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In the face of increasingly serious environmental pollution, the health of human lung tissues is also facing serious threats. Mogroside IIE (M2E) is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori. The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury (ALI). A lipopolysaccharide (LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting, co-immunoprecipitation, and quantitative real time-PCR analysis. The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA (Pla2g2a)-epidermal growth factor receptor (EGFR). The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation. In addition, M2E protected ALI induced with LPS against inflammatory and damage which w ere significantly dependent upon the downregulation of AKT and mTOR via the inhibition of Pla2g2a-EGFR. Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury, which may represent a promising strategy to treat ALI.


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Mogroside IIE,an in vivo metabolite of sweet agent,alleviates acute lung injury via Pla2g2a-EGFR inhibition

Show Author's information Weichao LüaGuoqing RenaKuniyoshi Shimizub,cRenshi Lia,b( )Chaofeng Zhanga,b,( )
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy,China Pharmaceutical University, Nanjing 211198, China
Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan

Peer review under responsibility of Tsinghua University Press.

Highlights

● Mogroside ⅡE was characterized by the highest anti-lung injury ability.

● Mogroside ⅡE is a natural Pla2g2a inhibitor among the mogrosides.

● Inhibiting the interaction of Pla2g2a and EGFR significantly relieves lung injury.

● Mogroside ⅡE inhibits the activation of EGFR-AKT-mTOR by inhibiting Pla2g2a.

Abstract

In the face of increasingly serious environmental pollution, the health of human lung tissues is also facing serious threats. Mogroside IIE (M2E) is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori. The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury (ALI). A lipopolysaccharide (LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting, co-immunoprecipitation, and quantitative real time-PCR analysis. The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA (Pla2g2a)-epidermal growth factor receptor (EGFR). The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation. In addition, M2E protected ALI induced with LPS against inflammatory and damage which w ere significantly dependent upon the downregulation of AKT and mTOR via the inhibition of Pla2g2a-EGFR. Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury, which may represent a promising strategy to treat ALI.

Keywords: Acute lung injury, Mogroside IIE, Secreted phospholipase A2 type IIA (Pla2g2a), Epidermal growth factor receptor (EGFR)

References(34)

[1]

X. Gong, N. Chen, K. Ren, et al., The fruits of Siraitia grosvenorii: a review of a Chinese food-medicine, Front. Pharmacol. 10 (2020) 1400. http://dx.doi.org/10.3389/fphar.2019.01400.

[2]

Y. Chen, X.B. Fan, Y.X. Wang, et al., Functional study of natural food sweetener mogrosides, China Food Addit. 1 (2006) 41-43.

[3]

R. Di, M.T. Huang, C.T. Ho, Anti-inflammatory activities of mogrosides from Momordica grosvenori in murine macrophages and a murine ear edema model, J. Agric. Food Chem. 59(13) (2011) 7474-7481. http://dx.doi.org/10.1021/jf201207m.

[4]

G.P. Lin, T. Jiang, X.B. Hu, et al., Effect of Siraitia grosvenorii polysaccharide on glucose and lipid of diabetic rabbits induced by feeding high fat/high sucrose chow, Exp. Diabetes Res. 2007 (2007) 67435. http://dx.doi.org/10.1155/2007/67435.

[5]

J. Xiao, K. Huang, H. Lin, et al., Mogroside IIE inhibits digestive enzymes via suppression of interleukin 9/interleukin 9 receptor signalling in acute pancreatitis, Front. Pharmacol. 11 (2020) 859. http://dx.doi.org/10.3389/fphar.2020.00859.

[6]

F. Xu, D.P. Li, Z.C. Huang, et al., Exploring in vitro, in vivo metabolism of mogroside V and distribution of its metabolites in rats by HPLC-ESI-ITTOF-MSn, J. Pharm. Biomed. Anal. 115 (2015) 418-430. http://dx.doi.org/10.1016/j.jpba.2015.07.024.

