Artemisia monosperma essential oil nanoformulations alleviate imiquimod-induced psoriasis-like dermatitis in mice.

Psoriasis is an inflammatory immune-mediated skin disease that affects nearly 2-3 % of the global population. The current study aimed to develop safe and efficient anti-psoriatic nanoformulations from Artemisia monosperma essential oil (EO). EO was extracted using hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and head-space solid-phase microextraction (HS-SPME), as well as GC/ MS was used for its analysis. EO nanoemulsion (NE) was prepared using the phase inversion method, while the biodegradable polymeric film (BF) was prepared using the solvent casting technique. A.monosperma EO contains a high percentage of non-oxygenated compounds, being 90.45 (HD), 82.62 (MADH), and 95.17 (HS-SPME). Acenaphthene represents the major aromatic hydrocarbon in HD (39.14 %) and MADH (48.60 %), while sabinene as monoterpene hydrocarbon (44.2 %) is the primary compound in the case of HS-SPME. The anti-psoriatic Effect of NE and BF on the successful delivery of A.monosperma EO was studied using the imiquimod (IMQ)-induced psoriatic model in mice. Five groups (n = 6 mice) were classified into control group, IMQ group, IMQ+standard group, IMQ+NE group, and IMQ+BF group. NE and BF significantly alleviated the psoriatic skin lesions and decreased the psoriasis area severity index, Baker's score, and spleen index. Also, they reduced the expression of Ki67 and attenuated the levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 17. Additionally, NE and NF were able to downregulate the NF-κB and GSK-3ß signaling pathways. Despite the healing properties of BF, NE showed a more prominent effect on treating the psoriatic model, which could be referred to as its high skin penetration ability and absorption. These results potentially contribute to documenting experimental and theoretical evidence for the clinical uses of A.monosperma EO nanoformulations for treating psoriasis.

Phenolic profiling and bioactivity assessment of in vitro propagated Psidium cattleianum Sabine: A promising study.

Psidium cattleianum Sabine (strawberry guava) is an evergreen shrub that is grown as a fruiting hedge and has received significant consideration in the food and pharmaceutical disciplines. This study aims to set a promising protocol for in vitro propagation of P. cattleianum, along with profiling the phenolic content of the original plant (OP), induced callus (IC), and regenerated plantlets (RP) extracts, ultimately, evaluating their anti-inflammatory, antioxidant, and anticancer potential. Seeds were treated with commercial bleaching, HCl, and H2O2 to enhance the germination percentage and minimize the contamination percentage. Culturing sterilized leaf explants onto Murashige and Skoog (MS) medium supplemented with benzyl adenine (BA), 2,4-dichloro phenoxy acetic acid, and kinetin showed the best callus induction, while supplementation of MS media with BA, adenine sulfate, naphthalene acetic acid, and gibberellic acid activated regeneration. Augmentation of MS media with indol-3-butyric acid recorded the maximum rooting percentage. Finally, the obtained rooted shoots were successfully acclimatized in sand and peat moss soil. HPLC-MS/MS profiles of OP, RP, and IC showed a variety of phenolic metabolites. IC extract decreased the viability of MCF-7, HepG2, and K-562 cancer cell lines. Also, OP exhibits strong antioxidant activity. P. cattleianum and its RP are profound sources of phenolic compounds promoted for promising applications in the food and pharmaceutical industries.

Quercus coccinea Münchh leaves polyphenols: Appraisal acute lung injury induced by lipopolysaccharide in mice.

Genus Quercus is a well-known source for its polyphenolic content and important biological activity. Plants belonging to the Quercus genus were traditionally used in asthma, inflammatory diseases, wound healing, acute diarrhea, and hemorrhoid. Our work intended to study the polyphenolic profile of the Q. coccinea (QC) leaves and to assess the protective activity of its 80% aqueous methanol extract (AME) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Together, the potential molecular mechanism was investigated. Nineteen polyphenolic compounds (1-18), including tannins, flavone, and flavonol glycosides. Phenolic acids and aglycones were purified and identified from the AME of QC leaves. Treatment with AME of QC showed an anti-inflammatory effect evidenced by a remarkable decline in the count of white blood cells and neutrophils which was in harmony with decreasing the levels of high mobility group box-1, nuclear factor kappa B, tumor necrosis factor-α, and interleukin 1 beta. In addition, the antioxidant activity of QC was documented through the significant reduction in malondialdehyde level and elevation of reduced glutathione level and superoxide dismutase activity. Furthermore, the mechanism involved in the pulmonary protective effect of QC involved the downregulation of the TLR4/MyD88 pathway. The AME of QC showed a protective effect against LPS-induced ALI through the powerful anti-inflammatory and antioxidant activities which are linked to its abundancy with polyphenols.

