Gynostemma Pentaphyllum ameliorates CCl

Gynostemma pentaphyllum Gypenoside A Hepatocyte apoptosis Liver protection Phosphoinositide dependent protein kinase-1 (PDK1)

Journal

Chinese medicine
ISSN: 1749-8546
Titre abrégé: Chin Med
Pays: England
ID NLM: 101265109

Informations de publication

Date de publication:
15 May 2024
Historique:
received: 13 03 2024
accepted: 05 05 2024
medline: 16 5 2024
pubmed: 16 5 2024
entrez: 15 5 2024
Statut: epublish

Résumé

Gynostemma pentaphyllum (Thunb.) Makino, commonly known as "southern ginseng", contains high amounts of ginsenoside derivatives and exhibits similar biological activities with Panax ginseng (C. A. MEY) (ginseng), which is usually used as a low-cost alternative to ginseng. G. pentaphyllum has therapeutic effects on liver diseases. However, the mechanisms underlying its hepatoprotective action have not been fully elucidated. The protective effects of the ethanolic extract of G. pentaphyllum (GPE) were evaluated using an experimental carbon tetrachloride (CCl The pathological examinations showed that GPE significantly alleviated hepatocyte necrosis and liver injury. GPE significantly downregulated Bax and cleaved-PARP expression and upregulated Bcl-2 expression during CCl These results suggested that G. pentaphyllum had a promising hepatoprotective effect, with its mechanism primarily involving the upregulation of the PDK1/Bcl-2 signaling pathway by GPA, thereby preventing cell apoptosis.

Sections du résumé

BACKGROUND BACKGROUND
Gynostemma pentaphyllum (Thunb.) Makino, commonly known as "southern ginseng", contains high amounts of ginsenoside derivatives and exhibits similar biological activities with Panax ginseng (C. A. MEY) (ginseng), which is usually used as a low-cost alternative to ginseng. G. pentaphyllum has therapeutic effects on liver diseases. However, the mechanisms underlying its hepatoprotective action have not been fully elucidated.
METHODS METHODS
The protective effects of the ethanolic extract of G. pentaphyllum (GPE) were evaluated using an experimental carbon tetrachloride (CCl
RESULTS RESULTS
The pathological examinations showed that GPE significantly alleviated hepatocyte necrosis and liver injury. GPE significantly downregulated Bax and cleaved-PARP expression and upregulated Bcl-2 expression during CCl
CONCLUSIONS CONCLUSIONS
These results suggested that G. pentaphyllum had a promising hepatoprotective effect, with its mechanism primarily involving the upregulation of the PDK1/Bcl-2 signaling pathway by GPA, thereby preventing cell apoptosis.

Identifiants

DOI: 10.1186/s13020-024-00942-w PMID: 38750545
pubmed: 38750545
doi: 10.1186/s13020-024-00942-w
pii: 10.1186/s13020-024-00942-w
doi:

Types de publication

Journal Article

Langues

eng

Pagination

70

Subventions

Organisme : National Natural Science Foundation of China
ID : 82074112
Organisme : The ability establishment of sustainable use for valuable Chinese medicine resources
ID : 2060302

Informations de copyright

© 2024. The Author(s).

