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Previously undescribed eremane, viscidane, and isozizaene diterpenoids, eremorigidanes A-F, along with six known O-methylated flavonoids and three known triterpenoids were isolated and identified from the leaves of Eremophila rigida Chinnock by combined use of high-resolution PTP1B inhibition profiling, semipreparative- and analytical-scale HPLC separations, HPLC-PDA-HRMS analysis, and NMR spectroscopy. The absolute configuration of the unreported diterpenoids were determined by comparison of their experimental and calculated ECD spectra as well as by biosynthetic arguments. All isolates were evaluated for their PTP1B inhibitory activities, which revealed the flavonoid penduletin (3) to show inhibition with an IC 50 value of 18.3 μM, and the triterpenoids 3,4-seco-olean-12-ene-3,28-dioic acid (15), oleanolic acid (16), and 3-oxo-oleanolic acid (17) to show inhibition with IC 50 values of 55.7, 9.9, and 6.3 μM, respectively. The preliminary structure-activity relationship (SAR) of isolated flavonoids and triterpenoids is discussed. Plausible biosynthetic steps involved in eremane and isozizaene metabolism are presented and discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Serrulatanes constitute a class of unique diterpenoids derived from all- Z nerylneryl diphosphate rather than the conventional all- E diterpenoid precursor geranylgeranyl diphosphate and thus provide an intriguing expansion of the chemical space of plant specialized metabolites. Plants of the Australian Eremophila genus are rich sources of structurally diverse serrulatanes. Here, we report the identification of 15 hitherto undescribed serrulatanes (eremoculatanes A-N), together with 16 previously reported compounds, from the EtOAc extract of Eremophila denticulata leaves. Isolation was performed by a combined use of systematic HPLC-PDA-HRMS-based phytochemical profiling and orthogonal reversed-phase C 18 and pentafluorophenyl separations. Among the new compounds isolated, eremoculatane A contains a C 12 backbone, for which the configuration was established by comparison of experimentally measured and theoretically calculated ECD spectra. The antihyperglycemic and antibacterial activities of the E. denticulata extract were investigated by high-resolution inhibition profiling, and they indicated that major constituents, mainly serrulatanes and flavonoids, contributed to the observed activity of the extract. One flavonoid, eupafolin ( 4 ), displayed moderate α-glucosidase inhibitory activity with an IC 50 value of 41.3 μM, and four serrulatanes ( 8 , 9 , 19g , and 19j ) showed more than 50% PTP1B inhibition at 200 μM.

Extracts of Eremophila phyllopoda subsp. phyllopoda showed α-glucosidase and PTP1B inhibitory activity with IC 50 values of 19.6 and 13.6 μg/mL, respectively. High-resolution α-glucosidase/PTP1B/radical scavenging profiling was performed to establish a triple high-resolution inhibition profile that allowed direct pinpointing of the constituents responsible for one or more of the observed bioactivities. Subsequent targeted isolation and purification by analytical-scale HPLC led to the identification of 21 previously undescribed serrulatane diterpenoids, eremophyllanes A-U, as well as two known serrulatane diterpenoids, 1β-trihydroxyserrulatane ( 8 ) and 1α-trihydroxyserrulatane ( 10d ), and five known furofuran lignans, (+)-piperitol ( 6 ), horsfieldin ( 7e ), (-)-sesamin ( 9 ), (+)-sesamin ( 10h ), and asarinin ( 10i ). Their structures were elucidated by extensive analysis of HRMS and 1D and 2D NMR spectroscopic data. The relative configurations of the previously undescribed compounds were established by analysis of ROESY spectra as well as by DFT-GIAO NMR calculations followed by DP4+ probability analysis. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. Serrulatane diterpenoids 7b and 14 exhibited α-glucosidase inhibitory activity with IC 50 values of 28.4 and 64.2 μM, respectively, while 11 , 12 , 14 , and 15 exhibited PTP1B inhibitory activity with IC 50 values ranging from 16.6 to 104.6 μM. Hypothetical routes for formation of all identified serrulatane diterpenoids are proposed.

The plant genus Eremophila is endemic to Australia and widespread in arid regions. Root bark extract of Eremophila longifolia (R.Br.) F.Muell. (Scrophulariaceae) was investigated by LC-PDA-HRMS, and dereplication suggested the presence of a series of diterpenoids. Using a combination of preparative- and analytical-scale HPLC separation as well as extensive 1D and 2D NMR analysis, the structures of 12 hitherto unreported serrulatane diterpenoids, eremolongine A-L, were established. These structures included serrulatanes with unusual side chain modifications to form hitherto unseen skeletons with, e.g., cyclopentane, oxepane, and bicyclic hexahydro-1H-cyclopenta[c]furan moieties. Serrulatane diterpenoids in Eremophila have recently been shown to originate from a common biosynthetic precursor with conserved stereochemical configuration, and this was used for tentative assignment of the relative and absolute configuration of the isolated compounds. Triple high-resolution α-glucosidase/α-amylase/PTP1B inhibition profiling demonstrated that several of the eremolongines had weak inhibitory activity towards targets important for management of type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eremophila (Scrophulariaceae) is a genus of Australian desert plants, which have been used by Australian Aboriginal people for various medicinal purposes. Crude extracts of the leaf resin of Eremophila glabra (R.Br.) Ostenf. showed α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC 50 values of 19.3 ± 1.2 μg/mL and 11.8 ± 2.1 μg/mL, respectively. Dual α-glucosidase/PTP1B high-resolution inhibition profiling combined with HPLC-PDA-HRMS and NMR were used to isolate and identify the compounds providing these activities. This resulted in isolation of seven undescribed serrulatane diterpenoids, eremoglabrane A-G, together with nine previously identified serrulatane diterpenoids and flavonoids. Three of the serrulatane diterpenoids showed PTP1B inhibitory activities with IC 50 values from 63.8 ± 5.8 μM to 104.5 ± 25.9 μM., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Osteoarthritis (OA) is a complex disease, source of pain and disability that affects millions of people worldwide. OA etiology is complex, multifactorial and joint-specific, with genetic, biological and biomechanical components. Recently, several studies have suggested a potential adjuvant role for natural extracts on OA progression, in terms of moderating chondrocyte inflammation and following cartilage injury, thus resulting in an overall improvement of joint pain. In this study, we first analyzed the phenylethanoid glycosides profile and the total amount of polyphenols present in a leaf aqueous extract of Verbascum thapsus L. We then investigated the anti-inflammatory and anti-osteoarthritic bioactive potential of the extract in murine monocyte/macrophage-like cells (RAW 264.7) and in human chondrocyte cells (HC), by gene expression analysis of specifics inflammatory cytokines, pro-inflammatory enzymes and metalloproteases. Six phenylethanoid glycosides were identified and the total phenolic content was 124.0 ± 0.7 mg gallic acid equivalent (GAE)/g of extract. The biological investigation showed that the extract is able to significantly decrease most of the cellular inflammatory markers, compared to both control cells and cells treated with Harpagophytum procumbens (Burch.) DC. ex Meisn, used as a positive control. Verbascum thapsus leaf aqueous extract has the potential to moderate the inflammatory response, representing an innovative possible approach for the inflammatory joint disease treatment.

