Natural products as a potential modulator of microglial polarization in neurodegenerative diseases

Neurodegenerative diseases (NDs) are characterized by the progressive loss of structure and function of neurons most common in elderly population, mainly including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Neuroinflammation caused by microglia as the resident macrophages of the central nervous system (CNS) plays a contributory role in the onset and progression of NDs. Activated microglia, as in macrophages, to be heterogeneous, can polarize into M1 (pro-inflammatory) and M2 (anti-inflammatory) functional phenotypes. The former elaborate pro-inflammatory mediators promoting neuroinflammation and neuronal damage. In contrast, the latter generate anti-inflammatory mediators and neurotrophins that inhibit neuroinflammation and promote neuronal healing. Consistently, the regulation of microglial polarization from M1 to M2 phenotype appears as an outstanding therapeutic and preventive approach for NDs treatment. Although non-steroidal anti-inflammatory drugs (NSAIDs) currently used to alleviate M1 microglia-associated neuroinflammation responsible for the development of NDs, these drugs have different degrees of adverse effects and limited efficacy. As the advantages of novel structure, multi-target, high efficiency and low toxicity, natural products as the modulators of microglial polarization have attracted considerable concerns in the therapeutic areas of NDs. In this review, we mainly summarized the therapeutic potential of natural products and their various molecular mechanisms for NDs treatment through modulating microglial polarization. The aim of the current review is expected to be useful to develop innovative modulators of microglial polarization from natural products for the amelioration and treatment of NDs.