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Abstract Ethnopharmacological relevance Acanthus mollis is a plant native to the Mediterranean region, traditionally used as diuretic, anti-inflammatory and soothing of the mucous membranes of the digestive and urinary tract and externally as healing of wounds and burns, also demonstrating analgesic and anti-inflammatory activities. However, studies focused on its phytochemical composition as well as scientific proof of Acanthus mollis efficacy are scarce. Aim of the study The proposed work aims to perform a phytochemical characterization and evaluation of the therapeutic potential of Acanthus mollis , based on biological properties that support its traditional uses. Material and methods In this study, an 96% ethanol extract from Acanthus mollis leaves was obtained and its phytochemical composition evaluated using High Performance Liquid Chromatography with Photodiode Array Detector coupled to Electrospray Ionization Mass Spectrometry (HPLC-PDA-ESI/MSn). The chemical structure of the compound isolated was elucidated using 1H and 13C Nuclear Magnetic Resonance (NMR), 1H-correlation spectroscopy (1H–COSY), heteronuclear single quantum correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC). The quantification of the constituents was performed using two external standards (2,4-dihydroxy-1,4-benzoxazin-3-one and verbascoside). The antioxidant activity was determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) assay. Anti-inflammatory activity was determined measuring the inhibition of nitric oxide production by RAW 264.7 macrophages stimulated with the TLR4 agonist lipopolysaccharide (LPS) and through lipoxygenase (LOX) inhibition assay. The cytotoxicity was screened on two lines (RAW 264.7 and HaCaT) using the resazurin assay. Results Compounds such as verbascoside and its derivatives, as well as benzoxazinoids were found as the main constituents. A percentage of 5.58% was verified for the 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) derivatives. DIBOA was the main compound of the extract. Significant concentrations were also found for phenylpropanoids, which constitute about 4.39% of the total compounds identified. This extract showed antioxidant capacity against DPPH (IC 50 = 40.00 ± 1.59 μg/mL) and superoxide anion (IC 50 = 29.42 ± 1.99 μg/mL). It also evidenced anti-inflammatory potential in RAW 264.7 macrophages, presenting capacity for nitric oxide reduction (IC 50 = 28.01 μg/mL). Moreover, in vitro studies have shown that this extract was able to inhibit the lipoxygenase, with an IC 50 of 104.39 ± 4.95 µg/mL. Importantly, all effective concentrations were devoid of cytotoxicity in keratinocytes, thus highlighting the safety of the extract for the treatment of skin inflammatory related diseases. Concerning macrophages it was also possible to disclose concentrations showing anti-inflammatory activity and without cytotoxicity (up to 30 µg/mL). The benzoxazinoid DIBOA demonstrated a considerable anti-inflammatory activity suggesting its important contribution to this activity. Conclusions These results corroborate the anti-inflammatory properties traditionally attributed to this plant. Among the compounds identified in this study, benzoxazinoids exhibited a significant anti-inflammatory activity that was never previously described. Ethanol seems to be a good option for the extraction of these bioactive compounds, since relevant antioxidant/anti-radical and anti-inflammatory activities were found for this extract. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Two new compounds, odoratisol E (1) and decurrenal A (2), together with 12 known compounds were isolated from the twig and leaf extracts of Mitrephora wangii HU (Annonaceae). All structures were elucidated by spectroscopic methods. The structure of compound (+)- 6 was also confirmed by X-ray diffraction analysis. The absolute configurations of odoratisol E and decurrenal A were determined by comparison of their electronic circular dichroism (ECD) spectra with those of related known compounds. Most of the isolated compounds were evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Compounds 4 and (+)- 6 displayed potent ABTS radical scavenging activity with IC 50 values of 11.9 ± 1.8 and 10.8 ± 1.7 μM, respectively, which is better than that of standard compound, ascorbic acid, (IC 50 = 19.3 ± 0.1 μM). Compound 9 showed moderate DPPH radical scavenging activity with an IC 50 value of 38.7 ± 0.8 μM. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

A new bakuchiol compound Δ 11 -12-hydroxy-12-dimethyl bakuchiol ( 1 ), a new flavanone compound 2( S )-6-methoxy-7- hydroxymethylene-4′-hydroxyl-flavanone ( 8 ), and two new isoflavanone compounds 4′,7-dihydroxy-3′-(6”β-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone ( 9 ) and 4′,7-dihydroxy-3′-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone ( 10 ) together with eight known compounds ( 2–7 , 11 , 12 ) were isolated from the P. corylifolia . Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3 , 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC 50 values ranging from 93.7 ± 1.3 to 96.2 ± 1.1 μM. Compound 1 showed inhibition activity on DGAT1 with IC 50 values 73.4 ± 1.3 μM and inhibition of DGAT2 with IC 50 value 121.1 ± 1.3 μM. [ABSTRACT FROM AUTHOR]

Seven new N -acylanthranilic acid derivatives ( 1–3 , 4a/4b , 5a/5b ) including two pairs of enantiomers ( 4a/4b and 5a/5b ) were isolated from the leaves of Isatis indigotica Fortune. Their chemical structures were elucidated by extensive spectroscopic data analyses. The absolute configurations of compounds 4a/4b and 5a/5b were determined by comparison of the experimental and calculated ECD spectra. All compounds were tested for their anti-A β 1–42 aggregation activity. As a result, compounds 1 (72.1%), 2 (79.8%) and 5a (81.8%) showed stronger inhibitory activity than the positive control curcumin (67.0%). By the comparison between 5a (81.8%) and 5b (63.1%), it was found that stereochemical configurations may affect A β 1–42 aggregation activity, which was discussed through the molecular docking results of compounds 5a and 5b . [ABSTRACT FROM AUTHOR]

Due to the great economic, health, and medicinal importance, Phoenix dactylifera seeds were chosen for the synthesis of silver nanoparticles (AgNPs) because of their ecofriendly, nonhazardous, cost effectiveness advancement over physical and chemical methods, as green methods are safe, one step, and simple and did not require any chemical reducing and stabilizing agents. The green synthesized AgNPs were characterized by UV-Vis spectroscopy, SEM, HR-TEM, and DLS. Further, the bactericidal activity of synthesized AgNPs against Methicillin-resistant Staphylococcus aureus (MRSA) was investigated by determining MIC/MBC, agar diffusion methods, and electron microscopy. TEM images of the so-formed AgNPs revealed that the NPs were spherical in shape, with a size range of 14–30 nm. The MIC and MBC of AgNPs for MRSA were found to be 10.67±0.94 and 17.33±1.89 μg/ml, respectively. The antibacterial activities were found to be increased with the increasing concentration of AgNPs. The zone of inhibition was greater (24mm) at highest concentrations (500μg/ml) of AgNPs, while smaller (11mm) at lowest concentrations (7.8μg/ml). The SEM images of treated MRSA cells showed wrinkled and damaged cell wall, indicating the disruption and disorganization of membrane. HR-TEM analysis exhibits extensive injury and complete disintegration of cell wall and membrane. Large translucent zones have been seen in the cytoplasm, due to either localized or complete separation of the cell membrane from the cell wall. Overall, these results indicate that green synthesized AgNPs should be considered as an effective treatment and prevention option for the medical devises related infections caused by deadly MRSA and other drug resistant pathogens. [ABSTRACT FROM AUTHOR]

Three new C-methylated phenylpropanoid glycosides (1, 2), a new 8-4′-oxyneolignan (3), together with two known analogs (4, 5), were isolated from the rhizomes of Imperata cylindrical Beauv. var. major (Nees) C. E. Hubb. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 2, and 5 (10 μM) exhibited pronounced hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays. Furthermore, their antioxidant activities against Fe2+-cysteine-induced rat liver microsomal lipid peroxidation and the effects on the secretion of TNF-α in murine peritoneal macrophages (RAW264.7) induced by lipopolysaccharides were evaluated. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the fruits from Trichilia connaroides led to the isolation of four rare 1,2- seco phragmalin-type limonoids ( 1 – 4 ) with C-7/28 δ -lactone ring along with two known triterpenoids ( 5 – 6 ). An oxygen bridge between C-1 and C-2 formed an rare 9- oxa -tricyclo[3.3.2.1 7,10 ]undecane-2-ene moiety in structure of 1 and 2 , and 3 – 4 possessed a bicyclo[5.2.1 4,10 ]decane skeleton. Their structures were established based on extensive spectroscopic methods and their absolute configurations of 1 were confirmed by TDDFT/ECD calculation and comparative analysis. Compounds 5–6 showed moderate inhibitory effects on Hela tumor cell lines with inhibition ratio values of 83.8% and 87.1% at concentration 40 μM, respectively. [ABSTRACT FROM AUTHOR]

