Biosynthesized ZnO Nanoparticles Using Albizia lebbeck Extract Induced Biochemical and Morphological Alterations in Wistar Rats

Nano-based particles synthesized via green routes have a particular structure that is useful in biomedical applications as they provide cheap, eco-friendly, and non-toxic nanoparticles. In the present study, we reported the effect of various concentrations of Zinc oxide nanoparticles synthesized using A. lebbeck stem bark extract (ZnO NPsAL) as stabilizing agent on rat biochemical profiles and tissue morphology. Adult Wistar rats weighing 170 ± 5 g were randomly classified into eight groups of five rats each; Group A served as a control fed with normal diet and water. Groups B1, B2, C1, C2, D1, D2, and E were treated with 40 mg/kg and 80 mg/kg of the 0.01, 0.05, and 0.1 M biosynthesized ZnO NPsAL and zinc nitrate daily by the gavage method, respectively. The rats were anesthetized 24 h after the last treatment, blood samples, kidney, heart, and liver tissues were collected for biochemical and histopathological analysis. The rats mean body weight, serum alkaline phosphatase, alanine aminotransferase, creatinine, urea, bilirubin, protein, albumin, globulin, total cholesterol, triacylglycerol, and high-density lipoprotein were significantly altered with an increased concentration of biosynthesized ZnO NPsAL when compared with the control group (p < 0.05; n ≥ 5). Furthermore, histopathological analysis of treated rats’ kidney, heart, and liver tissue revealed vascular congestion, tubular necrosis, inflammation, and cytoplasmic vacuolation. Biosynthesized ZnO NPsAL showed significant alteration in biochemical parameters and tissue morphology in rats with increasing concentrations of the nanoparticles.     

Benefits of Anthocyanin-Rich Black Rice Fraction and Wood Sterols to Control Plasma and Tissue Lipid Concentrations in Wistar Kyoto Rats Fed an Atherogenic Diet

Background: This study reports on the relative effects of administrating a cyanidin-3-O-glucoside-rich black rice fraction (BRF), a standardized wood sterol mixture (WS), and a combination of both to lower plasma and target tissue lipid concentrations in Wistar Kyoto (WKY) rats fed atherogenic diets. Methods: Male WKY (n = 40) rats were randomly divided into five groups, which included a nonatherogenic control diet and atherogenic diets that included a positive control and atherogenic diets supplemented with BRF or WS, respectively, and a combination of both BRF + WS. Plasma and target tissue liver, heart and aorta cholesterol, and triacylglycerides (TAG) content were also measured. Results: Rats fed atherogenic diets exhibited elevated hyperlipidemia compared to counterparts fed nonatherogenic diets (p < 0.001); this effect was mitigated by supplementing the atherogenic diets with BRF and WS, respectively (p < 0.05). Combining BRF with WS to enrich the supplement lowered cholesterol similar to the WS effect (p < 0.05) and lowered TAG characteristic to the BRF effect (p < 0.05). Conclusions: Rats fed diets containing BRF or WS effectively mitigate the hypercholesterolemia and elevated TAG induced by feeding an atherogenic diet. The benefit of adding BRF + WS together is relevant to the lipid parameter measured and is target tissue-specific.     

Phytic Acid Protects from Oxidative Stress Induced by Iron-Overload and High-Fat Diets in ß2-Microglobulin Knockout Mice

