Berbamine ameliorates isoproterenol‐induced myocardial infarction by inhibiting mitochondrial dysfunction and apoptosis in rats

Abstract

Berbamine (BBM), a bisbenzylisoquinoline alkaloid from roots, bark, and stem of Berberis plant such as Berberis aristata has a wide range of pharmacological activities. However, the evidence for the cardioprotective effect of BBM is inadequate and the molecular mechanism of BBM remains unclear. This study investigated the underlying molecular mechanism of BBM-mediated cardioprotection on isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. The assays of mitochondria antioxidant status, mitochondrial marker enzymes, and electron microscopic analysis of mitochondria revealed BBM significantly prevented the mitochondrial dysfunction induced by ISO. The ISO-induced elevation of mitochondrial oxidative stress was also curbed by BBM. Furthermore, pretreatment with BBM protected the heart tissue from ISO-induced apoptosis as evident from decreased terminal dUTP nickendlabeling positive cells and decreased expression of Bax, cytochrome c, cleaved caspase-9, and caspase-3, and poly (ADP-ribose) polymerase and increased expression of Bcl-2 in ISO-induced rats. These current findings suggest that BBM exerts a significant cardioprotective effect on ISO-induced myocardial infarction in rats. K E Y W O R D Sapoptosis, berbamine, isoproterenol, mitochondria, myocardial infarction J Cell Biochem. 2019;120:3101-3113.wileyonlinelibrary.com/journal/jcb

Protective Effect of Geraniol on Oxidative, Inflammatory and Apoptotic Alterations in Isoproterenol-Induced Cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR Pathways

“…The ISO-induced MI group showed numerous ECG alterations, presence of an infarct area, increase in the levels of cardiac enzymes, moderate-to-severe myocardial necrosis, edema, and extensive immune cells infiltration. It has been previously reported that ISO causes detrimental cardiac effects, including necrosis, apoptosis, mitochondrial modifications, oxidative injury, and inflammatory cell infiltration, comparable to what is observed in the ischemic human heart [ 8 , 23 , 25 , 26 ]. Compared to ISO-challenged animals, geraniol pretreatment led to a size reduction of the infarct region, attenuation of cardiac indicator enzymes, as well as diminished myocardial necrosis, edema, and immune cells infiltration.…”

“…In the current study, challenge with ISO caused the depletion of GSH, reduction of mitochondrial antioxidant enzymes activities, and increase of Keap1 levels, and it decreased Nrf2 and HO-1 mRNA and protein expressions levels, which is indicative of oxidative stress. Former studies demonstrated that ISO administration reduces the activity of mitochondrial antioxidant enzymes leading to cardiac contractile dysfunction and cardiotoxicity, finally resulting in myocardial necrosis [ 23 ]. In contrast, geraniol reduced Keap1 expression and increased the nuclear accumulation of Nrf2, which is associated with higher expression levels of HO-1, GSH, and mitochondrial antioxidant enzymes.…”

“…Mitochondria were isolated from the experimental animals’ heart tissues as previously described [ 23 ]. In brief, heart tissues were homogenized in ice-cold 50 mM Tris-Hcl containing 0.25 M sucrose (pH 7.4), and then centrifuged for 20 min at 700× g .…”

“…Western blot analysis to assess protein expression was performed as previously described [ 23 ]. Frozen hearts were mixed in RIPA buffer (with protease inhibitor), centrifuged (10,000 rpm, 8 min, 4 °C), and then the supernatant was assessed using a NanoDropLite spectrophotometer (Thermo Fisher Scientific, Austin, TX, USA) to determine the amount of protein.…”

Bisbenzylisoquinoline alkaloids of lotus ( Nelumbo nucifera Gaertn.) seed embryo inhibit lipopolysaccharide-induced macrophage activation via suppression of Ca 2+ -CaM/CaMKII pathway

“…Lotus seeds embryo mainly contains three structurally related bisbenzylisoquinoline alkaloids, including Neferine, Liensinine and Isoliensinine (chemical structures shown in Table 2; Sharma, Gautam, Adhikari, & Karki, 2017). Studies have documented that these three alkaloids exhibit a wide range of biological and pharmacological activities, such as cardiovascular protection (Saranya, Baskaran, Poornima, & Vijaya Padma, 2019;Yang et al, 2018), anticarcinogenesis (Yu, Liu, Chen, Li, & Li, 2018), neuroprotection (Cometa et al, 2012;Jung et al, 2010), antioxidation (Qian, 2002), and anti-inflammatory effects (Meng et al, 2017;Wu et al, 2018).…”