Anti-Culex pipiens activity of different pomegranate cultivars and determination of their bioactive compounds using LC-MS profiling.

INTRODUCTION: Pomegranate (Punica granatum L.) peels are rich in various bioactive compounds. Characterization of these compounds is crucial for the utilization of peel waste in industrial processing. OBJECTIVE: The study aimed (1) to establish and compare the metabolic profiles of the peel of seven pomegranate cultivars and (2) to identify bioactive compounds contributing to the larvicidal activity against the third instar larvae of Culex pipiens. MATERIALS AND METHODS: UPLC-ESI-MS/MS was utilized to analyze peel methanol extracts of different pomegranate cultivars. The larvicidal activity was determined by calculating the larval mortality among the third instar larvae of C. pipiens. Multivariate data analysis was conducted to identify the metabolites that exhibited a larvicidal effect. RESULTS: A total of 24 metabolites, including hydrolyzable tannins, flavonoids, and alkaloids, were tentatively identified in both negative and positive ionization modes. The extract of cultivar 'Black' exhibited the most potent larvicidal effect with LC50 values of 185.15, 156.84, and 138.12 ppm/mL after 24, 48, and 72 h of treatment, respectively. By applying chemometric techniques, the larvicidal activity could be directly correlated to the bioactive compounds punicalagin, quercetin-O-rhamnoside, quercetin-O-pentoside, and galloyl-HHDP-glucose. CONCLUSION: The present study implemented UPLC-ESI-MS/MS and chemometric techniques as potential tools for metabolomics analysis and differentiation between peels of different pomegranate cultivars. In addition, cultivar 'Black' extract could be a promising natural insecticide against mosquitoes since it is rich in bioactive compounds with larvicidal activity.

Long Non-coding RNA Genes Polymorphisms H19 (rs2251375) and MALAT1 (rs3200401) Association with Rheumatoid Arthritis and Their Correlation with Disease Activity in a Cohort of Egyptian Patients: A Pilot Study.

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory, autoimmune disease that could be disabling throughout its course. It affects people in their most reproductive years with relatively high morbidity and mortality. Long non-coding RNAs became one of the epigenetic mechanisms to prove a link to RA pathogenesis and development, including H19 and MALAT1 genes. These two genes' expressions had proved to increase in multiple diseases, attracting attention to their polymorphisms and their possible risk role. Assess the association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA and its disease activity. In this pilot study, 200 hundred subjects (100 RA patients and 100 healthy controls) were investigated for a possible link between the polymorphisms H19 SNP (rs2251375) and MALAT1 SNP (3200401) and RA susceptibility and disease activity. RA-related investigations and clinical assessment were done. Real-time PCR genotyping of both SNPs was done using TaqMan® MGB probes. There was no association between the SNPs and risk of developing RA. However, both SNPs had a significant association with high disease activity. H19 SNP (rs2251375) heterozygous genotype CA had an association with elevated levels of ESR (p = 0.04) and higher DAS28-ESR score (p = 0.03). MALAT1 (rs3200401) C allele had an association with elevated ESR (p = 0.001), DAS28-ESR (p = 0.03), and DAS28-CRP (p = 0.007), while CC genotype had an association with DAS28-CRP (p = 0.015). Linkage disequilibrium and haplotyping of the alleles of both SNPs were analyzed as both genes are present on chromosome 11, but no significant association was found between any of the combinations of the alleles (p > 0.05), denoting that (rs2251375) and (rs3200401) are not in linkage disequilibrium. There is no association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA. However, there is an association between H19 SNP (rs2251375) genotype CA and MALAT1 SNP (rs3200401) genotype CC with RA high disease activity.

Insights into the Role of Erythrina corallodendron L. in Alzheimer's Disease: in Vitro and in Silico Approach.