The objective of this study was to examine the protective effect of phytic acid (PA) in reducing oxidative stress in an animal model for human hereditary hemochromatosis (HH) fed high-fat diets. Sixty-four ß2 microglobulin knockout (β2m KO) mice were randomly assigned to three treatments by feeding: control (basal), atherogenic (AT), and polyunsaturated fatty acid (PUFA) diets. One-half of the mice in each treatment group were fed 2% (wt/wt) PA. The ß2m+/+ mice (wild type (WT)) were fed a basal diet. All seven groups were fed for 10 weeks with a 50-ppm iron-containing diet (AIN-93G). Free iron and lipids were measured in serum samples. Nonheme iron, thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase concentrations were measured in the liver tissue. Nonheme iron concentration in ß2m KO mice (on the basal diet) was 20× higher (p < 0.0001) than in the WT mice. Compared to the WT mice, ß2m KO mice had a significantly higher concentration of free iron in the serum (p < 0.0001), six-fold higher hepatic TBARs (p < 0.0001), and 18% lower hepatic SOD level. When PA was added to the β2m KO basal diet, a reduction (26 to 50%) of iron concentration was seen in the liver and heart. The addition of PA also significantly reduced TBARs in all three dietary groups of the iron-overloaded group, but most effectively in the control group. An increase in SOD concentration was seen only in the PUFA group, but serum triacylglycerol (TG) concentration was reduced in both dietary fat groups. In conclusion, our results suggest that PA protects against oxidative stress-induced by genetic iron overload alone or when fed high fat.     

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women

An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case–control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06–6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.     

Polysaccharide-Rich Red Algae (Gelidium amansii) Hot-Water Extracts Alleviate Abnormal Hepatic Lipid Metabolism without Suppression of Glucose Intolerance in a Streptozotocin/Nicotinamide-Induced Diabetic Rat Model

This study was designed to investigate the effects of polysaccharide-rich red algae (Gelidium amansii) hot-water extracts (GHE) on lipid and glucose metabolism in rats with streptozotocin (STZ)/nicotinamide (NA)-induced diabetes. Rats were divided into three groups: NC—normal control group), DM—diabetic group, and DG—diabetic group supplemented with GHE (5%). The experimental diet and drinking water were available ad libitum for 10 weeks. After the 10-week feeding duration, the body weight, liver weight, total adipose tissue weight, and hepatic TBARS and cholesterol levels were significantly increased, and hepatic glycogen content and adipose lipolysis rate were significantly decreased in the DM group, which could be effectively reversed by supplementation of GHE. However, GHE supplementation could not improve the glucose intolerance in DM rats. It was interesting to note that GHE supplementation could decrease the liver glucose-6-phosphotase activity, which was increased in DM rats. Taken together, these results suggested that GHE feeding may ameliorate abnormal hepatic lipid metabolism, but not glucose intolerance, in diabetic rats induced by STZ/NA.     

Acidified Nitrite Accelerates Wound Healing in Type 2 Diabetic Male Rats: A Histological and Stereological Evaluation

Impaired skin nitric oxide production contributes to delayed wound healing in type 2 diabetes (T2D). This study aims to determine improved wound healing mechanisms by acidified nitrite (AN) in rats with T2D. Wistar rats were assigned to four subgroups: Untreated control, AN-treated control, untreated diabetes, and AN-treated diabetes. AN was applied daily from day 3 to day 28 after wounding. On days 3, 7, 14, 21, and 28, the wound levels of vascular endothelial growth factor (VEGF) were measured, and histological and stereological evaluations were performed. AN in diabetic rats increased the numerical density of basal cells (1070 ± 15.2 vs. 936.6 ± 37.5/mm³) and epidermal thickness (58.5 ± 3.5 vs. 44.3 ± 3.4 μm) (all p < 0.05); The dermis total volume and numerical density of fibroblasts at days 14, 21, and 28 were also higher (all p < 0.05). The VEGF levels were increased in the treated diabetic wounds at days 7 and 14, as was the total volume of fibrous tissue and hydroxyproline content at days 14 and 21 (all p < 0.05). AN improved diabetic wound healing by accelerating the dermis reconstruction, neovascularization, and collagen deposition.     

