Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κß, and Upregulating Nrf2.

Potent hypoglycemic and antioxidant effects were recently reported for the apple-derived phenolic compound phloretamide (PLTM). The renoprotective effects of this compound are yet to be shown. This study aimed to examine the potential of PLTM to prevent diabetic nephropathy in streptozotocin-induced diabetic rats and to examine the possible mechanisms of protection. Non-diabetic and STZ-diabetic male rats were treated orally by gavage with either the vehicle or with PTLM (200 mg/kg; twice/week) for 12 weeks. PTLM significantly increased urine volume and prevented glomerular and tubular damage and vacuolization in STZ-diabetic rats. It also increased creatinine excretion and reduced urinary albumin levels and the renal levels of kidney injury molecule-1 (KIM-1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), neutrophil gelatinase-associated lipocalin (NGAL), and nephrin in the diabetic rats. PTLM also prevented an increase in the nuclear levels of NF-κß, as well as the total levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), caspase-3, and Bax in the kidneys of diabetic rats. These effects were associated with reduced serum levels of triglycerides, cholesterol, and low-density lipoprotein cholesterol. In both the control and diabetic rats, PTLM significantly reduced fasting plasma glucose and enhanced the renal mRNA and cytoplasmic levels of Nrf2, as well as the levels of Bcl2, superoxide dismutase (SOD), and glutathione (GSH). However, PTLM failed to alter the cytoplasmic levels of keap1 in diabetic rats. In conclusion, PTLM prevents renal damage and dysfunction in STZ-diabetic rats through its hypoglycemic and hypolipidemic activities, as well as through its antioxidant potential, which is mediated by activating the Nrf2/antioxidant axis.

Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects.

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKß). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.

Lepidium sativum alleviates diabetic nephropathy in a rat model by attenuating glucose levels, oxidative stress, and inflammation with concomitant suppression of TGF-ß1.

In this research, the treatment of diabetic nephropathy in rats induced by streptozotocin with L. sativium whole-plant aqueous extract was examined, and the mechanism of action was proposed. Adult male rats were grouped into: control, L. sativum, T1DM, and T1DM + L. sativum-treated groups. For 8 weeks, L. sativum S was given to rats at a final dose of 250 mg/kg. Treatment with L. sativum reduced the amount of fasting glucose, increased the amount of fasting insulin, and diminished the increase in hepatic and serum cholesterol, free fatty acid, and triglyceride levels. The level of serum LDL-c was reduced. At the level of the kidney, L. sativum reduced urine volume and albumin excretion and spiked creatinine excretion. It also attenuated the tubular damage in the rats' kidneys and reduced the amounts of major inflammatory markers, including nuclear factor-kappaα (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Interestingly, L. sativium reduced the amount of mRNA transforming growth factor-ß1 (TGF-ß1), stimulated mRNA superoxide dismutase (SOD) and catalase (CAT), reduced lipid peroxide levels (MDA), and increased the glutathione (GSH), SOD, and CAT in the rat kidneys of the control and T1DM-treated group. In conclusion, L. sativum is a novel therapy against DN owing to its hypoglycemic effect, insulin-releasing, and antioxidant potential.

Phloretamide Prevent Hepatic and Pancreatic Damage in Diabetic Male Rats by Modulating Nrf2 and NF-κB.

This study examined the effect of phloretamide, a metabolite of phloretin, on liver damage and steatosis in streptozotocin-induced diabetes mellitus (DM) in rats. Adult male rats were divided into two groups: control (nondiabetic) and STZ-treated rats, each of which was further treated orally with the vehicle phloretamide 100 mg or 200 mg. Treatments were conducted for 12 weeks. Phloretamide, at both doses, significantly attenuated STZ-mediated pancreatic ß-cell damage, reduced fasting glucose, and stimulated fasting insulin levels in STZ-treated rats. It also increased the levels of hexokinase, which coincided with a significant reduction in glucose-6 phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase 1 (PBP1) in the livers of these diabetic rats. Concomitantly, both doses of phloretamide reduced hepatic and serum levels of triglycerides (TGs) and cholesterol (CHOL), serum levels of low-density lipoprotein cholesterol (LDL-c), and hepatic ballooning. Furthermore, they reduced levels of lipid peroxidation, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), mRNA, and total and nuclear levels of NF-κB p65, but increased mRNA levels, total and nuclear levels of Nrf2, as well as levels of reduced glutathione (GSH), superoxide dismutase (SOD-1), catalase (CAT), and heme-oxygenase-1 (HO-1) in the livers of diabetic rats. All of these effects were dose-dependent. In conclusion, phloretamide is a novel drug that could ameliorate DM-associated hepatic steatosis via its powerful antioxidant and anti-inflammatory effects. Mechanisms of protection involve improving the ß-cell structure and hepatic insulin action, suppressing hepatic NF-κB, and stimulating hepatic Nrf2.

