Isolation of Continentalic Acid from Aralia Cachemirica and Its Immuno-biological Evaluation

In continuing search for compounds with immunomodulatory activity, plant Aralia cachemirica has been found to contain continentalic acid (CA). Isolation of this pharmacologically significant diterpinic acid from Aralia cachemirica is novel. Chemical structure of this compound was identified by spectral analysis as (-)-pimara-8(14), 15-dien-19-oic acid, which has been isolated from A. cordata and A. continentalis. This compound has been evaluated for its effect on immunomodulaion. CA was found to inhibit production of pro-inflammatory cytokines (IL-6, TNF-α) & nitric oxide (NO) in LPS induced macrophage activation, suppressed antibody titres & delayed type hypersensitivity reaction (DTH) when orally administered and increased the phagocytic activity by clearance of Candida albican infection from peritoneal cavity in mouse model system. INTRODUCTION: Immunomodulaion refers to any change in immune response of body involving induction, expression, amplification, or suppression. In some cases we require stimulation of immune response, whereas suppression of immune response is needed in other conditions. Immunosuppressors are required for the treatment of autoimmune diseases and allergies, and in case of organ/tissue transplantation to prevent graft rejection. Conversely, immunostimulators are known to enhance body’s resistance against a number of infections, allergies and cancers serving as immune potentiators in healthy persons and immunotherapeutic agents in case of persons with impaired immunity. Many synthetic and natural compounds are known to possess immunomodulatory activity, but limited efficacy and adverse side effects associated with traditional immunomodulatory drugs drive need to develop new, improved, and target specific immunomodulating agents. According to phylogenic and biogeographic analysis, approximately sixty eight accepted species of genus Aralia (Family Araliaceae) are distributed in Asia and North America . Several species of genus Aralia have pharmacological importance 4-8 and have been used in traditional medicine to treat rheumatic arthritis, nephritis, lumbago, lameness , gastritis 12 inflammation 13 and diabetes mellitus . Aralia cachemirica is a statuesque clump-forming herbaceous perennial, which is capable of forming upright stems 1 to 3m tall with large bright green tripinnate leaves, white flowers and purple-black fruit. In India it is mostly found in North Western Himalayas especially Kashmir, Uttarakhand and Himachal Pradesh . As per detailed literature survey, this plant species has been explored for investigation of essential oil composition 16, , isolation of aralosides & acids 18 and hypoglycemic activity . On biological studies of