Alzheimer's disease (AD) is a major health problem. Cholinergic transmission is greatly affected in AD. Phytochemical investigation of the alkaloid rich fraction (AF) of Erythrina corallodendron L leaves resulted in isolation of five known alkaloids: erysodine, erythrinine, 8-oxoerythrinine, erysovine N-oxide and erythrinine N-oxide. In this study, eysovine N-oxide was reported for the second time in nature. AF was assayed for cholinesterase inhibition at the concentration of 100 µg mL-1 . AF showed a higher percent inhibition for butyrylcholinesterase enzyme (BuChE) (83.28 %) compared to acetylcholinesterase enzyme (AChE) (64.64 %). The isolated alkaloids were also assayed for their anti-BuChE effect. In-silico docking study was done for the isolated compounds at the binding sites of AChE and BuChE to determine their binding pattern and interactions, also molecular dynamics were estimated for the compound displaying the best fit for AChE and BuChE. In addition, ADME parameters and toxicity were predicted for the isolated alkaloids compared to donepezil.

Essential Oil of Cestrum diurnum L.: GC/MS Analysis, in Vitro and in Silico Anti-HCoV-229E Effects and Inhibitory Activity against LPS-Induced Inflammation.

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC50 of 10.93 µg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC50 values of 119.9 and 148.2 µg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 µg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.

Ameliorating effects of probiotics on alterations in iron homeostasis and inflammation in COVID-19.

INTRODUCTION: The coronavirus disease (COVID-19) is caused by the severe acute syndrome coronavirus-2 (SARS-COV-2) and still threatens human life. This pandemic is still causing increased mortality throughout the world. Many recent studies have been conducted to discover the pathophysiology of this virus. MATERIAL AND METHODS: However, in this narrative review, we attempted to summarize some of the alterations in physiological pathways that were evident in this viral invasion. Excessive inflammation that progresses to cytokine storm, changes in humoral and cell-mediated immunity, and observed alterations in iron metabolism are included in the pathogenesis of the virus. Iron homeostasis disturbances may persist for more than two months after the onset of COVID-19, which may lead to reduced iron bioavailability, hypoferremia, hyperferritinemia, impaired hemoglobin, and red blood cell synthesis. Furthermore, hypoferriemia may impair immune system function. Until now, the traditional treatments discovered are still being tried. RESULTS: However, using probiotics as an adjuvant was shown to have beneficial effects on both iron homeostasis and immunity in COVID-19. Herein, we discussed the possible mechanisms achieved by probiotics to ameliorate iron and immunity changes based on the available literature. CONCLUSION: We concluded that supplementing probiotics with conventional therapy may improve COVID-19 symptoms and outcomes. Taking into consideration the use of good quality probiotics and appropriate dosage, undesirable effects can be avoided.

Cyclodepsipeptides: Isolation from Endophytic Fungi of Sarcophyton ehrenbergi and Verification of Their Larvicidal Activity via In-Vitro and In-Silico Studies.

Culex pipiens mosquitoes are vectors to many viruses and can transmit diseases such as filariasis and avian malaria. The present study evaluated the larvicidal activity of marine-derived endophytic fungi Aspergillus nomius and Aspergillus flavus from the soft coral Sarcophyton ehrenbergi along with two known cyclodepsipeptide compounds, scopularide A (1) and B (2), isolated from A. flavus extract, against third-instar larvae of C. pipiens, using distilled water as a negative control and toosenedanin as a positive control. The structures of the isolated compounds were confirmed by various spectroscopic analyses. The lethal concentrations (LC50 and LC90) were calculated by probit analysis. Scopularide A was the most potent after 96 h treatment, with LC50 and LC90 values of 58.96 and 994.31 ppm, respectively, and with 82.66% mortality at a concentration of 300 ppm. To unravel the biochemical mechanism of the tested extracts and compounds, their effects against protease, chitinase, phenoloxidases and lipase enzymes from the whole-body tissue of C. pipiens were evaluated after 72 h treatment at LC50 dose. Superior activity was observed for A. flavus extract against all tested enzymes. A molecular docking study was conducted for scopularide A and B on the four tested enzymes, to further verify the observed activity. Results revealed good binding affinities for both compounds as compared to the docked ligands, mainly via a number of hydrogen bonds. This was the first study to report the isolation of endophytic fungi A. flavus and A. nomius from the marine soft coral S. ehrenbergi. The endophytic fungal extract of A. flavus was found to be a promising source for a natural larvicidal agent against C. pipiens populations.

