TY - JOUR T1 - Antinociceptive and Antioxidant Activities of Methanolic Extract of Leaves of <em>Azadirachta Indica</em> (Neem) JF - bioRxiv DO - 10.1101/694505 SP - 694505 AU - Akash S Mali AU - Mahesh B Thorat AU - Dhairyasheel M. Ghadge AU - Kumodini A. Nikam AU - Shraddha Sawant AU - Farida Shaikh AU - Nayana Vhatkar AU - Swapnja Shinde AU - Kavyashree Gonghade AU - Munaf A. Tamboli Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/08/694505.abstract N2 - Background Azadirachta indica (Neem) is a communal plant of Meliaceae family called Neem Or Kadunimb in Maharashtra, India Neem stated anti-inflammatory through regulation of proinflammatory enzyme activities with COX and LOX enzyme. Previous studies show that Azadirachta Indica (neem) and its chief constituents play essential role in anticancer management via the modulation of different molecular pathways including NF-κB, p53, PI3K/Akt, Bcl-2, pTEN and VEGF. Many parts of the plant are traditionally used in the treatment of various pharmacological action, the analgesic activity of Neem Seed Oil has already reported but Neem Leaves.Methods The antinociceptive activity of Azadirachta Indica Leaves (AZIL) was examined using heat-induced-mechanical (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 50,100, and 200 mg/kg doses. ATP-sensitive K+ channel pathway, cyclic guanosine monophosphate (cGMP) pathway and involvement of opioid system was also tested using glibenclamide, methylene blue and naloxone/morphine respectively. The methanolic extract of leaves of A.Indica was assessed by using different in vitro antioxidant models of screening like scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical.Results AZIL showed antinociceptive activity and antioxidant activity. In both hot plate and tail immersion tests AZIL significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract repressed the number of abdominal writhing. Similarly, AZIL produced substantial dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplanar injection of formalin. As well, AZIL also expressively withdrawn cinnamaldehyde-induced pain and the glutamate-induced pain in mice. It was also proved that pretreatment with naloxone significantly reversed the antinociception produced by AZIL in mechanical tests signifying the involvement of opioid system in its effect. Furthermore, administration of methylene blue, enhanced AZIL induced antinociception while glibenclamide, an ATP-sensitive K+ channel antagonist, could not converse antinociceptive activity induced by AZIL.Conclusion Based on the results of the present study it can be said that AZIL keeps significant antinociceptive activity which acts in both central and peripheral mechanisms.Ethnopharmacological relevance Azadiracta Indica having family Melliases is one of the common medicinal plant in United states and south Asia including India, Pakistan, Bangladesh. Various parts of the plants used in treatment of many inflammatory conditions, skin diseases, tooth protection, antidiabetic in the form of oil and herbal porridge. ER -