Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway

Background: Smilax is a traditional medicine used for the clinical treatment of pelvic inflammatory disease (CPID), and its leaves have long been used as food by the Korean people in Asia. In previous studies, we found that flavonoids extract can improve CPID by inhibiting inflammation, which may be...

Full description

Bibliographic Details
Main Authors: Yun Ma, Tingting Pei, Luyao Song, Daoqi Zhu, Zhongxiao Han, Jiaxing Zhang, Xintao Huang, Xinhuan Qiu, Wei Xiao
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464623004024
_version_ 1797660407104536576
author Yun Ma
Tingting Pei
Luyao Song
Daoqi Zhu
Zhongxiao Han
Jiaxing Zhang
Xintao Huang
Xinhuan Qiu
Wei Xiao
author_facet Yun Ma
Tingting Pei
Luyao Song
Daoqi Zhu
Zhongxiao Han
Jiaxing Zhang
Xintao Huang
Xinhuan Qiu
Wei Xiao
author_sort Yun Ma
collection DOAJ
description Background: Smilax is a traditional medicine used for the clinical treatment of pelvic inflammatory disease (CPID), and its leaves have long been used as food by the Korean people in Asia. In previous studies, we found that flavonoids extract can improve CPID by inhibiting inflammation, which may be the main effective component of Smilax China, but its mechanism of action has not been fully elucidated. This study explores the mechanism by which Chinese rhizome flavonoids (FSCR) regulate the autophagy pathway of NLRP3 inflammasome and promote macrophage reprogramming. Methods: In the in vivo experiment, the sham surgery group and the CPID group were given physiological saline and FCSR for 7 days, respectively. We determined the expression of NLRP3 inflammasome autophagy pathway genes and proteins by observing the pathological damage of rat uteri through HE and Masson staining, immunofluorescence, RT-PCR, and WB experiments. Molecular docking simulation predicted the binding potential of flavonoids with the potential target VPS34, and knockdown experiments were conducted to validate the knockdown effect of lipopolysaccharide treatment on primary rat endometrial cells to simulate an in vitro CPID model. Results: FCSR significantly reduced serum IL-1β in CPID rats, TNF-α. The concentration of TAX2 reduced the infiltration of inflammatory cells and fibrosis of endometrial cells, promoted M2 polarization of macrophages, upregulated autophagy pathways, and inhibited the activation of NLRP3 inflammasomes. After knocking down the NLRP3 inflammasome autophagy target VPS34, the FSCR effect was eliminated. Conclusions: By targeting VPS34, FCSR potentially promotes autophagic cell reprogramming through the NLRP3 inflammasome related autophagy pathway.
first_indexed 2024-03-11T18:29:21Z
format Article
id doaj.art-d691f89eeddb49dbb85360d230e7e5f1
institution Directory Open Access Journal
issn 1756-4646
language English
last_indexed 2024-03-11T18:29:21Z
publishDate 2023-10-01
publisher Elsevier
record_format Article
series Journal of Functional Foods
spelling doaj.art-d691f89eeddb49dbb85360d230e7e5f12023-10-13T13:52:55ZengElsevierJournal of Functional Foods1756-46462023-10-01109105802Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathwayYun Ma0Tingting Pei1Luyao Song2Daoqi Zhu3Zhongxiao Han4Jiaxing Zhang5Xintao Huang6Xinhuan Qiu7Wei Xiao8Department of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaKey Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China; Corresponding author at: Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.Background: Smilax is a traditional medicine used for the clinical treatment of pelvic inflammatory disease (CPID), and its leaves have long been used as food by the Korean people in Asia. In previous studies, we found that flavonoids extract can improve CPID by inhibiting inflammation, which may be the main effective component of Smilax China, but its mechanism of action has not been fully elucidated. This study explores the mechanism by which Chinese rhizome flavonoids (FSCR) regulate the autophagy pathway of NLRP3 inflammasome and promote macrophage reprogramming. Methods: In the in vivo experiment, the sham surgery group and the CPID group were given physiological saline and FCSR for 7 days, respectively. We determined the expression of NLRP3 inflammasome autophagy pathway genes and proteins by observing the pathological damage of rat uteri through HE and Masson staining, immunofluorescence, RT-PCR, and WB experiments. Molecular docking simulation predicted the binding potential of flavonoids with the potential target VPS34, and knockdown experiments were conducted to validate the knockdown effect of lipopolysaccharide treatment on primary rat endometrial cells to simulate an in vitro CPID model. Results: FCSR significantly reduced serum IL-1β in CPID rats, TNF-α. The concentration of TAX2 reduced the infiltration of inflammatory cells and fibrosis of endometrial cells, promoted M2 polarization of macrophages, upregulated autophagy pathways, and inhibited the activation of NLRP3 inflammasomes. After knocking down the NLRP3 inflammasome autophagy target VPS34, the FSCR effect was eliminated. Conclusions: By targeting VPS34, FCSR potentially promotes autophagic cell reprogramming through the NLRP3 inflammasome related autophagy pathway.http://www.sciencedirect.com/science/article/pii/S1756464623004024Flavonoid extract of Smilax china L.Chronic pelvic inflammationMacrophage reprogrammingInflammasomeAutophagy
spellingShingle Yun Ma
Tingting Pei
Luyao Song
Daoqi Zhu
Zhongxiao Han
Jiaxing Zhang
Xintao Huang
Xinhuan Qiu
Wei Xiao
Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway
Journal of Functional Foods
Flavonoid extract of Smilax china L.
Chronic pelvic inflammation
Macrophage reprogramming
Inflammasome
Autophagy
title Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway
title_full Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway
title_fullStr Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway
title_full_unstemmed Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway
title_short Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway
title_sort flavonoids from smilax china l rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the nlrp3 inflammasome autophagy pathway
topic Flavonoid extract of Smilax china L.
Chronic pelvic inflammation
Macrophage reprogramming
Inflammasome
Autophagy
url http://www.sciencedirect.com/science/article/pii/S1756464623004024
work_keys_str_mv AT yunma flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT tingtingpei flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT luyaosong flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT daoqizhu flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT zhongxiaohan flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT jiaxingzhang flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT xintaohuang flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT xinhuanqiu flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway
AT weixiao flavonoidsfromsmilaxchinalrhizomeimprovechronicpelvicinflammatorydiseasebypromotingmacrophagereprogrammingviathenlrp3inflammasomeautophagypathway