Chemical investigation of Euphorbia helioscopia resulted in the identification of seven new triterpenes named euphorbatrine A-G ( 1 – 7 ), including two (19 α H)-lupane ( 1 – 2 ) and three (9 β H)-lanostane ( 4 – 6 ), which are very rare metabolites from plants. Their structures were elucidated by extensive spectroscopic analysis, X-ray crystallography and chemical methods. Compounds 5 and 6 triggered apoptosis of Hela −/− cell with EC 50 values of 1.59 ± 0.25 and 26.48 ± 0.78 μM, respectively. [ABSTRACT FROM AUTHOR]

The three new metabolites: thiotagetin B ( 2 ) [( Z )-1″-([2,2′-bithiophen]-5-yl)-8″-chloro-6″,11″-dimethylundeca-6″,10″-dien-2″-yn-9″-one], tagetannin A ( 9 ) [3,4-bis-(galloyl-3,5-dimethyl ether)-( α / β )- d -glucopyranose], and tagetannin B ( 10 ) [2,3-bis-(galloyl-3,5-dimethyl ether)-( α / β )- d -glucopyranose], along with ecliptal (5-formyl- α -terthiophene) ( 1 ), 5-(4-hydroxybut-1-ynyl)-2,2′-bithiophene ( 3 ), scopoletin ( 4 ), p -hydroxybenzoic acid ( 5 ), protocatechuic acid methyl ester ( 6 ), gallic acid ( 7 ), and patuletin 7-O- β - d -glucoside ( 8 ) were isolated from the aerial parts of Tagetes minuta L. (Asteraceae). Their structures were verified by extensive spectroscopic analyses as well as by comparison with literature data. The isolated compounds were evaluated for their antioxidant and anti-inflammatory activities using DPPH and enzyme-linked immunosorbent assays, respectively. Compounds 5 – 10 possessed the highest antioxidant potential with a scavenging activity (SCA) ≈ 74 to 93% of DPPH radicals. Moreover, 5 – 10 displayed significant anti-inflammatory potential, while 4 showed moderate activity. Compounds 5 – 10 exhibited significant decreases in NFκB p65, TNF-α, and IL-6 levels at all tested concentrations. [ABSTRACT FROM AUTHOR]

Twenty natural stilbenoids ( 1 − 20 ), including seven new stilbenoids ( 2 , 4 – 7 , 19 , 20 ) and thirteen known stilbenoids ( 1 , 3, 8 – 18 ), were isolated from the stem barks of Acanthopanax leucorrhizus , and six modified stilbenoid derivatives ( 1a , 2a , 4a , 4b , 7a and 17a ) were obtained via methylation, demethylation and isopentenylation of the corresponding isolates ( 1 , 2 , 4 , 7 and 17 ). These stilbenoids 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 (leukemia HL-60, hepatoma SMMC-7721 and breast carcinoma MCF-7) in vitro by MTT assay. The results showed that compounds 1a , 4a and 4b showed potent selective cytotoxicity against SMMC-7721 ( IC 50 = 10.16 ± 1.95 μM and 9.76 ± 1.32 μM) and MCF-7 ( IC 50 = 10.72 ± 2.78 μM) cell lines. The cytotoxic evaluation of these structurally modified stilbenoid derivatives have led to the establishment of a structure-activity relationship. [ABSTRACT FROM AUTHOR]

Four new naphthoquinones ( 1 – 4 ), named rhinacanthins S ( 1 ), T ( 2 ), U ( 3 ) and V ( 4 ), together with 13 known naphthoquinones were isolated from the leaf extract of Rhinacanthus nasutus . The structures of isolated compounds were elucidated by spectroscopic methods, especially 1D and 2D NMR spectroscopy and mass spectrometry. Rhinacanthin S ( 1 ) exhibited acetylcholinesterase inhibition activity with a % inhibition value of 48.04 ± 3.25. The known rhinacanthin A ( 5 ) showed cytotoxicity against a MCF-7 cell line with an IC 50 value of 8.79 μM, while rhinacanthin N ( 15 ) was active against the NCI-H187 cell line with an IC 50 = 2.24 μM and Vero cells (IC 50 = 3.00 μM) [ABSTRACT FROM AUTHOR]

Four new labdane diterpenoids, 12 β -hydroxy-15-norlabda-8(17),13(14)-dien-16-oic acid ( 1 ), ( E )-15-ethoxy-15-methoxylabda-8(17),12-dien-16-al ( 2 ), ( E )-15 α -ethoxy-14 α -hydroxylabda-8(17),12-dien-16-olide ( 3 ), and 15-ethoxy-12 β -hydroxylabda-8(17),13(14)-dien-16,15-olide ( 4 ) were isolated from the methanol extract of Curcuma amada rhizomes collected in Myanmar, together with 13 known analogs. Their structures were elucidated by extensive spectroscopic techniques. All of the isolates were evaluated for their antiproliferative activities against a small panel of five different human cancer cell lines (A549, human lung cancer; HeLa, human cervical cancer; MCF7, human breast cancer; PANC-1 and PSN-1, human pancreatic cancer). Among the isolates, compounds 2 − 4 , 7 , 8 , 12 , and 17 showed mild antiproliferative activities with IC 50 values ranging from 19.7 to 96.1 μM. ( E )-14-Hydroxy-15-norlabda-8(17),12-dien-16-al ( 11 ) exhibited strong antiproliferative activities selectively against HeLa, PANC-1, and PSN-1 cells, with IC 50 values of 5.88, 1.00, and 3.98 μM, respectively. These potencies were comparable to those of the positive control, 5-fluorouracil. [ABSTRACT FROM AUTHOR]

Five new isocoumarin derivatives, pestalactone A–C ( 1–3 ) and pestapyrone D–E ( 4–5 ), together with two known compounds ( 6–7 ) were isolated from the solid cultures of the endophytic fungus Pestalotiopsis sp. obtained from Photinia frasery . Their structures were mainly determined by extensive spectroscopic analysis, Mo 2 (OCOCH 3 ) 4 -induced electronic circular dichroism (ECD), and ECD calculation. Compounds 1 and 2 were rare isocoumarin derivatives and derived from distinctive polyketide pathways. Compound 3 exhibited potent antifungal activity against Candida glabrata (ATCC 90030) with an MIC 50 value of 3.49 ± 0.21 μg/mL. [ABSTRACT FROM AUTHOR]

