Chemical Composition,Antibacterial, Antibiofilm and Synergistic Properties of Essential Oils from Eucalyptus globulus Labill. and Seven Mediterranean Aromatic Plants

Essential oils (EOs) from Eucalyptus globulus Labill . ssp. globulus and from Mediterranean autochthonous aromatic plants – Thymus mastichina L., Mentha pulegium L., Rosmarinus officinalis L., Calamintha nepeta (L.) Savi ssp. nepeta, Cistus ladanifer L., Foeniculum vulgare L., Dittrichia viscosa (L.) Greuter ssp. viscosa – were extracted by hydrodistillation and characterized by GC‐FID and NMR spectroscopy. EOs were evaluated for antimicrobial properties against several bacterial strains, using diverse methods, namely, the agar disc‐diffusion method, the microdilution method, the crystal violet assay and the Live/Dead staining for assessment of biofilm formation. Potential synergy was assessed by a checkerboard method. EOs of R. officinalis and C. ladanifer showed a predominance in monoterpene hydrocarbons (> 60%); EOs of C. nepeta, M. pulegium, T. mastichina, E. globulus and F. vulgare were rich in oxygenated monoterpenes (62 – 96%) whereas EO of D. viscosa was mainly composed of oxygenated sesquiterpenes (54%). All EOs showed antimicrobial activity; M. pulegium and E. globulus generally had the strongest antimicrobial activity. EO of C. nepeta was the most promising in hampering the biofilm formation. The combinations D. viscosa/C. nepeta and E. globulus/T. mastichina were synergistic against Staphylococcus aureus. These results support the notion that EOs from the aromatic plants herein reported should be further explored as potential pharmaceuticals and/or food preservatives.     

Pentacyclic triterpenoids and other constituents isolated from the leaves of Gambeya lacourtiana and their antibacterial activity

The phytochemical study was done on the leaves of Gambeya lacourtiana. This plant has been used in traditional medicine to treat of different ailments such as uterine heamorrhage, metritis and other vaginal infections. Chromatographic fractionation and purification on the leaves crude extract afforded lupeol acetate (1), lupenone (2), lupeol (3), taraxerol (4) stigmasterol (5), erythrodiol (6), chamaedrydiol (7), methyl pheophorbide-a (8), corosolic acid (9), tormentic acid (10), epicatechin (11) and 22-dihydrospinasterol 3-O-β-D-glucopyranoside (12). The structures of compounds 1–12 were elucidated on the basis of 1D and 2D NMR, mass spectrometric and the spectroscopic data as well as comparison with the literature. Compounds 4, 7–10 and 12 were isolated for the first time from Gambeya genus. Crude extract, fractions and compounds 6–12 were evaluated for their antibacterial activity. Methyl pheophorbide-a (8) demonstrated moderate activity against Salmonella typhi CPC with MIC values of 62.5 μg/mL. The chemophenetic significance of these compounds is also discussed.     

Total Synthesis and Antibacterial Study of Cyclohexapeptides Desotamide B,Wollamide B and Their Analogs

As natural‐product‐derived antibiotics, desotamides A – D and wollamides exhibit growth inhibitory activity against Gram‐posivite bacteria (IC₅₀ 0.6 – 7 μm ) and are noncytotoxic to mammalian cells (IC₅₀ > 30 μm ). Herein we firstly report the total synthesis of above two cyclohexapeptides as well as a series of structural variants through solid phase peptide synthesis, of which 3 displayed a 2‐fold increase of antibacterial activity when compared with the original peptide 1 . This strategy may offer good improvements for the synthesis of other cyclic peptides.     

