PMID: 

Food Funct. 2019 Nov 1 ;10(11):7461-7475. Epub 2019 Oct 31. PMID: 31667483

Abstract Title: 

The effect of crocetin supplementation on markers of atherogenic risk in patients with coronary artery disease: a pilot, randomized, double-blind, placebo-controlled clinical trial.

Abstract: 

BACKGROUND AND PURPOSE: Molecular mechanisms of atherogenesis are considered to be emerging therapeutic targets for atherosclerosis prevention. Cell and animal studies have shown that crocetin can decelerate atherogenesis. However, the anti-atherogenic properties of crocetin in humans are still ambiguous.METHODS AND RESULTS: Fifty clinically diagnosed CAD patients were randomly divided into two parallel groups, crocetin and placebo, who received one capsule of crocetin (10 mg) and placebo per day, respectively, for two months. Serum circulating homocysteine (Hcy) [-1.09 (-1.64 to -0.54)μM, P = 0.001], heart-type fatty acid binding protein (h-FABP) [-2.07 (-2.72 to -1.43) ng mL, P = 0.001], intercellular adhesion molecule 1 [-14.92 (-21.92 to -7.92) ng mL, P = 0.001], vascular cell adhesion molecule 1 [-18.61 (-29.73 to -7.49) ng mL, P = 0.002], and monocyte chemoattractant protein 1 [-4.67 (-6.50 to -2.83) pg mL, P = 0.001] decreased significantly after the trial in the crocetin group, while high-density lipoprotein (HDL) significantly increased [+4.21 (0.68 to 7.73) mg mL, P = 0.021]. Also, systolic [-0.21 (-0.32 to -0.10) mmHg, P = 0.001] and diastolic [-0.20 (-0.34 to -0.07) mmHg, P = 0.004] blood pressures decreased significantly in the crocetin group. Nevertheless, clinically significant percentage changes were only observed in Hcy (-15.25± 3.15, μM), HDL (-10.70 ± 5.06, mg dL), and h-FABP (-21.10± 3.09, ng mL) in the crocetin group. Furthermore, the relative increase in the gene expressions of sirtuin1 and AMP-activated protein kinase and a decrease in the lectin-type oxidized LDL receptor 1 and nuclear factor-kappa B expression in isolated peripheral blood mononuclear cells in the crocetin group were significant at the end of the trial in comparison with the placebo.CONCLUSION: As the first human study, we showed the ability of crocetin to alter the expression of atherogenic genes and endothelial cell adhesion molecules in CAD patients. It appears that crocetin could be considered as a promising anti-atherogenic candidate for future studies.

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PMID: 

Mar Drugs. 2019 Nov 4 ;17(11). Epub 2019 Nov 4. PMID: 31690015

Abstract Title: 

Effects of Astaxanthin from Shrimp Shell on Oxidative Stress and Behavior in Animal Model of Alzheimer's Disease.

Abstract: 

This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp () shells on Wistar rats with Alzheimer's disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) Control, (2) sham operate, (3) negative control (vehicle) + Aβ, (4) ASX extract+Aβ, (5) commercial ASX + Aβ, (6) ASX powder + Aβ, (7) blank powder + Aβ, and (8) vitamin E + Aβ. All treatments were orally administrated for 30 days. At 14- and 29-days post injection, animals were observed in behavioral tests. On the 31st day, animals were sacrificed; the hippocampus and cortex were collected. Those two brain areas were then homogenized and stored for biochemical and histological analysis. The results showed that the Aβinfused group significantly reduced cognitive ability and increased memory loss, as assessed by the Morris water maze test, novel object recognition test, and novel object location test. Moreover, the Aβinfused group exhibited a deterioration of oxidative markers, including glutathione peroxidase enzymes (GPx), lipid peroxidation (MDA), products of protein oxidation, and superoxide anion in the cortex and the hippocampus. Meanwhile, ASX powder (10 mg/kg body weight) showed a significant reduction in cognitive and memory impairments and oxidative stress which is greater than ASX extract in the same dose of compound or vitamin E (100 mg/kg body weight). Our study indicates the beneficial properties of ASX in alleviation of cognitive functions and reducing neurodegeneration in Wistar rats induced by amyloid-β (1-42) peptides.

