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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Research article

Panax notoginseng saponins promote liver regeneration through activation of the PI3K/AKT/mTOR cell proliferation pathway and upregulation of the AKT/Bad cell survival pathway in mice

Authors: Hua Zhong, Hao Wu, He Bai, Menghao Wang, Jian Wen, Jianping Gong, Mingyong Miao, Fangchao Yuan

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Backgroud

The regenerative capacity of the liver is crucial for the host to survive after serious hepatic injuries, tumor resection, or living donor liver transplantation. Panax notoginseng saponins (PNS) have been reported to exert protective effects during organ injuries. The present study aimed to evaluate the effect of PNS on liver regeneration(LR) and on injuries induced by partial hepatectomy (PH).

Methods

We performed 70% partial PH on C57BL/6 J mice treated with or without PNS. LR was estimated by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were analyzed by Western blot.

Results

Different concentrations of PNS promoted hepatocyte proliferation in vitro. Mice in the PNS group showed higher liver/body weight ratios at 2 d and 7 d (P < 0.05) after PH and lower levels of serum ALT and AST (P < 0.05) compared to those of mice in the normal control (NC) group. Histological analysis showed that the expression of proliferating cell nuclear antigen(PCNA) at 2 d and 7 d after PH was significantly higher in the PNS group than in the NC group (P < 0.05). Mechanistically, the AKT/mTOR cell proliferation pathway and AKT/Bad cell survival pathway were activated by PNS, which accelerated hepatocyte proliferation and inhibited apoptosis (P < 0.05).

