In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>

<i>Cutibacterium acnes</i> (formerly <i>Propionibacterium acnes</i>) is a key pathogen involved in the development and progression of acne inflammation. The numerous bioactive properties of wild bitter melon (WBM) leaf extract and their medicinal applications have been recogn...

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Main Authors: Lu-Te Chuang, Ya-Hsin Shih, Wen-Cheng Huang, Lie-Chwen Lin, Chin Hsu, Jong-Ho Chyuan, Tsung-Hsien Tsai, Po-Jung Tsai
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/18/4277
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author Lu-Te Chuang
Ya-Hsin Shih
Wen-Cheng Huang
Lie-Chwen Lin
Chin Hsu
Jong-Ho Chyuan
Tsung-Hsien Tsai
Po-Jung Tsai
author_facet Lu-Te Chuang
Ya-Hsin Shih
Wen-Cheng Huang
Lie-Chwen Lin
Chin Hsu
Jong-Ho Chyuan
Tsung-Hsien Tsai
Po-Jung Tsai
author_sort Lu-Te Chuang
collection DOAJ
description <i>Cutibacterium acnes</i> (formerly <i>Propionibacterium acnes</i>) is a key pathogen involved in the development and progression of acne inflammation. The numerous bioactive properties of wild bitter melon (WBM) leaf extract and their medicinal applications have been recognized for many years. In this study, we examined the suppressive effect of a methanolic extract (ME) of WBM leaf and fractionated components thereof on live <i>C. acnes</i>-induced in vitro and in vivo inflammation. Following methanol extraction of WBM leaves, we confirmed anti-inflammatory properties of ME in <i>C. acnes</i>-treated human THP-1 monocyte and mouse ear edema models. Using a bioassay-monitored isolation approach and a combination of liquid–liquid extraction and column chromatography, the ME was then separated into <i>n</i>-hexane, ethyl acetate, <i>n</i>-butanol and water-soluble fractions. The hexane fraction exerted the most potent anti-inflammatory effect, suppressing <i>C. acnes</i>-induced interleukin-8 (IL-8) production by 36%. The ethanol-soluble fraction (ESF), which was separated from the <i>n</i>-hexane fraction, significantly inhibited <i>C. acne</i>s-induced activation of mitogen-activated protein kinase (MAPK)-mediated cellular IL-8 production. Similarly, the ESF protected against <i>C. acne</i>s-stimulated mouse ear swelling, as measured by ear thickness (20%) and biopsy weight (23%). Twenty-four compounds in the ESF were identified using gas chromatograph–mass spectrum (GC/MS) analysis. Using co-cultures of <i>C. acnes</i> and THP-1 cells, β-ionone, a compound of the ESF, reduced the production of IL-1β and IL-8 up to 40% and 18%, respectively. β-ionone also reduced epidermal microabscess, neutrophilic infiltration and IL-1β expression in mouse ear. We also found evidence of the presence of anti-inflammatory substances in an unfractionated phenolic extract of WBM leaf, and demonstrated that the ESF is a potential anti-inflammatory agent for modulating in vitro and in vivo <i>C. acnes</i>-induced inflammatory responses.
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spelling doaj.art-bb0ccc2b1d11438f895e673d5bad791e2023-11-20T14:12:51ZengMDPI AGMolecules1420-30492020-09-012518427710.3390/molecules25184277In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>Lu-Te Chuang0Ya-Hsin Shih1Wen-Cheng Huang2Lie-Chwen Lin3Chin Hsu4Jong-Ho Chyuan5Tsung-Hsien Tsai6Po-Jung Tsai7Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu 300, TaiwanDepartment of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, TaiwanDepartment of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, TaiwanDepartment of Exercise Health Science, National Taiwan University of Sport, Taichung 404, TaiwanHualien District Agricultural Research and Extension Station, Hualien 973, TaiwanDepartment of Dermatology, Taipei Municipal Wan Fang Hospital and Taipei Medical University, Taipei 116, TaiwanDepartment of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan<i>Cutibacterium acnes</i> (formerly <i>Propionibacterium acnes</i>) is a key pathogen involved in the development and progression of acne inflammation. The numerous bioactive properties of wild bitter melon (WBM) leaf extract and their medicinal applications have been recognized for many years. In this study, we examined the suppressive effect of a methanolic extract (ME) of WBM leaf and fractionated components thereof on live <i>C. acnes</i>-induced in vitro and in vivo inflammation. Following methanol extraction of WBM leaves, we confirmed anti-inflammatory properties of ME in <i>C. acnes</i>-treated human THP-1 monocyte and mouse ear edema models. Using a bioassay-monitored isolation approach and a combination of liquid–liquid extraction and column chromatography, the ME was then separated into <i>n</i>-hexane, ethyl acetate, <i>n</i>-butanol and water-soluble fractions. The hexane fraction exerted the most potent anti-inflammatory effect, suppressing <i>C. acnes</i>-induced interleukin-8 (IL-8) production by 36%. The ethanol-soluble fraction (ESF), which was separated from the <i>n</i>-hexane fraction, significantly inhibited <i>C. acne</i>s-induced activation of mitogen-activated protein kinase (MAPK)-mediated cellular IL-8 production. Similarly, the ESF protected against <i>C. acne</i>s-stimulated mouse ear swelling, as measured by ear thickness (20%) and biopsy weight (23%). Twenty-four compounds in the ESF were identified using gas chromatograph–mass spectrum (GC/MS) analysis. Using co-cultures of <i>C. acnes</i> and THP-1 cells, β-ionone, a compound of the ESF, reduced the production of IL-1β and IL-8 up to 40% and 18%, respectively. β-ionone also reduced epidermal microabscess, neutrophilic infiltration and IL-1β expression in mouse ear. We also found evidence of the presence of anti-inflammatory substances in an unfractionated phenolic extract of WBM leaf, and demonstrated that the ESF is a potential anti-inflammatory agent for modulating in vitro and in vivo <i>C. acnes</i>-induced inflammatory responses.https://www.mdpi.com/1420-3049/25/18/4277wild bitter melon (WBM)<i>Cutibacterium</i> <i>acnes</i>anti-inflammationβ-ionone
spellingShingle Lu-Te Chuang
Ya-Hsin Shih
Wen-Cheng Huang
Lie-Chwen Lin
Chin Hsu
Jong-Ho Chyuan
Tsung-Hsien Tsai
Po-Jung Tsai
In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>
Molecules
wild bitter melon (WBM)
<i>Cutibacterium</i> <i>acnes</i>
anti-inflammation
β-ionone
title In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>
title_full In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>
title_fullStr In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>
title_full_unstemmed In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>
title_short In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against <i>Cutibacterium acnes</i>
title_sort in vitro and in vivo screening of wild bitter melon leaf for anti inflammatory activity against i cutibacterium acnes i
topic wild bitter melon (WBM)
<i>Cutibacterium</i> <i>acnes</i>
anti-inflammation
β-ionone
url https://www.mdpi.com/1420-3049/25/18/4277
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