Three new cadinene-type sesquiterpenoids from the aerial parts of Ageratina adenophora.

Three new cadinene sesquiterpenoids 1-3, were isolated from the aerial sections of Ageratina adenophora using various chromatographic techniques. Their structures were characterised by comprehensive spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The cytotoxic activity of new compounds 1-3 were evaluated by testing in vitro tumour growth inhibitory rate against five human tumour cell lines, HL-60, A-549, SMMC-7721, MDA-MB-231, and SW480.

Unusual 5/5 fused bicyclosesquiterpenoids from Eupatorium adenophorum.

The chemical analysis on the aerial sections of Eupatorium adenophorum Spreng. resulted in the identification of four unprecedented 5/5 fused bicyclosesquiterpenoids, eupatorid A (1), and its analogues named eupatorester A-C (2-4) using various chromatographic techniques. Their structures were unambiguously confirmed by detailed spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The anti-inflammatory activities, in vitro tumor growth inhibitory activities and antibacterial activities of these compounds were evaluated.

New 5-methyl-4-hydroxycoumarin polyketide derivatives from Gerbera delavayi with anti-inflammatory activity.

Five new 5-methyl-4-hydroxycoumarin polyketide derivatives (MPDs), delavayicoumarins A-E (1-5), were isolated from the whole plants of Gerbera delavayi. Among them, compounds 1-3 are the common monoterpene polyketide coumarins (MPCs), while 4 is a modified MPC with both the lactone ring contracted to a five-membered furan ring and a carboxyl at C-3, and 5 is a pair of unusual phenylpropanoid polyketide coumarin enantiomers (5a and 5b), featuring a phenylpropanoid unit at C-3. The planar structures were elucidated by spectroscopic methods and biosynthetic arguments, and the absolute configurations of 1-3, 5a and 5b were confirmed by calculated electronic circular dichroism (ECD) experiment. Furthermore, compounds 1-3, (+)-5 and (-)-5 were tested for the nitric oxide (NO) inhibitory activity by using lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro. The results showed that compounds 1-3, (+)-5 and (-)-5 remarkably inhibited NO production at the concentration of 10.0 µM, exhibiting that they have significant anti-inflammatory activity.

Gerberdriasins A-F, six undescribed coumarin derivatives from Gerbera anandria (Linn) Sch-Bip and their protective effects on scopolamine-induced injury in PC12 cells.

A chemical investigation on the herb Gerbera anandria (Linn) Sch-Bip led to the isolation and identification of six previously undescribed coumarin derivatives, named Gerberdriasins A-F (1-6). Structurally, their chemical structures and absolute configurations were determined by nuclear magnetic resonance (1D and 2D NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), experimental and quantum mechanical nuclear magnetic resonance (QM-NMR) methods, Mosher's method and calculated electronic circular dichroism (ECD) experiments. The biological activity of the obtained compounds showed that they displayed significant neuroprotective effects against scopolamine-induced injury in PC12 cells at the concentrations 12.5, 25.0 and 50.0 nM. Further study demonstrated that 1 could inhibit cell apoptosis, decrease malondialdehyde (MDA) levels and increase superoxide dismutase (SOD) activity in scopolamine-treated PC12 cells.

Vlasouliodes A-D, four new C30 dimeric sesquiterpenes exhibiting potential inhibition of MCF-7 cells from Vladimiria souliei.

As our ongoing interest to search bioactive dimeric sesquiterpenes from the genus Vladimiria (Asteraceae), the plant of Vladimiria souliei was studied. Based on the repetitive chromatographic fractionation, a chemical investigation on the roots of Vladimiria souliei led to the isolation and the identification of four previously undescribed sesquiterpene dimers, vlasouliodes A-D (1-4). Their chemical structures were elucidated by comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR spectroscopic data. The absolute configurations of them were unambiguously established by the experimental and calculated ECD data. In the in vitro biological activity evaluation, 1 and 3 displayed pronounced inhibitory activity against human breast adenocarcinoma cell lines (MCF-7) with IC50 values of 17.12 ± 0.42 µM and 13.12 ± 0.10 µM, respectively. Additionally, treatment with 1 and 3 induced cell apoptosis in MCF-7 cells, down-regulated the expression of Caspase-3 and up-regulated the expression of Cleaved-caspase-3.

Five new C17/C15 sesquiterpene lactone dimers from Carpesium abrotanoides.

