Naringenin mitigates autoimmune features in lupus-prone mice by modulation of T-cell subsets and cytokines profile

Abstract

Naringenin is flavonoid mainly found in citrus fruits which has shown several biological properties. In this work, we evaluated the therapeutic potential of the flavonoid Naringenin. Fivemonth-old B6.MRL-Fas lpr /J lupus-prone mice were administered daily orally with Naringenin for seven months. We showed that Naringenin treatment at 50 or 100 mg/kg inhibited the splenomegaly and decreased the levels of anti-nuclear and anti-dsDNA autoantibodies. Furthermore, a reduction in serum concentration of TNF-α, IFN-γ and IL-6 was observed in the mice provided with Naringenin. Interestingly, serum levels of IL-10 increased. Naringenin decreased the frequency and absolute numbers of splenic effector memory T cells. Additionally, in order to be able to evaluate whether Naringenin prevented kidney damage, twelveweek-old MRL/MpJ-Fas lpr /J mice, an accelerated lupus model, were orally administered with Naringenin at 100 mg/kg for six weeks. Surprisingly, Naringenin treatment prevented kidney damage and reduced the development of fibrosis similar to cyclophosphamide group. Moreover, Naringenin treatment increased the percentage of regulatory T cells in this aggressive model of lupus. Together, these results suggest a potential ability of Naringenin to reduce the autoimmunity in lupus-prone mice by modulation of T-cell subsets and cytokines profile that mitigate the development of important lupus clinical manifestations.

Potential Mechanism of Tibetan Medicine Dali in the Treatment of Respiratory Diseases via Network Pharmacology

“…Through the screening of active components and target prediction of RAM, it could be seen that RAM mainly contains 92 chemical components such as naringenin, isorhamnetin, kaempferol and avicularin. A Study had reported that naringenin can regulate T cell subsets and reduce the serum concentration of proin ammatory cytokines such as TNF-α, INF-γ, IL-6, and the globular in ammatory reaction, so as to achieve the effect of treating in ammation (29). Isorhamnetin inhibited the activity of myeloperoxidase (MPO), the levels of TNF-α and IL-6, to abolish in ammation and support the mRNA expression of proin ammatory mediators (30).…”

Flavonoids in Treatment of Chronic Kidney Disease

“…Baicalin could also inhibit mTOR activation and Tfh cell differentiation while promoting Foxp3+ regulatory T cell differentiation in LN [ 196 ]. Naringenin decreased the levels of anti-nuclear and anti-dsDNA autoantibodies while increasing the percentage of Treg cells and preventing kidney damage and fibrosis of LN [ 197 ]. Icariin reduced the serum anti-dsDNA antibody level and immune complex deposition by suppressing the NLRP3 inflammasome, NF-κB activation, and TNF-α and C-C motif chemokine ligand 2 (CCL2) production in MRL/lpr mice [ 198 ].…”

Naringenin: A Promising Therapeutic Agent against Organ Fibrosis

“…In an animal model of renovascular hypertension established by performing 2-kidney, 1-clip surgery in rats, Wang et al observed that naringenin administration significantly ameliorated hypertensive renal damage in the nonclipped kidneys, including interstitial fibrosis as measured by histological analysis, by normalizing the imbalance of renin-angiotensin system [ 116 ]. Moreover, naringenin was identified to prevent autoimmune features and kidney injury, including renal fibrosis as evaluated by the decrease in collagen fibers, in lupus-prone mice, by modulating T-cell subsets and cytokines profile [ 117 ].…”