PMID: 

Reprod Toxicol. 2019 Jul 11. Epub 2019 Jul 11. PMID: 31302198

Abstract Title: 

A pilot study: Bisphenol-A and Bisphenol-A glucuronide levels in mother and child pairs in a South African population.

Abstract: 

: Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to determine serum levels of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) in South African mother-child pairs.METHOD: Third-trimester serum maternal samples and matching cord blood samples were analysed for BPA and BPA-g using LC-MS/MS.RESULTS: Ninety maternal and child pairs were analysed. BPA was detectable in more than 25% of maternal and cord blood samples. Spearman correlation demonstrated significant positive correlation between maternal and child BPA and BPA-g levels with correlation coefficients of 0.892 and 0.744, respectively. A significant positive association between cord BPA levels and child birth-weight (p = 0.02) as well as with maternal BMI (p = 0.04) was noted.CONCLUSION: This is the first study to describe the presence of detectable BPA levels using LC-MS/MS methodology in a South African population.

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PMID: 

Pak J Pharm Sci. 2019 May ;32(3):1043-1047. PMID: 31278718

Abstract Title: 

Testicular toxicity of orally administrated bisphenol A in rats and protective role of taurine and curcumin.

Abstract: 

Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the world. Curcumin, the yellow bioactive compound of turmeric has demonstrated its antioxidant activities. Taurine is a low-molecular weight organic compound in living organisms. The present study was aimed to investigate the adverse effects of BPA and its protection by taurine and curcumin. Oral BPA, curcumin and taurine administration in adult male rats at 130mg/kg bw, 100mg/kg bw and 100mg/kg bw, respectively for four weeks. Pathology and oxidative damages were investigated. The results show that BPA increased malondialdehyde (MDA) levels and decreased antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST)] in testes of rats compared to the control group. Co-treatment with curcumin or taurine with BPA led to reduce in MDA and increased GPx, GST, CAT, SOD activities compared to BPA group. Furthermore, while some pathological findings were observed in testis tissues in BPA treated group, less histopathological findings were shown in BPA plus curcumin and/or taurine treated groups. Consequently, curcumin and taurine significantly protect BPA induced testicular damage in rats.

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PMID: 

Reprod Toxicol. 2019 Jul 3 ;89:35-44. Epub 2019 Jul 3. PMID: 31278978

Abstract Title: 

Effects of Bisphenol A on endogenous retroviral envelopes expression and trophoblast fusion in BeWo cells.

Abstract: 

Placenta is a target organ of Bisphenol A (BPA). To investigate possible effects on syncytiotrophoblast, the exchanging surface between mother and fetus, we exposed a trophoblast model (BeWo) to BPA concentrations occurring in humans (1 and 50 nM). We assessed the gene and protein expression of three human endogenous retroviral envelopes, specifically expressed in placenta (ERVW-1, ERVFRD-1 and ERV3-1), the secretion of β-hCG, the extent of trophoblast fusion and the activity of apoptosis markers (caspases 8, 3, 9 and PARP); additionally, the gene expression of transcription factors regulating HERV expression (i.e. GCM1, PPARγ, ERα and ERβ) was evaluated. At 50 nM, BPA induced ERVW-1, ERVFRD-1 and the corresponding syncytin proteins, ERV3-1, PPARγ, ERα and ERβ expression, increased β-hCG secretion and BeWo cells fusion,thus promoting the syncytiotrophoblast phenotype. The results support placenta as a target organ of BPA. Possible implications on fetal and pregnancy health should be carefully considered.

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PMID: 

Immunopharmacol Immunotoxicol. 2018 Apr ;40(2):107-116. Epub 2018 Feb 6. PMID: 29405080

Abstract Title: 

Artesunate enhancesγδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells.

Abstract: 

OBJECTIVE: To explore the effect and mechanism of artesunate onγδ T cell-mediated antitumor immune responses against hepatoma carcinoma cells (HepG2) in vitro.METHODS: Humanγδ T cells or HepG2 were respectively treated with artesunate, subjected to co-culture as appropriate, and the following assays were subsequently conducted: CCK8 to examine cell viability; LDH release assay to detect the killing effect of γδ T cells on HepG2 cells; flow cytometry to examine theexpression of perforin (PFP) and granzyme B (GraB) of γδ T cells; ELISA to evaluate the levels of TGF-β1 and IL-10 in the collected supernatant of HepG2 cells pretreated with artesunate; and Western blot analysis to examine Fas, FasL, STAT3, p-STAT3 expression of HepG2 cells induced by artesunate.  Results: The results showed that the cytotoxicity effect of γδ T cells pretreated with artesunate on HepG2 cells was augmented via elevating the expression of GraB in γδ T cells. Furthermore, treatment with artesunate reversed the inhibition of HepG2 cells on γδ T cells by reducing the secretion of TGF-β1 in HepG2 cells supernatant and enhanced the antitumor effect of γδ T cells against HepG2 cells through increasing the expression of Fas on HepG2 cells, which may be attributed to the inhibition of STAT3 signaling protein.CONCLUSION: Artesunate has several mechanisms for augmenting the antitumor immune responses mediated byγδ T cells. These results suggested artesunate may be an efficacious agent in the treatment of hepatocellular carcinoma.