Phenylethanoid glycosides (PhGs) are compounds made of phenylethyl alcohol, caffeic acid and glycosyl moieties. The first published references about phenylethanoid glycosides concerned the isolation of echinacoside from Echinaceu ungustifolia (Asteraceae) in 1950 and verbascoside from Verbascum sinuatum (Scrophulariaceae) in 1963. Over the past 60 years, many compounds with these structural characteristics have been isolated from natural sources, and most of these compounds possess significant bioactivities, including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, and immunomodulatory activities, among others. In this review, we will summarize the phenylethanoid glycosides described in recent papers and list all the compounds that have been isolated over the past few decades. We will also attempt to present and assess recent studies about the separation, extraction, determination, and pharmacological activity of the excellent natural components, phenylethanoid glycosides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Pesticides are used to control and combat insects and pests in the agricultural sector, households, and public health programs. The frequent and disorderly use of these pesticides may lead to variety of undesired effects. Therefore, natural products have many advantages over to synthetic compounds to be used as insecticides. The goal of this study was to find natural products with insecticidal potential against Musca domestica and Mythimna separata. To achieve this goal, we developed predictive QSAR models using MuDRA, PLS, and RF approaches and performed virtual screening of 117 natural products. As a result of QSAR modeling, we formulated the recommendations regarding physico-chemical characteristics for promising compounds active against Musca domestica and Mythimna separata. Homology models were successfully built for both species and molecular docking of QSAR hits vs known insecticides allowed us to prioritize twenty-two compounds against Musca domestica and six against Mythimna separata. Our results suggest that pimarane diterpenes, abietanes diterpenes, dimeric diterpenes and scopadulane diterpenes obtained from aerial parts of species of the genus Calceolaria (Calceolariaceae: Scrophulariaceae) can be considered as potential insecticidal., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Eight furofuranone lignans with an endo , endo relationship between the oxygen atoms, an exo , exo relationship between the aryl groups, and a chair,chair conformation ( 1 - 4 and 6 - 9 ), in addition to the α-amino acid (3 S )-hydroxy-3',4'-dimethoxy-L-phenylalanine ( 5 ), veratric acid ( 10 ), and β-sitosterol ( 11 ), were isolated from the powdered and defatted air-dried aerial parts of Leucophyllum ambiguum . Four of these lignans, ciquitins A-D, 1 - 4 , were isolated for the first time as natural products. The structures of these compounds were established based on their spectrometric/spectroscopic data. Additionally, single-crystal X-ray crystallography confirmed the structure of ciquitin A ( 1 ), and derivatization with (9 S )-naproxen and X-ray diffraction crystallography data established its absolute configuration. Ciquitins A ( 1 ) and B ( 2 ) possess a 9-hydroxy group; this chemical characteristic grants these species conformational isomerism not seen in the other six lignans. The conformers of 1 and 2 are distinguishable via their 1 H and 13 C NMR spectroscopic data. This is the first report of this phenomenon, and hence, a complete assignment of the signals in both spectra of each conformer for each compound is presented. Compounds 1 - 9 were found to exhibit potent inhibitory activity in the 1.0 × 10 -3 to 2.2 μM range against acetylcholinesterase, an enzyme directly involved in the etiology of Alzheimer's disease and senile dementia. Thus, these natural products are promising agents that are potentially useful for the treatment of neurological degeneration.

Ten new branched-chain fatty acid (BCFA) dimers with a substituted cyclohexene structure, five new monomers, and two known monomers, (2 E ,4 Z ,6 E )-5-(acetoxymethyl)tetradeca-2,4,6-trienoic acid and its 5-hydroxymethyl analogue, were identified in the leaf extract of Eremophila oppositifolia subsp. angustifolia using a combination of HPLC-PDA-HRMS-SPE-NMR analysis and semipreparative-scale HPLC. The dimers could be classified as three types of Diels-Alder reaction products formed between monomers at two different sites of unsaturation of the dienophile. Two of the monomers represent potential biosynthetic intermediates of branched-chain fatty acids. Several compounds were found by high-resolution bioactivity profiling to inhibit PTP1B and were purified subsequently by semipreparative-scale HPLC. The dimers were generally more potent than the monomers with IC 50 values ranging from 2 to 66 μM, compared to 38-484 μM for the monomers. The ten fatty acid dimers represent both a novel class of compounds and a novel class of PTP1B inhibitors.

Ethnopharmacological Relevance: Lindernia crustacea (L.) F.Muell. (Scrophulariaceae) was selected for phytochemical investigation owing to its traditional use against human herpes virus infection and its anti-Epstein-Barr virus (EBV) effect., Aims of the Study: The present study focused on the phytochemical investigation of L. crustacea including the isolation and structure determination of its biologically active compounds. Compounds with anti-EBV effects were also investigated., Materials and Methods: The EtOH extract of L. crustacea was subsequently partitioned using different solvents. The EtOAc fraction was subjected to several chromatographic methods to obtain pure compounds. The structures of all isolates were established by spectroscopic analysis and compared with previously reported physical data. The anti-EBV effect was evaluated in an EBV-containing Burkitt's lymphoma cell line (P3HR1) to study the expression of EBV lytic proteins., Results: Thirty-three compounds, including one diterpene (1), four anthraquinones (2-5), two ionones (6 and 7), fourteen phenylpropanoid glycosides (8-21), five flavonoids (22-26), one lignan glycoside (27), one phenethyl alcohol glycoside (28), one phenylpropene glycoside (29), one glucosyl glycerol derivative (30), one furanone (31), and two cinnamic acid derivatives (32 and 33), were isolated from the ethanolic extract of the plant. All isolated compounds were obtained for the first time from Lindernia sp. The evaluation of the anti-EBV activity of L. crustacea crude extract, partitioned fractions, and constituents was performed for the first time. Phytol (1), aloe-emodin (2), byzantionoside B (7), a mixture of trans-martynoside (8) and cis-martynoside (9), a mixture of trans-isomartynoside (10) and cis-isomartynoside (11), luteolin-7-O-β-D-glucopyranoside (24), and apigenin-7-O-[β-D-apiofuranosyl (1→6)-β-D-glucopyranoside] (25) exhibited significant inhibitory effects on the EBV lytic cycle at 20 μg/mL in the immunoblot analysis. On the other hand, (6R,7E,9R)-3-oxo-α-ionol-β-D-glucopyranoside (6) and a mixture of trans-dolichandroside A (12) and cis-dolichandroside A (13) showed moderate anti-EBV activity at 20 μg/mL., Conclusions: L. crustacea and its active isolates could be developed as potential candidates against EBV. Our findings provide scientific evidence for the traditional use of L. crustacea for its antiviral effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Eremophila bignoniiflora is a shrub distributed throughout inland northern and eastern Australia, and it has been used in several medicinal applications by some Australian Aboriginal people. In our continued search for anti-diabetic constituents from natural resources, the crude ethyl acetate extract of E. bignoniiflora was found to have protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC 50 value of 23.9 ± 1.9 μg/mL. High-resolution PTP1B inhibition profiling combined with HRMS and NMR were subsequently used to investigate the individual compounds responsible for the observed bioactivity of the crude extract. This led to identification of five undescribed 2(5H)-furanone sesquiterpenes, together with 13 flavonoids and phenolic compounds. Dose-response curves of the isolated compounds revealed that two 2(5H)-furanone sesquiterpene cinnamates and three flavonoids exhibited moderate PTP1B inhibitory activity with IC 50 values from 41.4 ± 1.4 to 154.5 ± 8.9 μM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Phytochemical investigation on Hemiphragma heterophyllum led to the isolation of two new compounds, heterophyllumin A (1) and heterophylliol (3), along with nine known compounds, (‒)-sibiricumin A (2), iridolactone (4), jatamanin A (5), dihydrocatalpolgenin (6), 25-hydroperoxycycloart-23-en-3β-ol (7), 24-methylenecycloartanol (8), (+)-pinoresinol (9), hexadec-(4Z)-enoic acid (10), and 9,12, 15-octadecatrienoic acid (11). Their structures were elucidated on the basis of detailed spectroscopic analyses and by comparison with literature data. Further, the structure of compound 3 was unambiguously confirmed by single-crystal X-ray analysis. Some of those compounds showed moderate activity in the α-glucosidase inhibition assay.

