Matrine treatment reduces retinal ganglion cell apoptosis in experimental optic neuritis

Abstract

Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1+ macrophages/microglia and CD4+ T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs). Moreover, MAT treatment promoted Akt phosphorylation and shifted the Bcl-2/Bax ratio back towards an antiapoptotic one, which could be a mechanism for its therapeutic effect in the ON model. Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

Matrine promotes mitochondrial biosynthesis and reduces oxidative stress in experimental optic neuritis

“…ON, which usually occurs in patients with MS and its animal model, EAE ( Quinn et al, 2011 ; Murphy et al, 2020 ), can cause optic nerve damage and subsequently the death of RGCs ( Moore and Goldberg, 2010 ). It has been recently shown that MAT can limit the inflammation and demyelination of the optic nerve and reduce RGCs apoptosis ( Kang et al, 2021 ). However, the mechanism of this natural alkaloid during this process is still unclear.…”

“…As we reported before, MAT effectively suppresses CNS inflammation, demyelination, and axonal loss in optic nerves, as well as RGC apoptosis in EON (Kang et al, 2021). Briefly, we first induced an animal model of EON in Wister rats and then treated it from day 11 p.i., which resulted in a significant reduction in clinical scores for EAE and mitigation in weight loss in the MAT-treated group compared to saline-treated model rats.…”

“…Recent studies have shown that MAT can enhance mitochondrial function and inhibit oxidative stress in oligodendrocytes of EAE ( Wang et al, 2019 ). In addition, we have conducted a preliminary exploration of the protective effect of MAT in RGCs in EON ( Kang et al, 2021 ); however, the mechanism underlying this effect has not yet been elucidated. We focused on this issue in the present study and found that MAT regulates the expression and activation of PGC-1α and Nrf2 by activating SIRT1, promotes mitochondrial biosynthesis, and reduces oxidative stress, thus having a therapeutic effect on EON.…”

Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology Analysis

“…Among them, various ingredients showed anti-inflammatory activity. Matrine, a quinolizidine alkaloid extracted from Sophora flavescens , has the capacity to effectively suppress experimental autoimmune encephalomyelitis and optic neuritis [ 39 , 40 ]. Oxyberberine prevented lipopolysaccharide-induced acute lung injury and improved colitis [ 41 , 42 ].…”

Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms

“…Recently, a clinical case report of a group of COVID-19 patients showed that the effective cure rate of matrine-NaCl treatment for COVID-19 was 100% (Zhang et al 2020c ). In terms of neuroprotection, matrine could reduce the numbers of macrophages, microglia and CD 4+ T cells in experimental autoimmune encephalomyelitis rats by inhibiting NF-κB and MAPK- proteinkinase B (Akt) signaling pathways and mitigating the myelin damage by inhibiting the extravasation of the BBB (Kang et al 2021 ; Luo et al 2021 ; Zhang et al 2013 ).…”