PMID: 

Food Chem Toxicol. 2019 Jul 22:110694. Epub 2019 Jul 22. PMID: 31344369

Abstract Title: 

Long-term exposure to bisphenol A or S promotes glucose intolerance and changes hepatic mitochondrial metabolism in male Wistar rats.

Abstract: 

The present study evaluates the effects of low-level long-term exposure to bisphenol A (BPA) and bisphenol S (BPS) on serum biochemical markers, glucose homeostasis, mitochondrial energy metabolism, biogenesis and dynamics, and redox status in livers of Wistar rats. While only the exposure to BPS induces a significant body mass gain after 21 weeks, both compounds alter serum lipid levels and lead to the development of glucose intolerance. Regarding mitochondrial metabolism, both bisphenols augment the electron entry by complex II relative to complex I in the mitochondrial respiratory chain (MRC), and reduce mitochondrial content; BPA reduces OXPHOS capacity and uncouples respiration (relative to maximal capacity of MRC) but promotes a significant increase in fatty acid oxidation. Either exposure to BPA or BPS leads to an increase in mitochondrial-derived reactive oxygen species, mainly at complex I. Additionally, BPA and BPS significantly upregulate the expression levels of dynamin-related protein 1 related to mitochondrial fission, while BPA downregulates the expression of proliferator-activated receptor gamma coactivator 1 alpha, a master regulator of mitochondrial biogenesis. In summary, our data shows that exposure to both compounds alters metabolic homeostasis and mitochondrial energy metabolism, providing new mechanisms by which BPA and BPS impair the mitochondrial metabolism.

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PMID: 

Sci Rep. 2019 Jul 22 ;9(1):10584. Epub 2019 Jul 22. PMID: 31332285

Abstract Title: 

Effect of antioxidants on BPA-induced stress on sperm function in a mouse model.

Abstract: 

In the past few years, bisphenol A, (BPA) an endocrine-disrupting chemical, has received increasing attention because of its detrimental health effects. There is ample evidence to support that BPA interferes with the reproductive health of humans and animals. In spermatozoa, BPA-induced adverse effects are mostly caused by increased oxidative stress. Using an in vitro experimental model, we examined whether antioxidants (glutathione, vitamin C, and vitamin E) have defensive effects against BPA-induced stress in spermatozoa. The results showed that antioxidants inhibit the overproduction of reactive oxygen species (basically cellular peroxides) and increase intracellular ATP levels, thereby preventing motility loss and abnormal acrosome reaction in BPA-exposed spermatozoa. In particular, glutathione and vitamin E reduced the protein kinase A-dependent tyrosine phosphorylation in spermatozoa and, thus, prevented the precocious acrosome reaction from occurring. Furthermore, we found that the compromised fertilisation and early embryo development mediated by BPA-exposed spermatozoa can be improved following their supplementation with glutathione and vitamin E. Based on these findings, we suggest that antioxidants reduce oxidative stress in BPA-exposed spermatozoa, thus preventing detrimental effects on their function and fertility.

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PMID: 

Environ Res. 2019 Jul 11 ;177:108584. Epub 2019 Jul 11. PMID: 31326715

Abstract Title: 

Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only.

Abstract: 

BACKGROUND: Developmental exposure to low doses of the endocrine disruptor bisphenol A (BPA) is known to alter bone tissue in young rodents, although how bone tissue is affected in aged animals is not well known. We have recently shown that low-dose developmental exposure to BPA increases procollagen type I N-terminal propeptide (P1NP) levels, a peptide formed during type 1 collagen synthesis, in plasma of 5-week-old female rat offspring while male offspring showed reduced bone size.OBJECTIVE: To analyze offspring bone phenotype at 52 weeks of age and clarify whether the BPA-induced increase in P1NP levels at 5 weeks is an early sign of bone marrow fibrosis development.METHODS: As in our 5-week study, pregnant Fischer 344 rats were exposed to BPA via drinking water corresponding to 0.5 μg/kg BW/day (BPA0.5), which is in the range of human daily exposure, or 50 μg/kg BW/day (BPA50) from gestational day 3.5 until postnatal day 22. Controls were given only vehicle. The offspring were sacrificed at 52 weeks of age. Bone effects were analyzed using peripheral quantitative and micro-computed tomography (microCT), 3-point bending test, plasma markers and histological examination.RESULTS: Compared to a smaller bone size at 5 weeks, at the age of 52 weeks, femur size in male offspring had been normalized in developmentally BPA-exposed rats. The 52-week-old female offspring showed, like the 5-week-old siblings, higher plasma P1NP levels compared to controls but no general increasing bone growth or strength. However, 2 out of 14 BPA-exposed female offspring bones developed extremely thick cortices later in life, discovered by systematic in vivo microCT scanning during the study. This was not observed in male offspring or in female controls. Biomechanical testing revealed that both doses of developmental BPA exposure reduced femur stiffness only in female offspring. In addition, histological analysis showed an increased number of fibrotic lesions only in the bone marrow of female rat offspring developmentally exposed to BPA. In line with this, plasma markers of inflammation, Tnf (in BPA0.5) and Timp1 (in BPA50) were increased exclusively in female offspring.CONCLUSIONS: Developmental BPA exposure at an environmentally relevant concentration resulted in female-specific effects on bone as well as on plasma biomarkers of collagen synthesis and inflammation. Even a dose approximately eight times lower than the current temporary EFSA human tolerable daily intake of 4 μg/kg BW/day, appeared to induce bone stiffness reduction, bone marrow fibrosis and chronic inflammation in female rat offspring later in life.

