Ursolic acid represses influenza A virus-triggered inflammation and oxidative stress in A549 cells by modulating the miR-34c-5p/TLR5 axis

Wei, Xing; Lan, Yuying; Nong, Zhifei; Li, Chongjin; Feng, Zhiqiong; Mei, Xiaoping; Zhai, Yang; Zou, Min

doi:10.1016/j.cyto.2022.155947

Cited by 13 publications

(9 citation statements)

References 43 publications

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“…Beta-sitosterol is reported for its protection against influenza through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV) infected cells to suppress inflammatory response ( Zhou et al, 2020 ). Ursolic acid attenuates IAV-triggered inflammatory responses by regulating the miR-34c-5p/TLR5 axis ( Wei et al, 2022 ). Kaempferol exhibits a protective effect on virus-induced inflammation via suppression of TLR4/MyD88-mediated NF-κB and MAPK pathways ( Zhang et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

Tang

Wang²,

Zhang³

et al. 2022

Front. Microbiol.

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ObjectiveTo investigate the active ingredients, underlying anti-influenza virus effects, and mechanisms of Huoxiang Suling Shuanghua Decoction (HSSD).Materials and methodsThe therapeutic effect of HSSD were confirmed through the survival rate experiment of H1N1-infected mice. Then, the HSSD solution and the ingredients absorbed into the blood after treatment with HSSD in rats were identified by UPLC/Q-TOF MS, while the main contents of ingredients were detected by high performance liquid chromatography (HPLC). Next, a systems pharmacology approach incorporating target prediction, gene ontology (GO) enrichment, kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and molecular docking were performed to screen out the active compounds and critical pathways of HSSD in treating influenza. According to prediction results, real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry assay were used to detect the mRNA and protein expression levels of critical targets in H1N1-infected mice lungs.ResultsHuoxiang Suling Shuanghua Decoction improved the survival rate of H1N1-infected mice and prolonged the mice’s lifespan. Besides, HSSD exerts an antivirus effect by decreasing the levels of hemagglutinin (HA) and nucleoprotein (NP) to inhibit the replication and proliferation of H1N1, reducing the lung pathological state, inhibiting the cell apoptosis in the lung, and regulating the abnormal responses of peripheral blood, including GRA, LYM, white blood cell (WBC), PLT, and hemoglobin (HGB). Then, 87 compounds in the HSSD solution and 20 ingredients absorbed into the blood after treatment with HSSD were identified. Based on this, combined with the network analysis and previous research on antivirus, 16 compounds were screened out as the active components. Moreover, 16 potential targets were predicted by network pharmacology analysis. Next, molecular docking results showed stable binding modes between compounds and targets. Furthermore, experimental validation results indicated that HSSD regulates the contents of Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) in serum, modulating the levels of IFN-γ, IL-6, IL-10, MCP-1, MIP-1α, and IP-10 in the lung tissue, and significantly decreasing the mRNA and protein expressions of TLR4, CD14, MyD88, NF-κB p65, HIF1 α, VEGF, IL17A, and IL6 in the lung tissue.ConclusionHuoxiang Suling Shuanghua Decoction exerts an anti-influenza effect by affecting the expressions of mRNA and protein including TLR4, CD14, MyD88, NF-kB p65, HIF-1α, VEGF, IL17A, IL6, and inhibiting the accumulation of inflammation. Our study provided experimental pieces of evidence about the practical application of HSSD in treating influenza.

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Section: Discussionmentioning

confidence: 99%

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

Tang

Wang²,

Zhang³

et al. 2022

Front. Microbiol.

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“…miR-449a-5p could control the inflammatory responses of recipient T cells and induce apoptosis by AKT signaling ( 56 , 57 ). miR-34c-5p could promote GCs apoptosis and it has been shown to be closely related to inflammatory responses and oxidative stress ( 58 , 59 ). On the other hand, HS down-regulated miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Negative effects of heat stress on ovarian tissue in female rabbit

