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Obesity is the leading cause of non-alcoholic fatty liver disease by provoking hyperglycemia, hyperlipidemia, insulin resistance, oxidative stress, and inflammation. Low activity of AMP-activated protein kinase (AMPK) is linked to obesity, liver injury, and NAFLD. This study involves examining if the anti-steatosis effect of Xanthohumol (XH) in high-fat diet (HFD)-fed rats involves the regulation of AMPK. Adult male rats were divided into five groups (n = 8 each) as control (3.85 kcal/g); XH (control diet + 20 mg/kg), HFD (4.73 kcl/g), HFD + XH (20 mg/kg), and HFD + XH (30 mg/kg) + compound c (cc) (0.2 mg/kg). All treatments were conducted for 12 weeks. Treatment with XH attenuated the gain in body weight, fat pads, fasting glucose, and insulin in HFD rats. It also lowered serum leptin and free fatty acids (FFAs) and improved glucose and insulin tolerances in these rats. It also attenuated the increase in serum livers of liver marker enzymes and reduced serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), FFAs, as well as serum levels of low-density lipoproteins cholesterol (LDL-c) oxidized LDL-c. XH also reduced hepatic levels of malondialdehyde (MDA), nuclear accumulation of NF-κB, and the levels of tumor necrosis-factor-α (TNF-α) and interleukin-6 (IL-6) while stimulating the nuclear levels of Nrf2 and total levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in these HFD-fed rats. At the molecular levels, XH increased hepatic mRNA expression and phosphorylation of AMPK (Thr72) and reduced the expression of lipogenic genes SREBP1c and ACC-1. In concomitance, XH reduced hepatic liver droplet accumulation, reduced the number of apoptotic nuclei, and improved the structures of nuclei, mitochondria, and rough endoplasmic reticulum. Co-treatment with CC, an AMPK inhibitor, completely abolished all these effects of XH. In conclusion, XH attenuates obesity and HFD-mediated hepatic steatosis by activating hepatic AMPK. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) treatment in cancer patients leads to nephrotoxicity. The nephroprotective effect of Berberine (BBR), a herbal ingredient, is well documented as antioxidant and activation of the Nrf2 signalling. This study aimed to investigate if Nrf2 is a major protective mechanism of BBR in DOX animal models. Rats were divided as (n = 6 each): Control, BBR (100 mg/kg, orally), DOX (15 mg/kg, orally), BBR + DOX, and BBR + DOX + brusatol (0.2 mg/kg, i.p./twice per week) (an Nrf2 inhibitor). DOX was given as a single dose (day 10), whereas BBR was administered for 3 weeks on a daily basis. BBR reduced tubular degeneration and improved renal markers in DOX‐treated rats. It also reduced renal nuclear levels of NF‐κB p65, total reactive oxygen species (ROS), lipid peroxides, interleukin‐6 (IL‐6), and tumour necrosis factor‐α (TNF‐α), as well as mRNA levels of Bax and cleaved caspase‐3. However, BBR stimulated glutathione (GSH) and superoxide dismutase (SOD) levels, the transcription of Bcl2, and the mRNA, total cytoplasmic, and nuclear levels of Nrf2 with no effect on the cytoplasmic keap1 levels. All these effects disappeared by brusatol. In conclusion, BBR prevents DOX‐induced renal damage by activating Nrf2. [ABSTRACT FROM AUTHOR]

This study examined the impact of different cooking methods on fatty acid (FAs) composition of shrimp meat and the ability of these foods to protect against high cholesterol (HC) diet-induced non-alcoholic fatty liver disease (NAFLD) in rats. Shrimp were cooked for 10 min boiled, grilled, or fried in sunflower oil. Rats (n = 6/group) were fed a normal diet (ND)or high-cholesterol diet (HC) each containing boiled, grilled or fried shrimp powder (15% w/w) (NDBS, NDFS, NDGS for ND or HCBS, HCFS, HCDGS for HC diet). Frying alone significantly reduced total levels of saturated FAs (SFA) and increased total mono- and polyunsaturated FAs (MSFA, and PUFAs, respectively) in shrimp meat. It also increased levels of n-6 PUFAs and linoleic acid (LA) and decreased levels of n-3 PUFAs including eicosapentaenoic FAs (EPA) and docosahexaenoic fatty acid (DHA). When fed to HC rats, only diets containing the grilled and boiled shrimp powders significantly prevented the weight loss, lowered fasting and glucose levels, improved glucose and insulin tolerance, and prevented the increase in serum liver markers, ALT and AST. They also reduced hepatic fat accumulation, reduced serum levels and hepatic levels of cholesterol and triglycerides (TGs), reduced hepatic levels of MDA, tumor necrosis factor-alpha (TNF-α), and IL-6, and increased those of glutathione (GSH) and superoxide dismutase (SOD). No alterations in all these parameters were observed in HC-fed rats which fed fried shrimp. In conclusion, boiling and grilling but not frying are the best method to cook shrimp to preserve their fatty acid content and its nutritional value in ameliorating NAFLD. [ABSTRACT FROM AUTHOR]

This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress plays a key role in cadmium chloride (CdCl2)-induced nephrotoxicity. Sirtuin-1 (SIRT1) is a potent inhibitor of ER stress. In this study, we examined whether the protective effect of quercetin (QUR) against CdCl 2 -induced nephrotoxicity in rats involved modulation of SIRT1 and/or ER stress. Adult male rats were divided into five groups (n = 8, each) and treated for eight weeks as follows: control, control + QUR, CdCl 2 , CdCl 2 + QUR, and CdCl 2 + QUR + EX-527 (a SIRT1 inhibitor). Treatment of rats with QUR preserved the glomerulus and tubule structure, attenuated interstitial fibrosis, increased creatinine excretion, and reduced urinary levels of albumin, N-acetyl-β- D -glucosaminidase, and β2-microglobulin in CdCl 2 -treated rats. Concomitantly, QUR increased renal levels of Bcl-2, reduced mRNA levels of CHOP , and protein levels of Bax, caspase-3, and cleaved caspase-3, but failed to reduce the mRNA levels of GRP78 , PERK , eIf2α , ATF-6 , and xbp-1. QUR also reduced the renal levels of reactive oxygen species, tumour necrosis factor, and interleukin-6 and the nuclear activity of NF-κB in the control and CdCl 2 -treated rats but increased the nuclear activity of Nrf2 and levels of glutathione and manganese superoxide dismutase. Additionally, QUR increased the total levels and nuclear activity of SIRT1 and reduced the acetylation of eIf2α and xbp-1. The nephroprotective effects of QUR were abrogated by treatment with EX-527. Thus, QUR ameliorated CdCl 2 -induced nephrotoxicity through antioxidant and anti-inflammatory effects and suppressed ER stress mediated by the upregulation or activation of SIRT1-induced deacetylation of Nrf2, NF-κB p65, eIF2α, and xbp-1. A representative figure demonstrating that QUR protective effect against CdCl2-induced renal damage is mediated by antioxidant and anti-inflammatory effects, as well as suppression of XBP-1 and elf2α through activating SIRT1. GSH: glutathione; IL-6: interlukine-6; MDA: malondialdehyde; MnSOD: manganese superoxide dismutase; ROS: reactive oxygen species; TNF: tumor necrosis factor-α; and QUR: quercetin. [Display omitted] [ABSTRACT FROM AUTHOR]