Gymnema inodorum Leaf Extract Improves Cardiac Function in Experimental Mice Infected with Plasmodium Berghei.

Malaria-associated cardiac injury has been reported to be the primary cause of death due to severe malaria. The discovery of substances showing a protective effect on cardiac injury during malaria infection is urgently needed. Hence, the purpose of this study was to evaluate the efficacy of Gymnema inodorum leaf extract (GIE) on cardiac function in mice infected with Plasmodium berghei. ICR mice were treated with 1 × 107 infected red blood cells of P. berghei ANKA (PbANKA), administered orally with GIE in 100, 250 and 500 mg/kg body weight of mice. Creatine phosphokinase (CPK) and echocardiography were carried out. It was found that CPK and heart-weight to body-weight (HW/BW) ratios were significantly higher in untreated mice than the healthy control. Moreover, impaired cardiac function in the untreated group was observed as indicated by changes in echocardiography. Interestingly, GIE exerted a protective effect on cardiac injury induced by PbANKA infection. Our results demonstrated that the parasitemia percentage, CPK, HW/BW ratio, and echocardiography in GIE treated mice were improved. However, there was no significant difference between GIE dosages. Therefore, GIE possessed a cardio-protective effect during malaria infection in mice.

Suppression of cardiomyocyte functions by ß-CTX isolated from the Thai king cobra (Ophiophagus hannah) venom via an alternative method

Beta-cardiotoxin (ß-CTX), the three-finger toxin isolated from king cobra (Ophiophagus hannah) venom, possesses ß-blocker activity as indicated by its negative chronotropy and its binding property to both ß-1 and ß-2 adrenergic receptors and has been proposed as a novel ß-blocker candidate. Previously, ß-CTX was isolated and purified by FPLC. Here, we present an alternative method to purify this toxin. In addition, we tested its cytotoxicity against different mammalian muscle cell types and determined the impact on cardiac function in isolated cardiac myocyte so as to provide insights into the pharmacological action of this protein. Methods: ß-CTX was isolated from the crude venom of the Thai king cobra using reverse-phased and cation exchange HPLC. In vitro cellular viability MTT assays were performed on mouse myoblast (C2C12), rat smooth muscle (A7r5), and rat cardiac myoblast (H9c2) cells. Cell shortening and calcium transient dynamics were recorded on isolated rat cardiac myocytes over a range of ß-CTX concentration. Results: Purified ß-CTX was recovered from crude venom (0.53% w/w). MTT assays revealed 50% cytotoxicity on A7r5 cells at 9.41 ± 1.14 µM (n = 3), but no cytotoxicity on C2C12 and H9c2 cells up to 114.09 µM. ß-CTX suppressed the extend of rat cardiac cell shortening in a dose-dependent manner; the half-maximal inhibition concentration was 95.97 ± 50.10 nM (n = 3). In addition, the rates of cell shortening and re-lengthening were decreased in ß-CTX treated myocytes concomitant with a prolongation of the intracellular calcium transient decay, indicating depression of cardiac contractility secondary to altered cardiac calcium homeostasis. Conclusion: We present an alternative purification method for ß-CTX from king cobra venom. We reveal cytotoxicity towards smooth muscle and depression of cardiac contractility by this protein. These data are useful to aid future development of pharmacological agents derived from ß-CTX.(AU)