PMID: 

Eur J Nutr. 2019 Oct 16. Epub 2019 Oct 16. PMID: 31620886

Abstract Title: 

Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial.

Abstract: 

PURPOSE: The effects of heat-killed Lactobacillus plantarum L-137 (HK L-137) on inflammation and lipid metabolism were investigated in overweight volunteers.METHODS: One hundred healthy subjects with a body mass index from 23.0 to 29.9 (51 men and 49 women; mean age: 41.4 years) were enrolled in this randomized, double-blind, placebo-controlled, parallel group study. Subjects were randomly assigned to daily administration of a tablet containing HK L-137 (10 mg) or a placebo tablet for 12 weeks. Blood samples were collected every 4 weeks to measure biomarkers oflipid metabolism and inflammatory mediators.RESULTS: The percent change of concanavalin A-induced proliferation of peripheral blood mononuclear cells was significantly larger in the HK L-137 group than in the control group, similar to previous studies. The decreases of aspartate aminotransferase and alanine aminotransferase over time were significantly larger in the HK L-137 group than in the control group, as were the decreases of total cholesterol, low-density lipoprotein cholesterol, and the leukocyte count at one time point. These effects of HK L-137 were stronger in the subjects with higher C-reactive protein levels.CONCLUSIONS: These findings suggest that daily intake of HK L-137 can improve inflammation and lipid metabolism in subjects at risk of inflammation.

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PMID: 

Biochem Biophys Rep. 2019 Dec ;20:100691. Epub 2019 Oct 3. PMID: 31650040

Abstract Title: 

Extract ofstrain 06CC2 induces JNK/p38 MAPK pathway-mediated apoptosis through endoplasmic reticulum stress in Caco2 colorectal cancer cells.

Abstract: 

Colorectal cancer is a multi-factorial disease involving genetic, environmental and lifestyle risk factors. In recent years, many changes in the bacterial composition of the intestinal microflora have been reported in colorectal cancer, suggesting the involvement of the intestinal microflora in the development and progression of colorectal cancer. Along with these reports, research on lactic acid bacteria that have a beneficial effect on the human body for the purpose of improving the intestinal environment and treating intestinal diseases has advanced. Among these studies, biogenics (defined as a component derived from lactic acid bacteria that acts directly on diseases regardless of the state of intestinal microflora) is a recent concept derived from the work on probiotics. Based on this concept, it is important to evaluate the effectiveness of various components derived from lactic acid bacteria in the treatment to diseases from and apply them in prevention and treatment. In this study, we investigated the antitumor effect of an extract obtained fromstrain 06CC2 on colorectal cancer cells. In in vitro experiments, the extract derived from06CC2 significantly suppressed the proliferation of Caco2 colorectal cancer cells in comparison to control and non-cancer cells. Furthermore, we found that endoplasmic reticulum stress and the JNK/p38 MAPK signaling system are involved in the induction of apoptosis. These findings indicate the direct antitumor effect of the06CC2 extract on Caco2 colorectal cancer cells, and that this extract may have potential application as a biogenics.

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PMID: 

Probiotics Antimicrob Proteins. 2019 Nov 5. Epub 2019 Nov 5. PMID: 31691208

Abstract Title: 

Lactobacillus plantarum PS128 Ameliorated Visceral Hypersensitivity in Rats Through the Gut-Brain Axis.

Abstract: 

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain and alterations in bowel habits. Current treatments for IBS are unsatisfactory due to its multifactorial pathogenesis involving the microbiota-gut-brain axis. Lactobacillus plantarum PS128 (PS128) was reported to exhibit neuromodulatory activity which may be beneficial for improving IBS. This study aimed to investigate the effect of PS128 on visceral hypersensitivity (VH) and the gut-brain axis using a 5-hydroxytryptophan (5-HTP)-induced VH rat model without colonic inflammation induction, mimicking the characteristics of IBS. Male Sprague-Dawley rats were administered with PS128 (10 CFU in 0.2 mL saline/rat/day) or saline (0.2 mL saline/rat/day) for 14 days. Colorectal distension (CRD) with simultaneous electromyography recording was performed 30 min before and 30 min after the 5-HTP injection. Levels of neuropeptides and neurotrophins were analyzed. PS128 significantlyreduced VH induced by the 5-HTP injection and CRD. Neurotransmitter protein levels, substance P, CGRP, BDNF, and NGF, were decreased in the dorsal root ganglion but increased in the spinal cord in response to the 5-HTP injection; PS128 reversed these changes. The hypothalamic-pituitary-adrenal axiswas modulated by PS128 with decreased corticosterone concentration in serum and the expression of mineralocorticoid receptors in the amygdala. Oral administration of PS128 inhibited 5-HTP-induced VH during CRD. The ameliorative effect on VH suggests the potential application of PS128 for IBS.