UHPLC-MS profiles and antidiarrheal activity of Quercus coccinea münchh. and Quercus robur L. employing in vivo technique.

Introduction: Quercus L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several Quercus species were traditionally used to manage wound healing, acute diarrhea, hemorrhoid, and inflammatory diseases. The present study aims to investigate the phenolic content of the 80% aqueous methanol extract (AME) of Q. coccinea and Q. robur leaves as well as to assess their anti-diarrheal activity. Methods: Polyphenolic content of Q. coccinea and Q. robur AME were investigated using UHPLC/MS. The antidiarrheal potential of the obtained extracts was evaluated by conducting a castor oil-induced diarrhea in-vivo model. Result and Discussion: Twenty-five and twenty-six polyphenolic compounds were tentatively identified in Q. coccinea and Q. robur AME, respectively. The identified compounds are related to quercetin, kaempferol, isorhamnetin, and apigenin glycosides and their aglycones. In addition, hydrolyzable tannins, phenolic acid, phenyl propanoides derivatives, and cucurbitacin F were also identified in both species AME of Q. coccinea (250, 500, and 1000 mg/kg) exhibited a significant prolongation in the onset of diarrhea by 17.7 %, 42.6%, and 79.7% respectively while AME of Q. robur at the same doses significantly prolonged the onset of diarrhea by 38.6%, 77.3%, and 2.4 folds respectively as compared to the control. Moreover, the percentage of diarrheal inhibition of Q. coccinea was 23.8%, 28.57%, and 42,86% respectively, and for Q. robur 33.34%, 47.3%, and 57.14% respectively as compared to the control group. Both extracts significantly decreased the volume of intestinal fluid by 27%, 39.78%, and 50.1% for Q. coccinea respectively; and by 38.71%, 51.19%, and 60% for Q. robur respectively as compared to the control group. In addition, AME of Q. coccinea exhibited a peristaltic index of 53.48, 47.18, and 42.28 with significant inhibition of gastrointestinal transit by 18.98%, 28.53%, and 35.95 % respectively; while AME of Q. robur exhibited a peristaltic index of 47.71, 37, and 26.41 with significant inhibition of gastrointestinal transit by 27.72%, 43.89%, and 59.99% respectively as compared with the control group. Notably, Q. robur showed a better antidiarrheal effect in comparison with Q. coccinea and, the highest effect was observed for Q. robur at 1000 mg/kg as it was nonsignificant from the loperamide standard group in all measured parameters.

Essential oils of Psidium cattleianum Sabine leaves and flowers: Anti-inflammatory and cytotoxic activities.

Introduction: Psidium cattleianum Sabine is a Brazilian native shrub cultivated for its edible fruit araçá (strawberry guava). P. cattleianum is recognized for health and food applications, although the essential oils (EOs) from the Egyptian inhabitant are not fully explored. The current study investigated the anti-inflammatory and cytotoxic activities of EOs from P. cattleianum leaves and flowers. Materials and methods: The EOs were obtained by three different methods viz; the conventional hydro-distillation, microwave assisted hydro-distillation, and supercritical fluid extraction, while their analysis was accomplished using GC/MS. The derived EOs were screened for their anti-inflammatory activity in the 5-lipoxygenase, COX-1, and COX-2 enzyme based assays, while the anticancer potential was deduced from MTT cytotoxic assay, cell cycle, and western blotting analysis. Results and discussion: Among other methods, supercritical fluid extraction offered the highest EO yield, 0.62% (leaves) and 1.4% (flowers). GC/MS identified ß-caryophyllene and α-humulene in both organs with high but variable percentages. The leaves demonstrated strong activity in inhibiting the 5-lipoxygenase enzyme (IC50 2.38), while the flowers, in inhibiting COX-2 (IC50 2.575). Moreover, the leaves showed potent, selective cytotoxicity to MCF-7 cells (IC50 5.32) via apoptosis by modulating the p53/Bax/Bcl2 axis. The deduced activities are possible due to the synergism between the volatile components that endorses P. cattleianum leaves' EOs in the management of breast cancer and inflammatory disorders.