Conclusions

PNS promoted liver regeneration through activation of PI3K/AKT/mTOR and upregulated the AKT/Bad cell pathways in mice.
Literature
1.
Mukherjee S, Chellappa K, Moffitt A, Ndungu J, Dellinger RW, Davis JG, Agarwal B, Baur JA. Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration. Hepatology. 2017;65(2):616–30.CrossRef
2.
Michalopoulos GK. Liver regeneration. J Cell Physiol. 2007;213(2):286–300.CrossRef
3.
Lee MR, Yun BS, Sung CK. Comparative study of white and steamed black Panax ginseng, P. quinquefolium, and P. notoginseng on cholinesterase inhibitory and Antioxidative activity. J Ginseng Res. 2012;36(1):93–101.CrossRef
4.
Gu CZ, Lv JJ, Zhang XX, Qiao YJ, Yan H, Li Y, Wang D, Zhu HT, Luo HR, Yang CR, et al. Triterpenoids with promoting effects on the differentiation of PC12 cells from the steamed roots of Panax notoginseng. J Nat Prod. 2015;78(8):1829–40.CrossRef
5.
Wang N, Wang L, Qi L, Lu X. Construct a gene-to-metabolite network to screen the key genes of triterpene saponin biosynthetic pathway in Panax notoginseng. Biotechnol Appl Biochem. 2018;65(2):119–27.CrossRef
6.
Li X, Wang G, Sun J, Hao H, Xiong Y, Yan B, Zheng Y, Sheng L. Pharmacokinetic and absolute bioavailability study of total panax notoginsenoside, a typical multiple constituent traditional chinese medicine (TCM) in rats. Biol Pharm Bull. 2007;30(5):847–51.CrossRef
7.
Xu C, Weiwei W, Wang B, Zhang T, Cui X, Pu Y, Li N. Analytical methods and biological activities of Panax notoginseng saponins: recent trends. J Ethnopharmacol. 2019.
8.
Gui Q, Yang Y, Ying S, Zhang M. Xueshuantong improves cerebral blood perfusion in elderly patients with lacunar infarction. Neural Regen Res. 2013;8(9):792–801.PubMedPubMedCentral
9.
Shen K, Ji L, Gong C, Ma Y, Yang L, Fan Y, Hou M, Wang Z. Notoginsenoside Ft1 promotes angiogenesis via HIF-1alpha mediated VEGF secretion and the regulation of PI3K/AKT and Raf/MEK/ERK signaling pathways. Biochem Pharmacol. 2012;84(6):784–92.CrossRef
10.
Zhang EY, Gao B, Shi HL, Huang LF, Yang L, Wu XJ, Wang ZT. 20(S)-Protopanaxadiol enhances angiogenesis via HIF-1alpha-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice. Exp Mol Med. 2017;49(10):e387.CrossRef
11.
Chen SC, Cheng JJ, Hsieh MH, Chu YL, Kao PF, Cheng TH, Chan P. Molecular mechanism of the inhibitory effect of trilinolein on endothelin-1-induced hypertrophy of cultured neonatal rat cardiomyocytes. Planta Med. 2005;71(6):525–9.CrossRef
12.
Hui J, Gao J, Wang Y, Zhang J, Han Y, Wei L, Liu X, Wu J. Panax notoginseng saponins ameliorates experimental hepatic fibrosis and hepatic stellate cell proliferation by inhibiting the Jak2/ Stat3 pathways. J Tradit Chin Med. 2016;36(2):217–24.CrossRef
13.
Zhou L, Zhou C, Feng Z, Liu Z, Zhu H, Zhou X. Triptolide-induced hepatotoxicity can be alleviated when combined with Panax notoginseng saponins and Catapol. J Ethnopharmacol. 2018;214:232–9.CrossRef
14.
Ding RB, Tian K, Cao YW, Bao JL, Wang M, He C, Hu Y, Su H, Wan JB. Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress. J Agric Food Chem. 2015;63(9):2413–22.CrossRef
15.
Audebert C, Bekheit M, Bucur P, Vibert E, Vignon-Clementel IE. Partial hepatectomy hemodynamics changes: experimental data explained by closed-loop lumped modeling. J Biomech. 2017;50:202–8.CrossRef
16.
Choi SC, Kim SJ, Choi JH, Park CY, Shim WJ, Lim DS. Fibroblast growth factor-2 and -4 promote the proliferation of bone marrow mesenchymal stem cells by the activation of the PI3K-AKT and ERK1/2 signaling pathways. Stem Cells Dev. 2008;17(4):725–36.CrossRef
17.
Yu L, Xie J, Xin N, Wang Z. Panax notoginseng saponins promote wound repair of anterior cruciate ligament through phosphorylation of PI3K, AKT and ERK. Int J Clin Exp Pathol. 2015;8(1):441–9.PubMedPubMedCentral
18.
Yang CY, Wang J, Zhao Y, Shen L, Jiang X, Xie ZG, Liang N, Zhang L, Chen ZH. Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic components. J Ethnopharmacol. 2010;130(2):231–6.CrossRef
19.
Mitchell C, Willenbring H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat Protoc. 2008;3(7):1167–70.CrossRef
20.
Edwards M, Houseman L, Phillips IR, Shephard EA. Isolation of mouse hepatocytes. Methods Mol Biol. 2013;987:283–93.CrossRef
21.
Hong S, Lee JE, Kim CY, Seong GJ. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line. BMC Neurosci. 2007;8:81.CrossRef
22.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63.CrossRef
23.
