PMID: 

Nanomedicine (Lond). 2019 09 ;14(17):2355-2371. Epub 2019 Aug 15. PMID: 31414606

Abstract Title: 

Therapeutic efficacy ofcoated iron oxide nanoparticles in A549 lung cancer cell line.

Abstract: 

Present work was undertaken to fabricate iron oxide nanoparticles (IONPs) using a green approach for increased therapeutic efficacy.Two types of IONPs were synthesized, one without any coating (IONP) and other coated with(Amla) fruit extract (IONP). Both the IONPs were characterized using different techniques and therapeutic efficacy was evaluated in A549 human lung cancer cell line.IONPwere smaller in size with better dispersibility compared with IONP. They induced increased reactive oxygen species production, higher DNA damage and apoptosis, which resulted in increased toxicity to cancer cells in comparison to IONP.Higher uptake of IONPand active components coating the surface, may be responsible for the increased therapeutic efficacy in cancer cells.

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PMID: 

J Alzheimers Dis. 2020 Feb 17. Epub 2020 Feb 17. PMID: 32083581

Abstract Title: 

Amla Therapy as a Potential Modulator of Alzheimer's Disease Risk Factors and Physiological Change.

Abstract: 

 There is currently no effective treatment for Alzheimer's disease (AD), the most common form of dementia. It has been proposed, however, that a modest delay in onset can significantly reduce the number of cases. Thus, prevention and intervention strategies are currently the focus of much research.In the search for compounds that potentially confer benefit, the Amla fruit and its extracts have drawn attention. Amla preparations have been used for centuries in traditional Indian medicine systems such as Ayurveda, with various parts of the plant used to treat a variety of diseases. Here we review many animal-based studies, and some clinical trials, which have shown that Amla, and its extracts, exert many positive effects on dyslipidemia, hyperglycemia, inflammation, oxidative stress, apoptosis, and autophagy, that contribute to AD risk. Collectively, this evidence suggests that Amla maybe of value as part of an effective disease-delaying treatment for AD.

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PMID: 

Eur J Pharmacol. 2020 Feb 25:173031. Epub 2020 Feb 25. PMID: 32109457

Abstract Title: 

Combined effects of berberine and evodiamine on colorectal cancer cells and cardiomyocytes in vitro.

Abstract: 

Chemotherapy induces inevitable adverse effects, while complementary and alternative medicine employs many chemical substances. Herb pairs normally contain two herbal medicines, and they have satisfactory effects on cancer therapy. Zuojinwan, a well-known herb pair, is composed of Coptidis Rhizoma and Euodiae Fructus. Berberine and evodiamine are considered the most important compounds in the Zuojinwan herb pair. Previous reports have shown that combined use of evodiamine and berberine displays synergistic anticancer activities in various types of cancers, but this combination has not been tested in colorectal cancer. Hence, this study aimed to explore the combined effects of evodiamine and berberine on colorectal cancer cell lines and cardiomyocytes. We found that the combination of berberine and evodiamine showed synergistic anticancer activity in P-glycoprotein (P-gp)-positive colorectal cancer cells through attenuating the overexpression of P-gp mRNA independent of cell cycle arrest and cell apoptosis. However, berberine did not increase the cytotoxicity of evodiamine in normal human colon mucosal epithelial cells. Furthermore, berberine attenuated evodiamine-induced cardiotoxicity by regulating extrinsic apoptosis via nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent and reactive oxygen species-independent pathways. Therefore, we suggest that the combination of berberine and evodiamine displays high anticancer activity while reducing the side effects in specific cell lines.

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J Diabetes Res. 2020 ;2020:9481720. Epub 2020 Jan 31. PMID: 32076626

Abstract Title: 

Mangiferin Alleviates Renal Interstitial Fibrosis in Streptozotocin-Induced Diabetic Mice through Regulating the PTEN/PI3K/Akt Signaling Pathway.

Abstract: 