Anti-prostate cancer metabolites from the soil-derived Aspergillus neoniveus.

Prostate cancer (PCa) ranks as one of the most commonly diagnosed malignancies worldwide. Toxicity, lack of clinical efficacy, and development of resistance phenotypes are the main challenges in the control of prostate malignancies. Notably, castration-resistance prostate cancer (CRPCa) is a highly aggressive and metastatic phenotype of the disease with a poor prognosis and very limited therapeutic options. Herein, we report the isolation and genotypic identification of a soil-derived fungus Aspergillus neoniveus using the PCR-based internal transcribed spacer (ITS) region amplification approach. HPLC/MS investigation of the metabolic profile of the ethyl acetate extract from the fungal biomass revealed tentative identification of forty-five compounds belonging to various chemical classes including γ-butyrolactones, alkaloids, phenolics, and quinoids. Furthermore, the chromatographic purification of microbial extract enabled the identification of nervonic acid methyl ester (1) for the first time from endophytic fungi, as well as acetyl aszonalenin (2), and butyrolactone II (3) for the first time from A. neoniveus. The chemical frameworks of the isolated compounds were identified via extensive spectral analysis including 1 and 2D NMR and MS. The X-ray crystal structure and absolute configuration of acetyl aszonalenin (2) were also determined. Additionally, screening of in vitro anticancer activity of the fungal extract revealed its potential antiproliferative and anti-migratory activities against five different prostate cancer cells (PC3, PC-3M, DU-145, CWR-R1ca, and 22Rv1), including different cells with the castration-resistance phenotype. Moreover, the isolated metabolites significantly inhibited the proliferation, migration, and colonization of human prostate cancer cells at low micromolar levels, thus providing credence for future investigation of these metabolites in relevant anti-prostate cancer animal models. Furthermore, computational target prediction tools identified the cannabinoid G-protein coupled receptors type 1 (CB1) as a potential biological target mediating, at least in part, the anticancer effects of acetylaszonalenin (2). Moreover, molecular modeling and docking studies revealed a favorable binding pose at the CB1 receptor orthosteric ligand pocket aided by multiple polar and hydrophobic interactions with critical amino acids. In conclusion, the Aspergillus neoniveus-derived prenylated indole alkaloid acetylaszonalenin has promising anticancer activity and is amenable to further hit-to-lead optimization for the control of prostate malignancies via modulating CB1 receptors.

Melaleuca rugulosa (Link) Craven Tannins: Appraisal of anti-inflammatory, radical scavenging activities, and molecular modeling studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Genus Melaleuca or tea tree species are well known to be an important source of biological active oils and extracts. The biological significance appears in their usage for treatment of several clinical disorder owing to their traditional uses as anti-inflammatory, antibacterial, antifungal, and cytotoxic activities. AIM OF THE STUDY: Our study aimed to investigate the metabolic profile of the M. rugulosa polyphenol-rich fraction along with determination of its anti-inflammatory potential, free radical scavenging and antiaging activities supported with virtual understanding of the mode of action using molecular modeling strategy. MATERIALS AND METHODS: The anti-inflammatory activity of the phenolic rich fraction was investigated through measuring its inhibitory activity against inflammatory mediators viz tumor necrosing factor receptor-2 (TNF-α) and cyclooxygenases 1/2 (COX-1/2) in a cell free and cell-based assays. Moreover, the radical scavenging activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene assays, while the antiaging activity in anti-elastase, anti-collagenase, and anti-tyrosinase inhibitory assays. Finally, the biological findings were supported with molecular docking study using MOE software. RESULTS: The chromatographic purification of the polyphenol-rich fraction of Melaleuca rugulosa (Link) Craven afforded fourteen phytoconstituents (1-14). The anti-inflammatory gauging experiments demonstrated inhibition of inflammatory-linked enzymes COX-1/2 and the TNF-α at low µg/mL levels in the enzyme-based assays. Further investigation of the underlying mechanism was inferred from the quantification of protein levels and gene expression in the lipopolysaccharide (LPS)-activated murine macrophages (RAW264.7) in vitro model. The results revealed the reduction of protein synthesis of COX-1/2 and TNF-α with the down regulation of gene expression. The cell free in vitro radical scavenging assessment of the polyphenol-rich fraction revealed a significant DPPH reduction, peroxyl radicals scavenging, and ß-carotene peroxidation inhibition. Besides, the polyphenol-rich fraction showed a considerable inhibition of the skin aging-related enzymes as elastase, collagenase, and tyrosinase. Ultimately, the computational molecular modelling studies uncovered the potential binding poses and relevant molecular interactions of the identified polyphenols with their targeted enzymes. Particularly, terflavin C (8) which showed a favorable binding pose at the elastase binding pocket, while rosmarinic acid (14) demonstrated the best binding pose at the COX-2 catalytic domain. In short, natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions. CONCLUSION: Natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions.

