Bioassay-guided isolation of anti-inflammatory and antinociceptive metabolites among three Moroccan Juniperus leaves extract supported with in vitro enzyme inhibitory assays.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as "Al'Araar" for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals. AIM OF THE STUDY: The current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays. MATERIALS AND METHODS: Firstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds. RESULTS: The results showed that acute oral administration of the extracts (300-500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 µM, respectively. CONCLUSION: J. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved.

Mechanistic approach of the therapeutic potential of mesenchymal stem cells on brain damage in irradiated mice: emphasis on anti-inflammatory and anti-apoptotic effects.

BACKGROUND AND OBJECTIVES: Brain damage which has been induced by radiation generally occurs in radiotherapeutics patients. Stem cell transplantation represents a vital applicant for alleviating neurodegenerative disorders. This work aims at exploring the potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) on brain injury induced by γ radiation in mice and the possible underlying mechanisms were elucidated. MATERIALS AND METHODS: Mice were allocated into three groups; Group I (Control), Group II (Irradiated control) where mice submitted to 5 Gy of whole-body γ radiation, Group III (Irradiated + BM-MSCs) where mice were intravenously injected of BM-MSCs at a dose of 106 cells/mice 24 h following irradiation. Animals were sacrificed 28 d following exposure to γ radiation. RESULTS: It was observed that BM-MSCs therapy provided a valuable tissue repair as evidenced by a reduction in inflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), nuclear factor kappa (NF-κß), phosphorylated NF-κß-p65 (P-NF-κß-p65), interferon-gamma (IFNγ) and monocyte chemoattractant protein-1 (MCP-1) associated with decreased levels of transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) in brain tissues of irradiated mice. Furthermore, neuronal apoptosis was declined in brain tissues of the BM-MSCs group as remarkable inhibition of caspase-3 and Bax accompanied by elevation of Bcl-2 proteins expression. These results were supported by histopathological investigation. CONCLUSIONS: In conclusion, BM-MSCs could display a vital rule in alleviating brain injury in radio-therapeutic patients.

Design of pH-responsive polymeric nanocarrier for targeted delivery of pyrogallol with enhanced antitumor potential in colon cancer.

PURPOSE: To synthesize a polymeric pH-sensitive nanocarrier for the delivery of pyrogallol and investigate the anti-tumor activity of pyrogallol-loaded polymeric nanogel against colon cancer in rats. METHODS: Poly(ethylene glycol)/polyacrylic acid (PEG/PAAc) nanogel was performed using gamma irradiation technique at irradiation doses; 30,40, and 50 kGy. The particle size distribution and diameter were investigated under the influence of various parameters by using dynamic light scattering analysis (DLS). The particle size was diminished by increasing AAc content and irradiation dose. Characterization of the performed nanogel was performed by (FT-IR) and (TEM). In vitro drug release behavior of the nanogel towards pyrogallol drug was assessed. Furthermore, the anti-cancer therapeutic efficiency of pyrogallol loaded PEG/PAAc nanogel was evaluated in a chemically induced colon cancer model in rats. RESULTS: Pyrogallol/PEG/PAAc significantly reduced tumor incidence and volume as compared to DMH group. Also, it activated apoptotic pathway via up-regulating Bax, cytochrome C, cleaved caspase-3, p53, and down-regulating Bcl-2 expression. Furthermore, it attenuated cell cycle progression via reducing Cyclin A, Cyclin D1, and Cyclin E expression. It exhibited anti-proliferative activity through inhibiting PI3K/AKT signaling and downregulating the phosphorylation of AKT. It reduced pro-inflammatory cytokines TNF-α and IL-6. Results were confirmed by histopathological examination of colonic tissue. Interestingly, pyrogallol/PEG/PAAc demonstrated anti-tumor potential more efficiently than free pyrogallol, revealing localized drug delivery. CONCLUSION: This formulation could be considered as a promising agent in the treatment of colon cancer.

Optimization of catalytic properties of Mucor racemosus lipase through immobilization in a biocompatible alginate gelatin hydrogel matrix for free fatty acid production: a sustainable robust biocatalyst for ultrasound-assisted olive oil hydrolysis.

