PMID: 

Arzneimittelforschung. 1985 ;35(5):804-8. PMID: 4026903

Abstract Title: 

Polysorbate 80: a pharmacological study.

Abstract: 

Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes. It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum. A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg. The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg.

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PMID: 

J Toxicol Environ Health A. 2016 ;79(12):502-12. PMID: 27294299

Abstract Title: 

A brain proteome profile in rats exposed to methylmercury or thimerosal (ethylmercury).

Abstract: 

Exposure to organomercurials has been associated with harmful effects on the central nervous system (CNS). However, the mechanisms underlying organomercurial-mediated neurotoxic effects need to be elucidated. Exposure to toxic elements may promote cellular modifications such as alterations in protein synthesis in an attempt to protect tissues and organs from damage. In this context, the use of a"proteomic profile"is an important tool to identify potential early biomarkers or targets indicative of neurotoxicity. The aim of this study was to investigate potential modifications in rat cerebral cell proteome following exposure to methylmercury (MeHg) or ethylmercury (EtHg). For MeHg exposure, animals were administered by gavage daily 140µg/kg/d of Hg (as MeHg) for 60 d and sacrificed 24 h after the last treatment. For EtHg exposure, 800 µg/kg/d of Hg (as EtHg) was given intramuscularly (im) in a single dose and rats were sacrificed after 4 h. Control groups received saline either by gavage or im. After extraction of proteins fromwhole brain samples and separation by two-dimensional electrophoresis (2-DE), 26 differentially expressed proteins were identified from exposed animals by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF). Both MeHg and EtHg exposure induced an overexpression of calbindin,a protein that acts as a neuroprotective agent by (1) adjusting the concentration of Ca(2+) within cells and preventing neurodegenerative diseases and (2) decreasing expression of glutamine synthetase, a crucial protein involved in regulation of glutamate concentration in synaptic cleft. In contrast, expression of superoxide dismutase (SOD), a protein involved in antioxidant defense, was elevated in brain of MeHg-exposed animals. Taken together, our data provide new valuable information on the possible molecular mechanisms associated with MeHg- and EtHg-mediated toxicity in cerebral tissue. These observed protein alterations may be considered as biomarkers candidates for biological monitoring of organomercurial poisoning.

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PMID: 

J Biomed Biotechnol. 2012 ;2012:256965. Epub 2012 Jul 26. PMID: 22899883

Abstract Title: 

Mercury disposition in suckling rats: comparative assessment following parenteral exposure to thiomersal and mercuric chloride.

Abstract: 

Due to the facts that thiomersal-containing vaccine is still in use in many developing countries, and all forms of mercury have recognised neurotoxic, nephrotoxic, and other toxic effects, studies on disposition of ethylmercury and other mercury forms are still justified, especially at young age. Our investigation aimed at comparing mercury distribution and rate of excretion in the early period of life following exposure to either thiomersal (TM) or mercuric chloride (HgCl₂) in suckling rats. Three experimental groups were studied: control, TM, and HgCl₂, with 12 to18 pups in each. Both forms of mercury were administered subcutaneously in equimolar quantities (0.81 μmol/kg b.w.) three times during the suckling period (on the days of birth 7, 9, and 11) to mimic the vaccination regimen in infants. After the last administration of TM or HgCl₂, total mercury retention and excretion was assessed during following six days. In TM-exposed group mercury retention was higher in the brain, enteral excretion was similar, and urinary excretion was much lower compared to HgCl₂-exposed sucklings. More research is still needed to elucidate all aspects of toxicokinetics and most harmful neurotoxic potential of various forms of mercury, especially in the earliest period of life.

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PMID: 

Front Psychiatry. 2019 ;10:115. Epub 2019 Mar 13. PMID: 30918489

Abstract Title: 

The Therapeutic Potential of Mangosteen Pericarp as an Adjunctive Therapy for Bipolar Disorder and Schizophrenia.

Abstract: 

New treatments are urgently needed for serious mental illnesses including bipolar disorder and schizophrenia. This review proposes that. (mangosteen) pericarp is a possible adjunctive therapeutic agent for these disorders. Research to date demonstrates that neurobiological properties of the mangosteen pericarp are well aligned with the current understanding of the pathophysiology of bipolar disorder and schizophrenia. Mangosteen pericarp has antioxidant, putative neuroprotective, anti-inflammatory, and putative mitochondrial enhancing properties, with animal studies demonstrating favorable pharmacotherapeutic benefits with respect to these disorders. This review summarizes evidence of its properties and supports the case for future studies to assess the utility of mangosteen pericarp as an adjunctive treatment option for mood and psychotic disorders.

