Safety assessment of a novel water-soluble extract of Boswellia serrata gum resin: acute toxicity, 90-day sub-chronic toxicity, Ames' bacterial reverse mutation, and in vivo micronucleus assays.

Boswellia serrata gum resin extracts have demonstrated potential benefits in alleviating joint pain and discomfort of osteoarthritis. The major objective of the present study was to assess the safety of a water-soluble B. serrata gum resin extract (LI51202F1) in diverse models of acute oral, acute dermal, primary dermal irritation, eye irritation, and 90-day sub-chronic repeated dose toxicity studies, as well as Ames' bacterial reverse mutation assay and in vivo micronucleus assay. The acute oral and dermal toxicity studies in Sprague Dawley (SD) rats demonstrated that the median lethal dose (LD50) of LI51202F1 is >2000 mg/kg body weight (BW). The acute dermal and eye irritation tests in New Zealand white rabbits exhibited that LI51202F1 is non-irritating to the skin and mildly irritating to the eyes, respectively. The 90-days sub-chronic repeated oral dose study demonstrated that the LI51202F1-treated male and female SD rats did not show signs of toxicity on their BW, food intake, organ weights, thyroid hormones, and on the clinical pathology, gross pathology, and histopathological assessments. In male and female rats, the no-observed-adverse-effect level (NOAEL) of LI51202F1 was 500 mg/kg/day, the highest tested dose in the study. The results of the bacterial reverse mutation assay in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA (pKM101) strains in the presence or absence of S9 metabolic activation system and a micro-nucleus assay in mouse bone marrow erythrocytes demonstrated that LI51202F1 is neither mutagenic nor clastogenic. In conclusion, under the conditions of these studies, LI51202F1 demonstrated broad-spectrum safety.

Acute, Subacute, and Genotoxicity Assessments of a Proprietary Blend of Garcinia mangostana Fruit Rind and Cinnamomum tamala Leaf Extracts (CinDura®).

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the Garcinia mangostana fruit rind (GM) and the Cinnamomum tamala leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines. The acute oral toxicity study in Wistar rats suggests that the median lethal dose of CinDura® is at least 2000 mg/kg body weight. Acute dermal and eye irritation tests in New Zealand white rabbits indicate that the test item is nonirritant to the skin and eyes. A twenty-eight-day repeated dose oral toxicity study was conducted in male and female Wistar rats using daily doses of 250, 500, and 1000 mg/kg body weight, followed by a fourteen-day reversal period for two satellite groups. The CinDura®-supplemented animals did not show any sign of toxicity on their body weights, organ weights, and on the hematobiochemical parameters. The gross pathology and histopathological examinations indicated no treatment-related changes in the experimental animals. Overall, the no-observed-adverse-effect level (NOAEL) of the herbal blend is 1000 mg/kg body weight, the highest tested dose. Also, the results of the bacterial reverse mutation test and the erythrocyte micronucleus assay in mouse bone marrow suggest that CinDura® (GMCT) is neither mutagenic nor clastogenic.

Toxicological Assessment of a Standardized Boswellia serrata Gum Resin Extract.

The acidic and non-acidic fractions of Boswellia serrata gum resin extracts were combined to prepare a unique product, LI13019F1 (Serratrin). The present series of studies evaluated LI13019F1 for acute and subchronic (28-day) toxicity in Wistar rats and acute dermal and eye irritation in New Zealand white rabbits. The mutagenicity and clastogenicity of LI13019F1 were evaluated in bacteria and mouse bone marrow erythrocytes, respectively. All studies were performed following the Organization for Economic Co-operation and Development guidelines. Acute oral and acute dermal toxicity studies did not show mortality or signs of toxicity in Wistar rats at a limit dose of 2,000 mg/kg LI13019F1. LI13019F1 did not cause irritation to the skin or the eyes of New Zealand white rabbits. In a repeated dose 28-day oral toxicity study, LI13019F1-treated Wistar rats did not show dose-related signs of toxicity on their body weights, organ weights, and on the hematology and clinical chemistry parameters. The estimated no observed adverse effect level for LI13019F1 was 1,000 mg/kg/day in both male and female rats. The bacterial reverse mutation test and a micronucleus assay in mouse bone marrow erythrocytes revealed that LI13019F1 was neither mutagenic nor clastogenic. Together, the present observations demonstrate a broad-spectrum safety of LI13019F1.

Toxicological studies on the botanical supplement LI12542F6 containing extracts of Sphaeranthus indicus flower heads and Mangifera indica (mango tree) bark.

LI12542F6, a botanical extract composed of Sphaeranthus indicus and Mangifera indica, was evaluated for mutagenicity in bacteria, clastogenicity in mouse bone marrow, acute oral and dermal toxicity in the rat, irritation (dermal, eye) in rabbit, and subacute and subchronic toxicity (28 and 90 days) in the rat. All studies followed standard OECD test protocols, in accordance with the principles of Good Laboratory Practice (GLP). LI12542F6 did not induce mutations in the bacterial assay using Salmonella and Escherichia coli strains, nor did it induce genotoxic effects in erythrocytes from mouse bone marrow. LI12542F6 was found to have oral and dermal LD 50 values greater than the limit dose of 2,000 mg/kg body weight in the rat. In an eye irritation/corrosion test, LI12542F6 caused conjunctival redness, corneal opacity, and chemosis and is classified as Category 2A ("irritating to eyes - reversible eye effect"). Doses in the 28-day and 90-day rat oral toxicity studies were 0, 500, 1,000, and 1,500 and 0, 1,000, 1,500, and 2,000 mg/kg body weight/day, respectively, administered by gavage. Both studies featured a recovery period. Minor effects were random and not treatment related except for local irritation of the forestomach in the 28-day study, evidenced by histopathologic examination, in mid- and high-dose animals. The frequency and severity of these effects were reduced in the recovery group; irritation was not found in the forestomach of rats in the 90-day study. The no observed adverse effect level (NOAEL) was greater than the highest dose tested, that is, >2,000 mg/kg in the 90-day study. This botanical composition will be marketed commercially for muscle health as Myotor™.