Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice

Black ginseng (BG) is of great interest for its anti-cancer property. Its detailed mechanism, however, is still lacking. This study aims to evaluate the effectiveness of ginsenosides 20R-Rg3 and Rg5 enriched BG (Rg3/Rg5-BG), innovatively prepared by low temperature steam-heating process, against col...

Full description

Saved in:
Bibliographic Details
Main Authors: Peng Yu, Weiyin Xu, Yanqi Li, Zhaoyang Xie, Simeng Shao, Jianing Liu, Ying Wang, Long Wang, Hongmei Yang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Research in Food Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2665927125000097
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832589988623024128
author Peng Yu
Weiyin Xu
Yanqi Li
Zhaoyang Xie
Simeng Shao
Jianing Liu
Ying Wang
Long Wang
Hongmei Yang
author_facet Peng Yu
Weiyin Xu
Yanqi Li
Zhaoyang Xie
Simeng Shao
Jianing Liu
Ying Wang
Long Wang
Hongmei Yang
author_sort Peng Yu
collection DOAJ
description Black ginseng (BG) is of great interest for its anti-cancer property. Its detailed mechanism, however, is still lacking. This study aims to evaluate the effectiveness of ginsenosides 20R-Rg3 and Rg5 enriched BG (Rg3/Rg5-BG), innovatively prepared by low temperature steam-heating process, against colorectal cancer (CRC), and elucidate its potential molecular mechanism. Interestingly, much higher concentrations of rare ginsenosides were detected in this unique BG than those in red ginseng, especially 20R-Rg3 and Rg5, which may contribute to treatment of CRC. As expected, Rg3/Rg5-BG demonstrated a dose-dependent reduction in cancer cell viability, along with the induction of cell apoptosis and cell cycle arrest. Moreover, Rg3/Rg5-BG retarded tumor growth in the model mice, as evidenced by downregulation of anti-apoptotic Bcl-2 protein and phosphatidyl Akt, and upregulation of the apoptotic proteins Bax, caspase-8, and cleaved caspase-3, enhancing apoptosis of tumor cells. Additionally, Rg3/Rg5-BG treatment improved the gut microbiota and intervened with bacteria associated with cancer development, including increasing beneficial probiotics such as Candidatus_Saccharibacteria and Saccharibacteria_genera_incertae_sedis and decreasing pernicious bacteria (Vampirovibrio, Clostridium_XlVb, etc.). Our results manifested for the first time that Rg3/Rg5-BG exerted its anti-cancer effects: through activation of the caspase-3/Bax/Bcl-2 pathway and by altering the gut microbiome composition, thus paving the way for new therapeutic strategies that incorporate natural products in cancer treatment.
format Article
id doaj-art-87505a0be4f34063bc81e5d39b38091e
institution Kabale University
issn 2665-9271
language English
publishDate 2025-01-01
publisher Elsevier
record_format Article
series Current Research in Food Science
spelling doaj-art-87505a0be4f34063bc81e5d39b38091e2025-01-24T04:45:41ZengElsevierCurrent Research in Food Science2665-92712025-01-0110100978Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in micePeng Yu0Weiyin Xu1Yanqi Li2Zhaoyang Xie3Simeng Shao4Jianing Liu5Ying Wang6Long Wang7Hongmei Yang8College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, ChinaCollege of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, ChinaPublic Experimental Center, Changchun University of Chinese Medicine, 130117, Changchun, ChinaPublic Experimental Center, Changchun University of Chinese Medicine, 130117, Changchun, ChinaPublic Experimental Center, Changchun University of Chinese Medicine, 130117, Changchun, ChinaCollege of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, ChinaSchool of Medicine, Changchun Institute of Science and Technology, Changchun, 130600, ChinaPublic Experimental Center, Changchun University of Chinese Medicine, 130117, Changchun, ChinaPublic Experimental Center, Changchun University of Chinese Medicine, 130117, Changchun, China; Corresponding author. The Public Experimental Center, Changchun University of Chinese Medicine, Changchun, 130117, China.Black ginseng (BG) is of great interest for its anti-cancer property. Its detailed mechanism, however, is still lacking. This study aims to evaluate the effectiveness of ginsenosides 20R-Rg3 and Rg5 enriched BG (Rg3/Rg5-BG), innovatively prepared by low temperature steam-heating process, against colorectal cancer (CRC), and elucidate its potential molecular mechanism. Interestingly, much higher concentrations of rare ginsenosides were detected in this unique BG than those in red ginseng, especially 20R-Rg3 and Rg5, which may contribute to treatment of CRC. As expected, Rg3/Rg5-BG demonstrated a dose-dependent reduction in cancer cell viability, along with the induction of cell apoptosis and cell cycle arrest. Moreover, Rg3/Rg5-BG retarded tumor growth in the model mice, as evidenced by downregulation of anti-apoptotic Bcl-2 protein and phosphatidyl Akt, and upregulation of the apoptotic proteins Bax, caspase-8, and cleaved caspase-3, enhancing apoptosis of tumor cells. Additionally, Rg3/Rg5-BG treatment improved the gut microbiota and intervened with bacteria associated with cancer development, including increasing beneficial probiotics such as Candidatus_Saccharibacteria and Saccharibacteria_genera_incertae_sedis and decreasing pernicious bacteria (Vampirovibrio, Clostridium_XlVb, etc.). Our results manifested for the first time that Rg3/Rg5-BG exerted its anti-cancer effects: through activation of the caspase-3/Bax/Bcl-2 pathway and by altering the gut microbiome composition, thus paving the way for new therapeutic strategies that incorporate natural products in cancer treatment.http://www.sciencedirect.com/science/article/pii/S2665927125000097Anti-apoptosisBlack ginsengColorectal cancerRare ginsenosidesGut microbiota
spellingShingle Peng Yu
Weiyin Xu
Yanqi Li
Zhaoyang Xie
Simeng Shao
Jianing Liu
Ying Wang
Long Wang
Hongmei Yang
Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice
Current Research in Food Science
Anti-apoptosis
Black ginseng
Colorectal cancer
Rare ginsenosides
Gut microbiota
title Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice
title_full Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice
title_fullStr Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice
title_full_unstemmed Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice
title_short Ginsenosides 20R-Rg3 and Rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the Akt/Bax/caspase-3 pathway and modulating gut microbiota in mice
title_sort ginsenosides 20r rg3 and rg5 enriched black ginseng inhibits colorectal cancer tumor growth by activating the akt bax caspase 3 pathway and modulating gut microbiota in mice
topic Anti-apoptosis
Black ginseng
Colorectal cancer
Rare ginsenosides
Gut microbiota
url http://www.sciencedirect.com/science/article/pii/S2665927125000097
work_keys_str_mv AT pengyu ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT weiyinxu ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT yanqili ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT zhaoyangxie ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT simengshao ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT jianingliu ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT yingwang ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT longwang ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice
AT hongmeiyang ginsenosides20rrg3andrg5enrichedblackginsenginhibitscolorectalcancertumorgrowthbyactivatingtheaktbaxcaspase3pathwayandmodulatinggutmicrobiotainmice