Evidence map›Paper›PMID 34687898›Full record

ArticleOsteoarthritis and cartilage2022

Oral administration of berberine limits post-traumatic osteoarthritis development and associated pain via AMP-activated protein kinase (AMPK) in mice.

J Li, Y Wang, D Chen, R Liu-Bryan

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
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

41 citing papers in PubMed, 54 citations in OpenAlex.

  1. SIRT3-Dependent Actions of Berberine: From Molecular Therapies to Toxicity.Journal of biochemical and molecular toxicology · 2026
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  8. Molecular landscape of Berberine's therapeutic potential in gastrointestinal disorders.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026
    Review
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  16. NRH, a potent NADMetabolism: clinical and experimental · 2025
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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

4 authors at 4 institutions in 2 countries.

J LiDepartment of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA.
Y WangDepartment of Medicine, University of California San Diego, La Jolla, USA; Present address Valo Health, Lexington, MA, USA.
D ChenDepartment of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA; Present address: Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: di.chen@siat.ac.cn.
R Liu-BryanVA San Diego Healthcare System, San Diego, USA; Department of Medicine, University of California San Diego, La Jolla, USA. Electronic address: ruliu@health.ucsd.edu.
Rush University Medical Center · USShenzhen Institutes of Advanced Technology · CNUC San Diego Health System · USUniversity of California San Diego · US

Funding

The Role of MicroRNA in Osteoarthritis: Alzheimer's Administrative SupplementR01AR070222 · NIAMS · RUSH UNIVERSITY MEDICAL CENTER · PI HUANG, JIAN, ZHAO, LAN · 2017 to 2022
$2.1M
ATP-Citrate Lyase As A Novel Metabolic Target for OsteoarthritisI01BX002234 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI BRYAN, RU · 2015 to 2022
–
BLRD VA I01 BX002234NIAMS NIH HHS R01 AR070222
6 · The paper itself

Abstract

objectiveWe investigated the effect of berberine, a natural plant product that can activate AMP-activated protein kinase (AMPK), on Osteoarthritis (OA) development and associated pain in mice.

designHuman primary knee chondrocytes were utilized to investigate how AMPK is activated by berberine. Both global knockout (KO) of AMPKα1 and congenic wild type (WT) mice were subjected to the post-traumatic OA through destabilization of medial meniscus (DMM) surgery. Two weeks after surgery, the mice were randomly divided into two groups with one group receiving berberine chloride daily via drinking water and were sacrificed at 6 and 12 weeks after surgery. OA severity was assessed by histological and histomorphometric analyses of cartilage degradation, synovitis, and osteophyte formation. OA-associated pain behavior was also determined. Immunohistochemistry (IHC) analyses were carried out to examine changes in AMPK signaling.

resultsBerberine induced phosphorylation of AMPKα (Thr172) via liver kinase B1 (LKB1), the major upstream kinase of AMPK, in chondrocytes in vitro. Both WT and AMPKα1KO developed OA and associated pain post DMM surgery. However, treatment with berberine significantly reduced severity of OA and associated pain in WT but not AMPKα1KO mice. IHC analysis of WT DMM knee cartilage further revealed that berberine inhibited concomitant loss of expression and phosphorylation of AMPKα and expression of SIRT1 and SIRT3, suggesting an important role of activation of AMPK signaling in mediating beneficial effect of berberine.

conclusionsBerberine acts through AMPK to reduce joint structural damage and pain associated with post-traumatic OA in mice in vivo.

Indexed as

Administration, OralAMP-Activated Protein KinasesAnimalsArthralgiaBerberineJointsMaleMiceOsteoarthritisAMP-Activated Protein KinasesBerberineAMPKBerberineCartilageOsteoarthritisPain

Identifiers

PMID34687898
PMCPMC8712393
OpenAlexW3205652832

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.