Relationship between sputum periostin level and inflammatory asthma phenotypes in Egyptian patients.

INTRODUCTION: Asthma is a common chronic inflammatory air way disease which poses a high disease burden worldwide. Asthma is a heterogenous disease with various phenotypes and endotypes. Refractory asthma requires new and personalized approaches to manage it effectively. Periostin is a promising biomarker that may help in predicting severity, prognosis and could be a therapeutic target. We aimed in this study to investigate periostin levels in the sputum of asthmatic Egyptian patients of inflammatory phenotypes and its relation to asthma severity. SUBJECTS AND METHODS: This study included 96 adult asthmatic patients; 48 patients with mild-to-moderate bronchial asthma, 48 patients with severe bronchial asthma according to ATS criteria and 10 healthy controls. All participants were subjected to full history taking and clinical examination; pulmonary function tests; skin prick test; induced-sputum analysis for inflammatory cells and periostin. RESULTS: Sputum periostin concentrations were significantly higher in patients with asthma than in controls. Sputum periostin is strongly correlated with age and sputum TLC and inversely correlated with FEV1. It is correlated with sputum neutrophil count and sputum eosinophil percentage. Best cut off value for sputum periostin is >528.25 ng/ml to differentiate between mild-to-moderate and severe asthma. CONCLUSION: Sputum periostin levels provide a satisfying diagnostic accuracy in severe asthmatic with persistent airflow limitation than mild-to-moderate asthmatic adults. There is a modest positive correlation between sputum periostin and sputum eosinophilia.

Vicia plants-A comprehensive review on chemical composition and phytopharmacology.

The plants belonging to the genus Vicia are of great interest as a source of many bioactive compounds and micronutrients. A snapshot of their cultivation, habitat, main components, from which essential oils can be obtained, is given. The traditional medicinal uses of Vicia plants are also reported, as well as the wide spectrum of the main biological activities attributed to Vicia plants is discussed regarding potential health beneficial properties, in particular anti-Parkinson, anticholinesterase, antidepressant, anticonvulsant, antimicrobial, cytotoxic, antioxidant, antiinflammatory and antinociceptive, antidiabetic, antihemolytic, anticoagulant, estrogenic, diuretic, antihypoxic activities.

Phytochemical discrimination of Pinus species based on GC-MS and ATR-IR analyses and their impact on Helicobacter pylori.

INTRODUCTION: The leaves and cones of Pinus plants as well as their essential oils have been used in traditional medicine for the treatment of several ailments. OBJECTIVES: Phytochemical discrimination of Pinus species and investigation of their anti-Helicobacter pylori activity in vitro and in silico. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) and attenuated total reflectance infrared (ATR-IR) metabolic profiling of the essential oils of Pinus species. Principal component analysis (PCA) and hierarchal cluster analysis (HCA) were applied for discrimination and segregation of Pinus species. RESULTS: GC-MS revealed the presence of 76 constituents, where monoterpenes represented the major class with the dominance of α-pinene (72%) followed by ß-pinene (16%) for P. canariensis. ß-Pinene was the dominant component in P. pinea (24%) followed by terpinolene (11%). α-Pinene (17%) and caryophyllene (12%) were the major components in P. halepensis, while, 3-carene (33%) and α-pinene (17%) represented the major constituents of P. roxburghii oil. By applying PCA and HCA on GC-MS and ATR-IR data analysis, ATR-IR displayed much better discrimination for Pinus species. The pine oils showed promising inhibitory effects on Helicobacter pylori. Furthermore, in silico molecular modelling was carried out where the calculated free binding energies of phytochemicals identified ranged from -33.71 to -19.67 kcal/mol for urease and -41.18 to -16.57 kcal/mol for shikimate kinase. This suggests favourable binding of pine essential oil components to both enzymes, thus explaining their potential inhibitory activity on H. pylori. CONCLUSION: GC-MS and ATR-IR based metabolic analyses could discriminate between Pinus species. Pine essential oils can be used as promising therapeutic drugs to protect against H. pylori infection.

Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss.

