PMID: 

J Diabetes Res. 2018 ;2018:5391014. Epub 2018 Sep 10. PMID: 30276216

Abstract Title: 

Therapeutic Potential of Fulvic Acid in Chronic Inflammatory Diseases and Diabetes.

Abstract: 

Chronic inflammatory diseases like diabetes are on a rise in the Western world. Based on the tsunami of new cases every year, new therapeutic measures must be considered. A promising avenue might involve the attenuation of underlying inflammation through natural health products (NHPs). This is because most NHPs have a rich history in traditional medicine and might be considered safer under appropriate doses and conditions. However, the biggest impediment in NHP research is that rarely do these products come with verified health benefits or dosing schedules established through modern scientific research. Fulvic acid (FvA), one such NHP, comes from humic substances produced by microorganisms in soil. Traditional medicine and modern research claim FvA can modulate the immune system, influence the oxidative state of cells, and improve gastrointestinal function; all of which are hallmarks of diabetes. This minireview outlines the available peer-reviewed research on FvA and examines its anecdotal health claims. We show that although available research has been minimal, there is substantial evidence to pursue FvA research in preventing chronic inflammatory diseases, including diabetes.

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PMID: 

Sci Rep. 2019 Sep 30 ;9(1):14003. Epub 2019 Sep 30. PMID: 31570745

Abstract Title: 

Eugenol Reduces LDL Cholesterol and Hepatic Steatosis in Hypercholesterolemic Rats by Modulating TRPV1 Receptor.

Abstract: 

Eugenol, a component of essential oils of medicinal and food plants, has a hypolipidemic effect in experimental animals although its mechanism of action is still unclear. This study aims to explore the mechanism of the hypolipidemic effect of eugenol in rats fed a high cholesterol and fat diet (HCFD). Eugenol significantly reduced total cholesterol (TC), low-density lipoproteins (LDL), atherogenic index (AI) but not high-density lipoproteins (HDL) or triglycerides (TG). Eugenol also decreased steatosis and hepatic inflammation in liver sections, decreased hepatomegaly, and the hepatic marker enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activity and increased the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity in hypercholesterolemic rats. Eugenol did not inhibit hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase but caused down-regulation of transient receptor potential vanilloid (TRPV1) channels in the liver. Docking simulation using fast, rigid exhaustive docking (FRED) software indicated a tail-up/head-down interaction of eugenol with TRPV1 channel. Data indicate that eugenol does not inhibit HMG-CoA reductase but rather induces its action by interaction with TRPV1 channels.

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PMID: 

Molecules. 2019 Nov 3 ;24(21). Epub 2019 Nov 3. PMID: 31684176

Abstract Title: 

Eugenol Exerts Apoptotic Effect and Modulates the Sensitivity of HeLa Cells to Cisplatin and Radiation.

Abstract: 

Eugenol is a phytochemical present in different plant products, e.g., clove oil. Traditionally, it is used against a number of different disorders and it was suggested to have anticancer activity. In this study, the activity of eugenol was evaluated in a human cervical cancer (HeLa) cell line and cell proliferation was examined after treatment with various concentrations of eugenol and different treatment durations. Cytotoxicity was tested using lactate dehydrogenase (LDH) enzyme leakage. In order to assess eugenol's potential to act synergistically with chemotherapy and radiotherapy, cell survival was calculated after eugenol treatment in combination with cisplatin and X-rays. To elucidate its mechanism of action, caspase-3 activity was analyzed and the expression of various genes and proteins was checked by RT-PCR and western blot analyses. Eugenol clearly decreased the proliferation rate and increased LDH release in a concentration- and time-dependent manner. It showed synergistic effects with cisplatin and X-rays. Eugenol increased caspase-3 activity and the expression of, cytochrome c (Cyt-c), caspase-3, and caspase-9 and decreased the expression of, cyclooxygenase-2 (), and interleukin-1 beta (IL-1β) indicating that eugenol mainly induced cell death by apoptosis. In conclusion, eugenol showed antiproliferative and cytotoxic effects via apoptosis and also synergism with cisplatin and ionizing radiation in the human cervical cancer cell line.

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PMID: 

Inflammation. 2019 Nov 8. Epub 2019 Nov 8. PMID: 31705353

Abstract Title: 

Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions.

