No abstract

Natural metabolites with their specific bioactivities are being considered as a potential source of materials for pharmacological studies. In this study, we successfully isolated and identified five known clerodane diterpenes, namely 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (1), 16-hydroxy-cleroda-3,13-dien-15-oic acid (2), 16-hydroxy-cleroda-4(18),13-dien-16,15-olide (3), 3α,16α-dihydroxy-cleroda-4(18),13(14)Z-dien-15,16-olide (4), and 16α-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (5) from the methanolic extract of seeds of Polyalthia longifolia. Initially, all the isolated metabolites were investigated for COX-1, COX-2, and 5-LOX inhibitory activities using the standard inhibitory kits. Of which, compounds 3, 4, and 5 exhibited to be potent COX-1, COX-2, and 5-LOX inhibitors with the IC50 values similar or lower to those of the reference drugs. To understand the underlying mechanism, these compounds were subjected to molecular docking on COX-1, COX-2, and 5-LOX proteins. Interestingly, the in silico study results were in high accordance with in vitro studies where compounds 3, 4, and 5 hits assumed interactions and binding pattern comparable to that of reference drugs (indomethacin and diclofenac), as a co-crystallized ligand explaining their remarkable dual (COX/LOX) inhibitor actions. Taken together, our findings demonstrated that compounds 3, 4, and 5 functioned as dual inhibitors of COX/5-LOX and can contribute to the development of novel, more effective anti-inflammatory drugs with minimal side-effects.

Objective: This study prepared, evaluated immunomodulatory activity of nutraceutical formulation and studied the effect of self-mortification and cow urine distillate fortification methods on the immunomodulatory potential of nutraceutical formulation.Methods: Three types of nutraceutical formulations i.e. Nutraceutical formulation (NF), self fortitfied nutraceutical formulation (SFNF) and self fortitfied nutraceutical formulation fortified with cow urine distillate (SFNECUD) were prepared using fine powders of amla, apple, garlic, onion, wheat grass, papaya, turmeric and cow urine distillate by different methods. The immunomodulatory activity of nutraceutical formulations at a dose of 500 mg/kg was assessed by various immune function parameters like cell-mediated immunity (neutrophil adhesion, delayed type hypersensitivity (DTH) response and cyclophosphamide-induced neutropenia), humoral immunity (serum immunoglobulins level and haemoagglutination antibody titer), and phagocytic activity (carbon clearance and polymorphonuclear (PMN) cell activity).Results: Oral administration of NF, SFNF and SFNFCUD showed significant (p<0.01) increase in adhesion of neutrophils, potentiation of the DTH reaction and attenuation of cyclophosphamide-induced neutropenia. A significant increase in serum immunoglobulin levels and production of circulating antibody titer in response to sheep red blood cells (SRBCs) was also observed. In addition, an increase in the phagocytic index in carbon clearance assay and an increase in the phagocytic activity of PMN cells was observed. Conclusion:From the above results, it can be concluded that all three types of formulations showed significant immunostimulant activity. SFNF and SFNFCUD showed better immunomodulatory activity than NF suggesting the potentiation of immunomodulatory potential of NF activity by fortification methods.