Skip to main content

Advertisement

SpringerLink
Log in

Refined-JinQi-JiangTang tablet ameliorates hypertension through activation of FGF21/FGFR1 axis in fructose-fed rats

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the therapeutic effect of JQ-R on metabolic hypertension and its correlation with Fibroblast growth factor 21/Fibroblast growth factor receptors 1(FGF21/FGFR1) pathway. In this study, fructose-induced metabolic hypertension rats were used as hypertension models to detect the regulation effect of JQ-R on hypertension. The effects of JQ-R on blood glucose, blood lipids, serum insulin levels and other metabolic indicators of rats were also measured. The effects of JQ-R on FGF21/FGFR1 signaling pathway in model animals were detected by Real-time quantitative PCR and Western blotting. The results showed that JQ-R significantly reduce the blood pressure of model rats in a dose-dependent manner. Meanwhile, fasting insulin, fasting blood glucose, insulin resistance index, total cholesterol and triglyceride levels were significantly decreased, and glucose and lipid metabolism abnormalities were also significantly improved. JQ-R induces these changes along with FGFR1 phosphorylation, which was also detected in JQ-R treated FGF21 knockout mice. These results suggest that JQ-R can reduce blood pressure and improve glucose and lipid metabolism in fructose-induced hypertension rats. Activation of FGF21/FGFR1 signaling pathway to regulate downstream blood pressure and glucolipid metabolism-related pathways may be one of the important mechanisms of JQ-R in regulating blood pressure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Holmes E, Loo RL, Stamler J et al (2008) Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453:396–400. https://doi.org/10.1038/nature06882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Xu WL, Janocha AJ, Erzurum SC (2021) Metabolism in pulmonary hypertension. Annu Rev Physiol 83:551–576. https://doi.org/10.1146/annurev-physiol-031620-123956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chaudhary K, Buddineni JP, Nistala R et al (2011) Resistant hypertension in the high-risk metabolic patient. Curr Diab Rep 11(1):41–46. https://doi.org/10.1007/s11892-010-0155-x

    Article  PubMed  Google Scholar 

  4. Chakraborty S, Mandal J, Yang T et al (2020) Metabolites and hypertension: insights into hypertension as a metabolic disorder: 2019 harriet dustan award. Hypertension 75(6):1386–1396. https://doi.org/10.1161/HYPERTENSIONAHA.120.13896

    Article  CAS  PubMed  Google Scholar 

  5. Whelton PK, Carey RM, Aronow WS et al (2018) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 71(19): e127-e248. Doi: https://doi.org/10.1016/j.jacc.2017.11.006

  6. Laurent S, Schlaich M, Esler M (2012) New drugs, procedures, and devices for hypertension. Lancet 380(9841):591–600. https://doi.org/10.1016/S0140-6736(12)60825-3

    Article  CAS  PubMed  Google Scholar 

  7. Liu SH, Chuang WC, Lam W et al (2015) Safety surveillance of traditional Chinese medicine: current and future. Drug Saf 38(2):117–128. https://doi.org/10.1007/s40264-014-0250-z

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wang JG, Wong YK, Liao FL (2018) What has traditional Chinese medicine delivered for modern medicine. Expert Rev Mol Med 20:e4. https://doi.org/10.1017/erm.2018.3

    Article  CAS  PubMed  Google Scholar 

  9. Liu Y, Wang AT, Wen LN et al (2019) A Chinese medicine formula (Jinqi Jiangtang Tablet): A review on its chemical constituents, quality control, pharmacokinetics studies, pharmacological properties and clinical applications. J Ethnopharmacol 236:1–8. https://doi.org/10.1016/j.jep.2019.02.038

    Article  CAS  PubMed  Google Scholar 

  10. Cao Y, Yao GW, Sheng YY et al (2019) JinQi Jiangtang tablet regulates gut microbiota and improve insulin sensitivity in type 2 diabetes mice. J Diabetes Res 2019:1872134. https://doi.org/10.1155/2019/1872134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang H, Guo LP, Shang HC et al (2017) JinqiJiangtang tablets for pre-diabetes: a randomized, double-blind and placebo-controlled clinical trial. Sci Rep 7(1):11190. https://doi.org/10.1038/s41598-017-11583-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nishimoto Y, Tomida T, Matsui H et al (2002) Decrease in renal medullary endothelial nitric oxide synthase of fructose-fed, salt-sensitive hypertensive rats. Hypertension 40(2):190–194. https://doi.org/10.1161/01.hyp.0000024267.71656.0d

