PMID: 

J Agric Food Chem. 2020 Jan 12. Epub 2020 Jan 12. PMID: 31927917

Abstract Title: 

Pterostilbene Improves Hepatic Lipid Accumulation via the MiR-34a/Sirt1/SREBP-1 Pathway in Fructose-Fed Rats.

Abstract: 

High fructose intake promotes hepatic lipid accumulation. Pterostilbene, a natural analogue of resveratrol enriched in diet berries, exhibits hepatoprotective property. Here, we studied the protection by pterostilbene against fructose-induced hepatic lipid accumulation, and explored its possible mechanism. We observed high-expression of microRNA-34a (miR-34a, P

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PMID: 

Proc Natl Acad Sci U S A. 2020 Jan 7. Epub 2020 Jan 7. PMID: 31911474

Abstract Title: 

High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model.

Abstract: 

Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma coculture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intratumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intratumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intratumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and natural killer cells), and interleukin 12 production by antigen-presenting cells compared with single-agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.

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PMID: 

Environ Sci Pollut Res Int. 2019 Dec 10. Epub 2019 Dec 10. PMID: 31823260

Abstract Title: 

Red beetroot extract mitigates chlorpyrifos-induced reprotoxicity associated with oxidative stress, inflammation, and apoptosis in rats.

Abstract: 

The goal of our investigation is to evaluate the potential protective efficacy of red beetroot extract (RBR) against testicular toxicity produced by CPF in rats. CPF exposure decreased the weight of testis and the levels of luteinizing hormone, follicle stimulating hormone and testosterone. CPF impaired also the oxidative status in favor of pro-oxidant molecules in the testicular tissue. Additionally, CPF stimulated the production of pro-inflammatory cytokines and their gene expression. Concomitantly, an apoptotic cascade has been observed upon CPF intoxication. However, RBR administration protected the testis tissue through modulating the hormonal level, inhibiting the oxidative damage, inflammation and the apoptotic responses following CPF intoxication. The obtained data recommend the use of RBR to prevent CPF-induced testicular damage via antioxidant, anti-inflammatory, and anti-apoptotic pathways.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:3595761. Epub 2019 Nov 22. PMID: 31885644

Abstract Title: 

Nephroprotective Role ofL. Root Extract against Chlorpyrifos-Induced Renal Injury in Rats.

Abstract: 

Organophosphorus pesticides (OPs) are widely used for agricultural and housekeeping purposes. Exposure to OPs is associated with the progression of several health issues. Antioxidant agents may be powerful candidates to minimise adverse reactions caused by OPs. The aim of the present study was to evaluate the nephroprotective effects of red beetroot extract (RBR) against chlorpyrifos- (CPF-) induced renal impairments. CPF induced kidney dysfunction, as demonstrated by changes in serum creatinine and urea levels. Moreover, CPF exposure induced oxidative stress in the kidneys as determined by increased malondialdehyde and nitric oxide levels, decreased glutathione content, decreased catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, and decreased nuclear factor (erythroid-derived 2)-like-2 factor expression. In addition, CPF induced inflammation in renal tissue as evidenced by increased release of tumor necrosis factor-alpha and interleukin-1and upregulation of inducible nitric oxide synthase. Furthermore, CPF promoted cell death as demonstrated by decreased Bcl-2 and increased Bax and caspase-3 levels. Treatment with RBR one hour prior to CPF treatment blocked the effects observed in response to CPF alone. Our results suggest that RBR could be used to alleviate CPF-induced nephrotoxicity through antioxidant, anti-inflammatory, and antiapoptotic activities.

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PMID: 

J Strength Cond Res. 2020 Jan 6. Epub 2020 Jan 6. PMID: 31913252

Abstract Title: 

Effect of Acute Beetroot Juice Supplementation on Bench Press Power, Velocity, and Repetition Volume.

Abstract: 

Williams, TD, Martin, MP, Mintz, JA, Rogers, RR, and Ballmann, CG. Effect of acute beetroot juice supplementation on bench press power, velocity, and repetition volume. J Strength Cond Res XX(X): 000-000, 2019-The purpose of this study was to examine the effects of acute beetroot juice (BRJ) supplementation on power, velocity, and repetitions to failure (RTF) during bench press exercise. Resistance-trained male subjects (n = 11) were recruited for this study. Using a double-blinded, counterbalanced, crossover study design, subjects were supplemented with either 70 ml of BRJ or placebo (PL; black currant juice) 2 hours before exercise. During each exercise trial, subjects began by completing 2 sets× 2 repetitions of bench press at 70% 1 repetition maximum (1RM) with maximum explosive intent. Barbell velocity and power were measured using a linear position transducer. Subjects then completed 3 sets × RTF at 70% 1RM separated by 2 minutes of rest between each set. Maximum mean power, velocity, and repetitions were analyzed. Mean velocity (p = 0.011; effect size [ES] = 0.54) and mean power (p = 0.015; ES = 0.51) were significantly higher with BRJ when compared with PL. Total RTF (p = 0.002; ES = 0.46) was higher during the BRJ condition vs. PL. Results indicate that acute BRJ supplementation positively impacts velocity, power, and total repetitions during free-weight bench press exercise.

