A Review: Momordica charantia L.'s Biological Active Components and Its Potential Use in Traditional Therapies

Year 2020, Volume: 1 Issue: 2, 79 - 95, 27.08.2020

Gülşah Aydın Ertuğrul Kaya

Abstract

The use of herbs for therapeutic purposes has been widespread since ancient times. In traditional treatments, plants are applied in a variety of forms, either directly or prepared by isolation and / or enrichment of biologically active ingredients. Momordica charantia L. (bitter melon) is a popular bush that has traditional use as a supplement in the treatment of various diseases with its rich bioactive ingredient content. The plant has common pharmacological potential, including antimicrobial, antimutagenic, antifertility, antidiabetic, antioxidant, antilipolytic, hypoglycemic, anticancer, antimicrobial, antiviral and hepatoprotective activities. This review provides a short overview of the in vitro, in vivo and clinical studies conducted to evaluate the therapeutic efficacy and safety of Momordica charantia.

Keywords

Momordica Charantia, Bittermelon, Traditional Medicine

References

• Lij W, Veseras J. Drug Discovery and Natural products: end of an era or an endless frontier?[J]. Science. 2009;325(5937):161-165.
• Ji Y, Luo Y, Hou B, Wang W, Zhao J, Yang L, Xue Q, Ding X. Development of polymorphic microsatellite loci in M. charantia (Cucurbitaceae) and their transferability to other cucurbit species. Scientia horticulturae. 2012;140:115-118.
• Choi JS, Kim HY, Seo WT, Lee JH, Cho KM. Roasting enhances antioxidant effect of bitter melon (M. charantia L.) increasing in flavan-3-ol and phenolic acid contents. Food Science and Biotechnology. 2012;21(1):19-26.
• Yaldız G, Sekeroglu N, Kulak M, Demirkol G. Antimicrobial activity and agricultural properties of bitter melon (M. charantia L.) grown in northern parts of Turkey: a case study for adaptation. Natural product research. 2015;29(6):543-545.
• Mada S, Garba A, Mohammed H, Muhammad A, Olagunju A, Muhammad A. Antimicrobial activity and phytochemical screening of aqueous and ethanol extracts of M. charantia L. leaves. Journal of Medicinal Plants Research. 2013;7(10):579-586.
• Oragwa Leonard N, Efiom Otu O, Okwute Simon K. Phytochemicals, anti-microbial and free radical scavenging activities of M. charantia Linn (Palisota Reichb) seeds. African Journal of Pure and Applied. 2013;7(12):405-409.
• Ramprasath VR, Awad AB. Role of phytosterols in cancer prevention and treatment. Journal of AOAC International. 2015;98(3):735-738.
• Uddin MS, Sarker MZI, Ferdosh S, Akanda MJH, Easmin MS, Bt Shamsudin SH, Yunus KB. Phytosterols and their extraction from various plant matrices using supercritical carbon dioxide: a review. Journal of the Science of Food and Agriculture. 2015;95(7):1385-1394.
• Zhu Y, Soroka D, Sang S. Oxyphytosterols as active ingredients in wheat bran suppress human colon cancer cell growth: identification, chemical synthesis, and biological evaluation. Journal of agricultural and food chemistry. 2015;63(8):2264-2276.
• Li C-J, Tsang S-F, Tsai C-H, Tsai H-Y, Chyuan J-H, Hsu H-Y. M. charantia extract induces apoptosis in human cancer cells through caspase-and mitochondria-dependent pathways. Evidence-Based Complementary and Alternative Medicine. 2012;2012.
• Zhang J, Huang Y, Kikuchi T, Tokuda H, Suzuki N, Inafuku Ki, Miura M, Motohashi S, Suzuki T, Akihisa T. Cucurbitane triterpenoids from the leaves of M. charantia, and their cancer chemopreventive effects and cytotoxicities. Chemistry & biodiversity. 2012;9(2):428-440.
• Tuan NQ, Lee D-H, Oh J, Kim CS, Heo K-S, Myung C-S, Na M. Inhibition of proliferation of vascular smooth muscle cells by Cucurbitanes from M. charantia. Journal of natural products. 2017;80(7):2018-2025.
• Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, Perez-Jimenez F. Long chain omega-3 fatty acids and cardiovascular disease: a systematic review. British Journal of Nutrition. 2012;107(S2):S201-S213.
• Alva-Murillo N, Ochoa-Zarzosa A, López-Meza JE. Short chain fatty acids (propionic and hexanoic) decrease Staphylococcus aureus internalization into bovine mammary epithelial cells and modulate antimicrobial peptide expression. Veterinary microbiology. 2012;155(2-4):324-331.
• Urbanek A, Szadziewski R, Stepnowski P, Boros-Majewska J, Gabriel I, Dawgul M, Kamysz W, Sosnowska D, Gołębiowski M. Composition and antimicrobial activity of fatty acids detected in the hygroscopic secretion collected from the secretory setae of larvae of the biting midge Forcipomyia nigra (Diptera: Ceratopogonidae). Journal of insect physiology. 2012;58(9):1265-1276.
• Žilić S, Serpen A, Akıllıoğlu Gl, Gökmen V, Vančetović J. Phenolic compounds, carotenoids, anthocyanins, and antioxidant capacity of colored maize (Zea mays L.) kernels. Journal of Agricultural and Food Chemistry. 2012;60(5):1224-1231.
• Khoddami A, Wilkes MA, Roberts TH. Techniques for analysis of plant phenolic compounds. Molecules. 2013;18(2):2328-2375.
• Alves MJ, Ferreira IC, Froufe HJ, Abreu R, Martins A, Pintado M. Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies. Journal of applied microbiology. 2013;115(2):346-357.
• Ghasemzadeh A, Jaafar HZ. Profiling of phenolic compounds and their antioxidant and anticancer activities in pandan (Pandanus amaryllifolius Roxb.) extracts from different locations of Malaysia. BMC complementary and alternative medicine. 2013;13(1):341.
• Hu Q-F, Zhou B, Huang J-M, Gao X-M, Shu L-D, Yang G-Y, Che C-T. Antiviral phenolic compounds from Arundina gramnifolia. Journal of natural products. 2013;76(2):292-296.
• Sathya A, Ambikapathy V, Panneer S. Studies on the phytochemistry, antimicrobial activity and antioxidant properties of Cassia occidentalis L. Asian Journal of Plant Science and Research. 2012;2(4):530-533.
• Sood A, Kaur P, Gupta R. Phytochemical screening and antimicrobial assay of various seeds extract of Cucurbitaceae family. 2012.
• Dar UK, Owais F, Ahmad M, Rizwani GH. Biochemical analysis of the crude extract of M. charantia (L.). Pakistan journal of pharmaceutical sciences. 2014;27(6):2237-2240.
• Tan SP, Parks SE, Stathopoulos CE, Roach PD. Extraction of flavonoids from bitter melon. Food and Nutrition Sciences. 2014;2014.
• Yeo YL, Chia YY, Lee CH, Sow HS, Yap WS. Effectiveness of maceration periods with different extraction solvents on in-vitro antimicrobial activity from fruit of M. charantia L. Journal of Applied Pharmaceutical Science. 2014;4(10):16-23.
• Zhang F, Lin L, Xie J. A mini-review of chemical and biological properties of polysaccharides from M. charantia. International journal of biological macromolecules. 2016;92:246-253.
• Bourinbaiar AS, Lee-Huang S. The Activity of Plant-Derived Antiretroviral Proteins MAP30 and GAP31 against Herpes Simplex Virus Infectionin Vitro. Biochemical and biophysical research communications. 1996;219(3):923-929.
• Lee-Huang S, Huang PL, Chen H-C, Huang PL, Bourinbaiar A, Huang HI, Kung H-f. Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon. Gene. 1995;161(2):151-156.
• Lee-Huang S, Huang PL, Bourinbaiar A, Chen H, Kung H. Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proceedings of the National Academy of Sciences. 1995;92(19):8818-8822.
• Lee-Huang S, Huang PL, Sun Y, Chen HC, Kung HF, Murphy W. Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30. Anticancer Research. 2000;20(2A):653-659.
