Berberine mitigates IL-21/IL-21R mediated autophagic influx in fibroblast-like synoviocytes and regulates Th17/Treg imbalance in rheumatoid arthritis

Dinesh, Palani; Rasool, Mahaboobkhan

doi:10.1007/s10495-019-01548-6

Cited by 59 publications

(54 citation statements)

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“…via the utilization of p62 and suppression of C/EBP homologous protein (CHOP) transcription factor. 52 Interestingly, berberine is found to decrease the gene and protein levels of IL-21R complex in AAFLS cells and whereby suppress IL-21/IL-21R dependent-autophagy mediated through PI3K/Akt signalling via inhibiting autophagic mediators, p62 sequestration and promotion of CHOP in a dose-dependent manner. 52 Besides, this autophagic pathway is also known to evade apoptosis through induction of B-cell lymphoma 2 (Bcl-2) anti-apoptotic transcription factor and diminish the expression of Bcl-2 associated X protein (BAX) pro-apoptotic protein in AAFLS cells, which is markedly attenuated by berberine treatment.…”

Section: Beclin-1 and Lc3-phosphatidylethanolamine Conjugate 3-ii (Lcmentioning

confidence: 96%

“…50,51 It has been recently shown that IL-21/ IL-21 receptor (IL-21R) interaction can induce autophagic influx and consequent uncontrolled proliferation in adjuvant-induced arthritic FLS (AAFLS) cells through activating the PI3K/Akt proinflammatory signalling pathway that influences the expression of both apoptosis-and autophagy-related genes. 31,52 Upon IL-21 stimulation, autophagy is induced in AAFLS cells through promoting PI3K/Akt pathway that results in up-regulation of autophagy-related 5 (Atg5),…”

Section: Berberine Reverse Defective Autophagy In Fls Cellsmentioning

confidence: 99%

“…52 Besides, this autophagic pathway is also known to evade apoptosis through induction of B-cell lymphoma 2 (Bcl-2) anti-apoptotic transcription factor and diminish the expression of Bcl-2 associated X protein (BAX) pro-apoptotic protein in AAFLS cells, which is markedly attenuated by berberine treatment. 31,52 In conclusion, these findings indicate that each member of IL21/IL21R-autophagy mediators-PI3K/ Akt axis can serve an efficient therapeutic target for treating RA.…”

Section: Beclin-1 and Lc3-phosphatidylethanolamine Conjugate 3-ii (Lcmentioning

confidence: 99%

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Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Shen

Jiao

et al. 2020

J Cellular Molecular Medi

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Section: Beclin-1 and Lc3-phosphatidylethanolamine Conjugate 3-ii (Lcmentioning

confidence: 96%

Section: Berberine Reverse Defective Autophagy In Fls Cellsmentioning

confidence: 99%

Section: Beclin-1 and Lc3-phosphatidylethanolamine Conjugate 3-ii (Lcmentioning

confidence: 99%

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Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Shen

Jiao

et al. 2020

J Cellular Molecular Medi

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“…In reference to BBR and CIA specifically, prior studies using BBR to ameliorate clinically apparent CIA resulted in a suppression of T h 17 activity alongside the activation/proliferation of T reg , thereby resulting in an increased T reg /T h 17 ratio in BBR treated mice [45,51]. While a study by Yue et al (2017) [46] provides opposing evidence in which BBR did not appear to have significant effect on the frequency of T reg in a CIA model despite seeing amelioration of clinically apparent CIA, their particular model used PBMCs to assess T reg population and FOXP3 expression, as opposed to our study which used splenocytes and draining LN cells.…”

Section: Discussionmentioning

confidence: 99%

“…In regard to RA specifically, BBR has been successful at treating clinically apparent collagen induced arthritis (CIA) in vivo (the rodent model of RA) through a number of suggested mechanisms: such as (1) dendritic cell apoptosis [43], (2) interference with MAPK signaling via inhibition of p-ERK, p-38, and p-JNK [44], (3) attenuation of T h 17 activity via inducing cortistatin in the gut [46], (4) restoration between balance of T reg /T h 17 cells [45], (5) the suppression of Th17 differentiation/proliferation through inhibition of CD169 and RORγt transcription factor, and (6) induction of T reg differentiation through aryl hydrocarbon receptor (AhR) activation [51].…”

Section: Berberinementioning

confidence: 99%

Berberine delays onset of collagen induced arthritis through T cell suppression

Vita¹,

Lyons²,

Aljobaily³

et al. 2019

Preprint

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RUNNING TITLE (less than 50 characters): Berberine delays onset of collagen arthritis model KEY WORDS (5 words not in the title): CIA, berberine, RA, autoimmune, T cell ABSTRACT (250 words or less): Previous evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role from in vitro studies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4 + T cells, CXCR5 + T fh cells, and an increased proportion of T reg at both day 14 and day 28 endpoints, as well as decreased CD28 + and CD154 + CD4 + T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19 + B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity. and PBS controls ( Fig. 2B). When comparing anti-CII IgG levels between arthritic and nonarthritic mice within the BBR group specifically, however, anti-CI IgG1, IgG2a and total IgG were all significantly reduced in the non-arthritic mice compared to those who developed arthritis (Fig. 2C). Additionally, there appeared to be a vehicle-specific effect on circulating anti-CII IgG in which the administration of PBS with 0.01% DMSO elicited elevated levels of anti-CII IgG1 and total IgG in vehicle control mice ( Fig. 2A-B).Key CD4 + T cell population characteristics in response to berberine treatment-On day 14, we observed a significant reduction in populations of both CD4 + T cells and CXCR5 + T fh cells in the LNs and spleen of BBR-treated mice (Fig. 3A-B), as well as a reduction in the percentage of CD28 + and CD154 + CD4 + T cells in the spleen and LNs of BBR-treated mice (Fig. 3A-B). By the day 28 experimental endpoint we continued to observe a significant reduction in CD4 + T cells and CXCR5 + T fh cells in the spleen and LNs of BBR-treated mice ( Fig. 3C-D), however, there was no significant difference in the percentage of CD28 + and CD154 + CD4 + T cells between treatment groups (Fig 3C-D). Berberine treatment leads to increased proportion of FOXP3 + CD25 + CD4 + T cells-To examineBBRs effect on ...

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The Role of Chronic Inflammation in Various Diseases and Anti‐inflammatory Therapies Containing Natural Products

Wang

Zhou

et al. 2021

ChemMedChem

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Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.

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Berberine mitigates IL-21/IL-21R mediated autophagic influx in fibroblast-like synoviocytes and regulates Th17/Treg imbalance in rheumatoid arthritis

Cited by 59 publications

References 62 publications

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Berberine delays onset of collagen induced arthritis through T cell suppression

The Role of Chronic Inflammation in Various Diseases and Anti‐inflammatory Therapies Containing Natural Products

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