Renal interstitial fibrosis is considered to be the typical manifestation of diabetic nephropathy (DN). Mangiferin has shown positive effect on the prevention or treatment of diabetes and its complications. The aim of this study was to explore the inhibitive effect and mechanism of mangiferin on renal interstitial fibrosis in diabetic mice. Streptozotocin- (STZ-) induced diabetic mice were treated with mangiferin (15, 30, and 60 mg/kg/d) for 4 weeks. The morphology of kidneys was observed by Masson's trichrome staining, and the biochemical parameters (fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), serum creatinine (SCr), and urine protein) were determined by kits. In addition, the levels of inflammatory cytokines (tumor necrosis factor-(TNF-), interleukin- (IL-) 6, and IL-1), antioxidant enzymes (SOD, CAT, and GSH-Px), MDA, and ROS were assessed. Furthermore, the expressions of fibronectin (FN), collagen I (Col I), and-SMA were measured by immunohistochemistry. Regulations of TGF-1 and the PTEN/PI3K/Akt pathway were detected by Western blotting. Treatment with mangiferin significantly ameliorated renal dysfunction in diabetic mice, as evidenced by the increase in body weight and decreases in FBG, TG, TC, BUN, SCr, urine protein, and the kidney to body weight ratio (KW/BW). Furthermore, mangiferin treatment prevented renal interstitial fibrosis evidenced by decreases in the positive expression of FN, Col I, and-SMA, in comparison with morphological changes in the renal tissue. Meanwhile, mangiferin increased antioxidant enzymes, reduced the TNF-, IL-6, and IL-1, as well as MDA and ROS. Additionally, mangiferin administration also downregulated TGF-1, upregulated PTEN, and decreased the phosphorylation of both PI3K and Akt. These findings demonstrate that mangiferin may reduce inflammation and oxidative stress in DN, thereby inhibiting the renal interstitial fibrosis by reducing the TGF-1-mediated elevation of Col I, FN, and-SMA through the PTEN/PI3K/Akt pathway.

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PMID: 

Acta Biochim Biophys Sin (Shanghai). 2015 Aug ;47(8):604-11. Epub 2015 Jun 1. PMID: 26033789

Abstract Title: 

Effect of diosmetin on airway remodeling in a murine model of chronic asthma.

Abstract: 

Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. The anti-oxidant flavone aglycone diosmetin ameliorates the inflammation in pancreatitis, but little is known about its impact on asthma. In this study, the effects of diosmetin on chronic asthma were investigated with an emphasis on the modulation of airway remodeling in BALB/c mice challenged with ovalbumin (OVA). It was found that diosmetin significantly relieved inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in the lungs of asthmatic mice and notably reduced AHR in these animals. The OVA-induced increases in total cell and eosinophil counts in bronchoalveolar lavage fluid were reversed, and the level of OVA-specific immunoglobulin E in serum was attenuated by diosmetin administration, implying an anti-Th2 activity of diosmetin. Furthermore, diosmetin remarkably suppressed the expression of smooth muscle actin alpha chain, indicating a potent anti-proliferative effect of diosmetin on airway smooth muscle cells (ASMCs). Matrix metallopeptidase-9, transforming growth factor-β1, and vascular endothelial growth factor levels were also alleviated by diosmetin, suggesting that the remission of airway remodeling might be attributed to the decline of these proteins. Taken together, our findings provided a novel profile of diosmetin with anti-remodeling therapeutic benefits,highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma.

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PMID: 

Antonie Van Leeuwenhoek. 2015 Aug ;108(2):383-9. Epub 2015 May 29. PMID: 26021482

Abstract Title: 

Diosmetin inhibits the expression of alpha-hemolysin in Staphylococcus aureus.

Abstract: 

Staphylococcus aureus is a significant human pathogen that causes a wide range of diseases. Alpha-hemolysin (Hla), a pore-forming cytotoxin that is produced by most S. aureus strains, can cause tissue injury and plays a critical role in the virulence of this pathogen. In the present study, we discovered that diosmetin, a natural flavonoid that occurs primarily in citrus fruits and exhibits little anti-S. aureus activity, could diminish the production of Hla in culture supernatants in a concentration-dependent manner. The analysis of cytotoxicity in the co-culture system of S. aureus and A549 epithelial cells showed that such inhibition confers significant protection against S. aureus-mediated injury. Our results suggested that diosmetin has the potential to be a new anti-virulence drug for S. aureus infection, particularly for the targeting of Hla.

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PMID: 

Mol Med Rep. 2016 Mar ;13(3):2401-8. Epub 2016 Feb 5. PMID: 26847170

Abstract Title: 

Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP-2 and MMP-9.

Abstract: 

