Ginsenoside Rg1 Can Restore Hematopoietic Function by Inhibiting Bax Translocation-mediated Mitochondrial Apoptosis in Aplastic Anemia

Overview

Journal Sci Rep

Specialty Science

Date 2021 Jun 18

PMID 34140535

Citations 4

Authors

Huiqin Cao

Wei Wei

Ruirong Xu

Xing Cui

Affiliations

Soon will be listed here.

Abstract

The present study investigated, the anti-apoptotic activity of Ginsenoside Rg1 (Rg1) via inhibition of Bax translocation and the subsequent recovery of hematopoietic function. Mitochondrial apoptosis in bone marrow mononuclear cells (BMNCs) was observed in aplastic anemia (AA) patients. To establish a mouse model of AA, BALB/c mice were transplanted with lymph node cells from DBA/2 donor mice via vein injection after treatment with Co60 γ-radiation. After treatment with Rg1 for 14 days, the peripheral blood and Lin-Sca-1 + c-Kit + (LSK) cell counts of the treated group were increased compared with those of the untreated model mice. In in vivo and in vitro tests of LSKs, Rg1 was found to increase mitochondrial number and the ratio of Bcl-2/Bax and to decrease damage to the mitochondrial inner and outer membranes, the mitochondrial Bax level and the protein levels of mitochondrial apoptosis-related proteins AIF and Cyt-C by decreasing the ROS level. Rg1 also improved the concentration-time curve of MAO and COX and levels of ATP, ADP and AMP in an in vitro test. In addition, high levels of Bax mitochondrial translocation could be corrected by Rg1 treatment. Levels of markers of mitochondrial apoptosis in the Rg1-treated group were significantly better than those in the AA model group, implying that Rg1 might improve hematopoietic stem cells and thereby restore hematopoietic function in AA by suppressing the mitochondrial apoptosis mediated by Bax translocation.

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References

Zhang Y, Huang N, Xu J, Zheng W, Cui X . Homoharringtonine Exerts an Antimyeloma Effect by Promoting Excess Parkin-Dependent Mitophagy. Drug Des Devel Ther. 2020; 14:4749-4763. PMC: 7652225. DOI: 10.2147/DDDT.S279054. View

Ermak N, Lacour B, Drueke T, Vicca S . Role of reactive oxygen species and Bax in oxidized low density lipoprotein-induced apoptosis of human monocytes. Atherosclerosis. 2008; 200(2):247-56. DOI: 10.1016/j.atherosclerosis.2007.12.052. View

Xu S, Yu L, Fan Z, Wu Q, Yuan Y, Wei Y . Improvement of ginsenoside Rg1 on hematopoietic function in cyclophosphamide-induced myelosuppression mice. Eur J Pharmacol. 2012; 695(1-3):7-12. DOI: 10.1016/j.ejphar.2012.07.050. View

Cheng M, Liu L, Lao Y, Liao W, Liao M, Luo X . MicroRNA-181a suppresses parkin-mediated mitophagy and sensitizes neuroblastoma cells to mitochondrial uncoupler-induced apoptosis. Oncotarget. 2016; 7(27):42274-42287. PMC: 5173134. DOI: 10.18632/oncotarget.9786. View

Urao N, Ushio-Fukai M . Redox regulation of stem/progenitor cells and bone marrow niche. Free Radic Biol Med. 2012; 54:26-39. PMC: 3637653. DOI: 10.1016/j.freeradbiomed.2012.10.532. View

Hartman E, Brindley E, Papoin J, Ciciotte S, Zhao Y, Peters L . Increased Reactive Oxygen Species and Cell Cycle Defects Contribute to Anemia in the RASA3 Mutant Mouse Model s. Front Physiol. 2018; 9:689. PMC: 5996270. DOI: 10.3389/fphys.2018.00689. View

Martin-Pardillos A, Tsaalbi-Shtylik A, Chen S, Lazare S, van Os R, Dethmers-Ausema A . Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions. Blood. 2017; 130(13):1523-1534. PMC: 5620415. DOI: 10.1182/blood-2017-01-764274. View

Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I . Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004; 431(7011):997-1002. DOI: 10.1038/nature02989. View

Tang Y, Zhou Y, Wang Y, Wang J, Ding J . SIRT6/NF-κB signaling axis in ginsenoside Rg1-delayed hematopoietic stem/progenitor cell senescence. Int J Clin Exp Pathol. 2015; 8(5):5591-6. PMC: 4503140. View

10.

Li J, Cai D, Yao X, Zhang Y, Chen L, Jing P . Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging. Int J Mol Sci. 2016; 17(6). PMC: 4926383. DOI: 10.3390/ijms17060849. View

11.

Liu S, Zhou Y, Tang D, Zhou N, Zheng W, Tang Z . Rapamycin ameliorates immune-mediated aplastic anemia by inhibiting the proliferation and metabolism of T cells. Biochem Biophys Res Commun. 2019; 518(2):212-218. DOI: 10.1016/j.bbrc.2019.08.034. View

12.

Tang Y, Zhou Y, Wang Y, He Y, Ding J, Li Y . Ginsenoside Rg1 protects against Sca-1 HSC/HPC cell aging by regulating the SIRT1-FOXO3 and SIRT3-SOD2 signaling pathways in a γ-ray irradiation-induced aging mice model. Exp Ther Med. 2020; 20(2):1245-1252. PMC: 7388550. DOI: 10.3892/etm.2020.8810. View

13.

Suda T, Takubo K, Semenza G . Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell. 2011; 9(4):298-310. DOI: 10.1016/j.stem.2011.09.010. View

14.

Qin Q, Lin N, Huang H, Zhang X, Cao X, Wang Y . Ginsenoside Rg1 ameliorates cardiac oxidative stress and inflammation in streptozotocin-induced diabetic rats. Diabetes Metab Syndr Obes. 2019; 12:1091-1103. PMC: 6628146. DOI: 10.2147/DMSO.S208989. View

15.

Jiang N, Chen M, Yang G, Xiang L, He L, Hei T . Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow. Sci Rep. 2016; 6:36411. PMC: 5175267. DOI: 10.1038/srep36411. View

16.

Mancini M, Anderson B, Caldwell E, Sedghinasab M, Paty P, Hockenbery D . Mitochondrial proliferation and paradoxical membrane depolarization during terminal differentiation and apoptosis in a human colon carcinoma cell line. J Cell Biol. 1997; 138(2):449-69. PMC: 2138196. DOI: 10.1083/jcb.138.2.449. View

17.

Sun L, Chen T, Wang X, Chen Y, Wei X . Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells. Evid Based Complement Alternat Med. 2009; 2011:249090. PMC: 3136247. DOI: 10.1093/ecam/nep082. View

18.

Hatfill S, La Cock C, Laubscher R, Downing T, Kirby R . A role for mitochondrial DNA in the pathogenesis of radiation-induced myelodysplasia and secondary leukemia. Leuk Res. 1993; 17(11):907-13. DOI: 10.1016/0145-2126(93)90036-k. View

19.

Napolitano M, Shain D . Quantitating adenylate nucleotides in diverse organisms. J Biochem Biophys Methods. 2005; 63(1):69-77. DOI: 10.1016/j.jbbm.2005.03.001. View

20.

Zhu C, Wang Y, Liu H, Mu H, Lu Y, Zhang J . Oral administration of Ginsenoside Rg1 prevents cardiac toxicity induced by doxorubicin in mice through anti-apoptosis. Oncotarget. 2017; 8(48):83792-83801. PMC: 5663555. DOI: 10.18632/oncotarget.19698. View