Shikonin ameliorates experimental autoimmune encephalomyelitis (EAE) via immunomodulatory, anti-apoptotic and antioxidative activity

Abstract

Objectives Multiple sclerosis is a common autoimmune inflammatory disease of the central nervous system. There are several underlying mechanisms for the pathogenesis of the disease, including inflammation, oligodendrocyte apoptosis and oxidative stress. Methods The mechanism of action of shikonin was investigated in the C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Key findings The results revealed that EAE induction significantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with shikonin significantly decreased the extent of demyelination. Real-time polymerase chain reaction-based analysis of the brain samples from the EAE mice revealed significant enhancement in the expression levels of tumour necrosis factor-a (TNF-a), interferon-c (IFN-c) and Bax genes as well as a reduction in the expression levels of transforming growth factor-ß (TGF-b) and Bcl2. But, shikonin treatment significantly reduced the expression levels of TNF-a, IFN-c and Bax. On the other hand, the expression levels of TGF-b and Bcl2 as well as the activity of glutathione peroxidase-1 (GPX-1) enzyme were significantly increased following the shikonin treatment. Conclusions This study emphasized the immune-modulatory and antioxidative effects of shikonin, which may have an important healing effect on the severity of EAE.

Shikonin attenuates kidney tubular epithelial cells apoptosis, oxidative stress, and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model

“…In addition, shikonin could inhibit the increase of serum renal injury index (blood proteinuria, serum creatinine, and urea nitrogen) induced by CLP in rats, indicating that shikonin could prevent sepsis‐mediated AKI. Previous studies have shown that shikonin has good antiapoptotic, anti‐inflammatory, and antioxidant effects (Nasrollahzadeh Sabet et al, 2020; C. Yang et al, 2018). It has been reported that shikonin could significantly improve acute lung injury induced by sepsis in vitro and in vivo experiments, and the mechanism was to increase the expression of miRNA‐140‐5p, and then down‐regulate the expression of TLR4, thereby inhibit the downstream myeloid differentiation protein 88 and NF‐κB protein expression (Y. Y. Zhang et al, 2020).…”

“…Shikonin is a kind of naphthoquinone compounds from the roots of shikonin, which has a variety of pharmacological activities (C. Guo et al, 2019). Studies have shown that shikonin possessed antioxidant, antitumor, anti‐inflammatory, antiapoptotic, antiviral, and other biological characteristics (C. Chen et al, 2017; C. Huang et al, 2013; Nasrollahzadeh Sabet et al, 2020; J. Yang et al, 2017). The study showed that shikonin could significantly prevent acute lung injury in septic rats through immune regulation and inhibition of inflammation, and its mechanism might be related to miRNA‐140‐5p/TLR4 axis (Y. Y. Zhang et al, 2020).…”

Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling

“…Based on its ability to induce apoptosis in tumor tissue, SK has been widely investigated in cancer treatment [ 27 – 30 ]. In recent years, the antiapoptotic effects of SK have been gradually discovered in lung injury [ 31 ], myocardial ischemic/reperfusion injury [ 32 ], osteoarthritis [ 33 ], and nervous system diseases [ 18 , 20 , 34 ].…”

Potential Utility of Natural Products against Oxidative Stress in Animal Models of Multiple Sclerosis

“…In addition, the expression levels of TGF-β and Bcl2 and the activity of GPx1 were significantly increased after shikonin treatment. These results suggest that shikonin has good immunomodulatory and antioxidant effects in EAE and may contribute to the remission of EAE [ 186 ].…”