Appraisal on the Wound Healing Potential of Deverra tortuosa DC. and Deverra triradiata Hochst Essential Oil Nanoemulsion Topical Preparation.

Deverra tortuosa (Desf.) DC. and Deverra. triradiata Hochst. ex Bioss are perennial desert shrubs widely used traditionally for many purposes and they are characteristic for their essential oil. The objective of the present study was to investigate the in vivo wound healing activity of the essential oil (EO) of D. tortuosa and D. triradiata through their encapsulation into nanoemulsion. EO nanoemulsion was prepared using an aqueous phase titration method, and nanoemulsion zones were identified through the construction of phase diagrams. The EO was prepared by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and supercritical fluid extraction (SFE) and analyzed using GC/MS. D. tortuosa oil is rich in the non-oxygenated compound, representing 74.54, 73.02, and 41.19% in HD, MADH, and SFE, respectively, and sabinene represents the major monoterpene hydrocarbons. Moreover, D. triradiata is rich in oxygenated compounds being 69.77, 52.87, and 61.69% in HD, MADH, and SFE, respectively, with elemicin and myristicin as major phenylpropanoids. Topical application of the nanoemulsion of D. tortuosa and D. triradiata (1% or 2%) exhibited nearly 100% wound contraction and complete healing at day 16. Moreover, they exhibit significant antioxidant and anti-inflammatory effects and a significant increase in growth factors and hydroxyproline levels. Histopathological examination exhibited complete re-epithelialization accompanied by activated hair follicles and abundant collagen fibers, especially at a concentration of 2%. Therefore, the incorporation of the two Deverra species into nanoemulsion could professionally endorse different stages of wound healing.

Ethnopharmacological impact of Melaleuca rugulosa (Link) Craven leaves extract on liver inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed. AIM OF THE STUDY: The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. rugulosa leaves in relevance to their flavonoid content using an appropriate in vivo model. MATERIALS AND METHODS: The aqueous methanol extract of M. rugulosa leaves was administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for seven days prior to the initiation of liver-injury induced by paracetamol (3 g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum samples. The oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), were assessed in liver homogenate. The results were supported by histopathological and immuno-histochemical studies. The phytochemical investigation of the flavonoid-rich fraction of the aqueous methanol extract was accomplished using different chromatographic and spectroscopic techniques. RESULTS: The aqueous methanol extract of M. rugulosa leaves showed a powerful hepatoprotective activity evidenced by the significant reduction of MDA and NO levels, as well as increasing GSH and catalase activity. Moreover, the extract exhibited anti-inflammatory and antiapoptotic activities witnessed by decreasing TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract showed a significant decrease in liver weight/body weight (LW/BW) ratio, and total bilirubin induced by paracetamol. On the other hand, the chromatographic separation of the flavonoid-rich fraction afforded twenty known flavonoids namely; iso-orientin (1), orientin (2), isovitexin (3), vitexin (4), quercetin-3-O-ß-D-glucuronid methyl ether (5), quercetin-3-O-ß-D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), kaempferol-3-O-ß-D-mannuronopyranoside (9), kaempferol-7-O-methyl ether-3-O-ß-D-glucopyranoside (10), guaijaverin (11), avicularin (12), kaempferide-3-O-ß-D-glucopyranoside (13), astragalin (14), afzelin (15), luteolin (16), apigenin (17), quercetin (18), kaempferol (19), and catechin (20). CONCLUSION: The aqueous methanol extract of M. rugulosa leaves showed potential hepatoprotective, antioxidant, and anti-inflammatory activities against paracetamol-induced liver inflammation which is correlated at least in part to its considerable phenolic content.

