Peeling Back Immunity: Citrus Peel Extract as A Potential Natural Immunomodulator for Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by chronic inflammation and dysregulation of the immune system. Current treatments for SLE often involve general immunosuppressants and antimalarial medications, which can have significant side effects and may not be effective for all patients. This has led researchers to explore alternative therapeutic options, including natural compounds with anti-inflammatory and immunomodulatory properties. Citrus peel extract has emerged as a promising candidate for SLE treatment due to its rich content of bioactive compounds, mainly polyphenols. In various studies, various studies have shown that these compounds possess potent anti-inflammatory and immunomodulatory effects. This study investigated Citrus peel extract’s anti-inflammatory and immunomodulatory effects on peripheral blood mononuclear cells (PBMCs) from SLE patients. PBMCs from ANA-positive SLE patients were treated with Citrus peel extract at 25, 50, and 100 μg/mL. Flow cytometry was used to analyze Th1 (CD4+IFNγ+), Th17 (CD4+IL17A+), and Treg (CD4+CD25+Foxp3+) cell populations. Citrus peel extract significantly decreased Th1 and Th17 cells while increasing Treg cells dose-dependently by inducing interleukin-10 anti-inflammatory cytokine. At 100 μg/mL, the extract reduced Th1 cells from 12.70 to 7.83 % and Th17 cells from 18.47 to 11.67 % while increasing Treg cells from 0.14 to 3.67 %. Phytochemical screening revealed the presence of flavonoids, which likely mediate these immunomodulatory effects through suppression of inflammatory cytokines and transcription factors. These results suggest Citrus peel extract can help restore immune balance in SLE by suppressing pathogenic Th1/Th17 responses and promoting regulatory T cells and IL-10. The extract shows promise as a potential natural immunomodulatory adjuvant therapy for autoimmune conditions like SLE. Further research is needed to elucidate the molecular mechanisms and evaluate clinical efficacy. HIGHLIGHTS Citrus peel extract significantly modulates immune cell populations in SLE patients by decreasing pro-inflammatory, Th1 and Th17 cells. Citrus peel extract regulates immune responses in SLE by upregulating regulatory T cells. Immunomodulatory effects are likely mediated by flavonoids present in the extract. GRAPHICAL ABSTRACT