Hesperidin protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes

Abstract

Hesperidin is a vitamin P flavonoid compound primarily present in citrus fruits, which possesses an anti-inflammatory effect. The functional role of hesperidin in interleukin (IL)-1β-stimulated human osteoarthritis (OA) chondrocytes is still unknown. In the present study, anti-inflammatory effects of hesperidin in IL-1β-stimulated chondrocytes were investigated. The results demonstrated that hesperidin treatment markedly decreased nitric oxide and prostaglandin E2 production and markedly downregulated inducible nitric oxide synthase and cyclooxygenase-2 expression in IL-1β-stimulated OA chondrocytes. In addition, hesperidin markedly reduced IL-1β-induced matrix metalloproteinase (MMP)-3 and MMP-13 expression in human OA chondrocytes. Furthermore, hesperidin markedly decreased the activation of nuclear factor (NF)-κB in human OA chondrocytes. In conclusion, it was revealed for the first time that hesperidin inhibited inflammatory responses in IL-1β-stimulated human chondrocytes, potentially through inhibiting the activation of the NF-κB signaling pathway. These data suggest that hesperidin may be a potential agent for the treatment of OA.

Keywords: hesperidin; inflammation; nuclear factor κB; osteoarthritis.

Figure 1.

Effects of IL-1β on viability and inflammatory cytokine expression in human OA chondrocytes. (A) Effects of IL-1β on viability of human OA chondrocytes in vitro. IL-1β increased iNOS, COX-2, MMP-3 and MMP-13 (B) gene and (C) protein expression in human OA chondrocytes. **P<0.01. OA, osteoarthritis; IL, interleukin; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase. Control group, PBS-treated cells.

Figure 2.

Hesperidin regulates inflammation in IL-1β-stimulated human OA chondrocytes. (A) Hesperidin increases the viability of human OA chondrocytes in vitro. Effects of hesperidin on IL-1β and IL-17A (B) gene and (C) protein expression in IL-1β-stimulated human OA chondrocytes. Effects of hesperidin treatment on IL-6 and IL-10 (D) gene and (E) protein expression in IL-1β-stimulated human OA chondrocytes. **P<0.01. OA, osteoarthritis; IL, interleukin. Control group, PBS-treated cells.

Figure 3.

Effects of hesperidin on IL-1β-induced inflammation in human OA chondrocytes. Effects of hesperidin on (A) NO and (B) PGE2 production in IL-1β-stimulated OA chondrocytes. Effects of hesperidin on iNOS and COX-2 (C) gene and (D) protein expression in IL-1β-stimulated human OA chondrocytes. Effects of hesperidin on IL-1β-induced MMP-3 and MMP-13 (E) gene and (F) protein expression in human OA chondrocytes. **P<0.01 vs. control. OA, osteoarthritis; IL, interleukin; NO, nitric oxide; PGE2, prostaglandin E2; iNOS, inducible NO synthase; COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase. Control group, PBS-treated cells.

Figure 4.

Hesperidin inhibits IL-1β-stimulated inflammation by reducing NF-κB activity in human OA chondrocytes. (A) Hesperidin decreases the activation of NF-κB in IL-1β-stimulated human OA chondrocytes. Effects of NF-κBIR on iNOS, COX-2, MMP-3 and MMP-13 (B) gene and (C) protein expression in IL-1β-stimulated human OA chondrocytes. Effects of pNF-κB on iNOS, COX-2, MMP-3 and MMP-13 (D) gene and (E) protein expression in IL-1β-stimulated human OA chondrocytes. Effects of pNF-κB on hesperidin-inhibited IL-1β-stimulated iNOS, COX-2, MMP-3 and MMP-13 (F) gene and (G) protein expression in IL-1β-stimulated human OA chondrocytes. **P<0.01. OA, osteoarthritis; IL, interleukin; NF-κB, nuclear factor-κB; NO, nitric oxide; PGE2, prostaglandin E2; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase; NF-κBIR, NF-κB inhibitor; pNF-κB, NF-κB overexpression; pControl, empty pcDNA3.1.

Figure 4.

Hesperidin inhibits IL-1β-stimulated inflammation by reducing NF-κB activity in human OA chondrocytes. (A) Hesperidin decreases the activation of NF-κB in IL-1β-stimulated human OA chondrocytes. Effects of NF-κBIR on iNOS, COX-2, MMP-3 and MMP-13 (B) gene and (C) protein expression in IL-1β-stimulated human OA chondrocytes. Effects of pNF-κB on iNOS, COX-2, MMP-3 and MMP-13 (D) gene and (E) protein expression in IL-1β-stimulated human OA chondrocytes. Effects of pNF-κB on hesperidin-inhibited IL-1β-stimulated iNOS, COX-2, MMP-3 and MMP-13 (F) gene and (G) protein expression in IL-1β-stimulated human OA chondrocytes. **P<0.01. OA, osteoarthritis; IL, interleukin; NF-κB, nuclear factor-κB; NO, nitric oxide; PGE2, prostaglandin E2; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase; NF-κBIR, NF-κB inhibitor; pNF-κB, NF-κB overexpression; pControl, empty pcDNA3.1.