Three new 2-phenylnaphthalene derivatives, cherrevenaphthalenes A–C ( 1–3 ), and a new polyoxygenated cyclohexene derivative, (−)-uvaribonol F ( 4 ) together with six known compounds, 5–10 , were isolated from the stem and root extracts of Uvaria cherrevensis (Annonaceae). The structures of all isolated compounds were elucidated by spectroscopic analysis. The structures of 3 and 4 were further confirmed by single crystal X-ray diffraction methods. Compound 2 exhibited modest antiplasmodial activity against the P. falciparum stains TM4/8.2 and K1CB1 with IC 50 values of 18.8 ± 3.63 and 23.4 ± 4.08 μM, respectively, and weak cytotoxicity to a Vero cell line. Furthermore, compound 4 displayed cytotoxic activity against a KB cell line with an IC 50 value of 22.1 ± 0.42 μM but was non-cytotoxic to the Vero cell line. Compound 5 revealed stronger cytotoxicity towards the KB cell line, with an IC 50 value of 5.05 ± 0.86 μM and was nearly equally cytotoxic to the Vero cell line. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Corn silk or the stigma of Zea mays L. has traditionally been used in weight loss stimulation and treatment of cystitis, urinary infections and obesity. Purple corn silk, rich of polyphenolic substances, was reported on anti-diabetic and anti-obesity effect in animal studies. However, scientific evidence on mechanisms and targets of action of purple corn silk related to adipocyte life cycle has been limited. Aim of study To determine phytochemical compositions and investigate anti-obesity potential of the purple corn silk focusing on interruption of adipocyte life cycle; effect on pre-adipocyte proliferation, adipogenesis, adipocyte lipolysis, and apoptosis. Materials and methods The ethanolic purple corn silk extract (PCS) was prepared and investigated for phytochemical compositions by LC/MS/MS technique and anti-obesity potential using murine 3T3-L1 cell line. Using methyl thiazole tetrazolium (MTT) assay, the effects on pre-adipocytes and adipocyte viability and on pre-adipocytes proliferation at 24-, 48-, and 72-h incubation period were evaluated. In addition, anti-adipogenesis via inhibition on adipocyte differentiation and reduction of total lipid accumulation was evaluated using Oil Red O staining and spectrophotometric methods, respectively. The lipolysis effect was determined by measurement of glycerol released content using glycerol test kit after 48-h treatment of PCS to adipocytes. Apoptosis inductive effect was done by using 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining method. Results The polyphenols including anthocyanins, quercetin and phenolic acids and derivatives were found as the major chemical compositions of the PCS. With multiple-stages interruption on the adipocyte life cycle, anti-obesity effect of PCS was interestingly demonstrated. When compared to the control, the PCS at concentration range between 250–1000 μg/mL showed anti-adipogenesis effect as expressing of significant inhibition on pre-adipocyte proliferation at all incubation period (43.52±5.28 – 75.51±9.09%) and significant decreasing of total lipid accumulation at concentration of 500 μg/mL (80.22±6.58%) and 1000 μg/mL (69.62±5.42%). Moreover, the PCS exhibited lipolysis and apoptosis inductive effect with dose dependent manner and significance at concentration of 1000 μg/mL by increase of released glycerol content (173.88±6.13% of the control) and of nuclei condensing and apoptotic bodies (with relative apoptosis induction as 131.74±1.64% of the control). Conclusion Our data has evidenced the anti-obesity potential of PCS related interruption at multiple stages of adipocyte life cycle. Its potency was attributed to inhibition on adipocyte proliferation and adipogenesis as well as induction on lipolysis and apoptosis at high concentration. However, further in vivo investigation should be considered to insist the possibility in applications of PCS in prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The roots, stem and leaves of Morinda lucida are used in some African countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth. Aim of the study To determine the in vitro cell toxicity and anti-malarial activity of the extracts of stem bark of M. lucida and to identify the secondary metabolites in the extract that may be responsible for this activity. Materials and methods The cell toxicity studies of crude extract [dichloromethane (DCM): Methanol (MeOH) in a ratio of1:1 (v/v)] as well as compounds isolated from the same extract were carried out using human cervix adenocarcinoma cells (HeLa cells); while the anti-malarial activities of the same samples were performed against Plasmodium falciparum strain 3D7 using the parasite lactate dehydrogenase (pLDH) assay. The isolation of the active compounds was carried out using chromatographic techniques (column and thin layer chromatography) where as mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR) as well as 1D- and 2D- nuclear magnetic resonance (NMR) analyses were employed in the characterisation and identification of the isolated secondary metabolites. Results The pLDH and cell toxicity assays for the crude extract and the fractions of M. lucida indicated that some fractions reduced the malaria parasite viability by approximately 50% at 100 μg/mL and they were not significantly cytotoxic. An IC 50 done on the crude extract gave a value of 25 μg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Seven chemical constituents i.e. asperuloside ( 1 ), asperulosidic acid ( 2 ), stigmasterol ( 3a ), β-sitosterol ( 3b ), cycloartenol ( 3c ), campesterol ( 3d ) and 5,15-O-dimethylmorindol ( 4 ) were isolated from the DCM-MeOH extract of stem bark. The isolated compounds tested were not that active by themselves individually at 20 μM but their activities were increased when the isolated compounds were combined. As seen when compounds 2, 3 and 4 (% viability: 93, 123 and 101 respectively) were combined yielding an IC 50 value of 17 μM. Furthermore, this is the first report of compounds 1, 2, 3c, 3d and 4 isolated from M. lucida . Conclusion The crude extract completely suppressed the growth of P. falciparum . This indicates that the crude extract contains many compounds that might be acting in synergy. The observed activity of the crude extract and the samples containing a mixture of different compounds support the traditional use of M. lucida for the treatment of malaria. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Tetracera potatoria Afzel. Exg. Don (Dilleniaceae) is a medicinal plant used traditionally in Africa for the treatment of tuberculosis related ailments and respiratory infections. The antibacterial activity of the medium polar extracts of T. potatoria leaves and stem bark was recently reported against Mycobacterium smegmatis (MIC 25 µg/mL) and M. aurum (65 µg/mL), two fast-growing Mycobacterium strains used as model micro-organisms for the more pathogenic strain Mycobacterium tuberculosis ( Fomogne-Fodjo et al., 2014 ). The aim of this study was consequently to isolate the compounds possibly contributing to this activity, and which may therefore be promising precursors to be used for the development of novel anti-TB drugs. Materials and methods T. potatoria medium polar extract [MeOH/DCM (1:1, v/v)] was fractionated sequentially with petroleum ether to which EtOAC and MeOH were gradually added to increase the polarity. The examination of T. potatoria extract and its fractions was guided by bioassays for anti-mycobacterial activity against M. smegmatis (ATCC 23246) and M. aurum (NCTC 10437) using the minimum inhibitory concentration (MIC) method. All the isolated compounds were structurally elucidated using spectroscopic techniques and evaluated for their anti-mycobacterial activity. Results Two novel secondary metabolites ( 1 , 2 ) named tetraceranoate and N -hydroxy imidate-tetracerane, together with five known compounds [ β -stigmasterol ( 3 ), stigmast-5-en-3 β -yl acetate ( 4 ), betulinic acid ( 5 ), betulin ( 6 ) and lupeol ( 7 )] were isolated and identified. Tetraceranoate exhibited the best activity against M. smegmatis with a minimum inhibitory concentration (MIC) of 7.8 µg/mL, while β -stigmasterol, betulinic acid and betulin showed appreciable anti-mycobacterial activity against both strains (MIC 15 µg/mL). Conclusion Seven compounds were isolated from the medium polar extract [MeOH/DCM (1:1, v/v)] of T. potatoria stem bark. Only tetraceranoate one of the isolated compounds showed antibacterial activity against M. smegmatis having efficacy as high as rifampicin (one of a three drug regimen recommended in the initial phase short-course anti-tuberculosis therapy). Thus, tetraceranoate might be an interesting target for systematic testing of anti-TB treatment and management. This research supports the use of T. potatoria in African traditional medicine for the treatment of tuberculosis related symptoms. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Houttuynia cordata is an important traditional Chinese medicine used in heat-clearing and detoxifying, swelling and discharging pus, promoting diuresis and relieving stranguria which recorded in Pharmacopoeia of the people's Republic of China (2015 Edition). H. cordata has been recorded in the book Bencaogangmu which was written by Shizhen Li for the treatment of pyretic toxicity, carbuncle swelling, haemorrhoids, and rectocele diseases. Aim of the study Phytochemical investigation of the aerial parts of H. cordata and evaluation of their PTP1B inhibitory activities and hepatoprotective activities. Materials and methods The dried aerial parts of H. cordata were fractionated by liquid-liquid extraction to obtain CHCl 3 , ethyl acetate, and n-butanolic fractions. The CHCl 3 fraction was confirmed active fraction by the bioactivity-guided investigation, which was isolated and purified by chromatographing over silica gel, Sephadex LH-20, MPLC, and preparative HPLC. The chemical structures of the purified compounds were identified by their spectroscopic data and references. Results Eight new compounds ( 1 – 8 ), together with fourteen known compounds ( 9–22 ) were isolated from the aerial parts of H. cordata. The known compounds ( 9–22 ) were obtained from this plant for the first time. Among them, some compounds exhibited moderate bioactivities. Conclusion Compounds ( 1–8 ) were identified as new alkaloids, and the known alkaloids ( 9–22 ) were isolated from this plant for the first time. Compounds 1 , 4 , 14 , and 19 showed significant PTP1B inhibitory activities with IC 50 values of 1.254, 2.016, 2.672, and 1.862 µm, respectively. Compounds 1 , 3 , 6 , 11 , 17 , and 20 (10 µm) exhibited moderate hepatoprotective activities against D-galactosamine-induced WB-F344 cells damage. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Folium Ginkgo, the dried leaf of Ginkgo biloba L. is a traditional Chinese medicine listed in the Pharmacopoeia of the People's Republic of China with several therapeutic effects, including prevention of aging. It is used as herbal medicine for the treatment of several aging-related diseases. The therapeutic effects of Folium Ginkgo on aging-related diseases are suspected to be similar to the anti-aging effects of growth hormone release induced by ghrelin. Materials and methods Candidate components responsible for the anti-aging effects via the ghrelin receptor-activated pathway were searched from the known compounds found in Folium Ginkgo. Two acylated flavonoid diglycosides, tentatively named ginkgoghrelins in this study, were selected and isolated from the methanol extract of Folium Ginkgo, and their chemical structures were confirmed by spectroscopic analysis. These two compounds were examined for their capability of stimulating growth hormone release of rat primary anterior pituitary cells via activation of the ghrelin receptor. The major metabolites of ginkgoghrelins in rat bile were detected after intravenous injection and structurally analyzed by mass spectroscopy. Molecular modeling of ginkgoghrelins docking to the ghrelin receptor was exhibited to explore the possible interaction within the binding pocket. Results Similar to growth hormone-releasing hormone-6 (GHRP-6), a synthetic analog of ghrelin, ginkgoghrelins were demonstrated to stimulate growth hormone secretion of rat primary anterior pituitary cells in a dose dependent manner, and the stimulation was inhibited by [ d -Arg 1 , d -Phe 5 , d -Trp 7,9 , Leu 11 ]-substance P, an inverse agonist of the ghrelin receptor. Putative metabolites of ginkgoghrelins via glucuronidation and methylation were detected in bile of rats after intravenous injection. Molecular modeling and docking showed that ginkgoghrelins as well as GHRP-6 could fit in and adequately interact with the binding pocket of the ghrelin receptor. Conclusion The results suggest that ginkgoghrelins are putative components partly accounting for the anti-aging effects of Folium Ginkgo possibly via activation of the ghrelin receptor, and possess great potential to be developed as non-peptidyl analogs of ghrelin. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Salvia plebeia R. Br. is an edible plant widely spread in many countries. It has been used as a traditional medicine to treat common cold, flu, cough, hepatitis, hemorrhoids, etc. The purpose of the study is to explicate antiviral compounds responsible for its traditional use for the common cold or flu. Materials and methods The methanolic extract of the aerial parts of S. plebeia was extracted with CHCl 3 , EtOAc, and n -BuOH, successively. The EtOAc and CHCl 3 fractions were subjected to a successive of chromatographic method, which led to the isolation of fourteen compounds. Inhibition activities of the isolated compounds were evaluated against influenza A (H1N1) neuraminidase. Results Chemical investigation of the methanolic extracts of S. plebeia resulted in the isolation of two novel benzoylated monoterpene glycosides, named as plebeiosides A ( 1 ) and B ( 2 ), together with twelve known compounds including four flavonoids ( 4 – 5 , 7 , 10 ), two sesquiterpenoids ( 8 , 12 ), four phenolics ( 9 – 10 , 13 – 14 ), a steroid ( 6 ), and a triterpenoid ( 3 ). Their chemical structures were elucidated based on spectroscopic data and absolute stereochemistries of 1 and 2 were determined by comparison of optical rotations of their hydrolysates with literature values. Compounds 5 , 7 , 9 , and 11 exhibited potent enzymatic inhibition against H1N1 neuraminidase (IC 50 values ranging from 11.18±1.73 to 19.83±2.28 μM). Furthermore, two flavonoids ( 5 and 7 ) and one rosmarinic acid methyl ester ( 9 ) reduced cytopathic effects of the H1N1 virus during replication. Conclusions The antiviral activities of the flavonoids and phenolics isolated from the extracts of S. plebeia supported the traditional application of this medicine on common cold or flu. In this study, benzoylated monoterpene glycosides were first found to exist in this species. Moreover, the present study suggested potential of three compounds ( 5 , 7 , and 9 ) to be new lead structures for the development of new neuraminidase inhibitors in the future. [ABSTRACT FROM AUTHOR]