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PMID: 

Arch Med Res. 2019 Feb ;50(2):36-43. Epub 2019 Jun 3. PMID: 31349952

Abstract Title: 

Non-Ionizing Radiation Created by Mobile Phone Progresses Endometrial Hyperplasia: An Experimental Rat Study.

Abstract: 

BACKGROUND: Non-ionizing radiation is related with many pathologies.AIM: Determine association between non-ionizing radiation and endometrial hyperplasia.METHODS: Fifty oopherectomized Wistar albino rats were administered Estradiol hemihydrate (4 mg/kg) to induce hyperplasia, and were exposed to 1800 MHz radiation created by a mobile phone and a signal generator working as base station. This study was carried out with 5 groups in two phases. The study groups were. Control group without any exposure; group receiving estrogen in first phaseof the study; group receiving estrogen in both phases; group receiving estrogen in the first phase and exposed to non-ionizing radiation during second phase and group taking estrogen in both phases and exposed to non-ionizing radiation during the second phase. Following both phases, uterine horns were excised and evaluated based on glandular density (GD), epithelial cell height (ECH), and luminal epithelial cell height (LECH).RESULTS: Estrogen increased all parameters during both phases (LECH, GD, and ECH values were 12,2 vs. 16,5 (p = 0.001), 34 vs. 47 (p

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PMID: 

Food Chem. 2019 Nov 30 ;299:125095. Epub 2019 Jun 27. PMID: 31279124

Abstract Title: 

Effects of hydrogen-rich water on the nutrient composition and antioxidative characteristics of sprouted black barley.

Abstract: 

Hydrogen gas (H), a multifunctional signaling molecule, has received increasing attention in recent years. In the present study, hydrogen-rich water (HRW) (2 ppm) was used for the processing of sprouted black barley (Hordeum distichum L.), and the results showed that the HRW treatment could significantly increase the germination rate and growth rate of black barley (P 

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PMID: 

Int Immunopharmacol. 2019 Jun 26 ;74:105712. Epub 2019 Jun 26. PMID: 31254954

Abstract Title: 

Asiatic acid inhibits cardiac fibrosis throughNrf2/HO-1 and TGF-β1/Smads signaling pathways in spontaneous hypertension rats.

Abstract: 

OBJECTIVE: Asiatic acid (AA) has been suggested to inhibit pulmonary and hepatic fibrosis, while its influence on cardiac fibrosis remains unclear. We aimed to investigate whether AA could inhibit overpressure-induced cardiac fibrosis in spontaneous hypertension rats (SHRs).METHOD: SHRs were treated with AA (20 mg kg day) for 12 weeks and cultured cardiac fibroblasts (CFs) were treated with Ang II (10 mol/L) in vitro. Markers of oxidative stress were measured and extent of cardiac fibrosis was evaluated with Sirius Red staining. Levels of Superoxide Dismutase (SOD), Malondialdehyde (MDA), reactive oxygen spices (ROS) and Glutathione (GSH) were measured by using commercial assay kits. Collagendeposition was detected. The expression of relative protein and mRNA was measured by Western blot and real-time PCR, respectively.RESULTS: AA reduced systolic blood pressure, attenuated myocardial hypertrophy, reduced college deposition and the expression of collagen I and III, connective tissue growth factor, and plasminogen activator inhibitor-1, in mRNA and protein levels, with inhibition of TGF-β1 expression, phosphorylation of Smad2/3, and increase of Smad7 expression. AA reduced malondialdehyde and reactive oxygen spices, while increased the activities of superoxide dismutase and glutathione, accompanied with elevation of nuclear translocation of nuclear-factor erythroid 2-related factor 2 (Nrf2) and expression of heme oxygenase (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1) in vivo and in vitro. Moreover, pretreating CFs with siRNA for Smad7 or Nrf2 both partially reversed the inhibition of AA on Ang II-induced cardiac fibrosis.CONCLUSION: AA attenuates pressure overload-induced cardiac fibrosis via enhancing of Nrf2/HO-1 and suppressing TGF-β1/Smads phosphorylation.