Immobilization is a key technology that improves the operational stability of enzymes. In this study, alginate-gelatin (Alg-Gel) hydrogel matrix was synthesized and used as immobilization support for Mucor racemosus lipase (Lip). Enzyme catalyzed ultrasound-assisted hydrolysis of olive oil was also investigated. Alg-Gel matrix exhibited high entrapment efficiency (94.5%) with a degradation rate of 42% after 30 days. The hydrolysis of olive oil using Alg-Gel-Lip increased significantly (P < 0.05) as compared to free Lip. Optimum pH and temperature were determined as pH 5.0 and 40 °C, respectively. The Vmax values for free and immobilized Lip were determined to be 5.5 mM and 5.8 mM oleic acid/min/ml, respectively, and the Km values were 2.2 and 2.58 mM/ml respectively. Thermal stability was highly improved for Alg-Gel-Lip (t1/2 650 min and Ed 87.96 kJ/mol) over free Lip (t1/2 150 min and Ed 23.36 kJ/mol). The enzymatic activity of Alg-Gel-Lip was preserved at 96% after four consecutive cycles and 90% of the initial activity after storage for 60 days at 4 °C. Alg-Gel-Lip catalyzed olive oil hydrolysis using ultrasound showed a significant (P < 0.05) increase in hydrolysis rate compared to free Lip (from 0.0 to 58.2%, within the first 2 h). In contrast to traditional methodology, using ultrasonic improved temperature-dependent enzymatic catalyzed reactions and delivered greater reaction yields. Results suggest that Alg-Gel-Lip biocatalyst has great industrial application potential, particularly for free fatty acid production. In addition, the combined use of enzyme and ultrasound has the potential of eco-friendly technology.

Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside.

Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) showed high concentrations of polyphenol and flavonoid content, with notable antioxidant activity. Undescribed acylated diglucoside flavonol myricetin 3-O-ß-4C1-(6″-O-galloyl glucopyranoside) 7-O-ß-4C1-glucopyranoside (MGGG) was isolated from the aerial parts of AEEE, along with four known polyphenols that had not been characterized previously from AEEE. The inhibitory effects of MGGG, AEEE, and all compounds against α-amylase, pancreatic lipase and ß-glucosidase were assessed. In addition, molecular docking was used to determine the inhibition of digestive enzymes, and this confirmed that the MGGG interacted strongly with the active site residues of these enzymes, with the highest binding free energy against α-amylase (-8.99 kcal/mol), as compared to the commercial drug acarbose (-5.04 kcal/mol), thus justifying its use in the potential management of diabetes. In streptozotocin (STZ)-induced diabetic rats, AEEE significantly decreased high serum glucose, α-amylase activity and serum liver and kidney function markers, as well as increasing insulin blood level. Moreover, AEEE improved the lipid profile of diabetic animals, increased superoxide dismutase (SOD) activity, and inhibited lipid peroxidation. Histopathological studies proved the decrease in pancreas damage and supported the biochemical findings. These results provide evidence that AEEE and MGGG possess potent antidiabetic activity, which warrants additional investigation.

Synthesis, characterization and evaluation of resveratrol-loaded functionalized carbon nanotubes as a novel delivery system in radiation enteropathy.

Radiation-induced enteropathy is a major clinical challenge during radiotherapy. Resveratrol displays beneficial pharmacological activities; however, low oral bioavailability limits its effectiveness. This study aims at preparing methacrylic acid (MAAc) functionalized multi-walled carbon nanotubes (MWCNTs-MAAc) as carriers for pH triggered controlled release of resveratrol in an effort to improve the drug therapeutic potential. MWCNTs-MAAc were prepared using radiation technique and then characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier transform-infrared (FT-IR) spectroscopy. In vitro drug release profile at different pH values was analyzed. Furthermore, the designed RES-MWCNTs-MAAc nanocomplex was evaluated against radiation-induced enteropathy in rats. Oral administration of RES-MWCNTs-MAAc restored colonic redox state and elevated antioxidant enzymes activities glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) and reduced colonic inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interferone-γ (IFN-γ) contents in addition to declining the intrinsic apoptotic pathway as evidenced by down-regulation of Bax and caspase-3 proteins expression accompanied by up-regulation of Bcl-2 protein expression. RES-MWCNTs-MAAc was more efficient than free resveratrol due to the delivery system that allowed prolonged resveratrol release at target site. Thus, this formulation could serve as a beneficial anti-inflammatory approach for patients during radiotherapy.

Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression.

The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, ß-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, ß-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and ß-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression).

Nanoparticles in nanomedicine: a comprehensive updated review on current status, challenges and emerging opportunities.

The fast progress in nanomedicine and nanoparticles (NP) materials presents unconventional solutions which are expected to revolutionise health care with great potentials including, enhanced efficacy, bioavailability, drug targeting, and safety. This review provides a comprehensive update on widely used organic and inorganic NP with emphasis on the recent development, challenges and future prospective for bio applications where, further investigations into innovative synthesis methodologies, properties and applications of NP would possibly reveal new improved biomedical relevance. NP exhibits exceptional physical and chemical properties due to their high surface area to volume ratio and nanoscale size, which led to breakthroughs in therapeutic, diagnostic and screening techniques repeated line. Finally, an update of FDA-approved NP is explored where innovative design engineering allowed a paradigmatic shift in their market share. This review would serve as a discerning comprehensive source of information for learners who are seeking a cutting-edge review but have been astounded by the size of publications.

Radiation-synthesis of chitosan/poly (acrylic acid) nanogel for improving the antitumor potential of rutin in hepatocellular carcinoma.

The current study aimed to investigate the ability of chitosan/poly (acrylic acid) nanogel (CAN) to improve the bioavailability and anticancer potential of rutin. Synthesis of CAN was carried out by gamma radiation-induced polymerization of acrylic acid in an aqueous solution of chitosan. The relationship between the hydrodynamic radius of CAN and the absorbed radiation doses was also investigated. The prepared nanogels were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques, and then, it was used as a nano-drug carrier for rutin. The developed formulation was evaluated for its antitumor activity against chemically induced hepatocarcinoma in rats. The following parameters were measured: aspartate and alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, and total bilirubin as liver function test; vascular endothelial growth factor as an angiogenesis marker; α-fetoprotein as a tumor marker; and P53, caspase-3, Bax, and Bcl-2 as apoptosis markers. Histopathological examination was also confirmed. Significant enhanced anti-proliferative, anti-angiogenic, and apoptotic effects were observed for rutin-loaded CAN than free rutin, indicating that this formulation could provide a novel therapeutic approach to serve as a promising agent for treatment of hepatocellular carcinoma. Graphical abstract.

Molecular networking aided metabolomic profiling of beet leaves using three extraction solvents and in relation to its anti-obesity effects.

In the present study, the efficiency of three different solvents (H2O, acidified H2O, and 70% Methanol) for metabolites extraction from the leaves of sugar beet (Beta vulgaris subsp. vulgaris var. rubra) was investigated along with their inhibitory activity on pancreatic α-amylase and lipase for obesity management. The metabolic profile of the three extracts was analyzed by ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization high-resolution mass spectrometric (ESI-HRMS-MS). Mass spectrometry-based molecular networking was employed to aid in metabolites annotation and for the visual investigation of the known metabolites and their analogues. The study led to the tentative identification of 45 metabolites including amino acids, purine derivatives, phenolic acids, flavonoids, fatty acids, and an alkaloid, articulating 24 compounds as a first time report from beet leaves along with 2 new putatively identified compounds: a flavone feruloyl conjugate (39) and a malonylated acacetin diglycoside (40). The three extracting systems exhibited comparable efficiency for pulling out the secondary metabolites from the beet leaves. The in vitro study supported this finding and demonstrated that the three extracts inhibited the activity of both pancreatic α-amylase and lipase enzymes with no significant difference observed regarding the percentage of the inhibition of the enzymes. Conclusively, the extraction protocol has a minimal effect on the anti-obesity properties of beet leaves.

Novel antiproliferative agents bearing morpholinopyrimidine scaffold as PI3K inhibitors and apoptosis inducers; design, synthesis and molecular docking.

