Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria.

Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.

Two new 2-(2-phenylethyl)chromone derivatives and two sesquiterpenes from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Two new 2-(2-phenylethyl)chromones (1-2), two new sesquiterpenes (12-13), and twelve known compounds (3-11, 14-16) were isolated from agarwood of Aquilaria sinensis. These structures were confirmed by HRESIMS, 1D and 2D NMR spectra. The absolute configurations of two new sesquiterpenes were determined by comparing the experimental and calculated ECD spectra. Among them, 7,8-dihydroxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (2) was the first time found that the hydroxyl groups at both C-7/C-8 in agarwood. And Aseudesm B (13), the aldehyded methyl group at C-5 of eucalyptane sesquiterpenes was first discovered in natural products. In the bioassays, all compounds were evaluated for their inhibitory activity against lipopolysaccharide-activated nitric oxide (NO) production in RAW264.7 cells. Compounds 2-5, 7, 9-10, and 13-14 revealed notable inhibitory effects against NO production with IC50 values ranging from 4.0 to 13.0 µM.

Eight new 2-(2-phenylethyl)chromone derivatives from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Eight previously unknown 2-(2-phenylethyl)chromone derivatives, called aquichromones A - E (1-3, 5 and 6) and 8-epi-aquichromone C (4), including two pairs of enantiomers [(±)-1 and (±)-2] were isolated from the agarwood of Aquilaria sinensis. The structures and absolute stereochemistry of these natural products were elucidated by using spectroscopic and computational methods. The result of biological assay showed that two members of this group, 4 and 5, have significant dose-dependent anti-inflammatory activity.

Dimeric 2-(2-phenethyl)chromones from agarwood of Aquilaria filaria.

Four new 2-(2-phenethyl)chromone dimers (1-4) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria from Philippines. Their structures were elucidated by spectroscopic analysis (1D and 2D NMR, and HRESIMS) and comparison of the experimental and computed ECD curves. Compounds 1-4 exhibited inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range from 33.94 to 57.53 µM.

Syntheses, Molecular Docking and Biological Evaluation of 2-(2- hydrazinyl)thiazoles as Potential Antioxidant, Anti-Inflammatory and Significant Anticancer Agents.

BACKGROUND: Recently, researchers have worked on the development of new methods for the synthesis of bioactive heterocycles using polyethylene glycol as a green solvent. In this context, we report the synthesized 2-(2-hydrazinyl) thiazoles for their in vitro antioxidant, in vitro anti-inflammatory and in vitro anti-cancer activities. OBJECTIVE: The objective of the study was to develop novel antioxidant, anti-inflammatory and anti-cancer drugs. METHODS: At the outset, the condensation of substituted acetophenones 1, thiosemicarbazide 2, and α-haloketones 3 was carried out using PEG-400 (20 mL) in the presence of 5 mol% glacial acetic acid to afford thiosemicarbazones intermediate. Furthermore, these thiosemicarbazones were reacted with α-haloketones 3 to obtain appropriate 2-(2-hydrazinyl) thiazoles. The synthesized compounds were in vitro tested for their antioxidant, anti-inflammatory, and anti-cancer activity. RESULTS: In vitro evaluation report showed that nearly all molecules possessed potential antioxidant activity against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR) and hydrogen peroxide (H2O2) radical scavenging activity. Most 2-(2-hydrazinyl) thiazoles derivatives have shown potential anti-inflammatory activity as compared to diclofenac sodium as a reference standard. 2-(2-Hydrazinyl) thiazoles derivatives showed significant anticancer activity for human leukemia cell line K-562 compared to adriamycin as a reference standard. CONCLUSION: All tested compounds showed potential 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging activity. Among the tested series, 4b, 4d and 4e exhibited good hydrogen peroxide and 4b, 4e, 4f and 4g showed excellent superoxide radical scavenging activity. In addition, the 4b, 4e and 4g compounds revealed potent in vitro anti-inflammatory activity against standard diclofenac sodium drug. 2-(2-Hydrazinyl) thiazole derivatives, such as 4c and 4d, showed significant anticancer activity against human leukemia cell line K-562. Thus, these molecules provide an interesting template for the design and development of new antioxidant, anti-inflammatory, and anti-cancer agents.

Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation.

Opposing roles have been proposed for IL-22 in intestinal pathophysiology. We have optimized human small intestinal organoid (hSIO) culturing, constitutively generating all differentiated cell types while maintaining an active stem cell compartment. IL-22 does not promote the expansion of stem cells but rather slows the growth of hSIOs. In hSIOs, IL-22 is required for formation of Paneth cells, the prime producers of intestinal antimicrobial peptides (AMPs). Introduction of inflammatory bowel disease (IBD)-associated loss-of-function mutations in the IL-22 co-receptor gene IL10RB resulted in abolishment of Paneth cells in hSIOs. Moreover, IL-22 induced expression of host defense genes (such as REG1A, REG1B, and DMBT1) in enterocytes, goblet cells, Paneth cells, Tuft cells, and even stem cells. Thus, IL-22 does not directly control the regenerative capacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.

Seven new 2-(2-phenylethyl) chromone derivatives from agarwood of Aquilaria agallocha with inhibitory effects on nitric oxide production.

Seven new 2-(2-Phenethyl) chromone derivatives (1-7), including four 2-(2-Phenethyl) chromones (1-4), one 6, 7, 8 trihydroxy-2-(2-Phenethyl) chromone (5), one acetylated 5, 6, 7, 8-tetrahydroxy-2-(2-Phenethyl) chromone (6), and one chlorine-containing 5, 6, 7, 8-tetrahydro-2-(2-Phenethyl) chromone (7), along with eight known compounds (8-15), were isolated from agarwood originating from Aquilaria agallocha Roxb.. Their structures were determined mainly by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) analysis. The absolute configurations of 3-7 were resolved by electronic circular dichroism (ECD) calculations. Nearly all compounds were evaluated for their anti-inflammatory activities in RAW264.7 cells. Compounds 1 and 7-11 displayed significant anti-inflammatory activities with IC50 values ranging from 3.71 to 32.04 µM.

Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.

Ergosta-7,9(11),22-trien-3ß-ol Attenuates Inflammatory Responses via Inhibiting MAPK/AP-1 Induced IL-6/JAK/STAT Pathways and Activating Nrf2/HO-1 Signaling in LPS-Stimulated Macrophage-like Cells.

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3ß-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.

A Novel Bifunctional Fusion Protein, Vunakizumab-IL22, for Protection Against Pulmonary Immune Injury Caused by Influenza Virus.

Influenza A virus infection is usually associated with acute lung injury, which is typically characterized by tracheal mucosal barrier damage and an interleukin 17A (IL-17A)-mediated inflammatory response in lung tissues. Although targeting IL-17A has been proven to be beneficial for attenuating inflammation around lung cells, it still has a limited effect on pulmonary tissue recovery after influenza A virus infection. In this research, interleukin 22 (IL-22), a cytokine involved in the repair of the pulmonary mucosal barrier, was fused to the C-terminus of the anti-IL-17A antibody vunakizumab to endow the antibody with a tissue recovery function. The vunakizumab-IL22 (vmab-IL-22) fusion protein exhibits favorable stability and retains the biological activities of both the anti-IL-17A antibody and IL-22 in vitro. Mice infected with lethal H1N1 influenza A virus and treated with vmab-mIL22 showed attenuation of lung index scores and edema when compared to those of mice treated with saline or vmab or mIL22 alone. Our results also illustrate that vmab-mIL22 triggers the upregulation of MUC2 and ZO1, as well as the modulation of cytokines such as IL-1ß, HMGB1 and IL-10, indicating the recovery of pulmonary goblet cells and the suppression of excessive inflammation in mice after influenza A virus infection. Moreover, transcriptome profiling analysis suggest the downregulation of fibrosis-related genes and signaling pathways, including genes related to focal adhesion, the inflammatory response pathway, the TGF-ß signaling pathway and lung fibrosis upon vmab-mIL22 treatment, which indicates that the probable mechanism of vmab-mIL22 in ameliorating H1N1 influenza A-induced lung injury. Our results reveal that the bifunctional fusion protein vmab-mIL22 can trigger potent therapeutic effects in H1N1-infected mice by enhancing lung tissue recovery and inhibiting pulmonary inflammation, which highlights a potential approach for treating influenza A virus infection by targeting IL-17A and IL-22 simultaneously.