[7]

D.E. Schraufnagel, J.R. Balmes, C.T. Cowl, et al., Air pollution and noncommunicable diseases: a review by the forum of international respiratory societies’ environmental committee, part 2: air pollution and organ systems, Chest 155(2) (2019) 417-426. http://dx.doi.org/10.1016/j.chest.2018.10.041.

[8]

J.P. Reilly, Z. Zhao, M.G.S. Shashaty, et al., Low to moderate air pollutant exposure and acute respiratory distress syndrome after severe trauma, Am. J. Respir. Crit. Care. Med. 199(1) (2019) 62-70. http://dx.doi.org/10.1164/rccm.201803-0435OC.

[9]

L.B. Ware, M.A. Matthay, The acute respiratory distress syndrome, N. Eng. J. Med. 342(18) (2000) 1334-1349. http://dx.doi.org/10.1056/NEJM200005043421806.

[10]

Y. Imai, K. Kuba, G.G. Neely, et al., Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury, Cell 133(2) (2008) 235-249. http://dx.doi.org/10.1016/j.cell.2008.02.043.

[11]

M. Hernández, R. Martín, M.D. García-Cubillas, et al., Secreted PLA2 induces proliferation in astrocytoma through the EGF receptor: another inflammation-cancer link, Neuro. Oncol. 12 (2020) 1014-1023. http://dx.doi.org/10.1093/neuonc/noq078.

[12]

A.O. Akinkuolie, P.R. Lawler, A.Y. Chu, et al., Group IIA secretory phospholipase A2, vascular inflammation, and incident cardiovascular disease, Arterioscler. Thromb. Vasc. Biol. 39(6) (2019) 1182-1190. http://dx.doi.org/10.1161/ATVBAHA.118.311894.

[13]

S.Y. Zhang, D. Shao, H. Liu, et al., Metabolomics analysis reveals that benzo[a]pyrene, a component of PM2.5, promotes pulmonary injury by modifying lipid metabolism in a phospholipase A2-dependent manner in vivo and in vitro, Redox. Biol. 13 (2017) 459-469. http://dx.doi.org/10.1016/j.redox.2017.07.001.

[14]

A.S. Ali, S. Ali, B.F. El-Rayes, et al., Exploitation of protein kinase C: a useful target for cancer therapy, Cancer Treat. Rev. 35(1) (2009) 1-8. http://dx.doi.org/10.1016/j.ctrv.2008.07.006.

[15]

S. Papadopoulos, E. Kazepidou, M.H. Antonelou, et al., Secretory phospholipase A2-IIA protein and mrna pools in extracellular vesicles of bronchoalveolar lavage fluid from patients with early acute respiratory distress syndrome: a new perception in the dissemination of inflammation, Pharmaceuticals 13(11) (2020) 415. http://dx.doi.org/10.3390/ph13110415.

[16]

F.R. D’Alessio, Mouse models of acute lung injury and ARDS, Methods Mol. Biol. 1809 (2018) 341-350. http://dx.doi.org/10.1007/978-1-4939-8570-8_22.

[17]

L. Tao, F. Cao, G. Xu, et al., Mogroside IIIE attenuates LPS-induced acute lung injury in mice partly through regulation of the TLR4/MAPK/NF-κB axis via AMPK activation, Phytother. Res. 31 (2017) 1097-1106. http://dx.doi: 10.1002/ptr.5833.

[18]

H. Peng, C.R.G. Nickell, K.Y. Chen, et al., Increased expression of M1 and M2 phenotypic markers in isolated microglia after four-day binge alcohol exposure in male rats, Alcohol. 62 (2017) 29-40. http://dx.doi.org/10.1016/j.alcohol.2017.02.175.

[19]

K. Kowal, R. Silver, E. Sławińska, et al., CD163 and its role in inflammation, Folia. Histochem. Cytobiol. 49(3) (2011) 365-374. http://dx.doi.org/10.5603/fhc.2011.0052.

[20]

N.T. Mowery, W.T.H. Terzian, A.C. Nelson, Acute lung injury, Curr. Probl. Surg. 57(5) (2020) 100777. http://dx.doi.org/10.1016/j.cpsurg.2020.100777.

