Suppression of Inflammation in Adipocyte-Macrophage Coculture by Passion Fruit Seed Extract: Insights into the p38 and NF-Ò¡B Pathway.

Obesity, which is characterized by chronic low-grade inflammation, involves the infiltration of immune cells into adipose tissue, leading to the secretion of inflammatory cytokines and subsequent inflammation. Therefore, the aim of this study was to examine the potential of passion fruit seed extract (PSEE) in mitigating lipopolysaccharide (LPS)-induced inflammation in a coculture system comprising macrophages and adipocytes. PSEE demonstrated significant reductions in reactive oxygen species (ROS) and nitric oxide (NO) levels, primarily achieved through the downregulation of inducible nitric oxide synthase (iNOS) protein expression in LPS-induced adipocyte-macrophage cocultures. Furthermore, PSEE effectively suppressed the secretion of TNF-α and IL-1ß by attenuating the gene expression of these cytokines, as well as other inflammation-related genes such as MMP-2, IL-6, and MCP-1. Notably, PSEE exhibited potent inhibitory effects on the p38 and NF-κB signaling pathways, thus alleviating inflammation in the LPS-induced adipocyte-macrophage cocultures. Additionally, PSEE led to a decrease in the expression of ACC, HSL, and FaSN, while aP2 and ATGL showed increased expression in LPS-induced cocultured macrophages and adipocytes. These findings suggest that passion fruit seed extract effectively combats inflammation by suppressing the p38 and NF-κB signaling pathways, resulting in reduced levels of proinflammatory cytokines, NO, and ROS production.

Influence of dietary supplementation with new Lactobacillus strains on hematology, serum biochemistry, nutritional status, digestibility, enzyme activities, and immunity in dogs.

Background and Aim: The use of antibiotics is associated with many side effects, with the development of bacterial resistance being particularly important. It has been found that dogs and their owners host similar resistant bacteria. This contributes to increased concurrent bacterial resistance and a possible trend of increased bacterial resistance in humans. Thus, using probiotics in dogs is an alternative option for preventing and reducing the transmission of bacterial resistance from dogs to humans. Probiotics are characterized by their potential to endure low pH levels and high concentrations of bile acids in the gastrointestinal tract. Lactobacilli are more acid-tolerant and resistant to bile acid, so they are ideal probiotics to be added to the canine diet. According to the previous studies, the benefits of Lactobacillus are a stable nutritional status and greater digestibility, along with improved fecal scores and reduced ammonia in dogs. However, no studies have been conducted with Lactobacillus plantarum CM20-8 (TISTR 2676), Lactobacillus acidophilus Im10 (TISTR 2734), Lactobacillus rhamnosus L12-2 (TISTR 2716), Lactobacillus paracasei KT-5 (TISTR 2688), and Lactobacillus fermentum CM14-8 (TISTR 2720), or their use in combination. Hence, the aim of this study was to examine the possible effects of the aforementioned Lactobacillus on hematological indices, nutritional status, digestibility, enzyme activities, and immunity in dogs. From the results, a new and safe strain of Lactobacillus may emerge for use as a probiotic in the future. Materials and Methods: In this study, 35 dogs were allocated equally into seven groups: Group 1 received a basal diet (control), while Groups 2-7 received the same diet further supplemented with L. plantarum CM20-8 (TISTR 2676), L. acidophilus Im10 (TISTR 2734), L. rhamnosus L12-2 (TISTR 2716), L. paracasei KT-5 (TISTR 2688), L. fermentum CM14-8 (TISTR 2720), or a mixture of probiotics (L. plantarum, L. acidophilus, L. rhamnosus, L. paracasei, and L. fermentum), respectively. All probiotics were administered at a dose of 109 colony-forming unit/dog for 28 days. Nutritional status, hematology, serum biochemistry, digestibility, enzyme activities, and immunity parameters were assessed. Results: There were no differences among the groups in body weight, feed intake, body condition score, fecal score, and fecal dry matter on the different sampling days. The hematology and serum biochemical analyses showed a difference only in creatinine activity (p < 0.001), with higher values in group L. fermentum CM14-8 (TISTR 2720) and lower values in group L. paracasei KT-5 (TISTR 2688) than in controls. However, all measurements were within the normal laboratory reference ranges. Fecal characteristics (fecal ammonia and fecal pH), fecal digestive enzyme activities, serum immunoglobulin (IgG), and fecal IgA did not differ significantly among the groups (p > 0.05). Conclusion: Lactobacillus plantarum CM20-8 (TISTR 2676), L. acidophilus Im10 (TISTR 2734), L. rhamnosus L12-2 (TISTR 2716), L. paracasei KT-5 (TISTR 2688), and L. fermentum CM14-8 (TISTR 2720), along with their mixture are safe and non-pathogenic additives for use as new probiotic strains of Lactobacillus in dogs. Although the new Lactobacillus strains had no effect on hematology, serum biochemistry, nutritional status, digestive enzyme activities, immunity, body weight, feed intake, or body condition scores in dogs, further studies should investigate the intestinal microbiota and the development of clinical treatments.

