Ficus carica (Linn.) Leaf and Bud Extracts and Their Combination Attenuates Type-1 Diabetes and Its Complications via the Inhibition of Oxidative Stress.

The current work was designed to evaluate the antioxidant activity and antidiabetic effect of Ficus carica L. extracts. For that, the leaves and buds of Ficus carica L. were analyzed to determine their polyphenolic and flavonoid contents and antioxidant activity. Diabetes was induced by a single dose of alloxan monohydrate (65 mg/kg body weight), then diabetic rats were treated with a dose of 200 mg/kg body weight of the methanolic extracts of Ficus carica leaves or buds or their combination for 30 days. Throughout the experiment, blood sugar and body weight were measured every 5 and 7 days respectively. At the end of the experiment, serum and urine were collected for analysis of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, creatinine, uric acid, urea, proteins, sodium, potassium, and chloride. Pancreas, liver, and kidney were removed to estimate catalase, glutathione peroxidase, and glutathione activities; lipid peroxidation products were also determined. The results obtained revealed that alloxan has induced hyperglycemia, increased liver and renal biomarkers levels, reduced antioxidative enzymes, and induced lipid peroxidation. However, the treatment with Ficus carica leaf and bud extracts, especially their combination, has attenuated all pharmacological perturbations induced by alloxan.

Protective effect of bee pollen in acute kidney injury, proteinuria, and crystalluria induced by ethylene glycol ingestion in rats.

Oxidative stress plays a role in hyperoxaluria-induced kidney injury and crystallization. Bee pollen is a hive product with a high content of antioxidants. The antioxidant content and protective effect of bee pollen extract (BPE) against ethylene glycol (EG) induced crystalluria, and acute kidney injury (AKI) were investigated. The effect of BPE on the EG-induced liver injury and proteinuria was also examined. Ten groups of male Wister rats were treated daily with vehicle, cystone, BPE (100, 250, and 500 mg/kg b.wt.), and group 6-9 treated with EG, EG + BPE (100, 250, and 500 mg/kg b.wt.) and group 10 EG + cystone. The dose of EG was 0.75% v/v, and the dose of cystone was 500 mg/kg b.wt. On day 30, blood and urine samples were collected for analysis. Kidneys were removed for histopathological study. The antioxidant activity of BPE was assessed, and its total phenols and flavonoids were determined. EG significantly increased urine parameters (pH, volume, calcium, phosphorus, uric acid, and protein), blood urea, creatinine, and liver enzymes (P < 0.05). EG decreased creatinine clearance and urine magnesium and caused crystalluria. Treatment with BPE or cystone mitigates EG's effect; BPE was more potent than cystone (P < 0.05). BPE increases urine volume, sodium, and magnesium compared to the control and EG treated groups. BPE reduces proteinuria and prevents AKI, crystalluria, liver injury, and histopathological changes in the kidney tissue caused by EG. BPE might have a protective effect against EG-induced AKI, crystalluria, proteinuria, and stone deposition, most likely by its antioxidant content and activity.

Physicochemical characterization and in vitro evaluation of the antioxidant and anticandidal activities of Moroccan propolis.

Background and Aim: Human mycotic infections are one of the major health problems worldwide. Prolonged use of antimycotic drugs has contributed to the development of resistance in pathogenic fungi. This study was conducted to examine antioxidant and anticandidal activities of Moroccan propolis. Materials and Methods: Two ethanolic extracts of Moroccan propolis from the Fez-Meknes region were evaluated regarding the following physicochemical parameters: Yield, pH, total carbohydrates, total proteins, total lipids, minerals, total phenolic content, total flavonoid content, and antioxidant activity using ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. In addition, we assessed the in vitro anticandidal activity against vulvovaginal candidiasis strains, that is, Candida albicans, Candida glabrata, Candida parapsilosis, and Candida krusei, using the broth micromethod according to the CLSI/M27-A3 reference guidelines. Results: The propolis samples exhibited a mean yield of 16%, with an acidic pH ranging from 4.8 to 5.9; the sample from the Oued Amlil area (OAPEE) contained high levels of resin, balsam, moisture, total carbohydrates, and total lipids: 59.8%, 0.71%, 2%, 1.01 gGlcEq/g, and 120 mg/g, respectively. Moreover, the sample from the Sefrou area (SFPEE) was richer in total proteins and minerals, with values of 2.5 g/100 g and 1.84%, respectively. The total polyphenol and flavonoid content in the propolis extracts were 117.38 and 194.68 mg of gallic acid equivalent/g, and 17.45-27.79 mg of quercetin equivalent/g, respectively. Regarding the antioxidant activity, the most effective propolis extract was the sample from the Sefrou area, at 72.5 µg/mL and 118.78 µmoL Fe2+/g for ABTS-half-maximal inhibitory concentration and FRAP-half maximal effective concentration, respectively. The analysis of phenolic compounds using high-performance liquid chromatography with a diode-array detector revealed the presence of 13 polyphenols. The main compound in the OAPEE sample was epicatechin (310 mg/g), whereas in the SFPEE sample was apigenin (410 mg/g). Regarding the antifungal activity against Candida species, the minimum inhibitory concentration and minimum fungicidal concentration of the Moroccan propolis ethanolic extracts ranged between 31.2 and 62.5 µg/mL and 62.5 and 125 µg/mL, respectively, comparable with fluconazole (as a reference antimycotic). Conclusion: This study suggests that Moroccan propolis (31.2 and 125 µg/mL) may be an important source of bioactive molecules with anticandidal activity. Propolis may be a promising naturally-occurring candidate for the development of antimycotic drugs.