Orthosiphon stamineus Benth. (Lamiaceae) is an important plant in traditional folk medicine that is used to treat hypertension and kidney stones. In humans, this plant has been tested as an addition regiment for antihypertensive treatment. Among the treatments for hypertension, O. stamineus had been to have diuretic and vasorelaxant effects in animal models. There is still very little information regarding the vasorelaxant effect of O. stamineus. Therefore, the present study was designed to investigate the vasorelaxant activity and mechanism of action of the fractions of O. stamineus. The vasorelaxant activity and the underlying mechanisms of the chloroform fraction of the 50% methanolic extract of O. stamineus (CF) was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. CF caused relaxation of the aortic ring pre-contracted with phenylephrine in the presence and absence of endothelium, and pre-contracted with potassium chloride in endothelium-intact aortic ring. In the presence of endothelium, both indomethacin (a nonselective cyclooxygenase inhibitor) and -[1,2,4]Oxadiazolo[4,3-]quinoxalin-1-one (ODQ, selective soluble guanylate cyclase inhibitor) had a small effect on the vasorelaxation response. On the other hand, in the presence of Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), tetraethylammonium (, nonselective calcium activator channel blocker), 4-aminopyridine (4-AP, voltage-dependent channel blocker), barium chloride (, inwardly rectifying channel blocker), glibenclamide (nonspecific ATP-sensitive channel blocker), atropine (muscarinic receptor blocker) and propranolol (β-adrenergic receptor blocker), the vasorelaxant effect significantly reduced the relaxation stimulated by CF. CF was also found to be active in reducing release from the sarcoplasmic reticulum and blocking calcium channels. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Echinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. Aim of the study To examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. Material and methods The structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50 mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro . The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex® assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF). Results Chemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent budesonide and was verified as significantly reduced exhaled NO levels and concentration of Th2 cytokines in serum and BALF. The values of CBF were changed only insignificantly on long-term administration of Echinacea complex suggested its minimal negative impact on mucociliary clearance. Conclusion Pharmacodynamic studies have confirmed significant bronchodilatory and anti-inflammatory effects of Echinacea complex that was similar to effects of classic synthetic drugs. Thus, results provide a scientific basis for the application of this herb in traditional medicine as a supplementary treatment of allergic disorders of the airways, such as asthma. [ABSTRACT FROM AUTHOR]

Five new compounds ( 1 – 5 ), including three limonoids, one diterpenoid, and one phytosterol, along with four known limonoids ( 6 – 9 ), were isolated from the ethanolic extracts of whole plants of Munronia henryi . Their structures were elucidated by extensive spectroscopic analysis. In addition, the anti-tobacco mosaic virus (TMV) activities of all the isolated compounds were evaluated by the conventional half-leaf and leaf-disk methods along with Western blot analysis. Most of the tested compounds showed strong antiviral activities, with IC 50 values in the range of 14.8–34.0 μg/mL, compared with ningnanmycin as a positive control (IC 50 = 44.6 μg/mL), and their preliminary structure-activity relationships were also discussed. [ABSTRACT FROM AUTHOR]

Five new hexacyclic monoterpenoid indole alkaloids, rauvovertine A ( 1 ), 17- epi -rauvovertine A ( 2 ), rauvovertine B ( 3 ), 17- epi -rauvovertine B ( 4 ), and rauvovertine C ( 5 ) together with 17 known analogues were isolated from the stems of Rauvolfia verticillata . Compounds 1 / 2 and 3 / 4 were obtained as C-17 epimeric mixtures due to rapid hemiacetal tautomerism in solution. The structures of 1 – 5 were established by spectroscopic analysis and with the aid of molecular modeling. The new alkaloids were evaluated for their cytotoxicity in vitro against human tumor HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines. [ABSTRACT FROM AUTHOR]

A chemical investigation of callus cultures of Dysosma versipellis led to the isolation of five new flavonol dimers, dysoverines A − E ( 1 − 5 ), together with 12 known compounds ( 6 − 17 ). The structures of new compounds were determined by the extensive spectroscopic data analyses. The biosynthetic pathway of the new compounds was proposed to involve O -methylation, prenylation, and Diels–Alder cycloaddition, which successively occurred in cultured plant cells. Compounds 1 − 17 exhibited in vitro neuraminidase inhibitory activities with the IC 50 values of 31.0 − 93.9 μM. [ABSTRACT FROM AUTHOR]