: In this article the scientific activity carried out on stemarane diterpenes and diterpenoids, isolated over the world from various natural sources, was reviewed. The structure elucidation of stemarane diterpenes and diterpenoids was reported, in addition to their biogenesis and biosynthesis. Stemarane diterpenes and diterpenoids biotransformations and biological activity was also taken into account. Finally the work leading to the synthesis and enantiosynthesis of stemarane diterpenes and diterpenoids was described., Competing Interests: The authors declare no conflict of interest.

From two species of Sutera (S. foetida and S. cordata) (Scrophulariaceae tribe Limoselleae) were isolated three known secoiridoid glucosides (12-14) as well as four iridoid congeners (8-11), all biosynthetically derived from iridodial glucoside (and/or deoxyloganic acid). In addition, two previously unknown compounds were found, namely a terpenoid glucoside lactone (suterolide, 21) and the phenylethanoid glycoside 2''''-O-acetyl-angoroside A (19) as well as verbascoside, echinacoside and tubuloside A(15-17, respectively). Two other species, Jamesbrittenia dissecta and Lyperia antirrhinoides, previously considered to belong to the same genus (Sutera) were shown to be members of two different genera, respectively. Significantly, these two species contained iridoids derived from 8-epi-iridodial (and 8-epideoxyloganic acid), namely aucubin (2), melittoside (3) and acetylharpagide (4). In addition we investigated Melanospermum transvaalense, Lyperia tristis and Microdon dubius likewise from Limoselleae and all of these contained iridoid glucosides from the 8-epi-pathway. Thus, secoiridoid distribution confirms the DNA-based circumscription of Sutera and its sister-group relationship with Manulea. In addition, the results show that the clade including these two genera has a biosynthetic pathway to iridoids fundamentally different from the rest of the tribe and from the whole family Scrophulariaceae., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Five caffeoyl phenylethanoid glycosides, including two new ones linderruelliosides A (1) and B (2), were isolated from the leaves and stems of Lindernia ruellioides. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR and MS spectra. In addition, all these compounds were tested for their anti-HBV activity. Compounds 1, 3, and 4 showed anti-HBV activities, with IC 50 values of 54.87, 30.74, and 69.02 μM for HBsAg and 26.70, 5.17, and 7.08 μM for HBeAg, respectively.

The Eremophila plant family, which occurs in the arid zones of Australia, have witnessed extensive investigation, mostly inspired by Aboriginal traditional medicine. A wide and varied biological and phytochemical profile has been reported for over 18 individual species of Australian Eremophila, although E. macdonnellii from the Simpson Desert has not yet been investigated. Isolation and elucidation of one new and six known furofuran lignans are reported. The new lignan, epimethoxypiperitol, displayed moderate anti-cancer activity against the breast cancer cell line (MCF-7)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In an age of growing antimicrobial resistance, new antibacterial agents are desperately needed. A rapid antibacterial and phytochemical survey was designed to screen for antibacterial leads in plants. The survey was applied to over 90 Australian native plants from the genus Eremophila, revealing Eremophila complanata and E. nivea×E. drummondii as active against Gram positive bacteria. Thin layer chromatography with bioautography, flash chromatography and nuclear magnetic resonance led to the isolation and identification of two diastereomeric serrulatic acids. A single stereoisomer of 7,8,16-trihydroxyserrulat-19-oic acid has been previously described as its methyl ester. This paper describes the NMR of both serrulatic acids epimeric at C15 and their methyl esters, and demonstrates their Gram positive antibacterial activity. It is the first time that stereoisomers of this serrulatic acid have been found together in some Eremophila species. Further characterization of E. complanata additionally found an abundance of α-selinene and β-selinene. The study validates a rapid survey approach to finding antibacterial phytochemicals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recent reports of Eremophila glabra (R.Br.) Ostenf. (Scrophulariaceae) displaying antibacterial activity has led us to investigate the bioactive secondary metabolites responsible for this activity. Bioassay-directed fractionation of solvent extracts prepared from the leaves of E. glabra led to the isolation of seven serrulatane diterpenes, three flavonoids and the caffeoyl ester disaccharide verbascoside. Among these, four serrulatanes, namely 18-acetoxy-8, 20-dihydroxyserrulat-14-en-19-oic acid (14), 18,20-diacetoxy-8-hydroxyserrulat-14-en-19-oic acid (16), 8,18,20-triacetoxyserrulat-14-en-19-oic acid (17) and 18-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (18) are described for the first time, while 8,20-diacetoxyserrulat-14-en-19-oic acid (3), 8,18,20-trihydroxyserrulat-14-en-19-oic acid (5) and 20-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (19) were previously reported. All three flavonoids hispidulin (12), jaceosidin (13) and cirsimaritin (15) are known but reported for the first time in E. glabra. All compounds were tested in an agar diffusion antimicrobial assay against Staphylococcus aureus (NCTC 10442) and Staphylococcus epidermidis (ATCC 14990). Compounds 12, 13, 17, 18 and 19 exhibited moderate activity, with minimum inhibitory concentrations (MICs) ranging from 32 to 512μg/mL. Compound 19 demonstrated the highest activity against S. epidermidis ATCC 14990 with MIC of 32μg/mL, while 13 demonstrated the highest activity against S. aureus NCTC 10442 with MIC of 128μg/mL., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Eremophila sturtii and E. mitchellii are found in the arid and temperate regions of Australia and, because of their similar appearances, are often confused. Previous phytochemical investigations have described mitchellene sesquiterpenes (1-5) reported from E. mitchellii but are here demonstrated to be from E. sturtii. A previous study that described serrulatic acids (16 and 17) from a species reported as E. sturtii actually used E. mitchellii. In addition, two new C-15 modified analogues, mitchellenes F (14) and G (15), were isolated from E. sturtii. The absolute configuration of 14 was determined with the first X-ray structure of a compound with the mitchellene skeleton.

