β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice

Abstract

Context: β-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. Objective: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. Materials and methods: In vitro , bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 μM BS in the M1 or M2 polarization conditions. In vivo , either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 10 6 BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. Results: The phenotypes and function of BMDMs showed that 5, 25 and 50 μM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1β, CD86 and MHCII in 25 μM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 μM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit the production of pro-inflammatory cytokines ( p < 0.05). Depletion of IL-10 counteracted the effect of BS treatment (α-IL-10 vs. RatIgG1, p < 0.01 on day 16), highlighting the role of IL-10 in the anti-inflammatory response. Conclusions: These results suggested that BS could modulate the functions of macrophages and might be a promising agent for RA therapy.

WITHDRAWN: Sambucus Ebulus Fruits Extract Ameliorates Eosinophilic Nasal Polyposis: An in vitro Study

“…Our ndings decipher that SE fruits extract increased signi cantly two pro-apoptotic key genes Bax and Bad in NP tissues (P < 0.0001). On the other hand, Beta-sitosterol, one of major component of SEs extract (Table2) has a crucial role in inducing apoptosis in NP tissue [34].…”

Potential Molecular Mechanisms of Plantain in the Treatment of Gout and Hyperuricemia Based on Network Pharmacology

“…Previous studies have shown that plantain has significant anti-inflammatory activity and can reduce the secretion of TNF- α , IL-10, and IL-6 in the mouse leukemia cells of monocyte macrophage (RAW264.7) inflammatory model [ 71 , 72 ]. It has been proved that compounds dinatin [ 73 ], baicalein [ 35 ], baicalin [ 35 ], sitosterol [ 74 ], stigmasterol [ 44 ], and luteolin [ 45 ] can reduce the level of TNF- α . This suggests that plantain may be a potential treatment for gout and hyperuricemia by inhibiting TNF signaling pathway.…”

“…Sitosterol can treat cerebral aneurysms by reducing the expression of chemokines and inflammatory cytokines TNF- α , IL-8, IL-1 β , IL-17, IL-6, and MMP-2/9 [ 43 ]. It can reduce the level of IL-17, TNF- α , IL-1 β , IL-6, and IL-12 in RA mice and promote the production of anti-inflammatory cytokine IL-10 [ 44 , 74 ]. Sitosterol can also treat foot edema caused by MSU crystals in mice [ 96 ].…”

Ameliorative effects of sea buckthorn oil on DNCB induced atopic dermatitis model mice via regulation the balance of Th1/Th2

“…Some of the Fatty acids are required for innate immune activation and pathogen defense [ 35 ]. Sitosterol is the main constituent of many plants and vegetables and has the ability to modulate the functions of macrophages and anti-inflammation [ 36 , 37 ]. β-carotene also has been shown to suppress the cellular and tissue response to inflammation [ 38 , 39 ].…”