Affiliation:
1. Department of Pathology, Lorestan University of Medical Sciences, Khorramabad, Iran
2. Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
3. Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
4. Department of Medicine, Harvard Medical School, Boston,
Massachusetts, USA
5. Oriented Nursing Midwifery Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
6. Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background:
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb
organ function.
Objectives:
This systematic review study investigated fisetin's effects and possible mechanisms
in attenuating myocardial, cerebral, renal, and hepatic IRIs.
Methods:
This systematic review included studies earlier than Sep 2023 by following the
PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords,
bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase,
and Scopus databases, were used to search the relevant studies. Studies were imported in End-
Note X8, and the primary information was recorded in Excel.
Results:
Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant
enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione
peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by
activating phosphoinositide-3-kinase–protein kinase B/Akt (PI3K/Akt) and nuclear factor
erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the
activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor
kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases).
It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis
factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin
E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial
function, anti-apoptotic effects, promoting autophagy, and preserving tissues from
histological changes induced by IRIs.
Conclusion:
Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting
autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal,
and hepatic IRIs without any significant side effects.
Publisher
Bentham Science Publishers Ltd.