Two series of novel morpholinopyrimidine derivatives were synthesized and screened for their in-vitro cytotoxic activity against 60 tumor cell line by the National Cancer Institute, USA. The in-vitro cytotoxic IC50 values for the most active compounds 6e, 6g, and 6l against the most sensitive cell line leukemia SR were estimated (IC50 = 0.76, 13.59, and 4.37 uM, respectively). To investigate their PI3K enzyme inhibition activity, the assay was done on Class IA (α, ß, & δ) isoforms. The IC50 values were very promising: compound [6e = 11.73 (α), 6.09 (ß), 11.18 (δ)], compound [6g = 8.43 (α), 15.84 (ß), 30.62 (δ)], and compound [6l = 13.98 (α), 7.22 (ß), 10.94 (δ)], compared to the reference compound LY294002 = 6.28 (α), 4.51 (ß), 4.60 (δ) uM, respectively. Moreover, cell cycle analysis and annexin V-FITC staining were done on Leukemia SR, there was arrest at G2/M phase and apoptosis was induced. Finally, docking study was performed to analyze the interactive mode of these derivatives in PI3Kα ATP-binding site. These outcomes proved that compounds 6e, 6g, and 6l are potential leads for further optimization as antileukemic agents.

Low dose γ radiation enhances antidepressant effect of resveratrol: Behavioral and neurochemical studies.

The low dose of radiation (LDR) has received growing attention for its beneficial neuroprotective effect. This study was designed to investigate the enhancing effect of LDR on the antidepressant potential of resveratrol against diazepam-induced depression in mice. Female mice divided into five groups; control, diazepam (2 mg/kg), LDR (0.5Gy) + diazepam, resveratrol (20 mg/kg) + diazepam, LDR + resveratrol+diazepam. Mice received diazepam showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swimming and tail suspension tests integrated with a marked decline in biogenic amines (serotonin, norepinephrine, and dopamine) in brain tissues. These effects were ameliorated by LDR or resveratrol administration demonstrating an antidepressant activity. Interestingly, LDR triggered the antidepressant effect of resveratrol as it restored the changes in behavioral tests, neurotransmitters, and neuro-histoarchitecture. In conclusion, these findings suggested that LDR could be considered as a novel adjuvant that augmented the resveratrol antidepressant effect and might serve as a potential therapeutic approach for depression.

A Novel Biochemical Study of Anti-Ageing Potential of Eucalyptus Camaldulensis Bark Waste Standardized Extract and Silver Nanoparticles.

Eucalyptus camaldulensis Dehnh belongs to family Myrtaceae. They are massive in Egypt. Although reputed for high phenolic content, barks are considered waste. Ageing is a natural phenomenon caused by apoptosis and senescence resulting in wrinkles. The phytochemical analysis of the 70% ethanolic Eucalyptus camaldulensis bark extract (EBE) and evaluation of its anti-ageing potential and as silver nanoparticles (AgNPs) were conducted in this study. Ultra performance liquid chromatography / electrospray ionization mass spectrometry of EBE fingerprint revealed twenty compounds, where Rutin was major. EBE was standardized to contain 1.26 % Rutin. AgNPs synthesized by green synthesis, were characterized by transmission electron microscope and zeta potential measurement. Both EBE and AgNPs were subjected to MTT assay in HFB4 cells and cell cycle arrest. Flow cytometry was used to assess apoptosis and p16 INK4a. Genetic expression of p53 and p21 and telomerase level were determined. Anti-wrinkle enzyme assays were done. AgNps were spherical, 468.7 nm in size and with Poly dispersity index of 0.817 ± 0.129. EBE and AgNPs with IC50 0.156 mg/mL ± 0.05 and 2.315 ± 0.07 µg/mL expressed significant difference in % of cells (DNA content) at G2/M, apoptotic cells numbers, p53 and p21expression and p16INK4a vs aged cells (P < 0.0001). Both expressed significant increase in telomerase (P < 0.0001). They exhibited elastase, collagenase and tyrosinase inhibition (75 ± 4.3 and 75.9 ± 6.8 % at 300 µg/mL, 58 ± 4.8 and 63 ± 2.3, at 500 µg/mL, 51 ± 4.8 and 65 ± 5.87, at 500 µg/mL, respectively. Although it is considered waste, EBE and Ag NPs are anti-ageing candidates as they inhibit apoptosis, senescence and prevent wrinkles formation.