Polyphenolic profile and ethno pharmacological activities of Callistemonsubulatus (Cheel) Craven leaves cultivated in Egypt.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Callistemon (syn. Melaleuca) of the myrtle family (Myrtaceae) has been documented as an integral part in the ethnobotanical system of the indigenous people of Australian mainland and many of its islands. Several Callistemons including the species subulatus were used by aboriginal Australians for making rafts, roofs for shelters, bandages, and food recipes, in addition to the management of wounds, infections, pain, cough, bronchitis, and gastrointestinal tract (GIT) disorders. AIM OF THE STUDY: The current study is designed to document the therapeutic effect of the aqueous methanolic extract (AME) of C. sabulatus Chell (syn. M. sabulata) leaves in the management of diarrhea and pain. Also, its influence on additional pharmacological modalities that are related to oxidative stress just as skin aging. Ultimately, the polyphenolic profile of the extract is disclosed and correlated to the aforementioned bioactivities. MATERIALS AND METHODS: The extract was fractionated using various chromatography techniques and the structures of the isolated compounds were determined based on their chemical and spectral data. The antioxidant activity was assessed using multiple models, including 2,2-diphenyl-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene bleaching assays. The anti-skin aging effect was evaluated using different relevant enzymatic assays. The antinociceptive activity was investigated using acetic acid-induced writhing, hot plate test, and formalin-induced paw licking in mice models. The antidiarrheal activity was gauge using the castor oil induced diarrhea, enter pooling and gastrointestinal motility in vivo models. RESULTS: Diverse polyphenols, including quercetin-3-O-ß-D-glucuronopyranoside (1), kaempferol-3-O-ß-D-glucuronopyranoside (2), strictinin (3), quercetin-3-O-(2``-O-galloyl)-ß-D-glucuronopyranoside (4), afzelin (5), di-galloyl glucose (6), mono-galloyl glucose (7), acacetin (8), apigenin-6,7-dimethyl ether (9), kaempferol trimethyl ether (10), dimethoxy chrysin (11), quercetin (12), kaempferol (13), methyl gallate (14), and gallic acid (15) were identified. The extract exhibited as significant antioxidant activity even better than that of Trolox or BHT. Moreover, it exerts elastase, tyrosinase, and collagenase inhibition activities, in addition to the significant peripheral and central analgesic activity in a dose-dependent manner (P < 0.0001). In castor oil induced diarrhea model, AME significantly prolonged the diarrhea onset, decreased the frequency of defecation, and weight of feces. Likewise, it exhibited a significant reduction in the gastrointestinal motility in charcoal meal model (P < 0.0001) and a considerable inhibitory effect on gastrointestinal transit and peristaltic index with all investigated doses (P < 0.0001). CONCLUSION: Ethnobotanicals are versatile resources for the management of various ailments by indigenous people and the experimental research is utmost to validate and uncover their pharmacological relevance. C. sabulatus leaves have strong antioxidant, analgesic, anti-skin aging, and antidiarrheal activities which are validated for the first time by various in vitro and in vivo models. The metabolic profile of the unprecedented AME of C. sabulatus leaves compromises a wide array of bioactive polyphenolic metabolites including, flavonoids, tannins, and phenolic acids that are correlated to the observed bioactivities. Altogether, ethnobotanicals with high and diverse contents of polyphenols are potential candidates for the management of various human aliments including neuropathies, GIT disorders, and skin aging conditions.

Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves.

Endophytes are prolific producers of privileged secondary metabolites with diverse therapeutic potential, although their anticancer and antimicrobial potential still have a room for further investigation. Herein, seven known secondary metabolites namely, arugosin C (1), ergosterol (2), iso-emericellin (3), sterigmatocystin (4), dihydrosterigmatocystin (5), versicolorin B (6), and diorcinol (7) were isolated from the rice culture of Aspergillus sp. retrieved from Tecoma stans (L.) Juss. ex Kunth leaves. Their anticancer and antimicrobial activities were evaluated in MTT and agar well diffusion assays, respectively. The cytotoxicity results showed that metabolite 3 displayed the best viability inhibition on the MCF-7 breast cancer cells with IC50 = 225.21 µM, while 5 on the HepG2 hepatocellular carcinoma cells with IC50 = 161.81 µM. 5 demonstrated a 60% apoptotic mode of cell death which is virtually correlated to its high docking affinity to Hsp90 ATP binding cleft (binding score -8.4 Kcal/mol). On the other side, metabolites 4 and 5 displayed promising antimicrobial activity especially on Pseudomonas aeruginosa with MIC = 125 µg/ml. The observed effect may be likely related to their excellent in silico inhibition of the bacterial DNA-gyrase kinase domain (binding score -10.28 Kcal/mol). To the best of our knowledge, this study is the first to report the promising cytotoxic and antibacterial activities of metabolites 3, 4, and 5 which needs further investigation and renovation to therapeutic leads.

