Combining Lemon and Glycerin may Beneficially Regulate Blood Glucose Levels by Modulating Gut Microbiota in Non-obese Diabetic Mice

Both dietary lemon and glycerin have shown beneficial effects in diabetic humans and animals. It was hypothesized that there were potential therapeutic advantages of combining both agents in hyperglycemic and healthy mice. In a 6-month study using mature adult male non-obese diabetic (NOD) mice, oral treatment with either lemon or glycerin alone increased blood glucose levels during the third month glucose tolerance test and decreased the activity of the predicted glycolysis/gluconeogenesis pathways when compared to the vehicle control; however, this was no longer observed when lemon and glycerin were combined. Metabolomic analysis indicated that acetate was increased in the fecal samples after treatment with either glycerin or the combination. A 2-month study was also conducted in both male and female NOD mice and suggested that there were more gut microbiome changes at one month in comparison to six months. In older NOD male mice, treatment with the combination for six months decreased insulin resistance. In both adult male and female C57BL/6 mice, dosing with the combination for two months decreased blood glucose levels, as well as glucose tolerance and insulin resistance. In addition, treatment with the combination decreased body weights, especially in male mice, in all four studies. Overall, these studies suggest that lemon and glycerin in combination may reduce the side effects of individual treatments (e.g., transient hyperglycemia) and have some additional benefits (e.g., weight loss). Microbiome modulation likely contributed to the observed beneficial effects

Modulation of cytokine/chemokine production in human macrophages by bisphenol A: A comparison to analogues and interactions with genistein

The immunotoxicant bisphenol A (BPA) may produce toxic effects on organs and systems, in part, by altering the secretion of cytokines and chemokines. However, systematic studies of the effects of BPA, let alone of its analogs and in cases when there are interactions with other chemicals, on innate immunity and cytokine modulation are limited. The objectives of this study were to investigate the immunomodulatory effects of: (1) BPA and its analogs, BPS and BPAF; and (2) the interaction between BPA and genistein (GEN), a partial estrogen agonist or antagonist. BPA, BPS, and BPAF were incubated with PMA-differentiated-U937 cells (a widely used cell line for primary human macrophages) at concentrations of 0, 0.1, 1, 10, 100 µM for up to 96 h. BPA (0, 0.1, 1, 10 µM) and GEN (0, 1, 10 µM) were also applied at various combinations. Cell viability and 30 cytokines/chemokines were measured. The results showed that the cell viability-inhibiting effect of these three bisphenols was BPAF > BPA > BPS. At 0.1 µM, BPA and BPAF generally increased the secretion of cytokines/chemokines, while BPS had minimal effects. All three bisphenols generally suppressed the secretion of cytokines/chemokines at 1 µM, while increased their secretion at 10 µM. The most increased cytokines/chemokines were interferon (IFN)-γ, interleukin (IL)-1RA, IL-8 and MIP-1β, and the most decreased was IL-10. GEN increased cell viability at low BPA concentrations but had no effect when BPA levels were high. In general, GEN attenuated the BPA-induced secretion of cytokines/chemokines but enhanced it at low BPA concentrations. In conclusion, this study showed that BPA, BPS, and BPAF were immunotoxic to macrophages: BPS was the least toxic, while BPAF was the most toxic. Further, GEN reversed suppressive effects on macrophages that resulted from exposure to high concentrations of BPA and produced synergetic effects with BPA at low concentrations