PMID: 

Antioxidants (Basel). 2019 Aug 2 ;8(8). Epub 2019 Aug 2. PMID: 31382466

Abstract Title: 

Inhibition of LPS-Induced Oxidative Damages and Potential Anti-Inflammatory Effects ofExtract via Down-Regulating NF-κB, COX-2, and iNOS in RAW 264.7 Cells.

Abstract: 

is an edible nutraceutical and functional food in the Asia area with medicinal and nutritive importance. The fruit extract ofis currently considered to be one of the effective functional foods for flesh maintenance and disease treatments because of its antioxidative and immunomodulatory properties. We examined the antioxidant abilities of the fruit extract powder by carrying out 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, iron reducing power, and metal chelating activity analysis and showed excellent antioxidative results. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the result showed that the samples had no cytotoxic effect on RAW 264.7 cells even at a high concentration of 2 mg/mL. To investigate its immunomodulatory function, our estimation was to treat it with lipopolysaccharide (LPS) in RAW 264.7 cells to present anti-inflammatory capacities. The extract decreased reactive oxygen species (ROS) production levels in a dose-dependent manner measured by flow cytometry. We also examined various inflammatory mRNAs and proteins, including nuclear factor-κB (NF-κB), inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2). In quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting assay, all three targets were decreased by the extract, also in a dose-dependent manner. In conclusion,fruit extract powder not only lessened antioxidative stress damages, but also inhibited inflammatory reactions.

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PMID: 

Infect Disord Drug Targets. 2019 Aug 21. Epub 2019 Aug 21. PMID: 31433763

Abstract Title: 

Anti-infective potential of hydroalcoholic extract of Phyllanthus emblica seeds against selected human-pathogenic bacteria.

Abstract: 

INTRODUCTION: In context of the global threat of antimicrobial resistance among pathogenic bacteria against conventional bactericidal antibiotics, investigation on complementary/ alternative approaches to manage bacterial infections is warranted. Present study aimed at investigating the anti-pathogenic potential of Phyllanthus emblica seed extract (PESE) against four different pathogenic bacteria.METHODS: Hydroalcoholic extract of P. emblica seeds was tested for its possible in vitro quorum-modulatory potential against Chromobacterium violaceum, Serratia marcescens, Pseudomonas aeruginosa, and Staphylococcus aureus through broth dilution assay. In vivo efficacy of PESE was assayed employing Caenorhabditis elegans as the model host for these four pathogens.RESULTS: PESE was found to exert in vitro quorum-modulatory effect on C. violaceum, S. marcescens, P. aeruginosa, and S. aureus at≥50 µg/mL. This extract could curb the haemolytic activity of all the four test bacteria by 23-65%, inhibit biofilm formation, and was also able to modulate their antibiotic susceptibility and catalase activity. Susceptibility of P. aeruginosa and S. aureus to lysis by human serum was enhanced under the influence of this extract by 23% and 49% respectively. Repeated exposure of both these notorious pathogens to PESE did not induce resistance in them. In vivo assay confirmed the protective effect of this extract on C. elegans, when challenged with the PESE-treated pathogenic bacteria. PESE also showed notable prebiotic potential by promoting the growth of three probiotic strains.CONCLUSION: To the best of our awareness, this is the first report on quorum-modulatory potential of P. emblica seed extract, validating its anti-infective potential and prebiotic property.

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PMID: 

J Sci Food Agric. 2019 Sep 5. Epub 2019 Sep 5. PMID: 31487036

Abstract Title: 

Standardized Emblica officinalis fruit extract inhibited the activities of alpha-amylase, alpha-glucosidase, dipeptidyl peptidase-4 and displayed antioxidant potential.

