Chen Peng, Lei Jiexin, Chen Fuchao, Zhou Benhong
Department of Pharmacy, Renmin Hospital of Wuhan University Wuhan Hubei 430060 P. R. China
Department of Endocrinology, Renmin Hospital of Wuhan University Wuhan Hubei 430060 P. R. China.
RSC Adv. 2020 Feb 24;10(14):8027-8038. doi: 10.1039/d0ra00774a.
Urolithin A, a metabolite produced by human colon microflora from ellagic acid and related compounds, has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The present study investigates the protective effects of urolithin A (Uro A) on d-galactose (d-gal)-induced liver and kidney injury and the possible mechanisms in mice. In this study, we first investigated the antioxidant ability of Uro A . Then mice were treated with d-gal subcutaneously (150 mg kg d), followed by Uro A at different dosages (50, 100, 150 mg kg d, administered orally) for 8 weeks. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine (Cr) in the serum were tested. Histopathological features were assessed by hematoxylin and eosin (HE) staining followed by an assessment of the antioxidant and anti-inflammatory activities. Furthermore, we also evaluated the expression levels of the genes Bax, Bcl-2 and cleaved caspase-3 in the liver and kidney. The results showed that Uro A treatment obviously attenuated d-gal-induced liver and kidney damage. The beneficial effects of Uro A were accompanied by a decline in malondialdehyde (MDA) levels and a rise in the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) activity in the liver and kidney and downregulation of the levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), in serum. Moreover, Uro A could modulate the expression of Bax, Bcl-2 and cleaved caspase-3 in the livers and kidneys of aging mice. These findings suggested that Uro A ameliorated d-gal-induced liver and kidney injury through attenuating oxidative stress, inflammatory responses and apoptosis.
尿石素A是人体结肠微生物群从鞣花酸及相关化合物产生的一种代谢产物，据报道具有抗氧化、抗炎和抗凋亡特性。本研究探讨尿石素A（Uro A）对d-半乳糖（d-gal）诱导的小鼠肝肾损伤的保护作用及其可能机制。在本研究中，我们首先研究了Uro A的抗氧化能力。然后，小鼠皮下注射d-半乳糖（150 mg/kg），随后口服不同剂量（50、100、150 mg/kg）的Uro A，持续8周。检测血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、血尿素氮（BUN）和肌酐（Cr）水平。通过苏木精-伊红（HE）染色评估组织病理学特征，随后评估抗氧化和抗炎活性。此外，我们还评估了肝脏和肾脏中Bax、Bcl-2和裂解的半胱天冬酶-3基因的表达水平。结果表明，Uro A治疗明显减轻了d-gal诱导的肝肾损伤。Uro A的有益作用伴随着肝脏和肾脏中丙二醛（MDA）水平的下降以及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）和总抗氧化能力（T-AOC）活性的升高，以及血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）等炎症细胞因子水平的下调。此外，Uro A可以调节衰老小鼠肝脏和肾脏中Bax、Bcl-2和裂解的半胱天冬酶-3的表达。这些发现表明，Uro A通过减轻氧化应激、炎症反应和细胞凋亡来改善d-gal诱导的肝肾损伤。