Safety and Effects of Lactobacillus paracasei TISTR 2593 Supplementation on Improving Cholesterol Metabolism and Atherosclerosis-Related Parameters in Subjects with Hypercholesterolemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Probiotics have the potential as a multi-target approach to modulate hypercholesterolemia associated with premature atherosclerosis. Various strains of Lactobacillus paracasei have been reported to affect hypercholesterolemia positively. This study aimed to investigate the effects of L. paracasei TISTR 2593 on lipid profile, cholesterol metabolism, and atherosclerosis according to the registration of Thai Clinical Trial Registry as identification number TCTR 20220917002. A total of 50 participants with hypercholesterolemia were randomly and equally assigned to consume L. paracasei TISTR 2593 or a placebo in maltodextrin capsules daily. Biomarkers of lipid profiles, oxidative stress state, inflammatory state, and other biological indicators were examined on days 0, 45, and 90. The results showed that subjects taking the L. paracasei TISTR 2593 could significantly reduce the level of serum low-density lipoprotein-cholesterol (p < 0.05), malondialdehyde (p < 0.001), and tumor necrosis factor-α (p < 0.01). Moreover, L. paracasei TISTR 2593 increased the level of serum apolipoprotein E (p < 0.01) and adiponectin (p < 0.001) significantly. No changes in serum total cholesterol, high-density lipoprotein-cholesterol, triglyceride, total bile acids, and monocyte chemoattractant protein-1 were observed during L. paracasei TISTR 2593 supplementation. Therefore, L. paracasei TISTR 2593 could be an adjuvant probiotic supplement to ameliorate hypercholesterolemia and prevent or delay the development of atherosclerosis.

Antidyslipidemic, Antioxidant, and Anti-inflammatory Effects of Jelly Drink Containing Polyphenol-Rich Roselle Calyces Extract and Passion Fruit Juice with Pulp in Adults with Dyslipidemia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress and inflammation play key roles in the pathophysiology in the pathophysiology of dyslipidemia, which are positive risks that increase atherosclerosis leading to important healthcare problems. Therefore, we aimed to study the antioxidant, anti-inflammatory, and lipid-lowering effects of jelly drink containing polyphenol-rich roselle calyces extract and passion fruit juice with pulp concentrate (RP jelly drink) in comparison to a placebo jelly drink for 8 weeks. Forty-three adults with dyslipidemia were randomly assigned into two groups: the RP jelly drink group and the placebo group. Glucose, total cholesterol (TC) triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), oxidative stress biomarkers, inflammatory parameters, and monocyte chemotactic protein-1 (MCP-1) were measured with fasting blood samples at baseline, 4 weeks and 8 weeks of intervention. Results showed a significant decrease in LDL-C and TG, respectively, after 8 weeks of RP jelly drink consumption (LDL-C: 107.63 ± 22.98 mg/dL; TG: 109.79 ± 38.83 mg/dL) compared to baseline measurements (LDL-C: 128.43 ± 32.74 mg/dL; TG: 132.33 ± 75.11 mg/dL). These may be possible due to reduced inflammation and improvements in oxidative stress, as demonstrated by the reduction of tumor necrosis factor- (TNF-) α and malondialdehyde (MDA), and the enhancement of glutathione (GSH) after consuming the RP jelly drink for 8 weeks. However, no significant differences of treatment on glucose, total cholesterol, MCP-1, interleukin-6, and interleukin-10 were observed. In conclusion, daily consumption of RP jelly drink for 8 weeks resulted in significant improvement in lipid profiles in subjects with dyslipidemia. However, more research is needed to assess its nutritional and functional potential.