One new 9,10- seco -abietane derivative, crotontomentosin A ( 1 ), four new abietane-type diterpenoids, crotontomentosins B–E ( 2 – 5 ), one new ent -halimane-type diterpenoid, crotontomentosin F ( 6 ), along with five known diterpenoids ( 7 – 11 ) and one known sesquiterpenoid ( 12 ) were obtained from the twigs and leaves of Croton caudatus Geisel. var. tomentosus Hook. The structures of the compounds were established on the basis of extensive spectroscopic data. Compounds 1 – 4 and 11 exhibited moderate to weak inhibitory activity against the proliferation of the Hela, Hep G2, MDA-MB-231, or A549 cell lines selectively. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Nelumbo nucifera Geartn., known as sacred lotus, has been used traditionally in South East Asia as a traditional medicine for various CNS disorders including stress, fever, depression, insomnia, and cognitive conditions. Aim of the study To investigate the in vitro cannabinoid and opioid receptor binding affinities, and in vivo behavioral actions of Nelumbo flower extracts and to isolate the potential compounds to treat CNS associated disorders. Materials and methods The white and pink flowers of N. nucifera were extracted with 95% EtOH, followed by acid–base partitioning using CHCl 3 to give acidic and basic partitions. These partitions were subjected to Centrifugal Preparative TLC (CPTLC) to yield benzyltetrahydroisoquinoline (BTIQ) alkaloids and long chain fatty acids, identified by physical and spectroscopic methods. In addition, EtOH extracts and partitions were analyzed for chemical markers by UHPLC/MS and GC/MS. In vitro neuropharmacological effects were evaluated by cannabinoid (CB1 and CB2) and opioid [delta ( δ ), kappa ( ĸ ), and mu ( µ )] competitive radioligand binding and GTPγS functional assays. The in vivo behavioral effect was studied through the use of the mouse tetrad assay at 10, 30, 75 and 100 mg/kg/ip doses that revealed the effect on locomotion, catalepsy, body temperature, and nociception of acidic and basic CHCl 3 partitions, fractions, and compounds. Results Three aporphines, nuciferine ( 1 ), N- nor -nuciferine ( 2 ), asimilobine ( 3 ), and five BTIQs, armepavine ( 4 ), O-methylcoclaurine ( 5 ), N-methylcoclaurine ( 6 ), coclaurine ( 7 ), neferine ( 10 ), and a mixture of linoleic and palmitic acids (LA and PA), were identified and evaluated for cannabinoid and opioid receptor displacement activities. Compounds 5 – 7 showed binding affinities for the ĸ opioid receptor with equilibrium dissociation constant ( K i ) values of 3.5±0.3, 0.9±0.1, 2.2±0.2 μM, respectively. Compound 10 displayed affinities for δ -and µ - opioid receptors with K i values of 0.7±0.1 and 1.8±0.2 μM, respectively, and was determined to be a weak δ agonist by GTPγS functional assay. The mixture of LA and PA (1:1) showed an affinity for δ opioid receptor with a K i value of 9.2±1.1 μM. The acidic and basic CHCl 3 partitions, compounds 1 and 7, and 5 – 7 mixture were subjected to the tetrad assay, of which the acidic partition displayed decreased locomotion and increased catalepsy, antinociception, and hypothermia in animal at doses of 75–100 mg/kg/ip, and also showed clonic-tonic seizures upon touch at 100 mg/kg. Conclusion Bioassay-guided isolation revealed compounds 5 – 7 , 10 , and the mixture of LA and PA displayed various degrees of opioid receptor radioligand displacement affinities. The in vivo tetrad assay of acidic CHCl 3 partition, enriched with aporphines 1 and 2 , displayed actions on all four points of behavioral parameters. It can be concluded that the in vivo mild canabimimetic-type effect observed for the CHCl 3 partition is likely mediated through other CNS mechanisms since the extracts, partitions, and isolated compounds had no affinity for the in vitro CB1 and CB2 receptors. This work, along with traditional use and the reported bioactivities of the BTIQ alkaloids, suggested further studies on N. nucifera are needed to understand the roles that the extracts and/or individual compounds might contribute to the behavioral effects. [ABSTRACT FROM AUTHOR]

Three new cyanogenetic triglycosides linustatins A–C ( 1 – 3 ), and two new simple glycosides linustatins D and E ( 4 and 5 ) were isolated from the 70% ethanol extract of flaxseed meal ( Linum usitatissimum L.). Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates showed moderate activities against aldose reductase and weak activities against α -glucosidase, DPP-IV, and FBPase at the same concentrations as the positive control drugs. [ABSTRACT FROM AUTHOR]

Nine new sesquiterpenes ( 1 – 9 ), together with seventeen known ones ( 10 – 26 ), were isolated from Chinese eaglewood. Their structures were established by extensive spectroscopic analysis, and the absolute configuration of 6 was determined by the modified Mosher's method. Compounds 7 , 10 , 14 , 15 , and 21 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC 50 values in the range 7.1–53.8 μM. [ABSTRACT FROM AUTHOR]

