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The development of efficient biomarkers and probes for monitoring and treating cancer, specifically metastatic cancer, is a critical research area that can have a significant impact on both patient outcomes and drug discovery. In this context, TiNIR has been developed to detect tumor-initiating cells (TICs), with heme oxygenase 2 (HO2) as a promising therapeutic biomarker for tumor-initiating cells. In this study, TiNIR has demonstrated its effectiveness as an in vivo metastatic lung cancer tracker, highlighting its potential as a valuable tool in cancer research and therapy. The development of innovative approaches that selectively target metastatic cancers represents a promising avenue for improving survival rates and enhancing the quality of life of cancer patients. [ABSTRACT FROM AUTHOR]

Skin whitening has recently renewed attention on Chinese herbal medicines with whitening activity for esthetic applications. Stachys sieboldii has been used as herbal medicine since ancient times and has the potential for development as a cosmetic material because of its astringent effect. In this study, with an aim to develop new functional materials with whitening effects, S. sieboldii water extracts were fermented with different mushroom mycelia. Fermented with Hericium erinaceus mycelia showed the strongest tyrosinase inhibition effect and the lowest melanin content. Thus, H. erinaceus mycelia, the most potent inhibitor of melanogenesis, was used for large-scale fermentation and fractionated. The ethyl acetate fraction, which had the strongest whitening activity, was separated and purified using HPLC. Finally, the single compound was isolated and identified as acteoside, which has promising whitening activity. Acteoside inhibited melanin synthesis and intracellular tyrosinase activity in a dose-dependent manner. The effects of acteoside on the expression of TYR, TRP-1, TRP-2, and MITF were analyzed using Western blot analysis, which showed that acteoside reduced the protein in a dose-dependent manner. Our findings reveal the potential applicability of S. sieboldii extract fermented with H. erinaceus mycelia and its useful component, which is an acteosid, for skin lightening and the treatment of pigmentation. [ABSTRACT FROM AUTHOR]

The ameliorative effect of medicarpin (MC) was investigated by animal behavioral experiments such as Morris water maze (MWM), Y-maze, and passive avoidance test (PAT), using scopolamine-induced cognitively impaired mice. The scopolamine (5 mg/kg), donepezil (5 mg/kg), and MC (5 and 15 mg/kg) were administered by intraperitoneal injection at a volume of 0.3 mL. In the MWM, the escape latency times of MC-treated groups were significantly decreased compared with the scopolamine-treated negative control, and times spent in the platform zone of MC-treated groups were increased dose-dependently. In the Y-maze, the zone alternations of the MC-treated group were increased to the level of the donepezil-treated positive control. In the PAT, the crossing times of MC-treated groups were significantly higher than those of the negative control with dose-dependency. On the other hand, the monoamine oxidase (MAO)-A, MAO-B, and acetylcholinesterase (AChE) activities, relating to cognitive functions, in hippocampus treated with MC were decreased. In addition, the AChE activity in SH-SY5Y cells was significantly decreased. In Western blots, phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), phosphorylated protein kinase B (p-Akt), and dopamine D2 receptor (D2R) levels in the hippocampus were higher than those of the negative control. In addition, p-CREB, BDNF, p-Akt, and D2R levels in SH-SY5Y cells treated with MC were significantly increased. These results showed that MC ameliorated a cognitive function along with increased BDNF and D2R expressions, and they suggested that MC could be used for the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13. Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (Ki = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13. However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (−8.7 and −7.7 kcal/mol, respectively) were higher than those for hMAO-A (−3.4 and −7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders. [ABSTRACT FROM AUTHOR]

The Food and Agriculture Organization (FAO) has been estimating the potential of insects as human food since 2010, and for this reason, Tenebrio molitor larvae, also called mealworms, have been explored as an alternative protein source for various foods. In this study, in order to increase nutrient contents and improve preference as an alternative protein source, we fermented the T. molitor larvae by Cordyceps militaris mycelia. T. molitor larvae were prepared at optimal conditions for fermentation and fermented with C. militaris mycelia, and we analyzed T. molitor larvae change in functionality with proximate composition, β-glucan, cordycepin, adenosine, and free amino acids content. T. molitor larvae fermented by C. militaris mycelia showed higher total protein, total fiber, and β-glucan content than the unfermented larvae. In addition, the highest cordycepin content (13.75 mg/g) was observed in shaded dried T. molitor larvae fermented by C. militaris mycelia. Additionally, the isolated cordycepin from fermented T. molitor larvae showed similar cytotoxicity as standard cordycepin when treated with PC-9 cells. Therefore, we report that the optimized methods of T. molitor larvae fermented by C. militaris mycelia increase total protein, total fiber, β-glucan and produce the amount of cordycepin content, which can be contributed to healthy food and increase T. molitor larvae utilization. [ABSTRACT FROM AUTHOR]