Abstract: 

BACKGROUND: Emblica officinalis known as amla in Ayurveda has been used as folk medicine to treat numerous pathological conditions including diabetes. However, the novel extract of E. officinalis fruit extract (Amla Fruit Extract, AFE, Saberry®) containing 100 gm kgβ-glucogallin along with hydrolyzable tannins has not yet been extensively studied for its anti-diabetic potential.OBJECTIVE: The aim of the current study was to investigate the anti-diabetic, anti-oxidant activities and stability during gastric stress as well as thermo-stability of AFE.METHODS: The effect of AFE on the inhibition of pancreaticα-amylase and salivary α-amylase enzymes was studied using starch and yeast α-glucosidase enzyme using 4-nitrophenyl α-D-glucopyranoside as substrate. Further, DPPH radical scavenging and ROS inhibition assay was performed against AFE.RESULTS: AFE potently inhibited the activities ofα-amylase and α-glucosidase in a concentration dependent manner with the ICvalues of 135.70 and 106.70μg/ml respectively. Furthermore, it also showed inhibition of α-glucosidase (IC562.9μg/ml) and DPP-4 (IC3770μg/ml) enzyme activities. AFE is a potent anti-oxidant showing a free radical scavenging activity with an IC, of 2.37μg/ml and protecting against cellular reactive oxygen species IC, of 1.77μg/ml and the effects elicited could be attributed to its phytoconstituents.CONCLUSION: AFE showed significant gastric acid resistance and also found to be thermostable against the wet heat. Excellentα-amylase, α-glucosidase and DPP-4 inhibitory activities of AFE as well as antioxidant activities strongly recommend its use for the management of type 2 diabetes mellitus. This article is protected by copyright. All rights reserved.

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PMID: 

Neurotox Res. 2019 Feb ;35(2):318-330. Epub 2018 Sep 21. PMID: 30242626

Abstract Title: 

Amelioration of Aluminum Maltolate-Induced Inflammation and Endoplasmic Reticulum Stress-Mediated Apoptosis by Tannoid Principles of Emblica officinalis in Neuronal Cellular Model.

Abstract: 

The neuroprotective role of tannoid principles of Emblica officinalis (EoT), an Indian and Chinese traditional medicinal plant against memory loss in aluminum chloride-induced in vivo model of Alzheimer's disease through attenuating AChE activity, oxidative stress, amyloid and tau toxicity, and apoptosis, was recently reported in our lab. However, to further elucidate the mechanism of neuroprotective effect of EoT, the current study was designed to evaluate endoplasmic reticulum stress-suppressing and anti-inflammatory role of EoT in PC 12 and SH-SY 5Y cells. These cells were divided into four groups: control (aluminum maltolate (Al(mal)), EoT + Al(mal), and EoT alone based on 3-(4, 5-dimethyl 2-yl)-2, and 5-diphenyltetrazolium bromide (MTT) assay. EoT significantly reduced Al(mal)-induced cell death and attenuated ROS, mitochondrial membrane dysfunction, and apoptosis (protein expressions of Bax; Bcl-2; cleaved caspases 3, 6, 9, 12; and cytochrome c) by regulating endoplasmic reticulum stress (PKR-like ER kinase (PERK),α subunit of eukaryotic initiation factor 2 (EIF2-α), C/EBP-homologous protein (CHOP), and high-mobility group box 1 protein (HMGB1)). Moreover, inflammatory response (NF-κB, IL-1β, IL-6, and TNF-α) and Aβ toxicity (Aβ) triggered by Al(mal)was significantly normalized by EoT. Our results suggested that EoT could be a possible/promising and novel therapeutic lead against Al-induced neurotoxicity. However, further extensive research is needed to prove its efficacy in clinical studies.

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PMID: 

Sci Rep. 2018 Nov 13 ;8(1):16729. Epub 2018 Nov 13. PMID: 30425257

Abstract Title: 

Association of Serum Aluminum Levels with Mortality in Patients on Chronic Hemodialysis.

Abstract: 

Despite reported evidence on the relationship between higher serum aluminum levels and poor outcomes in patients on chronic hemodialysis (CHD), the acceptable cutoff value of serum aluminum for mortality remains unclear. A retrospective observational cohort study with 636 Taiwanese patients on CHD was conducted to investigate the impact of serum aluminum levels on mortality. The predictors were bivariate serum aluminum level (

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PMID: 

Physiol Res. 2019 03 6 ;68(1):67-74. Epub 2018 Oct 23. PMID: 30433801

Abstract Title: 

Synergistic potential of propolis and vitamin e against sub-acute toxicity of AlCl(3) in albino mice: in vivo study.