Preservation of Contractile Reserve and Diastolic Function by Inhibiting the NLRP3 Inflammasome with OLT1177® (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction

Interleukin-1β (IL-1β), a product of the NLRP3 inflammasome, modulates cardiac contractility and diastolic function. We proposed that OLT1177^® (dapansutrile), a novel NLRP3 inhibitor, could preserve contractile reserve and diastolic function after myocardial infarction (MI). We used an experimental murine model of severe ischemic cardiomyopathy through the ligation of the left coronary artery without reperfusion, and after 7 days randomly assigned mice showing large anterior MI (>4 akinetic segments), increased left ventricular (LV) dimensions ([LVEDD] > 4.4 mm), and reduced function (LV ejection fraction < 40%) to a diet that was enriched with OLT1177^® admixed with the chow in the diet at 3.75 g/kg (Group 1 [n = 10]) or 7.5 g/kg (Group 2 [n = 9]), or a standard diet as the no-treatment control group (Group 3 [n = 10]) for 9 weeks. We measured the cardiac function and contractile reserve with an isoproterenol challenge, and the diastolic function with cardiac catheterization at 10 weeks following the MI surgery. When compared with the control (Group 3), the mice treated with OLT1177 (Group 1 and 2) showed significantly greater preservation of their contractile reserve (the percent increase in the left ventricular ejection fraction [LVEF] after the isoproterenol challenge was +33 ± 11% and +40 ± 6% vs. +9 ± 7% in the standard diet; p < 0.05 and p < 0.005 for Group 1 and 2, respectively) and of diastolic function measured as the lower left ventricular end-diastolic pressure (3.2 ± 0.5 mmHg or 4.5 ± 0.5 mmHg vs. 10.0 ± 1.6 mmHg; p < 0.005 and p < 0.009 respectively). No differences were noted between the resting LVEF of the MI groups. These effects were independent of the effects on the ventricular remodeling after MI. NLRP3 inflammasome inhibition with OLT1177^® can preserve β-adrenergic responsiveness and prevent left ventricular diastolic dysfunction in a large non-reperfused anterior MI mouse model. OLT1177^® could therefore be used to prevent the development of heart failure in patients with ischemic cardiomyopathy.     

The Effect of Chrysin-Loaded Phytosomes on Insulin Resistance and Blood Sugar Control in Type 2 Diabetic db/db Mice

Although a variety of beneficial health effects of natural flavonoids, including chrysin, has been suggested, poor solubility and bioavailability limit their practical use. As a promising delivery system, chrysin-loaded phytosomes (CPs) were prepared using egg phospholipid (EPL) at a 1:3 molar ratio and its antidiabetic effects were assessed in db/db diabetic mice. Male C57BLKS/J-db/db mice were fed a normal diet (control), chrysin diet (100 mg chrysin/kg), CP diet (100 mg chrysin equivalent/kg), metformin diet (200 mg/kg) or EPL diet (vehicle, the same amount of EPL used for CP preparation) for 9 weeks. Administration of CP significantly decreased fasting blood glucose and insulin levels in db/db mice compared with the control. An oral glucose tolerance test and homeostatic model assessment for insulin resistance were significantly improved in the CP group (p < 0.05). CP treatment suppressed gluconeogenesis via downregulation of phosphoenolpyruvate carboxykinase while it promoted glucose uptake in the skeletal muscle and liver of db/db mice (p < 0.05). The CP-mediated improved glucose utilization in the muscle was confirmed by upregulation of glucose transporter type 4, hexokinase2 and peroxisome proliferator-activated receptor γ during treatment (p < 0.05). The CP-induced promotion of GLUT4 plasma translocation was confirmed in the skeletal muscle of db/db mice (p < 0.05). Based on the results, CP showed greater antidiabetic performance compared to the control by ameliorating insulin resistance in db/db mice and phytosome can be used as an effective antidiabetic agent.     

Secondary Metabolite Profiling,Anti-Inflammatory and Hepatoprotective Activity of Neptunia triquetra (Vahl) Benth

