Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.
Animals ; Caprylates ; Ginsenosides ; chemical synthesis ; pharmacology ; Mice ; Molecular Structure ; Neoplasms, Experimental ; drug therapy ; Saponins

To obtain ginsenoside Rg1 molecularly imprinted polymer (MIP) separating materials with high selectivity, enrichment and adsorption performance through directional separation of ginsenoside Rg1 and analogues. In this study, MIPs were respectively prepared by precipitation polymerization and surface imprinted polymerization. Their adsorption performances were compared. The results showed that ginsenoside Rg1 MIPs prepared by the above two methods had a high adsorption performance to template molecules, with the maximum apparent adsorbing capacity of up to 27.74, 46. 80 mg x g(-1), respectively. Moreover, MIPs prepared by surface imprinted polymerization showed higher adsorption capacity than that by precipitation polymerization. The experimental results indicated that as for ginsenoside Rg1 with higher polarity, MIPs prepared by surface imprinted polymerization showed higher selectivity and adsorption performance, which provides provide important reference for preparing imprinted polymers with good adsorption performance with active molecules with strong polarity.
Adsorption ; Chemical Fractionation ; methods ; Chemical Precipitation ; Ginsenosides ; chemistry ; isolation & purification ; Molecular Imprinting ; Polymerization ; Polymers ; chemical synthesis

AIMTo determine 20S-ginsenoside Rg3 in various tissues of rabbit eye and evaluate pharmacokinetics following its topical application.

METHODS45 rabbits were divided into 9 groups. Aqueous humor, cornea and iris-ciliary body were collected at 0.017, 0.033, 0.083, 0.167, 0.5, 1.0, 1.5, 2.0 and 3.0 h following topically applying 1% 20S-ginsenoside Rg3 eyeointment and the concentrations in eye tissues were measured by HPLC.

RESULTSThe pharmacokinetics of 20S-ginsenoside Rg3 in rabbit eye were described by one-compartment model. The peak times in aqueous humor, cornea and iris-ciliary body were 0.42, 0.16 and 0.19 h, and T(1/2) were 0.1, 0.9 and 0.8 h respectively.

CONCLUSIONThe method of determining 20S-ginsenoside Rg3 in rabbit eyes was established. The pharmacokinetics parameters were determined.

Administration, Topical ; Animals ; Aqueous Humor ; metabolism ; Area Under Curve ; Chromatography, High Pressure Liquid ; Ciliary Body ; metabolism ; Cornea ; metabolism ; Eye ; metabolism ; Ginsenosides ; administration & dosage ; blood ; chemical synthesis ; pharmacokinetics ; Iris ; metabolism ; Ointments ; Rabbits ; Tissue Distribution