Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

Modulation of arthritis in rats by Toxicodendron pubescens and its homeopathic dilutions.

BACKGROUND: Toxicodendron pubescens P. Mill (Anacardiaceae) known in homeopathy as Rhus toxicodendron (Rhus tox) is used as an anti-inflammatory medicine in homeopathic practice. In this study, Rhus tox in its crude form and homeopathic dilutions (3cH, 6cH, 30cH, 200cH) was evaluated for effects on Complete Freund's Adjuvant (CFA) induced arthritis in rats. METHOD: We assessed the severity of arthritis through observations including inflammatory lesions, body and organ weight and hematological parameters including C-reactive protein (CRP). Blinded radiological analysis of the affected joints and pain intensity determination was also carried out. RESULTS: Rhus tox protected rats from CFA-induced inflammatory lesions, body weight changes and hematological alterations. Rhus tox protected against radiological joint alterations due to arthritis. Arthritic pain scores were also favorably affected by Rhus tox. All the dilutions of Rhus tox including crude form showed anti-arthritic activity. The maximum protective effect was evident in the crude form at 10mg/kg/day, by mouth. CONCLUSION: This study supports claims in the homeopathic literature on the role of Rhus tox and its ultra dilutions in the treatment of arthritis and associated pain. Further study is needed to explain this anti-arthritic effect of Rhus tox.

Tumor-suppressing effect of bartogenic acid in ovarian (SKOV-3) xenograft mouse model.

Bartogenic acid (BA), a natural pentacyclic triterpenoid, proved to have chemomodulatory, anticancer, antidiabetic, anti-arthritic, and anti-inflammatory activity. Based on structure-activity relationship (SAR) approaches, BA has close structural resemblance to oleanolic acid and ursolic acid. These two pentacyclic triterpenoids are well accepted with respect to their therapeutic value in various ailments including anti-cancer activity. The aim of this study is to evaluate the efficacy of BA as a possible antitumor agent, along with its safety in SKOV-3 ovarian cancer. In vitro cytotoxicity of BA and paclitaxel on human ovarian cancer cells (SKOV-3) was assessed using MTT assay. Antitumor potential of BA alone, standard anticancer drug (paclitaxel) alone, and BA in combination with paclitaxel were evaluated in SKOV-3 xenografted SCID mice. Immunohistochemical analysis of NF-κB was performed and analyzed in SKOV-3 tumors. BA alone and BA in combination with paclitaxel significantly inhibited the tumor growth. IC50 of BA was found to be 15.72 µM. Similarly, paclitaxel showed significant antitumor effect with IC50 of 3.234 µM. Treatments of paclitaxel, BA, and combination of BA with paclitaxel were well tolerated during treatment period. Immunohistochemical analysis of NF-κB in SKOV-3 tumors treated with BA in combination with paclitaxel revealed antitumor effect in terms of inhibition of NF-κB. Our results suggested that BA exhibits promising antitumor effect in the restriction of SKOV-3 cells and tumors with considerable safety.