Isovitexin Inhibits Ginkgolic Acids-Induced Inflammation Through Downregulating SHP2 Activation

Overview

Journal Front Pharmacol

Date 2021 Aug 30

PMID 34456714

Citations 8

Authors

Yiwei Zhang

Zhipeng Qi

Wenjie Wang

Lei Wang

Fuliang Cao

Linguo Zhao

Xianying Fang

Affiliations

Soon will be listed here.

Abstract

It has been reported that Pers. is employed as a folk medicine for the treatment of inflammatory diseases. But the mechanism supporting its use as anti-inflammatory remains unclear. To investigate the anti-inflammatory of Pers. ICR mice were provided Pers. leaf extract (CLE) at 100, 200 mg/kg after ginkgolic acids (GA) sensitization. Our data showed that CLE and the main flavonoid isovitexin in CLE could ameliorate GA-induced contact dermatitis in mice. Ear swelling, inflammatory cell infiltration and splenomegaly were inhibited significantly by isovitexin, while the weight loss of mice in the isovitexin-treated group was much better than that in the dexamethasone-treated group (positive control drug). It has been reported in previous research that GA-induced inflammation is closely related to the T cell response. Therefore, T cells were the focus of the anti-inflammatory effect of isovitexin in this paper. The results showed that isovitexin (10, 20 mg/kg) inhibited the expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-17A) in lymph nodes, inhibited the secretion of cytokines into the serum from mice with contact dermatitis and promoted the expression of apoptosis-related proteins. , isovitexin also induced apoptosis and inhibited proinflammatory cytokine expression in Con A-activated T cells. Further study showed that the MAPK and STAT signaling pathways and the phosphorylation of SHP2 were inhibited by isovitexin. Both molecular docking and biological experiments indicated that SHP2 may be an anti-inflammatory target of isovitexin in T cells. Taken together, isovitexin can serve as a potential natural agent for the treatment or prevention of GA-induced inflammatory problems.

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References

Leonard A, Guttman-Yassky E . The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment. Clin Rev Allergy Immunol. 2018; 56(1):1-8. DOI: 10.1007/s12016-018-8685-0. View

Owen J, Vakharia P, Silverberg J . The Role and Diagnosis of Allergic Contact Dermatitis in Patients with Atopic Dermatitis. Am J Clin Dermatol. 2018; 19(3):293-302. PMC: 5948135. DOI: 10.1007/s40257-017-0340-7. View

Qian Y, Peng Y, Shang E, Zhao M, Yan L, Zhu Z . Metabolic profiling of the hepatotoxicity and nephrotoxicity of Ginkgolic acids in rats using ultra-performance liquid chromatography-high-definition mass spectrometry. Chem Biol Interact. 2017; 273:11-17. DOI: 10.1016/j.cbi.2017.05.020. View

Zehrmann N, Zidorn C, Ganzera M . Analysis of rare flavonoid C-glycosides in Celtis australis L. by micellar electrokinetic chromatography. J Pharm Biomed Anal. 2009; 51(5):1165-8. DOI: 10.1016/j.jpba.2009.11.028. View

Fransen H, Pelgrom S, Stewart-Knox B, de Kaste D, Verhagen H . Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba. Food Nutr Res. 2010; 54. PMC: 2950792. DOI: 10.3402/fnr.v54i0.5221. View

Ganesan R, Rasool M . Interleukin 17 regulates SHP-2 and IL-17RA/STAT-3 dependent Cyr61, IL-23 and GM-CSF expression and RANKL mediated osteoclastogenesis by fibroblast-like synoviocytes in rheumatoid arthritis. Mol Immunol. 2017; 91:134-144. DOI: 10.1016/j.molimm.2017.09.003. View

Chen Y, LaMarche M, Chan H, Fekkes P, Garcia-Fortanet J, Acker M . Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016; 535(7610):148-52. DOI: 10.1038/nature18621. View

Padua R, Sun Y, Marko I, Pitsawong W, Stiller J, Otten R . Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2. Nat Commun. 2018; 9(1):4507. PMC: 6207724. DOI: 10.1038/s41467-018-06814-w. View

Ude C, Schubert-Zsilavecz M, Wurglics M . Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet. 2013; 52(9):727-49. DOI: 10.1007/s40262-013-0074-5. View

10.

Fang X, Dong Y, Xie Y, Wang L, Wang J, Liu Y . Effects of β-glucosidase and α-rhamnosidase on the Contents of Flavonoids, Ginkgolides, and Aroma Components in Ginkgo Tea Drink. Molecules. 2019; 24(10). PMC: 6572456. DOI: 10.3390/molecules24102009. View

11.

Mei N, Guo X, Ren Z, Kobayashi D, Wada K, Guo L . Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2017; 35(1):1-28. PMC: 6373469. DOI: 10.1080/10590501.2016.1278298. View

12.

Yahfoufi N, Alsadi N, Jambi M, Matar C . The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients. 2018; 10(11). PMC: 6266803. DOI: 10.3390/nu10111618. View

13.

Jiang L, Xu W, Chen Y, Zhang Y . SHP2 inhibitor specifically suppresses the stemness of KRAS-mutant non-small cell lung cancer cells. Artif Cells Nanomed Biotechnol. 2019; 47(1):3231-3238. DOI: 10.1080/21691401.2019.1646748. View

14.

van Beek T, Montoro P . Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr A. 2009; 1216(11):2002-32. DOI: 10.1016/j.chroma.2009.01.013. View

15.

Honda T, Egawa G, Grabbe S, Kabashima K . Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol. 2012; 133(2):303-15. DOI: 10.1038/jid.2012.284. View

16.

Szczepanski A, Zhao Z, Sosnowski T, Goo Y, Bartom E, Wang L . ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer. Genome Med. 2020; 12(1):63. PMC: 7362484. DOI: 10.1186/s13073-020-00760-3. View

17.

Gorelik G, Fang J, Wu A, Sawalha A, Richardson B . Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus. J Immunol. 2007; 179(8):5553-63. DOI: 10.4049/jimmunol.179.8.5553. View

18.

Frankson R, Yu Z, Bai Y, Li Q, Zhang R, Zhang Z . Therapeutic Targeting of Oncogenic Tyrosine Phosphatases. Cancer Res. 2017; 77(21):5701-5705. PMC: 5827927. DOI: 10.1158/0008-5472.CAN-17-1510. View

19.

Rosa S, Rios-Santos F, Balogun S, de Oliveira Martins D . Vitexin reduces neutrophil migration to inflammatory focus by down-regulating pro-inflammatory mediators via inhibition of p38, ERK1/2 and JNK pathway. Phytomedicine. 2016; 23(1):9-17. DOI: 10.1016/j.phymed.2015.11.003. View

20.

Liu B, Huang B, Hu G, He D, Li Y, Ran X . Isovitexin-Mediated Regulation of Microglial Polarization in Lipopolysaccharide-Induced Neuroinflammation via Activation of the CaMKKβ/AMPK-PGC-1α Signaling Axis. Front Immunol. 2019; 10:2650. PMC: 6868066. DOI: 10.3389/fimmu.2019.02650. View