Polyphenolic Profile of Callistemon viminalis Aerial Parts: Antioxidant, Anticancer and In Silico 5-LOX Inhibitory Evaluations.

Five new compounds viz kaempferol 3-O-(4″-galloyl)-ß-d-glucopyranosyl-(1‴→6″)-O-ß-d-glucopyranoside (1), kaempferol 3-O-ß-d-mannuronopyranoside (2), kaempferol 3-O-ß-d-mannopyranoside (3), quercetin 3-O-ß-d-mannuronopyranoside (4), 2, 3 (S)- hexahydroxydiphenoyl]-d-glucose (5) along with fifteen known compounds were isolated from 80% aqueous methanol extract (AME) of C. viminalis. AME and compounds exerted similar or better antioxidant activity to ascorbic acid using DPPH, O2-, and NO inhibition methods. In addition, compounds 16, 4, and 7 showed cytotoxic activity against MCF-7 cell lines while 3, 7 and 16 exhibited strong activity against HepG2. An in silico analysis using molecular docking for polyphenolic compounds 2, 3, 7, 16 and 17 against human stable 5-LOX was performed and compared to that of ascorbic acid and quercetin. The binding mode as well as the enzyme-inhibitor interactions were evaluated. All compounds occupied the 5-LOX active site and showed binding affinity greater than ascorbic acid or quercetin. The data herein suggest that AME, a source of polyphenols, could be used against oxidative-stress-related disorders.

Pharmacological activity and flavonoids constituents of Artemisia judaica L aerial parts.

ETHNO-PHARMACOLOGICAL RELEVANCE: Artemisia judaica L is an aromatic medicinal plant growing widely in Saint Katherine, Sinai, Egypt, and used in traditional medicine as a herbal remedy for antibacterial, anthelmintic, antidiabetic, analgesic and anti-inflammatory activities. Additionally, other Arabic regions commonly used it in their folk medicines for the treatment of fungal infections, atherosclerosis, cancer, diabetes, arthritis, and inflammatory-related diseases. AIM OF THE STUDY: Based on the traditional medicinal uses of A. judaica, the present study was designed to validate some of the traditional uses as the analgesic, anti-inflammatory, antipyretic, hepatoprotective, antidiabetic, and antioxidant activities of 80% aqueous methanol extract (AME) of A. judaica aerial parts as well as isolation and identification of its flavonoid content. MATERIALS AND METHODS: AME of A. judaica aerial parts was fractionated using column chromatography and the structures of the isolated compounds were established using different spectroscopic data. Analgesic activity was evaluated using acetic acid-induced writhing in mice; antipyretic activity was assessed using yeast suspension-induced hyperthermia in rats; anti-inflammatory activity was evaluated using carrageenan-induced paw edema; the hepatoprotective effect was studied by measuring liver enzymes in carbon tetrachloride(CCl4)-induced hepatotoxicity rats while antidiabetic activity was estimated in alloxan hyperglycemia. RESULTS: Eight flavone compounds namely luteolin 4' methyl ether 7-O-ß-D-4C1-glucopyranoside (1), 8-methoxyapigenin 7-O-ß-D-4C1-galactopyranoside (2), isovitexin (3), 8-methoxyluteolin 7-O-ß-D-4C1-glucopyranoside (4), diosmetin (5), cirsimaritin (6), luteolin (7), and apigenin (8) were identified from AME of A. judaica. The AME was found to be non-toxic to mice up to 5 g/kg b.w. Moreover, it exhibits significant analgesic antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities in a dose-dependent manner. CONCLUSION: The AME was nontoxic; it exhibits significant analgesic, antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities. Moreover, the isolated flavone was identified from AME for the first time.

New Apigenin Glycoside, Polyphenolic Constituents, Anti-inflammatory and Hepatoprotective Activities of Gaillardia grandiflora and Gaillardia pulchella Aerial Parts.

