Safety and toxicological evaluation of a novel anti-obesity formulation LI85008F in animals.

LI85008F is a novel synergistic composition of Moringa oleifera, Murraya koenigi, and Curcuma longa. These herbs are well recognized and widely used in ayurvedic system of medicine for treating a variety of diseases and are also have been used for culinary purposes for thousands of years. LI85008F inhibits preadipocyte differentiation and potentiates lipid breakdown in mature adipocytes. In diet-induced obese rats, LI85008F significantly reduced weight gain and improved serum adiponectin levels. These findings motivated the authors to determine the broad-spectrum safety of LI85008F. Acute oral toxicity, acute dermal toxicity, primary skin irritation, primary eye irritation, and dose-dependent 28-day sub-acute toxicity studies were conducted. The acute oral LD50 of LI85008F was greater than 5000 mg/kg in female SD rats and no changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of LI85008F was greater than 2000 mg/kg. LI85008F was classified as non-irritating to skin in a primary dermal irritation study conducted using New Zealand Albino rabbits. LI85008F caused minimal irritation to eyes in a primary eye irritation test conducted on New Zealand Albino rabbits. A dose-dependent 28-day sub-acute toxicity study demonstrated no significant changes in selected organ weights. Evaluations on hematology, clinical chemistry, and histopathology did not show any significant adverse changes. The NOAEL of LI85008F was found to be greater than 2500 mg/kg body weight. These results demonstrate the broad spectrum safety of LI85008F in animal models.

Safety and toxicological evaluation of Aflapin: a novel Boswellia-derived anti-inflammatory product.

Boswellia serrata gum resin has been used for treatment of various ailments in different cultures for thousands of years. Aflapin(®) is a novel synergistic composition derived from B. serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. To assess the safety of Aflapin, a battery of acute and sub-acute toxicity studies were conducted in various animal models according to the OECD test guidelines. The acute oral LD50 of Aflapin was greater than 5000 mg/kg in female Sprague Dawley (SD) rats. Acute dermal LD50 of Aflapin was greater than 2000 mg/kg in SD rats. A primary dermal irritation study conducted using New Zealand White rabbits indicated that Aflapin is non-irritating to skin. Aflapin caused minimal ocular irritation in a primary eye irritation test conducted on New Zealand Albino rabbits. A repeat dose 28-day sub-acute oral toxicity study in SD rats demonstrated no significant signs of toxicity. Various evaluations including hematology, clinical chemistry, gross necropsy, and histopathology did not show any significant adverse changes. The NOAEL of Aflapin was found to be greater than 2500 mg/kg body weight. These studies demonstrate broad spectrum safety of Aflapin in animal models.

Safety and toxicological evaluation of demethylatedcurcuminoids; a novel standardized curcumin product.

Turmeric is a well recognized and highly recommended herb in ayurvedic systems of medicine and it has also been used for culinary purposes for thousands of years. Bis-O-demethylatedcurcumin (BDMC) was found to be more efficacious than curcumin and the increased potentcy was attributed to a higher number of phenolic groups in BDMC. A novel demethylatedcurcuminoid composition (DC) comprising minimum 95% of total demethylatedcurcuminoids (67.8% bisdemethylcurcumin, 20.7% demethylmonodemethoxycurcumin, 5.86% bisdemethoxycurcumin, 2.58% demethylcurcumin) was prepared (PCT/IN05/00337, dated October 13, 2005) starting from Curcuma longa extract containing 95% total curcuminoids (C95). DC exhibited superior neuroprotective and anti-inflammatory efficacy compared to C95 in a GeneChip study. Based on these interesting findings, this study sought to determine the broad-spectrum safety of DC. Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90 day sub-chronic toxicity studies were conducted. The acute oral LD50 of DC was found to be > 5000 mg/kg in female SD rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of DC was found to be > 2000 mg/kg. Based on the data from primary skin irritation test conducted on New Zealand Albino rabbits, DC was classified as minimally irritating. Similarly, primary eye irritation test was conducted with DC on rabbits and based on the test outcome DC was classified as mildly irritating to the eye. A dose-dependent 90-day sub-chronic toxicity study demonstrated no significant changes in selected organ weights and as percentages of body and brain weights. DC supplementation did not cause changes in hepatic DNA fragmentation. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the broad spectrum safety of DC.

Analytical study of Kuberaksha/Kantaki Karanja Patra Churna [Caesalpinia Bonduc (L.) Roxb. leaf powder].

Caesalpinia bonduc (L.) Roxb. (Kuberaksha) is an Ayurvedic herb used in the management of malaria, liver disorders, worms, edematous conditions, etc. Based on classical Ayurvedic textual indications and recent pharmacological studies, its leaf powder was selected for studying its effect clinically on filaria. Before conducting the clinical trails, this leaf powder was subjected to certain chemical studies to find the pH, ash value, extractive values, High Performance Thin Layer Chromatography (HPTLC), etc. for standardization of the drug.

Six new diterpene isonitriles from the sponge Acanthella cavernosa.

Six new diterpene isonitriles, 10-epi-isokalihinol F [1], 10-epi-isokalihinol H [2], 1-epi-kalihinene [4], 15-isothiocyanato-1-epi-kalihinene [5], 1,10-diepi-kalihinene [6], and kalihipyran [7] were isolated, together with the known compound isokalihinol B [3], from Acanthella cavernosa collected in the Seychelles. The structures of the new diterpenes were elucidated by interpretation of spectral data. The ring system of kalihipyran [7] differs from that of the kalihinols and kalihinenes.