• Raman A, Lau C. Anti-diabetic properties and phytochemistry of M. charantia L.(Cucurbitaceae). Phytomedicine. 1996;2(4):349-362.
• Ali L, Khan AKA, Mamun MIR, Mosihuzzaman M, Nahar N, Nur-E-Alam M, Rokeya B. Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of M. charantia on normal and diabetic model rats. Planta medica. 1993;59(05):408-412.
• Kisacik ÖG, Güneş ÜY. Yara iyileşmesinde kudret narının etkisi. Spatula DD. 2017;7(2):53-59.
• F Fang E, B Ng T. Bitter gourd (M. charantia) is a cornucopia of health: a review of its credited antidiabetic, anti-HIV, and antitumor properties. Current molecular medicine. 2011;11(5):417-436.
• Grover J, Yadav S. Pharmacological actions and potential uses of M. charantia: a review. Journal of ethnopharmacology. 2004;93(1):123-132.
• Ng T, Chan W, Yeung H. Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor and anti-AIDS activities from Cucurbitaceae plants. General Pharmacology: The Vascular System. 1992;23(4):575-590.
• Basch E, Gabardi S, Ulbricht C. Bitter melon (M. charantia): a review of efficacy and safety. American Journal of Health-System Pharmacy. 2003;60(4):356-359.
• Joseph B, Jini D. Antidiabetic effects of M. charantia (bitter melon) and its medicinal potency. Asian Pacific Journal of Tropical Disease. 2013;3(2):93-102.
• Palamthodi S, Lele S. Nutraceutical applications of gourd family vegetables: Benincasa hispida, Lagenaria siceraria and M. charantia. Biomedicine & Preventive Nutrition. 2014;4(1):15-21.
• Wu L, Ke L, Huang X, Liu S, Chen H, Rao P. Separation and characterization of the active ingredients of M. charantia L. and their protective and repairing effect on HIT-T15 cells damaged by alloxan in vitro. J Chin Inst Food Sci Tech (Chin). 2006;6(4):24-28.
• Xu X, Shan B, Liao C-H, Xie J-H, Wen P-W, Shi J-Y. Anti-diabetic properties of M. charantia L. polysaccharide in alloxan-induced diabetic mice. International journal of biological macromolecules. 2015;81:538-543.
• Ng T, Wong C, Li W, Yeung H. Insulin-like molecules in M. charantia seeds. Journal of ethnopharmacology. 1986;15(1):107-117.
• Ng T, Wong C, Li W, Yeung H. Isolation and characterization of a galactose binding lectin with insulinomimetic activities: from the seeds of the bitter gourd M. charantia (family Cucurbitaceae). International journal of peptide and protein research. 1986;28(2):163-172.
• Wong C, Ng T, Yeung H. Screening of Trichosanthes kirilowii, M. charantia AND Cucurbit a maxima (family cucurbitaceae) for compounds with antilipolytic activity. Journal of ethnopharmacology. 1985;13(3):313-321.
• Virdi J, Sivakami S, Shahani S, Suthar A, Banavalikar M, Biyani M. Antihyperglycemic effects of three extracts from M. charantia. Journal of ethnopharmacology. 2003;88(1):107-111.
• Kumar GS, Vijayalakshmi B, Salimath P. Effect of bitter gourd and spent turmeric on constituents of glycosaminoglycans in different tissues in streptozotocin induced diabetic rats. Molecular and cellular biochemistry. 2006;286(1-2):53.
• Dong Y, Zhang H. Studies on Components Wıth Antihyperglycemic Effect of M. charantia L. Polysaccharıdes. Acta Nutrimenta Sinica. 1956(01).
• Bin X, Dong Y, Zhang H, Cui H, Qi L. The antihyperglycemic effects of polysaccharide from M. charantia in STZ-induced diabetic mice. Acta Nutrimenta Sinica. 2004(05).
• He X, Liu Z. Study on HTS anti-diabetic antagonists from M. charantia L. Food Science. 2007;28(2):313-316.
• Simpson R, Morris GA. The anti-diabetic potential of polysaccharides extracted from members of the cucurbit family: A review. Bioactive Carbohydrates and Dietary Fibre. 2014;3(2):106-114.