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PMID: 

Nutr Metab (Lond). 2020 ;17:3. Epub 2020 Jan 7. PMID: 31921325

Abstract Title: 

Functional properties of beetroot () in management of cardio-metabolic diseases.

Abstract: 

Red beetroot (), as a naturally occurring root vegetable and a rich source of phytochemicals and bioactive compounds, is known for its beneficial roles in the improvement of several clinical and pathologic outcome. Chronic and acute beetroot juice supplementation, as a cost-effective strategy, is proposed to hold promises in controlling diabetes and insulin hemostasis, blood pressure and vascular function, renal health and the possible effect on microbiome abundance. The secondary outcome and physiological response of microbiome abundance modulation included the non- significant fluctuation of systolic and diastolic blood pressures. Also, some studies have suggested a reno-protective property of beetroot juice that is associated with the reduction of mortality rate and favorable changes in kidney's functional parameters among patients with renal disorders. Similarly, it is shown that the persistent consumption of beetroot juice effectively postpones the postprandial glycemic response and decreases the blood glucose peak. The significant blood pressure lowering effect has been seen among normotensive subjects, which tend to be more considerable among hypertensive individuals and progressive among overweight adults. Within this context, this review aims to provide a comprehensive overview on the therapeutic applications of beetroot juice in metabolic disorders and theirs underlying mechanisms. Despite the inconsistencies in the set of results from the reviewed studies, there is no doubt that further contributing factors must be investigated more deeply in future studies.

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PMID: 

Neurochem Res. 2019 Dec 19. Epub 2019 Dec 19. PMID: 31858376

Abstract Title: 

Betanin Attenuates Oxidative Stress Induced by 6-OHDA in PC12 Cells via SAPK/JNK and PI3 K Pathways.

Abstract: 

Parkinson's disease is a neurodegenerative disorder which accompanied with cognitive decline, chorei form moves and behavioral difficulties. Oxidative stress which promote the apoptotic cell death are responsible for neurodegeneration in Parkinson. The purpose of this study is to evaluate the protective effects of betanin against toxicity and oxidative damage induced by 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (HO) in PC12 cells as an appropriate model of Parkinson's cell damage. PC12 cells pretreated with betanin (1-200µM) for 24 h, and exposed to either 6-OHDA (100 µM) or HO(150µM) for 24 h. Cell survival and intracellular reactive oxygen species (ROS) production analyzed by resazurin and DCF-DA assay. The anti-apoptotic effects of betanin in PC12 cells were studied using flow cytometry of PI stained cells. Also, western blot analysis of survivin, Cyt c, Phospho SAPK/JNK,SAPK/JNK, Phospho-PI3 kinase P85, PI3 kinase P85 was performed for detection of apoptosis. Betanin (1-200 µM) significantly decreased the 6-OHDA and HOcytotoxicity also attenuated the ROS level. Cell apoptosis significantly increased after 6-OHDA (100µM) treatment, compared to the control. However, pretreatment with betanin (20 and 50 µM), protected against apoptosis. Western blot analysis of PC12 cells showed that 100 µM 6-OHDA could increase the proteins involved in apoptosis signaling and betanin (20 and 50 µM), could decrease the apoptosis. The results show that betanin has antioxidant and anti-apoptotic effects and may have the ability to prevent or delay the progress of neural death in Parkinson's disease.

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PMID: 

Acta Biochim Biophys Sin (Shanghai). 2020 Jan 8. Epub 2020 Jan 8. PMID: 31915810

Abstract Title: 

Betulinic acid induces apoptosis of gallbladder cancer cells via repressing SCD1.

Abstract: 

Gallbladder cancer (GBC) is the most common and aggressive malignancy of the biliary tract. Betulinic acid (BetA) has been reported to have anti-inflammatory and antitumor effects; however, the effect of BetA on GBC is still unknown. In this study, we investigated the effect of BetA on five GBC cell lines and found that BetA significantly inhibited the proliferation of NOZ cells but had little inhibitory effect on other GBC cells. BetA disturbed mitochondrial membrane potential and induced apoptosis in NOZ cells. Real-time polymerase chain reaction analysis revealed that stearoyl-coenzyme A desaturase 1 (SCD1) was highly expressed in NOZ cells but low expressed in other GBC cells. BetA inhibited SCD1 expression in a concentration-dependent manner in NOZ cells. Downregulation of SCD1 expression by RNA interference inhibited the proliferation of NOZ cells and induced cell apoptosis. Moreover, BetA inhibited the growth of xenografted tumors and suppressed SCD1 expression in nude mice. Thus, our results showed that BetA induced apoptosis through repressing SCD1 expression in GBC, suggesting that BetA might be an effective agent for the treatment of patients with GBC that highly expresses SCD1.