Abstract: 

Ischemia-reperfusion injury is an organ failure caused by hypoxia and reperfusion, which is closely associated with oxidative stress and inflammation. In this study, we investigated whether nobiletin had protective effects on inflammatory parameters, oxidative damage, iNOS-eNOS expressions, and histopathological structure of renal tissue in rats with renal ischemia-reperfusion injury. For this purpose, 24 rats were divided into 4 groups: group 1 (Control), group 2 (Ischemia-Reperfusion-IR), group 3 (Nobiletin-10 mg/kg p.o.), group 4 (Nobiletin + IR). The study was continued for 7 days. At the end of the study, urea (p

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PMID: 

Am J Clin Nutr. 2019 Nov 12. Epub 2019 Nov 12. PMID: 31711104

Abstract Title: 

Randomized placebo-controlled study of the memory effects of pomegranate juice in middle-aged and older adults.

Abstract: 

BACKGROUND: Antioxidant nutrients such as the polyphenols in pomegranate juice may prevent neuronal damage from the free radicals produced during normal metabolism. Previous research in animals and a short-term clinical trial in middle-aged and older adults support the potential memory benefits of pomegranate juice; however, the long-term effects of pomegranate juice consumption on cognition have not been studied.OBJECTIVE: In this study, we investigated the long-term effect of pomegranate juice on memory in nondemented middle-aged and older adults.METHODS: We performed a 12-month, randomized, double-blind, placebo-controlled trial of pomegranate juice in middle-aged and older adults. Two hundred and sixty-one subjects (aged 50-75 y) were randomly assigned to consume pomegranate juice [8 oz (236.5 mL) per day] or a placebo drink (8 oz, matched constituents of pomegranate juice except for pomegranate polyphenols). Memory measures [Brief Visuospatial Memory Test-Revised (BVMT-R) and Buschke Selective Reminding Test (SRT)] were assessed at 6 and 12 mo and analyzed using a mixed-effects general linear model.RESULTS: Twenty-eight subjects in the pomegranate juice group and 33 subjects in the placebo group dropped out before completing the study. Baseline variables in the 98 pomegranate juice and 102 placebo group subjects who completed the study did not differ significantly. Group by time interaction was statistically significant for BVMT-R Learning (F[2, 257]= 5.90, P  = 0.003; between-group effect size [ES] = 0.45): the change within the pomegranate group was not significant (ES = 0.15), whereas the placebo group showed a significant decline (ES = -0.35). Changes in the other BVMT-R scores as well as the SRT measures were not significantly different between groups.CONCLUSIONS: Daily consumption of pomegranate juice may stabilize the ability to learn visual information over a 12-mo period. This trial was registered at clinicaltrials.gov as NCT02093130.

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PMID: 

J Complement Integr Med. 2019 Sep 17. Epub 2019 Sep 17. PMID: 31527297

Abstract Title: 

Non-pharmacological management of gestational diabetes: The role of myo-inositol.

Abstract: 

Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM. A thorough knowledge of the risk factors and genes involved in the development of GDM, along with an understanding of the underlying pathophysiological mechanisms are crucial to properly identify patients at risk of developing this condition. There is growing evidence showing that myo-inositol, combined with an appropriate therapeutic regimen for GDM, can provide additional benefits to the patient. The aim of this review is to analyze the role of inositol isomers – especially myo-inositol (MYO-INS) – in the treatment of patients with GDM.

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PMID: 

Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):4089-4096. PMID: 31630562

Abstract Title: 

Neferine hinders choriocarcinoma cell proliferation, migration and invasion through repression of long noncoding RNA-CHRF.

Abstract: 

The comprehensive pathological peculiarities of Neferine (NEF) have been testified in disparate diseases. But, the functions of NEF in choriocarcinoma progression remain unexplored. The research endeavoured to uncover the anti-tumour action of NEF in choriocarcinoma cells. NEF at diverse doses was employed to dispose JEG-3 and HTR-8 cells, and cell viability assessment adopted CCK-8 assay. After 60μg/mL NEF management, BrdU-positive cells, apoptosis, migration, invasion and correlative factors were assessed. CHRF expression in choriocarcinoma tumour and choriocarcinoma cell lines was estimated via RT-qPCR. Then, the functions of overexpressed CHRF in NEF-disposed cells were determined. At last, impacts of NEF on PI3K/AKT/mTOR and ERK1/2 pathways were evaluated. Results showed that NEF restrained cell proliferation, triggered apoptosis and repressed migration and invasion in JEG-3 and HTR-8 cells. CHRF was ascended in choriocarcinoma tissues and NEF repressed CHRF expression in choriocarcinoma cell lines. Additionally, overexpressed CHRF abolished the above functions of NEF in choriocarcinoma cells proliferation, apoptosis, migration and invasion. Further, NEF impeded PI3K/AKT/mTOR and ERK1/2 pathways via repressing CHRF. The explorations testified that NEF exhibited the anti-tumour action in JEG-3 and HTR-8 cells via hindering PI3K/AKT/mTOR and ERK1/2 pathways by mediating CHRF.

