Anti-Obesity and Anti-Hyperglycemic Effects of Meretrix lusoria Protamex Hydrolysate in ob/ob Mice.

Meretrix lusoria (M. lusoria) is an economically important shellfish which is widely distributed in South Eastern Asia that contains bioactive peptides, proteins, and enzymes. In the present study, the extracted meat content of M. lusoria was enzymatic hydrolyzed using four different commercial proteases (neutrase, protamex, alcalase, and flavourzyme). Among the enzymatic hydrolysates, M. lusoria protamex hydrolysate (MLPH) fraction with MW ≤ 1 kDa exhibited the highest free radical scavenging ability. The MLPH fraction was further purified and an amino acid sequence (KDLEL, 617.35 Da) was identified by LC-MS/MS analysis. The purpose of this study was to investigate the anti-obesity and anti-hyperglycemic effects of MLPH containing antioxidant peptides using ob/ob mice. Treatment with MLPH for 6 weeks reduced body and organ weight and ameliorated the effects of hepatic steatosis and epididymal fat, including a constructive effect on hepatic and serum marker parameters. Moreover, hepatic antioxidant enzyme activities were upregulated and impaired glucose tolerance was improved in obese control mice. In addition, MLPH treatment markedly suppressed mRNA expression related to lipogenesis and hyperglycemia through activation of AMPK phosphorylation. These findings suggest that MLPH has anti-obesity and anti-hyperglycemic potential and could be effectively applied as a functional food ingredient or pharmaceutical.

Anti-Osteoporotic Effects of n-trans-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling.

Osteoporosis is characterized by the deterioration of bone structures and decreased bone mass, leading to an increased risk of fracture. Estrogen deficiency in postmenopausal women and aging are major factors of osteoporosis and are some of the reasons for reduced quality of life. In this study, we investigated the effects of n-trans-hibiscusamide (NHA) and its derivative 4-O-(E)-feruloyl-N-(E)-hibiscusamide (HAD) on receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL)-induced osteoclast differentiation and an ovariectomized osteoporosis mouse model. NHA and HAD significantly inhibited the differentiation of osteoclasts from bone marrow-derived macrophages (BMMs) and the expression of osteoclast differentiation-related genes. At the molecular level, NHA and HAD significantly downregulated the phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules. However, Akt and NF-κB phosphorylation was inhibited only after NHA or HAD treatment. In the ovariectomy (OVX)-induced osteoporosis model, both NHA and HAD effectively improved trabecular bone structure. C-terminal telopeptide (CTX), a bone resorption marker, and RANKL, an osteoclast stimulation factor, were significantly reduced by NHA and HAD. The tartrate-resistant acid phosphatase (TRAP)-stained area, which indicates the osteoclast area, was also decreased by these compounds. These results show the potential of NHA and HAD as therapeutic agents for osteoporosis.

Antioxidant and Anti-Stress Effects of Taurine Against Electric Foot-Shock-Induced Acute Stress in Rats.

In the present study, we evaluated the antioxidant and anti-stress activities of taurine in electric foot-shock stress model rats. Taurine supplementation markedly increased the hepatic glutathione (GSH) levels, compared to the levels in the stress group. In addition, activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were improved in the taurine-treated group. Plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels were significantly reduced in the taurine-supplemented group compared to those in the stress group. In contrast, the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were markedly increased in the taurine or betaine-treated group compared to those in the stress group. It may be concluded that taurine produces beneficial effects in the form of antioxidant status and biochemical alterations in foot-shock-induced acute stress in rats.

Laxative Effects of Taurine on Loperamide-Induced Constipation in Rats.

In the present study, we investigated the laxative effects of taurine in a rat model of loperamide-induced constipation. Rats were divided into six groups of six animals each: normal (NOR), control (CON), loperamide + Dulcolax (5.5 mg/kg, p.o.), and loperamide + various doses of taurine (7.5, 15, and 30 mg/kg, p.o.). Laxative activity was determined based on body weight, feeding characteristics, fecal properties, gastrointestinal transit (GIT) ratio, and the levels of serum gastrointestinal hormones. Taurine supplementation significantly increased the number, wet weight, and water content of fecal pellets in rats with loperamide-induced constipation. GIT ratio and loperamide-induced serum metabolic parameters, such as gastrin (GAS), motilin (MTL), and somatostatin (SS) significantly changed after supplementation with taurine in loperamide-induced constipated rats. We suggest that taurine had a potent effect against loperamide-induced constipation in part by increasing gastrointestinal motility.