Ethnopharmacological Relevance: The leaves, bark, and flowers of Paulownia tomentosa Steud. have been widely used as a traditional medicine in East Asia to treat inflammatory and infectious diseases., Aim of the Study: We investigated the protective effect of the methanol stem bark extract of P. tomentosa using an animal model of lipopolysaccharide (LPS)-induced acute lung injury (ALI)., Materials and Methods: The UPLC Q-TOF-MS profiles for the methanol extract of P. tomentosa stem bark showed that verbascoside and isoverbascoside were the predominant compounds. Raw 264.7 cells were used for inhibitory effects of cytokine production in vitro. C57BL/6N mice were administered intranasally with LPS (10μg/per mouse) to induce ALI. H&E staining was used to evaluate histological changes in the lung., Results: Treatment with P. tomentosa stem bark extract (PTBE) suppressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages, and the recruitment of neutrophils and macrophages in the BALF of mice with LPS-induced ALI. PTBE also decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines in the BALF. PTBE reduced the levels of nitric oxide (NO) in the serum and of inducible nitric oxide synthase (iNOS) in the lung of ALI mice. PTBE also attenuated the infiltration of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung. In addition, PTBE suppressed the activation of NF-κB and the reduced expression of superoxide dismutase 3 (SOD3) in the lung., Conclusion: The results suggest that PTBE has a protective effect on LPS-induced ALI., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Four new (1 - 4) and one known (5) acylated iridoid glycosides were isolated from the aerial parts of Veronicastrum sibiricum (L.) Pennell. The chemical structures of the isolated compounds were determined to be 3″,4″-dicinnamoyl-6-O-rhamnopyranosyl-10-O-bergaptol-5,7-bisdeoxycynanchoside (1), 3″,4″-dicinnamoyl-6-O-rhamnopyranosylpaulownioside (2), 2″,4″-dicinnamoyl-6-O-rhamnopyranosylcatalpol (3), 3″,4″-dicinnamoyl-6-O-rhamnopyranosylaucubin (4), and 3″,4″-dicinnamoyl-6-O-rhamnopyranosylcatalpol (5) using spectroscopic techniques. Among these compounds, compound 5 increased antioxidant response element (ARE) luciferase activity., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Investigation of the single plant source bee glue type originating from Southern Australia resulted in the isolation and structure elucidation of major serrulatane diterpenes, novel 7,8,18-trihydroxyserrulat-14-ene ( 1 ), along with its oxidized product, 5,18-epoxyserrulat-14-en-7,8-dione ( 3 ) and known (18 RS )-5,18-epoxyserrulat-14-en-8,18-diol ( 2 ). Exploration into the botanical origin revealed Myoporum insulare R. Br, as the plant source of the bee glue materials. This discovery was made through comparative analysis of the myoporum bee glue samples collected from the beehives, analyses of plant resinous exudate, and resin carried on the hind legs of bees foraging for bee glue., Competing Interests: The authors declare no conflict of interest.

Objectives: This study was designed to evaluate the antihyperglycaemic activity of the methanol leaf extract of Eremophila maculata (EMM) both in vitro and in vivo., Methods: The antihyperglycaemic activity was assessed in vitro using differentiated 3T3-L1 adipocytes, whereas in-vivo effect was evaluated in streptozotocin-induced diabetic rats. Chemical profiling of EMM was done using LC-ESI-MS techniques. Molecular modelling experiments of the identified compounds were performed using C-Docker protocol., Key Findings: Eremophila maculata slightly enhanced cellular glucose uptake and utilization in vitro by 3.92% relative to the untreated control. A stronger in-vivo effect was observed for EMM and its dichloromethane fraction. A pronounced elevation in serum insulin by 88.89 and 66.67%, respectively, accompanied by an apparent decline in fasting blood glucose (FBG) level by 65.60 and 70.37% comparable to streptozotocin-induced diabetic rats was observed. This effect was stronger than that of the reference drug glibenclamide (GLB). Chemical profiling of EMM revealed that leucoseptoside A, verbascoside, syringaresinol-4-O-β-D-glucopyranoside, pinoresinol-4-O-β-D-glucopyranoside and pinoresinol-4-O-[6″-O-(E)-feruloyl]-β-D-glucopyranoside are the major compounds. Molecular modelling showed that martynoside, verbascoside and phillygenin exhibited the highest inhibition to human pancreatic α-amylase (HPA), maltase glucoamylase (MGAM) and aldose reductase (AR), respectively., Conclusion: Eremophila maculata offers an interesting relatively safer antihyperglycaemic candidate comparable to synthetic analogues., (© 2017 Royal Pharmaceutical Society.)