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PMID: 

Neurosci Lett. 2020 Jan 1 ;714:134566. Epub 2019 Nov 4. PMID: 31698027

Abstract Title: 

Blackberry extract improves behavioral and neurochemical dysfunctions in a ketamine-induced rat model of mania.

Abstract: 

Bipolar disorder is a chronic mood disorder characterized by episodes of mania and depression. The aim of this study was to investigate the effects of blackberry extract on behavioral parameters, oxidative stress and inflammatory markers in a ketamine-induced model of mania. Animals were pretreated with extract (200 mg/kg, once a day for 14 days), lithium chloride (45 mg/kg, twice a day for 14 days), or vehicle. Between the 8th and 14th days, the animals received an injection of ketamine (25 mg/kg) or vehicle. On the 15th day, thirty minutes after ketamine administration, the animals' locomotion was assessed using open-field apparatus. After the experiments, the animals were euthanized and cerebral structures were removed for neurochemical analyses. The results showed that ketamine treatment induced hyperlocomotion and oxidative damage in the cerebral cortex, hippocampus and striatum. In contrast,pretreatment with the extract or lithium was able to prevent hyperlocomotion and oxidative damage in the cerebral cortex, hippocampus, and striatum. In addition, IL-6 and IL-10 levels were increased by ketamine, while the extract prevented these effects in the cerebral cortex. Pretreatment with theextract was also effective in decreasing IL-6 and increasing the level of IL-10 in the striatum. In summary, our findings suggest that blackberry consumption could help prevent or reduce manic episodes, since this extract have demonstrated neuroprotective properties as well as antioxidant and anti-inflammatory effects in the ketamine-induced mania model.

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PMID: 

J Food Sci. 2019 May ;84(5):1208-1215. Epub 2019 Apr 23. PMID: 31012974

Abstract Title: 

Mangosteen Vinegar Rind from Garcinia mangostana Prevents High-Fat Diet and Streptozotocin-Induced Type II Diabetes Nephropathy and Apoptosis.

Abstract: 

Type II diabetes (T2D) nephropathy, a major cause of end-stage kidney disease, progresses and develops from oxidative stress. Natural polyphenols can protect the kidney from diabetic nephropathy exerting antioxidant activities. The present approach enumerates the reno-protective and anti-apoptotic effects of mangosteen vinegar rind (MVR, a phenolic aqueous extract) against high-fat diet (5 g/day up to five weeks)-/streptozotocin (single ip, dose 30 mg/kgBW)-induced T2D nephropathy of albino mice. In vitro total phenolic content, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant capacity, and α-amylase inhibition activity as antidiabetic assay of MVR were performed. In vivo mice body weight, oral glucose, and maltose tolerance test, metabolic parameters (plasma glucose, insulin level, omeostasis model assessment-estimated insulin resistance), biochemical parameters (kidney hypertrophy, blood urea nitrogen, creatinine), oxidative stress parameters (malondialdehyde, superoxide dismutase, catalase) were estimated in an intervention study. Additionally, renal morphology and early apoptosis were observed following the H&E staining and TUNEL assay of the tissue frozen section. We found that the aqueous extract of MVR possesses potent in vitro antioxidative and antidiabetic activities. Animal intervention results showed that MVR 100, 200 mg/kgBW, and Glibenclamide 60 mg/kgBW treatments significantly improved (P 

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PMID: 

Pharm Biol. 2018 Dec ;56(1):455-464. PMID: 31070537

Abstract Title: 

Mangosteen ethanol extract alleviated the severity of collagen-induced arthritis in rats and produced synergistic effects with methotrexate.

Abstract: 

CONTEXT: Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases.OBJECTIVE: This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo.MATERIALS AND METHODS: Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment andserological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry.RESULTS: All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p 

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PMID: 

BMC Complement Altern Med. 2019 Dec 2 ;19(1):344. Epub 2019 Dec 2. PMID: 31791316

Abstract Title: 

Mangosteen (Garcinia mangostana) flesh supplementation attenuates biochemical and morphological changes in the liver and kidney of high fat diet-induced obese rats.

