Apple phlorizin attenuates oxidative stress in Drosophila melanogaster.

PMID: 

J Food Biochem. 2019 Mar ;43(3):e12744. Epub 2018 Dec 13. PMID: 31353567

Abstract Title: 

Apple phlorizin attenuates oxidative stress in Drosophila melanogaster.

Abstract: 

Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span-prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age-related decline of locomotor function. This life span-extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate-cysteine ligase catalytic subunit, cap-n-collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti-aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. PRACTICAL APPLICATIONS: Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.

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Protective effect of apple phlorizin on hydrogen peroxide-induced cell damage in HepG2 cells.

PMID: 

J Food Biochem. 2019 Sep 12:e13052. Epub 2019 Sep 12. PMID: 31515822

Abstract Title: 

Protective effect of apple phlorizin on hydrogen peroxide-induced cell damage in HepG2 cells.

Abstract: 

Apple phlorizin has many biological activities, such as antioxidant and liver protection. The present study aimed to evaluate the roles of apple phlorizin against hydrogen peroxide (HO)-induced oxidative damage in HepG2 cells. In this study, treatment with apple phlorizin (100 and 150 μg/ml) decreased the production of reactive oxygen species and alleviated apoptosis as well as DNA damage in HO-induced HepG2 cells. These effects were associated with the increased activity of antioxidant enzymes, enhanced the ARE-driven phase II antioxidant gene expression and its upstream Nrf2 protein expression, and decreased apoptosis-related gene expression. However, the phase II antioxidant gene expression and Nrf2 protein expression upregulated by phlorizin were reversed by Nrf2 shRNA transfection. These results showed that phlorizin relieves oxidative stress, DNA damage, and apoptosis in HO-induced HepG2 cells, at least partially, by regulating the expression of Nrf2 protein and apoptosis-related genes. PRACTICAL APPLICATIONS: Apple phlorizin is a polyphenol compound extracted from apple or apple juice. This report highlighted a protective effect of phlorizin on antioxidant stress, DNA damage, and apoptosis in HO-induced HepG2 cells. These results suggested that phlorizin may be developed for functional foods.

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Fenugreek seed extract ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

PMID: 

J Basic Clin Physiol Pharmacol. 2019 Jul 20 ;30(4). Epub 2019 Jul 20. PMID: 31326961

Abstract Title: 

Fenugreek seed extract ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

Abstract: 

Background Natural medicinal plants have been the focus of current research for developing neuroprotective agents to be used in the diabetes-linked cognitive dysfunction. Trigonella foenum-graecum seeds (known as fenugreek, methi in Hindi), is a well-known traditional medicinal herb and possesses anti-diabetic, anti-oxidant, and anti-inflammatory properties. Purpose This study was undertaken to explore the ameliorative effects of T. foenum-graecum seed extract on diabetes-induced cognitive dysfunction. Methods Experimental diabetes was induced by administering a single dose of streptozotocin (60 mg/kg) through intraperitoneal dose. Cognitive function was assessed using a T-maze and the Morris water maze. Lipid peroxidation levels and oxidative stress in the hippocampus was measured. Quantification of hippocampal CA1 and CA3 regions was done using cresyl violet stain. Results Diabetic rats demonstrated learning and memory impairment, which was evident from poor performance in behavioral tasks, i.e. T-maze and Morris water maze tasks. Learning and memory impairment in diabetic animals is associated with increased blood glucose levels, increased oxidative stress in the hippocampus and decreased number of neurons in the CA1 and CA3 regions of the hippocampus. The diabetic rats administered with T. foenum-graecum showed improved performance in behavioral tasks, and these changes were associated with decreased blood glucose levels, decreased oxidative stress in the hippocampus, and decreased neuronal loss from the CA1 and CA3 regions of the hippocampus. Conclusion In conclusion, administration of T. foenum-graecum seed extract ameliorates diabetes-linked cognitive dysfunction in rats by decreasing blood glucose levels, reducing lipid peroxidation and oxidative stress in the hippocampus, and preventing neuronal loss from the hippocampus.

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Dose-dependent effects of fenugreek seed extract on the biochemical and haematological parameters in high-fat diet-fed rats.

PMID: 

J Taibah Univ Med Sci. 2019 Aug ;14(4):383-389. Epub 2019 Jul 17. PMID: 31488972

Abstract Title: 

Dose-dependent effects of fenugreek seed extract on the biochemical and haematological parameters in high-fat diet-fed rats.