Background: Neurotrophic factors such as nerve growth factor (NGF) play important roles in nervous system. NGF is a potential therapeutic drug for treatment of neurodegenerative diseases. However, because of physicochemical property, NGF cannot pass through the blood-brain barrier (BBB). Hence, small molecules which exhibit NGF-mimic activity and can pass through the BBB are considered to be promising drug candidates for treatment of such diseases., Purpose: The present study was designed to isolate NGF-mimic substance from extract of natural products, determine their structures and investigate mechanism of action of the active substance., Methods: Extract of Lindernia crustacean was partitioned between water and ethyl acetate to obtain water layer and ethyl acetate layer samples, respectively, and then evaluated their neuritogenic activity in PC12 cells. The active sample was separated by open columns, followed by HPLC purification to obtain active compound. Then, specific inhibitors were used to investigate signaling pathway of neurite outgrowth induced by the active compound. Finally, western blot analysis was performed to confirm the pathway proposed by inhibitor experiments., Results: The ethyl acetate layer sample of extract of Lindernia crustacea exhibited significant neuritogenic activity. Two new compounds, named as linderside A and lindersin B, were isolated; their structures were elucidated by spectroscopic and chemical derivatization methods. Linderside A is a cucurbitane glycoside, whereas lindersin B is a cucurbitane triterpenoid. Each compound has an unusual isopentene unit, namely, a double bond bound to an unmodified isopropyl group at the end of cucurbitane triterpenoid side chain. Among them, lindersin B induced significant neurite outgrowth in PC12 cells, while linderside A was inactive against PC12 cells. Western blotting analysis results showed that lindersin B-induced neuritogenic activity depended on the activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). Moreover, tyrosine kinase A (TrKA) and phosphatidylinositol 3 kinase (PI3K) were also involved in the signaling pathway., Conclusions: Two new cucurbitane triterpenoids, linderside A and lindersin B, were isolated from Lindernia crustacean. Neurite outgrowth induced by lindersin B in PC12 cells depends on activation of TrkA/PI3K/ERK signaling pathway., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: The Australian plant Eremophila maculata F. Muell (Scrophulariaceae) is cultivated worldwide as an ornamental plant., Purpose: This study was designed to assess the antioxidant and hepatoprotective activities of a methanol extract from E. maculata leaves (EMM) both in vitro and in vivo (rats) experiments. Detailed phytochemical study was done on the extract followed by molecular docking experiments on TNF-α ascertain the efficacy of the isolated compounds., Methods: The antiproliferative activity was evaluated in the human cancer cell lines A-495, PC3 and HepG2 cells using the SRB method. The antioxidant activitywas evaluated in vitro using the DPPH• assay while the hepatoprotective properties were investigated by determining the amelioration of CCl 4 -induced cytotoxicity and oxidative stress in HepG2 cells. The activity was confirmed in vivo by studying tamoxifen-induced hepatotoxicity in rats. An in-depth phytochemical investigation of a methanol extract was performed using 1D and 2D NMR experiments. In silico molecular modeling studies of the isolated compounds on TNF-α (PDB ID 2AZ5) were carried out using Discovery Studio 2.5 software applying C-Docker protocol., Results: The IC 50 values of EMM were >500µg/ml for both PC3 and HepG2 cells indicating its safety. Similar to the standard drug silymarin, EMM could restore AST, ALT values; replenish GSH level, SOD activity and TAC in vitro. The hepatoprotective activity was confirmed in vivo in which the extract (20mg/kg body weight) decreased ALT and AST levels by 45.23 and 45.79%, respectively as compared to the tamoxifen treated groups. Oxidative stress was reduced by lowering of thiobarbituric acid reactive substances by 28.57%. Additionally, hepatocyte inflammation was improved by reducing the pro-inflammatory mediator TNF-α by 54.29%. Phytochemical investigation resulted in the isolation of a rare naturally-occurring lignan glycoside, namely pinoresinol-4-O-[6″-O-(E)-feruloyl]-β-D-glucopyranoside for the first time from the Scrophulariaceae in addition to 12 known compounds.Pinoresinol-4-O-[6''-O-(E)-feruloyl]-β-D-glucopyranoside was the strongest inhibitor of TNF-α as evidenced from its higher fitting scores comparable to lead compound., Conclusions: These findings highlighted for the first time that EMM could be an interesting candidate as a safe, natural liver supplement for relieving of various hepatic disorders and counteracting the effect of many xenobiotics., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The strongly aromatic Australian desert species Eremophila dalyana is an Aboriginal medicinal plant that continues to be used today in Central Australia in the treatment of respiratory complaints and Sarcoptes scabiei infestation. Using hydrodistillation of aerial parts of the plant, the new natural product myodesert-l- ene was isolated in two disjunct populations at up to 98% of the volatiles present in the hydrodistilled oils. Weak antimicrobial activities were observed for whole oils and myodesert-l-ene. Activities in the hydrodistilled oil were attributed to the antimicrobial sesquiterpenes elemol and eudesmol which showed good activity when isolated and were relatively abundant in the chemotype used medicinally. The biogenesis of myodesert-l-ene from iridodial is proposed.

Type 2 diabetes (T2D) constituted 90% of the global 387 million diabetes cases in 2014. The enzyme protein-tyrosine phosphatase 1B (PTP1B) has been recognized as a therapeutic target for treatment of T2D and its adverse complications. With the aim of accelerating the investigation of complex natural sources, such as crude plant extracts, for potential PTP1B inhibitors, we have developed a bio-analytical platform combining high-resolution PTP1B inhibition profiling and high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HR-bioassay/HPLC-HRMS-SPE-NMR. Human recombinant PTP1B enzyme was used for the microplate-based PTP1B inhibition assay, which was optimized for pH and substrate concentration to be compatible with rate measurements within the 10 min incubation time. Subsequently, analytical-scale HPLC-based microfractionation followed by colorimetric microplate-based PTP1B bioassaying enabled construction of a high-resolution inhibition profile corresponding to the HPLC profile. The high-resolution PTP1B inhibition profiling was validated using an artificial mixture of known PTP1B inhibitors and non-inhibiting compounds as negative controls. Finally, a proof-of-concept study with a real sample was performed using crude ethyl acetate extract of the phytochemically hitherto unexplored plant Eremophila lucida. This led to the identification of the first viscidane type diterpene, i.e., 5-hydroxyviscida-3,14-dien-20-oic acid (9) as PTP1B inhibitor with an IC50 value of 42.0 ± 5.9 μM. In addition, a series of flavonoids, i.e., luteolin (1), dinatin (3a), tricin (3b), 3,6-dimethoxyapigenin (4), jaceidin (5), and cirsimaritin (6) as well as a cembrene diterpene, (3Z, 7E, 11Z)-15-hydroxycembra-3,7,11-trien-19-oic acid (8), were also identified for the first time from E. lucida., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Australian native plants have a long history of therapeutic use in indigenous cultures, however, they have been poorly studied scientifically. We analysed the effects of 14 plant derived compounds from the species Pilidiostigma glabrum, Myoporum montanum, Geijera parviflora, and Rhodomyrtus psidioides for their potential wound healing properties by assessing their ability to induce or suppress Collagen I and Collagen III expression in human skin fibroblasts in culture. The compound 7-geranyloxycoumarin was able to significantly increase Collagen I (23.7%, p<0.0002) expression in comparison to control. Significant suppression of Collagen III was observed for the compounds flindersine (11.1%, p<0.02), and (N-acetoxymethyl) flindersine (27%, p<0.00005). The implications of these finding is that these compounds could potentially alter the expression of different collagens in the skin allowing for the potential development of new wound healing therapies and new approaches for treating various skin diseases as well as photo (sun) damaged, and aged skin., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity., (Copyright © 2015. Published by Elsevier Ltd.)

