NATURAL ALKANES FROM Senna siamea AS POSSIBLE CONTENDERS AGAINST INFLAMMATORY DISORDERS: AN IN SILICO AND METABOLOMICS PERSPECTIVE

Abstract

Inflammation is a response to host tissue injury occurring due to irritants or pathogenic infections. It increases levels of cytokines, immune-regulatory factors, cytokine receptors, etc. Cyclooxygenase (COX-1, COX-2, and COX-3) is an enzyme responsible for the formation of prostaglandins. So, by inhibiting this cyclooxygenase-2 enzyme, the treatment of inflammation disorders may be more accessible. Senna siamea is a well-known medicinally important tea plantation shade tree that has anti-inflammatory properties. GC-MS was done to find out the secondary metabolites present in the acetone extract of leaves. Alkanes like undecane,3,8-dimethyl; 2-methyltetracosane, hexadecane, heneicosane, etc. were predominantly detected by GC-MS. In silico studies of eicosane and heptadecane were conducted against pro-inflammatory cytokines like tumor necrosis factor, interleukin-6, and mediator cyclooxygenase. Molecular docking results showed that the two compounds are potential inhibitors of inflammation where eicosane had better binding affinity against all the selected proteins than heptadecane, with both having only one Lipinski violation. Molsoft, Molinspiration, and Swiss-ADMET software were applied to evaluate the two compounds' possible physicochemical, drug-like, and ADMET features. These two compounds can be developed and used as effective inhibitory agents against inflammation; however, more in vitro and in vivo research is needed before conducting clinical trials. Besides the metabolomics-based biosynthesis pathway of two compounds, biosynthetic pathways of other detected compounds were also established, which might help the scientific community to increase the yield of these compounds via the methodology of metabolic bioengineering in order to develop novel pharmaceutical products.