Physiological Effects and Organ Distribution of <i>Bacillus amyloliquefaciens</i> AS385 Culture Broth Powder Containing 1-Deoxynojirimycin in C57BL/6J Mice

Abstract

1-Deoxynojirimycin (DNJ) has been known as a potent a-glucosidase inhibitor from mulberry leaves and considered beneficial in prevention of type 2 diabetes. Due to limited amount of DNJ in mulberry leaves, recent studies have focused in finding alternative source that can produce higher amount of DNJ. Previously, we produced a high DNJ-containing culture medium from Bacillus amyloliquefaciens AS385 and constructed a concentration method of bacterial culture medium using cation exchange column. However, less complicated concentration procedure is necessary to save time and cost during the large-scale production. Therefore, we developed a simpler concentration method using anion exchange resin to yield B. amyloliquefaciens AS385 culture broth powder (CBP; 1% DNJ) and evaluated the physiological effects of 5-wk dietary CBP intake in C57BL/6J mice. CBP intake tended to suppress the elevation of blood glucose level during oral glucose tolerance test. Moreover, CBP intake significantly lowered the fasting plasma glucose level and white adipose tissue mass. Next, we evaluated the absorption and distribution of DNJ in mice organs after daily CBP intake. We found detectable amount of DNJ in organs with intestine and kidney as the major targeted organs. We concluded that the DNJ content in CBP is absorbed from digestive tract, distributed and accumulated in organs, which most likely to contribute to the alteration of blood glucose regulation and adiposity in C57BL/6J mice. Our study was the first to report the physiological effects of CBP produced from B. amyloliquefaciens AS385 and the organ distribution of DNJ from CBP.

Intestinal Absorption and Tissue Distribution of Aza-Sugars from Mulberry Leaves and Evaluation of Their Transport by Sugar Transporters

“…A previous study reported the uptake of DNJ and fagomine into some organs and their time-dependent decrease. 19 Furthermore, a relatively high concentration of DNJ and fagomine in the kidney after single administration in rats 19 and long-term feeding in mice 5 were also reported, which is in line with our results. Renal excretion has been considered as the major excretion route of aza-sugars and therefore might explain the high abundance of DNJ and fagomine in the kidney.…”

“…3,4 Moreover, some of these aza-sugars have also received attention for other functionalities, such as antiobesity activity. 5 To gain insight into the aza-sugars' bioavailability and the extent of their contribution to the beneficial properties of mulberry leaves, it is necessary to understand their pharmacokinetic profiles (i.e., absorption profile and organ uptake).…”

“…Aza-sugars are mimetics of saccharides with a nitrogen atom in the ring and are relatively abundant in mulberry leaves, with 1-deoxynojirimycin (DNJ), fagomine, and 2- O -α- d -galactopyranosyl-1-deoxynojirimycin (GAL-DNJ) accounting for over 80% of the aza-sugars in mulberry leaves (Figure ). All three have been known as potent inhibitors of α-glucosidase, a membrane enzyme that catalyzes the degradation of disaccharides into monosaccharides in the small intestine, consequently suppressing the rise in the blood glucose level, which is useful in prevention and treatment of diabetes. , Moreover, some of these aza-sugars have also received attention for other functionalities, such as antiobesity activity . To gain insight into the aza-sugars’ bioavailability and the extent of their contribution to the beneficial properties of mulberry leaves, it is necessary to understand their pharmacokinetic profiles (i.e., absorption profile and organ uptake).…”

The effect of 1-deoxynojirimycin isolated from logging residue of Bagassa guianensis on an in vitro cancer model

“…While 1-DNJ is also present in Morus sp. leaves, silkworm parts, and produced by bacteria like Bacillus velezensis, these sources do not yield the compound as abundantly (Yin et al, 2010;Parida et al, 2019;Lee et al, 2021;Marchetti et al, 2021).…”

1‐Deoxynojirimycin attenuates pathological markers of Alzheimer's disease in the in vitro model of neuronal insulin resistance

“…These shifts led to improved systemic insulin sensitivity, postprandial glucose regulation, and lipid processing in the above studies. Additionally, DNJ was detected in brain tissues post‐oral intake, with approximately 1.5 nmol DNJ/g tissue detected after a single oral intake of 40 μmol DNJ/kg BW, 21 and 17.0 ± 2.5 ng DNJ/g tissue detected after repeated intake of 10 mg DNJ/kg BW for five weeks 22 . This, coupled with its commendable safety profile, 12,23 makes DNJ a safe and viable option for short‐term and long‐term neuroprotective purposes.…”