• Ahmed I, Lakhani M, Gillett M, John A, Raza H. Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic M. charantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Research and Clinical Practice. 2001;51(3):155-161.
• Nkambo W, Anyama N, Onegi B. In vivo hypoglycemic effect of methanolic fruit extract of M. charantia L. African health sciences. 2013;13(4):933-939.
• Akhtar MS, Athar MA, Yaqub M. Effect of M. charantia on blood glucose level of normal and alloxan-diabetic rabbits. Planta Medica. 1981;42(07):205-212.
• Leatherdale B, Panesar R, Singh G, Atkins T, Bailey C, Bignell A. Improvement in glucose tolerance due to M. charantia (karela). Br Med J (Clin Res Ed). 1981;282(6279):1823-1824.
• Higashino H, Suzuki A, Tanaka Y, Pootakham K. Hypoglycemic effects of Siamese M. charantia and Phyllanthus urinaria extracts in streptozotocin-induced diabetic rats (the 1st report). Nihon yakurigaku zasshi Folia pharmacologica Japonica. 1992;100(5):415-421.
• Sarkar S, Pranava M, MARITA AR. Demonstration of the hypoglycemic action of M. charantia in a validated animal model of diabetes. Pharmacological Research. 1996;33(1):1-4.
• Day C, Cartwright T, Provost J, Bailey C. Hypoglycaemic effect of M. charantia extracts. Planta medica. 1990;56(05):426-429.
• Chaturvedi P. Antidiabetic potentials of M. charantia: multiple mechanisms behind the effects. Journal of Medicinal Food. 2012;15(2):101-107.
• Chaturvedi P, Akala H. Thyrogenic responses of M. charantia. J Applied Zool Res. 2003;14:191-194.
• Nerurkar PV, Lee YK, Motosue M, Adeli K, Nerurkar VR. M. charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions. British journal of nutrition. 2008;100(4):751-759.
• Singh N, Tyagi S, Agarwal S. Effects of long term feeding of acetone extract of M. charantia (whole fruit powder) on alloxan diabetic albino rats. Ind J Physiol Pharmac. 1989;33(2).
• Ojewole JA, Olayiwola G, Adewole SO. Hypoglycaemic and hypotensive effects of M. charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats: cardiovascular topics. Cardiovascular Journal of South Africa. 2006;17(5):227-232.
• Senanayake GV, Maruyama M, Shibuya K, Sakono M, Fukuda N, Morishita T, Yukizaki C, Kawano M, Ohta H. The effects of bitter melon (M. charantia) on serum and liver triglyceride levels in rats. Journal of ethnopharmacology. 2004;91(2-3):257-262.
• Chaturvedi P. Role of M. charantia in maintaining the normal levels of lipids and glucose in diabetic rats fed a high-fat and low-carbohydrate diet. British journal of biomedical science. 2005;62(3):124-126.
• Offor U, Naidu EC, Ogedengbe OO, Aniekan PI, Azu OO. M. charantia mitigates hepatic injury following adjuvant treatment with antiretroviral drugs in diabetic animal models. Toxicological Research. 2020;36(1):37-44.
• Offor U, Coleridge Stephen Naidu E, Olalekan Ogedengbe O, Isaac Jegede A, Imo Peter A, Azu Onyemaechi O. Renal histopathological and biochemical changes following adjuvant intervention of M. charantia and antiretroviral therapy in diabetic rats. Iranian Journal of Basic Medical Sciences. 2019;22(11):1359-1367.
• Gao H, Wen J-J, Hu J-L, Nie Q-X, Chen H-H, Xiong T, Nie S-P, Xie M-Y. Fermented M. charantia L. juice modulates hyperglycemia, lipid profile, and gut microbiota in type 2 diabetic rats. Food research international. 2019;121:367-378.
• Hartajanie L, Fatimah-Muis S, Heri-Nugroho HS K, Riwanto I, Sulchan M. Probiotics Fermented Bitter Melon Juice as Promising Complementary Agent for Diabetes Type 2: Study on Animal Model. Journal of nutrition and metabolism. 2020;2020.