Glucose-Taurine Reduced Exerts Neuroinflammatory Responses by Inhibition of NF-κB Activation in LPS-Induced BV2 Microglia.

We want to find the anti-neuroinflammatory action of the taurine derivative Glucose-Taurine Reduced (G-T-R). The anti-neuroinflammatory action by G-T-R were investigated in lipopolysaccharide (LPS)-induced BV2 microglia. G-T-R inhibited the production of nitric oxide and prostaglandin E2, and down-regulated the protein expression of inducible NO synthase and cyclooxygenase-2. In addition, G-T-R reduced the cytokines secretion such as tumor necrosis factor (TNF-α), interleukin (IL) -1ß and IL-6, in BV2 microglia treated with LPS. In addition, G-T-R dose-dependently decreased the activation of nuclear factor-kappa B. These findings confirmed the anti-neuroinflammatory activity of G-T-R, which may exert protective effects against neuroinflammatory-related diseases.

Anti-inflammatory Action of Glucose-Taurine Reduced by Inhibiting NF-κB Activation in LPS-Activated RAW264.7 Macrophages.

In the present study, we investigated the regulation of inflammatory effects by glucose-taurine reduced (G-T-R), a taurine-carbohydrate derivative, on lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The anti-inflammatory action of G-T-R revealed that this derivative markedly inhibited the nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages induced by LPS. Suppression of NO and PGE2 production was involved in the inhibitory action by G-T-R on the inducible nitric oxide synthase and cyclooxygenase-2 proteins expression. G-T-R decreased the production of a variety of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6. Moreover, G-T-R effectively suppressed the nuclear factor-kappa B (NF-κB) activation in LPS-stimulated RAW264.7 macrophages according to evaluation of the molecular inflammatory mechanisms. Thus, we suggest that G-T-R modulates several inflammatory pathways mediated by NF-κB activation, demonstrating its potential or preventing and treating inflammatory conditions.

Ribose-Taurine Suppresses Inflammation Through NF-κB Regulation in Activated RAW 264.7 Macrophages.

Ribose-taurine (Rib-T) suppressed the generation of inflammatory mediators and cytokines, such as nitric oxide (NO) and prostaglandin E2 (PGE2) through the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß induced by LPS was effectively blocked by Rib-T. Moreover, the anti-inflammatory actions of Rib-T were involved in its inhibitory effects against the nuclear translocation of nuclear factor-kappa B (NF-κB) p65, and NF-κB DNA-binding activity. These results suggest that the anti-inflammatory action of Rib-T is associated with NF-κB regulation.

Taurine Chloramine Prevents Neuronal HT22 Cell Damage Through Nrf2-Related Heme Oxygenase-1.

Oxidative cell damages are able to contribute to neuronal degeneration in several diseases of the central nervous system (CNS) including stroke as well as ischemia. Heme oxygenase (HO)-1 plays a major role in the pathogenesis of neuronal disorder. Taurine chloramine (TauCl) has been shown to possess strong neuronal activities; however, the direct effects of TauCl on neuronal cell death remain to be determined. Therefore, this study was designed to assess the neuroprotective effect of TauCl using oxidative stress-stimulated mouse hippocampal HT22 cells. TauCl showed protective effects against oxidative stress-induced neurotoxicity and inhibited the reactive oxygen species (ROS) production by inducing the heme oxygenase (HO)-1 expression in HT22 cells. TauCl upregulated HO-1 expression and it also increased the nuclear factor E2-related factor 2 (Nrf2) translocation to nuclear. Using an inhibitor of HO-1 activity, we verified that the oxidative stress-related HT22 cell death was significantly suppressed by TauCl. In addition, we found reduced TauCl-induced HO-1 expression and cytoprotection following treatment of the cells with an extracellular signal-regulated kinase (ERK) inhibitor (PD98059) or a p38 inhibitor (SB203580), but not following treatment with a SP600125 as a c-Jun NH2-terminal kinase (JNK) inhibitor. These findings suggest that TauCl improves cellular damage induced by glutamate or H2O2 through ERK and p38, Nrf2, and HO-1 pathways in HT22 cells.

