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Silybin has been used as a therapeutic agent in treating liver fibrosis worldwide with unclear mechanisms. In this study, mice were fed a CDAHFD for six weeks to induce liver steatosis and mild liver fibrosis. Metabolomic analysis of mouse liver mitochondria revealed that silybin reversed metabolic abnormalities and diminished succinate accumulation within the mitochondria. Lipidomic profiling revealed marked decreases in mitochondrial membrane phospholipids (PE, PS, PC, and PI) in CDAHFD-fed mice, along with a substantial reduction in cardiolipin (CL)—a critical component for succinate dehydrogenase (SDH) complex assembly. Silybin restored mitochondrial membrane phospholipids, enhanced CRLS1 expression, facilitated the assembly of SDHA and SDHB, and rejuvenated SDH activity. CRLS1 knockdown via siRNA significantly impaired SDH function, leading to mitochondrial succinate accumulation. Moreover, silybin inhibited succinate efflux by downregulating the expression of the MCT1 transporter. Conditioned medium from palmitic acid/silybin-treated hepatocytes, containing reduced succinate levels, effectively suppressed LX-2 activation. This research indicates that silybin alleviates MASH-induced liver fibrosis by inhibiting succinate generation and its extracellular release, thereby inactivating hepatic stellate cells. These results suggest that targeting succinate production or secretion may represent a promising therapeutic strategy against liver fibrosis progression.

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Insights into biological activities profile of gingerols and shogaols for potential pharmacological applications Anis Najwa Abdul Rani, Anand Gaurav, Vannajan Sanghiran Lee, Nadiah Mad Nasir, Sharifuddin Md Zain, Vaishali M. Patil, Ming Tatt Lee p. 638-675
NRF2 activation in cancer and overview of NRF2 small molecule inhibitors Hoang Hai Ngo, Bo-Yeong Yu, Jeong-Eun Lee, Hyunwoo Kim, Young-Sam Keum p. 676-705
Enhancer regulation in cancer : from epigenetics to m6A RNA modification Arathy Vasukutty, Poshan Yugal Bhattarai, Hong Seok Choi p. 706-735
9H-carbazole derivatives from a Streptomyces species under potassium iodide stress and their anti-inflammatory properties Pengcheng Yan, Yunlong Liu, Jibin Liu, Linmeng Chen, Ning Li, Weiming Zhu p. 736-744
(A) novel multi-target compound mitigates amyloid plaques, synaptic deficits, and neuroinflammation in Alzheimer’s disease models Yeongyeong Lee, Sukmin Han, Jeongmi Lee, Yongeun Cho, Jun-Sik Kim, Yeji Jeon, Heewon Cho, Heejin Yoo, Yujung Byun, Tai Kyoung Kim ... [et al.] p. 745-764
Curcumin monoglucuronide protects cartilage from progressive degeneration by blocking MMP-13 Himadri Shekhar Roy, Chirag Kulkarni, K.M. Neethu, Anand Babu, Malika Arora, Govindasamy Jayamurugan, Dipankar Mandal, Rajdeep Guha, Naibedya Chattopadhyay, Deepa Ghosh p. 765-781
Silybin inhibits succinate production and secretion in hepatocytes to reverse liver fibrosis Xule Yang, Yunge Lou, Huan Li, Yuanyuan Ma, Zihan Wang, Jiye Aa, Guangji Wang, Yuan Xie p. 782-797
Sphingolipid modulation and anti-tumor activity of Jaspine B in HepG2 bearing mice Jihoon Lee, Ji-Hyeon Jeon, Minyeong Pang, Min-Koo Choi, Dongjoo Lee, Im-Sook Song p. 798-813
Neuroprotective effects of taurine in a rodent model of Parkinson’s disease involve modulating astrocyte-mediated inflammation Sung Min Moon, Jaehoon Kim, Jaeheon Seol, Seonguk Yang, Duwon Jung, Chang Yup Kim, Chang Seok Kim, Ki Wung Chung, Young-Suk Jung, Seung-Cheol Chang, Hae Young Chung, Jaewon Lee p. 814-829

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