    Article  CAS  PubMed  Google Scholar 

  13. Klein AV, Kiat H (2015) The mechanisms underlying fructose-induced hypertension: a review. J Hypertens 33(5):912–920. https://doi.org/10.1097/HJH.0000000000000551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sun S, Xie ZS, Liu EH et al (2014) Chemical profiling of Jinqi Jiangtang tablets by HPLC-ESI-Q-TOF/MS. Chin J Nat Med 12(03):229–240. https://doi.org/10.1016/S1875-5364(14)60039-X

    Article  CAS  PubMed  Google Scholar 

  15. Chang YX, Ge AH, Donnapee S et al (2015) The multi-targets integrated fingerprinting for screening anti-diabetic compounds from a Chinese medicine Jinqi Jiangtang Tablet. J Ethnopharmacol 164:210–222. https://doi.org/10.1016/j.jep.2015.02.018

    Article  CAS  PubMed  Google Scholar 

  16. Jimenez V, Jambrina C, Casana E et al (2018) FGF21 gene therapy as treatment for obesity and insulin resistance. EMBO Mol Med 10(08):e8791. https://doi.org/10.15252/emmm.201708791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Domouzoglou EM, Naka KK, Vlahos AP et al (2015) Fibroblast growth factors in cardiovascular disease: the emerging role of FGF21. Am J Physiol Heart Circ Physiol 309(6):H1029–H1038. https://doi.org/10.1152/ajpheart.00527.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. He JL, Zhao M, Xia JJ et al (2016) FGF21 ameliorates the neurocontrol of blood pressure in the high fructose-drinking rats. Sci Rep 6:29582. https://doi.org/10.1038/srep29582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pan XB, Shao YH, Wu F et al (2018) FGF21 prevents angiotensin II-induced hypertension and vascular dysfunction by activation of ACE2/Angiotensin-(1–7) Axis in Mice. Cell Metab 27(6):1323-1337.e5. https://doi.org/10.1016/j.cmet.2018.04.002

    Article  CAS  PubMed  Google Scholar 

  20. Kilkenny DM, Rocheleau JV (2016) The FGF21 receptor signaling complex: Klothoβ, FGFR1c, and other regulatory interactions. Vitam Horm 101:17–58. https://doi.org/10.1016/bs.vh.2016.02.008

    Article  CAS  PubMed  Google Scholar 

  21. Marseglia G, Lodola A, Mor M et al (2019) Fibroblast growth factor receptor inhibitors: patent review (2015–2019). Expert Opin Ther Pat 29(12):965–977. https://doi.org/10.1080/13543776.2019.1688300

    Article  CAS  PubMed  Google Scholar 

  22. Ye LX, Wang X, Cai CC et al (2019) FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/β-klotho. Exp Neurol 317:34–50. https://doi.org/10.1016/j.expneurol.2019.02.013

    Article  CAS  PubMed  Google Scholar 

  23. Wang N, Li JY, Li S et al (2018) Fibroblast growth factor 21 regulates foam cells formation and inflammatory response in Ox-LDL-induced THP-1 macrophages. Biomed Pharmacother 108:1825–1834. https://doi.org/10.1016/j.biopha.2018.09.143

    Article  CAS  PubMed  Google Scholar 

  24. Li SM, Yu YH, Li L et al (2016) Treatment of CIA Mice with FGF21 Down-regulates TH17-IL-17 Axis. Inflammation 39(1):309–319. https://doi.org/10.1007/s10753-015-0251-9

    Article  CAS  PubMed  Google Scholar 

  25. Emanuelli B, Vienberg SG, Smyth G et al (2014) Interplay between FGF21 and insulin action in the liver regulates metabolism. J Clin Invest 124(2):515–527. https://doi.org/10.1172/JCI67353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yu D, Ye XL, Wu Q et al (2016) Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway. Endocrine 52(3):527–540. https://doi.org/10.1007/s12020-015-0801-9

