Protective Effect of Astragalus Membranaceus and Astragaloside IV in Sepsis-induced Acute Kidney Injury

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2022 Jul 21

PMID 35859295

Authors

Jia-Long Tang

Meng Xin

Li-Chao Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Acute kidney injury (AKI) is the most common target organ damage in sepsis. Sepsis-associated AKI (SA-AKI) may be characterized by damage to the renal tubular epithelium. In this study, the pharmacological mechanisms of Astragalus membranaceus and its active monomer Astragaloside IV (AS-IV) were predicted based on a network pharmacology approach and validated both and using the SA-AKI model.

Method: We constructed an sepsis model using a mouse cecum ligation puncture (CLP) and HK-2 cells were treated with lipopolysaccharide (LPS) to mimic Gram (-) induced sepsis to assess the renal-protective efficacy of Astragalus membranaceus and AS-IV.

Results: The findings demonstrated that Astragalus membranaceus and AS-IV attenuate renal tubular injury in mice with polymicrobial sepsis, including vacuolization, loss of brush border, mitochondrial ultrastructural changes, and increased staining of kidney injury molecule-1 (KIM-1). AS-IV protected human proximal tubular epithelial (HK-2) cells against LPS induced cell viability loss. Both Astragalus membranaceus and AS-IV activated the PI3K/AKT pathway both and , as shown by Western blot and immunohistochemistry analysis.

Conclusion: The findings demonstrate that Astragalus membranaceus and AS-IV protect against sepsis-induced kidney tubular injury by activating the PI3K/AKT pathway.

Citing Articles

Nephroprotective effects of substances of medicine food homology and traditional Chinese medicine phytochemicals against acute kidney injury.

Chen L, Deng Y, Hu J, Gong X Front Pharmacol. 2025; 16:1539886.

PMID: 40046749 PMC: 11880292. DOI: 10.3389/fphar.2025.1539886.

Therapeutic potential of -based Eefooton in patients with chronic kidney disease: from clinical to bench study.

Lu K, Kuo K, Wu S, Lin C, Lin C, Hou Y Int J Med Sci. 2025; 22(1):227-239.

PMID: 39744164 PMC: 11659832. DOI: 10.7150/ijms.102280.

Role of HSP90 in Type 2 Diabetes Mellitus and Its Association with Liver Diseases.

Nithyasree V, Magdalene P, Praveen Kumar P, Preethi J, Gromiha M Mol Biotechnol. 2024; .

PMID: 39162909 DOI: 10.1007/s12033-024-01251-1.

Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling.

Hao J, Zhang X, Hu R, Lu X, Wang H, Li Y J Transl Med. 2024; 22(1):555.

PMID: 38858642 PMC: 11163744. DOI: 10.1186/s12967-024-05355-9.

Mechanism of Astragaloside IV in Treatment of Renal Tubulointerstitial Fibrosis.

Wang X, Luan J, Guo Z Chin J Integr Med. 2024; .

PMID: 38850482 DOI: 10.1007/s11655-024-3805-6.

References

Cheng S, Zhang X, Feng Q, Chen J, Shen L, Yu P . Astragaloside IV exerts angiogenesis and cardioprotection after myocardial infarction via regulating PTEN/PI3K/Akt signaling pathway. Life Sci. 2019; 227:82-93. DOI: 10.1016/j.lfs.2019.04.040. View

Zhang R, Zhu X, Bai H, Ning K . Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment. Front Pharmacol. 2019; 10:123. PMC: 6393382. DOI: 10.3389/fphar.2019.00123. View

Hopkins A . Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008; 4(11):682-90. DOI: 10.1038/nchembio.118. View

Zhang J, Wu C, Gao L, Du G, Qin X . Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects. Adv Pharmacol. 2020; 87:89-112. DOI: 10.1016/bs.apha.2019.08.002. View

Shkondrov A, Krasteva I, Bucar F, Kunert O, Kondeva-Burdina M, Ionkova I . A new tetracyclic saponin from L. and its neuroprotective and hMAO-B inhibiting activity. Nat Prod Res. 2018; 34(4):511-517. DOI: 10.1080/14786419.2018.1491040. View