Hepatocellular carcinoma (HCC) is one of the most malignant types of tumor worldwide with a high rate of mortality. Diosmetin (DIOS) exhibits various activities, including anticancer activities. However, the role of DIOS in the metastasis of HCC, and its underlying molecular mechanism, remain to be fully elucidated. In the present study, the antimetastatic effects of DIOS were investigated in SK‑HEP‑1 and MHcc97H HCC cell lines. Cell proliferation, wound healing, motility, invasion and adhesion capacities were examined to evaluate the inhibitory effect of DIOS on the metastasis of HCC cells. Cell viability was detected using an MTT assay in order to verify the inhibitory effect of DIOSon the proliferation of HCC cells. Cell migration was assessed using would healing and motility assays in order to verify the inhibitory effect of DIOS on the migration of HCC cells. Cell invasion and adhesion assays were performed in order to verify the inhibitory effect of DIOS on the invasion and adhesion of HCC cells. Matrix metalloproteinase (MMP)‑2/9, proteins of the mitogen‑activated protein kinase (MAPK) pathway (c‑Jun N‑terminal kinase, extracellular signal‑regulated kinase and p38 MAPK) and protein kinase C‑δ were detected in order to verify the potential molecular mechanisms of DIOS in the inhibition of the metastasis of HCC cells. DIOS was observed to inhibit the metastasis of SK‑HEP‑1 and MHcc97H cells by downregulating the expression of MMP‑2/9 via the PKC/MAPK/MMP pathways. DIOS also inhibited the migration and invasion of the HCC cells, and may serve as a potential candidate agent for the prevention of HCC metastasis.

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PMID: 

Oncol Lett. 2016 Dec ;12(6):4385-4392. Epub 2016 Oct 19. PMID: 28101201

Abstract Title: 

Diosmetin inhibits cell proliferation and induces apoptosis by regulating autophagy via the mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells.

Abstract: 

Hepatocellular carcinoma (HCC), which is a type of malignant tumor, is the fifth most common cancer in men and ninth in women worldwide. The aim of the present study was to investigate the antitumor effect of diosmetin (DIOS) in hepatocellular carcinoma HepG2 cells. The proliferation, apoptosis and autophagy rates of HepG2 cells were measured following treatment with DIOS. The effects of DIOS treatment on HepG2 cell proliferation and apoptosis rates were analyzed using MTT assays and Annexin V staining, respectively. The effect of DIOS treatment on autophagy levels was assessed using transmission electron microscopy, green fluorescent protein (GFP)-microtubule-associated protein 1 light chain (LC3) transfection and LysoTracker Red staining. Furthermore, bafilomycin A1 (BA1), an autophagy inhibitor, was used to assess the association between DIOS and cell autophagy, proliferation and apoptosis. In addition, the expression of autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase, P70S6K, phosphoinositide-dependent kinase-1, extracellular signal-regulated kinase, 5'-AMP-activated protein kinase and Akt] and apoptosis-related proteins [B-cell lymphoma (Bcl)-2-associated X protein, Bak, p53, Bcl-2 and caspase-3] were analyzed by western blotting. The results revealed that DIOS significantly inhibited proliferation (P

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PMID: 

Vet Immunol Immunopathol. 2019 Jan ;207:62-68. Epub 2018 Dec 13. PMID: 30593352

Abstract Title: 

Dietary selenium supplementation enhances antiviral immunity in chickens challenged with low pathogenic avian influenza virus subtype H9N2.

Abstract: 

Selenium supplementation in poultry feeds has been known to have beneficial effects on the bird health and performance; however antiviral effects of selenium have remained largely unknown. In this study, we have evaluated the effects of supplementation of chicken diets with organic (Selenium Enriched Yeast; SEY) and inorganic selenium (Sodium Selenite; SS) on low pathogenicity avian influenza virus (H9N2) shedding in the cloacal and oropharyngeal swab samples as well as examined the expression of immune related genes. Chickens were fed two doses (High- 0.30 mg/kg of feed; Low- 0.15 mg/kg of feed) of selenium supplementation for 2 weeks followed by low pathogenicity avian influenza virus challenge. Our results showed that the cloacal shedding of virus in all the selenium supplemented groups was significantly lower when compared to the non-supplemented control groups. In addition, the oropharyngeal shedding of virus in chickens fed with organic selenium supplementation was significantly lower than that in the chickens that received either inorganic selenium supplemented feed or controls. Furthermore, the expression of interferon stimulated genes (Viperin, OAS: 2'-5' oligoadenylate synthetase and MDA5: melanoma differentiation-associated gene) in the cecal tonsils was significantly elevated in the selenium treated groups when compared to controls. Additionally, a significantly higher transcription of interferon (IFN)-α, IFN-β and IFN-γgenes in the cecal tonsils and spleens of chickens receiving SEY-L and SS-H supplemented feed was also observed at post virus challenge time points compared to untreated controls. The results of this study demonstrated that supplementation of chicken diets with selenium, can enhance antiviral defense and thus, may have a beneficial effect in controlling viral infections in poultry.

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PMID: 

Adv Nutr. 2015 Jan ;6(1):73-82. Epub 2015 Jan 15. PMID: 25593145

Abstract Title: 

Dietary selenium in adjuvant therapy of viral and bacterial infections.

Abstract: 

Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions.

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