Safety and Toxicological Evaluation of a Novel, Standardized 3-O-Acetyl-11-keto-β-Boswellic Acid (AKBA)-Enriched Boswellia serrata Extract (5-Loxin®)

Safety and Toxicological Evaluation of a Novel, Standardized 3-O-Acetyl-11-keto-β-Boswellic Acid (AKBA)-Enriched Boswellia serrata Extract (5-Loxin^®)

A. V. Krishnaraju, D. Sundararaju, U. Vamsikrishna, R. Suryachandra, G. Machiraju, K. Sengupta, G. Trimurtulu

(2010) TOXICOLOGY MECHANISMS AND METHODS 20:9, pages 556-563

Abstract

The novel anti-inflammatory properties of the gum resin derived from Boswellia serrata, also known as Salai guggal in Ayurvedic medicine, are well recognized and highly recommended for human consumption. The active constituents of the gum resin are boswellic acids (BAs). Among the BAs, AKBA potently inhibits 5-lipoxygenase product formation with an IC50 of 1.5 µM. We developed a novel Boswellia serrata extract enriched with 30% AKBA (US Patent 2004/0073060A1). The genetic basis of the anti-inflammatory effects of 5-Loxin was explored in a system of TNFα-induced gene expression in human microvascular endothelial cells. 5-Loxin significantly prevented the TNFα-induced expression of matrix metalloproteinases and adhesion molecules (ICAM-1 and VCAM-1), and inducible expression of the mediators of apoptosis. With such interesting findings, we planned to determine the broad-spectrum safety of 5-Loxin. Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90- day subchronic toxicity studies were conducted. In safety studies, acute oral LD50 of 5-LoxinQ was found to be greater than 5,000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of 5-Loxin   was found to be >2,000 mg/kg. Primary skin irritation test was conducted with 5-Loxin on New Zealand Albino rabbits and  5-Loxin was classified as nonirritating. Primary eye irritation test was conducted with 5-Loxin on rabbits and 5-Loxin   was classified as mildly irritating to the eye. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. 5-Loxin supplementation did not cause changes in hepatic DNA fragmentation on 30, 60, or 90 days of treatment. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, these results demonstrate the broad-spectrum safety of 5-Loxin.