Five new unusual C17/C15 sesquiterpene lactone dimers, carabrodilactones A-E (1-5), along with four known common C15/C15 SLDs, carpedilactones A and B (6 and 7), faberidilactone A (8), and faberidilactone C (9), were isolated from the whole plants of Carpesium abrotanoides. The structures of 1-5 featured a flexible C-11/C-13' linked single bond between two sesquiterpene units and a tailed acetyl connected to the C-13 position. The preferential conformation of 1-5 was elucidated by the diagnostic NMR data of geminal proton of H-13. The biogenetic pathway of 1-5 was proposed to involve Stetter and Michael addition reactions. In addition, compound 1 exhibited significant cytotoxicities against the four cell lines (A549, HCT116, MDA-MB, and BEL7404 cells) with IC50 value in the range of 3.08-8.05 µM, while compounds 2-5 showed weak cytotoxicities.

New chromane and chromene meroterpenoids from flowers of Rhododendron rubiginosum Franch. var. rubiginosum.

Six new chromane and chromene meroterpenoids rubiginosins A-F (1-2, and 4-7), together with three known ones, rubiginosin G (3) and anthopogochromenes A and B (8-9),were isolated from the flowers of Rhododendron rubiginosum Franch. var. rubiginosum. Among them, 1-4 were the chromane ones derived from an intramolecular [2 + 2] cycloaddition of their respective chromene precursors, making a 6/6/6/4- or 6/6/5/4-ring fused scaffold. The absolute configuration of the chiral center at C-2 of 1-9 was determined as S by chromane/chromene helicity rule and X-ray crystallograph. Notably, more attention should be paid to 6-carboxyl derivatives, since the 6-carboxyl derivatives showed an abnormal diagnostic Cotton effect (CE) with respect to their normal diagnostic CE. Compounds 1-9 were tested for cytotoxicity against four cell lines (A549, HCT116, SK-HEP-1, and HL-60), and only 1, 3, 5, and 9 showed moderate cytotoxicity, while others were inactive, discovering the 6-carboxyl is crucial for their low cytotoxicity.

Isolation, Structure Elucidation, and Absolute Configuration of Highly Oxygenated Germacranolides from Carpesium cernuum.

The new highly oxygenated germacranolides cernuumolides A-J (1-10) and the known compounds 11-20 were isolated from Carpesium cernuum. Among these compounds, 1-4 are 11-methoxymethylgermacranolides and 5-7 as well as 11-17 are 2,9-hemiacetal-linked germacranolides. Their structures were elucidated using NMR and HRESIMS analyses, and X-ray diffraction studies were used to confirm the absolute configurations of 1, 2, 5, 6, 8, and 9. Cernuumolides A-J were evaluated for their in vitro cytotoxicity against the A549, HCT116, MDA-MB-231, and BEL7404 cell lines, and 8 exhibited moderate cytotoxicity with IC50 values in the 0.87-2.02 µM range.

Three new sesquiterpene lactone dimers from Carpesium macrocephalum.

Three new sesquiterpene lactone dimers (SLDs), carpedilactones E-G (1-3), together with two known monomeric units, ivalin (4) and alantolactone (5), were isolated from the acetonic extract of Carpesium macrocephalum. Their chemical structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments, and the absolute configuration of 1-3 was resolved according to the (1)H NMR and CD spectrographic features of 1,3-/2,4-linked SLDs. Furthermore, 1 was unambiguously confirmed by Cu-Kα X-ray crystallographic analysis. Additionally, compounds 1 and 2 were revealed with potent cytotoxicities against human colon cancer HCT116 cells with IC50 values of 2.27 and 3.30 µM, respectively.

