Aleksandar Jovanovic,  Professor of Clinical Pharmacology and Therapeutics has recently published the following three articles:

Zhang X, Lu Z, Abdul KSM, Ma C, Tan KS, Jovanovic A, Tan W. 2020. Isosteviol sodium protects heart embryonic H9c2 cells against oxidative stress by activating Akt/GSK-3β signaling pathway. Pharmazie 75: 36-40.

Link: https://www.ingentaconnect.com/contentone/govi/pharmaz/2020/00000075/00000001/art00008

Abstract:

Oxidative stress plays a crucial role in pathogenesis of various cardiovascular diseases. Recent studies reported that isosteviol sodium (STVNa) harbor cardioprotective properties. Here, we explore the potential cardioprotective effect of STVNa on H2 O2 -induced oxidative stress on heart embryonic H9c2 cardiomyocytes and the underlying mechanism. We have found that STVNa pretreatment improved cell viability, nuclear morphology and prevented LDH release induced by oxidative stress. STVNa pretreatment also reduced production of reactive oxygen species, preserved mitochondrial function, restored biological antioxidant defense systems and prevented cell death. Western blotting analysis revealed that STVNa regulated the mitochondrial related pro- and anti-apoptotic protein (Bax and Bcl-2 respectively) levels, increased phosphorylation of Akt (ser473) and GSK-3β (ser9) and promoted binding between HK-II and mitochondria under the normal or oxidative stress conditions. LY294002, a PI3K inhibitor, abolished cytoprotective effects of STVNa by inhibiting activation of Akt and GSK-3β. Based on these findings, we conclude that STVNa protects H9c2 cells against oxidative stress by activating Akt/GSK-3β signaling pathway, which, in turn, leads to recruitment of HK-II to mitochondria and regulating Bcl2/Bax levels.

Du Q, Jovanovic S, Tulic L, Tulic I, Jovanovic A. 2019. Pregnancy-induced hypertension is associated with down-regulation of Kir6.1 in human myometrium. Pregnancy Hypertens. 18: 96-98.

Abstract:

It is generally accepted that activity of K+ channels maintain resting membrane potential and uterine quiescence during pregnancy, which is, at least in part, mediated by down-regulation of ATP-sensitive K+ (KATP) channels. Pregnancy-induced hypertension (PIH) is associated with pre-term and late pre-term labour. Here, we have used real time RT-PCR to compare mRNA levels of KATP channel subunits in PIH parturient and control parturient. We have found that Kir6.1, a pore forming, myometrial KATP channel subunit is down-regulated in PIH patients. This could perfectly explain increased rate of pre-term labour in patients suffering from PIH.

Chen Y, Beng H, Su H, Han F, Fan Z, Lv N, Jovanovic A, Tan W. 2019. Isosteviol prevents the development of isoprenaline-induced myocardial hypertrophy. Int. J. Mol. Med. 44: 1932-1942.

 Link: https://www.spandidos-publications.com/10.3892/ijmm.2019.4342

 Abstract:

Isosteviol sodium (STVNa), which is a derivate of the natural sweet‑tasting glycoside stevioside, has recently been developed and it has been determined that this compound exhibits neuro‑ and cardio‑protective properties. In the current study, whether STVNa interferes with the development of cardiac hypertrophy, which is induced by isoprenaline (Iso), was investigated in an experimental rat model. Rats were treated with a vehicle (0.9% NaCl; control), isoprenaline (Iso; 5 mg/kg) or Iso (5 mg/kg) with STVNa (4 mg/kg; Iso + STVNa). Cardiomyocytes were isolated using enzymatic dissociation and were treated with 5 µM Iso for 24 h and co‑treated with 5 µM STVNa. Brain natriuretic peptide (BNP) mRNA expression was determined using PCR analysis. Cell surface area, intracellular reactive oxygen species (ROS), mitochondrial transmembrane potential (ΔΨm), cytoplasmic Ca2+ and Ca2+ and contractile function were examined using a laser scanning confocal microscope. The current study demonstrated that STVNa inhibited Iso‑induced cardiac hypertrophy by inhibiting cardiomyocyte size. STVNa significantly reduced cell surface area and decreased BNP mRNA expression in ventricular cardiomyocyte Iso‑induced hypertrophy. STVNa was also revealed to restore ΔΨm and reduce ROS generation and intracellular Ca2+ concentration when compared with the Iso‑treated group. Additionally, STVNa preserved Ca2+ transients in hypertrophic cardiomyocytes. In conclusion, the present study demonstrated that STVNa protects against Iso‑induced myocardial hypertrophy by reducing oxidative stress, restoring ΔΨm and maintaining Ca2+ homeostasis.