The present study aimed to analyze the phytoconstituents of Neptunia triquetra (Vahl) Benth. Anti-inflammatory and hepatoprotective activities of ethanol (EE), chloroform (CE) and dichloromethane (DCME) of stem extracts were evaluated using in vivo experimental models. The extracts were analyzed for phytoconstituents using GC-HRMS. Anti-inflammatory activity of CE, EE and DCME was accessed using carrageenan-induced paw oedema, cotton pellet-induced granuloma and the carrageenan-induced air-pouch model in Wistar albino rats. The hepatotoxicity-induced animal models were investigated for the biochemical markers in serum (AST, ALT, ALP, GGT, total lipids and total protein) and liver (total protein, total lipids, GSH and wet liver weight). In the in vivo study, animals were divided into different groups (six in each group) for accessing the anti-inflammatory and hepatoprotective activity, respectively. GC-HRMS analysis revealed the presence of 102 compounds, among which 24 were active secondary metabolites. In vivo anti-inflammatory activity of stem extracts was found in the order: indomethacin > chloroform extract (CE) > dichloromethane extract (DCME) > ethanolic extract (EE), and hepatoprotective activity of stem extracts in the order: CE > silymarin > EE > DCME. The results indicate that N. triquetra stem has a higher hepatoprotective effect than silymarin, however the anti-inflammatory response was in accordance with or lower than indomethacin.     

Tart Cherry Juice and Seeds Affect Pro-Inflammatory Markers in Visceral Adipose Tissue of High-Fat Diet Obese Rats

Background: Tart cherries (Prunus cerasus L.) are a rich source of anthocyanins. They are phytochemical flavonoids found in red and blue fruits, and vegetables that can reduce hyperlipidemia. Visceral Adipose Tissue (VAT) has emerged as a major player in driving obesity-related inflammatory response. Methods: This study has investigated the potential positive effects of tart cherries on rats with Diet-Induced Obesity (DIO). In particular, the inflammatory status in retroperitoneal (RPW) and perigonadal (PGW) adipose tissue were studied. Rats were fed ad libitum for 17 weeks with a hypercaloric diet with the supplementation of tart cherries seeds powder (DS) and seeds powder plus tart cherries juice containing 1mg of anthocyanins (DJS). In RPW and PGW, expression of CRP, IL-1 β, TNF-α, CCL2 and CD36, were measured by qRT-PCR, Western blot and immunohistochemistry techniques. Results: No differences in the weight of RPW and PGW animals were found between DS and DJS groups compared to DIO rats. However, an increase of inflammatory markers was observed in DIO group in comparison with control lean rats. A modulation of these markers was evident upon tart cherry supplementation. Conclusion: Study results suggest that tart cherry enriched-diet did not modify the accumulation of visceral fat, but it decreased inflammatory markers in both tissues. Therefore, this supplementation could be useful, in combination with healthy lifestyles, to modify adipose tissue cell metabolism limiting-obesity related organ damage.     

Impact of Targeted Specific Antibiotic Delivery for Gut Microbiota Modulation on High-Fructose-Fed Rats

The objective of present investigation was to study the effect of gut microbiota alteration by oral administration of targeted delivery of pH sensitive cefdinir microspheres to high-fructose-fed (HFD) rats. Rats were fed with a high-fructose diet with or without cefdinir microsphere administration for 30 days. The fecal microbiota community, oral glucose tolerance, the markers of liver injury, plasma and hepatic lipids profile, and histological evaluation were investigated. The levels of blood glucose, liver injury markers, lipid profile in plasma and liver, and fat tissue were significantly increased in high-fructose-fed rats. However, after pH-sensitive cefdinir microsphere administration, the elevation of these parameters was significantly suppressed. Cef EL significantly lowered the increased AST (p?<?0.05) and ALT (p?<?0.001) levels in HFD group. There is a significant lower (p?<?0.01) AUC_glucose level in Cef EL group than HFD group The histological changes in the liver and the small and large intestines were more profound in HFD group as compared to cefdinir-treated HFD and control groups. Feeding of cefdinir microsphere sustained lactobacilli and bifidobacteria and significantly decreased (p?<?0.05) the number of Enterobacteriaceae induced by HFD. Experimental evidences demonstrated that the effectiveness of pH-specific cefdinir microsphere on reducing insulin resistance and development of metabolic changes in high-fructose-fed rats and suggested that it may be a promising therapeutic agent in treating type 2 diabetes. Intestinal-targeted antibiotic delivery needs to be further explored for its therapeutic applications.     

