Dual COX/ 5-LOX inhibitory potential and antioxidant activities by extracts isolated from Melia Azedarach L. leaves

Abstract

This study was aimed at evaluating the dual cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) enzyme inhibition and antioxidant activity of the crude extract (CE) and various solvent fractions from Melia azedarach leaves. Multiple solvents were used to fractionate the 80% ethanolic extract of the leaves, which was then examined for enzyme inhibitory effectiveness against COX and 5-LOX enzymes. All fractions and CE were examined for antioxidant activity, and phenolic acids and flavonoids were identified using Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC). The ethyl acetate fraction (EaF) had the greatest COX/5-LOX inhibitory impact among tested fractions.In vitro, COX activity studies showed that EaF and butanol fraction (BF) possess a higher COX-2 selectivity index than Indomethacin. Besides, the EaF exhibited the highest reduction potential among the control and the CE when tested for antioxidant activities. These findings support the traditional use of Melia azedarachas an anti-inflammatory drug, as the plant inhibited both COX/5-LOX and COX-2 with high selectivity.1.Introduction The most frequent chemical species that cause oxidative damage in the body are reactive oxygen species (ROS) like peroxides, superoxide, singlet oxygen, hydroxyl radical, hydrogen peroxides, and so on. These species produced in the body can cause various cardiovascular and other chronic diseases [1-3], neurodegenerative diseases [4,5], and inflammatory diseases [6,7]. Different inflammatory diseases are linked to oxidative stress (an imbalance between ROS and their removal by protective mechanisms such as antioxidants) [7-9]. Inflammatory mediators such as prostaglandins produced by the arachidonic acid pathway need to be reduced and inhibited as they mainly cause inflammation, pain, and fever in the body [10]. Currently, the symptomatic treatment of inflammation is mainly done by non-steroidal anti-inflammatory drugs (NSAIDs). However, the traditional NSAIDs used in COX reduction are non-selective, lead to gastrointestinal side effects, heart strokes and renal failure. On the other hand, the currently used selective COX-2 inhibitors like ‘coxibs' are reported for cardiovascular side effects [11]. In addition to COX-2, the increased level of leukotriene from the 5-LOX enzyme can result in bronchospasm [11]. In this regard, medicinal preparations that inhibit both Cyclooxygenase (COX-2) and 5-Lipoxygenase (5-LOX) pathways are superior to commonly used NSAIDs since they could produce a synergetic effect to achieve optimal anti-inflammatory activities [10,11]. This can be done by blocking the production of both leukotrienes and prostaglandins. Hence, indeed, there is a need for new, effective, and safe anti-inflammatory drugs with dual COX-2/5-LOX inhibition capacities, which may obliterate the side effects caused by the inhibition of COX-2 alone [12,13]. Melia azedarachL. (known commonly as “Chinaberry, bead tree, Bakain and Persian lilac") is a deciduous tree belonging to the Meliaceae family that is native to tropical Asia and Australia but has now spread throughout the world. [14-16]. The antioxidantand anti-inflammatory potential of Melia azedarachL. from various regions werereported by other groups [14,15, 17-21]. The plant with different species and some species of different cultivars markedly differin their phenolics, flavonoids and antioxidant activities [18,20]. The antioxidant and anti-inflammatory activities of plant extracts are closely linked to phytoconstituents like total phenolics and flavonoids [22-25]. There is no scientific report on the anti-inflammatory action and antioxidant potential of Taiwanese-originMelia azedarach. Therefore, the purpose of the current study is to investigate the dual COX-2 and 5-LOX inhibitor potential, antioxidant potential, quantification of key flavonoids and phenolic acids, as well as total phenolic and flavonoid content of Melia azedarach.