretion) and downregulates the mRNA levels of TNF-α, IL-6, IL1-ß, and inducible nitric oxide synthase in macrophages. BSE treatment reduced the levels of phosphorylated-NF-κB (P65), suggesting an anti-inflammatory activity mediated by blocking this key signal transduction pathway. In addition, BSE showed inhibition (p<0.05) of collagenase, elastase, hyaluronidase enzymes, and a reduction in reactive oxygen species and matrix-degrading proteins in RAW 264.7 macrophages stimulated with LPS. BSE treatment significantly (p<0.05) reduced the arthritic index, paw volume, and joint inflammation comparable to celecoxib in collagen-induced arthritis (CIA) in rats. The circulating anti-collagen antibodies were reduced in BSE and celecoxib-treated animals as compared to the CIA. In confirmation with in vitro data, BSE showed a significant (p<0.05) dose-dependent effect on C-reactive protein, prostaglandin E2, and erythrocyte sedimentation rate, which is widely used as a blood marker of inflammation. Further, BSE treatment suppressed the cartilage oligomeric matrix protein and significantly enhanced the hyaluronan levels in synovial fluid. As observed by collagen staining in joints, the loss of matrix proteins was lower in BSE-treated animals, suggesting that BSE could preserve the extracellular matrix in RA. The extract showed inhibition of collagenase enzyme activity in vitro, further strengthening this hypothesis. BSE treatment was found to be safe, and rats displayed no abnormal behavior or activities. The results suggest that Boswellin Super® mediates its activity by preserving matrix proteins, reducing pro-inflammatory mediators, and oxidative stress.

Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice.

Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), a chronic liver disease with a significant unmet clinical need. In this study, we examined the protective effects of Garcinia indica extract standardized to contain 20% w/w of Garcinol (GIE) and 95% Curcuminoids w/w from Curcuma longa (Curcuminoids) in a Stelic animal model (STAM) of NASH. The STAM mice developed steatosis, hepatocyte ballooning, and inflammation, which were significantly reduced by the combination of GIE and Curcuminoids, resulting in a lower NAFLD activity score. The treatment reduced fibrosis as observed by Sirius red staining, liver hydroxyproline content and mRNA levels of TGF- ß and collagen in the liver. Immunostaining with alpha-smooth muscle actin (α SMA) revealed a significant reduction in hepatic stellate cells. Intriguingly, the combination regimen markedly decreased the mRNA levels of MCP1 and CRP and both mRNA and protein levels of TNF-α. NF-kB, reduced the hepatic and circulating FGF21 levels and altered the nonenzymatic (glutathione) and enzymatic antioxidant markers (Glutathione peroxidase, and superoxide dismutase). Our results suggest that the combination of GIE and Curcuminoids can reduce the severity of NASH by reducing steatosis, fibrosis, oxidative stress, and inflammation. The results suggest that the combinatorial regimen could be an effective supplement to prevent the progression of liver steatosis to inflammation and fibrosis in NASH.

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.

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.