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PMID: 

Int J Appl Basic Med Res. 2014 Sep ;4(Suppl 1):S20-2. PMID: 25298937

Abstract Title: 

Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice.

Abstract: 

AIM: This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells.MATERIALS AND METHODS: The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h.RESULT: The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P

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PMID: 

Sci Rep. 2017 09 13 ;7(1):11479. Epub 2017 Sep 13. PMID: 28904369

Abstract Title: 

Antimutagenic and antioxidant activity of the essential oils of Citrus sinensis and Citrus latifolia.

Abstract: 

The essential oils of Citrus sinensis and Citrus latifolia showed antimycotic activity against Candida spp. isolated from the oral cavity; they are neither mutagenic on the Ames test nor cytotoxic. Their main components are R-(+)-limonene,β-thujene, α-myrcene and γ-terpinene. The aim of this work was to evaluate their antimutagenic and antioxidant capacities. Antimutagenic properties were evaluated against MNNG and ENNG on S. typhimurium TA100; against 2AA on strain TA98 and in front of 4NQO and NOR on strain TA102. Both were antimutagenic against MNNG (p 

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PMID: 

J BUON. 2019 Jul-Aug;24(4):1532-1537. PMID: 31646804

Abstract Title: 

Inhibition of cancer cell growth by Tangeretin flavone in drug-resistant MDA-MB-231 human breast carcinoma cells is facilitated via targeting cell apoptosis, cell cycle phase distribution, cell invasion and activation of numerous Caspases.

Abstract: 

PURPOSE: In this study, the anticancer effects of a natural flavonoid-Tangeretin, were examined against the drug-resistant MDA-MB-231 breast cancer (BC) cell line and the normal breast cell line Hs 841.T.METHODS: The MTT assay was employed for cell viability determination. Apoptosis was demonstrated by DAPI and Annexin V/propidium iodide (PI) staining. Flow cytometric analyses were performed to gain insights about cell cycle distribution. Western blot assay was used for protein expression determination.RESULTS: Tangeretin inhibited the growth of the drug-resistant MDA-MB-231 cells concentration-dependently and its IC50 was 9µM, whereas the IC50 was>100µM against the normal cells. The anti-proliferative effects were due to induction of apoptotic cell death. The apoptotic cell percentage was increased from 5.7% to around 69% as the concentration of Tangeretin was increased. Tangeretin also caused an increase in the Bax/Bcl-2 ratio and activation of the Caspase 3, 8 and 9. In addition, Tangeretin led to arrest of the cells at G2/M phase which was accompanied by depletion of cyclin B1 and D. Transwell assay showed that Tangeretin also reduced the invasion of the MDA-MB-231 cells.CONCLUSION: The findings of this study suggest that Tangeretin exerts potent anticancer effects on the MDA-MB-231 cells and may therefore prove a beneficial lead molecule in BC research.

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PMID: 

Microb Pathog. 2019 Oct 29:103826. Epub 2019 Oct 29. PMID: 31676364

Abstract Title: 

Tangeretin attenuates lipopolysaccharide-induced acute lung injury through Notch signaling pathway via suppressing Th17 cell response in mice.

Abstract: 

Tangeretin, a polymethoxylated flavonoid is abundant in citrus fruits, which has been reported to inhibit inflammation by inhibiting NF-κB activation and proinflammatory cytokines. Notch blockage inhibits Th17 cells response that are involved in the development of acute lung injury (ALI). This study investigated the protective effects of tangeretin on LPS-induced ALI in mice. Male C57BL/6 mice were treated with phosphate-bufferedsaline (PBS), lipopolysaccharide (LPS), LPS and tangeretin, or LPS and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, a Notch signaling inhibitor), which were harvested at 48 h after challenged by LPS. CD4T cells were treated with tangeretin or DAPT and harvested after 72 h. Tangeretin notably attenuated pathological changes and decreased the wet to dry weight ratio of the mouse lungs. The total cell and neutrophil counts, tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF), myeloperoxidase activity of lung tissue were markedly reduced by tangeretin. The percentage of CD4+IL-17 + T cells in the lungs and the concentration of interleukin (IL)-17 and IL-22 in BALF were significantly down-regulated by tangeretin. As with the positive control (DAPT), tangeretin inhibited the activity of the Notch signaling pathway accompanied with the down-regulation of acid-related orphan receptor gamma t and IL-23 receptor expression. This study demonstrated that tangeretin protects against LPS-induced ALI by suppressing Th17 response at least partially, through a Notch-dependent mechanism.