Oral Administration of Ethanolic Extract of Shrimp Shells-Loaded Liposome Protects against Aß-Induced Memory Impairment in Rats.

Alzheimer's disease is characterized by a progressive loss of memory and cognition. Accumulation of amyloid-beta (Aß) in the brain is a well-known pathological hallmark of the disease. In this study, the ethanolic extract of white shrimp (Litopenaous vannamei) shells and the ethanolic extract-loaded liposome were tested for the neuroprotective effects on Aß1-42-induced memory impairment in rats. The commercial astaxanthin was used as a control. Treatment with the ethanolic extract of shrimp shells (EESS) at the dose of 100 mg/kg BW showed no protective effect in Aß-treated rats. However, treatment with an EESS-loaded liposome at the dose of 100 mg/kg BW significantly improved memory ability in Morris water maze and object recognition tests. The beneficial effect of the EESS-loaded liposome was ensured by the increase of the memory-related proteins including BDNF/TrkB and pre- and post-synaptic protein markers GAP-43 and PSD-95 as well as pErk1/2/Erk1/2 in the cortex and hippocampus. These findings indicated the neuroprotective effects of the EESS-loaded liposome on Aß-induced memory impairment in rats. It produced beneficial effects on learning behavior probably through the function of BDNF/TrkB/pErk1/2/Erk1/2 signaling pathway and subsequently the upregulation of synaptic proteins. The present study provided evidence that the neuroprotective property of the ESSE-loaded liposome could be a promising strategy for AD protection.

Hibiscus sabdariffa extract improves hepatic steatosis, partially through IRS-1/Akt and Nrf2 signaling pathways in rats fed a high fat diet.

Non-alcoholic fatty liver disease (NAFLD) has become a major world-wide health problem and is characterized by lipid accumulation in the liver induced by high fat diet (HFD) consumption. It is usually associated with inflammation, oxidative stress, and insulin resistance. Roselle extract (Hibiscus sabdariffa) is an herb which is used in traditional medicine. However, further study is necessary to represent the mechanism of NAFLD and find new preventive strategies. This study aims to investigate the protective effects of roselle extract on NAFLD rat models. Male Sprague-Dawley rats (n = 35) were divided into 5 groups, control, HFD, HFD + Simvastatin (HFD + SIM), HFD + 250 mg/kg BW, and HFD + 500 mg/kg BW of roselle extract (HFD + R250 and HFD + R500, respectively). The results showed that roselle extract reduced hepatic lipid contents, de novo lipogenesis enzymes, microsomal triglyceride transfer protein, inflammatory cytokines, malondialdehyde, and increased antioxidant properties, transporter related with lipoprotein uptake, and insulin signal proteins. Comparing to SIM, the HFD + R500 group exhibited the greater benefit in terms of anti-hepatic steatosis, antioxidant properties, and an ability to improve insulin resistance. This study demonstrates that roselle extract improved antioxidant properties and attenuated hepatic steatosis, liver inflammation, oxidative stress, and insulin resistance in HFD-induced NAFLD in rats, which could be used for NAFLD prevention.

Suppressing Cdk5 Activity by Luteolin Inhibits MPP+-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3ß Pathways.

