Syringic acid inhibits apoptosis pathways via downregulation of p38MAPK and JNK signaling pathways in H9c2 cardiomyocytes following hypoxia/reoxygenation injury

Abstract

Syringic acid (SA), a naturally occur-ring O‑methy-lated trihydroxybenzoic acid monomer extracted from Dendrobium nobile Lindl., has been demonstrated to attenuate renal ischemia‑reperfusion (I/R) injury. However, the role of SA in myocardial I/R injury is unclear. The present study aimed to clarify the cardioprotective effect of SA in myocardial I/R injury in vitro and explore the potential molecular mechanisms. In the present study, it was revealed that pretreatment with SA increased the viability and inhibited oxidant stress in H9c2 cardiomyocytes that had suffered hypoxia/reoxygenation (H/R). SA also markedly downregulated B‑cell lymphoma 2 (Bcl‑2) expression and inhibited the expression of Bcl‑2‑like protein 4 (Bax) and cleaved caspase‑3 in H9c2 cardiomyocytes induced by H/R. In addition, SA significantly alleviated H/R-induced the phosphorylation of p38 mitogen‑activated protein kinase (p38MAPK) and c‑Jun N‑terminal kinase (JNK) in H9c2 cardiomyocytes. In conclusion, the present study demonstrated that SA inhibits the apoptosis of H9c2 cardiomyocytes following H/R injury via reduced activation of the p38MAPK and JNK signaling pathways. The results support the therapeutic usage of SA in the treatment of myocardial infarction.

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

“…24 In the current study, the activation of JNK and p38MAPK signaling was also observed to be enhanced by hypoxia, as the phosphorylation levels of JNK and p38MAPK were significantly upregulated by hypoxia as compared to normoxia (both P < .001, Figure 2A,B). And the enhanced activation of these two signalings participates in the progression of myocardial ischemia.…”

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

“…Betulinic acid protects H9c2 cells from MI/RI by inhibiting oxidative stress and apoptosis, and the Nrf2/HO-1, JNK, and p38 pathways are involved in mediating these protective effects [ 264 ]. Syringic acid, a natural O-methylated trihydroxybenzoic acid monomer that is extracted from Dendrobium nobile Lindl., protects H9c2 cardiomyocytes from H/R-induced apoptotic injury via inhibiting the activation of the p38 MAPK and JNK signaling pathways [ 265 ]. Injection of snakegourd peel, a traditional Chinese herbal medicine, inhibits the apoptosis of myocardial cells by reducing intracellular Ca 2+ overload, inhibiting the activation of caspase-3, and downregulating the phosphorylated JNK (p-JNK) and p38 MAPK (p-p38 MAPK) protein expression [ 266 ].…”

Effect of Syringic acid on antioxidant biomarkers and associated inflammatory markers in mice model of asthma

“…Syringic acid (4-Hydroxy-3,5-dimethoxybenzoic acid) is a naturally occurring phenolic compound mainly found in fruits of edible plants and mushrooms (Itoh et al, 2009;Pacheco-Palencia, Mertens-Talcott, & Talcott, 2008). It has wide range of pharmaceutical applications including antioxidant (Gao et al, 2018;Wang et al, 2016;Zhou et al, 2017), anti-diabetic (Muthukumaran, Srinivasan, Venkatesan, Ramachandran, & Muruganantham, 2013), hepatoprotective (Itoh et al, 2009;Itoh et al, 2010;Yan, Wang, Yen, Lee, & Yin, 2016), antihyperlipidemic (Ramachandran, 2010), cardioprotective (Ding et al, 2017;Rasheeda, Bharathy, & NishadFathima, 2018), neuroprotective (Rasheeda et al, 2018;Tokmak et al, 2017), and anti-inflammatory properties (Ham et al, 2016;Lee et al, 2012). Syringic acid extracted from Herba dendrobii has potential inhibiting activity on aldose reductase and its gene expression and thereby suppresses the diabetic cataract in eye lenses of rat model (Wei et al, 2012).…”