Hydrangenol inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-mediated HO-1 pathway

Kim, Hee-Ju; Kang, Chang‐Hee; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Dilshara, Matharage Gayani; Lee, Seungheon; Choi, Yung Hyun; Seo, Yong Taek; Kim, Gi‐Young

doi:10.1016/j.intimp.2016.03.022

Cited by 62 publications

(22 citation statements)

References 22 publications

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“…Hydrangenol (8-hydroxy-3-(4-hydroxyphenyl)-3,4-dihydroisochromen-1-one) is a natural dihydroisocoumarin mostly obtained from the Hydrangea species (Hydrangeaceae) leaves. Hydrangenol possesses antiinflammatory [250], antidiabetic [251], antioxidant [250,252], anticancer [253], and antiangiogenic activities [254]. It inhibited LPS-induced NO release and iNOS expression via suppression of NF-κB and consequently inhibiting NF-κB-DNA.…”

Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

View full text Add to dashboard Cite

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“…Another study has suggested that mice lacking HO-1 were vulnerable to pro-inflammatory stimuli and developed chronic inflammation due to reduced iron levels ( Chora et al, 2007 ). Furthermore, a recent study suggested that up-regulation of the Nrf2 and HO-1 pathways significantly inhibited the inflammatory reaction in activated microglia ( Kim et al, 2016 ). Nrf2 inhibited microglial hyperactivation by suppressing p38 MAPK and the NF-κB signaling pathway ( Kim B.W.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory Effects of Curcumin in Microglial Cells

et al. 2018

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Lipoteichoic acid (LTA) induces neuroinflammatory molecules, contributing to the pathogenesis of neurodegenerative diseases. Therefore, suppression of neuroinflammatory molecules could be developed as a therapeutic method. Although previous data supports an immune-modulating effect of curcumin, the underlying signaling pathways are largely unidentified. Here, we investigated curcumin’s anti-neuroinflammatory properties in LTA-stimulated BV-2 microglial cells. Inflammatory cytokine tumor necrosis factor-α [TNF-α, prostaglandin E2 (PGE2), and Nitric Oxide (NO] secretion in LTA-induced microglial cells were inhibited by curcumin. Curcumin also inhibited LTA-induced inducible NO synthases (iNOS) and cyclooxygenase-2 (COX-2) expression. Subsequently, our mechanistic studies revealed that curcumin inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including ERK, p38, Akt and translocation of NF-κB. Furthermore, curcumin induced hemeoxygenase (HO)-1HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf-2) expression in microglial cells. Inhibition of HO-1 reversed the inhibition effect of HO-1 on inflammatory mediators release in LTA-stimulated microglial cells. Taken together, our results suggest that curcumin could be a potential therapeutic agent for the treatment of neurodegenerative disorders via suppressing neuroinflammatory responses.

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“…Among these compounds, we previously reported that hydrangenol, a dihydroisocoumarin, possesses potential protective effects on cell viability, production of procollagen type I, MMP-1, and pro-inflammatory cytokines [ 7 ]. Moreover, it has been reported that hydrangenol exhibits anti-inflammatory [ 8 ], anti-microbial [ 9 ], anti-diabetic [ 10 ], anti-allergic [ 11 ], antimalarial [ 12 ], and anti-cancer activities [ 13 , 14 , 15 ]. It has been reported that the scheme for the biosynthesis of hydrangenol with the aid of C 14 -labelled compounds was found to be the condensation of an intact phenylpropanoid molecule with three molecules of acetate [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study

et al. 2020

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Previously, we reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1–R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.

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Hydrangenol inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-mediated HO-1 pathway

Cited by 62 publications

References 22 publications

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Anti-inflammatory Effects of Curcumin in Microglial Cells

Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study

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