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons. The cause of PD is still unclear. Oxidative stress and mitochondrial dysfunction have been linked to the development of PD. Luteolin, a non-toxic flavonoid, has become interested in an alternative medicine, according to its effects on anti-oxidative stress and anti-apoptosis, although the underlying mechanism of luteolin on PD has not been fully elucidated. This study aims to investigate whether luteolin prevents neurotoxicity induction by 1-methyl-4-phenylpyridinium iodide (MPP+), a neurotoxin in neuroblastoma SH-SY5Y cells. The results reveal that luteolin significantly improved cell viability and reduced apoptosis in MPP+-treated cells. Increasing lipid peroxidation and superoxide anion (O2-), including mitochondrial membrane potential (Δψm) disruption, is ameliorated by luteolin treatment. In addition, luteolin attenuated MPP+-induced neurite damage via GAP43 and synapsin-1. Furthermore, Cdk5 is found to be overactivated and correlated with elevation of cleaved caspase-3 activity in MPP+-exposed cells, while phosphorylation of Erk1/2, Drp1, Fak, Akt and GSK3ß are inhibited. In contrast, luteolin attenuated Cdk5 overactivation and supported phosphorylated level of Erk1/2, Drp1, Fak, Akt and GSK3ß with reducing in cleaved caspase-3 activity. Results indicate that luteolin exerts neuroprotective effects via Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3ß pathways, possibly representing a potential preventive agent for neuronal disorder.

Neuroprotective effects of Apium graveolens against focal cerebral ischemia occur partly via antioxidant, anti-inflammatory, and anti-apoptotic pathways.

BACKGROUND: Stroke is a neurological disease caused by a sudden disturbance of cerebral blood flow to the brain, leading to loss of brain function. Recently, accumulating lines of evidence have suggested that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, we investigated the possible protective effects of Apium graveolens, a medicinal plant with putative neuroprotective activity, against oxidative-stress-related brain damage and brain damage due to inflammation induced by focal cerebral ischemia. METHODS: Male adult Wistar rats were administered with an extract of A. graveolens orally 14 days before permanent occlusion of their right middle cerebral artery. The brain infarct volumes of rats in each group were determined by 2,3,5-triphenyltetrazolium chloride staining, and the density of neurons in the cortex and hippocampus of rats was determined by cresyl violet staining. The levels of malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase in the cerebral cortex and hippocampus of the rats were also quantified at the end of the study period. RESULTS: Our results show that A. graveolens extract significantly decreased infarct volume and improved neuronal density in the cortex and hippocampus of rats receiving A. graveolens extract compared with those rats receiving no treatment. This neuroprotective effect was found to occur partly due to antioxidant, anti-inflammatory, and anti-apoptotic effects. CONCLUSION: Our study demonstrates that A. graveolens helps to reduce the severity of cognitive damage caused by focal cerebral ischemia. © 2020 Society of Chemical Industry.

Anti-cancer effect of engineered recombinant interleukin 18.

BACKGROUND: Interleukin 18 (IL-18) is an inflammatory cytokine belonging to the interleukin 1 (IL-1) superfamily, and is known for its role in anti-cancer activity by promoting type 1 immune response, and thus may be applied to cancer immunotherapy. Our previous report has showed 16 times higher activity of engineered E6K+T63A IL-18 than of native IL-18 in vitro. However, no data has been acquired for its anti-cancer effect in animal model. OBJECTIVES: To investigate the anti-cancer effect of engineered E6K+T63A IL-18 as an immune stimulant in vivo. MATERIAL AND METHODS: Tumor-bearing mice were treated with native IL-18 or E6K or E6K+T63A IL-18 once a day for 10 days after the tumor reached the volume of 100 mm3. Tumor volume and the number of certain immune cell type in the tumor microenvironment were investigated in this study. RESULTS: The results showed that tumor progression in mice treated with E6K+T63A was slower than in mice treated with E6K and native IL-18. The volume of the tumor was also smaller and the lifespan longer in the E6K+T63A IL-18-treated mice. The proportions of type 1 helper T cell (Th1) and cytotoxic T lymphocyte (CTL) were significantly higher in mice treated with E6K+T63A IL-18. CONCLUSIONS: These results suggest that our engineered IL-18 conferred strong anti-tumor immunity in the animal model.

