Journal
PHARMACOLOGICAL REPORTS
Volume 73, Issue 5, Pages 1220-1229Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s43440-021-00261-z
Keywords
Daphnetin; Neuroprotection; Cytokines; JNK-MAPK; HSP-70; Nrf-2; HO-1; NF-κ B; TLR-4
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Funding
- Department of Science and Technology, Government of India under EMR [EMR/2016/005878]
- University Grants Commission under the RUSA 2.0 scheme
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Daphnetin, a compound derived from medicinal plants, shows neuroprotective effects by interacting with cellular mediators and signaling pathways to combat neurodegenerative diseases caused by reactive oxygen species and inflammatory mediators.
Daphnetin is a 7, 8 dihydroxy coumarin isolated from different medicinal plants of the Thymelaeaceae family and exhibits copious pharmacological activities including neuroprotection, anti-cancer, anti-malarial, anti-inflammatory, anti-parasitic and anti-arthritic activity. It has been proved to be an effective neuroprotective agent in several preclinical animal studies and cell line examinations. It is found to interact with different cellular mediators and signaling pathways to confer protection against neurodegeneration. The reactive oxygen species and inflammatory mediators are the major culprits of different neurodegenerative diseases. Oxidative stress activates the pro-apoptotic proteins and inhibits anti-apoptotic proteins, leading to neuronal cell death. Daphnetin restores cellular redox balance by upregulating the antioxidants level (GSH and SOD), anti-apoptotic protein (Bcl-2), as well as by reducing the levels of proinflammatory cytokines, executioner caspase-3, pro-apoptotic-Bax, and oxidative stress markers. Furthermore, activation of Nrf-2/HO-1 signaling and upregulation of HSP-70 governs the protection elicited by daphnetin against oxidative stress-induced neuronal apoptosis. Daphnetin modulated inhibition of JNK-MAPK, JAK-STAT, and TLR-4/NF-kappa B signaling pathways also contributed to its neuroprotective effect. The positive effects of daphnetin have been also related to its AChE, BChE, and BACE-1 inhibitory potential. The present review has been designed to explore the mechanistic interplay of various mediators in mediating the neuroprotective effects of daphnetin.
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