The enhanced expression of IL-17-secreting T cells during the early progression of atherosclerosis in ApoE-deficient mice fed on a western-type diet

Atherosclerosis is a chronic progressive inflammatory disorder and the leading cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell-derived cytokines, such as inteferon (IFN)-γ, interleukin (IL)-17 and IL-4, during the progression of atherosclerosis in apolipoprotein E-null (ApoE^−/−) mice, to understand the role of immune responses in different stages of atherosclerosis. Male ApoE^−/− mice were fed a high-fat, western-type diet (WD: 21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6 wild-type control mice fed a standard chow diet. Atherosclerotic lesions appeared in the aortic sinus of ApoE^−/− mice 4 weeks after WD and the lesions progressed and occupied >50% of the total sinus area 16 weeks after WD. Aortic IL-17 mRNA and protein expression started to increase in ApoE^−/− mice after 4 weeks on the WD and peaked at around 8–12 weeks on the WD. In terms of systemic expression of T-cell-derived cytokines, IL-17 production from splenocytes after anti-CD3/CD28 stimuli increased from 4 weeks on the WD, peaked at 12 weeks and returned to control levels at 16 weeks. The production of IFN-γ and IL-4 (Th1 and Th2 cytokines, respectively) from splenocytes was delayed compared with IL-17. Taken together, the present data indicate that Th17 cell response may be involved at an early stage in the development of atherosclerosis.     

Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1^Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p–Akt^Ser473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.     

Green synthesis of gold nanoparticles from Fritillaria cirrhosa and its anti-diabetic activity on Streptozotocin induced rats

To evaluate the anti-diabetic effect of Fritillaria cirrhosa gold nanoparticles on Streptozotocin (STZ) stimulated diabetic preclinical models. The albino rats of either sex were equally distributed to five different groups. Group-I represented as Control; Group-II represented as diabetic control (STZ alone); Group-III represented as 10 mg/kg body weight of Fritillaria cirrhosa gold nanoparticles + diabetes; Group-IV represented as 20 mg/kg body weight of Fritillaria cirrhosa gold nanoparticles + diabetes; Group-V represented as 0.1 mg/kg body weight of glibenclamide + diabetes. The animals were killed after the experimental period. The blood and organs samples were gathered and stored for the additional investigations. The gold nanoparticles were inspected via the UV spectrophotometer, HR-TEM, XRD and FT-IR techniques. The bodyweight, kidney and liver weight were tabulated. The food and water consumption were monitored in all the experimental rats. The serum markers, hepatic markers and renal markers were quantified in both normal and investigational rats. The lipid peroxidation and antioxidant status were quantified in the control and experimental rats. The histopathological alterations were also studied in all the experimental animals. The standard drug glibenclamide was used to compare the synthesized AuNPs. The study revealed that the AuNPs treatment restores the serum, hepatic and renal marker in the STZ-challenged diabetic rats. The AuNPs treatment modulates the antioxidants level and decreased the lipid peroxidation by its antioxidant properties. The pathology results revealed that the AuNPs treatment induces the regeneration of islets cells of pancreas in the experimental rats. The research study proved that the Fritillaria cirrhosa AuNPs exerts anti-diabetic properties.     

Lipolytic Postbiotic from Lactobacillus paracasei Manages Metabolic Syndrome in Albino Wistar Rats