BACKGROUND: Gaillardia grandiflora Hort. ex Van Houte and Gaillardia pulchella Foug are flowering plants widely cultivated in Egypt for their ornamental value. Previous reports demonstrated that sesquiterpene derivatives represent the major compounds in both species. Moreover, only few flavones were identified from genus Gaillardia and few studies on the cytotoxicity of G. pulchella were found. AIM OF THE STUDY: Investigation of the phenolic constituents of the aerial parts of both species and evaluation of their anti-inflammatory and hepatoprotective activities. MATERIALS AND METHODS: The 80% aqueous methanol extracts (AME) were prepared for both plants and evaluated for their biological activities. Phytochemical investigation of both extracts resulted in isolation of twelve compounds, which have been identified on the basis of ultraviolet, 1D and 2D nuclear magnetic resonance spectroscopy and negative ESI-MS. RESULTS: The new 8-hydroxyapigenin 6-O-ß-D-apiofuranosyl-(1'''→6'')-C-ß-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in nature, along with schaftoside, luteolin 6-C-ß-D-4C1-glucopyranoside 8-methyl ether, apigenin 6-C-ß-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin, as well as vicenin-2, vitexin, luteolin and apigenin, which were isolated from G. pulchella together with 6-methoxyluteolin. Furthermore, the AME of both species were found to be nontoxic to mice and exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner. CONCLUSION: Current results shed light on the phenolic constituents of G. grandiflora and G. pulchella aerial parts and the safety of the AME of both species, in addition to their significant anti-inflammatory and hepatoprotective activities. Both plant species may be promising candidates for natural anti-inflammatory and hepatoprotective drugs. SUMMARY: Phytochemical investigation of Gaillardia grandiflora and Gaillardia pulchella 80% aqueous methanol extracts of the aerial parts led to the isolation of twelve compoundsThe new compound 8-hydroxyapigenin 6-O-ß-D-apiofuranosyl-(1''''→6'')-C-ß-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in natureSchaftoside, luteolin 6-C-ß-D-4C1-glucopyranoside 8-methyl ether, apigenin 6-C-ß-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin were isolated from G. grandifloraVicenin-2, vitexin, luteolin, apigenin and 6-methoxyluteolin were isolated from G. pulchellaThe extracts of both species were nontoxic to mice up to 5 g/kg body weightBoth extracts exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner Abbreviations used: ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AME: The 80% aqueous methanol extract of G. grandiflora or G. pulchella aerial parts; AST: Aspartate aminotransferase; br d: Broad doublet; Comp-PC: Comparative paper chromatography; d: Doublet; 2D-PC: Two-dimensional paper chromatography; DMSO-d6: Deuterated dimethyl sulfoxide; G.: Gaillardia; GPx: Glutathione peroxidase; GRd: Glutathione reductase; GSH: glutathione; GST: Glutathione-S-transferase; J: Nuclear spin-spin coupling constant; m: Multiplet; [M-H]-: Molecular ion peak; MDA: Malondialdehyde; m/z: Mass/charge ratio; NO: Nitric oxide; p: Probability; PC: Paper chromatography; Rf: Retention flow; rpm: Rotation per minute; s: Singlet; SDE: The ethanol extract of Scoparia dulcis; SE: Standard error; SOD: Superoxide dismutase; TMS: Tetramethylsilane; λmax: Maximum fluorescence emission wavelength.

Spectroscopic identification of new ellagitannins and a trigalloyl-glucosylkaempferol from an extract of Euphorbia cotinifolia L. with antitumour and antioxidant activity.

From an extract of leaves and small branches of Euphorbia cotinifolia L., 17 polyphenols were isolated including two new ellagitannins and a trigalloyl-glucosylkaempferol. Based on extensive spectral data (UV, ESI-MS, 1H NMR, DEPT and 1D/2D NMR) and chemical studies, their structures were characterized as 1-O-galloyl-3,6-hexahydroxydiphenoyl-D-B1,4-glucopyranose (5), 1-O-galloyl-3,6-valoneoyl-D-B1,4-glucopyranose (6), and kaempferol 3-O-(2",3",6"-tri-O-galloyl)-beta-D-glucopyranoside (13). Biological evaluation indicated that the 80% aqueous methanol extract (AME), chloroform extract (CE), and some pure compounds have potent scavenging activity in the DPPH assay with SC50 values lower than that of ascorbic acid, especially 5, 7-9, and a mixture of hyperin 6"-gallate (11) and isoquercitrin 6"-gallate (12). Moreover, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay, 6 and 8 exhibited the highest inhibition of human hepatocellular carcinoma cells (Hep-G2), while AME, CE, 5, 7, 9, and the mixture of 11 and 12 were found to be moderate growth inhibitors according to their IC50 values. In addition, AME, 5, and 8 exhibited significant antiproliferative activity against colon carcinoma cells (HCT-116); however, CE and the other examined compounds displayed moderate to low antitumour activity against HCT-116 cells.

