Berberine attenuates CCN2-induced IL-1β expression and prevents cartilage degradation in a rat model of osteoarthritis

Liu, Shan‐Chi; Lee, Hsiang-Ping; Hung, Chun-Yin; Tsai, Chun‐Hao; Li, Te‐Mao; Tang, Chih-Hsin

doi:10.1016/j.taap.2015.08.020

Cited by 61 publications

(59 citation statements)

References 45 publications

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“…It has been recognized that berberine can decrease inflammatory agents-induced interleukin-1β and TNFα ensuing inflammation in human lung cells ( Lee et al, 2007 ). Many emerging evidences have shown that berberine contributes to cell survival and inhibition of inflammation by downregulating IL-1β expression ( Liu et al, 2015b , Liu et al, 2016 ). For example, berberine mediates inhibition of cartilage degeneration in IL-1β-stimulated rat chondrocytes through downregulation of IL-1β in a Akt-dependent fasion ( Zhao et al, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines

Maleki

Aboutaleb

Souri

2018

Journal of Chemical Neuroanatomy

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Section: Resultsmentioning

confidence: 99%

Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines

Maleki

Aboutaleb

Souri

2018

Journal of Chemical Neuroanatomy

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“…Indeed, berberine was reported to reduce the activation of signaling pathways like p38 MAPK and JNK in osteoarthritis synovial fibroblasts as well as cartilage destruction in a rat model of osteoarthritis (67), pointing to its anti-inflammatory properties. Further research is warranted to define the effects of berberine on CHIKV inflammatory disease markers in vivo.…”

Section: Discussionmentioning

confidence: 99%

The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling

Varghese

Thaa

Amrun

et al. 2016

J Virol

120

103

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Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a highthroughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH 2 -terminal kinase (JNK). Upon treatment with berberine, this virus-induced MAPK activation was markedly reduced. Subsequent analyses with specific inhibitors of these kinases indicated that the ERK and JNK signaling cascades are important for the generation of progeny virions. In contrast to specific MAPK inhibitors, berberine lowered virus-induced activation of all major MAPK pathways and resulted in a stronger reduction in viral titers. Further, we assessed the in vivo efficacy of berberine in a mouse model and measured a significant reduction of CHIKV-induced inflammatory disease. In summary, we demonstrate the efficacy of berberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. IMPORTANCEChikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated protein kinase signaling. The relevance of these signaling cascades in the viral life cycle was emphasized by specific inhibitors of these kinase pathways, which decreased the production of progeny virions. Berberine significantly reduced CHIKV-induced inflammatory disease in a mouse model, demonstrating efficacy of the drug in vivo. Overall, this work makes a strong case for pursuing berberine as a potential anti-CHIKV therapeutic compound and for exploring the MAPK signaling pathways as antiviral targets against alphavirus infections. C hikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease spread by Aedes mosquitoes and characterized by a sudden onset of febrile illness, nausea, headache, and most importantly, severe and persistent musculoskeletal pain (1). It reemerged in tropical Asia and Africa 1 decade ago and since 2013 has infected more than 1.5 million people in the Americas (2). So far, no licensed vaccine or antiviral treatment exists to counter this disease. Over the years, many research groups have focused on...

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“…Several studies have shown that ROS, such as superoxide anions, hydroxyl radicals and hydrogen peroxide (H 2 O 2 ), play a role in cartilage degeneration [ 15 , 16 ]. A high-level of ROS production commonly results in apoptosis and senescence of the chondrocytes, and thus associates with a decreased number of chondrocytes and altered cell phenotypes during OA [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus

Young

Chuang

Hsu

et al. 2017

BMC Complement Altern Med

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BackgroundDuring the onset of osteoarthritis (OA), certain biochemical events have been shown to accelerate cartilage degradation, including the dysregulation of cartilage ECM anabolism, abnormal generation of reactive oxygen species (ROS) and overproduction of proteolytic enzymes and inflammatory cytokines. The potency of aucubin in protecting cellular components against oxidative stress, inflammation and apoptosis effects are well documented, which makes it a potential candidate for OA treatment. In this study, we aimed to evaluate the protective benefits of aucubin against OA using H2O2 and compression induced OA-like chondrocyte models.MethodsThe effects of aucubin were studied in porcine chondrocytes after 1 mM H2O2 stimulation for 30 min or sustained compression for 24 h. Effects of aucubin on cell proliferation and cytotoxicity of chondrocytes were measured with WST-1 and LDH assays. ROS production was evaluated by the Total ROS/Superoxide Detection Kit. Caspase-3 activity was evaluated by the CaspACE assay system. The levels of apoptosis were evaluated by the Annexin V-FITC apoptosis detection kit. OA-related gene expression was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Total DNA quantification was evaluated by the DNeasy Blood and Tissue kit. Sulfated-glycosaminoglycans (sGAGs) production and content were evaluated by DMMB assay and Alcian blue staining.ResultsThe results showed that the ROS scavenge effects of aucubin appeared after 1 h of pretreatment. Aucubin could reduce the caspase-3 activity induced by H2O2, and reduced the apoptosis cell population in flowcytometry. In RT-qPCR results, aucubin could maintain ACAN and COL2A1 gene expressions, and prevent IL6 and MMP13 gene up-regulation induced by H2O2 and compression stimulations. In the DMMB assay and Alcian blue staining, aucubin could maintain the sGAG content and protect chondrocytes against compressive stress, but not oxidative stress from H2O2.ConclusionsThese results indicated that aucubin has protective effects in an osteoarthritic chondrocyte model induced by H2O2 and mechanical stimulus.

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Berberine attenuates CCN2-induced IL-1β expression and prevents cartilage degradation in a rat model of osteoarthritis

Cited by 61 publications

References 45 publications

Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines

Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines

The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus

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