Biflorin is an o-naphthoquinone isolated from the roots of the plant Capraria biflora L. (Scrophulariaceae). In this study, the cytotoxic effects of biflorin were verified, and late apoptosis was detected in various cancer cell lines by in situ analysis. The cytotoxicity was further evaluated exclusively for 48 h of treatment in different tumor and non-tumor cell lines (Hep-2, HeLa, HT-29, A-375, and A-549, and HEK-293, respectively). The results indicated that biflorin induced selective cytotoxicity in tumor cells. HeLa cells were more susceptible to biflorin, followed by HT-29, A-549, A-375, and Hep-2 at all concentrations (range 5-50 μg/mL), and the highest half-maximal inhibitory concentration IC50 (56.01 ± 1.17 μg/mL) was observed in HEK-293 cells. Late apoptotic/necrotic events, observed by in situ immunostaining with Annexin V, varied with each cell line; an increase in late apoptotic events was observed corresponding to the increase in biflorin dosage. Hep-2 cells showed a greater percentage of late apoptotic events among the tumor cell lines when treated with higher concentrations of biflorin (69.63 ± 2.28%). The non-tumor HEK-293 line showed greater resistance to late apoptotic events, as well as a lower level of cytotoxicity (77.69 ± 6.68%) than the tested tumor lines. The data presented indicate that biflorin showed an important, possibly selective, cytotoxicity against tumor cell lines, thereby revealing a promising novel substance with potential anticancer activity for tumor therapy.

In this paper, the popular domestic varieties and quality standard of Scrophulariaceae plants used in Tibetan medicine were analyzed. The results showed that there were 11 genera and 99 species (including varieties), as well as 28 medicinal materials varieties of Scrophulariaceae plants were recorded in the relevant literatures. In relevant Tibetan standards arid literatures, there are great differences in varieties, sources, parts, and efficacies of medicinal plant. Among them, about 41.4% (including 41 species) of endemic plants, about 15.2% (including 15 species) of the original plants have medicinal standard legal records, except the medicinal materials of Scrophalaria ningpoensis, Lagotis brevituba, Picrorhiza scrophulariiflora, Veronica eriogyne general, most varieties have not completed quality standard. Consequently it is necessary to reinforce the herbal textual, resources and the use present situation investigation, the effects of the species resources material foundation and biological activity, quality standard, specification the medical terms of the plants, and promote Tibetan medicinal vareties-terminologies-sources such as the criterion and quality standard system for enriching the varieties of Tibetan medicinal materials and Chinese medicinal resources.

Three new geranylated flavanones, named as paucatalinone A (1), B (2), and isopaucatalinone B (3), were isolated from the fruits of Paulownia catalpifolia Gong Tong (Scrophulariaceae). Their structures were well determined by means of IR, MS, 1D and 2D NMR, and CD techniques. Paucatalinone A (1) is the first sample as a dimeric geranylated flavanone derivative isolated from natural products. Paucatalinone A (1) displayed good antiproliferative effects on human lung cancer cells A549 and resulted in a clear increase of the percentage of cells in G1 phase and a decrease in the percentage of cells in S and G2/M phases in comparison with control cells., (Copyright © 2015. Published by Elsevier Ltd.)

Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR) and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS). The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures' photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

From Manulea altissima (Scrophulariaceae) were isolated five known secoiridoid glucosides sweroside, eustomoside, eustoside, secoxyloganin and secologanoside as well as the 4″-O-rhamnopyranosyl-feruloyl ester of adoxosidic acid, named altissimoside. Also, the caffeoyl phenylethanoid glycoside verbascoside was isolated. In addition two previously unknown terpenoid esters of 6β-hydroxy 8-epi-boschnaloside, named manucoside A and B were isolated from a formerly obtained fraction from the work-up of Manulea corymbosa. The distribution of iridoid glucosides in the Scrophulariaceae is discussed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Previous studies have demonstrated that the widely distributed desert plant Eremophila longifolia has at least six geographically defined essential oil chemotypes. The focus of the present study is to extend and enhance information concerning known chemotypes and to investigate the involvement of cell nuclei ploidy in this variation. Forty field collected specimens of E. longifolia were taken from most of the mainland states of Australia then subjected to hydrodistillation to produce essential oils, which were then chemically characterised. Ploidy was determined using relative fluorescence of cell nuclei stained with propidium iodide, measured in a flow cytometer. Using principal component analysis (PCA), at least three essential oil chemotypes, in addition to the six already described, were identified in the present study. Previously described high yielding essential oil chemotypes were also characterised in terms of diploidy. For the first time diploid populations were identified in New South Wales, correlating with high yielding isomenthone/menthone and karahanaenone chemotypes. Furthermore, the separate diploid population previously described from Western Australia was demonstrated to be the safrole/methyl eugenol type, which is restricted to a small geographic range in far north-west Western Australia (Murchison District). All other chemotypes were shown to be tetraploid, including apparently randomly emerging individuals, representative of chemotypes producing low yields of isomenthone/menthone and karahanaenone similar in composition to the high yielding diploid types., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Globularia alypum L., belonging to the Globulariaceae family, is a perennial wild shrub found throughout the Mediterranean area, Europe, and Africa. This plant is widely used to treat many diseases, but no previous work on the phytochemical composition of the Algerian G. alypum species has yet been reported., Objective: To investigate the phytoconstituents of the methanolic extract of G. alypum using an LC-ESI-QTOF-MS method., Methods: Ground air-dried leaves of G. alypum were macerated with methanol at room temperature for 24 h. The supernatant was filtered and concentrated to dryness under reduced pressure in a rotary evaporator, and extracts were recovered with methanol and filtered. Afterwards, the G. alypum extract was injected into the LC-ESI-QTOF-MS system., Results: The combined LC-MS/MS led to the tentative characterisation of 63 phytochemicals. In this work, a large number of compounds have been characterised in the leaf-extract analysis of this plant. Among others, 24 iridoids and secoiridoids were found, of which nine compounds have not previously been recorded in G. alypum. Also, nine unusual phenylethanoid glycosides were characterised for the first time in this species., Conclusion: The method used has proved to be a valued tool for the characterisation of a wide range of compounds from G. alypum leaves. This work constitutes a detailed investigation of the chemical composition of G. alypum leaves, which are widely used in different traditional systems of medicine., (Copyright © 2014 John Wiley & Sons, Ltd.)

