Crocus sativus L. produces anti-inflammatory effects and regulates the NLRP3–NF-κB pathway
Liang Yang, Huan Xu, Qian Hong, Nuo Xu, Yan Zhang, Rui Tao, Shuai Cheng Li, Zizheng Zhang, Jiahao Geng, Zihan Wang, Huizi Hu, Yan Dong, Zhaoyi Chu, Bin Zheng, Jinmiao Zhu, Ming Geng, Yue Gao
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.