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 LPSβ+βC. 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.

Keywords

Autophagy / Crocus sativus L / Inflammatory / NOD-like receptor thermal protein domain associated protein 3 / Nuclear factor kappa B

Conflict of interest statement

Yue Gao is an editorial board member of the journal. None of the other authors declare any conflicts of interest.

Funding

This work was supported by the National Natural Science Foundation of China (81873063); High-level talents Research project of Hefei Normal University (2020rcjj30); Key Project of Provincial Scientific Research Platform of Hefei Normal University in 2020 (2020PTZD14); Key Project of Universities Natural Science Foundation of Anhui province (KJ2021A0935, KJ2021A0932). Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202009).

Author contributions

Data curation: Zihan Wang and Yan Zhang; Funding acquisition: Liang Yang and Yue Gao; Investigation: Liang Yang, Qian Hong, and Huizi Hu; Resources: Yan Dong; Software: Huan Hua Xu; Supervision: Yue Gao; Visualization: Nuo Xu, Rui Tao, and Ming Geng; Writing - original draft: Liang Yang and Bin Zheng; Writing - review & editing: Jinmiao Zhu. All authors have read and agreed to the published version of the manuscript.

Ethical approval of studies and informed consent

The use of animals in this study was approved by the Animal Ethics Committee of Hefei Normal University (HFNUCM-2021013).

Acknowledgments

We thank the support from “Anhui Engineering Laboratory for Medicinal and Food Homologous Natural Resources Exploration.”

Data availability

All data generated or analyzed during this study are included in this published article.

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Acupuncture and Herbal Medicine