Ethnopharmacological Significance: Eremophila longifolia is considered by some Australian Aboriginal tribal groups to be among the most significant of the medicinal plants in contemporary and traditional use. Usage modalities traditionally involved lipophilic extraction into animal fats and most importantly, ceremonial or medicinal smoking applications, involving the fumigation of mothers and infants following childbirth or boys following circumcision. An attempt was made to replicate the smoking modalities used by Australian Aboriginal people in the laboratory to identify bioactive compounds., Materials and Methods: Two methods were used to produce smoke extracts; smoke was channelled through a condenser then bubbled into solvent, or bubbled directly into H2O then partitioned into chloroform followed by butanol. Extracts were used, firstly for antimicrobial screening using micro-titre plate broth dilution to produce minimum inhibitory concentrations (MIC), and secondly for chemical analysis. Structure elucidation of an abundant compound isolated from the smoke extract was performed using 2D-NMR and derivatisation., Results: Significant antimicrobial activity (<1.0 mg/ml) was produced using the smoke extracts against the Gram-positive species Staphylococcus aureus, Bacillus subtilis and the yeast Candida albicans. A major component of the smoke with strong antimicrobial activity (0.13-0.5 mg/ml) was isolated which we have named (-)-genifuranal. Structure elucidation using 2D-NMR and derivatisation demonstrated genifuranal to be 5,6-dihydro-4H-cyclopenta[c]furan-4-ylacetaldehyde. Genifuranal is not observed in the leaves before heating, but is produced in the smoking or heating process and is thought to derive from hydrolysis and rearrangement of geniposidic acid or a related glycoside. Only geographically specific specimens of Eremophila longifolia produced (-)-genifuranal, which strongly supports previous hypothesised geographical variation in traditional usage, reflective of phytochemical variation., Conclusion: It would appear that genifuranal is the medicinal principal involved in traditional use of Eremophila longifolia when smoking modalities are used. Topical treatments traditionally produced by lipophilic extraction into animal fats are not likely to have had genifuranal present, as the mechanism for its formation requires heat., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The effects of persistent organic pollutants (POPs) on humans and biodiversity are multiple and varied. Nowadays environmentally-friendly pesticides are strongly preferred to POPs. It is noteworthy that the crop protection role of pesticides and other techniques, i.e. biopesticides, plant extracts, prevention methods, organic methods, evaluation of plant resistance to certain pests under an integrated pest management (IPM), could improve the risks and benefits which must be assessed on a sound scientific basis. For this directive it is crucial to bring about a significant reduction in the use of chemical pesticides, not least through the promotion of sustainable alternative solutions such as organic farming and IPM. Biopesticides are derived from natural materials such as animals, plants, bacteria, and certain minerals. Most of them are biodegradable in relatively short periods of time. On this regard, substances from Calceolaria species emerge as a strong alternative to the use of POPs. The American genus Calceolaria species are regarded both as a notorious weeds and popular ornamental garden plants. Some have medicinal applications. Other taxa of Calceolaria are toxic to insects and resistant to microbial attack. These properties are probably associated with the presence of terpenes, iridoids, flavonoids, naphthoquinones and phenylpropanoids previously demonstrated to have interesting biological activities. In this article a comprehensive evaluation of the potential utilization of Calceolaria species as a source of biopesticides is made. The chemical profile of selected members of the Chilean Calceolaria integrifolia sensu lato complex represents a significant addition to previous studies. New secondary metabolites were isolated, identified and tested for their antifeedant, insect growth regulation and insecticidal activities against Spodoptera frugiperda and Drosophila melanogaster. These species serve as a model of insect pests using conventional procedures. Additionally, bactericidal and fungicidal activity were determined. Dunnione mixed with gallic acid was the most active fungistatic and fungicidal combination encountered. Several compounds as isorhamnetin, combined with ferulic and gallic acid quickly reduced cell viability, but cell viability was recovered quickly and did not differ from that of the control. The effect of these mixtures on cultures of Aspergillus niger, Fusarium moniliforme, Fusarium sporotrichum, Rhizoctonia solani, and Trichophyton mentagrophytes, was sublethal. However, when fungistatic isorhamnetin and dunnione were combined with sublethal amounts of both ferulic and gallic acid, respectively, strong fungicidal activity against theses strains was observed. Thus, dunnione combined with gallic acid completely restricted the recovery of cell viability. This apparent synergistic effect was probably due to the blockade of the recovery process from induced-stress. The same series of phenolics (iridoids, flavonoids, naphthoquinones and phenylpropanoids) were also tested against the Gram-negative bacteria Escherichia coli, Enterobacter agglomerans, and Salmonella typhi, and against the Gram-positive bacteria Bacillus subtilis, Sarcinia lutea, and Staphylococcus aureus and their effects compared with those that of kanamycin. Mixtures of isorhamnetin/dunnione/kaempferol/ferulic/gallic acid in various combinations were found to have the most potent bactericidal and fungicidal activity with MFC between 10 and 50 μg/ml. Quercetin was found to be the most potent fungistatic single compound with an MIC of 15 µg/ml. A time-kill curve study showed that quercetin was fungicidal against fungi assayed at any growth stage. This antifungal activity was slightly enhanced by combination with gallic acid. The primary antifungal action of the mixtures assayed likely comes from their ability to act as nonionic surfactants that disrupt the function of native membrane-associated proteins. Hence, the antifungal activity of isorhamnetin and other O-methyl flavonols appears to be mediated by biophysical processes. Maximum activity is obtained when the balance between hydrophilic and hydrophobic portions of the molecules of the mixtures becomes the most appropriate. Diterpenes, flavonoids, phenylpropanoids, iridoids and phenolic acids were identified by chromatographic procedures (HPLC-DAD), ESI-MS, and NMR hyphenated techniques., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Veronicastrum axillare (Sieb. et Zucc.) Yamazaki (Scrophulariaceae) embraces varieties of bioactivities such as anti-inflammatory, anti-pyresis and detoxification activity, while little is known of the phytochemical components of this medicinal plant., Objective: To isolate and identify bioactive constituents from the whole herb of V. axillare., Materials and Methods: Ethanol extract of the whole herb of V. axillare was subjected to successive column chromatography. Chemical structures of the compounds were elucidated by detailed spectroscopic analyses on the basis of NMR, IR and HR-MS data., Results: A new monoterpenoid, axillacetal A (1) and a known analogue, tarumal (2), were isolated from the whole herb of V. axillare. The structure of tarumal (2) was also revised according to our NMR data., Discussion and Conclusion: This is the first report on the isolation and authentication of novel chemical constituents from V. axillare.

The essential oils isolated from the fresh flowers, fresh leaves, and both fresh and air-dried stems of Eremophila maculata (Scrophulariaceae) were characterized by GC-FID and GC/MS analyses. Sabinene was the major component in most of the oils, followed by limonene, α-pinene, benzaldehyde, (Z)-β-ocimene, and spathulenol. The leaf and flower essential oils showed antibacterial and antifungal activity against five Gram-positive and four Gram-negative bacterial strains, multi-resistant clinical isolates from patients, i.e., methicillin-resistant Staphylococcus aureus (MRSA), as well as two yeasts. Minimum inhibitory concentrations (MICs) and minimum microbicidal concentrations (MMCs) were between 0.25 and 4 mg/ml., (Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.)