Arbutus Unedo Honey and Propolis Ameliorate Acute Kidney Injury, Acute Liver Injury, and Proteinuria via Hypoglycemic and Antioxidant Activity in Streptozotocin-Treated Rats.

BACKGROUND/AIMS: Honey and propolis have biological and therapeutic effects in various pathological and clinical conditions such as hyperglycemia and diabetes. However, the combined use of honey and propolis has not been reported. The study evaluated the protective effect of Arbutus unedo honey, propolis and their combination in streptozotocin (STR)-induced hyperglycemia, acute kidney injury (AKI), liver injury, dyslipidemia, and proteinuria in male Wistar rats. METHODS: The study identified physicochemical characteristics, mineral and antioxidant content, and antioxidant activity in honey and propolis. Rats were assigned to five groups, with five rats in each group; control, STR-treated, STR-treated + honey (1g/kg/day), STR-treated + propolis (100 mg/day), and STR-treated + honey and propolis. On day 15, blood glucose, insulin, HBA1c, kidney function tests, liver enzymes, lipid profile, hemoglobin, and urine protein, creatinine, glucose, and electrolytes were analyzed. Liver, pancreas, and kidney tissues were studied histologically. The mineral component in honey and propolis was determined by atomic absorption spectrometry. Honey analysis was performed by HPLC. Chemical characterization of propolis was performed by LC/DAD/ESI-MSn . Measurement of blood and urine parameters was carried out with an automated analyzer (Architect c8000) and XT-1800i Automated Hematology Analyzer. Insulin concentration was determined by Elisa and insulin resistance was estimated by using HOMA-IR. RESULTS: Honey and propolis contain a high quantity of antioxidants and exhibit in vitro antioxidant activity. In STR-treated rats, blood glucose, HBA1c, creatinine, blood urea, liver enzymes, and urine protein significantly increased compared to the control group (P<0.05), while insulin, hemoglobin, and body weight significantly decreased. Histological changes were evident in the pancreas, kidney, and liver tissues. These results indicated AKI, liver injury, and pancreatic injury, which was evident with reducing the number of the island of Langerhans and marked hyperglycemia. The use of honey and propolis significantly (P<0.05) attenuated liver and kidney injury, and proteinuria, and improved level of hemoglobin, HBA1c, and insulin toward the normal range. The combination of honey and propolis was more effective than honey or propolis individually (P<0.05). CONCLUSION: the combination of propolis and honey can prevent STR-induced AKI, liver injury, proteinuria, dyslipidemia, anemia, hyperglycemia, and body weight loss, most likely by their hypoglycemic and antioxidant activities.

The Synergistic Beneficial Effect of Thyme Honey and Olive Oil against Diabetes and Its Complications Induced by Alloxan in Wistar Rats.

Diabetes is a metabolic disorder characterized by a chronic increase in blood glucose. Owing to the limitations observed with antidiabetics in modern medicine, medicinal plants and bee products are known as good matrices for the search for new antidiabetic molecules. The present study focused on the evaluation of the hypoglycemic and the protective properties of two natural products widely used in complementary and alternative medicine (thyme honey and olive oil). To achieve this, the study was carried out on Wistar rats rendered diabetic by the injection of a single dose of alloxan monohydrate (65 mg/kg body weight (BW)). First, the physicochemical characterization and the phytochemical analysis of thyme honey and olive oil were carried out, and then in vivo study was conducted on 42 Wistar rats divided into seven groups: three groups were normal, one group was untreated diabetic, and three groups were diabetic rats treated with thyme honey (2 g/kg BW) or olive oil (10 mL/kg BW) or their combination ((1 g/kg BW of thyme honey) and (5 mL/kg BW of olive oil)). During the experiment, the glycemia was measured regularly every 10 days. After 30 days of treatment, the rats were sacrificed. The serum and urine were analyzed to determine hepatic enzymes levels (AST, ALT, ALP, and LDH), lipidic profile (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein), and kidney parameters (urea, uric acid, creatinine, total protein, sodium, potassium, and chloride). The liver, pancreas, and kidneys were analyzed to evaluate their histological changes and to determine their enzymatic antioxidant content (catalase, GSH, and GPx) and the levels of MDA. The results obtained showed that thyme honey or olive oil, and especially their combination, improved significantly the blood glucose levels and they protect against metabolic changes and the complications induced by diabetes.

