Investigating the Pro-Angiogenic Mechanism of Diammonium Glycyrrhizinate Injection in Zebrafish via Transcriptomic...

Area of Science:

• Pharmacology and Traditional Chinese Medicine
• Vascular Biology and Angiogenesis
• Molecular Mechanisms of Disease

Background:

• Glycyrrhizic acid (GA), a key metabolite from Glycyrrhiza glabra, is used in liver disease treatments.
• While GA's hepatoprotective effects are known, its role in promoting angiogenesis, crucial for ischemic diseases, remains unexplored.
• Existing GA preparations lack specific research into their pro-angiogenic potential.

Purpose of the Study:

• To investigate the pro-angiogenic activity of common GA preparations.
• To identify the most potent angiogenesis promoter among GA agents.
• To elucidate the molecular mechanisms underlying the pro-angiogenic effects of GA preparations.

Main Methods:

• A zebrafish vascular injury model induced by PTK787 was employed to assess pro-angiogenic effects.
• Systematic evaluation of diammonium glycyrrhizinate injection (DGI) on intersegmental vessels (ISVs) and subintestinal vein vessels (SIVs).
• Transcriptomics analysis and RT-qPCR validation were used to explore DGI's mechanism of action.

Main Results:

• Magnesium isoglycyrrhizinate injection (MII), DGI, compound glycyrrhizinate tablets (CGT), and diammonium glycyrrhizinate enteric-coated capsules (DGEC) all demonstrated significant pro-angiogenic effects.
• DGI exhibited the strongest pro-angiogenic activity among the tested GA preparations.
• Transcriptomic and RT-qPCR analyses revealed that DGI's pro-angiogenic effects are linked to the activation of the mTOR/HIF-1 signaling pathway.

Conclusions:

• GA preparations possess notable pro-angiogenic properties, with DGI showing particularly potent activity.
• The pro-angiogenic mechanism of DGI is primarily mediated through the activation of the mTOR/HIF-1 signaling pathway.
• This study expands the clinical applications of GA agents and offers insights into DGI's potential for treating ischemic diseases.