Abstract: 

BACKGROUND: Mangosteen is a native fruit from Southeast Asia. It is rich in phenolic compounds such as xanthones, anthocyanins and phenolic acids. Mangosteen pericarp extract showed inhibitory activity towards pancreatic lipase and may have potential use for obesity treatment. However, there is limited study on the beneficial effects of mangosteen flesh against obesity. This study aimed to investigate the effects of Garcinia mangostana flesh (GMF) on biochemical and morphological changes in the liver and kidney of high-fat diet-induced obese rats.METHODS: Forty healthy Sprague-Dawley rats were randomised into five groups (n = 8) with four groups were fed with high-fat diet (HFD) for 10 weeks and a control group was fed with rat chow diet. Supplementation with GMF in obese rats was continued for 7 weeks starting from week 10th after the initiation of HFD at different doses (200 mg/kg, 400 mg/kg and 600 mg/kg). The positive and negative control rats were given distilled water via oral gavage. Plasma lipid profile, antioxidant enzymes and pro-inflammatory markers were determined using commercial kits. Liver and kidney structure were defined by histology.RESULTS: The rats fed with HFD for 10 weeks increased plasma LDL-cholesterol, reduced plasma glutathione peroxidase level and had significantly higher body weight compared to normal control rats (p 

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PMID: 

Vet Res Forum. 2019 ;10(3):187-192. Epub 2019 Sep 15. PMID: 31737226

Abstract Title: 

Attenuating effects ofleaves ethanolic extract against acetamiprid induced reproductive toxicity in male guinea pigs.

Abstract: 

Acetamiprid (ACP) belonging to the neonicotinoid family used against wide array of pests in agriculture and domestic purposes. In this study, we evaluated the attenuating effects of ethanolic extract ofleaves (EEMI) in averting reproductive toxicity caused by ACP in male guinea pigs. Thirty male guinea pigs were randomly assigned to five treatment groups (n = 6). Group 1 (T0) received distilled water orally; group 2 (T0-) was given 80 mg kgof ACP and groups 3, 4 and 5 were treated, respectively, with EEMI at doses of 50, 100 and 200 mg kgplus ACP. After 90 days, the reaction time, sexual organ weights, sperm count, motility and anomalies, spermatozoa with entire plasma membrane, testicular histology, serum testosterone concentration, testicular malondialdehyde (MDA) level, reduced glutathione (GSH) concentration, testicular superoxide dismutase (SOD) and catalase (CAT) activities were assessed. Co-administration of EEMI significantly reduced the reaction time, sperm anomalies and testicular MDA, SOD and CAT levels compared to the T0- group. Co-treatment of EEMI significantly alleviated sperm count and motility, percentage of spermatozoa with the normal plasma membrane, serum testosterone concentration, accessory sex gland weights, and testicular GSH concentrations. The ACP treatment induced cell membrane degradation in the testis and this effect was prevented with the addition of EEMI. In conclusion, ACP negatively affected the animal reproductive function and induced oxidative stress. The addition of EEMI alleviated the toxic effects of ACP on the reproductive function of male guinea pigs.

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PMID: 

Aging (Albany NY). 2019 Dec 2 ;11. Epub 2019 Dec 2. PMID: 31790366

Abstract Title: 

Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1.

Abstract: 

Mangiferin has been identified as a potent cardioprotective factor that enhances high-density lipoprotein cholesterol levels in plasma. The aim of this study was to investigate the impact of mangiferin on macrophage cholesterol efflux and the development of atherosclerosis. The results showed that mangiferin injection significantly decreased atherosclerotic plaque size, and reduced plasma levels of low-density lipoprotein cholesterol, triglyceride, and total cholesterol in apoE knockout mice, whereas reverse cholesterol transport efficiency and high-density lipoprotein cholesterol levels were enhanced.study showed that mangiferin prevented lipid accumulation and promoted [H]-cholesterol efflux from acetylated LDL-loaded RAW264.7 macrophages with an increase in the expression of ATP binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, transfection of PPARγ siRNA or LXRα siRNA markedly abolished the positive effects of mangiferin on ABCA1/G1 expression and cholesterol efflux. The opposite effects were observed after treatment with PPARγ agonist rosiglitazone or LXRα agonist T0901317. In conclusion, mangiferin may attenuate atherogenesis by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/G1 pathway.

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