Soy Peptide Supplementation Mitigates Undernutrition through Reprogramming Hepatic Metabolism in a Novel Undernourished Non-Human Primate Model.

In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human-relevant criterion for determining undernutrition weight-for-age z-score (WAZ), with a cutoff point of ≤ -1.83 is established as the benchmark for identifying undernourished nonhuman primates (U-NHPs). In U-NHPs, pathological anomalies in multi-organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U-NHPs. Mitochondria dysfunction is typified by reduced mito-number, accumulated long-chain fatty acids, and disruption of OXPHOS complexes. Soy peptide-treated U-NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U-NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re-establish lipid metabolism balance and mitigated undernutrition.

Hericium erinaceus mycelium-Derived Polysaccharide Alleviates Ulcerative Colitis and Modulates Gut Microbiota in Cynomolgus Monkeys.

SCOPE: Ulcerative colitis (UC) is rapidly increasing worldwide but prolong use of available corticosteroids treatment is associated with numerous adverse effects. There is the urgent need to develop novel therapeutic options. However, this requires the use of suitable disease models, but current models are generated with chemical agents mainly in rodents, which are unable to recapitulate the human occurrence. The aim of this study is to validate the occurrence of spontaneous UC in cynomolgus monkeys and explore the potential of Hericium erinaceus mycelium-derived polysaccharide in reversing UC pathologies. METHODS AND RESULTS: Postmortem bowel evaluation and biochemical analysis including inflammatory markers and fecal occult blood testing (FOBT) as well as nutrition status parameters, confirm the non-artificial induced spontaneous occurrence of UC in cynomolgus monkeys. Subsequently, H. erinaceus mycelium-derived polysaccharide supplementation significantly attenuates UC pathologies, improves nutritional status, reduces the incidence of diarrhea, and reduces inflammation in UC monkeys. Importantly, the polysaccharides administration enhances intestinal function and reshapes the gut microbiota. CONCLUSION: The study confirms the spontaneous UC monkeys can closely mimic the occurrence of UC in humans. Moreover, H. erinaceus mycelium-derived polysaccharide can effectively restore UC in monkeys, which show the prospects as precision nutritional supplement for the management of UC.

Effects of particle size reduction combined with ß-cyclodextrin on the in vitro dissolution and in vivo relative bioavailability of ginsenosides in Panax ginseng.

The biological effects of ginsenosides are limited by their low oral bioavailability. This study aimed to investigate the effects of particle size reduction and dispersants on the dissolution and bioavailability of ginsenosides in ginseng. Fine ginseng powder (FGP), ultrafine ginseng powder (UGP), and ultrafine ginseng powder with ß-cyclodextrin as the dispersant (UGPD) were prepared using a planetary ball mill from coarse ginseng powder (CGP, as the control). The particle size, morphology, hydration, thermal properties, and in vitro dissolution behavior of ginseng powders were characterized. The relative oral bioavailability of ginsenosides (9 protopanaxadiol (PPD)-type and 7 protopanaxatriol (PPT)-type) was determined in a rat model. Both UGP and UGPD displayed improved physiochemical properties (e.g. reduced particle size, increased hydration and thermal properties). The total in vitro dissolution of ginsenosides from UGPD was ∼17.2% higher than that from CGP; in contrast, UGP did not differ from CGP. More importantly, the in vivo pharmacokinetic study showed that the relative bioavailability of a total of 16 ginsenosides in UGPD was 180.1 ± 9.9% (CGP set as 100%), which was significantly greater than that in FGP and UGP. This suggested that dispersants were essential for preserving the benefits of ultrafine milling by preventing ultra-pulverization induced agglomeration. In particular, PPD-type ginsenosides showed similar deglycosylation trends in in vitro and in vivo experiments; in contrast, the deglycosylation states of PPT-type ginsenosides varied, which might be attributed to the relatively low abundance, glycosylation linkage, and potential involvement of the gut microbiota metabolism. Conclusively, ultrafine milling combined with a dispersant provides a simple and scalable manufacturing process that can effectively improve the bioavailability of ginseng products.