Taurine Have Neuroprotective Activity against Oxidative Damage-Induced HT22 Cell Death through Heme Oxygenase-1 Pathway.

Glutamate-induced oxidative neurotoxicity plays a part role in neuronal degeneration on the disorders of central nervous system (CNS). The expression of heme oxygenase (HO)-1 mediated by Inducible nuclear factor-E2-related factor 2 (Nrf2) functions as an anti-oxidants that is able to play an important role in the pathogenesis of several neuronal disorders. In the present study, taurine showed the inhibitory effect against reactive oxygen species (ROS) induction and protective effects against neurotoxicity induced by glutamate- and H2O2 through induction of HO-1 expression in HT22 cells. Moreover, taurine promoted the Nrf2 nuclear translocation in HT22 cells. We also verified the oxidative stress-mediated cell death of HT22 cells was significantly repressed by taurine, using tin protoporphyrin (SnPP) as an HO activity inhibitor. In addition, we found that treatment of the cells with p38 inhibitor (SB203580) suppressed taurine-induced HO-1 expression and cytoprotection, but inhibitors of c-Jun NH2 terminal kinase (JNK) (SP600125) or extracellular signal regulated kinase (ERK) (PD98059) did not. These results suggest that taurine improves the resistance against oxidative damages induced by glutamate in HT22 cells via the p38/Nrf2-dependent HO-1 expression. Our results demonstrated the potential application of taurine as a therapeutic agent for neurodegenerative diseases.

Taurine Chloramine Suppresses LPS-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglial Cells.

The brain is sensitive to the inflammation and oxidative stress that can cause the aging or neurodegenerative diseases. We investigated the anti-neuroinflammatory activities of taurine chloramine (TauCl) on lipopolysaccharide (LPS)-treated mouse BV2 microglia mediated through heme oxygenase (HO)-1 expression. TauCl inhibited the protein expressions of prostaglandin E2 (PGE2), cyclooxygenase (COX)-2, nitric oxide (NO), and inducible nitric oxide synthase (iNOS) in LPS-treated BV2 microglia. TauCl markedly inhibited interleukin-6 (IL-6), interleukin-1𝛽 (IL-1𝛽) and tumor necrosis factor-𝛼 (TNF-𝛼) production. These effects were related to the suppression of the degradation and phosphorylation of inhibition of nuclear factor kappa B-𝛼 (I𝜅B-𝛼), translocation of nuclear factor kappa B (NF-𝜅B) as well as DNA binding activity. In addition, TauCl induced the HO-1 expression by increasing the nuclear factor E2-related factor 2 (Nrf2) translocation to the nucleus in mouse BV2 microglia. These findings suggest that TauCl has protective effects of neurodegenerative disorders caused by neuroinflammation.

Mussel (Mytilus coruscus) Water Extract Containing Taurine Prevents LPS-Induced Inflammatory Responses in Zebrafish Model.

Mussel (Mytilus coruscus) water extract had strong anti-inflammatory activities, but the effects and its mechanisms of mussel on anti-inflammatory properties in vivo remain to be determined. This study, therefore, was designed to investigate anti-inflammatory activities of mussel water extract containing a large amounts of taurine (151.96 nmol/mg) using the lipopolysaccharide (LPS)-induced inflammatory zebrafish model. In this study, mussel water extract containing taurine shows potent protective effects against the cell death stimulated by LPS exposure in zebrafish embryos. In addition, zebrafish subjected to LPS treatment exhibited significantly increased reactive oxygen species (ROS) and nitric oxide (NO) levels. However, mussel water extract markedly suppressed LPS-induced ROS and NO production. Our results indicate that mussel water extract attenuated inflammation by inhibiting the LPS-induced intracellular ROS and NO production in zebrafish embryos. These findings could demonstrate the anti-inflammatory activity of mussel water extract containing taurine, which might have a protective effects on inflammatory diseases.

Antioxidant Effects of Short-Neck Clam (Tapes philippinarum) Water Extract Containing Taurine Against AAPH-Induced Oxidative Stress in Zebrafish Embryos.