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PMID: 

Pharmacol Rep. 2018 Apr ;70(2):390-397. Epub 2017 Jun 15. PMID: 29397336

Abstract Title: 

Artesunate affords protection against aspirin-induced gastric injury by targeting oxidative stress and proinflammatory signaling.

Abstract: 

BACKGROUND: Prolonged use of aspirin, a commonly prescribed non steroidal anti-inflammatory drug, is well known to produce gastrointestinal toxicity which could be minimized by various anti-secretory agents. The present study was carried out to evaluate the protective effect of artesunate against aspirin induced gastric injury in rats.METHODS: Gastric injury was induced in fasted Wistar rats by oral administration of aspirin. The effect of 50 and 150mg/kg of artesunate was studied on macroscopic changes, gastric secretions, histology, oxidative stress and inflammatory markers in the stomach tissue after 5h of induction of gastric injury. Immunohistochemical analysis for the expression of IL-1β, IL-6, NF-κB(p65) and COX-2 was also carried out. The effect of artesunate was compared with that of standard anti-ulcer drug famotidine (20mg/kg).RESULTS: Artesunate pretreatment produced a dose-dependent reduction in aspirin induced gastric injury and restored the gastric juice parameters. It normalized the tissue levels of oxidative stress markers (glutathione, malondialdehyde and superoxide dismutase activity) and mediators of inflammation (myeloperoxidase and TNF-α). The protection afforded by artesunate was evident from the histoarchitecture of stomach tissue and marked reduction in tissue expression of IL-1β, IL-6, NF-κB(p65) and COX-2. The effect of artesunate was found to be comparable to that of standard drug famotidine.CONCLUSION: Artesunate markedly ameliorated aspirin induced gastric injury in rats by targeting oxidative stress and COX-2 dependent as well as COX-2 independent proinflammatory signaling pathways and could have a therapeutic potential in gastric ulcer disease.

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PMID: 

J Hematol Oncol. 2018 02 20 ;11(1):23. Epub 2018 Feb 20. PMID: 29458389

Abstract Title: 

Artesunate shows potent anti-tumor activity in B-cell lymphoma.

Abstract: 

BACKGROUND: Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate has previously been identified as a growth suppressor in some cancer types and was tested as a new treatment option in B-cell lymphoma.METHODS: We included artesunate in a cancer sensitivity drug screen in B lymphoma cell lines. The preclinical properties of artesunate was tested as single agent in vitro in 18 B-cell lymphoma cell lines representing different histologies and in vivo in an aggressive B-cell lymphoma xenograft model, using NSG mice. Artesunate-treated B lymphoma cell lines were analyzed by functional assays, gene expression profiling, and protein expression to identify the mechanism of action.RESULTS: Drug screening identified artesunate as a highly potent anti-lymphoma drug. Artesunate induced potent growth suppression in most B lymphoma cells with an ICcomparable to concentrations measured in serum from artesunate-treated malaria patients, while leaving normal B-cells unaffected. Artesunate markedly inhibited highly aggressive tumor growth in a xenograft model. Gene expression analysis identified endoplasmic reticulum (ER) stress and the unfolded protein response as the most affected pathways and artesunate-induced expression of the ER stress markers ATF-4 and DDIT3 was specifically upregulated in malignant B-cells, but not in normal B-cells. In addition, artesunate significantly suppressed the overall cell metabolism, affecting both respiration and glycolysis.CONCLUSIONS: Artesunate demonstrated potent apoptosis-inducing effects across a broad range of B-cell lymphoma cell lines in vitro, and a prominent anti-lymphoma activity in vivo, suggesting it to be a relevant drug for treatment of B-cell lymphoma.

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PMID: 

Mol Med Rep. 2018 May ;17(5):6639-6646. Epub 2018 Mar 1. PMID: 29512760

Abstract Title: 

Artesunate suppresses oxidative and inflammatory processes by activating Nrf2 and ROS‑dependent p38 MAPK and protects against cerebral ischemia‑reperfusion injury.

