Evidence map›Paper›PMID 40739373›Full record

ArticleArchives of pharmacal research2025

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

Abstract read
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In one paragraph

Article in Archives of pharmacal research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xule Yang *Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Yunge Lou *Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Huan LiKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Yuanyuan MaKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Zihan WangKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Jiye AaKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Guangji WangKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. guangjiwang@hotmail.com.
Yuan XieKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. yuanxie@cpu.edu.cn.ORCID http://orcid.org/0000-0002-2991-6763

Funding

Chinese Academy of Medical Sciences Initiative for Innovative Medicine 2021-I2M-5-011Leading technology foundation research project of Jiangsu province BK20192005Six Talent Peaks Project in Jiangsu Province SWYY-061the National Natural Science Foundation of China 81872932
6 · The paper itself

Abstract

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.

Indexed as

HepatocytesLiver CirrhosisSilybinSilymarinSuccinic AcidAnimalsMaleMiceMice, Inbred C57BLSilybinSilymarinSuccinic AcidCardiolipinCRLS1Liver fibrosisMASHSDHSuccinate

Identifiers

PMID40739373

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.