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Astragaloside IV in Hypoxic Pulmonary Hypertension: an In Vivo and In Vitro Experiments

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Abstract

The objective of study was to find the actions of astragaloside IV (ASIV) on PAH due to monocrotaline (MCT) in rats. Intraperitoneal injection of 60 mg/ kg MCT was injected to rats, come after by ASIV treatment with doses of 10 mg/kg daily once or 30 mg/kg of dose for twenty one days once daily. RVSP, serum inflammatory cytokines, RVH, and the other pathological parameters of the pulmonary arteries were evaluated. ASIV attenuated the increased pulmonary artery pressure and its structure in rat modification due to MCT. Additionally, ASIV avoided the rise in tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the blood serum, and their expression of gene in the pleural parts, which was caused by MCT. ASIV promoted apoptotic resistance of HPASMCs and weakened the hypoxia-induced proliferation. ASIV shows over expression of caspase-3, caspase-9, p21, p27, and Bax, while ASIV downregulated Bcl-2, phospho-ERK, HIF-1α, and protein appearance in HPASMCs. These findings of the in vitro and the in vivo experiment indicate that astragaloside IV exerts protective effects against pulmonary arterial pressure, and may have action to be improved into pharmacological drug for pulmonary arterial pressure treatment.

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References

  1. Gillespie, M. N., Goldblum, S. E., Cohen, D. A., & McClain, C. J. (1988). Interleukin-1 bioactivity in the lungs of rats with monocrotaline-induced pulmonary hypertension. Proceedings of the Society for Experimental Biology and Medicine, 187, 26–32.

    Article  CAS  PubMed  Google Scholar 

  2. Gillespie, M. N., Olson, J. W., Reinsel, C. N., & O’Connor, W. N. (1986). Altiere and RJ, Vascular hyperresponsiveness in perfused lungs from monocrotaline-treated rats. The American Journal of Physiology, 251, H109–H114.

    CAS  PubMed  Google Scholar 

  3. Todorovich-Hunter, L. J. D., Ranger, P., & Keeley, F. W. (1988). Rabinovitch and M, Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline. A biochemical and ultrastructural study. Laboratory Investigation, 58, 184–195.

    CAS  PubMed  Google Scholar 

  4. Hislop, A. R. L. (1979). Arterial changes in Crotalaria spectabilis-induced pulmonary hypertension in rats. British Journal of Experimental Pathology, 55, 153–163.

    Google Scholar 

  5. Huxtable, R. D. C. D., & Eisenstein, D. (1978). The effect of a pyrrolizidine alkaloid, monocrotaline, and a pyrrole, dehydroretronecine, on the biochemical functions of the pulmonary endothelium. Molecular Pharmacology, 14, 1189–1203.

    CAS  PubMed  Google Scholar 

  6. Lalich, J. J. J. W., Raczniak, J. J., & Shumaker, R. C. (1977). Fibrin thrombosis in monocrotaline pyrrole induced cor pulmonale in rats. Archives of Pathology & Laboratory Medicine, 101, 69–73.

    CAS  Google Scholar 

  7. Meyrick, B. G. W., & Reid, L. (1980). Development of Crotonolaria pulmonary hypertension: A hemodynamic and structural study. American Journal of Physiology, 239, H692–H702.

    CAS  PubMed  Google Scholar 

  8. Meyrick, B. R. L. (1979). Development of pulmonary arterial changes in rats fed Crotalaria spectabilis. American Journal of Physiology, 94, 37–50.

    CAS  Google Scholar 

  9. Valdiva, E. L. J., Hayashi, Y., & Sonnard, J. (1967). Alterations in pulmonary alveoli after a single injection of monocrotaline. Archives of Pathology, 84, 64–76.

    Google Scholar 

  10. Altiere, R. J. M. M., Petrenka, J., Olson, J. W., & Gillespie, M. N. (1986). Altered pulmonary vascular smooth muscle responsiveness in monocrotaline-induced pulmonary hypertension. J Pharmacology and Experimental Therapeutics, 236, 390–395.

    CAS  Google Scholar 

  11. Ghodsi, F. W. J. (1981). Changes in pulmonary structure and function induced by monocrotaline intoxication. American Journal of Physiology, 240, H149–H155.

