Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Enhancing Grip Strength and Inhibiting Protein Catabolism Induced by Exhaustive Exercise.

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance.

Black Ginger (Kaempferia parviflora) Extract Enhances Endurance Capacity by Improving Energy Metabolism and Substrate Utilization in Mice.

Black ginger (Kaempferia parviflora) extract (KPE), extracted from KP, a member of the ginger family that grows in Thailand, has a good promotion effect on cellular energy metabolism and therefore has been used to enhance exercise performance and treatment of obesity in previous studies. However, the effect of single-dose administration of KPE on endurance capacity has not been thoroughly studied, and whether the positive effect of KPE on cellular energy metabolism can have a positive effect on exercise capacity in a single dose is unknown. In the present study, we used a mouse model to study the effects of acute KPE administration 1 h before exercise on endurance capacity and the underlying mechanisms. The purpose of our study was to determine whether a single administration of KPE could affect endurance performance in mice and whether the effect was produced through a pro-cellular energy metabolic pathway. We found that a single administration of KPE (62.5 mg/kg·bodyweight) can significantly prolong the exercise time to exhaustion. By measuring the mRNA expression of Hk2, Slc2a4 (Glut4), Mct1, Ldh, Cd36, Cpt1ß, Cpt2, Lpl, Pnpla2 (Atgl), Aco, Acadm (Mcad), Hadh, Acacb (Acc2), Mlycd (Mcd), Pparg, Ppargc1a (Pgc-1α), Tfam, Gp, Gs, Pfkm, Pck1 (Pepck), G6pc (G6pase), Cs, and Pfkl in skeletal muscle and liver, we found that acute high-concentration KPE administration significantly changed the soleus muscle gene expression levels (p < 0.05) related to lipid, lactate, and glycogen metabolism and mitochondrial function. In gastrocnemius muscle and liver, glycogen metabolism-related gene expression is significantly changed by a single-dose administration of KPE. These results suggest that KPE has the potential to improve endurance capacity by enhancing energy metabolism and substrate utilization in muscles and liver.

Piper retrofractum extract and its component piperine promote lymphangiogenesis via an AKT- and ERK-dependent mechanism.

Administration of Piper retrofractum extract (PRE) has been reported to alleviate edema, but the mechanism underlying this effect is unknown. Promotion of lymphangiogenesis is known to improve lymphedema, but the effect of PRE on lymphangiogenesis remains unclear. In the present study, we investigated whether PRE and specifically, piperine, the main component of PRE, can induce lymphangiogenesis. Treatments with PRE and piperine significantly promoted the proliferation, migration, and tube formation in human dermal lymphatic microvascular endothelial cells (HDLECs) but had no effect on the expression of lymphangiogenic factors. Furthermore, PRE and piperine significantly promoted the phosphorylation of the AKT and ERK proteins in HDLECs, and pretreatment with AKT and ERK inhibitors significantly attenuated the PRE- and piperine-induced lymphangiogenesis. These results indicate that PRE and piperine promote lymphangiogenesis via an AKT- and ERK-dependent mechanism. PRACTICAL APPLICATIONS: The lymphatic system plays various roles such as maintaining tissue fluid homeostasis, immune defense, and metabolism. Disruption of the lymphatic system results in insufficient fluid drainage, which causes edema. Currently, there are no effective treatments for lymphedema; therefore, the development of novel treatment strategies is desirable. In this study, we showed that PRE and its main component piperine promote lymphangiogenesis in lymphatic endothelial cells. Therefore, PRE has the potential to be used as a novel functional food for relieving lymphedema.

Polymethoxyflavone purified from Kaempferia parviflora reduces visceral fat in Japanese overweight individuals: a randomised, double-blind, placebo-controlled study.

Visceral fat is a more important factor in obesity-associated disorders in Japanese individuals than in Caucasian individuals. The objective of this randomised, double-blind, placebo-controlled parallel group study, conducted in Japanese overweight adults, was to investigate the effects of polymethoxyflavone purified from Kaempferia parviflora on visceral fat. A total of 80 subjects (aged 20-64 years, 23.0 ≤ body mass index < 30 kg m-2) were randomly assigned in 1 : 1 ratio to either the active (polymethoxyflavone purified from K. parviflora) or placebo group. Over a 12-week period, each subject received two capsules containing polymethoxyflavone purified from K. parviflora (12 mg polymethoxyflavone per day) or placebo. The primary outcome was a reduction in visceral fat area (VFA), while the secondary outcome was a reduction in subcutaneous fat area (SFA) and total fat area (TFA). VFA was measured at 0, 8, and 12 weeks using computed tomography scanning. Results showed that VFA significantly reduced after 12 weeks in the active group and was significantly lower than in the placebo group at 8 and 12 weeks. A significant reduction was observed in SFA and TFA after 8 and 12 weeks in the active group; TFA was significantly lower than that in the placebo group at 8 and 12 weeks. No adverse events associated with the test supplements were observed in either group. Our study shows that administration of polymethoxyflavone purified from K. parviflora reduces visceral fat in Japanese overweight adults.

Extracellularly Extruded Syntaxin-4 Is a Potent Cornification Regulator of Epidermal Keratinocytes.

In the skin epidermis, keratinocytes undergo anchorage-dependent cornification, which gives rise to stratified multilayers, each with a distinct differentiation feature. The active formation of the cornified cell envelope (CCE), an important element in the skin barrier, occurs in keratinocytes of the upper epidermal layers and impacts their terminal differentiation. In the present study, we identified the extracellularly extruded syntaxin-4 as a potent differentiation regulator of epidermal keratinocytes. We found that differentiation stimuli led to the acceleration of syntaxin-4 exposure at the keratinocyte cell surface and that the artificial control of extracellular syntaxin-4, either by the forced expression of several syntaxin-4 mutants with structural alterations at the putative functional core site (AIEPQK), or by using antagonistic circular peptides containing this core sequence, dramatically influenced the CCE formation, with spatial misexpression of TGase1 and involucrin. We also found that the topical application of a peptide that exerted the most prominent antagonistic activity for syntaxin-4, named ST4n1, evidently prevented the formation of the hyperplastic and hyperkeratotic epidermis generated by physical irritation in HR-1 mice skin. Collectively, these results demonstrate that extracellularly extruded syntaxin-4 is a potent regulator of CCE differentiation, and that ST4n1 has potential as a clinically applicable reagent for keratotic skin lesions.