**3.2 Free radical cause nitric oxide**

In the lower doses, nitric oxide acts as a neurotransmitter of the neuronal cells, and it exerts antimicrobial activity invading microbes in macrophages [51]. Nitric oxide played an important role in the modulation of CO2-mediated cerebral blood flow [52]. Nitric oxide is a physiological signaling molecule produced from L-arginine by enzyme of nitric oxide synthase (NOS). This enzyme occurs in three forms as neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS). It increases the cGMP levels by acting as vasodilator and is involved in the neurotransmission between nervous system cells [53]. The positive association of oxidative stress and neurodegenerative conditions was observed in multiple sclerosis, stroke, and neurodegenerative disorders [54]. The ROS is actively involved in the oxidative damage to amyloid beta peptides, marker in the Alzheimer's disease [55]. The most abundant neurotransmitter in central nervous system is glutamate which acts as the initiator of NO formation, and H2S is highly expressed in brain which is involved in the pathogenesis of various neurological disorders [56].
