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.

Conjugate between hydrolyzed collagen from defatted seabass skin and epigallocatechin gallate (EGCG): characteristics, antioxidant activity and in vitro cellular bioactivity.

Conjugation between peptides and polyphenols, especially epigallocatechin gallate (EGCG) using covalent grafting, is a promising method that can modify peptides or augment their antioxidant activities. Moreover, the resulting conjugates can be intensively served as functional ingredient or supplement. Thus, the objectives of the present study were to investigate the grafting between hydrolyzed collagen (HC) from defatted seabass skin and EGCG and to study characteristics as well as bioactivities of the obtained HC-EGCG conjugate. Levels of EGCG used (1-5%, w/w) affected surface hydrophobicity (SH) and antioxidant activities of the conjugates. Overall, the addition of EGCG at 3% to HC (HC-3% EGCG) increased SH, ABTS radical scavenging and metal chelating activities (p < 0.05). FTIR spectra of HC-3% EGCG revealed the interaction between HC and EGCG via H-bonding and covalent interaction. Sephadex G-25 fraction of conjugate with molecular weight (MW) of 2771 Da rendered the highest redox ability. When HC-3% EGCG was applied in fibroblast (MRC-5) and keratinocyte (HaCaT) cells, all levels tested (125-1000 µg mL-1) had no toxicity on both cells. Higher proliferation of both cells were attained with increasing levels of HC-3% EGCG, particularly at 500 and 1000 µg mL-1 (p < 0.05). Moreover, both levels used had cytoprotective ability against reactive oxygen species (ROS) as evidenced by lowered ROS and cell death detected as compared to those found in cells induced with H2O2 or AAPH alone (p < 0.05) for both cells. HC-3% EGCG could serve as an effective antioxidant for application in foods or as supplement for skin nourishment.

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.

ECa 233 Suppresses LPS-Induced Proinflammatory Responses in Macrophages via Suppressing ERK1/2, p38 MAPK and Akt Pathways.

A current anti-inflammatory agent often targets the prevention of inflammatory disorder development. The standardized Centella asiatica ECa 233 extract has been previously reported for anti-inflammatory effect. This study aimed to investigate its anti-inflammatory effect and mechanisms of ECa 233 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nitric oxide (NO) assay, reactive oxygen species (ROS) production assay, enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Our results found that ECa 233 significantly inhibited LPS-stimulated pro-inflammatory mediators production including ROS, NO and prostaglandin E2 (PGE2), and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß without cytotoxicity. In addition, ECa 233 downregulated not only the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), but also the activation of nuclear factor-kappa B (NF-κB), activated protein kinase B (Akt), extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases (MAPK) induced by LPS. The inhibition of LPS-induced inflammation due to ECa 233 offered an opportunity as a tentatively potential candidate for the prevention and treatment of inflammatory diseases.

Metformin Promotes Neuronal Differentiation via Crosstalk between Cdk5 and Sox6 in Neuroblastoma Cells.

Metformin has recently emerged as a key player in promotion of neuroblastoma differentiation and neurite outgrowth. However, molecular mechanisms of how metformin promotes cellular differentiation have not yet been fully elucidated. In this study, we investigated how metformin promotes cell differentiation, via an inhibition of cell proliferation, by culturing SH-SY5Y neuroblastoma cells with or without metformin. Pretreatment with reactive oxygen species (ROS) scavenger, NAC, revealed that ROS plays a crucial role in induction of cell differentiation. Cell differentiation was observed under various morphological criteria: extension of neuritic processes and neuronal differentiation markers. Treatment with metformin significantly increased neurite length, number of cells with neurite, and expression of neuronal differentiation markers, ß-tubulin III and tyrosine hydroxylase (TH) compared with untreated control. Further investigation found that metformin significantly decreased Cdk5 but increased Sox6 during cell differentiation. Analysis of the mechanism underlying these changes using Cdk5 inhibitor, roscovitine, indicated that expressions of Cdk5 and Sox6 corresponded to metformin treatment. These results suggested that metformin produces neuronal differentiation via Cdk5 and Sox6. In addition, phosphorylated Erk1/2 was decreased while phosphorylated Akt was increased in metformin treatment. Taken together, these findings suggest that metformin promotes neuronal differentiation via ROS activation through Cdk5/Sox6 crosstalk, relating to Erk1/2 and Akt signaling.

Induction of keratinocyte migration by ECa 233 is mediated through FAK/Akt, ERK, and p38 MAPK signaling.

Centella asiatica is widely considered the most important medicinal plant for treating and relieving skin diseases. Recently developed standardized extract of Centella asiatica ECa 233 has demonstrated positive effects on wound healing of incision and burn wound in rats. However, knowledge associated with wound healing mechanism of ECa 233 was scare. Therefore, this study aimed to investigate the effect and underlying molecular mechanisms of ECa 233 on the migration of a human keratinocyte cell line (HaCaT) using scratch wound healing assay. Formation of filopodia, a key protein in cell migration as well as signaling pathways possibly involved were subsequently assessed. It was found that HaCaT cell migration was significantly enhanced by ECa 233 in a concentration- and time-dependent manner. The filopodia formations were accordingly increased in exposure to ECa 233 at concentrations of 0.1-100 µg/ml. Furthermore, ECa 233 was found to significantly upregulate the expression of Rac1 and RhoA and to induce phosphorylation of FAK and Akt as well as ERK and p38 MAPK. Taken all together, it is suggestive that ECa 233 induces cell migration and subsequently promotes wound healing activity, through the activation of FAK, Akt, and MAPK signaling pathways thereby supporting the role of ECa 233 to be further developed for the clinical treatment of wound.

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.

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.

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.