苦瓜(Bitter Melon/ Momordica charantia)三萜(Cucurbitane Triterpenoid) 抗癌&降血糖!

苦瓜抗癌 屏科大實驗證實拿下專利 2015-07-1418:46 〔記者邱芷柔／屏東報導〕許多人想到苦瓜的甘苦滋味不禁皺起眉頭，但屏東科技大學生物科技系天然物實驗室教授團隊，經過實驗證實，發現苦瓜中的「三萜類化合物」能抑制腫瘤生長，研究成果順利取得國內發明專利。 教授張誌益表示，實驗室中從苦瓜分離出「三萜類化合物」，經核磁共振光譜等精密儀器確認化合物結構，團隊再由結構推測可能的生物活性，並進行相關動物實驗，在科技部經費支持下完成研究，目前已取得國內發明專利，研究成果也發表於最新一期的SCI國際期刊中。 教授施玫玲說，過去常有苦瓜抗癌的說法，但一直未有實證，該實驗室透過裸鼠進行實驗，發現只有苦瓜可以分離出「三萜類化合物」，該化合物可以有效預防裸鼠皮下腫瘤的生長，並有降低B型肝炎病毒、血糖、血壓等功效。 教授鄭雪玲指出，目前所做的研究包括白苦瓜、綠苦瓜及山苦瓜，不論是瓜肉、種子或是苦瓜莖葉，都可分離出「三萜類化合物」，這項研究將可幫助農民增加收益，苦瓜可以賣到市場供消費者食用，其根莖葉不必再像過去燒掉，而可賣給生技業者進行化合物萃取。生技系主任陳又嘉也表示，苦瓜具有保健功能，市面上可見各種苦瓜保健品，屏科大食品系也開發了苦瓜露及苦瓜錠等產品，而該系團隊的研究成果，將能做為臨床藥劑使用，實驗室也準備與醫學院合作，進行苦瓜藥劑開發。

Bitter melon triterpenes work as insulin sensitizers and insulin substitutes in insulin-resistant cells  Journal of Functional Foods  Volume 13, March 2015, Pages 214–224 . The triterpenes 3β,25-dihydroxy-7β-methoxycucurbita-5,23(E)-diene (DHM) and 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (THC) were previously isolated from Momordica charantia (bitter melon) and identified as hypoglycaemic principles. This study further investigated their hypoglycaemic mechanisms. FL83B cells were treated with tumour necrosis factor-α to result in insulin resistance, a feature of type 2 diabetes. DHM and THC increased the tyrosine phosphorylation of insulin receptor substrate isoform 1 and the phosphorylation of Akt only in the presence of insulin in insulin-resistant cells, suggesting that they are insulin sensitizers. However, they enhanced the phosphorylation of AS160 (Akt substrate of 160 kDa), the migration of glucose transporter-4 and the glucose uptake of insulin-resistant cells in the absence of insulin, suggesting that they can substitute for insulin to promote glucose clearance. The insulin substitution function was blocked by an AMP-activated protein kinase (AMPK) inhibitor, whereas the insulin-sensitizing function may involve the inhibition of protein-tyrosine phosphatase-1B (PTP-1B). The IC50 of DHM and THC to PTP-1B is 92.84 µM and 25.42 µM, respectively. In summary, DHM and THC have insulin-sensitizing and insulin-substitution functions, which are likely correlated with their effects on inhibiting PTP-1B and activating AMPK, respectively.

Cucurbitane Triterpenoid from Momordica charantia Induces Apoptosis and Autophagy in Breast Cancer Cells, in Part, through Peroxisome Proliferator-Activated Receptor γ Activation.  Evid Based Complement Alternat Med. 2013;2013:935675.  Although the antitumor activity of the crude extract of wild bitter gourd (Momordica charantia L.) has been reported, its bioactive constituents and the underlying mechanism remain undefined. Here, we report that 3 β ,7 β -dihydroxy-25-methoxycucurbita-5,23-diene-19-al (DMC), a cucurbitane-type triterpene isolated from wild bitter gourd, induced apoptotic death in breast cancer cells through peroxisome proliferator-activated receptor (PPAR) γ activation. Luciferase reporter assays indicated the ability of DMC to activate PPAR γ , and pharmacological inhibition of PPAR γ protected cells from DMC's antiproliferative effect. Western blot analysis indicated that DMC suppressed the expression of many PPAR γ -targeted signaling effectors, including cyclin D1, CDK6, Bcl-2, XIAP, cyclooxygenase-2, NF- κ B, and estrogen receptor α , and induced endoplasmic reticulum stress, as manifested by the induction of GADD153 and GRP78 expression. Moreover, DMC inhibited mTOR-p70S6K signaling through Akt downregulation and AMPK activation. The ability of DMC to activate AMPK in liver kinase (LK) B1-deficient MDA-MB-231 cells suggests that this activation was independent of LKB1-regulated cellular metabolic status. However, DMC induced a cytoprotective autophagy presumably through mTOR inhibition, which could be overcome by the cotreatment with the autophagy inhibitor chloroquine. Together, the ability of DMC to modulate multiple PPAR γ -targeted signaling pathways provides a mechanistic basis to account for the antitumor activity of wild bitter gourd.