Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation

Incarvillea compacta Maxim is a traditional Tibetan medicine used to treat inflammation-related diseases, such as pneumonia, fever, jaundice, and otitis media. However, no studies have examined its anti-inflammatory mechanism. To validate the anti-inflammatory activity of I. compacta extract (ICE) a...

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Main Authors: Ji Zhang, Yujing Feng, Shengqiang Han, Xueting Guan, Ziliang He, Chao Song, Lingyun Lv, Qiaoyu Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1058012/full
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author Ji Zhang
Ji Zhang
Yujing Feng
Shengqiang Han
Xueting Guan
Ziliang He
Chao Song
Lingyun Lv
Qiaoyu Luo
author_facet Ji Zhang
Ji Zhang
Yujing Feng
Shengqiang Han
Xueting Guan
Ziliang He
Chao Song
Lingyun Lv
Qiaoyu Luo
author_sort Ji Zhang
collection DOAJ
description Incarvillea compacta Maxim is a traditional Tibetan medicine used to treat inflammation-related diseases, such as pneumonia, fever, jaundice, and otitis media. However, no studies have examined its anti-inflammatory mechanism. To validate the anti-inflammatory activity of I. compacta extract (ICE) and its protective effect on acute alcoholic gastritis, Phytochemicals of I. compacta were identified using Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Lipopolysaccharide (LPS)-induced RAW 264.7 macrophages were used in vitro along with an in vivo a mouse acute gastritis model. Pro-inflammatory mediators and cytokines were measured using the Griess reagent and Cytometric bead array (CBA) assay. Furthermore, inflammation-related molecules were analysed by Western blotting, RNA-Seq, and real-time quantitative PCR (RT-qPCR). The experimental results revealed that ICE decreased the nitric oxide (NO), IL-6, MCP-1, and TNF-α levels in LPS-stimulated RAW 264.7 cells, and downregulated the expression and phosphorylation of PDK1, AKT, and GSK3β. Moreover, ICE also downregulated the activation of NLRP3. The RNA-Seq analysis revealed that 340 differentially expressed genes (DEGs) response to ICE treatment was enriched in several inflammation-related biological processes. The results of the in vivo mouse acute gastritis model showed that ICE significantly reduced inflammatory lesions in the gastric mucosa and remarkably downregulated the expression of iNOS, TNF-α, IL-1β, and IL-6 mRNA in gastric tissue. Therefore, the results of this study obtained scientific evidence supporting the use of I. compacta.
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spelling doaj.art-8c6498e447b349c2b7120ca061f46a5e2022-12-22T04:34:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10580121058012Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activationJi Zhang0Ji Zhang1Yujing Feng2Shengqiang Han3Xueting Guan4Ziliang He5Chao Song6Lingyun Lv7Qiaoyu Luo8School of Life Sciences, Huaiyin Normal University, Huaian, ChinaQinghai Provincial Key Laboratory of Medicinal Plant and Animal Resources of Qinghai-Tibet Plateau, Qinghai Normal University, Xining, ChinaDepartment of Anesthesiology, Punan Hospital, Shanghai, ChinaSchool of Life Sciences, Huaiyin Normal University, Huaian, ChinaSchool of Life Sciences, Huaiyin Normal University, Huaian, ChinaSchool of Life Sciences, Huaiyin Normal University, Huaian, ChinaSchool of Life Sciences, Huaiyin Normal University, Huaian, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an, ChinaQinghai Provincial Key Laboratory of Medicinal Plant and Animal Resources of Qinghai-Tibet Plateau, Qinghai Normal University, Xining, ChinaIncarvillea compacta Maxim is a traditional Tibetan medicine used to treat inflammation-related diseases, such as pneumonia, fever, jaundice, and otitis media. However, no studies have examined its anti-inflammatory mechanism. To validate the anti-inflammatory activity of I. compacta extract (ICE) and its protective effect on acute alcoholic gastritis, Phytochemicals of I. compacta were identified using Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Lipopolysaccharide (LPS)-induced RAW 264.7 macrophages were used in vitro along with an in vivo a mouse acute gastritis model. Pro-inflammatory mediators and cytokines were measured using the Griess reagent and Cytometric bead array (CBA) assay. Furthermore, inflammation-related molecules were analysed by Western blotting, RNA-Seq, and real-time quantitative PCR (RT-qPCR). The experimental results revealed that ICE decreased the nitric oxide (NO), IL-6, MCP-1, and TNF-α levels in LPS-stimulated RAW 264.7 cells, and downregulated the expression and phosphorylation of PDK1, AKT, and GSK3β. Moreover, ICE also downregulated the activation of NLRP3. The RNA-Seq analysis revealed that 340 differentially expressed genes (DEGs) response to ICE treatment was enriched in several inflammation-related biological processes. The results of the in vivo mouse acute gastritis model showed that ICE significantly reduced inflammatory lesions in the gastric mucosa and remarkably downregulated the expression of iNOS, TNF-α, IL-1β, and IL-6 mRNA in gastric tissue. Therefore, the results of this study obtained scientific evidence supporting the use of I. compacta.https://www.frontiersin.org/articles/10.3389/fphar.2022.1058012/fullIncarvillea compacta Maximanti-inflammatoryRNA sequencingPI3K/Akt signaling pathwayacute gastritis
spellingShingle Ji Zhang
Ji Zhang
Yujing Feng
Shengqiang Han
Xueting Guan
Ziliang He
Chao Song
Lingyun Lv
Qiaoyu Luo
Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation
Frontiers in Pharmacology
Incarvillea compacta Maxim
anti-inflammatory
RNA sequencing
PI3K/Akt signaling pathway
acute gastritis
title Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation
title_full Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation
title_fullStr Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation
title_full_unstemmed Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation
title_short Incarvillea compacta Maxim ameliorates inflammatory response via inhibiting PI3K/AKT pathway and NLRP3 activation
title_sort incarvillea compacta maxim ameliorates inflammatory response via inhibiting pi3k akt pathway and nlrp3 activation
topic Incarvillea compacta Maxim
anti-inflammatory
RNA sequencing
PI3K/Akt signaling pathway
acute gastritis
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1058012/full
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