• Malekshahi H, Bahrami G, Miraghaee S, Ahmadi SA, Sajadimajd S, Hatami R, Mohammadi B, Keshavarzi S. M. charantia reverses type II diabetes in rat. Journal of food biochemistry. 2019;43(11):e13021.
• Welihinda J, Karunanayake E, Sheriff M, Jayasinghe K. Effect of M. charantia on the glucose tolerance in maturity onset diabetes. Journal of Ethnopharmacology. 1986;17(3):277-282.
• França EL, Ribeiro EB, Scherer EF, Cantarini DG, Pessôa RS, França FL, Honorio-França AC. Effects of M. charantia L. on the blood rheological properties in diabetic patients. BioMed research international. 2014;2014.
• Baldwa V, Bhandari C, Pangaria A, Goyal R. Clinical trial in patients with diabetes mellitus of an insulin-like compound obtained from plant source. Upsala journal of medical sciences. 1977;82(1):39-41.
• Srivastava Y, Venkatakrishna‐Bhatt H, Verma Y, Venkaiah K, Raval B. Antidiabetic and adaptogenic properties of M. charantia extract: an experimental and clinical evaluation. Phytotherapy Research. 1993;7(4):285-289.
• Gupta C, Khusro A, Salem AZ. Susceptibility of poultry associated bacterial pathogens to M. charantia fruits and evaluation of in vitro biological properties. Microbial pathogenesis. 2019;132:222-229.
• Cai Y, Liu M, Wu X, Wang Z, Liang C, Yang Y. Study on the antitumor and immune-stimulating activity of polysaccharide from M. charantia. Pharm. Clin Res. 2010;18(2):131-134.
• Zhang L, Zhang M, Huang W, Zhang Y, Zhang R, Wei Z. Optimization on cellulase and ultrasonic wave assisted extraction technology of M. charantia polysaccharides. Nongye Jixie Xuebao= Transactions of the Chinese Society for Agricultural Machinery. 2010;41(11):142-147.
• Panda BC, Mondal S, Devi KSP, Maiti TK, Khatua S, Acharya K, Islam SS. Pectic polysaccharide from the green fruits of M. charantia (Karela): structural characterization and study of immunoenhancing and antioxidant properties. Carbohydrate research. 2015;401:24-31.
• Meera S, Nagarjuna CG. Antistress and immunomodulatory activity of aqueous extract of M. charantia. Pharmacognosy Magazine. 2009;5(19):69.
• Biswas S. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxidative Med Cell Longev 2016: 1–9. In:2016.
• Dandawate PR, Subramaniam D, Padhye SB, Anant S. Bitter melon: a panacea for inflammation and cancer. Chinese journal of natural medicines. 2016;14(2):81-100.
• Chao C-Y, Sung P-J, Wang W-H, Kuo Y-H. Anti-inflammatory effect of M. charantia in sepsis mice. Molecules. 2014;19(8):12777-12788.
• Du Z, Zhang S, Lin Y, Zhou L, Wang Y, Yan G, Zhang M, Wang M, Li J, Tong Q. Momordicoside G regulates macrophage phenotypes to stimulate efficient repair of lung injury and prevent urethane-induced lung carcinoma lesions. Frontiers in pharmacology. 2019;10:321.
• Jones LD, Pangloli P, Krishnan HB, Dia VP. BG-4, a novel bioactive peptide from M. charantia, inhibits lipopolysaccharide-induced inflammation in THP-1 human macrophages. Phytomedicine. 2018;42:226-232.
• İlhan M, Bolat IE, Süntar İ, Köklü HK, Çankal DAU, Keleş H, Akkol EK. Topical application of olive oil macerate of M. charantia L. promotes healing of excisional and incisional wounds in rat buccal mucosa. Archives of oral biology. 2015;60(12):1708-1713.
• Bao B, Chen Y-G, Zhang L, Xu YLN, Wang X, Liu J, Qu W. M. charantia (Bitter Melon) reduces obesity-associated macrophage and mast cell infiltration as well as inflammatory cytokine expression in adipose tissues. PLoS One. 2013;8(12).