Iridoids from Pedicularis verticillata and Their Anti‐Complementary Activity

Three new iridoids named as pediverticilatasin A – C ( 1 – 3 , resp.), together with five known iridoids ( 4 – 8 , resp.) were isolated from the whole plants of Pedicularis verticillata. The structures of three new compounds were identified as (1S,7R)‐1‐ethoxy‐1,5,6,7‐tetrahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4(3H)‐one ( 1 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carboxylic acid ( 2 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carbaldehyde ( 3 ). Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, compounds 1 , 3 , and 6 exhibited anti‐complementary effects with CH₅₀ values ranging from 0.43 to 1.72 mm , which are plausible candidates for developing potent anti‐complementary agents.     

Oplopane Sesquiterpenes from Ligularia knorringiana and Their Anti‐Complementary Activity

Three new oplopane sesquiterpenes, knorringianalarins D – F ( 1 – 3 , respectively), and five known analogues ( 4 – 8 , respectively), were isolated from the roots and rhizomes of Ligularia knorringiana. The structures of three new compounds were identified as 4‐acetoxy‐11α,12‐epoxy‐2β‐hydroxy‐3β‐(2‐methylbutyryloxy)‐9α‐(4‐methylsenecioyloxy)oplop‐10(14)‐ene ( 1 ), 3β,4‐diacetoxy‐9α‐(4‐acetoxy‐4‐methylsenecioyloxy)‐11α,12‐epoxy‐8α‐(2‐methylbutyryloxy)oplop‐10(14)‐ene ( 2 ), and (1R,5R,6R,7R,9R)‐5,9,11‐trihydroxy‐4,15‐dinoroplop‐10(14)‐en‐3‐one ( 3 ) based on spectroscopic methods including 1D‐ and 2D‐NMR, mass spectrometry, and CD spectroscopy techniques. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, three oplopane sesquiterpenes ( 3 , 7 , and 8 ) exhibited better anti‐complementary effects with CH₅₀ values ranging from 0.33 to 0.89 mm , which are plausible candidates for developing potent anti‐complementary agents.     

In vitro Antiproliferative and Antibacterial Activities of Essential Oils from Four Species of Guatteria

The essential oils (EOs) extracted from four species of the genus Guatteria, G. australis, G. ferruginea, G. latifolia, and G. sellowiana were analyzed. A total of 24, 22, 25, and 19 constituents of the oils from four species, respectively, were identified by GC/MS. These oils showed qualitative and quantitative differences. All the oils contained the oxygenated sesquiterpenes spathulenol (11.04 – 40.29%) and caryophyllene oxide (7.74 – 40.13%) as predominant constituents. Evaluation of antiproliferative activity of the EOs showed strong selectivity (1.1 – 4.1 μg/ml) against the tumor cell line OVCAR‐03 (ovarian cancer), i.e., more active than the positive control doxorubicin (11.7 μg/ml). All EOs showed strong antibacterial activity (minimum inhibitory concentrations of 0.062 – 0.25 mg/ml) against strains of Rhodococcus equi.     

New Cyclohexadepsipeptides from an Entomogenous Fungus Fusarium proliferatum and Their Cytotoxicity and Autophagy‐Inducing Activity

Five new cyclohexadepsipeptides termed as enniatins R – V ( 1 – 5 ) and seven known cyclohexadepsipeptides ( 6 – 12 ) were isolated from the solid culture of Fusarium proliferatum, a fungus isolated from the cadaver of an unidentified insect collected in Tibet. Their structures were elucidated by NMR and MS spectroscopic analysis. The X‐ray single‐crystal structure of 6 was reported for the first time. Enniatins R and S represented the first enniatins incorporating with an unusual 2,3‐dihydroxy‐isovaleric acid (Div) residue. The cytotoxicity and autophagy‐inducing activities of 1 – 12 were evaluated in vitro. Beauvenniatin F ( 11 ) exhibited strong cytotoxicity against K562/A (adriamycin‐resistant K562) with IC₅₀ value of 3.78 μm , and also autophagy‐inducing activity at the concentration of 20 μm in GFP‐LC3 stable HeLa cells.     