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PMID: 

Mol Med Rep. 2019 Nov ;20(5):4612-4622. Epub 2019 Oct 1. PMID: 31702040

Abstract Title: 

Astragaloside IV alleviates myocardial damage induced by type 2 diabetes via improving energy metabolism.

Abstract: 

The aim of the present study was to evaluate the protective effect and mechanism of Astragaloside IV (ASIV) on myocardial injury induced by type 2 diabetes, with a focus on energy metabolism. Blood glucose, the hemodynamic index, left ventricular weight/heart weight (LVW/HW), the left ventricular systolic pressure (LVSP), the left ventricular end diastolic pressure (LVEDP) and cell survivalrate were measured in streptozotocin‑induced diabetes model rats. Western blot analysis, PCR, hematoxylin‑eosin and TUNEL staining, flow cytometry and ELISA were used to detect: i) Cardiomyocyte damage indicators such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cytochrome c (Cyt C), caspase‑3, cleaved caspase‑3 and the apoptotic rate; ii) energy metabolism indicators such as ATP/AMP and ADP/AMP; and iii) energy metabolism associated pathway proteins such as peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC‑1α) and nuclear respiratory factor 1 (NRF1). The present demonstrated increased blood glucose, LVW/HW, LVSP, LVEDP and the cardiomyocyte damage indicators (ANP, BNP, Cyt C and caspase‑3), in the diabetic and high glucose‑treated groups, which were decreased by ASIV. The expression of NRF‑1 and PGC‑1α significantly changed in the model group and was markedly improved following ASIV treatment. Furthermore, the abnormal energy metabolism in the model group was reversed by ASIV. According to the results, ASIV can regulate energy metabolism by regulating the release of PGC‑1α and NRF1 to rescue the abnormal energy metabolism caused by diabetes mellitus, thus decreasing the myocardial damage caused by diabetic cardiomyopathy.

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PMID: 

Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):4172-4181. PMID: 31713440

Abstract Title: 

Astragaloside-IV protects H9C2(2-1) cardiomyocytes from high glucose-induced injury via miR-34a-mediated autophagy pathway.

Abstract: 

Diabetic cardiomyopathy (DCM) is an important cardiac disorder in patients with diabetes. High glucose (HG) levels lead to inflammation of cardiomyocytes, oxidative stress, and long-term activation of autophagy, resulting in myocardial fibrosis and remodelling. Astragaloside-IV (AS-IV) has a wide range of pharmacological effects. This study aimed to investigate the effects of AS-IV on injury induced by HG in rat cardiomyocytes (H9C2(2-1)) and the involvement of the miR-34a-mediated autophagy pathway. An AS-IV concentration of 100 μM was selected based on H9C2(2-1) cell viability using the cell counting kit-8 (CCK-8). We found that 33 mM HG induced a morphologic change in cells and caused excessive oxidative stress, whereas AS-IV inhibited lipid peroxidation and increased superoxide dismutase activity. In terms of mRNAexpression, HG increased miR-34a and inhibited Bcl2 and Sirt1, whereas AS-IV and miR-34a-inhibitor reversed the above effects. Further, LC3-GFP adenovirus infection and western blotting showed that HG increased autophagy, which was reversed synergistically by AS-IV and miR-34a-inhibitor. Bcl2 and pAKT/AKT protein expressions in the HG group was significantly lower than that in controls, but AS-IV and miR-34a-inhibitor antagonized the process. Thus, AS-IV inhibits HG-induced oxidative stress and autophagy and protects cardiomyocytes from injury via the miR-34a/Bcl2/(LC3II/LC3I) and pAKT/Bcl2/(LC3II/LC3I) pathways.