Gleditsia species: An ethnomedical, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants in the genus Gleditsia, mainly distributed in central and Southeast Asia and North and South America, have been used as local and traditional medicines in many regions, especially in China, for the treatment of measles, indigestion, whooping, smallpox, arthrolithiasis, constipation, diarrhea, hematochezia, dysentery, carbuncle, etc. This present paper systemically reviews the miscellaneous information surrounding its traditional use, phytochemistry and pharmacology to provide opportunities and recommendations for the future research. MATERIALS AND METHODS: The scientific literatures were systematically searched from scientific databases (PubMed, Scopus, Elsevier, SpringerLink, SciFinder, Google Scholar and others). In addition, the ethnopharmacological information on this genus was mainly acquired from Chinese and Korean herbal classics, and library catalogs. RESULTS: More than 60 compounds including triterpenes, sterols, flavonoids, alkaloids, phenolics and their derivatives were isolated from Gleditsia japonica Miq., Gleditsia sinensis Lam., Gleditsia caspica Desf. and Gleditsia triacanthos L. Among these compounds, triterpenoid saponins were the main constituents of Gleditsia species. Moreover, the crude extracts and purified molecules were tested, revealing diverse biological activities such as anti-tumor, anti-inflammatory, anti-allergic, anti-hyperlipidemic, analgesic, antimutagenic, antioxidant, anti-HIV, antibacterial, antifungal activities, etc. Among these biological studies, the possible mechanisms of antitumor action are stressed in this review, and these include causing cytotoxicity to cancer cells, inhibition of proliferation of cancer cells by affecting their growth, regeneration and apoptosis, inhibition of basic fibroblast growth factor (bFGF) and nitric oxide (NO), modulation of the oncogenic expression and telomerase activity results, inhibition of the expression of pro-angiogenic proteins, as well as down-regulation of intra/extracellular proangiogenic modulators, etc. CONCLUSIONS: On the basis of preliminary research on Gleditsia genus it could be stated that saponins investigations may be more promising in future. Although 32 compounds of 67 identified compounds were saponins, modern pharmacological research on saponins were not a priority in Gleditsia species. Therefore, more bioactive experiments and in-depth mechanisms of action are required for elucidating their roles in physiological systems. Moreover, the present review also highlights that analgesic, anti-tumor and anti-HIV activities should have priority in saponins research. Additionally, it is imperative to explore more structure-activity relationships and possible synergistic actions of triterpenoid saponins for revaluating their pharmacological activities.

[Studies on sesquiterpene lactones from Carpesium faberi].

By using various chromatographic techniques,18 sesquiterpene lactones were isolated from the acetone extract of Carpesium faberi. Their structures were identified on the basis of comprehensive spectroscopic data, involving 2 carabrane sesquiterpenoids [carabrone(1), 4R-carabrol(2)], 3 eudesmane sesquiterpenoids [granilin(3), 3-epi-isotelekin(4), 1α-hydroxypinatifidin(5)], 8 guaiane sesquiterpenoids [4ß,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide(6), 8-epi-helenium lactone(7), 4-epi-isoinuviscolide(8), 9ß,10ß-epoxy-4α-hydroxy-1ß-H,11α-H-guaian-8α,12-olide(9), 4α,10α-dihydroxy-1ß(H),5ß(H)-guaian-11-(13)-en-8α,12-olide(10), 4α-hydroxy-9ß,10ß-epoxy-11ß-H,5α-H-guaian-11(13)-en-8α,12-olide(11), 4α-hydroxy-1ß,5α,11α-H-guaian-9(10)-en-8α,12-olide(12), inuviscolide(13)], 1 pseudoguaiane sesquiterpenoid [(+)-confertin(14)], 3 germacrane sesquiterpenoids [madolin B(15), carabrolactone A(16),11(13)-dehydroivaxillin(17)], 1 xanthane sesquiterpenoid [tomentosin(18)]. Furthermore, the absolute configuration of 1 was confirmed by Cu-Kα X-ray crystallographic analysis,and the R-configuration of the chiral center at C-4 in 2 was established by the modified Mosher's method.The compounds 2-5, 7 and 9-15 were isolated from this plant for the first time, and compounds 4-5, 7, and 12-15 were isolated from this genus for the first time.In addition, the neurotrophic activity of compounds 1-3, 6 and 17 were evaluated by morphological observation and statistical analysis of cells differentiation, using rat pheochromocytoma(PC12)cells as a model system. However, all compounds were inactive.

Periplanosides A-C: new insect-derived dihydroisocoumarin glucosides from Periplaneta americana stimulating collagen production in human dermal fibroblasts.

Three new dihydroisocoumarin glucosides, termed periplanosides A-C (1-3), a known analog, pericanaside (4), and the other twenty known compounds were isolated from the insect Periplaneta americana. Their structures including absolute configurations were determined by comprehensive spectroscopic analyses and computational methods. Biological evaluation showed that compound 2 could stimulate collagen production by 31.2% in human dermal fibroblasts-adult (HDFa) at the concentration of 30 µM, indicating its significance in skin repair and ulcer.