    CAS  PubMed  Google Scholar 

  12. Hilliker, K. S. B. T., & Roth, R. A. (1982). Pneumotoxicity and thrombocytopenia after single injection of monocrotaline. American Journal of Physiology, 242, H573–H579.

    CAS  PubMed  Google Scholar 

  13. Hilliker, K. S. R. R. (1985). Increased vascular responsiveness in lungs of rats with pulmonary hypertension induced by monocrotaline pyrrole. American Review of Respiratory Diseases, 131, 46–50.

    CAS  Google Scholar 

  14. Lai, Y. L. T. A. (1996). Diana JN Hypoxemia and elevated tachykinins in rat monocrotaline pneumotoxicity. Lung, 174, 195–203.

    CAS  PubMed  Google Scholar 

  15. Molteni, A. W. W., TsAo, C. H., Solliday, N. H., & Dunne, M. (1985). Monocrotaline-induced pulmonary fibrosis in rats: Amelioration by captopril and penicillamine. Proceedings of the Society for Experimental Biology and Medicine, 180, 112–120.

    Article  CAS  PubMed  Google Scholar 

  16. Stenmark, K. R. M. M., Remigo, L. K., Voelkel, N. F., Murphy, H. P. R. C., Mathias, M. M., & Reeves, J. T. (1985). Alveolar inflammation and arachidonate metabolism in monocrotaline-induced pulmonary hypertension. American Journal of Physiology, 248, 859–866.

    Google Scholar 

  17. Ceconi, C. C. E., Quinzanini, M., Rodella, A., Ferrari, R., & Noradrenaline, H. P. (1989). atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive cardiac failure. Cardiovascular Research, 23, 674–682.

    Article  CAS  PubMed  Google Scholar 

  18. Vogel HG, Drug discovery and evaluation: Pharmacological assays. 3 ed. 2007: Springer.

  19. Guo, H. L. M. (2013). Mechanism of traditional Chinese medicine in the treatment of allergic rhinitis. Chinese Medical Journal (Engl), 126(4), 756–760.

    CAS  Google Scholar 

  20. Ren, S. Z. H., & Mu, Y. (2013). Pharmacological effects of Astragaloside IV: A literature review. Journal of Traditional Chinese Medicine, 33(3), 413–416.

    Article  PubMed  Google Scholar 

  21. Li, L. H. X., & Xu, R. (2017). Research review on the pharmacological effects of astragaloside IV. Fundamental & Clinical Pharmacology, 31(1), 17–36.

    Article  CAS  Google Scholar 

  22. Yaochen, C. L. Z., & Wang, Y. U. (2019). Astragaloside IV attenuates renal fibrosis through repressing epithelial-to-mesenchymal transition by inhibiting microRNA-192 expression: And studies. The American Journal of Translational Research, 11, 5029–5038.

    Google Scholar 

  23. Ren, S. (2013). Pharmacological effects of Astragaloside IV A literature review. Journal of Traditional Chinese Medicine, 33(3), 413–416.

    Article  PubMed  Google Scholar 

  24. Zhang, J. W. C., & Gao, L. (2020). Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects. Advances in Pharmacological, 87, 89–120.

    Article  CAS  Google Scholar 

  25. Shumin, Q. J. Y., & Shaogang, H. (2019). Astragaloside IV protects ethanol-induced gastric mucosal injury by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway apoptosis in rats. Frontiers in Pharmacology, 10, 894.

    Article  Google Scholar 

  26. Yang, X. W. F. (2019). The effect of astragaloside IV on JAK2-STAT6 signalling pathway in mouse model of ovalbumin-induced asthma. Journal of Animal Physiology and Animal Nutrition (Berl), 103(5), 1578–1584.

    Article  CAS  Google Scholar 

  27. Zhang, X. C. J., & Xu, P. (2018). Protective effects of astragaloside IV against hypoxic pulmonary hypertension. Medicinal Chemistry Communications, 9(10), 1715–1721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Simonneau, G. M. D., & Celermajer, D. S. (2019). Haemodynamic definitions and updated clinical classification of pulmonary hypertension. European Respiratory Journal, 53(1), 1801913.

    Article  CAS  PubMed  Google Scholar 

  29. Fox, K. Pulmonary Arterial Hypertension. 2022 [cited 2022 16 January]; Available from: https://rarediseases.org/rare-diseases/pulmonary-arterial-hypertension/.