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PMID: 

J Ethnopharmacol. 2019 Nov 15:112404. Epub 2019 Nov 15. PMID: 31739105

Abstract Title: 

Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-β/Smads pathway.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. As one of the active ingredients of Astragalus membranaceus (Fisch.) Bunge, Astragaloside IV (ASG) has been showed the cardiac fibrosis inhibition via various mechanism, while no data suggest its action related to miRNAs regulation.AIM OF THE STUDY: The objective of this article is to investigate the inhibition effect of Astragaloside IV on cardiac fibrosis through the miR-135a-TRPM7-TGF-β/Smads pathway.MATERIALS AND METHODS: We used isoproterenol (ISO) to induce cardiac fibrosis in vivo and in vitro. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, and ASG (10 mg/kg/d) was given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 μM) and treated with ASG (10 μM) simultaneously for 24 h.RESULTS: The results showed that ASG treatment could significantly decrease the current and protein expression of TRPM7 which was proved as one target of miR-135a. The activation of TGF-β/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, we proved that there was a positive feedback between the activation of TGF-β/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis.CONCLUSIONS: All these findings suggested that ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-β/Smads pathway.

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PMID: 

J Agric Food Chem. 2019 Nov 11. Epub 2019 Nov 11. PMID: 31709793

Abstract Title: 

Studies on Protection of Astaxanthin from Oxidative Damage Induced by H2O2 in RAW264.7 Cells Based on 1H NMR Metabolomics.

Abstract: 

Astaxanthin (AST), a fat-soluble and non-vitamin A source of carotenoid which can quench reactive oxygen species and it has strong antioxidant, anti-inflammatory ability. Herein, we have used H2O2 to establish a model of oxidative damage to RAW 264.7 cells and cells treated with vitamin C as the positive control group. The changes in metabolome were examined using 1H NMR and the results demonstrated that H2O2 treatment, various metabolic pathways such as amino acid, glucose, and glycerolipid metabolism were downregulated which in turn affected citric acid cycle and energy status. AST could reverse downregulation of some of these metabolic pathways to a certain extent, and reduce cellular oxidative stress and death. The AST group differed from the vitamin C group in regulating D-glutamine, D-glutamic acid, pyruvate, and glycerolipid metabolism. The experimental results help to further understand the antioxidant effects of AST.

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PMID: 

J Clin Med. 2019 Nov 11 ;8(11). Epub 2019 Nov 11. PMID: 31718054

Abstract Title: 

The Effects of Postoperative Astaxanthin Administration on Nasal Mucosa Wound Healing.

Abstract: 

: .BACKGROUND: Wound healing of the nasal mucosa after endoscopic sinus surgery (ESS) is frequently complicated by scaring and consequently recurrences are encountered. Methods of optimizing results have been sought. In the present study we evaluated the effects of a powerful antioxidant, astaxanthin, on nasal mucosa healing after surgery, comparing it to the extensively studied properties of dexamethasone.MATERIALS AND METHODS: 63 Wistar rats were used. The nasal mucosa from one side was damaged employing the brushing method. They were randomly divided into three experimental groups, one treated with astaxanthin, the second treated with dexamethasone and the third one acted as the control and was given normal saline. The rats were killed on days 5, 14 and 28 following injury. We observed the temporal evolution of the wound healing process and quantified the results by assessing four parameters: the epithelial thickness index (ETI), the subepithelial thickness index (STI), the goblet cell count and the subepithelial fibrosis index (SFI).RESULTS: At 28 days, the ETI was significantly lower in the astaxanthin group (p

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PMID: 

Biomed Pharmacother. 2019 Nov 13 ;121:109629. Epub 2019 Nov 13. PMID: 31733573

Abstract Title: 

Maintenance of mitochondrial function by astaxanthin protects against bisphenol A-induced kidney toxicity in rats.