Références

Su C, Li N, Ren R, Wang Y, Su X, Lu F, et al. Progress in the medicinal value, bioactive compounds, and pharmacological activities of gynostemma pentaphyllum. Molecules. 2021;26(20).
Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases. Hepatology. 2018;68(2):723–50.
doi: 10.1002/hep.29913 pubmed: 29624699
Malhi H, Guicciardi ME, Gores GJ. Hepatocyte death: a clear and present danger. Physiol Rev. 2010;90(3):1165–94.
doi: 10.1152/physrev.00061.2009 pubmed: 20664081
Schuppan D, Kim YO. Evolving therapies for liver fibrosis. J Clin Investig. 2013;123(5):1887–901.
doi: 10.1172/JCI66028 pubmed: 23635787 pmcid: 3635731
Miao Z, Miao Z, Wang S, Shi X, Xu S. Quercetin antagonizes imidacloprid-induced mitochondrial apoptosis through PTEN/PI3K/AKT in grass carp hepatocytes. Environ Pollut. 2021;290:118036.
doi: 10.1016/j.envpol.2021.118036 pubmed: 34488159
Choi JH, Yang YR, Lee SK, Kim SH, Kim YH, Cha JY, et al. Potential inhibition of PDK1/Akt signaling by phenothiazines suppresses cancer cell proliferation and survival. Ann N Y Acad Sci. 2008;1138:393–403.
doi: 10.1196/annals.1414.041 pubmed: 18837915
Wong WY, Lee MM, Chan BD, Ma VW, Zhang W, Yip TT, et al. Gynostemma pentaphyllum saponins attenuate inflammation in vitro and in vivo by inhibition of NF-κB and STAT3 signaling. Oncotarget. 2017;8(50):87401–14.
doi: 10.18632/oncotarget.20997 pubmed: 29152090 pmcid: 5675642
Hernández-Alvarez MI, Sebastián D, Vives S, Ivanova S, Bartoccioni P, Kakimoto P, et al. Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease. Cell. 2019;177(4):881-895.e17.
doi: 10.1016/j.cell.2019.04.010 pubmed: 31051106
Eguchi A, De Mollerat Du, Jeu X, Johnson CD, Nektaria A, Feldstein AE. Liver bid suppression for treatment of fibrosis associated with non-alcoholic steatohepatitis. J Hepatol. 2016;64(3):699–707.
doi: 10.1016/j.jhep.2015.11.002 pubmed: 26555271
Aram G, Potter JJ, Liu X, Wang L, Torbenson MS, Mezey E. Deficiency of nicotinamide adenine dinucleotide phosphate, reduced form oxidase enhances hepatocellular injury but attenuates fibrosis after chronic carbon tetrachloride administration. Hepatology. 2009;49(3):911–9.
doi: 10.1002/hep.22708 pubmed: 19072832
Shao S, Zhang Y, Zhou F, Meng X, Yu Z, Li G, et al. LncRNA-Airn alleviates acute liver injury by inhibiting hepatocyte apoptosis via the NF-κB signaling pathway. Acta Biochim Biophys Sin. 2022;54(11):1619–29.
doi: 10.3724/abbs.2022167 pubmed: 36604144 pmcid: 9828194
Ru W, Wang D, Xu Y, He X, Sun YE, Qian L, et al. Chemical constituents and bioactivities of panax ginseng (C. A. Mey.). Drug Discov Ther. 2015;9(1):23–32.
doi: 10.5582/ddt.2015.01004 pubmed: 25788049
Meng F, Zhang Y, Li X, Wang J, Wang Z. Clinical significance of miR-138 in patients with malignant melanoma through targeting of PDK1 in the PI3K/AKT autophagy signaling pathway. Oncol Rep. 2017;38(3):1655–62.
doi: 10.3892/or.2017.5838 pubmed: 28731179
Bamodu OA, Chang HL, Ong JR, Lee WH, Yeh CT, Tsai JT. Elevated PDK1 expression drives PI3K/AKT/MTOR signaling promotes radiation-resistant and dedifferentiated phenotype of hepatocellular carcinoma. Cells. 2020;9(3).
Najafov A, Sommer Eeva M, Axten Jeffrey M, Deyoung MP, Alessi DR. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem J. 2010;433(2):357–69.
doi: 10.1042/BJ20101732
Zhang D, Zhang Y, Sun B. The molecular mechanisms of liver fibrosis and its potential therapy in application. Int J Mol Sci. 2022;433(2):357–69.
Nguyen NH, Ha TKQ, Yang JL, Pham HTT, Oh WK. Triterpenoids from the genus gynostemma: chemistry and pharmacological activities. J Ethnopharmacol. 2021;268: 113574.
doi: 10.1016/j.jep.2020.113574 pubmed: 33186700
Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5(1): e996.
doi: 10.1038/cddis.2013.499 pubmed: 24434519 pmcid: 4040708
Kim JH, Han YN. Dammarane-type saponins from gynostemma pentaphyllum. Phytochemistry. 2011;72(11–12):1453–9.
doi: 10.1016/j.phytochem.2011.04.003 pubmed: 21565370
Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481–507.
doi: 10.1146/annurev.biochem.67.1.481 pubmed: 9759495
Nakazato PCG, Victorino JP, Fina CF, Mendes KDS, Gomes MCJ, Evora PRB, et al. Liver ischemia and reperfusion injury pathophysiology and new horizons in preconditioning and therapy. Acta cirurgica brasileira. 2018;33(8):723–35.
doi: 10.1590/s0102-865020180080000008 pubmed: 30208134
Rong YP, Huang HT, Liu JS, Wei L. Protective effects of geniposide on hepatic ischemia/reperfusion injury. Transpl Proc. 2017;49(6):1455–60.
doi: 10.1016/j.transproceed.2017.02.063
Sheng M, Zhou Y, Yu W, Weng Y, Xu R, Du H. Protective effect of berberine pretreatment in hepatic ischemia/reperfusion injury of rat. Transpl Proc. 2015;47(2):275–82.
doi: 10.1016/j.transproceed.2015.01.010
Ericson K, Gan C, Cheong I, Rago C, Samuels Y, Velculescu VE, et al. Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. Proc Natl Acad Sci USA. 2010;107(6):2598–603.
doi: 10.1073/pnas.0914018107 pubmed: 20133737 pmcid: 2823889
Mucha BE, Banka S, Ajeawung NF, Molidperee S, Chen GG, Koenig MK, et al. Correction: a new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay. Genet Med. 2019;21(9):2159–60.
doi: 10.1038/s41436-018-0413-x pubmed: 30643220
Obata A, Kimura T, Obata Y, Shimoda M, Kinoshita T, Kohara K, et al. Correction to: vascular endothelial PDPK1 plays a pivotal role in the maintenance of pancreatic beta cell mass and function in adult male mice. Diabetologia. 2019;62(12):2375.
doi: 10.1007/s00125-019-04982-y pubmed: 31605154 pmcid: 6943388
Hu B, Zhang Y, Deng T, Gu J, Liu J, Yang H, et al. PDPK1 regulates autophagosome biogenesis by binding to PIK3C3. Autophagy. 2021;17(9):2166–83.
doi: 10.1080/15548627.2020.1817279 pubmed: 32876514

Auteurs

Linlan Hu (L)

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.

Xin Zhao (X)

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.

Xian He (X)

School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.

Yafei Guo (Y)

School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.

Hanxiao Cheng (H)

School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.

Shaoting Chen (S)

School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.

Guangde Zhou (G)

Centre for Clinical Pathology, Beijing You'an Hospital, Capital Medical University, No.8 Outside You'anmen, Fengtai District, Beijing, 100069, China. guangdez@sina.com.

Jiabo Wang (J)

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China. jiabo_wang@ccmu.edu.cn.
School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China. jiabo_wang@ccmu.edu.cn.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-DiHerbs, Beijing, 100700, China. jiabo_wang@ccmu.edu.cn.

Yawen Lu (Y)

School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China. ywlu0411@163.com.
ORCID: 0000-0003-3743-792X

Classifications MeSH