• Bai J, Zhu Y, Dong Y. Response of gut microbiota and inflammatory status to bitter melon (M. charantia L.) in high fat diet induced obese rats. Journal of Ethnopharmacology. 2016;194:717-726.
• Bai J, Zhu Y, Dong Y. Obese rats supplemented with bitter melon display marked shifts in the expression of genes controlling inflammatory response and lipid metabolism by RNA-Seq analysis of colonic mucosa. Genes & genomics. 2018;40(6):561-567.
• Raish M, Ahmad A, Ansari MA, Alkharfy KM, Aljenoobi FI, Jan BL, Al-Mohizea AM, Khan A, Ali N. M. charantia polysaccharides ameliorate oxidative stress, inflammation, and apoptosis in ethanol-induced gastritis in mucosa through NF-kB signaling pathway inhibition. International journal of biological macromolecules. 2018;111:193-199.
• Nerurkar PV, Johns LM, Buesa LM, Kipyakwai G, Volper E, Sato R, Shah P, Feher D, Williams PG, Nerurkar VR. M. charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation. Journal of neuroinflammation. 2011;8(1):64.
• Huang W-C, Tsai T-H, Huang C-J, Li Y-Y, Chyuan J-H, Chuang L-T, Tsai P-J. Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro. Food & function. 2015;6(8):2550-2560.
• Nerurkar PV, Orias D, Soares N, Kumar M, Nerurkar VR. M. charantia (bitter melon) modulates adipose tissue inflammasome gene expression and adipose-gut inflammatory cross talk in high-fat diet (HFD)-fed mice. The Journal of nutritional biochemistry. 2019;68:16-32.
• May LS, Sanip Z, Shokri AA, Kadir AA, Lazin MRM. The effects of M. charantia (bitter melon) supplementation in patients with primary knee osteoarthritis: A single-blinded, randomized controlled trial. Complementary therapies in clinical practice. 2018;32:181-186.
• Li J, Wang Y, Huang J, Xu X, Xiang C. Characterization of antioxidant polysaccharides in bitter gourd (M. charantia L.) cultivars. J Food Agric Environ. 2010;8(3&4):117-120.
• Tan H-F, Gan C-Y. Polysaccharide with antioxidant, α-amylase inhibitory and ACE inhibitory activities from M. charantia. International journal of biological macromolecules. 2016;85:487-496.
• Deng Y-Y, Yi Y, Zhang L-F, Zhang R-F, Zhang Y, Wei Z-C, Tang X-J, Zhang M-W. Immunomodulatory activity and partial characterisation of polysaccharides from M. charantia. Molecules. 2014;19(9):13432-13447.
• Liu X, Chen T, Hu Y, Li K, Yan L. Catalytic synthesis and antioxidant activity of sulfated polysaccharide from M. charantia L. Biopolymers. 2014;101(3):210-215.
• Wang Z-J, Xie J-H, Shen M-Y, Tang W, Wang H, Nie S-P, Xie M-Y. Carboxymethylation of polysaccharide from Cyclocarya paliurus and their characterization and antioxidant properties evaluation. Carbohydrate polymers. 2016;136:988-994.
• Xie J-H, Zhang F, Wang Z-J, Shen M-Y, Nie S-P, Xie M-Y. Preparation, characterization and antioxidant activities of acetylated polysaccharides from Cyclocarya paliurus leaves. Carbohydrate Polymers. 2015;133:596-604.
• Kim KB, Lee S, Kang I, Kim J-H. M. charantia ethanol extract attenuates H2O2-induced cell death by its antioxidant and anti-apoptotic properties in human neuroblastoma SK-N-MC cells. Nutrients. 2018;10(10):1368.
• Lin Z-Y, Liu X, Yang F, Yu Y-Q. Structural characterization and identification of five triterpenoid saponins isolated from Momordica cochinchinensis extracts by liquid chromatography/tandem mass spectrometry. International Journal of Mass Spectrometry. 2012;328:43-66.
• Liu C-H, Yen M-H, Tsang S-F, Gan K-H, Hsu H-Y, Lin C-N. Antioxidant triterpenoids from the stems of M. charantia. Food chemistry. 2010;118(3):751-756.