The current study investigates the capacity of a lipolytic Lactobacillus paracasei postbiotic as a possible regulator for lipid metabolism by targeting metabolic syndrome as a possibly safer anti-obesity and Anti-dyslipidemia agent replacing atorvastatin (ATOR) and other drugs with proven or suspected health hazards. The high DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS [2,2′-azino-bis (3-ethyl benzothiazoline-6-sulphonic acid)] scavenging activity and high activities of antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) of the Lactobacillus paracasei postbiotic (cell-free extract), coupled with considerable lipolytic activity, may support its action against metabolic syndrome. Lactobacillus paracasei isolate was obtained from an Egyptian cheese sample, identified and used for preparing the postbiotic. The postbiotic was characterized and administered to high-fat diet (HFD) albino rats (100 and 200 mg kg⁻¹) for nine weeks, as compared to atorvastatin (ATOR; 10 mg kg⁻¹). The postbiotic could correct the disruption in lipid metabolism and antioxidant enzymes in HFD rats more effectively than ATOR. The two levels of the postbiotic (100 and 200 mg kg⁻¹) reduced total serum lipids by 29% and 34% and serum triglyceride by 32–45% of the positive control level, compared to only 25% and 35% in ATOR’s case, respectively. Both ATOR and the postbiotic (200 mg kg⁻¹) equally decreased total serum cholesterol by about 40% and 39%, while equally raising HDL levels by 28% and 30% of the positive control. The postbiotic counteracted HFD-induced body weight increases more effectively than ATOR without affecting liver and kidney functions or liver histopathology, at the optimal dose of each. The postbiotic is a safer substitute for ATOR in treating metabolic syndrome.     

Evaluation of Wound-Healing and Antioxidant Effects of Marantodes pumilum (Blume) Kuntze in an Excision Wound Model

Marantodes pumilum (MP) is a great source of herbal medicine used traditionally by both men and women for various purposes. MP may have potential wound-healing effects due to its diverse biological properties. An extensive study was conducted in a normal male rat model for determining the effects of MP var. pumila (MPvp) and var. alata (MPva) on the wound healing process. Here, 126 male Sprague-Dawley rats were divided randomly into seven groups as follows: sham-operated (SH), vehicle dressing (VD), flavine dressing (FD), MPvp leaves (PL), MPvp roots (PR), MPva leaves (AL), and MPva roots (AR). The parameters studied were the percentage of wound contraction, histomorphology study by hematoxylin and eosin (H&E), Masson–Goldner trichrome (MGT), and immunohistochemistry (IHC) staining. In addition, the levels of enzymatic antioxidants and malondialdehyde were also measured in the wound tissue homogenates. Wounds treated with extracts (PL, PR, AL, and AR) showed significantly faster healing (p < 0.05) compared to untreated and control groups (SH, VD, and FD). Histological analysis among MP-treated groups revealed better re-epithelialization, higher collagen deposition, enhanced fibronectin content and fibroblast cells, and higher fiber transformation from collagen-III to collagen-I, accompanied with a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. MP has antioxidant effects that may enhance wound healing in the rat model.     

Resveratrol Hinders Postovulatory Aging by Modulating Oxidative Stress in Porcine Oocytes

Postovulatory aging of the mammalian oocytes causes deterioration of oocytes through several factors including oxidative stress. Keeping that in mind, we aimed to investigate the potential of a well-known antioxidant, resveratrol (RV), to evaluate the adverse effects of postovulatory aging in porcine oocytes. After in vitro maturation (IVM), a group of (25–30) oocytes (in three replicates) were exposed to 0, 1, 2, and 4 μmol/L of RV, respectively. The results revealed that the first polar body (PB1) extrusion rate of the oocytes significantly increased when the RV concentration reached up to 2 μmol/L (p < 0.05). Considering optimum RV concentration of 2 μmol/L, the potential of RV was evaluated in oocytes aged for 24 and 48 h. We used fluorescence microscopy to detect the relative level of reactive oxygen species (ROS), while GHS contents were measured through the enzymatic method. Our results revealed that aged groups (24 h and 48 h) treated with RV (2 μmol/L) showed higher (p < 0.05) ROS fluorescence intensity than the control group, but lower (p < 0.05) than untreated aged groups. The GSH content in untreated aged groups (24 h and 48 h) was lower (p < 0.05) than RV-treated groups, but both groups showed higher levels than the control. Similarly, the relative expression of the genes involved in antioxidant activity (CAT, GPXGSH-Px, and SOD1) in RV-treated groups was lower (p < 0.05) as compared to the control group but higher than that of untreated aged groups. Moreover, the relative mRNA expression of caspase-3 and Bax in RV-treated groups was higher (p < 0.05) than the control group but lower than untreated groups. Furthermore, the expression of Bcl-2 in the RV-treated group was significantly lower than control but higher than untreated aged groups. Taken together, our findings revealed that the RV can increase the expression of antioxidant genes by decreasing the level of ROS, and its potent antiapoptotic effects resisted against the decline in mitochondrial membrane potential in aged oocytes.     