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PMID: 

Front Pharmacol. 2019 ;10:1197. Epub 2019 Oct 15. PMID: 31680971

Abstract Title: 

Neferine Attenuates Acute Kidney Injury by Inhibiting NF-κB Signaling and Upregulating Klotho Expression.

Abstract: 

Morbidity associated with and mortality from acute kidney injury (AKI) is gradually increasing, and no efficient drug is available. We explored whether neferine, a bisbenzylisoquinoline alkaloid, attenuated AKI, and the possible mechanisms in playand.We induced AKI using ischemia-reperfusion (I/R) or lipopolysaccharide (LPS). C57 BL/6 male mice were randomized into two groups each containing four subgroups: control, neferine, I/R or LPS, and I/R or LPS + neferine. Mice were sacrificed 24 h after AKI induction and kidneys and sera were collected. NRK-52E cells were exposed to hypoxia/reoxygenation (H/R) or LPS.Neferine pretreatment significantly alleviated kidney functional loss and pathological damage. In the AKI mouse models induced by I/R or LPS, neferine inhibited the infiltration of inflammatory cells, including granulocytes and macrophages. Bothand, neferine attenuated apoptosis, suppressed inflammatory cytokine production, decreased degradation of IκB-α, and inhibited nuclear translocation of NF-κB. Furthermore, it also upregulated Klotho expression in AKI.Neferine mitigated renal injury in AKI models, perhaps by suppressing the activation of NF-κB and upregulating the expression of Klotho.

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PMID: 

J Nat Med. 2019 Nov 9. Epub 2019 Nov 9. PMID: 31707550

Abstract Title: 

BBB-permeable aporphine-type alkaloids in Nelumbo nucifera flowers with accelerative effects on neurite outgrowth in PC-12 cells.

Abstract: 

Blood-brain barrier (BBB)-permeable components in the methanolic extract of Nelumbo nucifera flowers showed accelerative effects on neurite outgrowth in PC-12 cells. Among the constituents isolated from N. nucifera flowers in our previous study, aporphine-type alkaloids, lirinidine, asimilobine, N-methylasimilobine, and pronuciferine, showed accelerative effects. Lirinidine, N-methylasimilobine, and an alkaloid-rich diethyl ether fraction at low concentrations increased the expression of mRNAs coding for TrkA, Vav3, and Rac1. In addition, good permeability of asimilobine and N-methylasimilobine was confirmed using an in vitro BBB model. Asimilobine and N-methylasimilobine are considered to be suitable as seed compounds of drugs for Alzheimer's disease, because of their activity and BBB permeability.

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PMID: 

Front Pharmacol. 2019 ;10:999. Epub 2019 Sep 4. PMID: 31551792

Abstract Title: 

Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells.

Abstract: 

Glucose transporter 4 (GLUT4) is involved in regulating glucose uptake in striated muscle, liver, and adipose tissue. Neferine is a dibenzyl isoquinoline alkaloid derived from dietary lotus seeds and has multiple pharmacological effects. Therefore, this study investigated neferine's role in glucose translocation to cell surface, glucose uptake, and GLUT4 expression. In our study, neferine upregulated GLUT4 expression, induced GLUT4 plasma membrane fusion, increased intracellular Ca, promoted glucose uptake, and alleviated insulin resistance in L6 cells. Furthermore, neferine significantly activated phosphorylation of AMP-activated protein kinase (AMPK) and protein kinase C (PKC). AMPK and PKC inhibitors blocked neferine-induced GLUT4 expression and increased intracellular Ca. While neferine-induced GLUT4 expression and intracellular Cawere inhibited by G protein and PLC inhibitors, only intracellular Cawas inhibited by inositol trisphosphate receptor (IPR) inhibitors. Thus, neferine promoted GLUT4 expressionthe G protein-PLC-PKC and AMPK pathways, inducing GLUT4 plasma membrane fusion and subsequent glucose uptake and increasing intracellular Cathrough the G protein-PLC-IP-IPR pathway. Treatment with 0 mM extracellular Ca+ Cachelator did not inhibit neferine-induced GLUT4 expression but blocked neferine-induced GLUT4 plasma membrane fusion and glucose uptake, suggesting the latter two are Ca-dependent. Therefore, we conclude that neferine is a potential treatment for type 2 diabetes.

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