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BackgroundObesity is a socioeconomic problem, and visceral obesity, in particular, is related to cardiovascular diseases or metabolic syndrome. Fermented grains and various microorganisms are known to help with anti-obesity effects and weight management. Studies on the relationship between Bacillus coagulans and anti-obesity effects are not well known, and studies on the application of fermented grains and microorganisms to the human body are also insufficient.ObjectivesThis study aimed to evaluate the efficacy of Curezyme–LAC, an ingredient mixed with six-grain types fermented by B. coagulans, in reducing fat mass in adults with obesity.MethodsIn this randomized double-blinded placebo-controlled study, 100 participants [aged 40–65 years; body mass index (BMI) ≥ 25 to ≤ 33 kg/m2) were randomly allocated to two groups: 4 g/day Curezyme–LAC administered as a granulated powder or placebo (steamed grain powder mixture).ResultsAfter 12 weeks, visceral adipose tissue decreased significantly in the Curezyme–LAC group compared with that in the placebo group (mean ± standard error, SE of −9.3 cm2 ± 5.1) vs. (6.8 cm2 ± 3.4; p = 0.008). Compared to the placebo group, the Curezyme–LAC group also showed significant reductions in total fat mass (−0.43 ± 0.24 kg vs. 0.31 ± 0.19 kg, p = 0.011), body weight (−0.4 ± 0.3 kg vs. 0.3 ± 0.2 kg, p = 0.021), BMI (−0.14 ± 0.12 vs. 0.10 ± 0.07, p = 0.028), and waist circumference (−0.6 ± 0.2 cm vs. −0.1 ± 0.2 cm, p = 0.018) without a change in dietary intake and physical activity.ConclusionCurezyme–LAC supplementation for 12 weeks may benefit individuals with obesity by reducing visceral fat mass.

Human hair follicle dermal papilla cells (HFDPCs) located in hair follicles (HFs) play a pivotal role in hair follicle morphogenesis, hair cycling, and hair growth. Over the past few decades, probiotic bacteria (PB) have been reported to have beneficial effects such as improved skin health, anti-obesity, and immuno-modulation for conditions including atopic dermatitis and inflammatory bowel disease (IBD). PB can secrete 50~150 nm sized extracellular vesicles (EVs) containing microbial DNA, miRNA, proteins, lipids, and cell wall components. These EVs can regulate communication between bacteria or between bacteria and their host. Although numerous biological effects of PB-EVs have been reported, the physiological roles of Leuconostoc holzapfelii (hs-Lh), which is isolated from human scalp tissue, and the extracellular vesicles derived from them (hs-LhEVs) are largely unknown. Herein, we investigated the effects of hs-LhEVs on hair growth in HFDPCs. We show that hs-LhEVs increase cell proliferation, migration, and regulate the cell cycle. Furthermore, hs-LhEVs were found to modulate the mRNA expression of hair-growth-related genes in vitro. These data demonstrate that hs-LhEVs can reduce apoptosis by modulating the cell cycle and promote hair growth by regulation via the Wnt/β-catenin signal transduction pathway.

Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin’s ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.

Limonin, one of the major components in dictamni radicis cortex (DRC), has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST) has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB.

This study investigated the effects of an ethanol extract of black pepper and its constituent, piperine, on odorant‐induced signal transduction in non‐chemosensory cells. An ethanol extract of black pepper decreased eugenol‐induced cAMP and calcium levels in preadipocyte 3T3‐L1 cells with no toxicity. Phosphorylation of CREB (cAMP response element‐binding protein) was down‐regulated by the black pepper extract. The concentration (133.8 mg/g) and retention time (5.5 min) of piperine in the ethanol extract were quantified using UPLC–MS/MS. Pretreatment with piperine decreased eugenol‐induced cAMP and calcium levels in 3T3‐L1 cells. Piperine also decreased the phosphorylation of CREB, which is up‐regulated by eugenol. These results suggest that piperine inhibits the eugenol‐induced signal transduction pathway through modulation of cAMP and calcium levels and phosphorylation of CREB in non‐chemosensory cells.