Pomegranate Seed Oil and Bitter Melon Extract Affect Fatty Acids Composition and Metabolism in Hepatic Tissue in Rats

Pomegranate seed oil (PSO) and bitter melon dried fruits (BME) are used as natural remedies in folk medicine and as dietary supplements. However, the exact mechanism of their beneficial action is not known. The aim of study was to assess how the diet supplementation with PSO and/or with an aqueous solution of Momordica charantia affects the metabolism of fatty acids, fatty acids composition and the level of prostaglandin E₂ (PGE₂) in rat liver. Animals (Sprague-Dawley female rats, n = 48) were divide into four equinumerous groups and fed as a control diet or experimental diets supplemented with PSO, BME or both PSO and BME for 21 weeks. Fatty acids were determined using gas chromatography with flame ionization detection. PSO added to the diet increased the rumenic acid content (p < 0.0001) and increased accumulation of n-6 fatty acids (p = 0.0001) in hepatic tissue. Enrichment of the diet either with PSO or with BME reduced the activity of Δ⁶-desaturase (D6D) (p = 0.0019), whereas the combination of those dietary factors only slightly increased the effect. Applied dietary supplements significantly reduced the PGE₂ level (p = 0.0021). No significant intensification of the influence on the investigated parameters resulted from combined application of PSO and BME. PSO and BME have potential health-promoting properties because they influence fatty acids composition and exhibit an inhibiting effect on the activity of desaturases and thus they contribute to the reduction in the metabolites of arachidonic acid (especially PGE₂).     

Contrasting Roles of Ang II and ACEA in the Regulation of IL10 and IL1β Gene Expression in Primary SHR Astroglial Cultures

Angiotensin (Ang) II is well-known to have potent pro-oxidant and pro-inflammatory effects in the brain. Extensive crosstalk between the primary Ang II receptor, Ang type 1 receptor (AT1R), and the cannabinoid type 1 receptor (CB1R) has been demonstrated by various groups in the last decade. Since activation of glial CB1R has been demonstrated to play a key role in the resolution of inflammatory states, we investigated the role of Ang II (100 nM) and/or ACEA (10 nM), a potent CB1R-specific agonist in the regulation of inflammatory markers in astrocytes from spontaneously hypertensive rats (SHR) and Wistar rats. Astrocytes were cultured from brainstems and cerebellums of SHR and Wistar rats and assayed for IL1β and IL10 gene expression and secreted fraction, in treated and non-treated cells, by employing qPCR and ELISA, respectively. mRNA expression of both IL10 and IL1β were significantly elevated in untreated brainstem and cerebellar astrocytes isolated from SHR when compared to Wistar astrocytes. No changes were observed in the secreted fraction. While ACEA-treatment resulted in a significant increase in IL10 gene expression in Wistar brainstem astrocytes (Log2FC ≥ 1, p < 0.05), its effect in SHR brainstem astrocytes was diminished. Ang II treatment resulted in a strong inhibitory effect on IL10 gene expression in astrocytes from both brain regions of SHR and Wistar rats (Log2FC ≤ −1, p < 0.05), and an increase in IL1β gene expression in brainstem astrocytes from both strains (Log2FC ≥ 1, p < 0.05). Co-treatment of Ang II and ACEA resulted in neutralization of Ang II-mediated effect in Wistar brainstem and cerebellar astrocytes, but not SHR astrocytes. Neither Ang II nor ACEA resulted in any significant changes in IL10 or IL1β secreted proteins. These data suggest that Ang II and ACEA have opposing roles in the regulation of inflammatory gene signature in astrocytes isolated from SHR and Wistar rats. This however does not translate into changes in their secreted fractions.