Four new phenolic acids, clerodens A–D ( 1 – 4 ) possessing an unusual bicycle [2.2.2] octane moiety were isolated from the whole plants of Clerodendranthus spicatus . Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD data. All isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7, and compound 4 showed significant inhibitory activities with IC 50 value of 6.8 μM. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Leonotis nepetifolia (L) R. Br., Lamiaceae, a pantropical shrub, popularly known in Brazil as “cordão-de-frade”, “rubim”, is reportedly used in Brazilian ethnomedicine as well as in different countries in the treatments of ailments such as infections, inflammations, wounds, stomach disorders, among others. Aim of the study To evaluate its potential cytotoxicity and antibacterial mode of action of the hydroethanolic extract of L. nepetifolia (HE Ln ) leaves, including phytochemical analysis. Materials and methods The cytotoxicity of HE Ln was investigated by Alamar blue assay, using CHO–K1 cells. Antibacterial activity of HE Ln was tested by broth microdilution methods against a panel of bacteria of clinical interest. The mode of action of L. nepetifolia was studied by targeting bacterial membranes. Phytochemical analysis was performed by determining total secondary metabolites with spectrophotometric assays and HPLC. Results HE Ln is not cytotoxic in the in vitro evaluation (IC 50 >200 μg/mL). It demonstrated a good spectrum of antibacterial activity with major activity against Shigella flexneri, Enterococcus faecalis, Staphylococcus aureus and Bacillus subtilis with MIC=6.25 µg/mL, Helicobacter pylori with MIC of 25 µg/mL and Streptococcus pyogenes with MIC of 50 µg/mL. Its mode of action is associated, at least partly, with changes in the permeability of bacterial membranes, as evidenced by the increased entry of hydrophobic antibiotics in Shigella flexneri and intense efflux of K + and nucleotide leakage in E. faecalis and Shigella flexneri . In addition, the presence of phenols, flavonoids and carotenoids, described in the literature to possess antibacterial effects, were detected in the composition of HE Ln , with high phenol content (11.55%), especially the flavonoids (6.47%). Conclusion The results indicate that HE Ln has low cytotoxicity and potent antibacterial activity. It is bacteriostatic in nature, possibly acting at the level of bacterial membranes, especially on the cytoplasmic membrane and outer membrane, thus supporting its popular use in infectious processes. In addition, the presence of phenols, flavonoids, carotenoids, fatty acids and steroids, described in the literature as possessing antimicrobial activity, were detected in the composition of HE Ln . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Areca catechu Linn. (Arecaceae) nut is a popular folk remedy for the treatment of migraine in Kerala and Tamil Nadu states of India. Aim of the study This study was designed to investigate the effect of hydroalcoholic extract of A. catechu L. nut (ANE) treatment on migraine pain in rat models to strengthen its use as an anti-migraine therapy. Materials and methods Bradykinin (0.1 μmol/kg) injection in to left femoral vein of rat produced PPE which was measured with luminescence spectrometer. Vocalizations were produced in rats with 10 μg of bradykinin infusion into common carotid artery. Phonogram was recorded before, during and for 5 min after bradykinin injection and sumatriptan was used as a standard anti-migraine drug. In both models, the ANE was orally administered at doses of 250 and 500 mg/kg, 60 min before bradykinin infusion. Results The PPE was reduced in both ANE treated groups of rats. The percent fluorescein was significantly increased in positive control group (97.00±1.7%; p <0.0001) compared to negative control (63.87±1.2%). With ANE treatments (250 and 500 mg/kg) PPE was significantly decreased to 88.88±1.4% ( p <0.01) and 83.55±0.1% ( p <0.0001) compared to positive control group, respectively. On the other hand in the model of vocalization, with 250 and 500 mg/kg ANE treatment, vocalization was significantly reduced to 33.33% and 16.66%, respectively, compared to saline treated rats. The reduction in vocalization is comparable to the reference drug sumatriptan. Conclusion The findings provide the strong evidence for anti-migraine potential of ANE in rat models of migraine. In summary, therapeutic intervention with ANE treatment could be a promising strategy for prevention of migraine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Schefflera octophylla (Lour.) Harms, a traditional Chinese herb mainly distributed in Southeast Asia, is extensively prescribed to alleviate pain and treat rheumatoid arthritis (RA), influenza, throat swelling, pain, etc. In this paper, the antinociceptive and anti-inflammatory activities of the ethanol extract and its five different polar fractions of this plant were evaluated. Furthermore, the anti-rheumatoid arthritis activity of the ethanol extract and its active fraction (CHCl 3 fraction) were evaluated. And the chemical constituents of the CHCl 3 active fraction displayed significant antinociceptive and anti-inflammatory activities were investigated. Materials and methods Antinociceptive and anti-inflammatory activities were investigated by hot plate test, acetic acid-induced abdominal writhing test and formalin test, xylene-induced ear edema test. The anti-rheumatoid arthritis activity was evaluated through the model of adjuvant-induced arthritis (AA) in rats, paw swelling, pain response, arthritis index and histopathological changes of ankle, the levels of TNF-α, IL-1β, IL-6 and rheumatoid factor (RF) of rats were detected. The chemical constituents of the CHCl 3 fraction were isolated using chromatographic techniques. Their structures were elucidated by spectroscopic data analysis. Results The results showed that the ethanol extract of S. octophylla has significant dose-dependent anti-inflammatory and antinociceptive activities. And its five different polar fractions especially the CHCl 3 fraction significantly inhibited the abdominal writhing induced by acetic acid and ear edema induced by xylene, also increased pain threshold in hot plate test in 120 min and reduced ticking times in formalin test. The ethanol extract of S. octophylla and the CHCl 3 fraction demonstrated an anti-RA effect in a dose-dependent manner. The levels of TNF-α, IL-1β and IL-6 in ethanol extract (600 mg/kg) and CHCl 3 fraction (300 mg/kg) groups were significantly lower than those of the model group. The chemical constituents study of the CHCl 3 fraction from S. octophylla led to six triterpenoids which were identified as taraxerone ( 1 ), 3-epi-taraxerol ( 2 ), aleuritolic acid ( 3 ), 3-oxofriedelan-28-oic acid ( 4 ), 3β,19α -dihydroxy-urs-12-ene- 24,28-dioic acid ( 5 ) and asiatic acid ( 6 ). Compounds 1 – 5 were obtained from this plant for the first time. Conclusion This study proved the antinociceptive, anti-inflammatory and anti-rheumatoid arthritis activities of S. octophylla. Triterpenoids obtained from its CHCl 3 fraction may be responsible for those activities. These results could support the fact that S. octophylla is used traditionally to cure inflammatory and pain diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Asclepias subulata Decne. is a shrub occurring in Sonora–Arizona desert (Mexico–USA). The ethnic groups, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. Aim of the study To isolate the compounds responsible for antiproliferative activity of the methanol extract of A. subulata . Materials and methods A bioguided fractionation of methanol extract of A. subulata was performed using MTT assay to measure the antiproliferative activity of different compounds on three human cancer cell lines (A549, LS 180 and PC-3), one murine cancer cell line (RAW 264.7) and one human normal cell line (ARPE-19). The methanol extract was partitioned with hexane, ethyl acetate and ethanol. The active fractions, ethanol and residual, were fractioned by silica-column chromatography and active sub-fractions were separated using HPLC. The chemical structures of isolated compounds were elucidated with different chemical and spectroscopic methods. Results A new cardenolide glycoside, 12, 16-dihydroxycalotropin, and three known, calotropin, corotoxigenin 3- O -glucopyranoside and desglucouzarin, were isolated of active sub-fractions. All isolated compounds showed a strong antiproliferative activity in human cancer cells. Calotropin was the more active with IC 50 values of 0.0013, 0.06 and 0.41 µM on A549, LS 180 and PC-3 cell lines, respectively; while 12, 16-dihydroxycalotropin reached values of 2.48, 5.62 and 11.70 µM, on the same cells; corotoxigenin 3 -O -glucopyranoside had IC 50 of 2.64, 3.15 and 6.62 µM and desglucouzarin showed values of 0.90, 6.57 and 6.62, µM. Doxorubicin, positive control, showed IC 50 values of 1.78, 6.99 and 3.18 µM, respectively. The isolated compounds had a weak effect on murine cancer cells and human normal cells, exhibiting selectivity to human cancer cells. Conclusion In this study, we found that 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3- O -glucopyranoside and desglucouzarin are responsible of antiproliferative properties of A. subulata , and that these compounds are highly selective to human cancer cells. Further studies are needed in order to establish the action mechanisms of the isolated compounds. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Lafoensia pacari A. St.-Hil. (Lythraceae), known popularly as “pacari” or “mangaba-brava” is popularly used in the state of Goiás, Brazil. The stem bark or leaves are used to treat cancer, gastric disorders, inflammation and as a tonic to treat loss of enthusiasm. Aim of the study Previous results suggest that the ethanol:water 7:3 extract of the stem bark of L. pacari (PEx) has antidepressant-like activity in male mice. Our aim was to perform the PEx׳s bioguided fractionation and evaluate the monoaminergic system involvement in the antidepressant effect as well as progress in the study of L. pacari mechanism of action. Material and methods Mice (30–35 g) orally treated (24, 5 and 1 h) with PEx (100, 300 or 1000 mg/kg), chloroform (ChloF—70 mg/kg), ethyl acetate (180 mg/kg), n -butanol (370 mg/kg) and aqueous (1 g/kg) fractions were submitted to the forced swimming test. To assess the mechanism of action, different groups of mice were pretreated with p -chlorophenylalanine (PCPA—100 mg/kg, 4 days, i.p.) and alpha-methyl- p -tyrosine (AMPT—100 mg/kg, 4 h, i.p.) to assess the involvement of serotoninergic and catecholaminergic systems in the ChloF effects, respectively. A putative in vitro inhibition of monoamine oxidase (MAO) activity as well as the ex vivo hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Phytochemical screening, spectroscopy and chromatography analysis were used for identification of compounds present in ChloF. Results and discussion After the fractionation, the ChloF 70 mg/kg was the most active fraction, reducing the immobility time by 22%. Pre-treatments with both PCPA and AMPT abolished the ChloF effects, suggesting that ChloF antidepressant-like effect is dependent on serotonergic and catecholaminergic systems. ChloF did not inhibited MAO-A or MAO-B activity, excluding this as possible mechanism of action. ChloF augmented hippocampal BDNF level, which could be accounted for its antidepressant-like effect. Phytochemical screening showed the presence of saponins, tannins, steroids and triterpene in the PEx, and the presence of triterpene and steroids in ChloF. The spectroscopy and chromatography analysis identified lupeol, β-sitosterol and stigmasterol in ChloF. Conclusion ChloF is the fraction that better retained the crude extract active constituents. ChloF presents antidepressant-like effect that involves both serotonergic and catecholaminergic systems without inhibiting MAO enzymatic activity; this fraction also increases the hippocampal BDNF levels. [ABSTRACT FROM AUTHOR]

Chromatographic separation of an aqueous acetone extract of the galls from Tamarix aphylla using gels resulted in isolation of an ellagitannin, phyllagallin M1 ( 13 ), a gallo-ellagitannin, phyllagallin D1 ( 14 ), and four gallotannins, phyllagallin M2 ( 15 ) and phyllagallins D2–D4 ( 16 – 18 ), in addition to four known ellagitannins and three phenolics of lower molecular weight structurally related to hydrolyzable tannins. The structures of the six new tannins were elucidated based on spectroscopic and chemical data. Among the phenolics, flavogallonic acid dilactone ( 8 ), which is presumed to be biogenetically produced by C–C oxidative coupling of an ellagic acid unit with a galloyl residue, shows an exceptional oxidative pattern of gallic acid residues in plants of the family Tamaricaceae. Although the ellagitannin tamarixellagic acid ( 4 ) was reported to be a constituent of the galls of T. aphylla , such compounds with anomalous location of the DHDG moiety at O-3 on the glucopyranose core have not been observed among the tannins of tamaricaceous plants. [ABSTRACT FROM AUTHOR]

