Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin.

Collagen hydrolysate is a well-known dietary supplement for the treatment of skin aging; however, its mode of action remains unknown. Previous studies have shown that the oral ingestion of collagen hydrolysate leads to elevated levels of collagen-derived peptides in the blood, but whether these peptides reach the skin remains unclear. Here, we analyzed the plasma concentration of collagen-derived peptides after ingestion of high tripeptide containing collagen hydrolysate in humans. We identified 17 types of collagen-derived peptides transiently, with a particular enrichment in Gly-Pro-Hyp. This was also observed using an in vivo mouse model in the plasma and skin, albeit with a higher enrichment of Pro-Hyp in the skin. Interestingly, this Pro-Hyp enrichment in the skin was derived from Gly-Pro-Hyp hydrolysis, as the administration of pure Gly-Pro-Hyp peptide led to similar results. Therefore, we propose that functional peptides can be transferred to the skin by dietary supplements of collagen.

Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice.

The senescence accelerated mouse prone 8 substrain (SAM-P8), widely accepted as an animal model for studying aging and antiaging drugs, was used to examine the effects of dietary supplementation with extracts of Cistanche deserticola (ECD) which has been used extensively in traditional Chinese medicine because of its perceived ability to promote immune function in the elderly. Eight-month-old male SAM-P8 mice were treated with ECD by daily oral administrations for 4 weeks. The results showed that dietary supplementation of 150 mg/kg and 450 mg/kg of ECD could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner. Dietary supplementation of SAM-P8 mice for 4 weeks with 100, 500, and 2500 mg/kg of ECD was shown to result in significant increases in both naive T and natural killer cells in blood and spleen cell populations. In contrast, peripheral memory T cells and proinflammatory cytokine, IL-6 in serum, were substantially decreased in the mice that ingested 100 and 500 mg/kg of ECD daily. Additionally, Sca-1 positive cells, the recognized progenitors of peripheral naive T cells, were restored in parallel. Our results provide clear experimental support for long standing clinical observational studies showing that Cistanche deserticola possesses significant effects in extending life span and suggest this is achieved by antagonizing immunosenescence.

Fomiroid A, a novel compound from the mushroom Fomitopsis nigra, inhibits NPC1L1-mediated cholesterol uptake via a mode of action distinct from that of ezetimibe.

Hypercholesterolemia is one of the key risk factors for coronary heart disease, a major cause of death in developed countries. Suppression of NPC1L1-mediated dietary and biliary cholesterol absorption is predicted to be one of the most effective ways to reduce the risk of hypercholesterolemia. In a screen for natural products that inhibit ezetimibe glucuronide binding to NPC1L1, we found a novel compound, fomiroid A, in extracts of the mushroom Fomitopsis nigra. Fomiroid A is a lanosterone derivative with molecular formula C30H48O3. Fomiroid A inhibited ezetimibe glucuronide binding to NPC1L1, and dose-dependently prevented NPC1L1-mediated cholesterol uptake and formation of esterified cholesterol in NPC1L1-expressing Caco2 cells. Fomiroid A exhibited a pharmacological chaperone activity that corrected trafficking defects of the L1072T/L1168I mutant of NPC1L1. Because ezetimibe does not have such an activity, the binding site and mode of action of fomiroid A are likely to be distinct from those of ezetimibe.

Melanin biosynthesis inhibitors from Tarragon Artemisia dracunculus.

The EtOH extract of tarragon Artemisia dracunculus, a perennial herb in the family Asteraceae, was found to potently inhibit α-melanocyte-stimulating hormone (α-MSH) induced melanin production in B16 mouse melanoma cells. Bioassay-guided fractionation led to the isolation of two alkamide compounds, isobutyl (1) and piperidiyl (2) amides of undeca-2E,4E-dien-8,10-dynoic acid. The respective EC(50) values for melanin biosynthesis inhibition were 1.8 and 2.3 µg/mL for 1 and 2.

Inhibitory effects of bakuchiol, bavachin, and isobavachalcone isolated from Piper longum on melanin production in B16 mouse melanoma cells.

An EtOH extract of fruits of Piper longum was found to exhibit a potent inhibitory effect against alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin production in B16 mouse melanoma cells. Bioassay-directed fractionation led to the isolation of prenylated phenolic compounds bakuchiol, bavachin, and isobavachalcone. These compounds and the crude extract of the fruits of P. longum may have suppressive effects against pigmentation by melanin in the skin.

