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*

Objective To observe the changes and significance of the protein expression levels of nuclear factor-κB p65 (NF-κB p65), transforming long factor-β1 (TGF-β1) and apoptosis-related factors Bcl-2 and Bax in myocardial tissue of Bama miniature pig model of diabetic cardiomyopathy (DCM). Methods Ten healthy male Guangxi Bama miniature pigs, aged 4 to 5 months old, were selected and divided into control group and model group according to the random number table method, with 5 pigs in each group. After 12 hours of fasting in the two groups, the DCM model was replicated by intravenous injection of streptozotocin (STZ) 150 mg/kg; for the Bama miniature pigs in the control group, citric acid-sodium citrate buffer 150 mg/kg was injected intravenously. After 10 months of modeling, the basic conditions of the two groups of animals were observed and their fasting blood glucose (FPG) levels were detected. The protein expression levels of NF-κB p65, TGF-β1, Bcl-2 and Bax in myocardial tissue of two groups were detected by Western Blot and the pathological changes of myocardial tissue were observed under electron microscope. Results In the model group, 4 models were successfully established, and 1 died. The model pigs had symptoms such as polydipsia, polyphagia, polyuria and decreased body weight. The FPG level in the model group was significantly higher than that in the control group (mmol/L: 25.53±3.75 vs. 4.68±0.77, P < 0.01). Compared with the control group, the protein expression levels of NF-κB p65, Bax and TGF-β1 in the myocardial tissue of model group were significantly increased (NF-κB p65/GAPDH: 0.46±0.05 vs. 0.38±0.02, Bax/GAPDH: 0.46±0.01 vs. 0.35±0.01, TGF-β1/GAPDH: 0.39±0.01 vs. 0.33±0.01, all P < 0.05) and the expression level of Bcl-2 protein was significantly decreased (Bcl-2/GAPDH: 0.33±0.01 vs. 0.42±0.01, P < 0.01). Electron microscopy results showed that the myofibrils of myocardial tissue in the DCM model group were disordered, and the number of mitochondria in the gap was significantly reduced. A large number of mitochondria with vacuolar degeneration were observed. Conclusions The DCM model of Bama miniature pigs can be successfully replicated after 10 months of high-dose STZ disposable ear vein injection. The DCM model miniature pigs have obvious glucose metabolism disorder, and their myocardial tissue has inflammatory reaction, cardiomyocyte apoptosis and fibrosis.

Objective To evaluate the positions and forms of temporomandibular joints(TMJ) with different vertical skeletal patterns in Class Ⅱ division 1 patients.Methods Cone-beam CT scans of 117 Class Ⅱ division 1 adolescent patients (including 30 patients with high angle,58 with average angle and 29 with low angle) were selected and reconstructed using Mimics 10.0 software.Fourteen measurements related to the positions and forms of condyle,forms of fossa and joint spaces were performed.Results Compared with high and average angle patients,the condyles in low angle patients located more posteriorly and inferiorly [the vertical distances between condyle and S was (20.67 ± 1.99) mm and the antero-posterior distances between condyle and S was (9.15± 1.61) mm].The joint fossae were deeper[the fosse depths was (7.83 ± 1.06) mm].The angles of posterior joint node bevels were bigger[the inclinations were (28.91 ±3.94)°].The condyles were shorter,thicker,tipped more anteriorly and positioned more posteriorly[the proportions of post-positioned condyles of low angle,average angle and high angle patients were 26％,4％,0％ respectively].Conclusions Class Ⅱ division 1 adolescents with different vertical skeletal patterns had different forms of fossae,and different positions and forms of condyles.