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PMID: 

Food Sci Technol Int. 2019 Nov 5:1082013219883465. Epub 2019 Nov 5. PMID: 31684768

Abstract Title: 

Grapefruit essential oils inhibit quorum sensing of Pseudomonas aeruginosa.

Abstract: 

Citrus essential oils are used in food to confer flavor and aromas. The citrus essential oils have been granted as GRAS and could be used as antimicrobial additives to control bacterial quorum sensing from potential food bacterial pathogens. The chemical composition and inhibitory activity of(grapefruit) essential oils obtained by cold-pressed method (EOP) and cold-pressed method followed by steam distillation, againstwere determinedThe GC-MS analyses of the oil indicated the amount of the essential oil components was highest with D-limonene in both cases. However, the extraction method modified the chemical composition. EOP had higher amount of coumarins and flavonoid as well as less oxygenated terpenoids. At 0.1 mg/mL essential oils were not able to modify the bacterial development but inhibited thebiofilm production between 52% and 55%, sessile viability between 45% and 48%, autoinducer production and elastase activity between 30% and 56%. Limonene was less effective at inhibiting P. aeruginosa than the essential oils, suggesting a synergistic effect of the minor components. According to our results, grapefruit essential oils could be used as a food preservative to controlvirulence.

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PMID: 

Nutrients. 2019 Nov 4 ;11(11). Epub 2019 Nov 4. PMID: 31689949

Abstract Title: 

Discovery of Nobiletin from Citrus Peel as a Potent Inhibitor ofβ-Amyloid Peptide Toxicity.

Abstract: 

Increasing evidence has demonstrated that amyloid-β peptide (Aβ), the hallmark of Alzheimer's disease (AD), evokes oxidative and inflammatory cascades, which ultimately lead to the death of neurons. The purpose of the present study is to demonstrate the effect of nobiletin, a representative compound of citrus peel, in preventive and therapeutic approaches against neuronal damage by exposure to Aβ. Nobiletin significantly ameliorated Aβmediated cell death by restoring abnormal changes in intracellular oxidative stress, cell cycle, nuclear morphology, and activity of apoptotic caspase. Regarding anti-inflammatory responses, nobiletin significantly suppressed interleukin-1β, tumor necrosis factor-α, nitric oxide (NO), and prostaglandin Eproduction in response to Aβ stimulation. Moreover, nobiletin inhibited Aβ-stimulated inducible NO synthase and cyclooxygenase-2 expression, which was attributed to the blockade of nuclear factor-κB p65 and phosphorylation of its inhibitor, IκB-α. Interestingly, nobiletin decreased expression of c-Jun N-terminal kinase and p38 without affecting extracellular signal-regulated kinase 1/2 activation. Taken together, the novel data implicate nobiletin as a potential candidate for the prevention of AD through the inhibition of oxidative stress, apoptosis, and inflammation.

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PMID: 

Biomolecules. 2019 Nov 3 ;9(11). Epub 2019 Nov 3. PMID: 31684142

Abstract Title: 

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective.

Abstract: 

As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the complex pathophysiological mechanisms behind the neurodegeneration, investigating effective and multi-target treatments has remained a clinical challenge. Besides, appropriate neuroprotective agents are still lacking, which raises the need for new therapeutic agents. In recent years, several reports have introduced naturally-derived compounds as promising alternative treatments for NDs. Among natural entities, flavonoids are multi-target alternatives affecting different pathogenesis mechanisms in neurodegeneration. Naringenin is a natural flavonoid possessing neuroprotective activities. Increasing evidence has attained special attention on the variety of therapeutic targets along with complex signaling pathways for naringenin, which suggest its possible therapeutic applications in several NDs. Here, in this review, the neuroprotective effects of naringenin, as well as its related pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective, are described. Moreover, the need to develop novel naringenin delivery systems is also discussed to solve its widespread pharmacokinetic limitation.

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