From an extract of Manulea corymbosa were isolated four known secoiridoid glucosides (1-4), 10 new monoterpenoid esters of secologanol, namely, manuleosides A-I (5-11, 13, and 14) and dimethyl rhodanthoside A (12), and four new phenylpropanoid esters of carbocyclic iridoid glucosides, manucorymbosides I-IV (15-18). Also, the caffeoyl phenylethanoid glycoside verbascoside was isolated. The presence of secoiridoids apparently derived from loganic acid in the family Scrophulariaceae is unprecedented and greatly unexpected.

This study was undertaken to isolate and quantify azafrin in Alectra parasitica (Scrophulariaceae) rhizomes. A simple method for the isolation of carotenoid, azafrin, involves solvent extraction of the dried rhizome powder using a single solvent and further purification by recrystallisation. The structure of the compound was elucidated and confirmed by thin-layer chromatography, infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectral analysis. A specific and rapid reversed-phase high-performance liquid chromatography (HPLC) method was developed for the analysis of azafrin. The method was validated for accuracy, precision, linearity and specificity. Validation revealed that the method is specific, accurate, precise, reliable and reproducible. The proposed HPLC method can be used for the identification and quantitative analysis of azafrin in A. parasitica rhizomes.

A new iridoid glucoside has been isolated from the Chilean native Alonsoa meridionalis (L.f.) Kuntze. Its structure has been assigned as 6'-O-β-d-glucopyranosyl-8-O-acetylharpagide (1) by using spectroscopic methods. Harpagoside (2), laterioside (3) and verbascoside (4) were also identified.

Extracts, fractions and compounds from Calceolaria talcana and C. integrifolia exhibited strong inhibitory effects of the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the in vitro Ellman's method. The most active samples were from the ethyl acetate extract, which caused a mixed-type inhibition against AChE (69.8% and 79.5% at 100 and 200 μg/ml, respectively) and against BChE (98.5% and 99.8% at 100 and 200 μg/ml, respectively) and its major components verbascoside 8 (50.9% and 70.0% at 200 μg/ml, against AChE and BChE, respectively), martynoside 9, and fraction F-7 (which corresponds to a mixture of 8, 9, and other phenylethanoids and phenolics that remain unidentified) (80.2% and 85.3% at 100 and 200 μg/ml, against AChE, respectively and 99.1% and 99.7% at 100 and 200 μg/ml, against BChE, respectively) inhibited the acetylcholinesterase enzyme competitively. The most polar fraction F-5 from n-hexane extract (a mixture of naphthoquinones: 2-hydroxy-3-(1,1-dimethylallyl-1,4-naphthoquinone) 6, α-dunnione 7 and other polar compounds that remain unidentified) showed a mixed-type inhibition (71.5% and 72.1% against AChE and BChE at 200 μg/ml, respectively). Finally, the methanol-soluble residue presented a complex, mixed-type inhibition (39.9% and 67.9% against AChE and BChE at 200 μg/ml, respectively). The mixture F-3 with diterpenes was obtained from the n-hexane extract: (1,10-cyclopropyl-9-epi-ent-isopimarol) 1, 19-α-hydroxy-abietatriene 2, and F-4 a mixture of triterpenes α-lupeol 3, β-sitosterol 4, ursolic acid 5 together with a complex mixture of terpenes that did not show activity. In summary, extracts and natural compounds from C. talcana and C. integrifolia were isolated, identified and characterized as cholinesterase inhibitors.

A new pentacyclic triterpenoid constituent, characterized as 3-oxo-olean-12(13),18(19)-dien-29α-carboxylic acid (1) on the basis of detailed spectral studies, was isolated from the aerial parts and roots of Limnophila indica (Scrophulariaceae). Compound 1 exhibited considerable antibacterial activity against three Gram-positive bacteria viz. Bacillus subtilis, Staphylococcus aureus and Listeria monocytogenes (MICs within a range of 25-30 μg/ml) and moderate activity against four Gram-negative bacteria Salmonella typhimurium, Escherichia coli, Pseudomonas aeruginosa, and Pantoea ananatis (MICs within a range of 30-100 μg/ml). The plant pathogenic bacterium P. ananatis and human pathogenic S. typhimurium responded at comparatively higher concentrations of the compound 1, which were 75 and 100 μg/ml respectively. The compound inhibited the growth of Gram-positive B. subtilis and Gram-negative P. aeruginosa completely with a clear bactericidal mode of action at their MIC values. The compound upon treatment on both B. subtilis and P. aeruginosa released substantial amount of nucleic acid in the external medium and also effected the change of morphology towards pleomorphicity, thereby indicating its probable action on cell membrane. Furthermore, the triterpenoid 1 was found not to inhibit a probiotic lactic acid bacterium Lactococcus lactis subsp. lactis LABW4 under in vitro condition and to possess no toxicity in Swiss albino mice., (© 2013.)

Objectives: Eremophila (Scrophulariaceae) is an endemic Australian genus with 214 species, which is commonly known as Fuchsia bush, Emu bush or Poverty bush. Plants of this genus played an important role for the Australian Aborigines who used them widely for medicinal and ceremonial purposes. Many studies have been carried out on many species of this genus and have generated immense data about the chemical composition and corresponding biological activity of extracts and isolated secondary metabolites., Key Findings: Thorough phytochemical investigations of different Eremophila species have resulted in the isolation of more than 200 secondary metabolites of different classes with diterpenes as major constituents. Biological studies and traditional clinical practice demonstrated that Eremophila and its bioactive compounds possess various pharmacological properties. Plants were employed especially as a cardiotonic drug and also as potent anti-inflammatory, antimicrobial and antiviral agents., Summary: Further investigations are required to explore other Eremophila species, to evaluate the different biological activities of either their extracts or the isolated compounds and the possible underlying modes of action., (© 2013 Royal Pharmaceutical Society.)

As a defense mechanism of the aerial parts of Calceolaria talcana (Calceolariaceae; formerly Scrophulariaceae) against herbivore offenses and insect pest attack, diterpenoids, triterpenoids, phenylethanoids, flavonoids, and iridoids are rapidly accumulated along the aerial parts, resulting in a unique natural biopesticide complex from this plant. In addition to verbascoside a series of known compounds were screened for their inhibitory activity against mushroom tyrosinase and protease enzymes. Ethyl acetate and n-hexane extracts, together with cyclopropyl-7,15-ent-pimaradiene (1), abietatriene (2), ursolic acid (3), α-lupeol (4), β-sitosterol (5), 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (6), α-dunnione (7), verbascoside (8), martynoside (9), and some known model compounds proved to be inhibitors of oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an IC50 between 10.0 and 200 ppm or μM, respectively, suggesting that phenolic moieties in the molecules assayed are important for the activity.

Two new discovered C-geranylated flavonoids tomentomimulol (1) and mimulone B (2) were isolated from the methanol extract of Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits by exhaustive chromatographic separation together with one known compound tanariflavanone D (3). The identification of compounds and structure elucidation was carried out using 1D and 2D NMR experiments, as well as mass spectroscopy, ultra-violet, infra red and CD experiments.