Fenugreek Seed Galactomannan Aqueous and Extract Protects against Diabetic Nephropathy and Liver Damage by Targeting NF-κB and Keap1/Nrf2 Axis.

This investigation was conducted to test the potential of the galactomannan (F-GAL) and aqueous extract (FS-AE) of the Fenugreek seed aqueous to prevent liver and kidney damage extracts in streptozotocin (STZ)-induced T1DM in rats. Non-diabetic and diabetic rats received the normal saline as a vehicle or were treated with FS-EA or F-GAL at a final concentration of 500 mg/kg/each. Treatments with both drugs reduced fasting hyperglycemia and improved serum and hepatic lipid profiles in the control and diabetic rats. Additionally, F-GAL and FS-AE attenuated the associated reduction in the mass and structure of the islets of Langerhans in diabetic rats and improved the structure of the kidneys and livers. In association, they also reduced the generation of reactive oxygen species (ROS), lipid peroxides, factor (TNF-α), interleukin-6 (IL-6), and nuclear levels of NF-κB p65, and improved serum levels of ALT, AST, albumin, and creatinine. However, both treatments increased hepatic and renal superoxide dismutase (SOD) in the livers and kidneys of both the control and diabetic-treated rats, which coincided with a significant increase in transcription, translation, and nuclear localization of Nrf2. In conclusion, FS-AE and F-GAL are effective therapeutic options that may afford a possible treatment for T1DM by attenuating pancreatic damage, hyperglycemia, hyperlipidemia, and hepatic and renal damage.

Icariin ameliorates metabolic syndrome-induced benign prostatic hyperplasia in rats.

Metabolic syndrome (MetS) is an immense health issue that causes serious complications in aging males including BPH. Icariin (ICA) is a flavonol glycoside that exerts a plethora of pharmacological effects. The present investigation tested the potential of ICA to ameliorate benign prostatic hyperplasia (BPH) induced by MetS in rats. Animals were allocated to 5 groups in which the first and second groups were kept on water and regular food pellets. MetS was induced in the third, fourth, and fifth groups by keeping the animals on high fructose and salt diets for twelve consecutive weeks. These groups were given vehicle, ICA (25 mg/kg), and ICA (50 mg/kg), respectively. MetS was confirmed by an increase in rats' weight, accumulation of visceral fat, insulin resistance, and dyslipidemia. This was accompanied by manifestation of BPH including increased prostate weight, prostate index, and histopathological alterations. Treating the animals with both doses of ICA significantly ameliorated the increase in weight and index of the prostate as well as altered prostate histopathology. In addition, ICA significantly decreased cyclin D1 expression, upregulated Bax, and downregulated Bcl2 mRNA expression. ICA prevented lipid peroxidation, reduced glutathione depletion, and catalase exhaustion, which further lowered markers of prostate inflammation such as interleukin-6 and tumor necrosis factor-α. Moreover, ICA prevented the decrease in prostate content of phosphorylated 5'-adenosine monophosphate (AMP)-activated protein kinase (pAMPK). In conclusion, ICA protects against MetS-induced BPH. This is due to its antiproliferative, proapoptotic, antioxidant, and anti-inflammatory activities as well as the activation of AMPK.

The Synergistic Protective Effect of γ-Oryzanol (OZ) and N-Acetylcysteine (NAC) against Experimentally Induced NAFLD in Rats Entails Hypoglycemic, Antioxidant, and PPARα Stimulatory Effects.

This study estimated that the combined effect of γ-Oryzanol and N-acetylcysteine (NAC) against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats also estimated some of their mechanisms of action. Adult male rats were divided into seven groups (n = 8 each) as control, control + NAC, control + γ-Oryzanol, HFD, HFD + NAC, HFD + γ-Oryzanol, and HFD + NAC + γ-Oryzanol. NAC was administered orally at a final concentration of 200 mg/kg, whereas γ-Oryzanol was added to diets at a concentration of 0.16. All treatments were conducted for 17 weeks and daily. Both NAC and γ-Oryzanol were able to reduce final body weights, fat weights, fasting glucose, fasting insulin, serum, and serum levels of liver function enzymes as well as the inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6), and leptin in HFD-fed rats. They also improved hepatic structure and glucose tolerance, increased adiponectin levels, and reduced serum and hepatic levels of triglycerides (TGs) and cholesterol (CHOL) in these rats. These effects were concomitant with a reduction in the hepatic levels of lipid peroxides (MDA) and serum levels of LDL-C, but also with an increment in the hepatic levels of superoxide dismutase (SOD) and glutathione (GSH). Interestingly, only treatment with γ-Oryzanol stimulated the mRNA levels of proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) in the liver and white adipose tissue (WAT) of rats. Of note, the combination therapy of both drugs resulted in maximum effects and restored almost normal liver structure and basal levels of all the above-mentioned metabolic parameters. In conclusion, a combination therapy of γ-Oryzanol and NAC is an effective therapy to treat NAFLD, which can act via several mechanisms on the liver and adipose tissue.

