Regulatory Role of Chinese Herbal Medicine in Regulated Neuronal Death

Ischemic neuronal injury results from a complex series of pathophysiological events, including oxidative, excitotoxicity, inflammation and nitrative stress. Consequently, many of these events can induce cell death, including necrosis (unregulated cell death) and apoptosis (a type of regulated cell death). These are long-established paradigms to which newly discovered regulated cell death processes have been added, such as necroptosis (a regulated form of necrosis) and autophagydependent cell death. Moreover, many researchers have targeted products associated with Chinese herbal medicine at regulated pathways for the treatment of ischemic neuronal injury. In East Asia, these drugs have been known for centuries to protect and improve the nervous system. Herbal extracts, especially those used in Chinese herbal medicine, have emerged as new pharmaceuticals for the treatment of ischemic neuronal injury. Here, we review the evidence from preclinical studies investigating the neuroprotective properties and therapeutic application of Chinese herbal medicines (Chinese herbal monomer, extract, and medicinal compounds) and highlight the potential mechanisms underlying their therapeutic effects via targeting differently regulated cell death pathways. Notably, many herbs have been shown to target multiple mechanisms of regulated cell death and, in combination, may exert synergistic effects on signaling pathways, thereby attenuating multiple aspects of ischemic pathology. In this review, we summarize a generally regulated pathway of cell death as a target for novel natural herbal regimens against ischemic neuronal injury.