Chemical Composition and Biological Investigations of Eryngium triquetrum Essential Oil from Algeria

The chemical composition, antibacterial and antioxidant activities of the essential oil obtained from Eryngium triquetrum from Algeria were studied. The chemical composition of sample oils from 25 locations was investigated using GC‐FID and GC/MS. Twenty‐four components representing always more than 87% were identified in essential oils from total aerial parts of plants, stems, flowers and roots. Falcarinol is highly dominant in the essential oil from the roots (95.5%). The relative abundance of falcarinol in the aerial parts correlates with the phenological stages of the plant. Aerial parts of E. triquetrum produce an essential oil dominated by falcarinol during the early flowering stage, and then there is a decrease in falcarinol and rebalancing of octanal during the flowering stage. To our knowledge, the present study is the first report of the chemical composition of E. triquetrum essential oil. Evaluation of the antibacterial activity by means of the paper disc diffusion method and minimum inhibitory concentration assays, showed a moderate efficiency of E. triquetrum essential oil. Using the DPPH method, the interesting antioxidant activity of E. triquetrum essential oil was established. These activities could be attributed to the dominance of falcarinol. The outcome of our literature search on the occurrence of falcarinol in essential oils suggests that E. triquetrum from Algeria could be considered as a possible source of natural falcarinol.     

NMR,HS‐SPME‐GC/MS,and HPLC/MSn Analyses of Phytoconstituents and Aroma Profile of Rosmarinus eriocalyx

In this work, a comprehensive study on the chemical constituents of the aerial parts of Rosmarinus eriocalyx (Lamiaceae), an aromatic shrub traditionally consumed as a food and herbal remedy in Algeria, is presented. The aroma profile was analysed by headspace solid phase microextraction (HS‐SPME) coupled with gas chromatography‐mass spectrometry (GC/MS), whereas the crude extract constituents were analyzed by ¹H‐NMR and by high performance liquid chromatography coupled with mass spectrometry (HPLC/MSⁿ). Thirty‐nine volatile compounds, most of them being monoterpenes, have been identified, with camphor, camphene, and α‐pinene as the most abundant constituents. ¹H‐NMR analysis revealed the presence of phenolic compounds and betulinic acid while HPLC/MSⁿ allowed the identification of glycosilated and aglyconic flavonoids as well as phenylpropanoid derivatives. Some of these constituents, namely as betulinic acid, rosmanol, and cirsimaritin were reported for the first time in R. eriocalyx.     

New Acetophenone Derivatives from Acronychia oligophlebia and Their Anti‐inflammatory and Antioxidant Activities

Seven new acetophenone derivatives (acroliones A – G, 1  –  7 ) and three known ones ( 8  –  10 ) were isolated from the leaves of Acronychia oligophlebia. Their structures were elucidated based on extensive spectroscopic analyses (IR, UV, HR‐ESI‐MS, 1D‐ and 2D‐NMR), X‐ray diffraction and comparison with literature data. The anti‐inflammatory and antioxidant activities of all isolates were evaluated.     

Phytochemical Profile and Biological Activities of Helianthemum canum l. baumg. from Turkey

In the current study, antioxidant, antibacterial activities, and the phenolic compositions of extracts from Helianthemum canum L. Baumg . (Apiaceae) aerial parts were investigated for the first time. The H . canum was extracted with 70% methanol (HCM eOH ) and water (HCW ). Both extracts were determined by total phenolic contents (3 mg/ml), flavonoids (1.5 mg/ml), flavonols (1.5 mg/ml), qualitative–quantitative compositions, iron (II ) chelation activities (0.1 – 5 mg/ml), free radical scavenging activities (DPPH ^?: 0.01 – 0.6 mg/ml and ABTS ^+?: 0.125 – 0.5 mg/ml) and the effect upon inhibition of β ‐carotene/linoleic acid co‐oxidation (1 mg/ml). The peroxidation level was also determined using the thiobarbituric acid method (0.01 – 1.5 mg/ml). The results of the activity tests given as IC ₅₀ values were estimated from non‐linear algorithm and compared with standards. Antibacterial activities of extracts and standards were evaluated against Gram‐ negative and ‐positive ten standard strains using disc diffusion and broth microdilution methods. The MIC results (312.5 – 2500 μg/ml) against tested microorganisms varied from 625 to 2500 μg/ml. In HPLC analysis, 3,5‐dihydroxybenzoic acid was found as the main substance in both extracts. These results showed that HCM eOH was richer in phenolic compounds (284.13 ± 0.30 mg GAE /g extract) from HCW (244.55 ± 0.35 mg GAE /g extract)_. In conclusion, H . canum extracts showed in vitro antibacterial and antioxidant activities.     

