Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

Abstract

Introduction: Among the most frequent demyelinating autoimmune disorders of the central nervous system (CNS) is multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is used as an animal model of multiple sclerosis. Berberine is an alkaloid found in some medicinal plants with anti-inflammatory effects. Methods: C57BL/6 female mice were used and divided into three groups: (1) The control group received PBS, (2) the low-dose treatment group received 10 mg/kg of berberine, and (3) The high-dose treatment group received 30 mg/kg of berberine.Myelin Oligodendrocyte Glycoprotein and complete Freund's adjuvant were subcutaneously administered to induce EAE. Mice were given intraperitoneal injections of pertussis toxin on the day of immunization and 2 days later.Histological studies showed low lymphocyte infiltration and demyelination of CNS in the treated groups. Results:The clinical scores of the treatment group with low-dose berberine (T1: 2 ± 0.13) and high-dose berberine (T2: 1.5 ± 0.14) were significantly (p < .001) lower than the control group (CTRL: 4.5 ± 0.13). Treatment groups decreased proinflammatory cytokines (IFN-γ, TNF-α, interleukin [IL]-17) (p < .001) as well as increased anti-inflammatory cytokine expression (IL-4, IL-10, IL-27, IL-33, IL-35, TGF-β) (p < .01) when compared to the CTRL group. Treatment groups with berberine reduced expression of the Th1 and Th17 cytokines and transcription factors (p < .001) and increased expression of transcription factors and Th2 and Treg cytokines (p < .01) in contrast to CTRL group. Conclusion:Berberine appears to have a protective effect on disease development and alleviating disease status in EAE, which appears to be due

Berberine: A natural modulator of immune cells in multiple sclerosis

“…Another study on mice with EAE indicated that Berberine suppresses the differentiation of naive CD4+ T cells into pathogenic Th17 cells through direct actions on the JAK/STAT pathway, resulting in the amelioration of inflammation in EAE‐induced mice 75 . We are confirmed by a study on EAE mice that showed treatment with Berberine significantly downregulates the expression of transcription factors (RORγt) and pro‐inflammatory cytokine derived from Th17 such as IL‐17, which was accompanied by reduced CNS inflammation and demyelination 23 . Collectively, results from studies point to the promising role Berberine has in suppressing pathogenic Th17 cells in EAE.…”

“…94,104 Berberine could promote the differentiation of Th2 cells which play a protective role in disease development and alleviating autoreactive inflammatory responses. 21,23 The potential for Berberine to favor Th2 type response may be an effective therapeutic agent to ameliorate Th1-skewed inflammatory and autoimmune diseases, such as MS, RA, Crohn's disease, and type 1 diabetes. 105 An in vitro study demonstrated that Berberine exhibits its immunomodulatory and anti-inflammatory potential by skewing the Th1/Th2 balance toward the Th2 polarization in mouse primary splenocytes.…”

“…The related mechanisms of Berberine against autoimmune diseases and associated inflammatory disorders mainly involve inhibiting inflammation, modulation of Th17/Treg balance favor to Treg, and modulation of Th1/Th2 balance favor to Th2 21–23 . Of note, this effect is accompanied by inhibiting pro‐inflammatory mediators and upregulating anti‐inflammatory mediators 20–22 (Figure 2).…”

“…Berberine can prevent the differentiation of naïve CD4 + T cells into Th1 via decreased phosphorylation of STAT1 and STAT4 that activated following IL‐12 signaling, as well as suppression of T‐bet representation 23,74–76 . It was demonstrated in EAE mice that berberine therapy resulted in a decrease in the number of Th1 cells by blocking the effects of IL‐12 signaling on naive T cells 75 .…”

https://restorativemedicine.org/digest/berberine-neurological-health/

“…In addition, berberine activity led to the protection of dopamine neurons by restoring autophagy. 17 A study of berberine in an experimental model of multiple sclerosis (MS), found that treated mice had lower levels of the proinflammatory cytokines IFN-?, TNF-?, and IL-17; and increased levels of the anti-inflammatory cytokines IL-4, IL-10, IL-27, IL-33, IL-35, and TGF-? compared to control animals.…”