Synthesis and antitumor activity of three novel ginsenoside M1 derivatives with 3'-ester modifications.

Ginsenoside M1 (M1) was considered to be the main antitumor component of ginsenoside metabolites in the body. In order to enhance its potency on antitumor effect, three novel M1 3'-ester derivatives (1c, 2c, 3c) were synthesized and evaluated. The yield of these derivatives was between 41% and 69%. Compared with M1, 2c and 3c can improve the efficacy of the inhibition on breast cancer MCF-7 and MDA-MB-231 cells, especially for MCF-7 (fold: 0.7-4.2, p < 0.0001). Further study suggested that 2c and 3c may cause cell autophagy and promote apoptosis in MCF-7 cells. The results indicated the 3'-ester modified M1 derivatives 2c and 3c possess higher abilities of inhibition growth towards triple-positive breast cancer and provided a new source for synthesis of potential anti-breast cancer drugs.

Synthesis of esters of ginsenoside metabolite M1 and their cytotoxicity on MGC80-3 cells.

Monoesters of ginsenoside metabolite M1 at the 3-OH, 4-OH and 6-OH positions of the glucose moiety at M1 were synthesized via the reaction of M1 with acyl chloride, or acid-N,N'-diisopropylcarbodiimide in the presence of DMAP. Their structures were fully characterized by spectral methods. The cytotoxicity of these compounds against then MGC80-3 human gastric cancer cell line was also assessed. High inhibitory effects were found at a concentration of 100 µg/mL.

Nicotinamide overload may play a role in the development of type 2 diabetes.

AIM: To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N(1)-methylnicotinamide on glucose metabolism, plasma H(2)O(2) levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS: Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 +/- 0.13 micromol/L vs 0.6 +/- 0.13 micromol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. Moreover, cumulative exposure to N(1)-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N(1)-methylnicotinamide clearance. CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.