Abstract: 

Current study evaluated the synergistic potential of propolis and vitamin E against sub-acute toxicity of aluminum chloride on different biochemical parameters and liver histology. Swiss albino mice (n=42) were randomly divided into seven groups. Group I received 0.2 ml of 0.9 % saline solution, Group II received Propolis (50 mg/kg b.w.), Group III received vitamin E (150 mg/kg b.w.), Group IV received AlCl(3) 50 mg/kg b.w., Group V received AlCl(3) + Propolis, Group VI received AlCl(3) + vitamin E and Group VII received AlCl(3) + propolis + vitamin E. Blood and tissue samples were collected after 7 and 21 days. The body weight of the animals significantly increased in all groups except Group IV. The concentration of serum high density lipoprotein significantly decreased in Group IV and increased in Group V, VI and VII. The level of aspartate aminotransferase, alanine transferase, alkaline phosphatase, triglycerides, total cholesterol, and low density lipoprotein significantly increased in AlCl(3) treated group and increased in Group V, VI and VII. Tissue sections were processed and stained by hematoxylin and eosin. Group II showed cellular necrosis. Group V, VI showed decreased number of vacuolization, sinusoidal spacing and macrophage cell infiltration. Group VI showed less degenerative changes in the third week. Vitamin E and propolis in combination with Al provides more protection against AlCl(3) induced toxicity.

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PMID: 

Life Sci. 2019 Jan 15 ;217:202-211. Epub 2018 Dec 5. PMID: 30528774

Abstract Title: 

Acute aluminum chloride toxicity revisited: Study on DNA damage and histopathological, biochemical and neurochemical alterations in rat brain.

Abstract: 

AIMS: Due to rapid increase in industrialization in the last few years, use of aluminum (Al) and its alloys have been increased in different industrial fields. Ample evidence supports the neurotoxic effects of chronic aluminum chloride (AlCl) administration in rats but acute Al toxicity has been less described so the present study was aimed to investigate the neurotoxic effects of acute AlCl.MAIN METHODS: To investigate such effects 12 male albino Wistar rats were randomly divided into control and test rats. AlClat a dose of 150 mg/kg was intraperitoneally injected to test rats for 7 days. Rats were subjected to behavioral assessments 24 h after last dose and after behavioral assessment rats were sacrificed to collect brain samples for further neurochemical, biochemical and histopathological examinations.KEY FINDINGS: In the present study acute administration of AlClresulted in noticeable behavioral deficits. Cognitive deficits and neuropsychiatric disturbances were evident in AlClinjected rats. Test rats also exhibited marked antioxidant enzymes, cholinergic, serotonergic and dopaminergic dysfunctions and DNA fragmentation. Histopathological alterations were observed in hippocampus and cortex of rats injected with AlCl.SIGNIFICANCE: The observed effects may be due to pro-oxidant nature of Al and its participation in free radical mediated cellular injury. Al by promoting oxidative stress, impairing antioxidant defense system and altering brain neurochemistry may act as a potent neurotoxic agent as evident from observed histopathological alterations in brain of test rats. This investigation may further confirm and shed some more light on deleterious effects of acute Al intoxication on brain.

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PMID: 

Cell Mol Gastroenterol Hepatol. 2019 ;7(1):185-196. Epub 2018 Sep 20. PMID: 30534582

Abstract Title: 

Aluminum Ingestion Promotes Colorectal Hypersensitivity in Rodents.

Abstract: 

Background & Aims: Irritable bowel syndrome (IBS) is a multifactorial disease arising from a complex interplay between genetic predisposition and environmental influences. To date, environmental triggers are not well known. Aluminum is commonly present in food, notably by its use as food additive. We investigated the effects of aluminum ingestion in rodent models of visceral hypersensitivity, and the mechanisms involved.Methods: Visceral hypersensitivity was recorded by colorectal distension in rats administered with oral low doses of aluminum. Inflammation was analyzed in the colon of aluminum-treated rats by quantitative PCR for cytokine expression and by immunohistochemistry for immune cells quantification. Involvement of mast cells in the aluminum-induced hypersensitivity was determined by cromoglycate administration of rats and in mast cell-deficient mice (Kit). Proteinase-activated receptor-2 (PAR2) activation in response to aluminum was evaluated and its implication in aluminum-induced hypersensitivity was assessed in PAR2 knockout mice.Results: Orally administered low-dose aluminum induced visceral hypersensitivity in rats and mice. Visceral pain induced by aluminum persisted over time even after cessation of treatment, reappeared and was amplified when treatment resumed. As observed in humans, female animals were more sensitive than males. Major mediators of nociception were up-regulated in the colon by aluminum. Activation of mast cells and PAR2 were required for aluminum-induced hypersensitivity.Conclusions: These findings indicate that oral exposure to aluminum at human dietary level reproduces clinical and molecular features of IBS, highlighting a new pathway of prevention and treatment of visceral pain in some susceptible patients.