Nonsyndromic hearing loss is an extremely heterogeneous disorder. Thus, clinical diagnostics is challenging, in particular due to differences in the etiology of hearing loss between populations. With this study, we wanted to elucidate the genetic basis of hearing loss in 61 consanguineous Egyptian families. In 25 families, linkage analysis was used as a prescreening to identify regions for targeted sequencing of candidate genes. Initially, the coding regions of 12 and later of 94 genes associated with hearing loss were enriched and subjected to massively parallel sequencing (MPS) with diagnostic yields of 36% and 75%, respectively. Causative variants were identified in 48 families (79%). They were found in 23 different genes with the majority being located in MYO15A (15.3%), SLC26A4 (9.7%), GJB2 (8.3%), and MYO7A (6.4%). As many as 32 variants were novel ones at the time of detection. Five variants were shared by two, three, or even four families. Our study provides a first survey of the mutational spectrum of deaf patients in Egypt revealing less GJB2 variants than in many European populations. It underlines the value of targeted enrichment of well-selected deafness genes in combination with MPS in the diagnostics of this frequent and genetically heterogeneous disorder.

Cytotoxic and anti-inflammatory effects of lignans and diterpenes from Cupressus macrocarpa.

Cupressus macrocarpa is a windbreak tree and is reported to have various cytotoxic effects. A natural product study on the leaves of C. macrocarpa has yielded ten secondary metabolites, including three new diterpenoids (1-3), four known diterpenoids (4-7), and three known lignans (8-10). The structures of all isolated compounds were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. In the cytotoxic assays, compounds 1-3 and 7-10 showed inhibition effect against HepG2, MDA-MB-231, and A549 cells with IC50 values ranging from 0.004 to 19.9 µg/mL. Moreover, the anti-inflammatory assays revealed that (-)-matairesinol (8) had significant inhibitory activities on superoxide anion generation (IC50 = 2.7 ± 0.3 µM) and elastase release (IC50 = 6.6 ± 0.7 µM).

Achillea spp.: A comprehensive review on its ethnobotany, phytochemistry, phytopharmacology and industrial applications.

The genus Achillea genus houses more than 100 species, a number of them are popularly used in traditional medicine for spasmodic gastrointestinal, gynecological and hepatobiliary disorders, hemorrhages, pneumonia, rheumatic pain, inflammation, wounds healing etc. Members of the genus contain a wide variety of volatile and non-volatile secondary metabolites, including terpenes, polyphenols, flavonoids and others. Multiple studies have assessed the biological effects and other aspects of Achillea spp. In a number of preclinical studies, Achillea plants and their essential oils have demonstrated promising antibacterial properties against a number of human and plant pathogens. Besides, the plants have displayed strong antioxidative and potent anti-proliferative and anticancer properties in various cellular and animal models. Achillea plants have widely been used as food preservative in food industry. Clinical studies have indicated its potential against multiple sclerosis (MS), irritable bowel syndrome (IBS), ulcerative colitis, episiotomy wound, primary dysmenorrhea, oral mucositis etc. The present work focuses to provide a brief overview on folk knowledge, phytochemistry, biological activity and applications of Achillea plants. There is a close relationship between the traditional ethnobotanical usage and pharmacological and clinical data from different Achillea spp. The application of Achillea plants and their extracts seems to be a promising alternative for antimicrobial and antioxidant purposes in food, pharmaceutical and cosmetic industries.

Protective Role of Casuarinin from Melaleuca leucadendra against Ethanol-Induced Gastric Ulcer in Rats.

Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra. Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF-α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources.

Breaking Down the Barriers to a Natural Antiviral Agent: Antiviral Activity and Molecular Docking of Erythrina speciosa Extract, Fractions, and the Major Compound.

