Abstract
Cutibacterium acnes (formerly Propionibacterium acnes) 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 C. acnes-induced in vitro and in vivo inflammation. Following methanol extraction of WBM leaves, we confirmed anti-inflammatory properties of ME in C. acnes-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 n-hexane, ethyl acetate, n-butanol and water-soluble fractions. The hexane fraction exerted the most potent anti-inflammatory effect, suppressing C. acnes-induced interleukin-8 (IL-8) production by 36%. The ethanol-soluble fraction (ESF), which was separated from the n-hexane fraction, significantly inhibited C. acnes-induced activation of mitogen-activated protein kinase (MAPK)-mediated cellular IL-8 production. Similarly, the ESF protected against C. acnes-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 C. acnes 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 C. acnes-induced inflammatory responses.
Highlights
Acne vulgaris is one of the most common and chronic inflammatory skin diseases associated with abnormal keratinization, increasing sebum production, bacterial colonization and inflammation [1]
Since IL-8 is a neutrophilic chemokine which plays a critical role in the development of acne vulgaris, we measured the production of IL-8 by THP-1 cells in order to determine whether tested samples suppressed C. acnes-induced inflammation
Using the C. acnes-induced mouse ear edema model, we investigate the in vivo anti-inflammatory effects of the methanolic extract (ME) of wild bitter melon (WBM) leaf
Summary
Acne vulgaris (acne) is one of the most common and chronic inflammatory skin diseases associated with abnormal keratinization, increasing sebum production, bacterial colonization and inflammation [1]. Since anti-cytokine therapies have been applied for various inflammatory diseases [6], identifying new agents that suppress C. acnes-induced inflammation might be useful in treating acne vulgaris. WBM leaf extracts possessed significant antioxidant, cytoprotective and anti-melanogenic activities [13], and suppressed C. acnes-induced inflammation [14]. These findings indicate that extracts of WBM contain antioxidant and anti-inflammatory substances that might be used to treat acne vulgaris and perhaps other ailments as well. We explore bioactive components in WBM leaf extracts which might account for anti-inflammatory properties To this end, we first used bioassay-guided fractionation methods to isolate and identify active compounds in a methanolic extract (ME) of WBM leaves. This study provides new understanding regarding how active ingredients of WBM extracts modulate in vitro and in vivo inflammatory responses
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