Comparison of Phytochemical Composition and Biological Activities of Rubus ulmifolius Extracts Originating from Four Regions of Tunisia

In the current study, the phenolic composition, antioxidant and antimicrobial activities of extracts from Rubus ulmifolius Schott leaves harvested in four localities (Sejnen, Tabarka, Faija and Ain drahem) in Tunisia were investigated for the first time. Great differences were found for the chemical composition, total phenol contents and biological activities among the evaluated extracts. HPLC analysis of methanolic extracts showed that the dominant compounds were kaempferol 3‐O‐rutinoside and naringenine. In addition, significant correlations were observed between antioxidant activities and phenolic contents. In fact, leaves collected from Sejnen presented higher total phenol content (53.32 mg GAE/g DW) and antioxidant activities (IC₅₀ = 39.40 mg/l) than the others samples. All extracts showed significant antimicrobial activity against six used bacteria with the inhibition zones diameters and minimal inhibitory concentration values were in the range of 8 – 16 mm and 6.25 – 25 mg/ml, respectively. The highest antimicrobial activities were recorded in Sejnen extract against Gram‐positive bacteria.     

Antimalarial and Antileishmanial Activities of Phytophenolics and Their Synthetic Analogues

Thirty‐seven phytophenolics and their synthetic analogues were evaluated for activity against two protozoal pathogens, Leishmania donovani and Plasmodium falciparum (D6 and W2 clones), respectively. 4,6‐Dimethoxyaurone demonstrated the highest activity with IC₅₀ values of 13.2 and 16.9 μm against L. donovani and P. falciparum (W2 clone), respectively, without undesired cytotoxicity against VERO cells. The moiety having two benzene rings was critical to maintain the antiprotozoal activities based on the observation that both coumaranones and chromones were inactive while other test compounds, including coumarans and aurones, remained active. There was no correlation between antiprotozoal activities and previously evaluated insect antifeedant activity against common cutworms (Spodoptera litura). Flavonoids, including aurones, pterocarpans, and lignan like dihydrobenzofurans, structural analogues of coumarans, are abundant in fruits and vegetables, so these phytophenolics may act as natural antiprotozoal agents in humans.     

Antiviral Activity of Faramea hyacinthina and Faramea truncata Leaves on Dengue Virus Type‐2 and Their Major Compounds

The defatted fractions of the Faramea hyacinthina and F. truncata (Rubiaceae) leaf MeOH extracts showed in vitro non‐cytotoxic and anti‐dengue virus serotype 2 (DENV2) activity in human hepatocarcinoma cell lineage (HepG2). Submitting these fractions to the developed RP‐SPE method allowed isolating the antiviral flavanone (2S)‐isosakuranetin‐7‐O‐β‐d ‐apiofuranosyl‐(1→6)‐β‐d ‐glucopyranoside ( 1 ) from both species and yielded less active sub‐fractions. The new diastereoisomeric epimer pair (2S) + (2R) of 5,3′,5′‐trihydroxyflavanone‐7‐O‐β‐d ‐apiofuranosyl‐(1→6)‐β‐d ‐glucopyranoside ( 2a / 2b ) from F. hyacinthina; the known narigenin‐7‐O‐β‐d ‐apiofuranosyl‐(1→6)‐β‐d ‐glucopyranoside ( 3 ) from both species; rutin ( 4 ) and quercetin‐4′‐β‐d ‐O‐glucopyranosyl‐3‐O‐rutinoside ( 5 ) from F. hyacinthina, and kaempferol‐3‐O‐rutinoside ( 6 ), erythroxyloside A ( 7 ) and asperuloside ( 8 ) from F. truncata have been isolated from these sub‐fractions. Compounds 4  –  8 are reported for the first time in Faramea spp.     

