Hesperidin is a potent natural antioxidant that increases antioxidant enzymes and reduces oxidants to prevent ototoxicity ( 3.1.11 Mangiferin (MGF) and pycnogenol Extracted from the genus Mangiferin, MGF protects against cisplatin-associated ototoxicity by down-regulating ROS accumulation, restoring mitochondrial function, and inhibiting apoptosis in in vitro (HEI-OC1 cells and cochlear hair cells) and in vivo (zebrafish larvae and C57BL/6 J mice) models and, the molecular mechanism of which may be attributed to its inhibition of the ROS-MAPK-caspase-3 signalling pathway ( 3.1.12 Silymarin Silymarin, a lipophilic extract from the seeds of Silybum marianum, is protective against ototoxicity by inhibiting the expression of caspase-3 and PARP in cisplatin-induced cleavage through mechanisms such as scavenging of free radicals, reduction of ROS formation, and inhibition of fatty acid peroxidation ( 3.2 Non-flavonoids 3.2.1 Ferulic acid (FA) FA belongs to the phenolic acid family and is abundant in fruits and vegetables.FA acts as a potent antioxidant by up-regulating the cytoprotective system for scavenging free radicals and enhancing cellular stress response ( 3.2.2 Resveratrol Resveratrol belongs to the group of stilbenes and is widely found in a variety of plants such as berries, grapes and nuts
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