Rizq Akaber T, Sirwi Alaa, El-Agamy Dina S, Abdallah Hossam M, Ibrahim Sabrin R M, Mohamed Gamal A
Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Biology (Basel). 2023 Jun 30;12(7):938. doi: 10.3390/biology12070938.
Cepabiflas B and C (CBs) are flavonoid dimers separated from . They demonstrated antioxidant and α-glucosidase and protein tyrosine phosphatase 1B inhibition capacities. However, their anti-inflammatory activities and their effects on endotoxemia are unknown. The current study aimed at exploring the protective activities of CBs on lipopolysaccharide (LPS)-induced kidney and liver damage in mice and investigating the possible molecular mechanisms. Mice were orally treated with a low (40 mg/kg) or high (60 mg/kg) dose of CBs for five days prior to a single intraperitoneal injection of LPS (10 mg/kg). Samples of serum and hepatic and kidney tissues were collected 24 h after the LPS challenge. Changes in serum indices of hepatic and renal injury, pathological changes, molecular biological parameters, and proteins/genes related to inflammation and apoptosis of these organs were estimated. LPS injection resulted in deleterious injury to both organs as indicated by elevation of serum ALT, AST, creatinine, and BUN. The deteriorated histopathology of hepatic and renal tissues confirmed the biochemical indices. CBs treated groups showed a reduction in these parameters and improved histopathological injurious effects of LPS. LPS-induced hepatorenal injury was linked to elevated oxidative stress as indicated by high levels of MDA, 4-HNE, as well as repressed antioxidants (TAC, SOD, and GSH) in hepatic and kidney tissues. This was accompanied with suppressed Nrf2/HO-1 activity. Additionally, there was a remarkable inflammatory response in both organs as NF-κB signalling was activated and high levels of downstream cytokines were produced following the LPS challenge. Apoptotic changes were observed as the level and gene expression of Bax and caspase-3 were elevated along with declined level and gene expression of Bcl2. Interestingly, CBs reversed all these molecular and genetic changes and restricted oxidative inflammatory and apoptotic parameters after LPS-injection. Collectedly, our findings suggested the marked anti-inflammatory and anti-apoptotic activity of CBs which encouraged its use as a new candidate for septic patients.
Cepabiflas B和C（CBs）是从……中分离出的黄酮类二聚体。它们具有抗氧化、α-葡萄糖苷酶抑制和蛋白酪氨酸磷酸酶1B抑制能力。然而，它们的抗炎活性及其对内毒素血症的影响尚不清楚。本研究旨在探讨CBs对脂多糖（LPS）诱导的小鼠肾和肝损伤的保护作用，并研究其可能的分子机制。在单次腹腔注射LPS（10 mg/kg）前5天，给小鼠口服低剂量（40 mg/kg）或高剂量（60 mg/kg）的CBs。在LPS攻击后24小时收集血清、肝和肾组织样本。评估肝和肾损伤的血清指标变化、病理变化、分子生物学参数以及与这些器官炎症和凋亡相关的蛋白质/基因。LPS注射导致两个器官出现有害损伤，血清谷丙转氨酶、谷草转氨酶、肌酐和尿素氮升高表明了这一点。肝和肾组织恶化的组织病理学证实了生化指标。CBs治疗组这些参数有所降低，LPS的组织病理学损伤作用得到改善。LPS诱导的肝肾损伤与氧化应激升高有关，肝和肾组织中丙二醛、4-羟基壬烯醛水平升高以及抗氧化剂（总抗氧化能力、超氧化物歧化酶和谷胱甘肽）受到抑制表明了这一点。这伴随着Nrf2/HO-1活性的抑制。此外，LPS攻击后，两个器官均出现明显的炎症反应，因为NF-κB信号被激活，下游细胞因子水平升高。观察到凋亡变化，因为Bax和caspase-3的水平和基因表达升高，同时Bcl2的水平和基因表达下降。有趣的是，CBs逆转了所有这些分子和基因变化，并限制了LPS注射后的氧化、炎症和凋亡参数。总体而言，我们的研究结果表明CBs具有显著的抗炎和抗凋亡活性，这促使其成为脓毒症患者的新候选药物。