alpha-Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae)

In addition to fatty acids, a mixture of sterols (beta-sitosterol, stigmasterol, campesterol and stigmastanol), lupeol, arctigenin methylether, sesamin, vanillic acid (1), 2,6-dimethoxy-1,4-benzoquinone (2), betulinic acid and two pentacyclic triterpene acetates were isolated from Fagara tessmannii Engl. They were identified as 3beta-acetoxy-16beta-hydroxybetulinic acid (3a) and 3beta,16beta-diacetoxybetulinic acid (3b), and their structures were established using 1 and 2D NMR spectra and by comparison with published data. Two derivatives of the compounds were prepared. Some isolated compounds were evaluated for their antifungal and antibacterial activities. Compounds 1 and 3a showed significant inhibition of alpha-glucosidase.     

Structural Modification of Stilbenoids from Acanthopanax leucorrhizus and Their Cytotoxic Activity

A new cis‐stilbenoid, 1,9‐dihydroxy‐10‐methoxy‐6H‐dibenzo[b,f]oxocin‐6‐one ( 2 ) was isolated from the AcOEt extract of the stem barks of Acanthopanax leucorrhizus, along with three known stilbenoids, 9‐hydroxy‐10‐methoxy‐6H‐dibenzo[b,f]oxocin‐6‐one ( 1 ), 5‐O‐methyl‐(E)‐resveratrol 3‐O‐β‐d ‐glucopyranoside ( 3 ), and (E)‐resveratrol 3‐O‐β‐d ‐xylopyranoside ( 4 ). Two derivatives ( 2a and 2b ) were synthesized by the structural modification of compound 2, which exhibited certain cytotoxic activities against HT‐29 and HeLa cell lines in vitro. All compounds were structurally characterized by comprehensive analysis of their spectroscopic data and comparison with literature information, and evaluated for their cytotoxic activities against three human tumor cell lines (HL‐60, HT‐29, and HeLa) by the standard MTT assay in vitro. The results showed that derivatives 2a and 2b exhibited strong activities than compounds 2 against HT‐29 and HeLa cell lines.     

Synergistic Hepatoprotective and Antioxidant Effect of Artichoke,Fig, Blackberry Herbal Mixture on HepG2 Cells and Their Metabolic Profiling Using NMR Coupled with Chemometrics

The edible plants have long been reported to possess a lot of biological activities. Herein, the hepatoprotective and the antioxidant activities of the aqueous infusion of the edible parts of Cynara cardunculus, Ficus carica, and Morus nigra and their herbal mixture (CFM) was investigated in vitro using CCl₄ induced damage in HepG2 cells. The highest amelioration was observed via the consumption of CFM at 1 mg/ml showing 47.00% and 37.09% decline in aspartate transaminase and alanine transaminase and 77.32% and 101.02% increase in reduced glutathione and superoxide dismutase comparable to CCl₄ treated cells. Metabolic profiling of their aqueous infusions was done using nuclear magnetic resonance spectroscopic experiments coupled with chemometrics particularly hierarchical cluster analysis (HCA) and principal component analysis (PCA). The structural closeness of the various metabolites existing in black berry and the mixture as reflected in the PCA score plot and HCA processed from the ¹H‐NMR spectral data could eventually explained the close values in their biological behavior. For fig and artichoke, the existence of different phenolic metabolites that act synergistically could greatly interpret their potent biological behavior. Thus, it can be concluded that a herbal mixture composed of black berry, artichoke, and fig could afford an excellent natural candidate to combat oxidative stress and counteract hepatic toxins owing to its phenolic compounds.     