The in vitro cytotoxic activity in Vero cells and the antiviral activity of Erythrina speciosa methanol extract, fractions, and isolated vitexin were studied. The results revealed that E. speciosa leaves ethyl acetate soluble fraction of the methanol extract (ESLE) was the most active against herpes simplex virus type 1 (HSV-1). Bioactivity-guided fractionation was performed on ESLE to isolate the bioactive compounds responsible for this activity. One sub-fraction from ESLE (ESLE IV) showed the highest activity against HSV-1 and Hepatitis A HAV-H10 viruses. Vitexin isolated from ESLE VI exhibited a significant antiviral activity (EC50 =35±2.7 and 18±3.3 µg/mL against HAV-H10 and HSV-1 virus, respectively), which was notably greater than the activity of the extract and the fractions. Molecular docking studies were carried out to explore the molecular interactions of vitexin with different macromolecular targets. Analysis of the in silico data together with the in vitro studies validated the antiviral activity associated with vitexin. These outcomes indicated that vitexin is a potential candidate to be utilized commendably in lead optimization for the development of antiviral agents.

The Therapeutic Mechanisms of Propolis Against CCl4 -Mediated Liver Injury by Mediating Apoptosis of Activated Hepatic Stellate Cells and Improving the Hepatic Architecture through PI3K/AKT/mTOR, TGF-ß/Smad2, Bcl2/BAX/P53 and iNOS Signaling Pathways.

BACKGROUND/AIMS: Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis. METHODS: Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA. RESULTS: We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-ß followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice. CONCLUSION: Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.

Hepatoprotective activity of praecoxin A isolated from Melaleuca ericifolia against carbon tetrachloride-induced hepatotoxicity in mice. Impact on oxidative stress, inflammation, and apoptosis.

The hepatoprotective activity of praecoxin A, an ellagitannin from Melaleuca ericifolia, was determined against CCl4 -induced toxicity in mice. Praecoxin A was administered (25, 50, and 100 mg/kg) for 5 days followed by CCl4 . Praecoxin A markedly ameliorated the CCl4 -induced increase in AST (by 19, 52, and 56%), ALP (22, 45, and 48%), ALT (11, 47, and 54%), total bilirubin (14, 27, and 28%), and MDA (26, 44, and 51%) at the tested doses, respectively, as compared with CCl4 group. It was evident that praecoxin A significantly (p < 0.001) increased the antioxidant parameters GSH (45, 99, and 137%) and SOD (61, 129, and 159%). Histological findings revealed a marked amelioration of hepatocyte degeneration, necrosis, inflammatory cell infiltration, and hemorrhage in the groups treated with praecoxin A. COX-2 and caspase-3 hepatic expressions were significantly downregulated (p < 0.001) in praecoxin A-treated groups (up to 57, 83, and 93% for COX-2 and by 30, 82, and 99% for caspase-3). These findings suggest that praecoxin A exerts a beneficial effect against oxidative stress by reducing lipid peroxidation, enhancing the antioxidant defense status, and protecting against the histopathological changes induced by CCl4 . This study highlights a promising natural hepatoprotective candidate derived from M. ericifolia that might be an alternative to silymarin.

Potential role of MicroRNA 200c gene expression in assessment of colorectal cancer.

BACKGROUND AND AIM: Colorectal cancer (CRC) is a common cancer worldwide that affects men and women of all racial and ethnic groups. Recent evidence supports the role of microRNAs in CRC. We planned to investigate microRNA200c expression and its relation with diagnosis, prognosis, metastasis and overall survival in CRC patients. This study enrolled 90 subjects (3'0 CRC patients, 30 patients with benign colorectal polyps and 30 healthy control subjects). METHODS: Laboratory investigations included measurement of serum CA19-9 and CEA by enzyme linked immunosorbent assay (ELISA) method and relative quantitation (RQ) of microRNA200c gene expression by real time PCR technique. RESULTS: Significant higher MicroRNA200c expression levels in CRC patients versus both benign (P < 0.011) and control groups (P < 0.001), additionally, benign group had elevated levels versus control (P < 0.001). MicroRNA 200c at cutoff >4.56 had sensitivity 86.67% and specificity 73.33% (P < 0.001) for CRC discrimination. Kaplan-Meier survival analysis revealed significant association (P = 0.028) of high expression of microRNA200c with decreased overall survival. CONCLUSION: Noticeable up-regulation of microRNA200c in CRC and its remarkable relation with unfavorable survival suggesting its potential dual use as a diagnostic and prognostic biomarker for CRC.