    Article  CAS  PubMed  Google Scholar 

  27. Gao LH, Liu Q, Liu SN et al (2014) A refined-JinQi-JiangTang tablet ameliorates prediabetes by reducing insulin resistance and improving beta cell function in mice. J Ethnopharmacol 151(1):675–685. https://doi.org/10.1016/j.jep.2013.11.024

    Article  PubMed  Google Scholar 

  28. Liu Q, Liu SN, Gao LH et al (2017) Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-R in vitro and in diabetic KK Ay mice. Acta Pharm Sin B 7(4):461–469. https://doi.org/10.1016/j.apsb.2017.04.010

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zhou FY, My B, Zhnag YQ et al (2018) Berberine-induced activation of AMPK increases hepatic FGF21 expression via NUR77-ScienceDirect. Biochem Biophys Res Commun 495(2):1936–1941. https://doi.org/10.1016/j.bbrc.2017.12.070

    Article  CAS  PubMed  Google Scholar 

  30. Sun YX, Xia MF, Yan HM et al (2018) Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21. Br J Pharmacol 175(2):374–387. https://doi.org/10.1111/bph.14079

    Article  CAS  PubMed  Google Scholar 

  31. Ferrario CM (2011) ACE2: more of Ang-(1–7) or less AngII. Curr Opin Nephrol Hypertens 20(1):1–6. https://doi.org/10.1097/MNH.0b013e3283406f57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sostre-Colón J, Uehara K, Garcia WA et al (2021) Hepatic AKT orchestrates adipose tissue thermogenesis via FGF21-dependent and -independent mechanisms. Cell Rep 35(7):109128. https://doi.org/10.1016/J.CELREP.2021.109128

    Article  PubMed  PubMed Central  Google Scholar 

  33. Izumiya Y, Bina HA, Ouchi N et al (2008) FGF21 is an Akt-regulated myokine. FEBS Lett 582(27):3805–3810. https://doi.org/10.1016/j.febslet.2008.10.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81903787) and the Natural Science Foundation of Heilongjiang Province (No. YQ2021H002).

Author information

Authors and Affiliations

  1. School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China

    Siming Li, Xiaoling Li, Xinhang Jia, Fangxin Dong, Haoyang Mao, Chen Zhang & Lijun Yan

  2. College of Food Engineering, Harbin University of Commerce, Harbin, 150076, China

    Jing Fan & Na Zhang

  3. College of Life Sciences, Northeast Agricultural University, Harbin, 150006, China

    Hemeng Wang, Wenfei Wang & Ye Jiang

  4. College of Life Sciences, Tarim University, Alar, 843300, China

    Hemeng Wang

Authors
  1. Siming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinhang Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hemeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fangxin Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Haoyang Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wenfei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ye Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lijun Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Na Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lijun Yan or Na Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

11418_2022_1626_MOESM1_ESM.tif

Fig S1 HPLC fingerprint of Refined-JinQi-JiangTang Tablet. The mobile phase consisted of acetonitrile (0.3% formic acid and 0.3% triethylamine) (1) and water (0.3% formic acid and 0.3% triethylamine) (2). The mobile phase gradient elution procedure was 0-10 min, 16% A. 10 ~ 20 min, 16% ~ 19% (1); 20-26 min, 19% (1); 26 ~ 50 min, 19% ~ 42% (1); 50 ~ 60 min, 42% ~ 100% (1); Volume flow 1.0 mL/min; The detection wavelength was set at 345 nm and 270 nm, respectively.2-Chlorogenic acid, 13-Rutin, 15-4, 5-Dicaffeoylquinic acid, 17-Luteolin, 23-Jatrorrhizine hydrochloride, 27-Palmatine hydrochloride, 28-Berberine hydrochloride. (TIF 1270 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, S., Li, X., Fan, J. et al. Refined-JinQi-JiangTang tablet ameliorates hypertension through activation of FGF21/FGFR1 axis in fructose-fed rats. J Nat Med 76, 765–773 (2022). https://doi.org/10.1007/s11418-022-01626-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-022-01626-1

Keywords

Search

Navigation