Ginsenoside Rg5 (Rg5) has been certified to have superior activity in relieving the symptoms of non-alcoholic steatohepatitis (NASH). Nevertheless, the potential application of Rg5 is limited owing to its instability during storage. This study aims to enhance the stability of Rg5 through structural modification and evaluate its efficacy in treating NASH.

MATERIALS AND METHODS:

The modification involved the hydrogenation of the double bonds at C-20 (22) and C-24 (25) to form 2H-ginsenoside Rg5 (2HRg5). We used spectroscopic techniques including H-NMR, C-NMR, and high-resolution mass spectrometry to characterize the structure of 2HRg5. In addition, we used High-performance liquid chromatography (HPLC) to study the stability changes through stability experiments at 25 or 60°C for 25 days. We created NASH models in vitro and in vivo and used transcriptomics, molecular docking, and molecular dynamics simulations to examine the impact of 2HRg5 on NASH lipid accumulation, fibrosis, and liver inflammation.

KEY FINDINGS:

After 25 days at 60°C, 2HRg5 retained 82.7% of the active content compared to 9.4% for Rg5, with superior reduction in lipid accumulation, inflammation, and fibrosis in NASH mice. 2HRg5 inhibits the STING-TBK1-IRF3 pathway and reduces type I interferon release and inflammation. Moreover, the high binding efficiency and remarkable system stability between 2HRg5 and STING further support our findings.

SIGNIFICANCE:

2HRg5 provides improved storage stability and efficacy, making it a promising therapeutic candidate for NASH.

01 Aug 2025·PHYTOMEDICINE

Ginsenoside Rg5 ameliorates lipopolysaccharide (LPS)-induced acute liver injury via interfering Autophagy/Nrf2/Ferroptosis signal axis

Article

Author: Li, Hai-Jun ; Zhang, Yu-Xin ; Gao, Zhi-Cheng ; Shan, Guan-Yue ; Wan, Hui ; Shi, Yun-Peng

BACKGROUND:

Ginseng is a widely known Chinese herb, exerts its pharmacological effects primarily through ginsenosides. Ginsenoside-Rg5 is isolated from ginseng, has been shown to protect the liver and activate Nrf2 expression.

PURPOSE:

The protective effect of Rg5 on acute liver injury (ALI) and the related mechanisms will be discussed.

METHODS:

In vitro experiments, an ALI model was established using HepG2 cells. The DCFH-DA, the JC-1 and the ferrous ion fluorescent probe detected the ROS level, the mitochondrial membrane potential change, and the iron ions level. The oxidative stress indexes were detected by biochemical analysis. Western Blot was used to detected the autophagy, Nrf2, and ferroptosis signaling pathways. In vivo experiments, C57BL/6 J mice were injected with LPS to create ALI model.

RESULTS:

In vitro, Rg5 significantly inhibited the production of ROS, while restoring mitochondrial membrane potential. Biochemical analysis showed that Rg5 increased the SOD and GSH levels while decreased the MDA and ferric ion significantly. In vivo, Rg5 reduced the liver/body ratio, serum ALT and AST levels. Rg5 suppressed autophagy-related protein expression, promote Nrf2 and the ferroptosis negative regulatory proteins. This study first confirms that Rg5 exerts a protective effect on the liver by inhibiting ferroptosis, enriching the pharmacological properties of Rg5.

CONCLUSION:

The protective role of Rg5 against LPS-triggered ALI was mediated via autophagy/Nrf2-dependent suppression of ferroptosis.

01 Jul 2025·Journal of Ginseng Research

Ginsenoside Rg5 modulates the TLR4 and BCL-2 pathways by inhibiting NOX1, thereby alleviating inflammation, apoptosis and pyroptosis in hyperuricemia nephropathy

Article

Author: Liu, Yi-Ying ; Sun, Zi-Jun ; Gao, Zhi-Cheng ; Wan, Hui ; Li, Hai-Jun ; Zhang, Yu-Xin ; Shan, Guan-Yue ; Cheng, Jun-Ya ; Shi, Wen-Na

Background:

Hyperuricemia nephropathy (HN) is a form of renal injury caused by hyperuricemia, which can progress to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Ginsenoside Rg5, a major bioactive compound isolated from Panax ginseng, is recognized for its notable effects, including anti-inflammatory, antioxidant, and anticancer activities.

Method:

The toxic doses of MSU crystals and Rg5-induced HK-2 cell damage were assessed using the CCK-8 assay and quantifying oxidative stress markers (MDA, GSH, SOD). Intracellular stress was evaluated with JC-1 and DCFH-DA probes. Bioinformatics analysis identified NOX1, TLR4, and Bcl-2 as potential targets. The protein expression associated with stress, inflammation, pyroptosis, and apoptosis in HK-2 cells was evaluated through a combination of Western blotting, ELISA, flow cytometry, immunofluorescence, and overexpression methods. An HN mice model was established through administration of YE and adenine, and the effects of Rg5 were evaluated. The in vivo mechanisms were further verified.

