Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium.
Objective: A rat model is here used to test a hypothesis thatMomordica charantia(Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease.Methods: Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin-water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup.Results: Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio-an outcome associated with decreased risk of atherosclerotic disease.Conclusions: BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases.
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. czompa.attila@pharm.unideb.hu.
Attila
A
Czompa
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. gyongyosi.alexandra@pharm.unideb.hu.
Alexandra
A
Gyongyosi
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. szoke.kitti@pharm.unideb.hu.
Kitti
K
Szoke
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. bak.istvan@pharm.unideb.hu.
Istvan
I
Bak
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. csepanyi.evelin@pharm.unideb.hu.
Evelin
E
Csepanyi
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. donald.david.haines@pharm.unideb.hu.
David D
DD
Haines
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. tosaki.arpad@pharm.unideb.hu.
Arpad
A
Tosaki
Faculty of Pharmacy, Department of Pharmacology, University of Debrecen, Debrecen 4032, Hungary. lekli.istvan@pharm.unideb.hu.
Istvan
I
Lekli
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests / Q000187:drug effects; D008297:Male; D029777:Momordica charantia / Q000737:chemistry*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker
D010936:Plant Extracts; C505410:Casp3 protein, rat; D053148:Caspase 3
bitter melon; diabetes; ischemia