• Padmashree A, Sharma GK, Semwal AD, Bawa AS. Studies on the antioxygenic activity of bitter gourd (M. charantia) and its fractions using various in vitro models. Journal of the Science of Food and Agriculture. 2011;91(4):776-782.
• Kim HY, Sin SM, Lee S, Cho KM, Cho EJ. The butanol fraction of bitter melon (M. charantia) scavenges free radicals and attenuates oxidative stress. Preventive nutrition and food science. 2013;18(1):18.
• Zhou R, Tu N-y, Cong M, Kan G-s, Ren D-m, Chen H-m. Purification and hepatoprotective effect of Momordica polysaccharides. Food Science and Technology. 2013;2.
• Salehi B, Zucca P, Sharifi‐Rad M, Pezzani R, Rajabi S, Setzer WN, Varoni EM, Iriti M, Kobarfard F, Sharifi‐Rad J. Phytotherapeutics in cancer invasion and metastasis. Phytotherapy Research. 2018;32(8):1425-1449.
• Nerurkar P, Ray RB. Bitter melon: antagonist to cancer. Pharmaceutical research. 2010;27(6):1049-1053.
• Farooqi AA, Khalid S, Tahir F, Sabitaliyevich UY, Yaylim I, Attar R, Xu B. Bitter gourd (M. charantia) as a rich source of bioactive components to combat cancer naturally: Are we on the right track to fully unlock its potential as inhibitor of deregulated signaling pathways. Food and Chemical Toxicology. 2018;119:98-105.
• Huang X, Nie S. The structure of mushroom polysaccharides and their beneficial role in health. Food & function. 2015;6(10):3205-3217.
• Wu J, Zhou J, Lang Y, Yao L, Xu H, Shi H, Xu S. A polysaccharide from Armillaria mellea exhibits strong in vitro anticancer activity via apoptosis-involved mechanisms. International journal of biological macromolecules. 2012;51(4):663-667.
• LI Z-t, ZHANG J, XIE J, SUN R-g. The inhibition effect of two different M. charantia polysaccharides on the proliferation of human leukemia cell in vitro. Journal of Shaanxi Normal University (Natural Science Edition). 2013;2.
• Guan L. Synthesis and anti-tumour activities of sulphated polysaccharide obtained from M. charantia. Natural product research. 2012;26(14):1303-1309.
• Yue J, Sun Y, Xu J, Cao J, Chen G, Zhang H, Zhang X, Zhao Y. Cucurbitane triterpenoids from the fruit of M. charantia L. and their anti-hepatic fibrosis and anti-hepatoma activities. Phytochemistry. 2019;157:21-27.
• Somasagara RR, Deep G, Shrotriya S, Patel M, Agarwal C, Agarwal R. Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells. International journal of oncology. 2015;46(4):1849-1857.
• Dhar D, Deep G, Kumar S, Wempe MF, Raina K, Agarwal C, Agarwal R. Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells. Molecular carcinogenesis. 2018;57(9):1166-1180.
• Wang Y-X, Jacob J, Wingfield PT, Palmer I, Stahl SJ, Kaufman JD, Huang PL, Huang PL, Lee-Huang S, Torchia DA. Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and β-sheet topology with the A chain of ricin, a type-II RIP. Protein Science. 2000;9(1):138-144.
• Ping-ping Z, Jin-fu L, Chang-lu W, Yan-ting Y, Jin-hai X. Study on the Antimicrobial Activities of the Extracts from M. charantia L. Natural Product Research & Development. 2008;20(4).
• Fang EF, Zhang CZY, Fong WP, Ng TB. RNase MC2: a new M. charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways. Apoptosis. 2012;17(4):377-387.
• Fang EF, Zhang CZY, Ng TB, Wong JH, Pan WL, Ye XJ, Chan YS, Fong WP. M. charantia lectin, a type II ribosome inactivating protein, exhibits antitumor activity toward human nasopharyngeal carcinoma cells in vitro and in vivo. Cancer Prevention Research. 2012;5(1):109-121.
