Ghorbanpour Atefeh, Salari Sepide, Baluchnejadmojarad Tourandokht, Roghani Mehrdad
School of Medicine, Shahed University, Tehran, Iran.
Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Heliyon. 2023 Mar 1;9(3):e14205. doi: 10.1016/j.heliyon.2023.e14205. eCollection 2023 Mar.
Capsaicin is the main pungent bioactive constituent in red chili with promising therapeutic properties due to its anti-oxidative and anti-inflammatory effects. No evidence exists on the beneficial effect of capsaicin on apoptosis and mitochondrial function in acute liver injury (ALI) under septic conditions. For inducing septic ALI, lipopolysaccharide (LPS, 50 μg/kg) and d-galactose (D-Gal, 400 mg/kg) was intraperitoneally injected and capsaicin was given orally at 5 or 20 mg/kg. Functional markers of liver function and mitochondrial dysfunction were determined as well as hepatic assessment of apoptotic, oxidative, and inflammatory factors. Capsaicin at the higher dose appropriately decreased serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in addition to reducing hepatic level of malondialdehyde (MDA), reactive oxygen species (ROS), nitrite, NF-kB, TLR4, IL-1β, TNF-α, caspase 3, DNA fragmentation and boosting sirtuin 1, Nrf2, superoxide dismutase (SOD) activity, and heme oxygenase (HO-1). These beneficial effects of capsaicin were associated with reversal and/or improvement of gene expression for pro-apoptotic Bax, anti-apoptotic Bcl2, mitochondrial and metabolic regulators PGC-1α, sirtuin 1, and AMPK, and inflammation-associated factors. Additionally, capsaicin exerted a hepatoprotective effect, as revealed by its reduction of liver histopathological changes. These findings evidently indicate hepatoprotective property of capsaicin under septic conditions that can be attributed to its down-regulation of oxidative and inflammatory processes besides its potential to attenuate mitochondrial dysfunction and apoptosis.
辣椒素是红辣椒中的主要辛辣生物活性成分，因其抗氧化和抗炎作用而具有潜在的治疗特性。目前尚无证据表明辣椒素对脓毒症条件下急性肝损伤（ALI）的细胞凋亡和线粒体功能有有益影响。为诱导脓毒症ALI，腹腔注射脂多糖（LPS，50μg/kg）和d-半乳糖（D-Gal，400mg/kg），并以5或20mg/kg的剂量口服辣椒素。测定肝功能和线粒体功能障碍的功能标志物以及肝脏细胞凋亡、氧化和炎症因子的评估。高剂量辣椒素除了降低肝丙二醛（MDA）、活性氧（ROS）、亚硝酸盐、NF-κB、TLR4、IL-1β、TNF-α、caspase 3水平和DNA片段化外，还适当降低了血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平，并提高了沉默调节蛋白1、Nrf2、超氧化物歧化酶（SOD）活性和血红素加氧酶（HO-1）水平。辣椒素的这些有益作用与促凋亡蛋白Bax、抗凋亡蛋白Bcl2、线粒体和代谢调节因子PGC-1α、沉默调节蛋白1和AMPK以及炎症相关因子的基因表达的逆转和/或改善有关。此外，辣椒素具有肝脏保护作用，这可通过其减轻肝脏组织病理学变化得以体现。这些发现明显表明，脓毒症条件下辣椒素具有肝脏保护特性，这可归因于其下调氧化和炎症过程，以及减轻线粒体功能障碍和细胞凋亡的潜力。