Abstract: 

Objective: The present study was carried out to assess the effects of fenugreek seed extract on various biochemical and haematological parameters in high-fat diet (HFD)-fed rats.Methods: Female Wistar rats were allocated into five groups (n = 6): 1) control rats, 2) HFD-fed control rats 3) rats fed with HFD and fenugreek (FG) seed extract at doses of 200 mg/kg/day, 300 mg/kg/day, and 400 mg/kg/day for 12 weeks. Blood was collected to examine the biochemical and haematological parameters using a veterinary blood cell counter; blood indices such as MCV, MCH, MCHC, red blood cell distribution width, haemoglobin (Hb) levels, haematocrit, and platelet counts were measured. Blood samples were centrifuged at 3000 rpm for 10 min at room temperature to obtain serum for the estimation of lipid profiles, and aspartate transaminase and alanine transaminase levels.Results: Rats fed with FG at a dose of 400 mg/kg/day showed a significant increase in the red blood cell count, Hb levels, haematocrit, and MCV, and a significant decrease in the lymphocyte count. The total cholesterol, triglyceride, and low-density lipoprotein levels increased significantly ( 

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Attenuation of diabetic nephropathy by dietary fenugreek and onion.

PMID: 

Nutrition. 2019 Jul 1 ;67-68:110543. Epub 2019 Jul 1. PMID: 31408826

Abstract Title: 

Attenuation of diabetic nephropathy by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) via suppression of glucose transporters and renin-angiotensin system.

Abstract: 

OBJECTIVES: The aim of this study was to determine the effects of dietary fenugreek (Trigonella foenum-graecum) seeds and onion on the hyperglycemia-stimulated glucose transporters and activation of renin-angiotensin system-mediated cascade of events leading to renal lesions in diabetic animals.METHODS: The mechanistic aspects of nephroprotective influence of dietary fenugreek seeds (10%) and onion (3%) on diabetic renal lesions was investigated in streptozotocin diabetic rats. Renal damage was assessed by measuring proteinuria, enzymuria, expression of glucose transporters, renin-angiotensin system, and activities of polyol pathway enzymes.RESULTS: Diabetes resulted in an upregulation of glucose transporters in kidney tissue, which was countered by these dietary interventions. The upregulation of renal angiotensin-converting enzyme and its receptor was also countered by these dietary interventions. Dietary fenugreek and onion significantly reduced metabolites of polyol pathway, nitric oxide, and N-acetyl-β-d-glucosaminidase activity. Markers of podocyte damage in kidney (nephrin, podocin, and podocalyxin) and their urinary excretion were normalized along with downregulation of the expression of kidney injury molecule-1 by these dietary interventions. Dietary fenugreek and onion effectively countered the diabetes-induced structural abnormalities of renal tissue.CONCLUSION: Feeding fiber-rich fenugreek seeds and sulfur compounds-rich onion produced a blockade in glucose translocation and renin-angiotensin system in the early stage of diabetic nephropathy. This involved a downregulation of the expression of polyol pathway enzymes, partial restoration of the podocyte damage, revival of renal architecture and functional abnormality. The present study also suggested that these two dietary interventions offer a higher renoprotective influence when consumed together.

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Allium vegetables for possible future of cancer treatment.

PMID: 

Phytother Res. 2019 Aug 29. Epub 2019 Aug 29. PMID: 31464060

Abstract Title: 

Allium vegetables for possible future of cancer treatment.

Abstract: 

Natural resources such as plants are an upright curing option in treating cancers and reducing the side effects of current therapeutic modalities. Allium genus vegetables are of the most interesting herbs in restricting cancers that includes garlic, onions, leeks, chives, and shallots. These plants have been exploited in folk medicine because of their beneficial health effects in improving numerous diseases. The phytochemical analysis of various Allium genus members showed that, to date, 16 species have proved potential anticancer properties due to the accumulation of various sulfur and organic compounds like S-allyl mercaptocysteine, quercetin, flavonoids, and ajoene. These compounds with various mechanisms such as hindering cell cycle, inhibiting signaling pathways, inducing apoptosis, and antioxidant activity interfere with diverse stages of formation, growth, differentiation, and metastasis of cancer cells. Similar to garlic and onion, other species have exhibited anticancer activities, so that active natural molecules extracted from them might serve as possible anticancer agents. Therefore, evaluating the main ingredients and studying their anticancer mechanisms are of great importance. In this review, we aim to summarize the available data on anticancer mechanisms of 16 species of Allium genus and their major compounds to assist further researches on the treatment and prevention of cancers.

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Tulsi has the potential to be developed into an antimicrobial agent against cariogenic bacteria, specifically S. mutans.

PMID: 

J Indian Soc Pedod Prev Dent. 2019 Jan-Mar;37(1):87-91. PMID: 30804313

Abstract Title: 

Estimation of salivary pH and viability ofon chewing of Tulsi leaves in children.

