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. 2019 Oct 7;19(1):264.
doi: 10.1186/s12906-019-2673-7.

Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats

Zhiguang Qiao  1 , Jiaxin Tang  1 , Wen Wu  1 , Jian Tang  1 , Ming Liu  2
Affiliations

Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats

Zhiguang Qiao et al. BMC Complement Altern Med. .

Abstract

Background: Osteoarthritis (OA) is a common degenerative disease of synovial joints caused by inflammation. Acteoside (ACT), a major component and lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha, has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of ACT on inflammatory responses and joint protection in OA rats.

Methods: Cell proliferation was examined by MTT and colony formation assay. Apoptosis was analyzed using flow cytometry with Annexin V/PI staining. ELISA was employed to examine the concentration of inflammatory cytokines. OA rat model was established by surgery stimulation.

Results: ACT treatment significantly inhibited the upregulation of inflammatory cytokines induced by IL-1β in primary chondrocytes, including IL-6, IL-12, TNF-α and IFN-γ. ACT stimulation also enhanced the cell proliferation, while inhibited cell apoptosis in IL-1β-treated chondrocytes. Consistently, ACT treatment led to downregulation of cleaved-caspase-3 and apoptosis regulator Bax, and upregulation of Bcl-2. Furthermore, ACT treatment inhibited IL-1β-induced activation of JAK/STAT pathway. The results were confirmed in surgery-induced OA rat model. Moreover, ACT treatment significantly inhibited synovial inflammation and articular chondrocyte apoptosis in OA rats.

Conclusion: Our findings indicate that ACT has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating JAK/STAT signaling pathway.

Keywords: Acteoside; Apoptosis; Inflammation; JAK/STAT; Osteoarthritis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
ACT doesn’t affect primary chondrocyte cell viability. Rat primary chondrocytes were isolated and cultured in vitro. a Cell morphologies of chondrocytes were examined with a microscope. b Toluidine blue staining of primary rat chondrocytes. c Collagen II staining for primary rat chondrocytes were performed to identify the chondrocytes. d The molecular structure of ACT was shown. e Primary rat chondrocytes were treated with ACT (0, 10, 50, 100 μM) for 24 h, CCK-8 assay was employed to detect cell viability. a-c were representative data from three independent experiments. e was representative result from three independent experiments with triplicates
Fig. 2
Fig. 2
ACT inhibits inflammatory cytokine production in primary chondrocytes induced by IL-1β stimulation. Rat primary chondrocytes were untreated or treated with 10 ng/mL IL-1β together with different concentration of ACT or ACE (positive control, 30 μM) for 24 h. a-d The expression levels of IL-6, IL-12, TNF-α and IFN-γ in culture supernatants were measured by ELISA assay. *** p < 0.001, ** p < 0.01 and * p < 0.05 compared with blank group. ## p < 0.01 and # p < 0.05 compared with IL-1β group. The experiment was repeated three times and the representative results were shown
Fig. 3
Fig. 3
ACT promotes cell proliferation and inhibits cell apoptosis in primary chondrocyte stimulated by IL-1β. Rat primary chondrocytes were untreated or treated with 10 ng/mL IL-1β together with different concentration of ACT ACE (positive control, 30 μM) for 24 h. a MTT assay was performed to examine chondrocyte viability. b chondrocyte proliferation was measured by colony formation assay. c Annexin V/PI staining was performed to examine the chondrocyte apoptosis. d The protein expression of Bcl-2, Bax, and Cleaved-caspase 3 were analyzed. *** p < 0.001, ** p < 0.01 and * p < 0.05 compared with blank group. ## p < 0.01 and # p < 0.05 compared with IL-1β group. The experiment was repeated three times and the representative results were shown
Fig. 4
Fig. 4
ACT inhibits JAK/STAT signaling in primary chondrocytes. Rat primary chondrocytes were untreated or treated with 10 ng/mL IL-1β together with different concentration of ACT ACE (positive control, 30 μM) for 24 h. a, b JAK, p-JAK, STAT3 and p-STAT3 were analyzed. ** p < 0.01 and * p < 0.05 compared with blank group. # p < 0.05 compared with IL-1β group. The experiment was repeated three times and the representative results were shown in (a)
Fig. 5
Fig. 5
ACT inhibits inflammatory cytokine production in synovial tissue of surgery-stimulated OA rats. SD rats were surgery-stimulated to induce OA and treated with ACT (100 mg/kg, i.p. injection). The generations of (a) IL-1β, (b) IL-6, (c) IL-12, (d) TNF-α and (e) IFN-γ in synovial fluid of knee joint were measured by ELISA assay. ** p < 0.01 and * p < 0.05 compared with sham group. # p < 0.05 compared with OA/NC group. The experiment was repeated three times and the representative results were shown
Fig. 6
Fig. 6
ACT protects cartilage in surgery-induced OA rat. SD rats were surgery-stimulated to induce OA and treated with ACT (100 mg/kg, i.p. injection). a, b The expressions of Bcl-2, Bax, Cleaved-caspase3, JAK, p-JAK, STAT3 and pSTAT3 in the tibial cartilage was measured by western blotting. Results were repeated three times and representative data was shown. *** p < 0.001, and ** p < 0.01 compared with sham group. # p < 0.05 compared with OA/NC group
Fig. 7
Fig. 7
The diagram of mechanisms how acteoside inhibits inflammatory response via JAK/STAT signaling pathway in primary chondrocytes
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