Analgesic and anti-inflammatory activities of epicatechin gallate from Bauhinia hookeri.

Hit, Lead & Candidate Discovery The acetic acid-induced writhing and hot plate models in mice were utilized to determine the analgesic effect of epicatechin gallate (ECG) isolated from Bauhinia hookeri. The anti-inflammatory activity of ECG was determined using carrageenan-induced paw edema model. The pro-inflammatory mediators (PGE2 , TNF-α, IL-1ß, and IL-6) were estimated in the plasma of different treatment groups. ECG was tested at doses of 100, 200, and 400 mg/kg p.o. and diclofenac sodium was used as a standard drug (100 mg/kg) in all experiments. ECG significantly (p < .001) suppressed the writhing response in mice. The inhibition percentages were 32, 52, and 62%, at the tested doses of ECG, respectively as compared to the positive control group receiving acetic acid only. Furthermore, ECG significantly (p < .001) increased the reaction time in hot plate model. The maximum analgesic effect was evident after 120 min. ECG demonstrated a significant anti-inflammatory activity as evidenced by the inhibition of carrageenan-induced paw edema (46, 50, and 58%, at the tested doses, respectively). This effect was persistent all over the experimental period. ECG produced a significant (p < .001) reduction in plasma PGE2 (by 27, 38, and 50%), TNF-α (15, 33, and 41%), IL-1ß (17, 25, and 33%), and IL-6 (22, 32, and 43%), at the tested doses, respectively. This study supports the use of ECG as both analgesic and anti-inflammatory agent.

Anti-inflammatory and analgesic activities of cupressuflavone from Cupressus macrocarpa: Impact on pro-inflammatory mediators.

Hit, Lead & Candidate Discovery Inflammation is a complex biological process that is generally occurs in response to pathological triggers. Both neurodegenerative diseases and cancer have been linked to inflammation. The analgesic and anti-inflammatory effects of cupressuflavone (CUF) isolated from Cupressus macrocarpa were examined. The analgesic effects of CUF (40, 80 and 160 mg/kg po) were assessed in the acetic acid-induced writhing and hot plate models in mice with diclofenac sodium as the reference standard (100 mg/kg). CUF dose-dependently inhibited the writhing response in mice by 25, 48, and 62%, at the three CUF doses with 160 mg/kg being equivalent to the diclofenac control. CUF dose-dependently increased the hot plate model reaction time with a maximal effect after 120 min. In the carrageenan-induced paw edema model of inflammation, CUF demonstrated anti-inflammatory activity by inhibiting paw edema by 55, 60, and 64% at doses of 40, 80, and 160 mg/kg po, respectively. CUF also reduced the plasma pro-inflammatory mediators PGE2 (44, 54, and 58%), TNF-α (26, 37, and 53%), IL-1ß (19, 33, and 41%), and IL-6 (32, 44, and 55%) at the three doses tested with the highest dose having similar effects to diclofenac sodium (100 mg/kg). This finding from this study indicates that CUF has both analgesic and anti-inflammatory effects.

Effect of the types of dietary fats and non-dietary oils on bone metabolism.

Nutrients beyond calcium and vitamin D have a role on bone health, and in treatment and prevention of osteoporosis. Quality and quantity of dietary fat may have consequences on skeletal health. Diets with highly saturated fat content produce deleterious effects on bone mineralization in growing animals. Conversely, dietary n-3-long chain polyunsaturated fatty acids play an important role in bone metabolism and may help in prevention and treatment of bone disease. Some reports suggest a correlation between the dietary ratio of n-6 and n-3 polyunsaturated fatty acids and bone formation. Specific dietary fatty acids were found to modulate prostanoid synthesis in bone tissue and improve bone formation in both animal and clinical trials. The skeletal benefits of dietary isoprenoids are extremely documented. Higher isoprenoids intake may relate to higher bone mineral density. Dietary supplements containing fish oil, individual polyunsaturated fatty acids, and isoprenoids could be used as adjuvant with bone medications in osteoportic conditions but their doses must be considered to avoid detrimental effect of over dosages.