Antiviral activity of Lavandula angustifolia L. and Salvia officinalis L. essential oils against avian influenza H5N1 virus.

Nowadays, viral infection is considered a major cause of mortality all over the world such as covid-19 pandemic. In this context, searching for antiviral agents are major researchers interests. In this study, essential oils (EO) of Lavandula angustifolia (lavender) and Salvia officinalis (salvia) were subjected to combat avian influenza H5N1 virus. Laboratory trials were performed to identify Lavender and salvia EOs and evaluate their antioxidant, anti-inflammatory and antiviral activity against an avian influenza H5N1 virus. EOs were prepared by the hydrodistillation of air-dried plants and analyzed by GC-MS methods. The results revealed that salvia has the highest EOs yield 1.3% than lavender 1%. The dominant constituents of lavender EO were linalyl acetate and linalool while camphor and α-thujone were the dominant compounds of salvia. Both oils exhibited antioxidant activity in DPPH and ABTS and total antioxidant capacity assays. The results suggest the use of salvia and lavender EOs as effective natural anti-inflammatory, antioxidant and antiviral agents.

The potential of BEN815 as an anti-inflammatory, antiviral and antioxidant agent for the treatment of COVID-19.

Background: The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal. Purpose: Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves (Psidium guajava), green tea leaves (Camellia sinensis), and rose petals (Rosa hybrida), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19. Study design: We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells. Methods: The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining. Results: BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells. Conclusion: BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19.

Meta-analysis Exploring Sinopulmonary Outcomes of Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

OBJECTIVE: The objective of this study is to explore the sinopulmonary outcomes of aspirin desensitization through a systematic review and meta-analysis. DATA SOURCES: Embase and OVID Medline databases. REVIEW METHODS: A systematic review of published articles on outcomes following aspirin desensitization in any language for relevant articles was performed in February 2019. Outcomes included sinonasal quality-of-life assessment, sense-of-smell scores, FEV-1 (forced expiratory volume in 1 second), and medication/steroid use. RESULTS: Thirteen studies met the inclusion criteria out of 6055 articles screened. Aspirin desensitization resulted in significant improvement in FEV-1 and reduction in asthma medication/steroid use (P < .05). There was no significant improvement in the sinonasal quality of life of patients who underwent aspirin desensitization (P = .098). CONCLUSION: Aspirin desensitization appears to be effective in improving pulmonary outcomes and should be considered in the treatment of patients with aspirin-exacerbated respiratory disease. However, good-quality studies are still needed to determine the ideal protocol tailored to individual patients.

(E)-2-(2-Allylidenehydrazinyl)thiazole derivatives: Design, green synthesis, in silico and in vitro antimycobacterial and radical scavenging studies.

By understanding the rampant infections of Mycobacterium tuberculosis (Mtb) and inflammations caused due to the generation of radical species during the Mtb infection, a series of (E)-2-(2-allylidenehydrazinyl)thiazole derivatives, with dual-action properties, was designed. The molecules were designed with a considerable variation in LogP, one of the critical parameters in physicochemical properties, and analyzed for their drug-likeness. For the synthesis, a simple, green, and multicomponent one-pot synthesis method was developed. The in vitro inhibition potentials were evaluated against Mtb H37 Rv by the microplate Alamar Blue assay. The results reveal that compound 6 was potent, with a MIC value of 6.5 µg/ml, and showed better interactions with the KasA protein with binding free energy (ΔG) of -9.4 kcal/mol. Also, the radical scavenging properties were studied to establish the dual-action properties of the molecules. Compound 9 exhibited promising antioxidant and nitric oxide radical scavenging activities, with 81.7% and 81.0%, respectively, at 1,000-µg/ml concentration.

Anti-inflammatory 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones from agarwood of Aquilaria sinensis.