Self-assembled polydopamine nanoparticles improve treatment in Parkinson's disease model mice and suppress dopamine-induced dyskinesia.

Although Levodopa (l-DOPA), a dopamine precursor, exhibits a high risk of dyskinesia, it remains the primary treatment in Parkinson's disease (PD), a progressive neurodegenerative disorder. In this study, we designed poly(l-DOPA)-based self-assembled nanodrug (NanoDOPA) from amphiphilic block copolymer possessing poly(l-DOPA(OAc)2), which is a precursor of l-DOPA as a hydrophobic segment, for treatment in a PD model mouse. Under physiological enzyme treatment, the poly(l-DOPA(OAc)2) in the block copolymer was hydrolyzed to liberate l-DOPA gradually. Using the MPTP-induced PD mouse model, we observed that mice treated with NanoDOPA demonstrated a significant improvement of PD symptoms compared to the l-DOPA treatment. Interestingly, the NanoDOPA treatment did not cause the dyskinesia symptoms, which was clearly observed in the l-DOPA-treated mice. Furthermore, NanoDOPA exhibited remarkably lower toxicity in vitro compared to l-DOPA, in addition with no noticeable NanoDOPA toxicity observed in the treated mice. These results suggested that self-assembled NanoDOPA is a promising therapeutic in the treatment of PD. STATEMENT OF SIGNIFICANCE: In this study, we proposed a therapeutic approach for the effective treatment of Parkinson's disease (PD) using newly designed poly(l-DOPA)-based self-assembled nanodrug (NanoDOPA) prepared from amphiphilic block copolymers possessing poly(l-DOPA(OAc)2), which is a precursor of l-DOPA as a hydrophobic segment, for treatment in a PD model mouse. Under physiological enzyme treatments, NanoDOPA was hydrolyzed to liberate l-DOPA gradually, improving the pharmacokinetic value of l-DOPA. The mice treated with NanoDOPA significantly improved PD symptoms compared to the l-DOPA treatment in a neurotoxin-induced PD mouse model. Interestingly, NanoDOPA treatment did not cause dyskinesia symptoms, which was observed in the l-DOPA-treated mice. The obtained results in this study suggested that self-assembled NanoDOPA is a promising therapeutic in the treatment of PD.

Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway.

BACKGROUND: Metformin, an antidiabetic drug, has been previously reported to have anti-cancer activities. However, its role in the control of cancer cell migration remains elusive. METHODS: To examine the possible effect of metformin on migration of cervical cancer cells. The related mechanisms were further determined by immunocytochemistry and Western's blotting assay. RESULTS: The results showed that metformin treatment substantially inhibited the migration ability of cervical cancer cells. Consistently, the filopodia and lamellipodia formation were depleted after exposure to metformin. The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment. CONCLUSION: Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein. We propose that metformin could be a novel potential candidate as an antimetastatic cancer drug in the cervical cancer management.

Effects of Astaxanthin from Shrimp Shell on Oxidative Stress and Behavior in Animal Model of Alzheimer's Disease.