Application of Native or Exotic Arbuscular Mycorrhizal Fungi Complexes and Monospecific Isolates from Saline Semi-Arid Mediterranean Ecosystems Improved Phoenix dactylifera's Growth and Mitigated Salt Stress Negative Effects.

The date, the palm tree (Phoenix dactylifera L.) is an important component of arid and semi-arid Mediterranean ecosystems, particularly in Morocco where it plays a considerable socio-economic and ecological role. This species is largely affected by desertification, global warming, and anthropic pressure. Salinity is a very worrying problem that negatively affects the growth and the physiological and biochemical activities of the date palm. In these arid zones, the main challenge is to develop new environmentally friendly technologies that improve crop tolerance to abiotic restraints including salinity. In this sense, Arbuscular mycorrhizal fungi (AMF) have received much attention due to their capability in promoting plant growth and tolerance to abiotic and biotic stresses. It is thus fitting that the current research work was undertaken to evaluate and compare the effects of native AMF on the development of the growth and tolerance of date palm to salt stress along with testing their role as biofertilizers. To achieve this goal, two complexes and two monospecific isolates of native and non-native AMF were used to inoculate date palm seedlings under saline stress (0 g·L-1 Na Cl, 10 g·L-1, and 20 g·L-1 Na Cl). The obtained results showed that salinity drastically affected the physiological parameters and growth of date palm seedlings, whilst the application of selected AMF significantly improved growth parameters and promoted the activities of antioxidant enzymes as a protective strategy. Inoculation with non-native AMF complex and monospecific isolates showed higher responses for all analyzed parameters when compared with the native complex and isolate. It therefore becomes necessary to glamorize the fungal communities associated with date palm for their use in the inoculation of Phoenix dactylifera L. seedlings.

Chemical Characterization and Antioxidant, Antimicrobial, and Insecticidal Properties of Essential Oil from Mentha pulegium L.

The chemical composition and antibacterial, insecticidal, and antioxidant properties of the essential oil from Mentha pulegium L. (M. pulegium) growing in Morocco were investigated in this work. To achieve this goal, the oils were obtained by using hydrodistillation before being characterized by GC-MS. The antibacterial and antifungal activities were conducted against pathogenic strains using the disc diffusion and MICS bioassays. The insecticidal activity was carried out versus C. maculatus using contact and inhalation tests. The antioxidant activity was performed by using DPPH and total antioxidant capacity bioassays. The chemical analysis of the oil showed that 20 compounds were identified, which represented 98.91% of the total oil. In the oil, the main components detected were R-(+)-pulegone (76.35%), carvone (5.84%), dihydrocarvone (5.09%), and octanol-3 (2.25%). The essential oil has moderate-to-strong broad-spectrum antibacterial and antifungal properties; the results showed that B. subtilis was the most sensitive strain to M. pulegium oil, with the largest inhibition diameter (25 ± 0.33). For the antifungal activity, the results obtained indicated that Aspergillus niger was the most sensitive fungal strain to M. pulegium oil with an inhibition percentage up to 100%. Regarding the insecticidal activity, the inhalation test showed a high efficacy (100% mortality), and a lethal concentration of LC50 = 1.41 + 0.48 µL/L air was obtained after 24 hours of exposure. Moreover, the contact test showed that a total reduction in fertility and emergence was obtained with a dose of 20 µL/mL of acetone. Regarding the antioxidant activity, the sample concentration necessary to inhibit 50% of HE radicals (IC50) was 7.659 mg/mL (DPPH) and 583.066 57.05 mg EAA/g EO (TAC).

Promising Antioxidant and Anticorrosion Activities of Mild Steel in 1.0 M Hydrochloric Acid Solution by Withania frutescens L. Essential Oil.

The present study was conducted to evaluate the anticorrosive and antioxidant activities of essential oil from Withania frutescens L. In the present study, the extraction of Withania frutescens L. essential oil (Wf-EO) was conducted using hydrodistillation before being characterized by gas chromatographic analysis (GC/MS) and flame ionization detector (GC/FID). Four bioassays were used for antioxidant testing including 2,2-diphenyl-1-picrylhydrazyl (DPPH), total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP), and ß-carotene bleaching. The inhibiting effect of Wf-EO on the corrosion behavior of mild steel in 1.0 M HCl was conducted by using polarization curves and electrochemical impedance spectroscopy techniques. The yield of Wf-EO was 0.46% including 175 compounds identified by GC-MS. The oil was mostly constituted of camphor (37.86%), followed by thujone (26.47%), carvacrol (6.84%), eucalyptol (3.18%), and linalool (2.20%). The anti-free radical activity of Wf-EO was 34.41 ± 0.91 µg/ml (DPPH), 9.67 ± 0.15 mg/ml (FRAP), 3.78 ± 0.41 mg AAE/g (TAC), and 89.94 ± 1.44% (ß-carotene). The Wf-EO showed potent antioxidant activity in all bioassays used for testing. The anticorrosion activity, polarization curves as well as EIS diagrams indicated that the Wf-EO exhibited anticorrosive properties and reacted as a suitable corrosion inhibitor in an acidic medium.

