尋常性痤瘡(acne vulgaris)俗稱青春痘，其致病因子複雜。痤瘡丙酸桿菌(Propionibacterium acnes)在痤瘡病灶中增殖並活化角質與皮脂腺細胞等釋出過量的促發炎介質(例如interleukin (IL)-8、tumor necrosis factor (TNF)-α或IL-1β)，是發炎性痤瘡(inflammatory acne)的主要致病因子之一。山苦瓜(Momordica charantia Linn. var. abbreviata Ser.)為台灣坊間常見的一種具醫藥用途的蔬菜。
本研究以P. acnes刺激人類單核球THP-1細胞作為生物活性導向方法，探討山苦瓜中具抑制P. acnes誘導發炎之活性物質，並釐清該活性成分的作用機轉。另外也分析存在於山苦瓜葉甲醇萃取物己烷層的活性物質和存在於苦瓜種子之癸酸(capric acid)對於P. acnes誘導發炎反應的影響。
實驗結果發現山苦瓜葉乙醇/乙酸乙酯萃取物有效抑制P. acnes誘導發炎反應，此萃取物含有多酚類與三萜類化合物。利用液相層析或管柱層析等方法分離並鑑定其組成分，包括酚類化合物(gallic, chlorogenic, caffeic, ferulic, and cinnamic acids, myricetin, quercetin, luteolin, apigenin, and thymol)與葫蘆烷型三萜類化合物(5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol 和3β,7β,25-trihydroxycucurbita-5,23-dien-19-al)。利用GC/MS分析比對發現於山苦瓜葉甲醇萃取物己烷層的活性成分為β-ionone。
山苦瓜葉萃取物之酚類化合物、三萜類化合物、β-ionone與capric acid皆能有效降低促發炎細胞激素生成。這些化合物(如山苦瓜葉萃取物、三萜類化合物與capric acid)可經由抑制mitogen-activated protein kinases (MAPKs)或nuclear factor-kappa B (NF-κB)的活化作用、抑制促發炎細胞激素mRNA表現，因而抑制P. acnes誘導的發炎介質釋出。而葫蘆烷型三萜類化合物和β-ionone另可透過抑制MyD88、caspase-1等訊息傳遞途徑達到降低P. acnes引起之發炎反應。
以P. acnes注射小鼠耳朵誘發腫脹模式的結果顯示，山苦瓜葉乙醇/乙酸乙酯萃取物、葫蘆烷型三萜類化合物、β-ionone與capric acid均能有效降低免疫細胞浸潤現象、緩解耳朵發炎腫脹。除此之外，山苦瓜葉乙醇/乙酸乙酯萃取物、葫蘆烷型三萜類化合物和β-ionone可顯著減少小鼠耳朵發炎病灶IL-1β的生成，而capric acid亦可降低小鼠耳朵P. acnes活菌生長。
綜合上述結果，本研究推論山苦瓜葉萃取物和其活性組成分具有緩解發炎性痤瘡發炎之應用潛力。

Acne vulgaris, the medical term for common acne, is the most common skin disease with multiple pathogenic factors. Propionibacterium acnes is a key pathogen involved in acne inflammation by activating inflammatory cells, keratinocytes and sebocytes to secrete pro-inflammatory cytokines such as interleukin (IL)-8, IL-1β, and tumor necrosis factor (TNF)-α.
Wild bitter melon (WBM, Momordica charantia L. var. abbreviate Seringe), is consumed as both a vegetable and as folk medicine in Taiwan. Activity-directed fractionation and purification processes were employed to identify the anti-inflammatory active compounds using P. acnes-stimulated human monocytic THP-1 cells in vitro. The inhibitory activity and action mechanism of ethanol/ethyl acetate extract of WBM leaf on P. acnes-induced inflammatory responses were examined. Secondly, the effects of the bioactive components in the hexane layer of methanolic extract from WBM leaf and capric acid (present in seeds of bitter melon) on P. acnes-induced inflammatory responses were also investigated.
Our results showed that ethanol/ethyl acetate extract significantly suppressed P. acnes-induced cytokine releases. The bioactive compounds of ethanol/ethyl acetate extract were identified as phenolics (gallic, chlorogenic, caffeic, ferulic, and cinnamic acids, myricetin, quercetin, luteolin, apigenin, and thymol) and cucurbitane type triterpenoids (5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al) by using a column chromatography method. In addition, β-ionone was found in hexane layer of methanolic extract, and measured by GC/MS.

These ten phenolics, two cucurbitane type triterpenoids, β-ionone, and capric acid effectively inhibited P. acnes-induced pro-inflammatory cytokine production or mRNA level, such as IL-8, TNF-α or IL-1β. Some of the above compounds (including extract of WBM leaf, cucurbitane type triterpenoid and capric acid) inhibited the activations of mitogen-activated protein kinases (MAPKs) or nuclear factor-kappa B (NF-κB) in vitro, these actions may partially account for their inhibitory effect on cytokine production. In addition, both cucurbitane type triterpenoids and β-ionone also suppressed MyD88 and caspase-1 signaling.
Ethanol/ethyl acetate extract, two cucurbitane type triterpenoids, β-ionone, and capric acid significantly attenuated P. acnes-induced ear swelling in mice along with microabscess. Treatments of ethanol/ethyl acetate extract, two cucurbitane type triterpenoids and β-ionone significantly decreased the migration of neutrophils and IL-1β+ populations in vivo. Capric acid exhibited anti-microbial activity against P. acnes in vitro and in vivo.
Our results suggested that WBM leaf extract and its bioactive components can be potential therapeutic agents against P. acnes-induced skin inflammation.

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