Margaria J, Campa C, De Santis M, Hirsch E, Franco I . The PI3K/Akt/mTOR pathway in polycystic kidney disease: A complex interaction with polycystins and primary cilium. Cell Signal. 2019; 66:109468. DOI: 10.1016/j.cellsig.2019.109468. View

Li X, Qu L, Dong Y, Han L, Liu E, Fang S . A review of recent research progress on the astragalus genus. Molecules. 2014; 19(11):18850-80. PMC: 6270929. DOI: 10.3390/molecules191118850. View

Liu F, Sun L, You G, Liu H, Ren X, Wang M . Effects of Astragalus polysaccharide on the solubility and stability of 15 flavonoids. Int J Biol Macromol. 2019; 143:873-880. DOI: 10.1016/j.ijbiomac.2019.09.148. View

Aladaileh S, Hussein O, Abukhalil M, Saghir S, Bin-Jumah M, Alfwuaires M . Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats. Antioxidants (Basel). 2019; 8(10). PMC: 6827027. DOI: 10.3390/antiox8100430. View

10.

Zhang Y, Tan R, Zhang X, Yu Y, Yu C . Calycosin Ameliorates Diabetes-Induced Renal Inflammation via the NF-κB Pathway In Vitro and In Vivo. Med Sci Monit. 2019; 25:1671-1678. PMC: 6413560. DOI: 10.12659/MSM.915242. View

11.

Xu Y, Han F, Tan J . Edaravone protects the retina against ischemia/reperfusion‑induced oxidative injury through the PI3K/Akt/Nrf2 pathway. Mol Med Rep. 2017; 16(6):9210-9216. DOI: 10.3892/mmr.2017.7739. View

12.

Ren J, Xue H, Liu Y, Wei Y, Divid Adelson , Chen X . [Purification and biochemical function of Astragalus membtanaceus pathogenesis-related protein 10]. Zhongguo Zhong Yao Za Zhi. 2018; 43(18):3662-3667. DOI: 10.19540/j.cnki.cjcmm.20180702.003. View

13.

Edwards L, Thiessen B, Dragowska W, Daynard T, Bally M, Dedhar S . Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth. Oncogene. 2005; 24(22):3596-605. DOI: 10.1038/sj.onc.1208427. View

14.

Wang H, Wang Y, Gao H, Wang B, Dou L, Li Y . Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways. Oncol Lett. 2018; 15(2):1423-1428. PMC: 5774427. DOI: 10.3892/ol.2017.7498. View

15.

Wang J, Wong Y, Liao F . What has traditional Chinese medicine delivered for modern medicine?. Expert Rev Mol Med. 2018; 20:e4. DOI: 10.1017/erm.2018.3. View

16.

Singer M, Deutschman C, Seymour C, Shankar-Hari M, Annane D, Bauer M . The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. PMC: 4968574. DOI: 10.1001/jama.2016.0287. View

17.

Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J . A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2013; 41(1):3-11. PMC: 3918942. DOI: 10.1097/SHK.0000000000000052. View

18.

Ge B, Li S, Li F . Astragaloside-IV regulates endoplasmic reticulum stress-mediated neuronal apoptosis in a murine model of Parkinson's disease via the lincRNA-p21/CHOP pathway. Exp Mol Pathol. 2020; 115:104478. DOI: 10.1016/j.yexmp.2020.104478. View

19.

Sun J, Zhang J, Tian J, Virzi G, Digvijay K, Cueto L . Mitochondria in Sepsis-Induced AKI. J Am Soc Nephrol. 2019; 30(7):1151-1161. PMC: 6622414. DOI: 10.1681/ASN.2018111126. View

20.

Ding X, Lv J, Luan J, Zhang J . Calycosin may Alleviate Ang II-Induced Pro-proliferative Effects on Glomerular Mesangial Cells via Partially Inhibiting Autophagy and ERK Signaling Pathway. Biol Pharm Bull. 2020; 43(12):1893-1898. DOI: 10.1248/bpb.b20-00520. View