Crocus sativus L. produces anti-inflammatory effects and regulates the NLRP3–NF-κB pathway

Abstract

Objective: This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus (Crocus sativus) and explore the underlying mechanism. Methods: Local and systemic inflammation models were used to investigate the anti-inflammatory effects of C. sativus. A xylene-induced inflammation model or lipopolysaccharide (LPS)-induced inflammation model was used in this study. C. sativus petal and stamen extracts were each administered to the mice in the xylene and LPS models by gavage for 14 d at 0.1 and 0.4 g/kg doses, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in mouse serum. Hematoxylin and eosin (H&E) staining was used to observe the pathological changes in the ear in the xylene-induced inflammation model and in the spleen in the LPS-induced inflammation model. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) protein levels within the nuclear factor-kappa B (NF-κB) pathway were assessed using western blotting. RAW264.7 cells were treated with LPS (5 μg/mL) and LPS + C. sativus (0.05, 0.1, and 0.2 mg/mL) for 24 h, and a Cell Counting Kit-8 was used to measure cell proliferation. Changes in NLRP3 and NF-κB levels were evaluated by western blotting. Results: Petal and stamen extracts of C. sativus attenuated the anti-inflammatory effects in local or systemic inflammatory models and repaired pathological changes in the ear in the xylene-induced inflammation model and spleen in the LPS-induced inflammation model. These extracts also decreased the concentrations of TNF-α and IL-1β in the mouse serum in the LPS-induced inflammation model. C. sativus downregulated NLRP3 protein level through the NF-κB pathway and downregulated LC-3 and BECLIN1 in vivo and in vitro. Carbonyl Cyanide3-ChloroPhenylhydrazone (CCCP) weakened the effects of C. sativus on the NLRP3–NF-κB pathway. Conclusion: C. sativus has anti-inflammatory effects and regulates the NLRP3-NF-κB pathway.