Cerebral ischemia-reperfusion injury (CI/RI) can lead to a range of impairments and even permanent disability.This systematic review was designed to comprehensively investigate the biological effects of silymarin and silibinin in mitigating CI/RI. To find studies published before January 02, 2024, a comprehensive electronic search was carried out across multiple databases, including Cochrane Library, PubMed, Embase, Web of Science, and Scopus. Data including study characteristics, methods, and biological mechanisms were extracted. Silymarin and silibinin potentially improved endogenous antioxidants and reduced lipid peroxidation, nitric oxide (NO), and malondialdehyde (MDA) levels. They also enhances the nuclear factor erythroid 2-related factor 2 (Nrf2) expression and upregulated HO-1 and NAD(P)H: quinone oxidoreductase 1 (NQO1). They also protected the activity of Na+-K+ ATPase, activating mitochondrial membrane potential that suppresses mitochondrial permeability transition pores (mPTP). Moreover, they upregulated proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), uncoupling protein 2 (UCP2), nuclear respiratory factor 1 (NRF1), and reduced inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), and myeloperoxidase (MPO) expression. They inhibited transcription factors, including nuclear factor-kappa B (NF-κB) and IκB-α degradation. They also attenuated tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. Anti-apoptotic properties were revealed by increasing protein Bcl-2 and reducing p53, Bax, caspase-3, and 9 expressions. silymarin improves pathological changes, behavioral tests, and decreases cerebral infarct size. Silymarin and silibinin indicated promising effects on CI/RI through various mechanisms. However, well-designed clinical trials are needed to validate these findings in human subjects.
Mardani-Nafchi et al. (Mon,) studied this question.