One new 19-norbufadienolide ( 1 ) and one new bufogargarizin ( 2 ), together with twelve known bufadienolides ( 3–14 , resp.) were isolated from Chan Su, a traditional Chinese medicine that is used in the treatment of cancer. Their structures were elucidated on the basis of detailed spectroscopic analysis and comparison of corresponding data that is previously reported. The cytotoxic activities of the isolated compounds were evaluated on HeLa and A549 cell lines. Though 1 and 2 showed weak cytotoxic activities on both cell lines, compounds 4 and 5 showed lower IC 50 values than bufalin, the most widely studied bufadienolide in Chan Su. Furthermore, four 3-ester derivatives ( 15–18 ) of compound 4 were synthesized and their cytotoxic activities were also evaluated. Analysis of the structure–activity relationship indicated that bufadienolides with aldehyde group at C-10 or α -hydroxyl group at C-11 exhibit stronger cytotoxic activities on both cell lines. The cytotoxic activity of arenobufagin-3-ester derivative 17 was 4-fold higher than compound 4 . [ABSTRACT FROM AUTHOR]

Equisetum hyemale species is considered a medicinal plant used in the form of infusions to combat infectious or inflammation diseases and also diuretic effects, presenting several compounds related to these actions. In previous studies different species of Equisetum showed several phenolic compounds. The objective of this study was, for the first time, based on phytochemistry analysis to evaluate the antioxidant and antimicrobial activity. The 70% ethanolic and methanolic extracts of E. hyemale were characterized by spectrophotometric and high-performance liquid chromatography with pulsed amperometric detector analyses, as well as its antioxidant potential based on the scavenger activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH). In addition was verified the antimicrobial activity by broth microdilution technique against bacteria and fungi. The extracts showed phytochemical similarity, which demonstrated the presence of phenolic compounds, the scavenging activity for free radicals was about 30% and was observed better antifungal activity against dermatophyte fungi, with minimum inhibitory concentration and minimum fungicidal concentration of 0.62 mg/mL to Trichophyton rubrum and Microsporum canis. The extracts exhibits great potential to therapeutic applications or product development, since both possess antifungal activity and antioxidant action associated with little difference in their phytochemical composition. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bolbostemma paniculatum (Maxim.) Franquet ( B. paniculatum ), also named “Tu-bei-mu” in Chinese folk medicines, has been described in application for the treatment of tumors, warts, inflammation and toxication in traditional Chinese medicinal books. The major constituents in B. paniculatum are triterpenoid saponins, which have been proved to possess dramatically cytotoxic activity and antivirus activity. The aim of this study is to isolate and identify the active triterpenoid saponin from the bulb of B. paniculatum by a bioassay-guided method. Materials and methods Four cucurbitacine triterpenoid sapogenins and 11 triterpenoid saponins were isolated from the active EtOAc and n-BuOH extract of B. paniculatum by using bioassay-guided screening. Their structures were elucidated based on the spectroscopic methods and compared with published data. Cytotoxic activities of isolated compounds were determined by MTT assay. Results Four cucurbitacine triterpenoid sapogenins, isocucurbitacin B( 1 ), 23,24-dihydroisocucurbitacin B( 2 ), cucurbitacin E( 3 ), 23,24-dihydrocucurbitacin E( 4 ), and 11 triterpenoid saponins, tubeimosideI( 5 ), tubeimoside III( 6 ), tubeimoside V( 7 ), dexylosyltubeimoside III( 8 ), lobatoside C( 9 ), tubeimoside A( 10 ), tumeimoside B( 11 ), lobatoside A( 12 ), tubeimoside C( 13 ), tubeimoside IV( 14 ), 7 β ,18,20,26-tetrahydroxy-(20 S )-dammar-24E-en-3- O - α- L -(4-acetyl)arabinopyranosyl-(1→2)- β- D -glucopyranoside( 15 ) were isolated from the active EtOAc and n-BuOH extracts. Of them, compounds 2 , 4 , 9 and 12 were firstly isolated from the Bolbostemma genus. MTT assay revealed that compounds 1 , 3 and 4 had significantly activities against HeLa and HT-29 human cancer cells with IC 50 values ranging from 0.93 to 9.73 μM. It is worth mentioning that compound 4׳ s activities against the two cell lines are 12- and 8-fold that of the positive control drug (5-Fu). Whereas, the cyclic bisdesmosides 5 – 9 exerted significantly activities on BGC-823, HeLa, HT-29 and MCF-7 cancer cells with IC 50 values ranging from 1.30 to 15.64 μM. And 6׳ s activities against the four cell lines are 6-, 3-, 10- and 16-fold that of 5-Fu and 8׳ s activities against the four cell lines are 5-, 3-, 14- and 9-fold that of 5-Fu. Conclusion The cytotoxic activity of the bulbs of B. paniculatum is mainly ascribable to cucurbitacine triterpenoid sapogenins (1–4) and the cyclic bisdesmosides (5–9). The cyclic bisdesmosides are the main anti-cancer active compounds of B. paniculatum . The above results provide scientific evidence to support, to some extent, the ethnomedicinal use of B. paniculatum as anticancer remedies in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Fagara tessmannii is a shrub of the African rainforests used to treat bacterial infections, cancers, swellings and inflammation. In the present study, the methanol extract from the leaves (FTL), bark (FTB), and roots (FTR) of this plant as well as fractions (FTR1-5) and compounds isolated from FTR namely β -sitosterol-3- O-β- d -glucopyranoside ( 1 ), nitidine chloride ( 2 ) and buesgenine ( 3 ), were tested for their antimicrobial activities against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes. Materials and methods The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; Column chromatography was used for the fractionation and purification of the roots extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Results Results of the MIC determinations indicated that the crude extracts from the roots as well as fraction FTRa4 were active on all the 26 tested bacterial strains. MIC values below 100 µg/mL were obtained with roots, leaves and bark extract respectively against 30.8%, 15.4% and 11.5% tested bacteria. The lowest MIC value below of 8 µg/mL was obtained with extract from the roots against Escherichia coli MC100 strain. The lowest MIC value of 4 µg/mL was also obtained with compound 3 against E. coli AG102 and Klebsiella pneumoniae ATCC11296 Conclusions The present study demonstrates that F. tessmannii is a potential source of antimicrobial drugs to fight against MDR bacteria. Benzophenanthrine alkaloids 2 and 3 are the main antibacterial consituents of the roots of the plant. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Propolis has long been used as a popular folk medicine due to its wide spectrum of alleged biological and pharmaceutical properties. In Chile, propolis is widely used by folklore medicine as an anti-inflammatory agent; however, this property has not been demonstrated by scientific methods. Aim of the study The objective of this study was to determine the anti-inflammatory activity in vivo and in vitro and to establish the phenolic profile of propolis collected in two localities in Región Metropolitana de Santiago (RM), Chile. Materials and methods Propolis was collected in the areas of Caleu and Buin, RM Chile. Following that, the samples were unwaxed to obtain the global ethanolic extracts of propolis (EEPs) and, from these, the serial extracts of dichloromethane (EEP-DCMs) and ethanol (EEP-EtOHs). The topic anti-inflammatory effect was evaluated through mice ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) at a dose of 3 mg/ear. Nitric oxide (NO) measurements were determined spectrophotometrically (Greiss reagent) by the accumulation of nitrite in the medium of macrophages RAW 264.7 stimulated with the lipopolysaccharide (LPS, 1 μg/mL) for 20 h at different concentrations of the EEPs, EEP-DCMs and EEP-EtOHs (6.25–50.00 μg/mL). The content of total phenols and flavonoids were determined through the methods of Folin–Ciocalteau and AlCl 3 , respectively. The profile of phenolic compounds was determined by HPLC–UV–ESI-MS/MS. Results The EEP-EtOH (64%) and EEP (59%) of Buin were the most active in the inflammation induced by TPA and AA respectively, being the anti-inflammatory effect stronger than the same Caleu extracts. Regarding the release of NO, all the extracts from the Buin propolis inhibited significantly its release in a concentration-dependent manner, this inhibition was stronger than the extracts from Caleu propolis. Conclusions Our research shows for the first time a comparative study of the topical in vivo activity of two Chilean propolis. Both propolis showed in vivo topical anti-inflammatory activity against AA and TPA, the most active was Buin propolis and this difference is due in part to the variations in total phenols and flavonoids content and the phenolic profile. The phenols and flavonoids content of Buin propolis was higher than Caleu propolis. The extracts from Buin propolis result in a lower release of NO. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. Aim of the study The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Materials and methods For sake of screening effective cholinesterase inhibitors, trace compounds were isolated from seeds of P. harmala through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The inhibitory activities on AChE and BChE were assessed using an improved Ellman method by UPLC-ESI-MS/MS to determine the common final product choline. Results The activity-guided fractionation led to the isolation of two new alkaloids 2-aldehyde-tetrahydroharmine ( 10 ), 2-carboxyl-3,4-dihydroquinazoline ( 19 ), one syringin structure analog 1-O- β - D -xylopyranose sinapyl alcohol ( 22) , and along with 19 known compounds. Compounds acetylnorharmine ( 6 ), harmic acid methy ester ( 7 ), harmine N -oxide ( 13 ), 6-methoxyindoline ( 14 ), syringin ( 21 ) were first found from genus Peganum and compounds 3-hydroxylated harmine ( 4 ), 1-hydroxy-7-methoxy- β -carboline ( 5 ) were new natural products. The results showed that the 2-aldehyde-tetrahydroharmine ( 10 ) has a potential inbibitive effect on both AChE and BChE with IC 50 values of 12.35±0.24 and 5.51±0.33 µM, respectively. Deoxyvasicine ( 15 ) and vasicine ( 16 ) showed the strongest BChE inhibitory activity with IC 50 values of 0.04±0.01 and 0.1±0.01 µM. The analysis of the structure-activity relationship indicated that the saturation of pyridine ring and the presence of substitution at indole ring, C-1, C-3, C-7 and N-2, for β-carbolines, were essential for effective inhibition of both AChE and BChE and the five-membered ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9, for quinazolines, were important to both the AChE/BChE-inhibitory activity. Conclusions Bioassay-guided fractionation has led to the isolation of AChE and BChE inhibitors from the seeds of P. harmala . These results are in agreement with the traditional uses of the seeds of P. harmala . [ABSTRACT FROM AUTHOR]