Auraptene is a citrus-derived natural monoterpene that has been shown to exert anti-cancer, anti-bacterial, anti-inflammatory, and antioxidant roles. Since little is known about other biological functions of auraptene, we examined the efficacy of auraptene for stimulating angiogenesis in human umbilical vein endothelial cells (HUVECs). Treatment with low concentrations of auraptene stimulated endothelial cell proliferation, migration, and tube formation. Furthermore, auraptene activated Erk, Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production. Auraptene also partially induced the phosphorylation of VEGFR2. Furthermore, auraptene-induced activation of Erk, Akt, and eNOS were significantly inhibited by the inhibitors PD98059, LY294002, and l-NIO dihydrochloride. These results suggest that auraptene stimulates angiogenesis by regulating the VEGFR2, Erk, and PI3K/Akt-eNOS signaling pathways.

Gramine is an alkaloid found in giant reed and maple. Many reports discuss the health-beneficial effects of gramine in inflammation, angiogenesis, and cell growth. However, the physiological role of gramine in the odorant-induced signal transduction pathway has not yet been investigated. Therefore, in this study, we aimed to evaluate the effects of gramine on odorant-stimulated non-neuronal 3T3-L1 cells endogenously expressing the murine eugenol receptor, olfr73. We showed that gramine inhibited the eugenol-induced calcium influx and cyclic AMP (cAMP) elevation in the 3T3-L1 cells without any toxicity. In addition, gramine decreased the phosphorylation of protein kinase A and cAMP response element binding protein (CREB), which are known as downstream targets of cAMP, in eugenolstimulated 3T3-L1 cells. These results indicate that gramine suppresses the eugenol-induced signal transduction pathway in non-neuronal 3T3-L1 cells by modulating calcium influx, cAMP levels, and CREB phosphorylation. [ABSTRACT FROM AUTHOR]

Equol is a nonsteroidal estrogen metabolized from the soy isoflavone daidzein by intestinal bacteria. Although its clinical benefits remain unclear, many reports have demonstrated that equol plays various biological roles in cancer, osteoporosis, and cardiovascular disease. Contrary to reports in other systems, the function of equol in the olfactory system has not been well understood. In the olfactory system, various odorants can bind to their receptors on olfactory sensory neurons and subsequently activate adenylyl cyclase (AC). Increased cAMP levels via the activated AC modulate Ca2+ influx and lead to altered membrane potential. This process results in transmission of electric signals to the brain. Because cAMP signal transduction and Ca2+ levels play crucial roles in the olfactory system, we investigated the effects of equol on the cAMP pathway and Ca2+ influx after stimulation by the odorant eugenol in gastric adenocarcinoma cells. Our results reveal that the upregulated cAMP level by eugenol was significantly decreased by equol treatment. Phosphorylation of PKA and CREB, downstream targets of cAMP, was also reduced. Furthermore, the odorant-induced Ca2+ levels were decreased in the presence of equol. Taken together, these data suggest that equol inhibits the odorant-induced signaling pathway through modulation of PKA/CREB signaling transduction. [ABSTRACT FROM AUTHOR]

Diindolylmethane is a well-known molecule derived from indole-3-carbinol found in cruciferous vegetables. It plays many biological roles in angiogenesis, apoptosis, inflammation, hormone control, cell cycle, and tumor growth. However, the functions of DIM in the olfactory system have not been well understood. Because cAMP and Ca2+ signal transduction plays a pivotal role in the olfactory system, we investigated the effects of DIM on cAMP, its downstream target CREB, and Ca2+ in gastric adenocarcinoma cells infected with adenovirus expressing the eugenol receptor. Our results demonstrate the upregulation of cAMP and Ca2+ levels, and the phosphorylation of CREB by eugenol in AGS cells. This upregulation was significantly decreased by treatment with DIM. The data suggest that DIM inhibits the odorant-induced signal pathway. [ABSTRACT FROM AUTHOR]