Protective Effect of Honey and Propolis against Gentamicin-Induced Oxidative Stress and Hepatorenal Damages.

Bee products are a promising source of phenolic compounds with strong antioxidant activity. The present study was designed to explore the protective effect of honey, propolis, and their combination on gentamicin-induced oxidative stress and hepatorenal dysfunction. This study was conducted on male Wistar rats by intraperitoneal injections of gentamicin (120 mg/kg BW/day, i.p.) or normal saline (1 ml/kg BW/day, i.p.) for 10 consecutive days. Honey (2 g/kg BW), propolis (100 mg/kg BW), or their combination were given daily by gavage to normal and gentamicin groups. Honey and propolis samples were evaluated for their phytochemical composition and antioxidant capacity. The in vitro investigations showed that the evaluated samples especially propolis extract have high antioxidant power associated with the presence of several phenolic compounds such as flavonoids, flavan-3-ols, hydroxybenzoic acids, hydroxycinnamic acids, and stilbenes, while honey contains only hydroxybenzoic acids and hydroxycinnamic acids. It was also shown that simultaneous treatment with honey or propolis extract alone or in association prevented changes caused by gentamicin administration and improved hepatic and renal functions. Changes caused by gentamicin administration, observed by in vivo experiments, include significant elevation of uric acid, urea, creatinine, and hepatic enzyme levels (ALT, AST, and ALP) and kidney biochemical changes (an increase of urea, uric acid, and creatinine and a decrease of albumin and total protein) as well as remarkable changes of renal and liver oxidative stress markers (CAT, GPx, and GSH) and elevation of MDA levels. Overall, it can be concluded that honey and propolis might be useful in the management of liver and renal diseases induced by xenobiotics.

Moroccan Bee Bread Improves Biochemical and Histological Changes of the Brain, Liver, and Kidneys Induced by Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO2) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO2) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics.

Chemical composition and antioxidant content of Thymus vulgaris honey and Origanum vulgare essential oil; their effect on carbon tetrachloride-induced toxicity.

AIM: The study investigated the chemical composition, antioxidant content, and antioxidant activity of Thymus vulgaris honey (TVH) and Origanum vulgare essential oil (OVEO) and their mixture effect on carbon tetrachloride (CCl4)-induced toxicity. MATERIALS AND METHODS: The study conducted physicochemical characterization and chemical analysis of TVH and OVEO with the use of gas chromatography-mass spectrometry and high-performance liquid chromatograph (HPLC). The antioxidant activity of TVH and OVEO was done with the use of 1,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The study used nine groups of rats to investigate the effect of TVH, OVEO, and a mixture of TVH and OVEO (HEM) on CCl4-induced toxicity. Intraperitoneal injection of CCl4 (1 mL/100 g) was used to induce toxicity. The doses of TVH and OVEO were 1 mg/kg.b.wt, and 50 mg/kg.b.wt, respectively. HEM contains TVH (1 mg/kg.b.wt) and OVEO (50 mg/kg.b.wt). RESULTS: TVH has a high content of phenols, flavonoids, and flavanols. HPLC analysis showed that TVH contains, for the 1st time, epicatechin gallate, and at a high concentration. OVEO includes a high percentage of carvacrol and thymol. With the use of DPPH, OVEO was more potent than TVH. CCl4 caused significant liver and kidney damage and lipid disorders, which were alleviated by HVT, OVEO, and HEM. HVT was more potent than OVEO (p<0.05), and HEM was more potent than HVT and OVEO (p<0.05). CONCLUSION: The study identified high content of epicatechin gallate for the 1st time in TVH, and OVEO contains a high percentage of thymol and carvacrol. Epicatechin gallate might be useful as a marker for TVH. Mixing OVEO and TVH significantly potentiated their protection against CCl4-induced liver and kidney toxicity.

Effect of antioxidant-rich propolis and bee pollen extracts against D-glucose induced type 2 diabetes in rats.