• Pitchakarn P, Suzuki S, Ogawa K, Pompimon W, Takahashi S, Asamoto M, Limtrakul P, Shirai T. Kuguacin J, a triterpeniod from M. charantia leaf, modulates the progression of androgen-independent human prostate cancer cell line, PC3. Food and chemical toxicology. 2012;50(3-4):840-847.
• Shim SH, Sur S, Steele R, Albert CJ, Huang C, Ford DA, Ray RB. Disrupting cholesterol esterification by bitter melon suppresses triple‐negative breast cancer cell growth. Molecular carcinogenesis. 2018;57(11):1599-1607.
• Duan Z-Z, Zhou X-L, Li Y-H, Zhang F, Li F-Y, Su-Hua Q. Protection of M. charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway. Journal of Receptors and Signal Transduction. 2015;35(6):523-529.
• Gong J, Sun F, Li Y, Zhou X, Duan Z, Duan F, Zhao L, Chen H, Qi S, Shen J. M. charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway. Neuropharmacology. 2015;91:123-134.
• Perveen H, Dey A, Nilavar NM, Chandra GK, Islam SS, Chattopadhyay S. Dietary CCPS from bitter gourd attenuates sodium arsenite induced female reproductive ailments cum infertility in wistar rats: anti-inflammatory and anti-apoptotic role. Food and Chemical Toxicology. 2019;131:110545.
• Hulin A, Wavelet M, Desbordes J. Intoxication aiguë par M. charantia (Sorrossi)(à propos de deux cas). Médecine d'Afrique Noire. 1988;35(9):671-674.
• Tennekoon KH, Jeevathayaparan S, Angunawala P, Karunanayake EH, Jayasinghe K. Effect of M. charantia on key hepatic enzymes. Journal of ethnopharmacology. 1994;44(2):93-97.
• Dutta P, Chakravarty A, Chowdhury U, Pakrashi S. Studies on Indian Medicinal-Plants. 64. Vicine, A Favism-Inducing Toxin From Momordica-Charantia Linn Seeds. Indian Journal of Chemistry Section B-Organic Chemistry Including Medicinal Chemistry. 1981;20(8):669-671.
• Aguwa C, Mittal G. Abortifacient effects of the roots of Momordica angustisepala. Journal of ethnopharmacology. 1983;7(2):169-173.
• Chan W, Tam P, Yeung H. The termination of early pregnancy in the mouse by β-momorcharin. Contraception. 1984;29(1):91-100.
• Leung S, Yeung H, Leung K. The immunosuppressive activities of two abortifacient proteins isolated from the seeds of bitter melon (M. charantia). Immunopharmacology. 1987;13(3):159-171.
• Stepka W, Wilson K, Madge G. Antifertility investigation on Momordica. Lloydia. 1974;37(4):645c.
• Dixit V, Khanna P, Bhargava S. Effects of M. charantia L. fruit extract on the testicular function of dog. Planta medica. 1978;34(07):280-286.
• Schreiber CA, Wan L, Sun Y, Lu L, Krey LC, Lee-Huang S. The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1. Fertility and sterility. 1999;72(4):686-690.
• Khan MF, Abutaha N, Nasr FA, Alqahtani AS, Noman OM, Wadaan MA. Bitter gourd (M. charantia) possess developmental toxicity as revealed by screening the seeds and fruit extracts in zebrafish embryos. BMC complementary and alternative medicine. 2019;19(1):1-13.
• Beniwal P, Gaur N, Singh S, Raveendran N, Malhotra V. How harmful can herbal remedies be? A case of severe acute tubulointerstitial nephritis. Indian journal of nephrology. 2017;27(6):459.
• Mardani S, Nasri H, Hajian S, Ahmadi A, Kazemi R, Rafieian-Kopaei M. Impact of M. charantia extract on kidney function and structure in mice. Journal of nephropathology. 2014;3(1):35.
• Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine. 1995;2(2):137-189.
• Aslam M, Stockley I. Interaction between curry ingredient (karela) and drug (chlorpropamide). The Lancet. 1979;313(8116):607.
• Akter S, Goto A, Mizoue T. Smoking and the risk of type 2 diabetes in Japan: a systematic review and meta-analysis. Journal of epidemiology. 2017;27(12):553-561.