Results:

Rg5 reduced serum uric acid, BUN, ADH, and creatinine levels in MSU crystals-stimulated HK-2 cells and hyperuricemic mice, alleviating renal damage. Rg5 inhibited NOX1 and suppressed the TLR4 pathway, reducing oxidative stress, inflammation, pyroptosis, and apoptosis. NOX1 overexpression reversed the effects of Rg5, while TLR4 overexpression had no effect. Rg5's efficacy was similar to NOX1 inhibitor ML171.

Conclusion:

These results indicate that Rg5 can modulate the TLR4 and BCL-2 pathways by inhibiting NOX1, thereby alleviating oxidative stress, inflammation, pyroptosis, and apoptosis in HN, highlighting its potential as a therapeutic approach for controlling HN.

News (Medical) associated with Ginsenoside Rg5

26 Jan 2024

·www.prnewswire.com

Three Journal of Pharmaceutical Analysis Studies Explore the Use of Traditional Chinese Medicine for Various Diseases

XI'AN, China, Jan. 26, 2024 /PRNewswire/ -- Despite demonstrating significant clinical efficacy against various diseases, the widespread use of Traditional Chinese Medicine (TCM) is still limited. This is mainly due to the complexity in their formulation and lack of sufficient pharmacological and safety-related data. To address this gap, a new issue of the Journal of Pharmaceutical Analysis presents three independent studies which assessed the potency of TCM-based compounds for various human diseases, along with their molecular mechanisms of action. Continue Reading Latest research unveils the potential of Traditional Chinese Medicine compounds for the treatment of human diseases The accumulation of excess fat in the liver leads to non-alcoholic fatty liver disease (NAFLD). Oridonin (ORI), a TCM derived from the Chinese herb Rabdosia rubescens, exhibits anti-inflammatory effects. An article available online on 21 August 2023 and published in Volume 13, Issue 11 of the journal in November 2023, now reveals that ORI regulates lipid homeostasis in the liver by maintaining the balance between triglyceride (TG) and phosphatidylethanolamine (PE), through modulation of adipose triglyceride lipase (ATGL) and ethanolamine phosphotransferase 1 (EPT1) expression via the liver X receptor alpha (LXRα) signaling pathway. "When the TG-PE lipid balance is disturbed, the seesaw tilts towards TG, increasing the risk of NAFLD. Restoring lipid homeostasis using compounds like oridonin can alleviate lipid accumulation and liver cytotoxicity," explains Professor Lan Tang. Tumor heterogeneity compromises the efficacy of radiotherapy for treating lung cancer. Radiosensitizers help prime tumor cells and improve their response to radiation. Now, in an article available online on 7 June 2023 and published in Volume 13, Issue 11 of the journal in November 2023, researchers found that ginsenoside Rg5 induced cell-cycle arrest and enhanced radiation-induced cell death. Ginsenoside Rg5 interacts with heat shock protein alpha (HSP90α) with high affinity and reduces the binding between HSP90 and cell division cycle 37 (CDC37), promoting HSP90-CDC37 client protein degradation. "Ginsenoside Rg5 can be potentially developed into a new drug for improving the sensitivity of lung cancer and other types of tumors to radiation therapy," the authors explain. Diabetic retinopathy (DR) is characterized by the activation of oxidative stress pathways in response to high glucose. In a study available online on 12 May 2023 and published in Volume 13, Issue 11 of the journal in November 2023, researchers synthesized a polymeric drug complex by combining a natural flavonoid antioxidant known as dihydromyricetin (DMY) with iron (Fe) ions in nano-coordinated polymer particles (NCPs). Fe-DMY NCPs can alleviate glucose-induced oxidative damage and reverse the pathological features of DR by decreasing the expression of key proteins involved in microvascular dysfunction. Fe-DMY NCPs could also inhibit the activation of Poldip2-Nox4-H2O2 signaling pathway and down-regulate important vascular function indicators such as VCAM-1, HIF-1α, and VEGF. Explaining its applications, the authors say, "We report for the first time the synthesis and validation of ultra-small Fe-DMY NCPs. Fe-DMY complexes bear the potential to alleviate the impact of DR on vision, thus improving the quality of life of affected individuals." These studies provide a scientific basis for the development of TCM-based compounds into effective targeted therapies for various diseases. Reference Titles of original papers: Oridonin restores hepatic lipid homeostasis in an LXRa-ATGL/EPT1 axis-dependent manner Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy Journal name: Journal of Pharmaceutical Analysis DOI: Media contact Mengjie Wang [email protected] Xi'an, China +86-(0)29-88960092 SOURCE Journal of Pharmaceutical Analysis

100 Deals associated with Ginsenoside Rg5

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiomyopathies	Preclinical	China	Guangdong Pharmaceutical University	13 Jun 2025
Cardiomyopathies	Preclinical	China	Beijing Institute of Radiation Medicine	13 Jun 2025
Encephalitis, Herpes Simplex	Preclinical	South Korea	Korea Institute of Oriental Medicine	01 Jul 2024
Glioblastoma	Preclinical	China	The First Hospital Of China Medical University	01 Jul 2024
Heart Diseases	Preclinical	China	Sichuan Cancer Hospital	24 May 2024
Nonalcoholic Steatohepatitis	Preclinical	China	Northwest University (China)	01 Feb 2024

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