The present study was designed to investigate the preventive effect of propolis, bee pollen and their combination on Type 2 diabetes induced by D-glucose in rats. The study was carried out by feeding daily two concentrations (100 and 200 mg/Kg BW) of propolis or bee pollen (or their combination to normal (non-diabetic) and diabetic rats for a period of 16 weeks. In vivo biochemical changes associated to diabetes are induced by drinking a solution containing 10% of D-glucose (diabetic rats). The in vitro antioxidant activity was also evaluated and the chemical composition of propolis and bee pollen extracts was determined by UHPLC-DAD. Phytochemical composition of propolis and bee pollen revealed the presence of several natural antioxidants, such as hydroxycinnamic acids, hydroxybenzoic acids, flavonoids, flavan-3-ols and stilbens. The major antioxidant compound present in propolis was Naringin (290.19 ± 0.2 mg/Kg) and in bee pollen was apigenin (162.85 ± 17.7 mg/Kg). These results have been related with a high antioxidant activity, more intense in propolis extract. In rats, the administration of D-glucose had induced hyperglycemia (13.2 ± 0.82 mmol/L), increased plasmatic insulin levels (25.10 ± 2.12 U/L) and HOMA-IR index (14.72 ± 0.85) accompanied with dyslipidemia, elevation of hepatic enzyme levels, and a change in both serum renal biomarkers and plasmatic calcium. The co-administration of propolis and bee pollen extracts alone or in combination restored these biochemical parameters and attenuated the deleterious effects of D-glucose on liver and kidney functions. Furthermore, these effects were better attenuated in the combined therapy-prevented diabetic rats. Hence, it is possible to conclude that propolis and bee pollen can be used as a preventive natural product against diabetes induced dyslipidemia and hepato-renal damage.

Beneficial Effects of Apple Vinegar on Hyperglycemia and Hyperlipidemia in Hypercaloric-Fed Rats.

The main objective of this study is to determine the effects of apple vinegar on the metabolic changes caused by hypercaloric diet in Wistar rats. Apple vinegar was first analyzed to find out the total acidity, the polyphenolic and flavonoid contents, the total antioxidant capacity, and the free radical scavenging activity. In vivo study on adult male and female Wistar rats was conducted by administering a drink containing either 10% D-glucose or water (control) for five weeks. Apple vinegar is administered daily by gavage (2 mL/kg) to rats fed D-glucose for 5 weeks. The results showed that the polyphenolic content in apple vinegar was 148.02 ± 10.16 mg GAE/100 mL, flavonoid content was 22.93 ± 0.73 QE/100 mL, and total antioxidant capacity was 13.4 ± 0.47 mg AAE/100 mL. Free radical IC50 apple vinegar scavenging activity (DPPH) was 0.74 ± 0.154 µL/mL. The total acidity was (3.24 ± 0.02 mg AAE/100 mL). The treatment during five weeks with D-glucose leads to increased plasma glucose, lipid profile, hepatic enzyme levels, urea, and creatinine. Simultaneous treatment with apple vinegar improves the parameters studied. These results clearly show that the daily consumption of vinegar can reduce the rise in blood sugar and lipid profile induced by hypercaloric diet in rats. Therefore, the use of apple vinegar would have a very beneficial effect in the prevention of metabolic disorders caused by high-caloric food.

The Antioxidant Content and Protective Effect of Argan Oil and Syzygium aromaticum Essential Oil in Hydrogen Peroxide-Induced Biochemical and Histological Changes.

Oxidative stress is an important etiology of chronic diseases and many studies have shown that natural products might alleviate oxidative stress-induced pathogenesis. The study aims to evaluate the effect of Argan oil and Syzygium aromaticum essential oil on hydrogen peroxide (H2O2)-induced liver, brain and kidney tissue toxicity as well as biochemical changes in wistar rats. The antioxidant content of Argan oil and Syzygium aromaticum essential oil was studied with the use of gas chromatography. The animals received daily by gavage, for 21 days, either distilled water, Syzygium aromaticum essential oil, Argan oil, H2O2 alone, H2O2 and Syzygium aromaticum essential oil, or H2O2 and Argan oil. Blood samples were withdrawn on day 21 for the biochemical blood tests, and the kidney, liver and brain tissue samples were prepared for histopathology examination. The results showed that the content of antioxidant compounds in Syzygium aromaticum essential oil is higher than that found in Argan oil. H2O2 increased level of blood urea, liver enzymes, total cholesterol, Low Density Lipoprotein (LDL-C), Triglycerides (TG) and Very Low Density Lipoprotein (VLDL), and decreased the total protein, albumin and High Density Lipoprotein-cholesterol (HDL-C). There was no significant effect on blood electrolyte or serum creatinine. The histopathology examination demonstrated that H2O2 induces dilatation in the central vein, inflammation and binucleation in the liver, congestion and hemorrhage in the brain, and congestion in the kidney. The H2O2-induced histopathological and biochemical changes have been significantly alleviated by Syzygium aromaticum essential oil or Argan oil. It is concluded that the Argan oil and especially the mixture of Argan oil with Syzygium aromaticum essential oil can reduce the oxidative damage caused by H2O2, and this will pave the way to investigate the protective effects of these natural substances in the diseases attributed to the high oxidative stress.