et al. 2022

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Numerous studies have highlighted the role of miRNA in the deformation and necrosis of cells of ovarian tissue caused by heat stress (HS), which ultimately affects ovarian function. Although the role of small RNAs has been investigated in alterations in ovarian tissue functioning in response to HS, the expression profile of ovarian miRNA has been explored to a lesser extent. In this study, female rabbits were subject to HS treatment by using electrical heater. The current work demonstrated that HS could significantly change physiological performance of female rabbits including body weight, rectal temperature and relative ovary weight, and significantly reduce serum IL-2, IL-8, CAT, and GSH-Px concentrations by enzyme-linked immunosorbent assay (ELISA) technique. As a result, an increase in apoptosis in ovarian cells, as well as unhealthy follicles, were observed by Hematoxylin-eosin (HE) and TUNEL staining. Additionally, small RNA-seq revealed changes in the miRNA expression profile of rabbit ovaries under HS. Five hundred fourteen miRNAs were obtained including known miRNAs 442 and novel miRNAs 72. Among these miRNAs, 23 miRNAs were significantly expressed under HS. Eleven differentially expressed miRNAs (DE miRNAs) and 9 their predicted targets were confirmed by qPCR, which were expected miRNA–mRNA negative regulation pattern. Among the DE miRNAs and targets, miR-141-39 may target COQ6, miR-449a-5p and miR-34c-5p may control RFC5 and RTN2 together, miR-449a-5p may target ACADVL, miR-34c-5p potentially targets Bcl-2 and miR-196b-5p potentially regulates CASK and HOXB6. Thus, the current work suggested the negative effects of HS on the ovarian tissue of female rabbits, and in conclusion these changes could be caused by decreased serum IL-2, IL-8, CAT and GSH-Px levels, increased ovarian apoptosis, and changed the expression of miRNAs.

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“…Tobacco smoke extract, benzo(a)pyrene, azoxymethane and other chemical agents, 29,31,52,53 as well as reactive oxygen species generators (e.g. hydrogen peroxide), 54,55 ionising radiation 56 and Epstein–Barr virus (viral pathogens), were all tested 30,57,58 …”

Section: Therapeutic Potential Of Uamentioning

confidence: 99%

“…hydrogen peroxide), 54,55 ionising radiation 56 and Epstein-Barr virus (viral pathogens), were all tested. 30,57,58 Anti-inflammatory activity Many disorders, including neurological, cardiovascular and cancerous ones, are connected with the complex process called inflammation. 59 Inflammatory gene expression is regulated by the NF-κB signalling pathway.…”

Section: Other Factorsmentioning

confidence: 99%

“…The purity of UA and its derivatives extract can be increased by using different preparation methods based on chromatography fractionation of the crude extracts. For example, more than 95% purity can be achieved through an RP‐C18 reverse phase column 30 or thin layer chromatography 31 . Additionally, it has been documented that solvent fractionation may purify UA to a purity of 98%–99.5% before precipitation and recovery utilising solvents such as distilled water, ethanol, petroleum ether, acetone and ethyl acetate.…”

Section: Extraction Of Uamentioning

confidence: 99%

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Therapeutic potential and novel formulations of ursolic acid and its derivatives: an updated review

Namdeo

Gidwani²,

Tiwari

et al. 2023

J Sci Food Agric

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Plants produce biologically active metabolites that have been utilised to cure a variety of severe and persistent illnesses. There is a possibility that understanding how these bioactive molecules work would allow researchers to come up with better treatments for diseases including malignancy, cardiac disease and neurological disorders. A triterpene called ursolic acid (UA) is a pentacyclic prevalent triterpenoid found in fruits, leaves, herbs and blooms. The biological and chemical aspects of UA, as well as their presence, plant sources and biosynthesis, and traditional and newer technologies of extraction, are discussed in this review. Because of its biological function in the creation of new therapeutic techniques, UA is a feasible option for the evolution and medical management of a wide range of medical conditions, including cancer and other life threatening diseases. Despite this, the substance's poor solubility in aquatic environments makes it unsuitable for medicinal purposes. This hurdle was resolved in many different ways. The inclusion of UA into various pharmaceutical delivery approaches was found to be quite effective in this respect. This review also describes the properties of UA and its pharmacokinetics, as well as therapeutic applications of UA for cancer, inflammatory and cardiovascular diseases, in addition to its anti‐diabetic, immunomodulatory, hepatoprotective and anti‐microbial properties. Some of the recent findings related to novel nano‐sized carriers as a delivery system for UA and the patents related to the applications of UA and its various derivatives are covered in this review. The analytical study of UA, oleanolic acid and other phytoconstituents by UV, HPLC, high‐performance thin‐layer chromatography and gas chromatography is also discussed. In the future, UA could be explored in vivo using various animal models and, in addition, the regulatory status regarding UA needs to be explored. © 2023 Society of Chemical Industry.

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Ursolic acid represses influenza A virus-triggered inflammation and oxidative stress in A549 cells by modulating the miR-34c-5p/TLR5 axis

Cited by 13 publications

References 43 publications

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

Negative effects of heat stress on ovarian tissue in female rabbit

Therapeutic potential and novel formulations of ursolic acid and its derivatives: an updated review

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