Using an UPLC/MS-based untargeted metabolomics approach for assessing the antioxidant capacity and anti-aging potential of selected herbs.

Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis, Lavandula officinalis, Matricaria chamomilla, Camellia sinensis and Pelargonium graveolens. The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties.

Bradykinin-potentiating factor isolated from Leiurus quinquestriatus scorpion venom alleviates cardiomyopathy in irradiated rats via remodelling of the RAAS pathway.

The objective of this work was to evaluate the effect of a bradykinin-potentiating factor (BPF) isolated from Leiurus quinquestriatus scorpion venom as a natural modulator of radiation-induced cardiac damage. Four groups of rats were treated as follows; control group, group receiving BPF (1 µg/g b.wt i.p./biweekly) for 4 weeks, group irradiated at 6 Gy, group receiving BPF post-irradiation for 4 weeks. Irradiation induced a significant elevation of myocardial parameters: atrial natriuretic peptide (ANP), cardiac troponin I (cTnI), potassium (K+ ) and creatine kinase (CK); vascular indices: lactate dehydrogenase (LDH), inducible nitric oxide synthase (iNOS) and endothelin I; oxidative stress indices: malondialdehyde (MDA) associated with a significant depletion of both reduced glutathione (GSH) in the cardiac tissue homogenate and serum ferric reducing antioxidant power (FRAP) depletion and significantly reinforced elevation of Renin Angiotensin Aldosterone System (RAAS) indices: serum angiotensin II (AngII) and aldosterone, and also protein expression of cleaved caspase-3 and cyclophilin A. BPF administration altered the biochemical damage of radiation, specifically inhibited AngII formation, aldosterone release and prevented the histopathological and immunohistochemical alterations which were observed in cardiac tissue with significant reduction in mean arterial blood pressure (MAP) caused by irradiation. In conclusion, biochemical assays, histopathological and immunohistochemical findings of the present study demonstrated that exogenous BPF isolated from scorpion venom reduced the cardiomyopathy alterations induced by irradiation via remodelling of the RAAS pathway.

Resveratrol attenuates intestinal injury in irradiated rats via PI3K/Akt/mTOR signaling pathway.

Radiation-induced enteritis is one of the greatest challenges in radiotherapy. The current study was designed to evaluate the ameliorative effect of resveratrol, which exhibits anti-inflammatory property, against radiation-induced intestinal injury in rats and to explore the underlying mechanism. Rats were exposed to a single dose of 5 Gy. Resveratrol (20 mg/kg/day) was orally administered to irradiated rats over 3 weeks. Results showed that resveratrol ameliorated the intestinal oxidative stress parameters; malondialdehyde (MDA) content, glutathione (GSH) level, and catalase (CAT) activity compared to irradiated group. Furthermore, resveratrol reduced the contents of inflammatory cytokines; tumor necrosis factor α (TNF-α), nuclear factor-kappa (NF-κB), and interleukin 1ß (IL-1ß) in intestine. Western blotting analysis revealed that resveratrol down-regulated the proteins expression of phosphoinositide 3-kinases (PI3K), protein kinase B (Akt) as well as the mammalian target of rapamycin (mTOR) in intestinal tissues of irradiated rats and thus reduced the inflammatory mediator production. These results were confirmed by histopathological investigation. In conclusion, resveratrol attenuated intestinal inflammation following irradiation via modulating PI3K/Akt/mTOR pathway and thereby could be a promising adjuvant in radiotherapy.

Prophylactic Effect of Opuntia ficus indica Fruit Peel Extract against Irradiation-Induced Colon Injury in Rats.