Abstract: 

Artesunate is a semi-synthetic derivative of artemisinin that is used in the treatment of patients with malaria. Artesunate has also been reported to exert immune‑regulatory, antitumor, hepatoprotective, anti‑inflammatory and smooth muscle relaxing functions. The present study aimed to investigate the putative protective effects of artesunate against cerebral ischemia/reperfusion injury (CIRI), and to elucidate the molecular mechanisms underlying its effects. A CIRI mouse model was created via middle cerebral artery occlusion for 2 h, followed by 22 h of reperfusion. Mice were treated with 10‑40 mg/kg artesunate. The present results demonstrated that treatment with artesunate significantly reduced the cerebral infarct volume and potentiated the recovery of neurological function in CIRI mice. Oxidative stress and inflammation markers were revealed to be significantly downregulated following treatment with artesunate in CIRI mice. Furthermore, artesunate was demonstrated to activate nuclear factor erythroid 2‑related factor 2 (Nrf2), inhibit caspase‑3 activity, reduce the apoptosis regulator BAX/apoptosis regulator Bcl‑2 expression ratio and suppress the phosphorylation of the mitogen‑activated protein kinase (MAPK) p38 in CIRI mice. In conclusion, the present findings suggested that artesunate may exert protective effects against CIRI through the suppression of oxidative and inflammatory processes, via activating Nrf2 and downregulating ROS‑dependent p38 MAPK in mice.

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PMID: 

Am J Transl Res. 2019 ;11(5):3039-3047. Epub 2019 May 15. PMID: 31217873

Abstract Title: 

Effect of astaxanthin on apoptosis of rat renal tubular epithelial cells induced by iohexol.

Abstract: 

Contrast acute kidney injury refers to acute renal failure due to the application of contrast agents. Astaxanthin, as an antioxidant, can improve early acute kidney injury in severely burned rats. However, the mechanism of astaxanthin for renal protection is still unclear. In this study, the rat renal tubular epithelial cells (NRK-52E) were treated with iohexol, astaxanthin, astaxanthin plus nicotinamide and nicotinamide. Subsequently, the nuclear morphology was observed by fluorescence staining of DAPI DNA, the apoptosis was detected by flow cytometry, the mitochondrial membrane potential was detected by JC-1 and the SIRT1, P53, Bax, Bcl-2 protein expression level was detected by Western blotting. We found that astaxanthin can reduce nuclear pyknosis and nuclear deep staining, decrease the number of apoptotic cells, up-regulate the expression of proapoptotic proteins P53 and Bax and up-regulate the expression of anti-apoptotic protein Bcl-2 by increasing SIRT1 expression level, thereby exerting protective effects on renal tubular epithelial cells. At the same time, nicotinamide has the opposite effect on the NRK-52E compared with astaxanthin. These results indicated that astaxanthin may provide a new option for the prevention of contrast-induced acute kidney injury.

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So ancient a love affair exists between saffron and our species, that this plant can no longer reproduce without human help. No wonder it has been exquisitely designed to return the favor by lifting our spirits, even increasing our own desire to make love…

“Flowers always make people better, happier, and more helpful; they are sunshine, food and medicine for the soul.” ~ Luther Burbank

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PMID: 

Onco Targets Ther. 2019 ;12:5087-5096. Epub 2019 Jul 1. PMID: 31308688

Abstract Title: 

Dietary natural astaxanthin at an early stage inhibits-nitrosomethylbenzylamine-induced esophageal cancer oxidative stress and inflammation via downregulation of NFκB and COX2 in F344 rats.

Abstract: 

Esophageal cancer is a common malignant tumor that develops rapidly and has a poor prognosis clinically. Astaxanthin (AST) is a carotenoid pigment with strong antioxidant, anti-inflammation, and antitumor activities. However, little is known about the effects of astaxanthin in esophageal cancer. The present study aimed to investigate the protective effects and related mechanisms of natural astaxanthin against-nitrosomethylbenzylamine (NMBA)-induced esophageal cancer in rats.F344 rats were induced subcutaneously with NMBA dissolved in dimethyl sulfoxide (0.35 mg/kg body weight three times per week for 5 weeks). Rats were fed normal diets with or without 25 mg/kg/day AST at different stages. At different time points, levels of oxidative stress factors in serum and esophagus tissue were analyzed. Western blotting was performed to observe the expression of NFκB and COX2 in esophagus tissue.AST clearly reduced the incidence of visible tumors in esophageal cancer during the early-stage intervention group. Furthermore, when compared with the simple exposed group, AST significantly increased levels of GPx and SOD activity, decreased the activity level of malondialdehyde (all

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