Abstract: 

Background: The current concepts of dental caries focus on cariogenic bacteria such as Streptococcus mutans fermenting carbohydrates to form organic acids, which cause a drop in pH, resulting in demineralization of the tooth surface.Studies show that Tulsi has broad-spectrum antimicrobial activity.Hence, this study aimed at estimating the change in salivary pH and viability of S. mutans on chewing of Tulsi leaves, in children.Aims: This study aimed to estimate the change in salivary pH and viability of S. mutans on chewing of Tulsi leaves.Materials and Methods: The study was carried out on thirty children aged 9-12 years. Oral prophylaxis was performed prior to sample collection. Three samples were collected per child, one before and two after chewing of Tulsi leaves. The change in salivary pH and viability of S. mutans was assessed.Statistical Analysis: The obtained data were analyzed using Friedman test and Wilcoxon's test. The level of significance was set at P

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These results are the first to highlight the beneficial role and relevant mechanisms of Isoliquiritigenin in LPS-induced acute lung injury.

PMID: 

Front Immunol. 2017 ;8:1518. Epub 2017 Nov 9. PMID: 29163554

Abstract Title: 

Isoliquiritigenin Activates Nuclear Factor Erythroid-2 Related Factor 2 to Suppress the NOD-Like Receptor Protein 3 Inflammasome and Inhibits the NF-κB Pathway in Macrophages and in Acute Lung Injury.

Abstract: 

Among the cellular response mechanisms, the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway is considered a survival pathway that alleviates oxidative injury, while both the NOD-like receptor protein 3 (NLRP3) and NF-κB pathways are pro-inflammatory pathways that cause damage to cells. These pathways are implicated in the development and resolution of acute lung injury (ALI). Isoliquiritigenin (ISL), a flavonoid from the liquorice compound, is suggested to be a regulator of the above pathways, but the mechanisms of how the NLRP3/NF-κB pathway interacts with Nrf2 and its protective effects in ALI remain unknown. In the present study, ISL inhibited reactive oxygen species (ROS) generation and cytotoxicity induced by t-BHP and pro-inflammatory enzymes production induced by LPS in RAW 264.7 cells. Such cytoprotective effects coincided with the induction of AMP-activated protein kinase (AMPK)/Nrf2/antioxidant response element (ARE) signaling and the suppression of the NLRP3 and NF-κB pathways. Consistent with these findings, ISL treatment significantly alleviated lung injury in LPS-induced ALI mice, which was reflected by reductions in histopathological changes, pulmonary edema, and protein leakage. At the same time, the increased levels of inflammatory cell exudation and pro-inflammatory mediators, the enhanced production of ROS, myeloperoxidase, and malondialdehyde, and the depleted expressionof GSH and superoxide dismutase induced by LPS were ameliorated by ISL. Furthermore, ISL notably activated AMPK/Nrf2/ARE signaling and inhibited LPS-induced NLRP3 and NF-κB activation in the lung. Moreover, although inhibition of the LPS-induced histopathological changes and ROS production were attenuated in Nrf2-deficient mice, the repression of the NLRP3 and NF-κB pathways by ISL was Nrf2-dependent and Nrf2-independent, respectively. In conclusion, our results are the first to highlight the beneficial role and relevant mechanisms of ISL in LPS-induced ALI and provide novel insight into itsapplication.

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Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

PMID: 

Biochem Biophys Res Commun. 2018 02 5 ;496(2):245-252. Epub 2017 Nov 24. PMID: 29180018

Abstract Title: 

Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

Abstract: 

Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries.

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Isoliquiritigenin inhibits the proliferation and induces the differentiation of human glioma stem cells.

PMID: 

Oncol Rep. 2018 Feb ;39(2):687-694. Epub 2017 Dec 13. PMID: 29251326

Abstract Title: 

Isoliquiritigenin inhibits the proliferation and induces the differentiation of human glioma stem cells.

Abstract: 

Glioma stem cells (GSCs) have been proven to be resistant to various therapeutic strategies, such as temozolomide chemotherapy and radiotherapy, leading to glioma recurrence. Isoliquiritigenin (ISL), a menber of the flavonoids isolated from liquorice has been found to be a potent stimulator of cell differentiation and has potential application for treating various types of cancer including human brain glioma. However, the antitumor activity of ISL on GSCs and the signaling pathway underlying its therapeutic effects are poorly understood. In the present study, GSCs were isolated from SHG44 human glioma cells by serum-free culture and treated with ISL or DAPT (a Notch/γ-secretase inhibitor). It was found that ISL dose-dependently inhibited GSC growth after 72 h of treatment and decreased the formation of tumor spheres. Meanwhile, GSCs differentiated into astrocytes and neurons. Furthermore, these therapeutic effects were accompanied by downregulation of Notch1 and Hes1 at the protein and mRNA levels. Taken together, our results demonstrated that ISL exhibits antitumor effects on GSCs by inhibiting proliferation and inducing differentiation. The therapeutic effect may be related to downregulation of the Notch1 signaling pathway. Application of ISL presents potential benefits for the treatment of human brain glioma.

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