The purpose of this study was to investigate the antioxidant activities of short-neck clam water extract (SNC-WE) enriched in taurine. In the present study, the half-maximal inhibitory concentration (IC50) values of the SNC-WE for DPPH, superoxide, and alkyl radical scavenging activities determined by an electron spin resonance (ESR) spectrometer were 3.16, 1.54 and 0.58 mg/mL, respectively. Furthermore, we evaluated the inhibitory effect of taurine enriched SNC-WE against the oxidative stress induced by 2,2'-azobis dihydrochloride (AAPH) in zebrafish embryos. In the present study, we observed that taurine enriched SNC-WE significantly suppressed reactive oxygen species (ROS) production, lipid peroxidation as well as cell death in the zebrafish model. These results indicate that taurine enriched SNC-WE might have antioxidant effects in both in vitro and in vivo zebrafish model.

Hepatoprotective Effects of Xylose-Taurine Reduced Against Hydrogen Peroxide-Induced Oxidative Stress in Cultured Hepatocytes.

In this study, Xylose-Taurine reduced (X-T-R) was synthesized to enhance biological activities. Hence, we investigated the hepatoprotective effects of X-T-R against H2O2-induced hepatocyte damage and apoptosis. The results showed that X-T-R led to the cytoprotective effect against H2O2-induced oxidative stress in cultured hepatocytes such as the improvement of cell viability and the reduction of reactive oxygen species (ROS) production. Additionally, pre-treatment with X-T-R increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase:quinone 1 (NQO1) and heme oxygenase 1 (HO-1) in cultured hepatocytes. Furthermore, X-T-R protected the cells against apoptosis via regulating the expression level of Bcl-2/Bax as well as the activation of caspase-3. According to the results obtained, X-T-R may be a bio-material for the therapy of hepatic diseases.

Anti-inflammatory Effects of Galactose-Taurine Sodium Salt: A Taurine Derivate in Zebrafish In Vivo Model.

Taurine, the plentiful amino acids in mammalian cells exerts various biological activities including antioxidant and anti-inflammatory effects. Inflammation can cause several diseases such as cancer, heart disease, rheumatoid arthritis and immune system reactions. Here, we investigated anti-inflammatory effects of Galactose-Taurine sodium salt (Gal-Tau), a newly synthesized taurine derivate in LPS-stimulated zebrafish embryos in vivo model. The result showed that Gal-Tau improved the survival rate and the edema in LPS-treated zebrafish embryos. Also, Gal-Tau effectively reduced the productions of nitric oxide (NO), reactive oxygen species (ROS) and cell death induced by LPS in zebrafish embryos. In addition, Gal-Tau regulated the expression levels of inflammatory mediators such as inducible NOS (iNOS) and cycloxygenase 2 (COX-2) as well as IL-6 and TNF-α, inflammatory cytokines known as important key mediators of inflammation. Taken together, this study first indicates that Gal-Tau could be considered as an effective anti-inflammatory material with its anti-inflammatory activity.

Xylose-Taurine Reduced Suppresses the Inflammatory Responses in Lipopolysaccharide-Stimulated Raw264.7 Macrophages.

Here, the anti-inflammatory effect of Xylose-Taurine reduced (X-T-R), a taurine derivate was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. X-T-R reduced the generations of nitric oxide (NO) and prostaglandin E2 (PGE2) induced by the stimulation of LPS in RAW 264.7 by suppressing the protein expression of iNOS and COX-2 known as inflammatory mediators. Also, X-R-T reduced the expression levels of the pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF-α). Moreover, X-T-R inhibited the activation of nuclear factor-κB (NF-κB) and the phosphorylation of inhibitor κB (IκB)-α. In conclusion, these results first indicate that X-T-R inhibits LPS-induced inflammation by regulating the NF-κB signal pathway in macrophages.

Protective Effects of Xylose-Taurine Reduced against Damages Caused by Oxidative Stress in Zebrafish Embryos In Vivo Model.