This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer's disease, induced by amyloid-ß (1-42) peptides. In this task, the rats were divided into eight groups: (1) Control, (2) sham operate, (3) negative control (vehicle) + Aß1-42, (4) ASX extract+Aß1-42, (5) commercial ASX + Aß1-42, (6) ASX powder + Aß1-42, (7) blank powder + Aß1-42, and (8) vitamin E + Aß1-42. All treatments were orally administrated for 30 days. At 14- and 29-days post injection, animals were observed in behavioral tests. On the 31st day, animals were sacrificed; the hippocampus and cortex were collected. Those two brain areas were then homogenized and stored for biochemical and histological analysis. The results showed that the Aß1-42 infused group significantly reduced cognitive ability and increased memory loss, as assessed by the Morris water maze test, novel object recognition test, and novel object location test. Moreover, the Aß1-42 infused group exhibited a deterioration of oxidative markers, including glutathione peroxidase enzymes (GPx), lipid peroxidation (MDA), products of protein oxidation, and superoxide anion in the cortex and the hippocampus. Meanwhile, ASX powder (10 mg/kg body weight) showed a significant reduction in cognitive and memory impairments and oxidative stress which is greater than ASX extract in the same dose of compound or vitamin E (100 mg/kg body weight). Our study indicates the beneficial properties of ASX in alleviation of cognitive functions and reducing neurodegeneration in Wistar rats induced by amyloid-ß (1-42) peptides.

The antioxidant and neurochemical activity of Apium graveolens L. and its ameliorative effect on MPTP-induced Parkinson-like symptoms in mice.

BACKGROUND: Apium graveolens L. is a traditional Chinese medicine prescribed as a treatment for hypertension, gout, and diabetes. This study aimed to determine the neuroprotective effects of A. graveolens extract against a Parkinson's disease (PD) model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6 mice. METHODS: Male C57BL/6 mice treated with MPTP were orally dosed with A. graveolens extract daily for 21 days. Behavioral tests, including a rotarod apparatus, a narrow beam test, a drag test, a grid walk test, a swimming test, and a resting tremor evaluation, were performed. Thereafter, the mice were sacrificed, and monoamine oxidase A and B activity, lipid peroxidation activity, and superoxide anion levels were measured. Immunohistochemical staining of tyrosine hydroxylase was performed to identify dopaminergic neurons. RESULTS: We found that treatment with A. graveolens at dose of 375 mg/kg demonstrated the highest effect and led to significant improvements in behavioral performance, oxidative stress parameters, and monoamine oxidase A and B activity compared with the untreated group (p < 0.05). Moreover, the extract increased the number of neurons immunopositive for tyrosine hydroxylase expression compared with MPTP alone or MPTP with a positive control drug (p < 0.05). CONCLUSIONS: We speculated that A. graveolens ameliorated behavioral performance by mediating neuroprotection against MPTP-induced PD via antioxidant effects, related neurotransmitter pathways and an increase in the number of dopaminergic neurons.

Chronic treatment with a smart antioxidative nanoparticle for inhibition of amyloid plaque propagation in Tg2576 mouse model of Alzheimer's disease.

The present study aimed to assess whether our newly developed redox nanoparticle (RNPN) that has antioxidant potential decreases Aß levels or prevents Aß aggregation associated with oxidative stress. The transgenic Tg2576 Alzheimer's disease (AD) mice were used to investigate the effect of chronic ad libitum drinking of RNPN solution for 6 months, including memory and learning functions, antioxidant activity, and amyloid plaque aggregation. The results showed that RNPN-treated mice had significantly attenuated cognitive deficits of both spatial and non-spatial memories, reduced oxidative stress of lipid peroxide, and DNA oxidation. RNPN treatment increased the percent inhibition of superoxide anion and glutathione peroxidase activity, neuronal densities in the cortex and hippocampus, decreased Aß(1-40), Aß(1-42) and gamma (γ)-secretase levels, and reduced Aß plaque observed using immunohistochemistry analysis and thioflavin S staining. Our results suggest that RNPN may be a promising candidate for AD therapy because of its antioxidant properties and reduction in Aß aggregation, thereby suppressing its adverse side effect.

Apium graveolens extract influences mood and cognition in healthy mice.

