PMID- 38286072 OWN - NLM STAT- MEDLINE DCOM- 20240208 LR - 20240208 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 128 DP - 2024 Feb 15 TI - Crocetin inhibits mast cell-dependent immediate-type allergic reactions through Ca(2+)/PLC/IP3 and TNF pathway. PG - 111583 LID - S1567-5769(24)00101-2 [pii] LID - 10.1016/j.intimp.2024.111583 [doi] AB - Crocetin is a kind of glycocone naturally occurring in Crocus sativus L.. It is an active metabolite produced by biohydrolysis of Crocus sativus L.. Crocetin has anti-cardiovascular diseases and antioxidant effects, but its anti-allergic effect has not been reported. In this study, the inhibitory effect of crocetin on immunoglobulin E (IgE) - mediated allergic reaction and the mechanism of action were investigated. The passive cutaneous anaphylaxis (PCA) was used to elucidate the anti-allergic effects of crocetin in vivo. Degranulation assay, calcium imaging, and cytokine release assay were to evaluate the anti-allergic effect of crocetin in vitro. We found that crocetin IgE-mediated RBL-2H3 cell degranulation and allergy both in vitro and in vivo. The TNF pathway was inhibited by crocetin in our RNA-seq sequences, Furthermore, crocetin inhibits IgE-mediated calcium influx, and PLC / IP3 phosphorylation in RBL-2H3 cells. Our findings suggested that crocetin revealed prominent anti-allergy activity through TNF and Ca(2+)/PLC/IP3 pathway. CI - Copyright (c) 2024 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Fan, Ting AU - Fan T AD - Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. FAU - Jiang, Kai AU - Jiang K AD - Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. FAU - Wang, Zixiao AU - Wang Z AD - Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. FAU - Chang, Yu AU - Chang Y AD - Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. FAU - Tian, Hua AU - Tian H AD - Department of Respiratory and geriatrics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. Electronic address: tianhua80@sina.com. FAU - Huang, Jing AU - Huang J AD - Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. Electronic address: huangjing87206@126.com. LA - eng PT - Journal Article DEP - 20240128 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - SY7Q814VUP (Calcium) RN - 0 (trans-sodium crocetinate) RN - 37341-29-0 (Immunoglobulin E) RN - 0 (Anti-Allergic Agents) RN - 36-88-4 (Carotenoids) RN - 11103-57-4 (Vitamin A) SB - IM MH - Humans MH - Mast Cells MH - Calcium/metabolism MH - *Hypersensitivity/drug therapy MH - Immunoglobulin E/metabolism MH - *Hypersensitivity, Immediate MH - *Anti-Allergic Agents/therapeutic use MH - Cell Degranulation MH - *Carotenoids MH - Vitamin A/*analogs & derivatives OTO - NOTNLM OT - Allergy OT - Crocetin OT - Mast cell OT - TNF pathway COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/29 19:57 MHDA- 2024/02/08 06:43 CRDT- 2024/01/29 18:02 PHST- 2023/11/29 00:00 [received] PHST- 2024/01/21 00:00 [revised] PHST- 2024/01/22 00:00 [accepted] PHST- 2024/02/08 06:43 [medline] PHST- 2024/01/29 19:57 [pubmed] PHST- 2024/01/29 18:02 [entrez] AID - S1567-5769(24)00101-2 [pii] AID - 10.1016/j.intimp.2024.111583 [doi] PST - ppublish SO - Int Immunopharmacol. 2024 Feb 15;128:111583. doi: 10.1016/j.intimp.2024.111583. Epub 2024 Jan 28.