Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease

Abstract

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson's disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects in glial cells. Our results demonstrate that securinine significantly and dose-dependently suppressed the nitric oxide production in microglia and astrocytic cultures. In addition, securinine inhibited the activation of the inflammatory mediator NF-κB, as well as mitogen-activated protein kinases in lipopolysaccharide- (LPS-) stimulated BV2 cells. Additionally, securinine also inhibited interferon-γ- (IFN-γ-) induced nitric oxide levels and iNOS mRNA expression. Furthermore, conditioned media (CM) from securinine pretreated BV2 cells significantly reduced mesencephalic dopaminergic neurotoxicity compared with CM from LPS stimulated microglia. These findings suggest that securinine may be a potential candidate for the treatment of neurodegenerative diseases related to neuroinflammation.

Modulation the Neuro-toxicity Induced by Aluminum Chloride in Rats Using Beetroots and Broccli Extracts

“…The increase in enzymes activity may be due to an indicator of liver injury or dysfunction [31]. Aluminum exposure can result in its accumulation in the liver and leads to liver damage because of increased enzymes levels in the serum [32]. The present data showed that serum creatinine and uric acid levels increased in Aluminium exposure group, which is accurately linked with the renal function dysfunction.…”

Diversity and antimicrobial activity of endophytic fungi isolated from Securinega suffruticosa in the Yellow River Delta

“…Pharmacological studies have shown that S. suffruticosa can promote blood circulation, relax the muscles and tendons, invigorate the spleen and kidney, and relieve rheumatic pains. Moreover, this shrub is effective for the treatment of neurasthenia, facial nerve paralysis, post-polio syndrome, dizziness, deafness, narcolepsy, impotence, and acute liver injury, and other diseases [7][8][9][10]. It possesses an extremely high application value [4].…”

Securinine suppresses osteoclastogenesis and ameliorates inflammatory bone loss

“…Securinine (Sec) was first extracted, purified, and structurally characterized from the roots of Securinega suffruticosa in 1963 and has been traditionally used in oriental medicine. Sec has been reported to inhibit inflammation and neuronal damage in activated neuroglial cells (Leonoudakis et al, 2017). Sec has been developed as a drug to treat neurological conditions such as ALS, polio, and multiple sclerosis (Buravtseva, 1958).…”