Polyphenolic profile and bioactivity study of Oenothera speciosa Nutt. aerial parts.

Two new flavonol glycosides, myricetin 4'-O-alpha-L-rhamnopyranoside (1) and quercetin 3'-O-alpha-L-rhamnopyranoside (2), together with a novel biflavonol compound, speciin (3), as well as eleven phenolic metabolites, namely myricitrin (4), europetin 3-O-alpha-L-(1)C(4)-rhamnopyranoside (5), quercitrin (6), hyperin (7), rhamnetin 3-O-beta-galacto-pyranoside (8), caffeic acid (9), caffeic acid methyl ester (10), chlorogenic acid (11), chlorogenic acid methyl ester (12), gallic acid (13) and gallic acid methyl ester (14), were identified from the 80 % methanol extract of the aerial parts (leaves and stems) of Oenothera speciosa Nutt. (Onagraceae). In addition myricetin (15), quercetin (16) and ellagic acid (17) were identified from the chloroform extract. The structures were established depending on their chemical and physical analyses (UV, HR-ESIMS, 1D and 2D NMR). It was found that 80 % aqueous methanol extract of O. speciosa is non-toxic to mice up to 5 g kg(-1)b wt. The investigated extract exhibited significant antihyperglycaemic and anti-inflammatory activities in a dose dependant manner. Also, the 80 % methanol extract, myricitrin(4) and hyperin(7) showed potent antioxidant activity in vitro using 1,1-diphenyl 2-picryl hydrazyl (DPPH) radical assay.

Anticancer and antioxidant tannins from Pimenta dioica leaves.

Two galloylglucosides, 6-hydroxy-eugenol 4-O-(6'-O-galloyl)-beta-D-4C1-glucopyranoside (4) and 3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol-2-O-(2',6'-di-O-galloyl)-beta-D -4C1-glucopyranoside (7), and two C-glycosidic tannins, vascalaginone (10) and grandininol (14), together with fourteen known metabolites, gallic acid (1), methyl gallate (2), nilocitin (3), 1-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-(alpha/beta)-D-glucopyranose (5), 4,6-(S)-hexahydroxydiphenoyl-(alpha/beta)-D-glucopyranose (6), 3,4,6-valoneoyl-(alpha/beta)-D-glucopyranose (8), pedunculagin (9), casuariin (11), castalagin (12), vascalagin (13), casuarinin (15), grandinin (16), methyl-flavogallonate (17) and ellagic acid (18), were identified from the leaves of Pimenta dioica (Merr.) L. (Myrtaceae) on the basis of their chemical and physicochemical analysis (UV, HRESI-MS, 1D and 2D NMR). It was found that 9 is the most cytotoxic compound against solid tumour cancer cells, the most potent scavenger against the artificial radical DPPH and physiological radicals including ROO*, OH*, and O2-*, and strongly inhibited the NO generation and induced the proliferation of T-lymphocytes and macrophages. On the other hand, 3 was the strongest NO inhibitor and 16 the highest stimulator for the proliferation of T-lymphocytes, while 10 was the most active inducer of macrophage proliferation.

Antioxidant flavonol glycosides from Schinus molle.

Chromatographic separation of aqueous MeOH extract of the leaves of Schinus molle L. has yielded two new acylated quercetin glycosides, named isoquercitrin 6''-O-p-hydroxybenzoate (12) and 2''-O-alpha-L-rhamnopyranosyl-hyperin 6''-O-gallate (13), together with 12 known polyphenolic metabolites for the first time from this species, namely gallic acid (1), methyl gallate (2), chlorogenic acid (3), 2''-alpha-L-rhamnopyranosyl-hyperin (4), quercetin 3-O-beta-D-neohesperidoside (5), miquelianin (6), quercetin 3-O-beta-D-galacturonopyranoside (7), isoquercitrin (8), hyperin (9), isoquercitrin 6''-gallate (10), hyperin 6''-O-gallate (11) and (+)-catechin (14). Their structures were established on the basis of chromatographic properties, chemical, spectroscopic (UV, 1H, 13C NMR) and ESI-MS (positive and negative modes) analyses. Compounds 4-9 and 11 exhibited moderate to strong radical scavenging properties on lipid peroxidation, hydroxyl radical and superoxide anion generations with the highest activities shown by 6 and 7 in comparison with that of quercetin as a positive control in vitro.