Abstract: 

Bisphenol A (BPA), a global environmental pollutant, has been reported to have the potential to induced organs toxicity. This study explored the potential benefits of astaxanthin (ATX), a natural antioxidant, against BPA toxicity in the kidney, and explored whether mitochondria are involved in this condition. Male Wistar rats were fed with a vehicle, BPA, BPA plus ATX, ATX and were evaluated after five weeks. ATX treatment significantly reversed BPA-induced changes in body weight, kidney/body weight, and renal function related markers. When treated simultaneously with ATX, the imbalance of the oxidative-antioxidant status caused by BPA was also alleviated. The high expression of BPA-induced pro-inflammatory cytokines were inhibited by ATX treatment. ATX treatment also lessened the effects of BPA-induced caspase-3, -8, -9 and -10 gene expression and enzyme activity. The benefits of ATX were associated with enhanced mitochondrial function, which led to increased mitochondrial-encoded gene expression, mitochondrial copy number, and increased mitochondrial respiratory chain complex enzyme activity. Our results demonstrate the efficacy of ATX in protecting BPA-induced kidney damage, in part by regulating oxidative imbalance and improving mitochondrial function. Collectively, these findings provide a new perspective for the rational use of ATX in the treatment of BPA-induced kidney disease.

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PMID: 

Int J Mol Sci. 2019 Oct 31 ;20(21). Epub 2019 Oct 31. PMID: 31683671

Abstract Title: 

Downregulated Expression of Virulence Factors Induced by Benzyl Isothiocyanate in: A Transcriptomic Analysis.

Abstract: 

() is a common foodborne pathogen that leads to various diseases; therefore, we urgently need to identify different means to control this harmful pathogen in food. In this study, we monitored the transcriptional changes ofby RNA-seq analysis to better understand the effect of benzyl isothiocyanate (BITC) on the virulence inhibition ofand determined the bacteriostatic effect of BITC at subinhibitory concentrations. Our results revealed that, compared with the control group (SAC), the BITC-treated experimental group (SAQ_BITC) had 708 differentially expressed genes (DEGs), of which 333 genes were downregulated and the capsular polysaccharide () was significantly downregulated. Furthermore, we screened five of the most virulent factors of, including the capsular polysaccharide biosynthesis protein (), capsular polysaccharide synthesis enzyme (), thermonuclease (), clumping factor (), and protein A (), and verified the accuracy of these significantly downregulated genes by qRT-PCR. At the same time, we used light microscopy, scanning electron microscopy (SEM) and inverted fluorescence microscopy (IFM) to observe changes in biofilm associated with theand. Therefore, these results will help to further study the basis of BITC for the antibacterial action of foodborne pathogenic bacteria.

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PMID: 

Int J Environ Res Public Health. 2019 Oct 25 ;16(21). Epub 2019 Oct 25. PMID: 31731436

Abstract Title: 

Environmental Pollution as a Risk Factor in Testicular Tumour Development: Focus on the Interaction between Bisphenol A and the Associated Immune Response.

Abstract: 

Bisphenol A (BPA) is an endocrine disruptor to which animals and humans are highly exposed. Many reports have established a relationship between BPA exposure and breast cancer incidence, especially during critical periods of development. However, its effects on the immune response in testicular tumour growth have not yet been described. Thus, we wanted to analyse the effect of perinatal BPA exposure in pregnant female mice and the immune response modulation and tumour growth in an intratesticular cancer model in offspring male mice. Pregnant female mice were exposed to a dose of 250 mg/kg/day/body weight of BPA in their drinking water. In adulthood, male offspring underwent intrascrotal inoculation with 4T1 cancer cells. On day 21 after inoculation, mice were euthanised, and serum was obtained to measure BPA levels using HPLC coupled to mass spectrometry. The percentages of immune cell populations in peripheral lymph nodes (PLN), the spleen and tumours were evaluated by flow cytometry. In addition, the tumour expression of IL-10, TNF-α and TGF-β was analysed by RT-PCR. Of note, we found detectable circulating levels of BPA in the offspring of mothers exposed to it while pregnant. Remarkably, BPA treatment promoted tumour growth by about 75% compared to mice coming from female mice that did not receive the compound. Perinatal exposure to BPA modulated the percentages of different immune cells in the spleen and PLN. In addition, the expression of inflammatory-related cytokines (IL-10 and TNF-α) in the tumours was significantly enhanced compared to control and vehicle groups. In conclusion, the perinatal BPA administrationin pregnant female mice modulated different cellular and molecular immune components that resulted in outstanding testicular tumour size in male offspring.