The genus Carpesium: a review of its ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants in the genus Carpesium, which grow naturally in Asia and Europe, have long been used in traditional Chinese, Korean and Japanese medicines. The antipyretic, antimalarial, haemostatic, anti-inflammatory and detoxifying properties of their extracts enabled their use in the treatment of several diseases, such as fevers, colds, contusions, diarrhoea, mastitis, mumps, hepatitis, malaria, etc. This review summarises the state-of-the-art and comprehensive information surrounding its use as traditional medicine, phytochemistry, pharmacology, and toxicology to reveal the potential therapeutic effects of Carpesium plants and to establish a solid foundation for directing future research. MATERIALS AND METHODS: The extensive reading and investigation were actualised by systematically searching the scientific literatures including Chinese, Korean and Japanese herbal classics, library catalogs and scientific databases (PubMed, Scopus, SciFinder and the Web of Science), were systematically searched for topics related to factors like the chemical constituents, pharmacognostic research and pharmacological effects of the Carpesium species. RESULTS: Carpesium plants have been studied extensively as traditional folk medicines in China, Korea and Japan all the time. In past, phytochemical research was the focal point of this genus, and the recent studies of the members of this genus have been focused on the pharmacological activity and potential therapeutic applications of these plants. The research performed revealed that 143 compounds including sesquiterpenoid lactone monomers, sesquiterpenoid lactone dimers, monoterpenes, diterpenoids, phenolic compounds, and several other type of compounds, were isolated and identified within this genus in recent years, and certain of these constituents had demonstrated to possess anti-inflammatory, anti-tumor, anti-plasmodial, anti-oxidant, anti-fungal and anti-bacterial effects. CONCLUSIONS: This review shows that approximately 50 active compounds possess therapeutic potential during the treatment of cancer, inflammatory, parasitosis, etc. However, apart from those bioactive molecules, a considerable part of compounds, including a lot of sesquiterpenes, and several other type of compounds that have been previously isolated but have not been tested biologically need to be further tested. Therefore, more pharmacological experiments should be focused on these untested chemical constituents. Additionally, another issue concerns that most pharmacological studies were only performed in vitro-based experiments, so additional in vivo tests in animal models are required to estimate their side effects for the safety approval of therapeutic applications. Finally, further studies through well controlled, double-blind clinical trials are required to re-evaluate their efficacious and possible side effects, and more pharmacological mechanisms on main active compounds will also be needed for illuminating correlations between ehnopharmacology and pharmacology in future.

Carpedilactones A-D, four new isomeric sesquiterpene lactone dimers with potent cytotoxicity from Carpesium faberi.

Four new isomeric sesquiterpene lactone dimers, carpedilactones A-D (1-4), were isolated from the acetonic extract of Carpesium faberi. Among them, 1-3 are the first three 2,4-linked exo-Diels-Alder adducts between a eudesmanolide dienophile and a guaianolide diene. The absolute configurations of 1-4 were unambiguously established by Cu Kα X-ray crystallographic analyses. Compounds 1-4 exhibited potent cytotoxicities against human leukemia (CCRF-CEM) cells with IC50 value of 0.14, 0.32, 0.35, and 0.16 µM, respectively.

[Chemical constituents from leaves of Rhododendron rubiginosum var rubiginosum].

Thirteen compounds were isolated from the leaves of Rhododendron rubiginosum var. rubiginosum by various chromatographic techniques. On the basis of spectroscopic data, their structures were elucidated as 3,9-dihydroxy-megastigma-5-ene (1), 3 beta-hydroxy-5alpha ,6 alpha-epoxy-7-megastigmen-9-one (2), loliolide (3), ursolic acid(4), 2 alpha, 3 beta-dihydroxy-urs-12-en-28-oic acid (5), 2 alpha, 3 beta,23-trihydroxy-urs-12-en-28-oic acid (6), 7,9-dimethoxyrhododendrol (7), 7-methoxyrhododendrol (8), zingerone (9), isofraxidin (10), scopoletin (11), (+)-pinoresinol (12) and 3'-O-demethylepipinorisenol (13). All compounds were isolated from this plant for the first time, and compounds 1-3, 7-9, and 11-13 were isolated from the genus Rhododendron for the first time.

Anthraquinone derivatives from Rumex plants and endophytic Aspergillus fumigatus and their effects on diabetic nephropathy.

Two new oxanthrone C-glycosides, patientosides A (14) and B (15), together with three known ones (11-13), were isolated from Rumex patientia. Their structures were identified on the basis of spectroscopic methods. The absolute configuration for 14 and 15 were deduced by analysis of their CD spectra and comparison with those of known similar compounds. Compounds 11-15, and 14 known anthraquinones (1-4, 6-10, 16-20) previously isolated from Rumex nepalensis, Rumex hastatus, and endophytic Aspergillus fumigatus, respectively, as well as a commercially available compound rhein (5) were evaluated for their inhibitory effects on IL-6 and extracellular matrix production in mesangial cells.