Emerging targets to relieve fat stress-induced liver diseases: UDCA, tocotrienol, -3 PUFAs, and IgY targeted NPC1L1 cholesterol transporter.

Cha JY, Park JM, Lee HJ, Bae JS, Han YM, Oh BC, Ko KH, Hahm KB.

Curr Pharm Des. 2017 Jul 14. doi: 10.2174/1381612823666170714124824. [Epub ahead of print]

Abstract

Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to non-alcoholic steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined. Although obesity, sedentary life-style, altered dietary pattern, insulin resistance, altered intestinal barrier function, inflammatory cytokines, and oxidative stress have been acknowledged as contributing factors because of the indefinite pathogenesis of metabolic diseases, the only reliable treatment is lifestyle intervention composed of restrictive diet and exercise. Additionally, some existing medications such as pioglitazone and antioxidants such as vitamin E were reported to be effective; in this review, several novel agents especifically targeting non-alcoholic fatty liver disease pathogenesis under clinical trial will be introduced. These include an NPC1L1 blocker (ezetimibe), which significantly improved histological and symptomatic scores associated with steatohepatitis and fibrosis; clofibrate, phentoxyfylline, ursodeoxycholic acid, and tocopherol, all of which are prescribed to relieve fat stress; and additional IgY targeted NPC1L1, tocotrienol, ursodeoxycholic acid, and -3 polyunsaturated fatty acids, which are actively under investigation to confirm the safety of long-term use.

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Potential role of natural compounds as anti-angiogenic agents in cancer.

Shanmugam MK, Warrier S, Kumar AP, Sethi G, Arfuso F.

Curr Vasc Pharmacol. 2017 Jul 12. doi: 10.2174/1570161115666170713094319. [Epub ahead of print]

Abstract

BACKGROUND:

Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis. The leakiness in the tumor microvasculature is attributed to the tumor cells migrating to distal site organs and forming colonies.

METHODS:

In this article, we briefly review the various mediators involved in the angiogenic process and the anti-angiogenic potential of selected natural compounds against various malignancies.

RESULTS:

Several growth factors and their receptors such as vascular endothelial growth factor and receptor (VEGF/VEGFR), basic fibroblast growth factor and receptor (bFGF/FGFR), angiopoietins, and hypoxia inducible factors facilitate the development of angiogenesis and are attractive anti-cancer targets. Natural products represent a rich diversity of compounds for drug discovery and are currently being actively exploited to target tumor angiogenesis.

CONCLUSION:

Agents such as curcumin, artemisinin and its semi-synthetic derivatives, EGCG, pentacyclic triterpenoids, resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of natural compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering the drugs to the sites of tumor angiogenesis.

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The effect of almonds on vitamin E status and cardiovascular risk factors in Korean adults: a randomized clinical trial.

Jung H, Chen CO, Blumberg JB, Kwak HK.

Eur J Nutr. 2017 Jul 10. doi: 10.1007/s00394-017-1480-5. [Epub ahead of print]

Abstract

PURPOSE:

Almonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic populations but this relationship has never been tested in Koreans. Thus, we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors.

METHODS:

We conducted a randomized, crossover trial in a free-living setting with a 2-week run-in period, two 4-week intervention phases, and a 2-week washout period between interventions. Eighty four overweight/obese participants (11 M/73 F; 52.4 ± 0.6 year; 25.4 ± 0.22 kg/m2) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks.

RESULTS:

Mean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by 192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased by the almonds, but body weight, waist circumference, and body composition were not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C, and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control (P ≤ 0.05). Almonds increased plasma α-tocopherol by 8.5% (P ≤ 0.05) from the baseline and tended to increase its value as compared to cookies (P = 0.055). Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL. Of serum inflammatory markers, IL-10 was decreased by almond intake (P ≤ 0.05), and ICAM-1, IL-1β, and IL-6 tended to be lower with almonds, compared to the cookies.

CONCLUSIONS:

Almonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and decreasing % energy intake from carbohydrate. Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus, including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD.

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Evaluation of the possible nephroprotective effects of vitamin E and rosuvastatin in amikacin-induced renal injury in rats.

Selim A, Khalaf MM, Gad AM, Abd El-Raouf OM.

J Biochem Mol Toxicol. 2017 Jul 6. doi: 10.1002/jbt.21957. [Epub ahead of print]

Abstract

Amikacin (AMIK) is an aminoglycoside antibiotic that possesses considerable nephrotoxic adverse effects. This study examined the protective effects of vitamin E (VIT. E) or rosuvastatin (ROSU) against AMIK-induced nephrotoxicity. For this purpose, eight groups of rats were used. Two control groups received saline and vehicle, AMIK group (1.2 g/kg, i.p.), VIT. E group (1000 mg/kg; p.o.), ROSU group (10 mg/kg; p.o.), AMIK + VIT. E group, AMIK + ROSU group, and combination group. The results showed that AMIK significantly increased serum levels of urea and creatinine. Meanwhile, serum levels of total protein and albumin were decreased. The kidney content of malondialdehyde was increased, whereas glutathione content and catalase activity were decreased. Tumor necrosis factor-α and nuclear transcriptional factor levels were increased. Conversely, administration of VIT. E and/or ROSU with AMIK ameliorated such damage and reduced DNA fragmentation, apoptosis, and necrosis. In conclusion, co-administration of VIT. E, ROSU, or their combination alleviated AMIK-induced nephrotoxicity.