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PMID: 

Exp Mol Pathol. 2019 04 ;107:32-42. Epub 2019 Jan 17. PMID: 30659797

Abstract Title: 

Aluminum disrupts the prenatal development of the male and female gerbil prostate (Meriones unguiculatus).

Abstract: 

Normal prostate development is highly dependent of an equilibrated hormonal regulation, so that sensible interferences during this period may predispose the gland to lesions during aging. Industrial activities have increased the exposure of this gland to active elements found in environment, such as aluminum (Al). Al presents toxic effect for living beings, having the potential to disrupt the development and growth of several organs and systems. Therefore, the aim of this study was to evaluate whether the prenatal exposure to Al may alter the development and morphophysiology of the gerbil prostate (Meriones unguiculatus). Pregnant females were orally exposed to aluminum chloride (100 mg/kg/day) from 17th to 21th gestational day. Following the birth, the male and female pups were euthanized with 1 (PN1) and 90-days-old (PN90). The prostates were collected for biometrical, three-dimensional reconstruction, morphometrical, stereological, and immunohistochemical analysis. Resultsindicated that Al decreases the body weight of PN1 males and females, and also reduce the anogenital distance of PN1 females. Moreover, Al changed the prostate developmental patterns of PN1 animals, causing an increase in proliferative status and decreasing androgen receptor immunostaining. The results suggest that Al-promoted changes were permanent, since low androgen receptor frequency, increased serum testosterone levels and high proliferation index were observed in adult gerbils. This study demonstrated that body and prostatic changes were more pronounced in females than in males, and that Al performed as an endocrine-disrupting chemical in gerbils.

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PMID: 

Biol Pharm Bull. 2019 ;42(8):1384-1393. PMID: 31366873

Abstract Title: 

Bacopa monnieri (L.) Ameliorates Cognitive Deficits Caused in a Trimethyltin-Induced Neurotoxicity Model Mice.

Abstract: 

We previously demonstrated that Bacopa monnier (L.) WETTST. extract (BME) ameliorated cognitive dysfunction in animal models of dementia by enhancing synaptic plasticity-related signaling in the hippocampus and protecting cholinergic neurons in the medial septum. To further clarify the pharmacological features and availability of BME as a novel anti-dementia agent, we investigated whether BME affects neuronal repair using a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampus. Mice pretreated with TMT (2.8 mg/kg, intraperitoneally (i.p.)) on day 0 were given BME (50 mg/kg, per os (p.o.)) once daily for 15-30 d. Cognitive performance of the animals was elucidated twice by the object location test and modified Y maze test on days 17-20 (Phase I) and days 32-35 (Phase II) or by the passive avoidance test on Phase II. TMT impaired hippocampus-dependent spatial working memory and amygdala-dependent fear-motivated memory. The administration of BME significantly prevented TMT-induced cognitive deficits. The protective effects of BME on the spatial memory deficits were confirmed by Nissl stainingof hippocampal tissues and propidium iodide staining of organotypic hippocampal slice cultures. Immunohistochemical studies conducted on days 17 and 32 revealed that thirty days of treatment with BME increased the number of 5-bromo-2'-deoxyuridine (BrdU)-immunopositive cells in the dentate gyrus region of TMT-treated mice, whereas fifteen days of treatment with BME had no effect. These results suggest that BME ameliorates TMT-induced cognition dysfunction mainly via protecting the hippocampal neurons from TMT-induced hippocampal lesions and partly via promoting neuroregeneration in the dentate gyrus regions.

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