New Lignans from the Flower of Forsythia koreana and Their Suppression Effect on VCAM‐1 Expression in MOVAS Cells

Six lignans including two new lignans were obtained as the principal components of the Forsythia koreana flowers via silica gel (SiO₂), octadecyl SiO₂ (ODS) as well as Sephadex LH‐20 column chromatography. In addition to two new lignans, named koreanaside A ((7R,8S,7′R,8′S)‐7,7′‐diepoxy‐5′‐hydroxy‐3,3′‐dimethoxylignan 4‐O‐β‐d ‐glucopyranoside) and koreanaside B ((7R,8S,7′S,8′R)‐7,9′‐epoxy‐9,5′,7′‐trihydroxy‐3,3′‐dimethoxylignan 4‐O‐β‐d ‐glucopyranoside), four known lignans were identified to be (+)‐phylligenin, (?)‐epipinoresinol, pinoresinol, and tinosposide A. The structures and absolute configurations of koreanasides A and B were established by means of analysis of spectroscopic data (NMR, IR, FAB‐MS, and CD), whereas the structures of known lignans were identified by comparison their NMR and MS values with those in the reported literature. Their chemical structures including configuration were established by means of analysis of spectroscopic data (NMR, IR, FAB‐MS, and CD) but also comparison of their NMR and MS values with those in the reported literature. This is the first article for isolation of six lignans of F. koreana flowers. Koreanasides A and B showed high radical scavenging activity with oxygen radical absorbance capacity (ORAC) values of 0.97 ± 0.01 and 1.02 ± 0.01, respectively. Koreanaside A also prohibited expressing VCAM‐1 in MOVAS cells with 80.5% at 25 mg/mL.     

Exploratory Studies on the in Vitro Anti‐inflammatory Potential of Two Herbal Teas (Annona muricata L. and Jasminum grandiflorum L.), and Relation with Their Phenolic Composition

The need of new anti‐inflammatory drugs has led to the search for safer and more potent molecules in distinct sources, such as natural products. This work aimed to explore the anti‐inflammatory potential of aqueous extracts from two herbal teas (Annona muricata L. and Jasminum grandiflorum L.) in RAW 264.7 macrophages cells and in cell‐free assays. Furthermore, the phenolic composition of both extracts and of their hydrolysates was characterized by HPLC‐DAD, in order to establish possible relationships with the biological activity. In a general way, A. muricata displayed a stronger capacity to inhibit nitric oxide (NO) production and the activity of phospholipase A₂ (PLA₂), displaying an IC₅₀ value of 142 μg/ml against this enzyme. A deeper look at phenolic compounds revealed that aglycones had more capacity to inhibit NO and PLA₂ than their corresponding glycosides, quercetin being clearly the most potent one (IC₅₀ = 7.47 and 1.36 μm , respectively). In addition, 5‐O‐caffeoylquinic acid, at 1.56 μm , could also inhibit PLA₂ (ca. 35%). Our findings suggest that the consumption of both herbal teas may be a preventive approach to inflammatory disorders.     

Terpenes from Euphorbia antiquorum and Their in Vitro Anti‐HIV Activity

Three new compounds ( 1 – 3 ), including two euphane type triterpenes, 24,24‐dimethoxy‐25,26,27‐trinoreuphan‐3β‐ol ( 1 ) and (24S)‐24‐hydroperoxyeupha‐8,25‐dien‐3β‐ol ( 2 ), and an ent‐atisine diterpene, ent‐atisane‐3α,16α,17‐triol ( 3 ), were isolated from an acetone extract of the stems of Euphorbia antiquorum, together with eight known diterpenes ( 4 – 11 ). The structures of compounds ( 1 – 11 ) were elucidated using NMR and MS spectroscopic methods. Compound 7 showed moderate activity against HIV‐1 replication in vitro (EC₅₀ = 1.38 μm ).