[21]

J.M. Snider, J.K. You, X. Wang, et al., Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality, J. Clin. Invest. 131(19) (2021) e149236. http://dx.doi.org/10.1172/JCI149236.

[22]

E. Dore, E. Boilard, Roles of secreted phospholipase A(2) group IIA in inflammation and host defense, Biochim. Biophys. Acta. Mol. Cell. Biol. Lipids 1864(6) (2019) 789-802. http://dx.doi.org/10.1016/j.bbalip.2018.08.017.

[23]

L.H. Boudreau, A.C. Duchez, N. Cloutier, et al., Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation, Blood 124(14) (2014) 2173-2183. http://dx.doi.org/10.1182/blood-2014-05-573543.

[24]

E. Hurt-Camejo, G. Camejo, H. Peilot, et al., Phospholipase A(2) in vascular disease, Circ. Res. 89(4) (2001) 298-304. http://dx.doi.org/10.1161/hh1601.095598.

[25]

F. Chilton, Would the real role(s) for secretory PLA2s please stand up, J. Clin. Invest. 97(10) (1996) 2161-2162. http://dx.doi.org/10.1172/JCI118654.

[26]

M. Murakami, Y. Nakatani, G.I. Atsumi, et al., Regulatory Functions of Phospholipase A2, Crit. Rev. Immunol. 37(2/3/4/5/6) (2017) 127-195. http://dx.doi.org/10.1615/CritRevImmunol.v37.i2-6.20.

[27]

S.K. Ku, J.S. Bae, Inhibitory effect of FXa on secretory group IIA phospholipase A2, Inflammation 38(3) (2015) 987-994. http://dx.doi.org/10.1007/s10753-014-0062-4.

[28]

W.S. Qu, D.S. Tian, Z.B. Guo, et al., Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury, J. Neuroinflammation 9 (2012) 178. http://dx.doi.org/10.1186/1742-2094-9-178.

[29]

H. Tao, N. Li, Z. Zhang, et al., Erlotinib protects LPS-induced acute lung injury in mice by inhibiting EGFR/TLR4 signaling pathway, Shock 51(1) (2019) 131-138. http://dx.doi.org/10.1097/SHK.0000000000001124.

[30]

C.Y. Huang, J.S. Deng, W.C. Huang, et al., Attenuation of lipopolysaccharide-induced acute lung injury by hispolon in mice, through regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 pathways, and suppressing oxidative stress-mediated ER stress-induced apoptosis and autophagy, Nutrients 12(6) (2020) 1742. https://dx.doi.org/10.3390/nu12061742.

[31]

K.M. Keppler-Noreuil, V.E.R. Parker, T.N. Darling, et al., Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies, Am. J. Med. Genet. C Semin. Med. Genet. 172 (2016) 402-421. http://dx.doi.org/10.1002/ajmg.c.31531.

[32]

G.J. Huang, C.M. Yang, Y.S. Chang, et al., Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and ERK signaling pathways, J. Agric. Food Chem. 58 (2010) 9468-9475. http://dx.doi.org/10.1021/jf101508r.

[33]

J. Tang, B. Zhou, M.J. Scott, et al., EGFR signaling augments TLR4 cell surface expression and function in macrophages via regulation of Rab5a activation, Protein Cell 11(2) (2020) 144-149. http://dx.doi.org/10.1007/s13238-019-00668-8.

[34]

K.Y. Lee, P.W. Shueng, C.M. Chou, et al., Elevation of CD109 promotes metastasis and drug resistance in lung cancer via activation of EGFR-AKTmTOR signaling, Cancer Sci. 111(5) (2020) 1652-1662. http://dx.doi.org/10.1111/cas.14373.

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Publication history

Received: 28 February 2022
Revised: 23 April 2022
Accepted: 08 May 2022
Published: 01 June 2023
Issue date: January 2024

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© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

Acknowledgements

Acknowledgements

We would like to thank the National Natural Science Foundation (81773982; 82003937), and Youth Academic leaders of the Qinglan Project in Jiangsu province for financial support. We would like to express our gratitude to EditSprings (https://www.editsprings.com/) for the expert linguistic services provided.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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