In this study, Sophora flavescens (SF) from Yeongcheon (YSF) and Mt. Jiri (JiSF), and Angelica gias (AG) from Yeongcheon (YAG), Mt. Jiri (JiAG), and Jecheon (JeAG) were extracted using three concentrations of ethanol, 95% (95Et), 70% (70Et), and 50% (50Et), and hot water (DW) to evaluate the inhibitions of monoamine oxidases (MAOs; MAO-A and B), cholinesterases (ChEs; AChE and BChE) and β-secretase (BACE1) for targeting depression and neurodegenerative diseases. There were no significant differences in constituent compounds depending on herbal origins, except that YSF-95Et and JiSF-95Et showed a distinct non-polar spot upper maackiain position, and JiAG and JeAG showed a higher amount of decursin than YAG. Ethanolic YAG and JeAG extracts showed the highest MAO-A inhibition, and YSF-95Et mostly inhibited MAO-B. JiSF-95Et showed the highest AChE inhibition and YSF-70Et, JiSF-95Et, and -70Et showed the highest BChE inhibition. Interestingly, ethanolic AG extracts showed extremely potent BACE1 inhibition, especially for JiAG-95Et and JeAG-50Et, whereas there have been no reports about BACE1 inhibition of decursin, the major compound, or AG extracts in other studies. All extracts were nontoxic to MDCK and SH-SY5Y with a low toxicity to HL-60. The results showed a different pattern of inhibitory activities of the extracts toward target enzymes depending on the origins, and multi-target abilities, especially for MAO-B and BChE by YSF-95Et, for AChE and BChE by JiSF-95Et, and for MAO-B and BACE1 by JiAG-95Et. It is suggested that those extracts are potential candidates for finding novel compounds with multi-target inhibitory activities, and herbal origin is an important factor to be considered in selection of the plants. [ABSTRACT FROM AUTHOR]

Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg) for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP) activity. The bone mineral density (BMD) and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT) c1, dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs). Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Lichens, composite organisms resulting from the symbiotic association between the fungi and algae, produce a variety of secondary metabolites that exhibit pharmacological activities. This study aimed to investigate the anti-inflammatory activities of the secondary metabolite atraric acid produced by Heterodermia hypoleuca. The results confirmed that atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygenase-2 enzyme expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Meanwhile, atraric acid downregulated the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results indicate that atraric acid has an anti-inflammatory effect, which may be the underlying molecular mechanism involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]

2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG), an active polyphenolic component of Polygonum multiflorum, exhibits many pharmacological activities including antioxidant, anti-inflammation, and anti-aging effects. A previous study demonstrated that TSG protected MC3T3-E1 cells from hydrogen peroxide (H2O2) induced cell damage and the inhibition of osteoblastic differentiation. However, no studies have investigated the prevention of ovariectomy-induced bone loss in mice. Therefore, we investigated the effects of TSG on bone loss in ovariectomized mice (OVX). Treatment with TSG (1 and 3 μg/g; i.p.) for six weeks positively affected body weight, uterine weight, organ weight, bone length, and weight change because of estrogen deficiency. The levels of the serum biochemical markers of calcium (Ca), inorganic phosphorus (IP), alkaline phosphatase (ALP), and total cholesterol (TCHO) decreased in the TSG-treated mice when compared with the OVX mice. Additionally, the serum bone alkaline phosphatase (BALP) levels in the TSG-treated OVX mice were significantly increased compared with the OVX mice, while the tartrate-resistant acid phosphatase (TRAP) activity was significantly reduced. Furthermore, the OVX mice treated with TSG showed a significantly reduced bone loss compared to the untreated OVX mice upon micro-computed tomography (CT) analysis. Consequently, bone destruction in osteoporotic mice as a result of ovariectomy was inhibited by the administration of TSG. These findings indicate that TSG effectively prevents bone loss in OVX mice; therefore, it can be considered as a potential therapeutic for the treatment of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The development of efficient biomarkers and probes for monitoring and treating cancer, specifically metastatic cancer, is a critical research area that can have a significant impact on both patient outcomes and drug discovery. In this context, TiNIR has been developed to detect tumor-initiating cells (TICs), with heme oxygenase 2 (HO2) as a promising therapeutic biomarker for tumor-initiating cells. In this study, TiNIR has demonstrated its effectiveness as an in vivo metastatic lung cancer tracker, highlighting its potential as a valuable tool in cancer research and therapy. The development of innovative approaches that selectively target metastatic cancers represents a promising avenue for improving survival rates and enhancing the quality of life of cancer patients.

Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC 50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13 . Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (K i = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13 . However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders.

Although astaxanthin has a variety of biological activities such as anti-oxidant effects, inhibitory effects on skin deterioration and anti-inflammatory effects, its effect on asthma has not been studied. In this paper, the inhibitory effect of astaxanthin on airway inflammation in a mouse model of ovalbumin (OVA)-induced asthma was investigated. We evaluated the number of total cells, Th1/2 mediated inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness as well as histological structure. The level of total IgE, IgG1, IgG2a, OVA-specific IgG1, and OVA-specific IgG2a were also examined. The oral administration of 50 mg/mL astaxanthin inhibited the respiratory system resistance, elastance, newtonian resistance, tissue damping, and tissue elastance. Also, astaxanthin suppressed the total cell number, IL-4, and IL-5, and increased the IFN-γ in the BALF. In the sera, total IgE, IgG1, and OVA-specific IgG1 were reduced by astaxanthin exposure and IgG2a and OVA-specific IgG2a were enhanced via oral administration of astaxanthin. Infiltration of inflammatory cells in the lung, production of mucus, lung fibrosis, and expression of caspase-1 or caspase-3 were suppressed in OVA-induced asthmatic animal treated with astaxanthin. These results suggest that astaxanthin may have therapeutic potential for treating asthma via inhibiting Th2-mediated cytokine and enhancing Th1-mediated cytokine., Competing Interests: The authors declare no conflict of interest.