2021 年 8 巻 2 号 p. 98-109
Purpose: One of the measures against glycative stress is a method of promoting the decomposition and metabolism of accumulated advanced glycation end products (AGEs). We screened a large number of plants using indicators such as the action of directly cleaving the AGE crosslinks and the enhancing action for the oxidized protein hydrolase (OPH) activity that is involved in the decomposition of the glycated proteins. As a result, we identified that Trigonella foenum-graecum (fenugreek, seeds), Foeniculum vulgare (fennel, seeds) and Hibiscus sabdariffa (hibiscus, calyxes and bracts) have both actions. In addition, it has been reported that the mixed herb extract (MHE) consisting of these 3 herbs demonstrated various anti-glycation effects and physiological functions in our exploratory clinical trial with two groups, 100 mg/day (low-dose group) and 300 mg/day (high-dose group), in the previous study. Therefore, in this study, we conducted a randomized, placebo-controlled parallel-group study with the same amount of MHE as the low-dose group in the previous study to verify its anti-glycation effect and its effects on the skin. Method: The subjects were 40 Japanese women (20 in the MHE group, 20 in the placebo group) aged 40 to 64 years who had high amounts of AGEs deposits on the skin (as measured by AGE Reader mu). MHE was used as the test food, which was administered in soft capsules of 100 mg per day for 12 weeks. The subjects underwent blood tests, urine tests, skin-related tests, physical tests, body measurements and medical interviews before administration as well as after 6 and 12 weeks of administration. Note that this study has been conducted upon approval by an ethics review committee. (UMIN Clinical Trial ID: UMIN000037855). Results: During the study, 4 subjects withdrew and 1 was subject to the trial exclusion criteria, therefore, the number of subjects analyzed was 19 in the MHE group and 16 in the placebo group. A subgroup analysis was performed for pentosidine, the primary outcome, with 10 subjects in the MHE group and 6 subjects in the placebo group who were below the mean value of all the subjects for analysis, excluding 1 subject whose result was judged to be an outlier using the interquartile range. A significant decrease was observed only in the MHE group when comparing the results from pre-administration to after 12 weeks of administration. A significant decrease was also observed in the group compared to the placebo group. A subgroup analysis was conducted for Nε-(carboxymethyl) lysine (CML) with 7 subjects in the MHE group and 5 subjects in the placebo group whose BMI were 22.0 or higher, excluding 1 subject whose result was judged to be an outlier using the interquartile range. A tendency to decrease was observed only in the MHE group when comparing the results from pre-administration to after 12 weeks of administration. In the results of imaging analysis by VISIA for all cases, only the MHE group showed a decrease in the wrinkle parameter after administration compared to the pre-administration levels, and the group also indicated a significant tendency to decrease against the placebo group. In addition, improvement effects were observed in the MHE group in the secondary outcomes of skin texture and brown spots. Conclusion: Administration of MHE improved glycation indices as well wrinkles, texture and brown spots of the skin. It is considered that the AGE crosslink cleaving activity and the OPH activity enhancing action of the MHE may have contributed to these effects.
