Neuroprotective effect of 6-paradol in focal cerebral ischemia involves the attenuation of neuroinflammatory responses in activated microglia

PloS One
Bhakta Prasad GaireJi Woong Choi

Abstract

Paradols are non-pungent and biotransformed metabolites of shogaols and reduce inflammatory responses as well as oxidative stress as shogaols. Recently, shogaol has been noted to possess therapeutic potential against several central nervous system (CNS) disorders, including cerebral ischemia, by reducing neuroinflammation in microglia. Therefore, paradol could be used to improve neuroinflammation-associated CNS disorders. Here, we synthesized paradol derivatives (2- to 10-paradols). Through the initial screening for anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated BV2 microglia, 6-paradol was chosen to be the most effective compound without cytotoxicity. Pretreatment with 6-paradol reduced neuroinflammatory responses in LPS-stimulated BV2 microglia by a concentration-dependent manner, which includes reduced NO production by inhibiting iNOS upregulation and lowered secretion of proinflammatory cytokines (IL-6 and TNF-α). To pursue whether the beneficial in vitro effects of 6-paradol leads towards in vivo therapeutic effects on transient focal cerebral ischemia characterized by neuroinflammation, we employed middle cerebral artery occlusion (MCAO)/reperfusion (M/R). Administration of 6-paradol immediately af...Continue Reading

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Citations

Feb 13, 2016·Journal of Agricultural and Food Chemistry·Shuichi SetoguchiJiro Takata
Nov 12, 2015·Biochemical Pharmacology·Mithilesh Kumar JhaKyoungho Suk
Mar 10, 2017·Bioorganic & Medicinal Chemistry Letters·Hyeong Jun KimHye Hyun Yoo
Jun 12, 2019·Biomolecules & Therapeutics·Bhakta Prasad GaireJi Woong Choi
Jan 30, 2020·International Journal of Molecular Sciences·Lalita SubediSun Yeou Kim
Mar 3, 2020·Frontiers in Cellular Neuroscience·Ruqayya AfridiKyoungho Suk
Jan 15, 2021·BMC Complementary Medicine and Therapies·Misbahuddin RafeeqAli M El-Halawany
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May 6, 2021·International Journal of Molecular Sciences·Lalita SubediSun-Yeou Kim
May 11, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Lalita Subedi, Bhakta Prasad Gaire
Jun 5, 2021·International Journal of Biological Macromolecules·Taurin HughesZulfiqar Ahmad
Jun 4, 2021·Neurochemistry International·Qi-Qi LiRui Sheng
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Aug 31, 2021·Cellular and Molecular Neurobiology·Bhakta Prasad Gaire
Nov 11, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Naiana da RosaFabrícia Petronilho

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Methods Mentioned

BETA
SiO
PCR
confocal microscopy
ELISA
FACS

Software Mentioned

ImageMaster 2D Elite
Adobe Photoshop
Cell Quest
ImageJ
Statistical Analysis System ( SAS )

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