Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

Numerous epidemiological studies have reported that particulate matter 2.5 (PM<sub>2.5</sub>) causes skin aging and skin inflammation and impairs skin homeostasis. Hesperidin, a bioflavonoid that is abundant in citrus species, reportedly has anti-inflammatory properties. In this study, w...

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Main Authors: Pincha Devage Sameera Madushan Fernando, Mei Jing Piao, Kyoung Ah Kang, Ao Xuan Zhen, Herath Mudiyanselage Udari Lakmini Herath, Hee Kyoung Kang, Yung Hyun Choi, Jin Won Hyun
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/7/1363
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author Pincha Devage Sameera Madushan Fernando
Mei Jing Piao
Kyoung Ah Kang
Ao Xuan Zhen
Herath Mudiyanselage Udari Lakmini Herath
Hee Kyoung Kang
Yung Hyun Choi
Jin Won Hyun
author_facet Pincha Devage Sameera Madushan Fernando
Mei Jing Piao
Kyoung Ah Kang
Ao Xuan Zhen
Herath Mudiyanselage Udari Lakmini Herath
Hee Kyoung Kang
Yung Hyun Choi
Jin Won Hyun
author_sort Pincha Devage Sameera Madushan Fernando
collection DOAJ
description Numerous epidemiological studies have reported that particulate matter 2.5 (PM<sub>2.5</sub>) causes skin aging and skin inflammation and impairs skin homeostasis. Hesperidin, a bioflavonoid that is abundant in citrus species, reportedly has anti-inflammatory properties. In this study, we evaluated the cytoprotective effect of hesperidin against PM<sub>2.5</sub>-mediated damage in a human skin cell line (HaCaT). Hesperidin reduced PM<sub>2.5</sub>-induced intracellular reactive oxygen species (ROS) generation and oxidative cellular/organelle damage. PM<sub>2.5</sub> increased the proportion of acridine orange-positive cells, levels of autophagy-related proteins, beclin-1 and microtubule-associated protein light chain 3, and apoptosis-related proteins, B-cell lymphoma-2-associated X protein, cleaved caspase-3, and cleaved caspase-9. However, hesperidin ameliorated PM<sub>2.5</sub>-induced autophagy and apoptosis. PM<sub>2.5</sub> promoted cellular apoptosis via mitogen-activated protein kinase (MAPK) activation by promoting the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. The MAPK inhibitors U0126, SP600125, and SB203580 along with hesperidin exerted a protective effect against PM<sub>2.5</sub>-induced cellular apoptosis. Furthermore, hesperidin restored PM<sub>2.5</sub>-mediated reduction in cell viability via Akt activation; this was also confirmed using LY294002 (a phosphoinositide 3-kinase inhibitor). Overall, hesperidin shows therapeutic potential against PM<sub>2.5</sub>-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis.
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spelling doaj.art-606e7e387ac84d79bebdeff6426109912023-12-03T14:34:13ZengMDPI AGAntioxidants2076-39212022-07-01117136310.3390/antiox11071363Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and AutophagyPincha Devage Sameera Madushan Fernando0Mei Jing Piao1Kyoung Ah Kang2Ao Xuan Zhen3Herath Mudiyanselage Udari Lakmini Herath4Hee Kyoung Kang5Yung Hyun Choi6Jin Won Hyun7Department of Biochemistry, College of Medicine, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Medicine, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Medicine, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Medicine, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Medicine, Jeju National University, Jeju 63243, KoreaJeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, Dongeui University College of Korean Medicine, Busan 47227, KoreaDepartment of Biochemistry, College of Medicine, Jeju National University, Jeju 63243, KoreaNumerous epidemiological studies have reported that particulate matter 2.5 (PM<sub>2.5</sub>) causes skin aging and skin inflammation and impairs skin homeostasis. Hesperidin, a bioflavonoid that is abundant in citrus species, reportedly has anti-inflammatory properties. In this study, we evaluated the cytoprotective effect of hesperidin against PM<sub>2.5</sub>-mediated damage in a human skin cell line (HaCaT). Hesperidin reduced PM<sub>2.5</sub>-induced intracellular reactive oxygen species (ROS) generation and oxidative cellular/organelle damage. PM<sub>2.5</sub> increased the proportion of acridine orange-positive cells, levels of autophagy-related proteins, beclin-1 and microtubule-associated protein light chain 3, and apoptosis-related proteins, B-cell lymphoma-2-associated X protein, cleaved caspase-3, and cleaved caspase-9. However, hesperidin ameliorated PM<sub>2.5</sub>-induced autophagy and apoptosis. PM<sub>2.5</sub> promoted cellular apoptosis via mitogen-activated protein kinase (MAPK) activation by promoting the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. The MAPK inhibitors U0126, SP600125, and SB203580 along with hesperidin exerted a protective effect against PM<sub>2.5</sub>-induced cellular apoptosis. Furthermore, hesperidin restored PM<sub>2.5</sub>-mediated reduction in cell viability via Akt activation; this was also confirmed using LY294002 (a phosphoinositide 3-kinase inhibitor). Overall, hesperidin shows therapeutic potential against PM<sub>2.5</sub>-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis.https://www.mdpi.com/2076-3921/11/7/1363hesperidinparticulate matter 2.5human keratinocyteautophagyapoptosismitogen-activated protein kinase
spellingShingle Pincha Devage Sameera Madushan Fernando
Mei Jing Piao
Kyoung Ah Kang
Ao Xuan Zhen
Herath Mudiyanselage Udari Lakmini Herath
Hee Kyoung Kang
Yung Hyun Choi
Jin Won Hyun
Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy
Antioxidants
hesperidin
particulate matter 2.5
human keratinocyte
autophagy
apoptosis
mitogen-activated protein kinase
title Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy
title_full Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy
title_fullStr Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy
title_full_unstemmed Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy
title_short Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy
title_sort hesperidin protects human hacat keratinocytes from particulate matter 2 5 induced apoptosis via the inhibition of oxidative stress and autophagy
topic hesperidin
particulate matter 2.5
human keratinocyte
autophagy
apoptosis
mitogen-activated protein kinase
url https://www.mdpi.com/2076-3921/11/7/1363
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