Komeili-Movahhed Tahereh, Heidari Fatemeh, Moslehi Azam
Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Physiol Int. 2023 Mar 6;110(1):19-33. doi: 10.1556/2060.2023.00132. Print 2023 Mar 10.
Chlorogenic acid (CA) is a polyphenolic compound, found in many herbs and foods including coffee, berries and potatoes. Anti-inflammatory, anti-oxidant, anti-cancer and anti-apoptotic effects of CA have been proven in many tissues. Testicular inflammation and apoptosis are essential factors in male infertility that could result from endoplasmic reticulum (ER) stress. ER stress leads to unfolding and misfolding of nascent proteins and thereby provokes cellular inflammatory and apoptotic pathways. This study was designed to assess the effects of CA on ER stress-induced testis inflammation and apoptosis.
To do this, male mice were divided into six groups. The control, vehicle and CA groups received saline, DMSO and 50 mg kg-1 CA. Tunicamycin (TM (was injected to induce ER stress (TM group). In the CA20-TM and CA50-TM groups, 20 mg kg-1 CA and 50 mg kg-1 CA were administered one hour before TM injection. After thirty hours, animals were sacrificed and testes were removed. Hematoxylin & eosin staining, ELISA assay and real-time PCR were performed.
CA administration significantly downregulated gene expression of TNFα, IL6, P53, Bax/Bcl2 ratio and caspase3. It also reduced testis levels of ALP, NF-κB, TNFα and caspse3. Finally, CA relieved structural changes in seminiferous tubules.
This study demonstrated that the positive effects of CA on the attenuation of ER-stress induced inflammation and apoptosis might be due to the inhibition of NF-κB and thereby suppression of inflammatory and apoptotic pathways.
绿原酸(CA)是一种多酚类化合物,存在于许多草药和食物中,包括咖啡、浆果和土豆。CA的抗炎、抗氧化、抗癌和抗凋亡作用已在许多组织中得到证实。睾丸炎症和凋亡是男性不育的重要因素,可能由内质网(ER)应激引起。ER应激导致新生蛋白质的展开和错误折叠,从而引发细胞炎症和凋亡途径。本研究旨在评估CA对内质网应激诱导的睾丸炎症和凋亡的影响。
为此,将雄性小鼠分为六组。对照组、溶剂组和CA组分别接受生理盐水、二甲基亚砜(DMSO)和50 mg/kg CA。注射衣霉素(TM)以诱导内质网应激(TM组)。在CA20-TM组和CA50-TM组中,在注射TM前1小时给予20 mg/kg CA和50 mg/kg CA。30小时后,处死动物并取出睾丸。进行苏木精和伊红染色、酶联免疫吸附测定(ELISA)和实时聚合酶链反应(PCR)。
给予CA可显著下调肿瘤坏死因子α(TNFα)、白细胞介素6(IL6)、P53、Bax/Bcl2比值和半胱天冬酶3(caspase3)的基因表达。它还降低了睾丸中碱性磷酸酶(ALP)、核因子κB(NF-κB)、TNFα和caspase3的水平。最后,CA减轻了生精小管的结构变化。
本研究表明,CA对内质网应激诱导的炎症和凋亡的减轻具有积极作用,可能是由于抑制了NF-κB,从而抑制了炎症和凋亡途径。