PMID- 35623408 OWN - NLM STAT- MEDLINE DCOM- 20220714 LR - 20220725 IS - 1873-2968 (Electronic) IS - 0006-2952 (Linking) VI - 202 DP - 2022 Aug TI - Panax notoginseng saponin R1 attenuates allergic rhinitis through AMPK/Drp1 mediated mitochondrial fission. PG - 115106 LID - S0006-2952(22)00200-3 [pii] LID - 10.1016/j.bcp.2022.115106 [doi] AB - We investigated whether Panax notoginseng saponin (PNS-R1) attenuates allergic rhinitis (AR) through AMPK/Drp1-mediated mitochondrial fission. AR model was established in mice by Ovalbumin (OVA). In vitro, human nasal epithelial cells (HNEpCs) were stimulated using recombinant human interleukin 13 (IL-13). PNS-R1 was administrated in vivo and in vitro. Then, HE staining of nasal tissue, ELISA detection of immunoglobulin E (IgE) and proinflammatory cytokine levels in serum and nasal lavage fluid, flow cytometry analysis of Th1/Th2 ratio and apoptosis, TUNEL staining, Western blot, detection of reactive oxygen species (ROS) and mitochondrial ROS, immunofluorescence analysis of Tom20 and mitochondrial fission protein Drp1 co-localization, and mitochondrial membrane potential detection, were performed. PNS-R1 attenuated allergic symptoms in AR mice, decreased OVA-specific IgE, IL-4, IL-6, IL-8, IL-13, and TNF-alpha levels, and restored the Th1/Th2 imbalance. Meanwhile, we found that PNS-R1 treatment significantly reduced apoptosis, ROS production, and co-localization of Tom20 and Drp1 in the nasal epithelium of AR mice. In vitro, we found that PNS-R1 upregulated mitochondrial membrane potential and reduced ROS and mitochondrial ROS production as well as Cleaved-caspase-3/9, Bax, Cyt-c, Apaf-1 expression and mitochondrial fission. Mechanistically, we found that PNS-R1 downregulated Drp1 phosphorylation (Ser 616) and Drp1 translocation in an AMPK-dependent manner, promoted MFN2 expression, and reduced TXNIP, NLRP3, Caspase-1, and IL-1beta expression. PNS-R1 may protect mitochondrial integrity by inhibiting AMPK/Drp1 and TXNIP/NLRP3 signaling pathway, thereby alleviating AR symptoms in mice. PNS-R1 may have great potential as a therapeutic agent for AR. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Zhang, Yalin AU - Zhang Y AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Otorhinolaryngology, Affiliated Hospital of Yanbian University, Yanji 133000, PR China. FAU - Song, Yilan AU - Song Y AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, PR China. FAU - Wang, Chongyang AU - Wang C AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, PR China. FAU - Jiang, Jingzhi AU - Jiang J AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, PR China. FAU - Liu, Siqi AU - Liu S AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Otorhinolaryngology, Affiliated Hospital of Yanbian University, Yanji 133000, PR China. FAU - Bai, Qiaoyun AU - Bai Q AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, PR China. FAU - Li, Liangchang AU - Li L AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, PR China. FAU - Jin, Hainan AU - Jin H AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Otorhinolaryngology, Affiliated Hospital of Yanbian University, Yanji 133000, PR China. FAU - Jin, Yongde AU - Jin Y AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Otorhinolaryngology, Affiliated Hospital of Yanbian University, Yanji 133000, PR China. Electronic address: jyd0091@126.com. FAU - Yan, Guanghai AU - Yan G AD - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, PR China; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji 133002, PR China. Electronic address: ghyan@ybu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220524 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Interleukin-13) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 0 (Saponins) RN - 37341-29-0 (Immunoglobulin E) RN - 9006-59-1 (Ovalbumin) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases MH - Animals MH - Disease Models, Animal MH - Humans MH - Immunoglobulin E MH - Interleukin-13/therapeutic use MH - Mice MH - Mitochondrial Dynamics MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Ovalbumin MH - *Panax notoginseng/metabolism MH - Reactive Oxygen Species/metabolism MH - *Rhinitis, Allergic/chemically induced/drug therapy MH - *Saponins/pharmacology/therapeutic use OTO - NOTNLM OT - AMPK OT - Drp1 OT - Mitochondrial fission OT - NLRP3 OT - PNS-R1 OT - TXNIP EDAT- 2022/05/28 06:00 MHDA- 2022/07/15 06:00 CRDT- 2022/05/27 19:23 PHST- 2022/03/30 00:00 [received] PHST- 2022/05/19 00:00 [revised] PHST- 2022/05/19 00:00 [accepted] PHST- 2022/05/28 06:00 [pubmed] PHST- 2022/07/15 06:00 [medline] PHST- 2022/05/27 19:23 [entrez] AID - S0006-2952(22)00200-3 [pii] AID - 10.1016/j.bcp.2022.115106 [doi] PST - ppublish SO - Biochem Pharmacol. 2022 Aug;202:115106. doi: 10.1016/j.bcp.2022.115106. Epub 2022 May 24.