Targeting Mediators Of Chronic Inflammation: A Promising Alternative Therapeutic Use Of Plant-Derived Remedies With Potent Bioactivity And Lower Cytotoxicity

Abstract

Abstract Introduction/Objective Medicinal plants have a long history of use and has been exploited for basic health care needs for many centuries. The various parts of plants are rich sources of a plethora of pharmacologically active remedies that has remained largely unexplored for their therapeutic capabilities. Grewia mollis is one of the medicinal plants that are used to treat painful inflammatory conditions including rheumatism and associated fever. The inhibition of enzymes involved in prostaglandin (PG) synthesis are of great interest in combating chronic inflammation. Cyclooxygenases (COX) and Lipoxygenases (LOX), in particular COX-2 and 5-LOX utilize different pathways for PG synthesis and are important drivers of chronic inflammation. However, the use of conventional anti-inflammatory drugs and specific enzyme inhibitors against them are associated with severe adverse side-effects and organ toxicities. Therefore, attention has shifted to the search for potent and safer alternative strategies to treat chronic inflammation involving these mediators Methods The leaf part of G. mollis was extracted with solvents of varying polarities. The extracts were tested in vitro against COX-1, 2 and 5-LOX. In addition, the cytotoxicity and selectivity index of the plant extracts were evaluated using vero monkey kidney cells Results The hexane fraction of G. mollis leaf extracts had better inhibition against COX-1 (0,97±1,9 µg/mL) and COX-2 (1,13±0,2 µg/mL) when compared with the indomethacin control (1,30±0,6 µg/mL) and (1,52±0,2 µg/mL) respectively. Also, the butanol fraction inhibited 5-LOX (12,48±2,9 µg/mL) better than quercetin positive control (61,82±5,5 µg/mL). Overall, the extracts and fractions indicated reduced cytotoxicity (30,56-689,39 µg/mL) relative to the doxorubicin control (2,59 µg/mL). Conclusion The results indicated that extracts of G. mollis contained bioactive molecules capable of inhibiting the activities of C0X and 5-LOX with lower cytotoxicity. Pharmacologically active molecules with safety profile could be used, at least as a part of the template for remedies against mediators of chronic inflammation