在體外及體內試驗模式下探討薏苡籽實乙醇萃取物對於經痛的影響

Abstract

原發型經痛（primary dysmenorrhea）為婦科疾病常見症狀，具高盛行率，且影響女性生活品質甚鉅。經痛發生的可能原因為子宮內膜分泌過多前列腺素F2α（prostaglandin F2α, PGF2α），刺激子宮平滑肌過度收縮，組織缺血引起疼痛。薏苡（Coix lacryma-jobi L. var. ma-yuen Stapf.）為藥食兼用的食材，然而，許多傳統中醫藥典籍卻明確記載孕婦不宜食用。事實上，薏苡籽實不同部位於子宮收縮有不同效果。先前文獻指出，糙薏仁水萃物可促進懷孕母鼠子宮收縮；薏苡殼甲醇萃取物、薏苡種皮乙醇萃取物抑制子宮平滑肌過度收縮，顯示不同化學成分有不同影響。故本研究目的為：（一）利用PGF2α誘導大鼠及人類子宮平滑肌過度收縮，探討薏苡籽實乙醇萃取物之生物活性及影響機制。（二）進行有效區分層成分分析，尋找活性成分。（三）探討薏苡籽實乙醇萃取物於催產素誘導經痛小鼠模式、醋酸扭體疼痛模式之效果。實驗結果顯示：（一）薏苡殼、種皮乙醇萃取物乙酸乙酯層具抑制大鼠及人類子宮平滑肌過度收縮效果，可能機制為藉由抑制胞外鈣離子的流入而減緩平滑肌過度收縮。此外，乙酸乙酯層亦具預防過度收縮之潛力。（二）3,5,7,4’-tetramethoxyflavone、nobiletin、tangeretin、naringenin、linoleic acid抑制子宮過度收縮；stigmasterol促進自發性收縮。（三）薏苡殼、種皮乙醇萃取物乙酸乙酯層可改善催產素誘導經痛小鼠之扭體情形，且薏苡種皮乙醇萃取物乙酸乙酯層於醋酸扭體疼痛試驗中亦具緩解疼痛之效果。綜合以上結果，薏苡殼、種皮乙醇萃取物具調節子宮平滑肌收縮之能力，並進一步以體內模式印證，以期望提供薏苡於改善原發型經痛保健食品開發之更多科學證據。

Primary dysmenorrhea is highly prevalent in the world, and is related to elevated prostaglandin F2α (PGF2α) levels. Non-steroidal anti-inflammatory drugs (NSAIDs) can provide effective pain relief. Since many severe side effects may occur after long-term use of NSAIDs, Chinese medicinal therapy has been considered as a feasible alternative medicine. Adlay (Coix lacryma-jobi L. var. ma-yuen Stapf.) has long been used in traditional Chinese medicine. Nevertheless, some medical reports have suggested the use of adlay with caution while pregnancy. Published studies have demonstrated that dehulled adlay water extracts (DAW) enhanced uterine contractions. On the other hand, adlay hull methanolic extracts (AHM) and adlay testa ethanolic extracts (ATE) showed inhibitory effects on uterine contractions. In summary, different parts of adlay seeds and different extractions gave various effects because of various active compounds. Therefore, the aims of the study are (1) to investigate the effects and mechanisms of the adlay ethanolic extracts on PGF2α-induced uterine contractions in the rats and human in vitro; (2) to understand the possible active compounds for regulating the uterine contractions; (3) to confirm effects of the adlay ethanolic extracts on oxytocin-induced dysmenorrheal model and acetic acid writhing test in mice in vivo. The present results demonstrated that (1) AHE-EA and ATE-EA have inhibitory effects on PGF2α-induced uterine contractions in the rats and human by blocking external calcium influx, and AHE-EA and ATE-EA are potent for preventing uterine overcontractions; (2) 3,5,7,4’-tetramethoxyflavone, nobiletin, tangeretin, naringenin, linoleic acid inhibit PGF2α-induced uterine contractions, while stigmasterol stimulates spontaneous uterine contractions in the rats; (3) AHE-EA and ATE-EA could remarkably reduce the writhing times and prolong the latent period in oxytocin-induced dysmenorrheal model, and furthermore ATE-EA are pain relieving in acetic acid writhing test. In conclusion, AHE and ATE have the potential for regulating the dysmenorrheal models in vitro and in vivo.