Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: Applications for natural product efficacy with omics and systemic biology.

The diagram illustrates the interactions of ROS/RNS with inflammatory molecules and the application of Omics for studying such interactions, and discovering Chinese Medicine compounds and formulae. During the cerebral ischemia-reperfusion injury, the central nervous system interacts with and peripheral system. ROS/RNS interacts with inflammatory cells and factors for mediating ischemic stroke injury. Chinse medicine compounds and TCM formulae can target those interactions for neuroprotection. Omics techniques serve as useful tools for understanding the interaction of ROS/RNS with inflammation, and investigating the mechanisms of Chinse medicine compounds and formulae for treating stroke. Reactive oxygen species (ROS); Reactive nitrogen species (RNS); Advanced glycation end products (RAGE); Toll-like receptor 2/4 (TLR2/4); poly (ADP-ribose) polymerase (PARP); TCM, Traditional Chinese Medicine. • Interactions of oxidative/nitrosative stress, neuroimmune and inflammatory responses in ischemic brain injury. • Omics and systematic biology approach reveal network regulations related to oxidative stress and inflammation in the pathology of stroke. • Active compounds from medicinal herbs with the bioactivity of anti-oxidative stress and anti-inflammation for reducing ischemic brain injury. • Omics approach for exploring the molecular mechanisms and active compounds of Traditional Chinese Medicine for neuroprotection. Oxidative/nitrosative stress and neuroinflammation are critical pathological processes in cerebral ischemia-reperfusion injury, and their intimate interactions mediate neuronal damage, blood-brain barrier (BBB) damage and hemorrhagic transformation (HT) during ischemic stroke. We review current progress towards understanding the interactions of oxidative/nitrosative stress and inflammatory responses in ischemic brain injury. The interactions between reactive oxygen species (ROS)/reactive nitrogen species (RNS) and innate immune receptors such as TLR2/4, NOD-like receptor, RAGE, and scavenger receptors are crucial pathological mechanisms that amplify brain damage during cerebral ischemic injury. Furthermore, we review the current progress of omics and systematic biology approaches for studying complex network regulations related to oxidative/nitrosative stress and inflammation in the pathology of ischemic stroke. Targeting oxidative/nitrosative stress and neuroinflammation could be a promising therapeutic strategy for ischemic stroke treatment. We then review recent advances in discovering compounds from medicinal herbs with the bioactivities of simultaneously regulating oxidative/nitrosative stress and pro-inflammatory molecules for minimizing ischemic brain injury. These compounds include sesamin, baicalin, salvianolic acid A, 6-paradol, silymarin, apocynin, 3H-1,2-Dithiole-3-thione, (−)-epicatechin, rutin, Dl-3 -N- butylphthalide, and naringin. We finally summarize recent developments of the omics and systematic biology approaches for exploring the molecular mechanisms and active compounds of Traditional Chinese Medicine (TCM) formulae with the properties of antioxidant and anti-inflammation for neuroprotection. The comprehensive omics and systematic biology approaches provide powerful tools for exploring therapeutic principles of TCM formulae and developing precision medicine for stroke treatment. [ABSTRACT FROM AUTHOR]