Metabolites of Rg3 are Expected to Increase the Anti-cancer Properties of Rg3
01 Jan

Metabolites of Rg3 are Expected to Increase the Anti-cancer Properties of Rg3

Introduction

Rare ginsenoside Rg3, an active extract from Panax ginseng, is reported to possess a wide range of pharmacological properties including anti-angiogenesis and anti-cancer, with high lipophilicity (estimated log P4) and a low water solubility at pH7.4. Nevertheless, its permeability and bioavailability are relatively low, and production procedures are complex. Remarkably, the metabolites of Rg3 have similar and even stronger activity than Rg3, opening up new opportunities for future adjuvant cancer therapy.

The association of ginsenoside Rg3 and its metabolites

There are two epimers of ginsenoside Rg3, which can be subsequently deglycosylated into epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD).

The anti-cancer properties of Rg3 metabolites

Angiogenesis and tumor cell proliferation are both interdependent factors in tumor progression. In terms of anti-proliferation, Rg3 metabolites, who induce S-phase arrest and necroptosis in a human triple negative breast cancer cell line MDA-MB-231 as well as G0/G1 arrest and apoptosis in human umbilical vein endothelial cells (HUVECs), are more potent than Rg3. The clinically relevant target of Rg3 metabolites are the endothelial cells. Anti-angiogenic effects are evaluated using loop formation assay. Among Rg3 metabolites, S-Rh2 is the most potent inhibitor of loop formation.

VEGFR2 and AQP1 as the targets of Rh2

According to the prediction by in silico molecular docking, there is a good binding score between Rh2/PPD and the ATP-binding pocket of VEGFR2, a dominant regulator controlling both physiological and pathological angiogenesis. Through VEGF bioassay, it is discovered that S-Rh2 is a most potent anti-angiogenic candidate with allosteric modulatory action on VEGFR2 function.



In addition, Rh2 and PPD have the potential of blocking AQP1 and AQP5, two members of the aquaporin family with vital roles in proliferation, migration, invasion and angiogenesis. Moreover, Rg3 is more selective for AQP1 and does not show a good binding score with AQP5. In light of this, blocking the water channel function of AQP1 may have an immediate role in inhibition of loop formation and anti-angiogenic effects of Rh2.

Conclusion

Metabolites of Rg3 could potentially increase the anti-cancer properties of Rg3. The application of these molecules alone or together may be potent alternatives for future adjuvant cancer therapy.

Reference

Nakhjavani M, Smith E, Yeo K, et al. Differential antiangiogenic and anticancer activities of the active metabolites of ginsenoside Rg3. J Ginseng Res. 2024;48(2):171-180. doi:10.1016/j.jgr.2021.05.008

BONTAC Ginsenosides

BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team. BONTAC has rich R&D experience and advanced technology in the biosynthesis of rare ginsenosides Rh2/Rg3, with pure raw materials, higher conversion rate and higher content (up to 99%). One-stop service for customized product solution is available in BONTAC. With unique Bonzyme enzymatic synthesis technology, both S-type and R-type isomers can be accurately synthesized here, with stronger activity and precise targeting action. Our products are subjected to strict third-party self-inspection, which are worth of trustworthy.

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Disclaimer

This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC.

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