Xu Yudan, Zhang Lei, Fu Tengteng, Yang Xujin, Lan Enna, Deng Yuling, Tao Yi
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China.
J Pharm Biomed Anal. 2025 Oct 15;264:116955. doi: 10.1016/j.jpba.2025.116955. Epub 2025 May 14.
The global incidence of acute liver injury continues to rise, posing a significant threat to public health. While both raw and processed Rubus idaeus Linnaeus (RI) demonstrate hepatoprotective properties, their mechanisms require further elucidation. This study employed UPLC-Q-TOF/MS-based serum metabolomics to delineate the distinct liver-protective mechanisms of raw and processed RI in a murine model of acute liver injury. Following ten days of intragastric administration with low, medium, and high doses of raw and processed RI extracts, mice received intraperitoneal injection of 50 % carbon tetrachloride in olive oil. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), as well as liver levels of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (Hyp), were measured via ELISA. Liver histopathology was examined using Hematoxylin and Eosin (HE), Masson, and Sirius Red staining. Treatment with both raw and processed RI significantly reduced serum AST, ALT, and ALP levels while decreasing hepatic MDA and Hyp content compared to the model group. Conversely, SOD activity showed marked elevation. Metabolomic profiling identified 39 significantly altered endogenous metabolites in the model group, with subsequent characterization of 22, 23, and 7 distinctive biomarkers in the raw, salt-processed, and wine-processed RI treatment groups, respectively. These biomarkers predominantly associated with energy metabolism and arginine metabolism. Furthermore, the phenolic and flavonoid compounds in RI, known for their anti-inflammatory and antioxidant properties, played a key role in mitigating liver damage induced by CCl₄. These findings provide strong evidence supporting the potential use of both raw and processed RI in the development of hepatoprotective health products.
急性肝损伤的全球发病率持续上升，对公众健康构成重大威胁。虽然生的和加工过的覆盆子（RI）均显示出肝脏保护特性，但其作用机制仍需进一步阐明。本研究采用基于超高效液相色谱-四极杆-飞行时间质谱联用（UPLC-Q-TOF/MS）的血清代谢组学方法，在急性肝损伤小鼠模型中描绘生的和加工过的RI不同的肝脏保护机制。在分别用低、中、高剂量的生的和加工过的RI提取物进行十天胃内给药后，小鼠腹腔注射50%的四氯化碳橄榄油溶液。通过酶联免疫吸附测定（ELISA）测量血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）水平，以及肝脏中超氧化物歧化酶（SOD）、丙二醛（MDA）和羟脯氨酸（Hyp）水平。使用苏木精和伊红（HE）染色、Masson染色和天狼星红染色检查肝脏组织病理学。与模型组相比，生的和加工过的RI治疗均显著降低血清AST、ALT和ALP水平，同时降低肝脏MDA和Hyp含量。相反，SOD活性显著升高。代谢组学分析确定模型组中有39种内源性代谢物发生显著变化，随后分别在生的、盐制和酒制RI治疗组中鉴定出22种、23种和7种独特的生物标志物。这些生物标志物主要与能量代谢和精氨酸代谢相关。此外，RI中的酚类和黄酮类化合物以其抗炎和抗氧化特性著称，在减轻四氯化碳诱导的肝损伤中起关键作用。这些发现提供了有力证据，支持生的和加工过的RI在开发肝脏保护健康产品方面的潜在用途。