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H. Pylori Natural Treatment Protocol

Helicobacter pylori (H. pylori) can cause a wide range of problems, from chronic gastritis, peptic ulcer disease, iron deficiency anemia, and stomach cancer to diseases of the liver, cardiovascular system, skin, and many other body systems. If you suffer from this infection, an H. pylori natural treatment plan can be a safe solution. H. pylori infection is closely linked to coronary heart disease, rosacea, asthma, Parkinson’s disease, migraines, and fibromyalgia.

Herbal extracts and phytonutrients, many with antibacterial actions, are often used by natural practitioners to help eradicate H. pyloriitamin C, vitamin E, and selenium supplementation will help lower your risk of dying from stomach or esophageal cancer after H. pylori infection has been treated. This combination of antioxidant nutrients was studied in a large placebo controlled trial involving thousands of people with H. pylori.

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Vitamin E As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies.

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S.

Front Pharmacol. 2017 Jul 5;8:444. doi: 10.3389/fphar.2017.00444. eCollection 2017.

Abstract

A constellation of medical conditions inclusive of central obesity, hyperglycemia, hypertension, and dyslipidemia is known as metabolic syndrome (MetS). The safest option in curtailing the progression of MetS is through maintaining a healthy lifestyle, which by itself, is a long-term commitment entailing much determination. A combination of pharmacological and non-pharmacological approach, as well as lifestyle modification is a more holistic alternative in the management of MetS. Vitamin E has been revealed to possess anti-oxidative, anti-inflammatory, anti-obesity, anti-hyperglycemic, anti-hypertensive and anti-hypercholesterolemic properties. The pathways regulated by vitamin E are critical in the development of MetS and its components. Therefore, we postulate that vitamin E may exert some health benefits on MetS patients. This review intends to summarize the evidence in animal and human studies on the effects of vitamin E and articulate the contrasting potential of tocopherol (TF) and tocotrienol (T3) in preventing the medical conditions associated with MetS. As a conclusion, this review suggests that vitamin E may be a promising agent for attenuating MetS.

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Co-Administration of Vitamin E and Testosterone Attenuates The Atrazine-Induced Toxic Effects on Sperm Quality and Testes in Rats.

Rezaie Agdam H, Razi M, Amniattalab A, Malekinejad H, Molavi M.

Cell J. 2017 Jul-Sep;19(2):292-305. doi: 10.22074/cellj.2016.490. Epub 2017 Feb 22.

Abstract

OBJECTIVE:

Atrazine (ATZ) as a widely used herbicide is considered as a potent endocrine disrupter which adversely affects reproductive systems in both genders. This study aimed to assess the effects of testosterone (T)- and vitamin E (VitE)- alone and their coadministration on testicular function and sperm parameters after exposure to ATZ in rats.

MATERIALS AND METHODS:

In this experimental study, the rats (n=30) are assigned into the following 5 groups: control-sham group (n=6) receiving corn oil, ATZ group (n=6) receiving 200 mg/kg ATZ alone, ATZ+VitE group (n=6) receiving 150 mg/kg ATZ+VitE, ATZ+T group (n=6) receiving 400 µg/kg ATZ+T, and ATZ+VitE+T group (n=6) receiving ATZ+VitE+T for 48 consecutive days. Total antioxidant capacity (TAC), total thiol molecules (TTM), and malondialdehyde (MDA) were analyzed. Serum levels of T, luteinizing hormone (LH), and inhibin-B (IN-B) were also determined. Histological examination and sperm analysis were performed. The data were analyzed using Graph-Pad Prism software version 2.01.

RESULTS:

Co-administration of VitE and T significantly (P<0.05) increased ATZ-decreased TAC and TTM levels and reduced ATZ-increased MDA content. T and VitE significantly (P<0.05) increased serum levels of ATZ-reduced T (1.94 ± 0.96), IN-B (122.10 ± 24.33) and LH (0.40 ± 0.10). The T+VitE animals showed a reduction in apoptotic cells and an increase in Leydig cells steroidogenesis. Co-administration of T and VitE significantly (P<0.05) reduced the ATZ-induced DNA disintegrity and chromatin de-condensation. VitE and T protected germinal cells RNA and protein contents against ATZ-induced damages.

CONCLUSION:

T and VitE in simultaneous form of administration were able to normalize the ATZ-induced derangements through promoting antioxidant capacity and endocrine function.

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