Three new prenylated flavonoids, macarindicins A–C ( 1–3 ), as well as seven known compounds ( 4–10 ) were isolated from the twigs of Macaranga indica . Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 2 and 3 enriched the diversity of prenyl moiety in genus Macaranga especially in the aspect of various lengths of prenyl chain. All the known compounds were isolated from M. indica for the first time and this plant was found to contain large number of ellagic acid. Compounds 1–10 were tested for their cytotoxicity against four cancer cell lines (MCF-7, Hep G2, Hela and P388) and showed IC 50 values in the range of 2.61–20.35 μ g/mL. [ABSTRACT FROM AUTHOR]

Inhibitors of protein tyrosine phosphatase 1B (PTP1B) are promising agents for the treatment of type 2 diabetes and obesity. The bioactivity-guided isolation led to the separation of two new compounds, (±)-tradescantin ( 13 ) and tradescantoside ( 16 ), along with fourteen known compounds ( 1 – 12 , 14 , and 15 ) from the aerial parts of Tradescantia spathacea Sw. (Commelinaceae). Their chemical structures were elucidated by spectroscopic methods as well as by comparing with those reported in the literature. The isolated compounds ( 1 – 16 ) were then examined for their inhibitory activity toward PTP1B. The results indicated that compounds 2 , 6 , 8 , and 12 possessed potent inhibition with IC 50 values of 7.82 ± 0.79, 6.80 ± 0.89, 4.55 ± 0.92, and 6.38 ± 0.14 μM, respectively. Kinetic study of compounds 2 , 6 , 8 , 12 , 13 , and 16 was conducted and the structure–activity relationships of the isolated compounds ( 1 – 16 ) were also discussed herein. To the best of our knowledge, all the isolates were separated for the first time from this plant. [ABSTRACT FROM AUTHOR]

Ten flavonoid glycosides, apetalumosides A ( 1 ), B 1 –B 7 ( 2 – 8 ), and C ( 9 ), quercetin 3- O -(2,6-di- O - β - d -glucopyranosyl)- β - d -glucopyranoside ( 10 ), were obtained from the seeds of Lepidium apetalum Willd. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, NMR, and HRESI-TOF-MS). 1 – 9 were new isolates. The NMR data for 10 was reported here for the first time. On the other hand, activity screening results showed that 1 – 3 and 10 had triglyceride accumulation inhibitory effects in HepG2 cells. Preliminary structure–activity relationship study revealed that 7-hydroxyl group is an essential moiety. [ABSTRACT FROM AUTHOR]

Five new benzylphenanthrenes, cremaphenanthrenes L–P ( 1 – 5 ) were isolated from the EtOAc-soluble extract of the tubers of Cremastra appendiculata . Their structures were elucidated based on the spectroscopic data and chemical methods. Compounds 1 – 5 were tested in vitro for their cytotoxic effects against colon (HCT-116), cervix (Hela), and breast (MCF-7 and MDA-MB-231) cancer cell lines. Compound 1 showed moderate cytotoxic activities against HCT-116, MCF-7, and MDA-MB-231 cancer cell lines with IC 50 values ranging from 15.84 to 24.18 μM and weak cytotoxicity to Hela cell line with IC 50 value of 68.81 μM. [ABSTRACT FROM AUTHOR]

Four new neolignans ( 1 – 4 ), together with two known lignans ( 5 and 6 ), were isolated from the root of Paeonia lactiflora . Compounds 1 and 2 were two racemates and were separated by chiral high performance liquid chromatography (HPLC) to give all of the four stereoisomeric forms sharing a common planar structure. Compounds 3 and 4 were two neolignan glycoside diastereomers but interestingly appeared to be enantiomers: they had the extremely similar 1 H and 13 C NMR spectra and had to be solved only by chiral HPLC. Their structures were determined by spectroscopic analysis, including 1D and 2D NMR, HRESIMS and electronic circular dichroism experiments. All compounds were evaluated for their inhibitory effects on β-amyloid aggregation, and the optical pure compound 2b was found to show the optimal Aβ 1–42 aggregation inhibition potency (81.1% at 20 μM). In addition, despite large amount of chemical studies performed on genus Paeonia , the lignans were reported for the first time. [ABSTRACT FROM AUTHOR]

A new prenylated isoflavan, iconisoflavan ( 1 ), and a new prenylated isoflav-3-ene, iconisoflaven ( 2 ) were isolated from the roots of Glycyrrhiza iconica together with four known ones namely ( 3S )-licoricidin ( 3 ), licorisoflavan A ( 4 ), topazolin ( 5 ) and glycycoumarin ( 6 ). The structures were elucidated on the basis of extensive spectroscopic analysis including 1D and 2D NMR as well as HR–MS. Furthermore, the absolute configurations of compounds 1 , 3 and 4 were established by electronic circular dichroism (ECD). All the isolated compounds ( 1 – 6 ) were evaluated for their in vitro antimicrobial activities against five pathogenic bacteria and one yeast ( Candida albicans ) using an in vitro microdilution method. Compounds 1 and 3 – 5 displayed significant activity against Salmonella typhimurium ATCC 13311 with MIC values ranging from 2 to 8 μg/mL. Additionally, all compounds were screened for their in vitro free radical scavenging activities using an in vitro microdilution DPPH assay spectrofotometrically. The tested compounds exhibited IC 50 values in the range of 0.18–0.56 mg/mL, suggesting an activity comparable with that of ascorbic acid (IC 50 : 0.07 mg/mL). To the best of our knowledge, the present study constitutes the first phytochemical and bioactivity investigation on G. iconica . [ABSTRACT FROM AUTHOR]

Four new flavones, tobaflavones E–H ( 1 – 4 ), together with two known flavones ( 5 and 6 ), were isolated from the leaves of Dali Tiandeng tobacco (a variety of Yunnan local air cured tobacco). Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Compound 2 is the first naturally occurring flavone bearing a (4-hydroxy-6-methyl-2-oxo-2 H -pyran-3-yl)methyl moiety. These compounds were also evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. The results revealed that compounds 1 and 2 exhibited high anti-TMV activity with inhibition rate of 35.3% and 39.6%, respectively. The rates are higher than those of positive control. The other compounds also showed potential anti-TMV activity with inhibition rates in the range of 18.7–28.4%, respectively. [ABSTRACT FROM AUTHOR]