Apium graveolens is a food flavoring which possesses various health promoting effects. This study investigates the effect of a sub-acute administration of A. graveolens on cognition and anti-depression behaviors via antioxidant and related neurotransmitter systems in mice brains. Cognition and depression was assessed by various models of behavior. The antioxidant system of glutathione peroxidase (GPx), % inhibition of superoxide anion (O2-), and lipid peroxidation were studied. In addition, neurochemical parameters including acetylcholinesterase (AChE) and monoamine oxidase-type A (MAO-A) were also evaluated. Nine groups of male mice were fed for 30 days with different substances-a control, vehicle, A. graveolens extract (65-500 mg/kg), and reference drugs (donepezil and fluoxetine). The results indicated that the effect of the intake of A. graveolens extract (125-500 mg/kg) was similar to the reference drugs, as it improved both spatial and non-spatial memories. Moreover, there was a decrease in immobility time in both the forced swimming and tail suspension tests. In addition, the A. graveolens extract reduced lipid peroxidation of the brain and increased GPx activity and the % inhibition of O2-, whereas the activities of AChE and MAO-A were decreased. Thus, our data have shown that the consumption of A. graveolens extract improved cognitive function and anti-depression activities as well as modulating the endogenous antioxidant and neurotransmitter systems in the brain, resulting in increased neuronal density. This result indicated an important role for A. graveolens extract in preventing age-associated decline in cognitive function associated with depression.

Anxiolytic and free radical scavenging potential of Chinese celery (Apium graveolens) extract in mice

Objective: To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens (A. graveolens) in adult C57BL/6 mice. Methods: Sixty male mice were divided into 6 groups:control, vehicle, positive control and A. graveolens (125, 250 and 500 mg/kg). Different behavioral models of elevated plus maze, open field, light/dark, hole-board and pentobarbital-induced sleep were used to assess anxiety-like behavior. Biochemical parameters including monoamine oxidase-A (MAO-A) activity, lipid peroxidation,%inhibition of superoxide anion and glutathione peroxidase activity were measured. Histologic studies were also examined. Results: Mice receiving various doses of A. graveolens (125, 250 and 500 mg/kg) showed an alleviation of anxiety-like behavior as evidenced by the battery of behavioral tests. Likewise, A. graveolens treatment was found to significantly decrease MAO-A activity, lipid peroxidation as well as cause a significant increase of%inhibition of su-peroxide anion and glutathione peroxidase activity in both cortex and striatum. The total number of survival neurons found in the frontal cortex and striatum was significantly higher than that of the vehicle-treated group. Conclusions: Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAO-A activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.

Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats.

Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund's adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity.

Redox Nanoparticle Therapeutics for Acetaminophen-Induced Hepatotoxicity in Mice.

The purpose of this study was to evaluate the hepatoprotective effect of an antioxidative nanoparticle (RNP(N)) recently developed against APAP-induced hepatotoxicity in mice. The effects of oral administration of RNP(N) to APAP-treated mice were assessed for various biochemical liver function parameters: alanine transaminase (ALT) activity, aspartate transaminase (AST) activity, alkaline phosphatase (ALP) activity, prothrombin time, and serum albumin (ALB) level. The treatment effects were assessed in terms of free radical parameters: malondialdehyde (MDA) accumulation, glutathione peroxidase (GPx) activity, % inhibition of superoxide anion (O2 (-∙)), and histopathological examination. The N-acetylcysteine (NAC)-treated group exhibited an enhanced prothrombin time relative to the control group, while RNP(N) did not prolong prothrombin time. The RNP(N)-treated animals exhibited lower levels of ALT, AST, and ALP, while increased ALB levels were measured in these animals compared to those in the other groups. The RNP(N)-treated animals furthermore exhibited improved MDA levels, GPx activity, and % inhibition of O2 (-∙), which relate to oxidative damage. Histological staining of liver tissues from RNP(N)-treated animals did not reveal any microscopic changes relative to the other groups. The findings of this study suggest that RNP(N) possesses effective hepatoprotective properties and does not exhibit the notable adverse effects associated with NAC treatment.

Effects of Astaxanthin from Litopenaeus Vannamei on Carrageenan-Induced Edema and Pain Behavior in Mice.

Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior.

Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice.

Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8) mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.