Suppressive effects of Anoectochilus formosanus extract on osteoclast formation in vitro and bone resorption in vivo.

Anoectochilus formosanus, a plant native to Taiwan, is used as a folk medicine. It was found that oral administration of A. formosanus extract (AFE) (500 mg/kg) for 4 weeks suppressed bone weight loss and trabecular bone loss in ovariectomized mice, an experimental model of osteoporosis. Although AFE at 12.5 and 25 mug/ml inhibited osteoclast formation in co-culture of osteoblasts and bone marrow cells, AFE did not inhibit the formation of osteoclast progenitor cells and preosteoclast cells in bone marrow cells and RAW264 cells. However, AFE (at 12.5 and 25 microg/ml) decreased RANKL expression. These results suggested that AFE might suppress the bone loss caused by estrogen deficiency through suppression of RANKL expression required for osteoclast formation.

Effects of fenugreek seeds (Trigonella foenum greaecum) extract on endurance capacity in mice.

The present study was designed to determine the effect of fenugreek seed extract (FG) on endurance capacity in male mice aged 4 wk. Mice were given orally either vehicle or FG (150, 300 mg/kg body weight) by stomach intubation for 4 wk. The 300 mg/ kg FG group showed a significant increase in swimming time to exhaustion as compared to the control group. In the FG groups, blood lactate concentration was significantly lower than in the control group. In the control group, plasma non-esterified fatty acid (NEFA) and plasma glucose were decreased by swimming exercise. But in the FG group, NEFA and plasma glucose were significantly increased by swimming. FG treatment also significantly decreased fat accumulation. These results suggest that improvement in swimming endurance by the administration of FG is caused by the increase in utilization of fatty acids as an energy source.

Osteoclast-forming suppressive compounds from Makomotake, Zizania latifolia infected with Ustilago esculenta.

A novel compound (1) and a known one (2) were isolated from Makomotake, Zizania latifolia infected with Ustilago esculenta, as osteoclast-forming suppressive substances.

Inhibitory effects of pasuchaca (Geranium dielsiaum) extract on alpha-glucosidase in mouse.

The methanolic extract of pasuchaca (Geranium dielsiaum) (PsEx) was found to suppress blood glucose elevation after oral administration of sucrose, maltose, and starch, but not after oral administration of glucose, in the mouse. In vitro examination of the inhibitory effect of PsEx on maltase activity revealed that PsEx strongly inhibited mouse small intestine maltase activity. Taken together, these results suggest that the inhibitory effect of PsEx on alpha-glucosidase activity might contribute to delay in carbohydrate digestion and subsequent lowering of the blood glucose level, thereby leading to prevention and cure of diabetes.

Effects of fenugreek seed extract in obese mice fed a high-fat diet.

It was found that fenugreek seed extract reduced the body weight gain induced by a high-fat diet in obese mice. The extract decreased plasma triglyceride gain induced by oil administration. The major component of the extract, 4-hydroxyisoleucine, also decreased plasma triglyceride gain. Consequently, fenugreek seed extract is expected to prevent the obesity induced by a high-fat diet.

Effects of Anoectochilus formosanus on endurance capacity in mice.

The present study was designed to determine the effects of Anoectochilus formosanus exract (AFE) on endurance capacity in mice. Four wk-old male mice were given either a vehicle (distilled water) or AFE (500, 1,000 mg/kg) through stomach intubations for 4 wk. Mice were made to perform swimming exercises with weights attached to their tails corresponding to 10% of their body weight. Endurance capacity was evaluated by swimming time to exhaustion. The group treated with 1,000 mg/kg AFE showed a significant improvement (p<0.05) in endurance performance time. The mice were made to swim for 15 min with loads corresponding to 5% of their body weight. In the 1,000 mg/kg body weight of AFE administration group, blood lactate concentration was significantly lower than in the control group. In the AFE administration group, the plasma non-esterfied fatty acid (NEFA) was significantly increased by swimming exercise. AFE treatment also significantly decreased fat accumulation. Liver and gastrocnemius muscle glycogen after 15 min of swimming remained at significantly higher levels in the mice fed 1,000 mg/kg of AFE as compared to the control group. These results suggest that AFE activated utilization of lipid more than glucose as the energy source for performance.