Zhang M, Guan Y, Xu J, Qin J, Li C, Ma X, Zhang Z, Zhang B, Tang J. Evaluating the protective mechanism of panax notoginseng saponins against oxidative stress damage by quantifying the biomechanical properties of single cell. Anal Chim Acta. 2019;1048:186–93.CrossRef
24.
Ge ZR, Xu MC, Huang YU, Zhang CJ, Lin JE, Ruan CW. Cardioprotective effect of notoginsenoside R1 in a rabbit lung remote ischemic postconditioning model via activation of the TGF-beta1/TAK1 signaling pathway. Exp Ther Med. 2016;11(6):2341–8.CrossRef
25.
Li Z, Li H, Zhao C, Lv C, Zhong C, Xin W, Zhang W. Protective effect of Notoginsenoside R1 on an APP/PS1 mouse model of Alzheimer's disease by up-regulating insulin degrading enzyme and inhibiting Abeta accumulation. CNS Neurol Disord Drug Targets. 2015;14(3):360–9.CrossRef
26.
Yan YT, Li SD, Li C, Xiong YX, Lu XH, Zhou XF, Yang LQ, Pu LJ, Luo HY. Panax notoginsenoside saponins Rb1 regulates the expressions of AKT/ mTOR/PTEN signals in the hippocampus after focal cerebral ischemia in rats. Behav Brain Res. 2018;345:83–92.CrossRef
27.
Wu Q, Deng J, Fan D, Duan Z, Zhu C, Fu R, Wang S. Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 2018;148:64–74.CrossRef
28.
Arumugam TV, Gleichmann M, Tang SC, Mattson MP. Hormesis/preconditioning mechanisms, the nervous system and aging. Ageing Res Rev. 2006;5(2):165–78.CrossRef
29.
Brunet A, Datta SR, Greenberg ME. Transcription-dependent and -independent control of neuronal survival by the PI3K-AKT signaling pathway. Curr Opin Neurobiol. 2001;11(3):297–305.CrossRef
30.
Ming M, Feng L, Shea CR, Soltani K, Zhao B, Han W, Smart RC, Trempus CS, He YY. PTEN positively regulates UVB-induced DNA damage repair. Cancer Res. 2011;71(15):5287–95.CrossRef
31.
Nguyen-Tu MS, da Silva Xavier G, Leclerc I, Rutter GA. Transcription factor-7-like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase to control mTOR signaling, beta cell growth, and insulin secretion. J Biol Chem. 2018;293(36):14178–89.CrossRef
32.
Lee MY, Luciano AK, Ackah E, Rodriguez-Vita J, Bancroft TA, Eichmann A, Simons M, Kyriakides TR, Morales-Ruiz M, Sessa WC. Endothelial AKT1 mediates angiogenesis by phosphorylating multiple angiogenic substrates. Proc Natl Acad Sci U S A. 2014;111(35):12865–70.CrossRef
33.
Moris D, Vernadakis S, Papalampros A, Vailas M, Dimitrokallis N, Petrou A, Dimitroulis D. Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy. World J Gastroenterol. 2016;22(33):7613–24.CrossRef
34.
Fan JS, Liu DN, Huang G, Xu ZZ, Jia Y, Zhang HG, Li XH, He FT. Panax notoginseng saponins attenuate atherosclerosis via reciprocal regulation of lipid metabolism and inflammation by inducing liver X receptor alpha expression. J Ethnopharmacol. 2012;142(3):732–8.CrossRef
35.
Araujo TG, de Oliveira AG, Tobar N, Saad MJ, Moreira LR, Reis ER, Nicola EM, de Jorge GL, dos Tartaro RR, Boin IF, et al. Liver regeneration following partial hepatectomy is improved by enhancing the HGF/met axis and AKT and Erk pathways after low-power laser irradiation in rats. Lasers Med Sci. 2013;28(6):1511–7.CrossRef
36.
Borowiak M, Garratt AN, Wustefeld T, Strehle M, Trautwein C, Birchmeier C. Met provides essential signals for liver regeneration. Proc Natl Acad Sci U S A. 2004;101(29):10608–13.CrossRef
37.
Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. AKT phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997;91(2):231–41.CrossRef
38.
Zhang H, Xiong Z, Wang J, Zhang S, Lei L, Yang L, Zhang Z. Glucagon-like peptide-1 protects cardiomyocytes from advanced oxidation protein product-induced apoptosis via the PI3K/AKT/bad signaling pathway. Mol Med Rep. 2016;13(2):1593–601.CrossRef
39.
Tang B, Tang F, Wang Z, Qi G, Liang X, Li B, Yuan S, Liu J, Yu S, He S. Upregulation of AKT/NF-kappaB-regulated inflammation and AKT/bad-related apoptosis signaling pathway involved in hepatic carcinoma process: suppression by carnosic acid nanoparticle. Int J Nanomedicine. 2016;11:6401–20.CrossRef
40.
Yang X, Wei A, Liu Y, He G, Zhou Z, Yu Z. IGF-1 protects retinal ganglion cells from hypoxia-induced apoptosis by activating the Erk-1/2 and AKT pathways. Mol Vis. 2013;19:1901–12.PubMedPubMedCentral
Metadata
Title
Panax notoginseng saponins promote liver regeneration through activation of the PI3K/AKT/mTOR cell proliferation pathway and upregulation of the AKT/Bad cell survival pathway in mice
Authors
Hua Zhong
Hao Wu
He Bai
Menghao Wang
Jian Wen
Jianping Gong
Mingyong Miao
Fangchao Yuan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2536-2

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