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PMID: 

Exp Ther Med. 2019 Jun ;17(6):4687-4692. Epub 2019 Apr 17. PMID: 31086602

Abstract Title: 

Protective effects of Asiatic acid against pelvic inflammatory disease in rats.

Abstract: 

Asiatic acid (AA) is one of the major components of the Chinese herband exerts a variety of pharmacological activities. However, the pharmacological effects of AA on pelvic inflammatory disease (PID) remain unknown. The purpose of the present study was to investigate the therapeutic efficacy and potential mechanisms of AA on PID in rats. A total of 75 female Sprague Dawley rats were randomly divided into the following five groups: A control group; a PID group; a PID + AA 5 mg/kg group; a PID + AA 35 mg/kg group; and a PID + AA 75 mg/kg group. Changes in cytokine and chemokine levels, myeloperoxidase (MPO) activity, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome and nuclear factor-κB (NF-κB) activation, oxidative stress and cleaved caspase-3 were measured. AA treatment significantly decreased the excessive production of cytokines and chemokines and suppressed MPO activity and the activation of NLRP3 inflammasome, NF-κB and caspase-3, as well as oxidative stress. These results suggest that AA exhibits potent anti-inflammatory and antioxidant effects in rats with pathogen-induced PID and that the mechanism of these anti-inflammatory effects may be associated with the suppression of NLRP3 inflammasome activation and the NF-κB pathway.

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PMID: 

Biomol Ther (Seoul). 2019 Apr 10. Epub 2019 Apr 10. PMID: 30971058

Abstract Title: 

Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial Ros Production.

Abstract: 

This study sought to evaluate the effects of Asiatic acid in LPS-induced BV2 microglia cells and 1-methyl-4-phenyl-pyridine (MPP)-induced SH-SY5Y cells, to investigate the potential anti-inflammatory mechanisms of Asiatic acid in Parkinson’s disease (PD). SH-SY5Y cells were induced using MPPto establish as anmodel of PD, so that the effects of Asiatic acid on dopaminergic neurons could be examined. The NLRP3 inflammasome was activated in BV2 microglia cells to explore potential mechanisms for the neuroprotective effects of Asiatic acid. We showed that Asiatic acid reduced intracellular production of mitochondrial reactive oxygen species and altered the mitochondrial membrane potential to regulate mitochondrial dysfunction, and suppressed the NLRP3 inflammasome in microglia cells. We additionally found that treatment with Asiatic acid directly improved SH-SY5Y cell viability and mitochondrial dysfunction induced by MPP. These data demonstrate that Asiatic acid both inhibits the activation of the NLRP3 inflammasome by downregulating mitochondrial reactive oxygen species directly to protect dopaminergic neurons from, and improves mitochondrial dysfunction in SH-SY5Y cells, which were established as a model of Parkinson’s disease. Our finding reveals that Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing NLRP3 inflammasome activation in microglia cells as well as protecting dopaminergic neurons directly. This suggests a promising clinical use of Asiatic acid for PD therapy.

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PMID: 

Front Microbiol. 2018 ;9:2125. Epub 2018 Sep 7. PMID: 30245677

Abstract Title: 

Antimicrobial Effect of Asiatic Acid AgainstIs Associated With Disruption of Membrane Permeability.

Abstract: 

Antibiotic resistance is a major concern in, the causative agent of antibiotic-associated diarrhea. Reduced susceptibility to first- and second-line agents is widespread, therefore various attempts have been made to seek alternative preventive and therapeutic strategies against this pathogen. In this work, the antimicrobial properties of asiatic acid were evaluated against. Asiatic acid displayed substantial inhibitory effects on 19isolates collected from different sources with minimal inhibitory concentrations ranging from 10 to 20μg/ml. Time kill analysis and minimal bactericidal concentration revealed potential bactericidal activity of this compound. Asiatic acid induced membrane damages and alterations in morphological ultrastructure in, thereby causing the leakage of intracellular substances. Moreover, asiatic acid also displayed an inhibitory effect on cell motility, but did not interfere with biofilm formation and spore germination. Analysis of drug combination showed no synergistic effect between asiatic acid and vancomycin/metronidazole. Altogether, asiatic acid exhibited strong antimicrobial activity against vegetative cells and could serve as an alternative resource for tackling.

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PMID: 

Biol Pharm Bull. 2019 ;42(8):1358-1365. PMID: 31366870

Abstract Title: 

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

Abstract: 

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 E(PGE), and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β 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.

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