Objective To investigate the ameliorative effect of combination of schisandrin B (Sch B) and platycodin D (PD) on pulmonary fibrosis, and explore whether it acts by inhibiting Janus kinase 2 (JAK2)/signal transducer and activator of transcription 6 (STAT6) pathway and regulating the balance of macrophage M1/M2 polarization. Methods A rat model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. The rats were randomly divided into control group, model group, prednisone (5 mg/kg) group, Sch B (10 mg/kg) group, PD (20 mg/kg) group and Sch B + PD group, with eight rats in each group. After 28 d of administration, lung index was measured. Pathological changes in lung tissue were observed using hematoxylin-eosin (HE), Masson and Sirius red staining. Levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), as well as hydroxyproline (Hyp) level in lung tissue were detected. Expressions of α-smooth muscle actin (α-SMA) and E-cadherin in lung tissue were assessed by immunofluorescence. The mRNA expressions of M1/M2 macrophage markers [inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, cluster of differentiation 206 (CD206), arginase 1 (Arg1) and IL-10] in lung tissue were measured by qRT-PCR. The expressions of JAK2/STAT6 pathway related proteins in lung tissue was determined by Western blotting. In vitro experiments, the effect of Sch B combined with PD on JAK2/STAT6 pathway were validated using an IL-4/IL-13-induced macrophage M2 polarization model. Results Compared with control group, lung index of rats in model group was significantly increased (P < 0.01), with a large amount of inflammatory cell infiltration in alveoli, increased alveolar diaphragmatic rupture and severe alveolar damage, levels of IL-1β, TNF-α, IL-6 in BALF and Hyp in lung tissue were significantly increased (P < 0.01); The expression of α-SMA in lung tissue was significantly increased (P < 0.01), while the expression of E-cadherin was significantly decreased (P < 0.01); The expression levels of iNOS, TNF-α, IL-1β, CD206 and Arg1 mRNA in lung tissue were significantly increased (P < 0.01), while the expression level of IL-10 mRNA was significantly decreased (P < 0.01); The expression levels of JAK2 and p-STAT6/STAT6 proteins in lung tissue were significantly increased (P < 0.01). Compared with model group, the combination of Sch B and PD could significantly reduce the lung index of rats (P < 0.01), improve pulmonary fibrosis pathological damage, inhibit the release of inflammatory factors and Hyp level in lung tissue (P < 0.01), reduce α-SMA expression (P < 0.01), partially restore E-cadherin expression (P < 0.01), significantly down-regulate iNOS, TNF-α, IL-1β, CD206, Arg1 mRNA expressions in lung tissue (P < 0.01), up-regulate IL-10 mRNA expression (P < 0.01), inhibit JAK2 and p-STAT6/STAT6 protein expressions (P < 0.01). The in vitro experimental results showed that compared with control group, the expression levels of CD206 and Arg1 mRNA in model group were significantly increased (P < 0.01), and the expressions of JAK2 and p-STAT6/STAT6 proteins were significantly up-regulated (P < 0.01); Compared with model group, the combination of Sch B and PD significantly inhibited the expressions of M2 polarization markers CD206 and Arg1 (P < 0.01), and down-regulated the expressions of JAK2 and p-STAT6/STAT6 proteins (P < 0.01). Compared with the group treated alone, the combination of Sch B and PD showed better efficacy (P < 0.05, 0.01). Conclusion The combination of Sch B and PD could synergistically alleviate pulmonary fibrosis, and its mechanism may be related to inhibiting the activation of JAK2/STAT6 pathway, thereby correcting the imbalance of M1/M2 macrophage polarization.

schisandrin B  /  platycodin D  /  pulmonary fibrosis  /  macrophage polarization  /  JAK/STAT pathway