In an animal model, bitter melon extract showed hypoglycemic activity by suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase enzymes in the liver ⁽¹⁴⁾. It improved insulin sensitivity, glucose tolerance, and insulin signaling ⁽¹⁵⁾. It also reduced insulin resistance by influencing PPAR alpha and gamma expression ⁽¹⁶⁾ and by modulating phosphorylation status of insulin receptors and downstream signaling molecules ⁽¹⁷⁾. Preventive effects against insulin resistance may also occur via modulation of NF-kappa B and JNK pathways ⁽³⁶⁾.

Animals fed bitter melon showed lower fatty acid synthase ⁽¹⁸⁾. It may affect fat and carbohydrate metabolism by stimulating thyroid hormones and adiponectin, and by enhancing AMPK activity ⁽¹⁹⁾. In another study, it prevented inflammation and oxidative stress, modulated mitochondrial activity, suppressed apoptosis activation, and inhibited lipid accumulation during the development of fatty liver ⁽³²⁾.

Other experiments suggest cytotoxic activity with isolated components such as ribosome-inactivating proteins which inhibited HDAC-1 activity and induced apoptosis in prostate cancer cells ⁽¹⁾. A triterpene extracted from bitter melon activated PPAR gamma and induced apoptosis in breast cancer cells ⁽²⁰⁾. Bitter melon juice also caused apoptosis by inducing caspase-3 activation through AMPK in pancreatic cell lines ⁽³⁾. Similar effects were observed with methanol extracts which increased Bax and decreased the antiapoptotic protein Bcl-2 ^(21) (22). Other studies demonstrated reduction in metastasis via suppression of MMP-2 and MMP-9 enzymatic activities in lung adenocarcinoma cells ⁽²³⁾. Bitter melon juice decreased phosphorylation of protein kinases Akt and ERK1/2, and viability of gemcitabine-resistant pancreatic cancer cells ⁽³⁷⁾.