The zebrafish (Danio rerio) is useful and convenient vertebrate models in various studies in human disease and drug discovery. In this present study, we first evaluated whether Xylose-Taurine reduced (X-T-R), a taurine derivate protects zebrafish embryos against oxidative stress caused by AAPH (2,2'-Azobis(2-amidinopropane) dihydrochloride). First of all, we selected the concentration of X-T-R showing no toxicity in zebrafish embryos. We identified that X-T-R significantly increased the survival of zebrafish embryo reduced by treatment of AAPH. Also, X-T-R effectively inhibited the productions of reactive oxygen species (ROS) and nitric oxide (NO) as well as the formation of cell death in zebrafish embryos. Moreover, X-T-R down-regulated the expression levels of Bax, caspase-3, caspase-9 and p53 known as pro-apoptotic molecules, whereas up-regulated those of Bcl-2, an anti-apoptotic molecule in AAPH-treated zebrafish embryos. From these results, this study reveals that X-T-R, a taurine derivate might be a potential protector against various damages caused by oxidative stress.

Anti-inflammatory Effects of Galactose-Taurine Sodium Salt in LPS-Activated RAW 264.7 Cells.

In this study, we synthesized Galactose-Taurine sodium salt (G-T) as a functional food ingredient to enhance biological activities of taurine. Also, anti-inflammatory effects of G-T were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. G-T found to reduce the generations of the LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) via down-regulating the expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Also, G-T reduced the secretion of inflammatory cytokines including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF-α) in LPS-treated RAW 264.7 cells. Finally, we identified that G-T inhibits the activation of nuclear factor-κB (NF-κB) and the phosphorylation of inhibitor κB (IκB)-α. From these results, this study first suggests that G-T could be considered as an effective anti-inflammatory agent.

Anti-inflammatory effects of trans-1,3-diphenyl-2,3-epoxypropane-1-one in zebrafish embryos in vivo model.

In this study, trans-1,3-diphenyl-2,3-epoxypropane-1-one (DPEP) was evaluated for its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated zebrafish embryos. In the present study, DPEP exhibited potential protective effect in the zebrafish embryos as confirmed by survival rate. DPEP acts as an effective agent against reactive oxygen species (ROS) formation induced by LPS. Moreover, DPEP effectively inhibited LPS-induced nitric oxide (NO) production in zebrafish embryos. In addition, DPEP significantly reduced the expression of inducible NOS (iNOS) and cycloxygenase 2 (COX-2), which generate NO as a key mediator of inflammation in a concentration-dependent manner. According to these results, DPEP could be considered an effective anti-inflammatory agent, which might be further developed as a functional ingredient. This is the first report of the anti-inflammatory activity of DPEP in the LPS-stimulated zebrafish model.

Fatsia japonica extract exerts antioxidant and anti-neuroinflammatory effects on neuronal cells and a zebrafish model.

ETHNOPHARMACOLOGICAL RELEVANCE: Fatsia japonica is a traditional medicine used to treat various diseases, including inflammation-related disorders. However, its antineuroinflammatory and neuroprotective effects remain unclear. AIM OF THE STUDY: We aimed to evaluate the anti-neuroinflammatory and neuroprotective effects of F. japonica extract to identify the underlying mechanisms. MATERIALS AND METHODS: The components of F. japonica extract were profiled using ultra-high-performance liquid chromatography-mass spectrometry. The effects of F. japonica extract were investigated in BV2 microglia and HT22 hippocampal cells. Furthermore, in vivo effects of F. japonica extract were assessed using zebrafish models treated with H2O2 and LPS to evaluate the effects of in vivo. RESULTS: We identified 27 compounds in the F. japonica extract. F. japonica extract demonstrated anti-inflammatory properties by suppressing LPS-induced inflammatory responses in both BV2 cells and zebrafish, along with inhibiting the activation of the nuclear factor (NF)-κB (p65) pathway. The protective effects of this extract were also observed on glutamate-treated HT22 cells and in H2O2-induced zebrafish. Furthermore, F. japonica extract upregulated nuclear factor E2-related (Nrf) 2/heme oxygenase (HO)-1 expression in BV2 and HT22 cells. CONCLUSIONS: F. japonica extract exerted anti-neuroinflammatory and neuroprotective effects through Nrf2/HO-1 and the NF-κB pathway.

Bioactive Peptides from Meretrix lusoria Enzymatic Hydrolysate as a Potential Treatment for Obesity in db/db Mice.

Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Meretrix lusoria Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient db/db mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in db/db mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to db/db control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in db/db mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.