An Efficient Method to Separate the Main Components from Black Ginseng of Panax quinquefolium L. by Recycling and Consecutive High‐Speed Counter‐Current Chromatography Coupled With Evaporative Light Scattering Detection

Article

Author: Sun, Huaming ; Wang, Zheng ; Van Le, Thi Hong ; Cao, Guiyun ; Sohail, Ammara ; Qin, Xiuheng ; Yu, Hongxia ; Wang, Daijie ; Zhao, Yan ; Meng, Zhaoqing ; Dong, Xiaodi ; Park, Jeonghill

ABSTRACTBlack ginseng (BG), a novel manufactured ginseng product, is gaining market attention due to its high polarity and similar structure constituents. In this work, the primary constituents of Panax quinquefolium L. BG, including ginsenosides and derivatives, were separated using high‐speed counter‐current chromatography in conjunction with evaporative light scattering detection by recycling and consecutive mode, as well as the elution‐extrusion method for continuous sample loading. Sample loading and mobile phase ratios were among the optimized primary separation parameters. Nine compounds, including ginsenoside Rg6 (1), 22(E)‐ginsenoside F4 (2), ginsenoside Rk3 (3), ginsenoside Rh4 (4), ginsenoside Rg3 (5), 20(R)‐ginsenoside Rg3 (6), (3R,9R,10R)‐panaxytriol (7), ginsenoside Rk1 (8), and ginsenoside Rg5 (9), were ultimately effectively isolated. Mass spectrometry and nuclear magnetic resonance spectrometry were used to investigate the structures. Based on our research, the developed process was a successful way to separate the primary ingredients from BG. Purification of additional comparable high‐polarity chemicals from complicated natural products might be accomplished using the stated methodology.

01 Sep 2024·British Journal of Pharmacology

Ginsenoside Rh4 prevents endothelial dysfunction as a novel AMPK activator

Article

Author: Liu, Xuyun ; Kang, Jiahao ; Zhang, Jiawei ; Cao, Ke ; Lv, Weiqiang ; Su, Jiacan ; Liu, Jiankang ; Zhang, Qi ; Liu, Fuying ; Sun, Zhenyu ; Zeng, Mengqi ; Ma, Shaozhou

Background and PurposeThe AMP‐activated protein kinase (AMPK) signalling pathway is a desirable target for various cardiovascular diseases (CVD), while the involvement of AMPK‐mediated specific downstream pathways and effective interventions in hyperlipidaemia‐induced endothelial dysfunction remain largely unknown. Herein, we aim to identify an effective AMPK activator and to explore its efficacy and mechanism against endothelial dysfunction.Experimental ApproachMolecular docking technique was adopted to screen for the potent AMPK activator among 11 most common rare ginsenosides. In vivo, poloxamer 407 (P407) was used to induce acute hyperlipidaemia in C57BL/6J mice. In vitro, palmitic acid (PA) was used to induce lipid toxicity in HAEC cells.Key ResultsWe discovered the strongest binding of ginsenoside Rh4 to AMPKα1 and confirmed the action of Rh4 on AMPK activation. Rh4 effectively attenuated hyperlipidaemia‐related endothelial injury and oxidative stress both in vivo and in vitro and restored cell viability, mitochondrial membrane potential and mitochondrial oxygen consumption rate in HAEC cells. Mechanistically, Rh4 bound to AMPKα1 and simultaneously up‐regulated AKT/eNOS‐mediated NO release, promoted PGC‐1α‐mediated mitochondrial biogenesis and inhibited P38 MAPK/NFκB‐mediated inflammatory responses in both P407‐treated mice and PA‐treated HAEC cells. The AMPK inhibitor Compound C treatment completely abrogated the regulation of Rh4 on the above pathways and weakened the lowering effect of Rh4 on endothelial impairment markers, suggesting that the beneficial effects of Rh4 are AMPK dependent.Conclusion and ImplicationsRh4 may serve as a novel AMPK activator to protect against hyperlipidaemia‐induced endothelial dysfunction, providing new insights into the prevention and treatment of endothelial injury‐associated CVD.

01 Jul 2024·Journal of Advanced Research

Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism

Article

Author: Duan, Zhiguang ; Fu, Rongzhan ; Zhu, Chenhui ; Zhang, Zhuo ; Deng, Jianjun ; Fan, Daidi ; Bai, Xue

INTRODUCTIONDysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored.OBJECTIVESWe investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota.METHODSWe used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC.RESULTSOur research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC.CONCLUSIONOur results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.

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Indication	Highest Phase	Country/Location	Organization	Date
Endothelial dysfunction	Preclinical	China	Xi'an Jiaotong University	16 May 2024
Cardiomyopathy, Hypertrophic	Preclinical	China	First Affiliated Hospital of Dalian Medical University	01 Mar 2024
Myocardial fibrosis	Preclinical	China	First Affiliated Hospital of Dalian Medical University	01 Mar 2024
Renal Cell Carcinoma	Preclinical	China	Henan University of Traditional Chinese Medicine	01 Jan 2024
Breast Cancer	Preclinical	China	China Northwest University	01 Apr 2018

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