Four new 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, aqulisinone A (1), (5S, 6R,7S,8S)-8-chloro-5,6,7-trihydroxy-2-[2-(4'-methoxyphenylethyl)]-5,6,7,8-tetrahydrochromone (2), (5S,6R,7S,8S)-8-chloro-5,6,7-trihydroxy-2-(2-phenylethyl)-5,6,7,8-tetrahydrochromone (3), (5S*,6R*,7R*,8S*)-8-chloro-5-ethoxy-6,7-dihydroxy-2-[2-(3'-hydroxy-4'-methoxy-phenylethyl)-5,6,7,8-tetrahydrochromone (4), and seven known analogues (5-11) were isolated from agarwood produced of Aquilaria sinensis. Among the new compounds, 4 is an artifact. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. The absolute configurations of 1-3 were defined based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) data. Compound 1 features a (5,5'')-carbon-carbon bond linkage connecting two 2-(2-phenylethyl)chromone monomeric units. All the new compounds were evaluated for their anti-inflammatory activities by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) release in RAW264.7 cells, 2 with an IC50 value of 3.46 µM.

Anti-inflammatory quinoline alkaloids from the root bark of Dictamnus dasycarpus.

Six undescribed quinoline alkaloids, named dasycarines A-E, and 18 known ones were isolated from the root bark of Dictamnus dasycarpus. All the structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, and HRMS spectroscopic data, and the absolute configurations were assigned via comparison of the calculated and experimental ECD data. (+)-Dasycarine A (1a) and (-)-Dasycarine A (1b) are a pair of enantiomers of dimeric furoquinoline alkaloid, which are the first dimeric via [2 + 2] cycloaddition of furan. The structure and absolute configuration of (-)-dasycarine A was determined via X-ray crystallography. Additionally, all the isolated compounds were tested for their inhibitory effects on NO production stimulated by LPS in BV-2 microglial cells. Three compounds showed strong inhibition with IC50 values below 5.0 µM; nine compounds exhibited inhibition with IC50 values in the range of 7.8-28.4 µM. Furthermore, we demonstrated that preskimmianine suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB) in LPS-induced BV-2 microglial cells.

Anti-inflammatory kavalactones from Alpinia zerumbet.

Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm. (Zingiberaceae) is a perennial plant native to the East Indies and is widely distributed in South America, Oceania, and Asia. The mature fruits of the plant have been used in traditional medicine in China. In this study, we compared the chemical constituents in the methanol extracts of the leaves, the placenta, the pericarps, and the seeds obtained from the same plant using LC-MS, and we examined the NO inhibitory activities of the respective extracts and the isolated compounds. As a result of LC-MS analyses, kavalactone derivatives (1-6) were detected in the methanol extracts of the leaves, placenta, and pericarps. Of these, compound 6 was identified as a new asymmetrical cyclobutane dimer of 5,6-dehydrokawain. Quantitative analysis showed that the total amounts of kavalactone derivatives were highest in the methanol extract of the pericarps. Moreover, the results of measurements of the anti-inflammatory activity revealed that the pericarps extract showed the strongest activity. The compounds responsible for the anti-inflammatory activity of the extracts from A. zerumbet were identified. Of these, five were known kavalactone derivatives and one was a new kavalactone derivative (aniba dimer C). The results showed that the pericarps of A. zerumbet are a rich source of kavalactone derivatives, and that the pericarps of A. zerumbet can be utilized as an important medicinal resource.

Synthesis, pharmacological evaluation and molecular docking of novel R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid as dual anti-inflammatory anti-platelet aggregation agents.