  30. Groth, A. V. B., Brock, M., Speich, R., Ulrich, S., & Huber, L. C. (2014). Inflammatory cytokines in pulmonary hypertension. Respiratory Research, 15, 47.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wang, Q. Z. X., Wang, Y. Y., Xie, W. P., Wang, H., & Zhang, M. (2013). Monocrotaline-induced pulmonary arterial hypertension is attenuated by TNF-α antagonists via the suppression of TNF-α expression and NF-κB pathway in rats. Vascular Pharmacology, 58, 71–77.

    Article  CAS  PubMed  Google Scholar 

  32. E CMaS, Pulmonary arterial hypertension in adult‑onset still's disease: Rapid response to anakinra. Case Reports in Rheumatology, 2012: 537613

  33. Jiang, P. M. D., Wang, X., Wang, Y., Bi, Y., Yang, J., Wang, X., & Li, X. (2018). Astragaloside IV prevents obesity-associated hypertension by improving pro-inflammatory reaction and leptin resistance. Molecules and Cells, 41, 244–255.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Meiqian, Z. L. Z., & Chang, C. (2018). Astragaloside IV inhibits cigarette smoke-induced pulmonary inflammation in mice. Inflammation, 41, 1671–1680.

    Article  CAS  PubMed  Google Scholar 

  35. ED, P. R. A. M. (2014). The metabolic theory of pulmonary arterial hypertension. Circulation Research, 115, 148–164.

    Article  Google Scholar 

  36. Ball, M. K. W. G., Mungai, P. T., Nielsen, J. M., Czech, L., Dudley, V. J., Beussink, L., Dettman, R. W., Berkelhamer, S. K., & Steinhorn, R. H. (2014). Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1α. American Journal of Respiratory and Critical Care Medicine, 189, 314–324.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wang, G. W. J., Fu, X. L., Guang, R., & To, S. T. (2017). Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review). Oncology Reports, 37, 657–60.

    Article  CAS  PubMed  Google Scholar 

  38. Jin, H. J. Y., Guo, L., Ma, Y., Zhao, R., Li, X., Shen, L., Zhou, Z., Kim, S. C., & Liu, J. (2021). Astragaloside IV blocks monocrotaline-induced pulmonary arterial hypertension by improving inflammation and pulmonary artery remodeling. International Journal of Molecular Medicine, 47(2), 595–606.

    Article  CAS  PubMed  Google Scholar 

  39. Ashok, C. O. S., Srijyothi, L., Selvam, M., Ponne, S., & Baluchamy, S. (2019). A feedback regulation of CREB activation through the CUL4A and ERK signaling. Medical Oncology, 36, 20.

    Article  PubMed  Google Scholar 

  40. Humbert, M. G. C., Bonnet, S., Dorfmüller, P., Klinger, J. R., Nicolls, M. R., Olschewski, A. J., Pullamsetti, S. S., Schermuly, R. T., Stenmark, K. R., & Rabinovitch, M. (2019). Pathology and pathobiology of pulmonary hypertension: State of the art and research perspectives. The European Respiratory Journal, 53, 1801887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Cardiology, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihuamen Street, Xian 710003, China

    XinTian

  2. Department of Nephrology, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihuamen Street, Xian 710003, China

    Xiaofeng Zhang

  3. School of Graduate, Shaanxi University of Chinese Medicine, No.1 Middle Weiyang Road, Xianyang, 712046, China

    Yi Feng, Xiaolong Gao, Xuan Hao, Junru Zhang, Yunhong Long &  RongFang

  4. School of Basic Medicine, Fourth Military Medical University, No. 169 Changle West Road, Xian, 710032, China

    Shumiao Zhang

  5. Department of Geriatrics, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihuamen Street, Xian 710003, China

    Ling Li

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  1. XinTian
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All authors contributed equally.

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Correspondence to Ling Li.

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The experiment was approved by the animal ethics committee of the institute (Protocol number 15BvCG).

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XinTian, Zhang, X., Feng, Y. et al. Astragaloside IV in Hypoxic Pulmonary Hypertension: an In Vivo and In Vitro Experiments. Appl Biochem Biotechnol 194, 6319–6334 (2022). https://doi.org/10.1007/s12010-022-04027-y

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