Opuntia ficus-indica extract has been used in traditional folk medicine for several purposes and exhibits anti-inflammatory properties. This study was directed to explore the prophylactic effect of O. ficus-indica fruit peel extract against irradiation-induced colitis in rats. GC/MS analysis of the petroleum ether extract led to recognition of 33 compounds in the unsaponifiable fraction and 15 fatty acid methyl esters in the saponifiable part. Thirteen terpenes and sterols were isolated and identified from which ten compounds were not isolated from any part of this species before. Data showed that irradiation induced colon injury as manifested by elevated contents of malondialdehyde, nitric oxide, myeloperoxidase, intercellular adhesion molecule-1, cyclooxygenase-2, tumor necrosis factor alpha, and nuclear factor kappa B, while it reduced superoxide dismutase activity and interleukin 10 content in colonic tissues, which was confirmed by histopathological examination. Pretreatment with O. ficus-indica extract attenuated the alteration in the measured parameters. It could be concluded that O. ficus-indica fruit peel extract can be regarded as a potential agent in limiting colonic complications due to irradiation, possibly by its antioxidant and anti-inflammatory properties.

Body Mass Index and C-reactive Protein Are Potential Predictors of Asthma Development in Egyptian Polycystic Ovary Syndrome Patients.

BACKGROUND: Recent studies suggest asthma prevalence in polycystic ovary syndrome (PCOS) patients. This is the first study to explore asthma prevalence among Egyptian PCOS patients. It highlighted common findings in PCOS and asthma. It investigated whether these findings could serve as potential predictors of asthma. METHODS: A hundred PCOS patients, sixty asthmatic patients and thirty apparently healthy females of matched age were included. Body mass index (BMI), C-reactive protein (CRP), IL-6, IgE, 25 (OH) vitamin D, testosterone and lipid profile were measured. RESULTS: Both PCOS and asthmatics had significantly higher BMI, Total cholesterol (TC), LDL-C, IgE, CRP and IL-6 (P<0.001) and lower 25 (OH) vitamin D levels (P<0.001) compared to controls. Within the PCOS group, 47 patients developed asthma with a significant increase in BMI (P=0.003), CRP and IgE levels (P<0.001) compared to non-asthmatic PCOS. Both asthmatic PCOS and asthmatics expressed elevated BMI, IgE, IL-6 and CRP levels, but with no significant difference between them. Asthmatic PCOS showed significantly higher testosterone and dyslipidemia profile. Multivariate regression revealed that BMI and CRP could predict asthma development within PCOS (OR=1.104, C.I 1.004-1.2 and OR=1, C.I. 1-1.02), respectively. Receiver operating characteristic (ROC) curve showed that BMI and CRP at a cutoff value 28.5 kg/m2 and 117.6 nmol/L respectively could differentiate between asthmatic and non-asthmatic PCOS with sensitivity 63.8 % and specificity 62% for BMI, and sensitivity and specificity of 66% for CRP. CONCLUSIONS: This study shows that BMI and CRP are predictors of asthma development in Egyptian PCOS.

Decreased Serum Level of Gamma-amino Butyric Acid in Egyptian Infertile Females with Polycystic Ovary Syndrome is Correlated with Dyslipidemia, Total Testosterone and 25(OH) Vitamin D Levels.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders around the world. Increasing evidence suggests that neurotransmitter Gamma-aminobutyric acid (GABA) is involved in the pathogenesis of PCOS through its central role in the hypothalamus. However, the peripheral role of GABA in PCOS has not been sufficiently investigated in spite of its existence in peripheral organs. First, the aim of this study is to, investigate serum GABA level in Egyptian PCOS patients. Second, to explore the correlation between serum GABA level with Body Mass Index (BMI), dyslipidemia, totaltestosterone and 25 (OH) vitamin D. METHODS: Eighty PCOS patients and eighty age-matched healthy females were included in this study. All parameters were assessed colourimetrically or with ELISA. RESULTS: PCOS patients exhibited significantly decreased serum GABA level compared to controls (p < 0.001). There was a significant positive correlation between serum GABA and 25(OH) vitamin D levels (r = 0.26, p = 0.018), and a significant negative correlation with total testosterone (r = - 0.3, p = 0.02), total cholesterol (TC) (r = - 0.31, p = 0.01) and LDL-Cholesterol (LDL-C) (r = - 0.23, p = 0.045), respectively. CONCLUSIONS: The findings of this study suggest that disrupted GABA level in the peripheral circulation is an additional contributing factor to PCOS manifestations. GABA deficiency was correlated with 25 (OH) vitamin D deficiency, dyslipidemia, and total testosterone. Further investigations for GABA adjustment might provide a promising means for better management of PCOS symptoms.