R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA), marine-derived anti-inflammatory antiplatelet drugs, were initially synthesised in our group. However, preliminary research showed that R-/S-HPABA were eliminated rapidly because of extensive hydroxylation metabolism of phenyl ring in vivo. In order to reduce significant hydroxylation metabolism to improve pharmacological activity and bioavailability, trifluoromethyl group was incorporated into R-/S-HPABA to synthesise R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid (R-/S-HFBA), respectively. The purposes of this study were to report the synthesis of R-/S-HFBA and compare the anti-inflammatory antiplatelet effect and pharmacokinetic properties of R-/S-HFBA with those of R-/S-HPABA. Carrageenan-induced rat paw edema assay was used for the evaluation of the anti-inflammatory activity. R-/S-HFBA showed better results in inhibiting edema and were able to prolong the anti-inflammatory effect after carrageenan injection. The antiplatelet aggregation activity of R-/S-HFBA and R-/S-HPABA was studied on arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. The aggregation inhibition rate of R-/S-HFBA was significantly (p < 0.05) higher than that of R-/S-HPABA, respectively. Molecular docking study revealed that R-/S-HFBA possess more potent binding affinity with COX-1/COX-2 than R-/S-HPABA, respectively, and that the presence of trifluoromethyl group leads to increase in activity of R-/S-HFBA. R-/S-HFBA also afford more favorable pharmacokinetic properties than R-/S-HPABA, respectively, such as higher Cmax, larger AUC0-∞, and longer t1/2, which, as expected, are more metabolically stable.

Effect of Byrsonima sericea DC. leaf extracts on mice gastrointestinal tract.

Byrsonima sericea DC. (Malpighiaceae) leaves are popularly folk medicine in Brazil used to treat gastro-intestinal disorders including diarrhea and gastric diseases. Ethanol extract (BSEE), ethyl acetate extract (BSEAE) and hexane extract (BSHE) of the leaf part of Byrsonima sericea DC were characterized for their total phenolics, proanthocyanidins and flavonoids content. The total antioxidant capacity of extracts was determined. The ethnopharmacological use of B. sericea leaves was evaluated by assaying BSEE for gastroprotective activity in stomach ulcer induced by indomethacin, intestinal motility and toxicity. Abundance of phenols mainly tannins was found in BSEE. Total phenolics, flavonoids and proanthocyanidins content in BSEE were found to be 0.371, 0.172 and 1.3 × 10-4 (mg/g) respectively. BSEE showed concentration dependent significant scavenging of DPPH values 90.0 (%) respectively. Moreover, oral doses of 500 and 1000 mg/kg did not cause mortality, and there was no difference in animals weight, organs relative weight and alanine transaminase (ALT) and aspartate transaminase (AST), as compared to the control group. Doses of 250, 500 and 1000 mg/kg inhibited the gastric lesions induced by indomethacin in 52, 60 and 62 % respectively. The dose of 1000 mg/kg decreased intestinal motility in animals. The presence of phenolic compounds, including tannins could be associated with the anti-diarrheal action and the antioxidant properties could collaborate to the gastroprotective and anti- diarrheal activities, confirming its popular use of the plant.

Chemical composition and biological activity of the essential oil from the root of Jatropha pelargoniifolia Courb. native to Saudi Arabia.

The chemical composition of the essential oil from Jatropha pelargoniifolia roots was determined via GC-FID. There were 80 compounds, representing 99.99% of the total oil constituents. Among these, 77.31% were sesquiterpenes, 14.62% were fatty acids, 7.21% were other components (i.e., phenolics, hydrocarbons, etc.), and 0.85% were monoterpenes. The major compounds in the oil were γ-eudesmol (35.31%), 5-guaien-11-ol (14.43%), epi-cedrol (8.19%), oleic acid (5.23%), bulnesol (4.45%), α-linoleic acid (4.20%), 3,4-dimethoxycinnamic acid (3.83%), palmitic acid (2.69%), isolongifolanone (2.68%), eicosane (1.41%), and cedrol (1.14%). Oxygenated sesquiterpenes were found to represent more than 50% percent of the total oil content. Moreover, the essential oil was evaluated for anti-inflammatory, antioxidant, antipyretic, and antinociceptive activities using in vivo and in vitro models. Additionally, the antioxidant potential of the oil was evaluated using various in vitro antioxidant tests, including DPPH•, ABTS•+ and FRAP. At a dose of 240 µl/kg, the oil showed anti-inflammatory (59.12%), antipyretic (37.00 ±â€¯0.11), and antinociceptive (47.58%) activities and showed significant (p < 0.001) effect as compared to a standard drug (phenylbutazone and indomethacin). These findings demonstrated that the essential oil of Jatropha pelargoniifolia root could be used as a natural source for their anti-inflammatory, antinociceptive, antipyretic, and antioxidant effects.