The Potential of Exploiting Economical Solar Dryer in Food Preservation: Storability, Physicochemical Properties, and Antioxidant Capacity of Solar-Dried Tomato (Solanum lycopersicum) Fruits.

This study investigated the effect of solar drying on storability and physiochemical and antioxidant capacities of dried tomatoes. Sliced fruit was dried at 45 ± 2 °C for 24 h under a solar tunnel dryer and stored at ambient temperature for 90 and 180 days. Solar drying treatments significantly (p < 0.05) reduced the bacterial and mold load, and eliminated Staphylococcus aureus, S. saprophyticus, and Escherichia coli in all samples. Solar drying treatment reduced the water activity of the dried tomato's to 0.31 that remained at the same level during storage period 180 days. Storage of dried tomato slices resulted in the decrease of both color and vitamin C content while it increased the total carotenoid, lycopene, phenolic compound content, and antioxidant activity. Furthermore, the principle component analysis (PCA) revealed that solar drying of tomato slices enhanced its physicochemical properties, antioxidant capacity particularly after storage for 90 and 180 days. Interestingly, the solar drying process enhanced tomato slices storage and physicochemical characteristics, that resulted in extending the shelf life by up to 6 months, indicating the great potential application of low-tech solar in food industry and could become an emerging effective post-harvest preservative method for seasonal perishable vegetable and fruit, particularly in developing countries.

Effects of microwave heat treatment on fungal growth, functional properties, total phenolic content, and antioxidant activity of sorghum (Sorghum bicolor L.) grain.

Sorghum grains were subjected to microwave heating at different power levels 350 and 500 W for application times of 15, 30, and 45 s. The effect of microwave heating on fungal growth, protein content, in vitro digestibility, protein solubility, and functional and antioxidant properties of sorghum grain was investigated. The microwave heating at 350 and 500 W significantly reduced fungal incidence in the grain up to 26.2 and 33.4%. No significant changes were found in the crude protein and digestibility of protein, water holding capacity, and oil holding capacity of sorghum. However, application of microwave energy at 500 W for 30 & 45 s caused a sharp reduction on the protein solubility (8.2-7.6%), foaming capacity (6.47-0.98%), emulsion capacity (0.43-0.32 mL/g) and the emulsion stability (2.2-1.6%) of sorghum grain, respectively. Conversely, a significant increment of grain total phenolic content up to 47.1 and 50.8 mg GAE/g and the antioxidant activity up to 40.9 and 59.1% after microwave heat treatment at 350 and 500 W for 45 s, respectively, was observed. These findings revealed that sorghum grain should be treated with microwave at 350 and 500 W for 45 and 15 s, respectively, in order to maintained and enhanced its functional and nutritional properties. Accordingly, microwave heating, particularly at low power, may be an effective emerging method for improving the physicochemical and nutritional properties of sorghum grain.

Icariin enhances AMP-activated protein kinase and prevents high fructose and high salt-induced metabolic syndrome in rats.

Metabolic syndrome (MetS) is an increasing health threat and often leads to cardiovascular complications. The aim of this study was to evaluate icariin's ability to combat MetS induced in rats and outline the involved mechanisms of action. Rats were grouped in four batches. The controls received a regular diet and water. MetS was induced in the remaining three groups using a high-salt high-fructose diet. Groups 1 and 2 were given daily doses of saline, while Groups 3 and 4 received 25 and 50 mg/kg icariin, respectively, for 12 weeks in total. The experimental protocol was carried out for 12 weeks consecutively. Icariin significantly decreased body mass index (BMI), adiposity index and body weight. Further, icariin protected against dyslipidemia, hyperglycemia, and hyperinsulinemia and improved insulin resistance as given by the homeostatic model assessment of insulin resistance (HOMA-IR) values. Icariin guarded against the rise in serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). In addition, it significantly inhibited the decrease in mRNA expression of glucose transporter type 4 (GLUT4) and liver kinase B1 (LKB1). These effects were accompanied by decreased liver content of nuclear factor kappa B (NFκB) and enhanced serum levels of phosphorylated 5'-adenosine monophosphate-activated protein kinase (p-AMPK). Further, icariin significantly increased p-AMPK/AMPK ratio in liver tissues. Conclusively, icariin offers protection in experimentally induced MetS, partially due to AMPK activation.