PMID: 

BMC Cancer. 2020 Jan 2 ;20(1):4. Epub 2020 Jan 2. PMID: 31898540

Abstract Title: 

Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling.

Abstract: 

BACKGROUND: Cell migration and invasion are essential processes for metastatic dissemination of cancer cells. Significant progress has been made in developing new therapies against oncogenic signaling to eliminate cancer cells and shrink tumors. However, inherent heterogeneity and treatment-induced adaptation to drugs commonly enable subsets of cancer cells to survive therapy. In addition to local recurrence, these cells escape a primary tumor and migrate through the stroma to access the circulation and metastasize to different organs, leading to an incurable disease. As such, therapeutics that block migration and invasion of cancer cells may inhibit or reduce metastasis and significantly improve cancer therapy. This is particularly more important for cancers, such as triple negative breast cancer, that currently lack targeted drugs.METHODS: We used cell migration, 3D invasion, zebrafish metastasis model, and phosphorylation analysis of 43 protein kinases in nine triple negative breast cancer (TNBC) cell lines to study effects of fisetin and quercetin on inhibition of TNBC cell migration, invasion, and metastasis.RESULTS: Fisetin and quercetin were highly effective against migration of all nine TNBC cell lines with up to 76 and 74% inhibitory effects, respectively. In addition, treatments significantly reduced 3D invasion of highly motile TNBC cells from spheroids into a collagen matrix and their metastasis in vivo. Fisetin and quercetin commonly targeted different components and substrates of the oncogenic PI3K/AKT pathway and significantly reduced their activities. Additionally, both compounds disrupted activities of several protein kinases in MAPK and STAT pathways. We used molecular inhibitors specific to these signaling proteins to establish the migration-inhibitory role of the two phytochemicals against TNBC cells.CONCLUSIONS: We established that fisetin and quercetin potently inhibit migration of metastatic TNBC cells by interfering with activities of oncogenic protein kinases in multiple pathways.

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PMID: 

Biomed Pharmacother. 2020 Feb ;122:109772. Epub 2019 Dec 30. PMID: 31918290

Abstract Title: 

Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice.

Abstract: 

BACKGROUND: Sepsis is defined as end-organ dysfunction resulting from the host's inflammatory response to infection. One of the most common sepsis-injured organs is the kidneys, resulting in acute kidney injury (AKI) that contributes to the high morbidity and mortality, especially patients in the intensive care unit. Fisetin, a naturally occurring flavonoid, has been reported to protect against the rat of lipopolysaccharide (LPS)-induced acute lung injury. However, the effect of fisetin on septic AKI remains unknown.PURPOSE: The current study proposed to systematically investigate the renoprotective effects and the underlying mechanisms of fisetin in septic AKI mice.METHODS: The model of septic AKI was established on male C57BL/6 J mice by a single intraperitoneal injection of LPS (10 mg/kg). Fisetin was administrated by gavage at 100 mg/kg for 3 consecutive days before LPS injection and the mice were sacrificed at 16 h after LPS injection. The serum and kidney samples were evaluated for biochemical analysis, histopathological examinations as well as inflammation and apoptosis related gene/protein expression.RESULTS: Pretreatment with fisetin significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in LPS-treated mice. Consistently, LPS induced renal damage as implied by histopathological score and the increased injury markers NGAL and KIM-1, which was attenuated by fisetin. Meanwhile, LPS injection triggered proinflammatory cytokine production and inflammation related proteins in the kidneys. However, fisetin inhibited renal expression of IL-6, IL-1β, TNF-α, HMGB1, iNOS and COX-2 to improve inflammatory response. Furthermore, fisetin effectively reduced the number of TUNEL positive apoptotic cells and suppressed apoptotic protein of Bcl-2, BAX and cleaved caspase-3 in the kidneys of LPS-induced septic AKI. Mechanistically, LPS stimulated theexpression of TLR4 and the phosphorylation of NF-κB p65, MAPK (p38, ERK1/2 and JNK), Src and AKT in the injured kidneys, while fisetin notably suppressed the corresponding protein expression.CONCLUSION: Fisetin alleviated kidney inflammation and apoptosis to protect against LPS-induced septic AKI mice via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways.

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