Qing-Xin Liu

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.

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.

Structurally novel C17-sesquiterpene lactones from Ainsliaea pertyoides

Pertyolides A (1) and B (2), two unprecedented C17-eudesmanolides with extended side chains, and one rare C17-guaianolide, pertyolide C (3), along with 15 known sesquiterpene lactones were isolated from the whole plant of Ainsliaea pertyoides. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of compound 1 was assigned by X-ray crystallography. All isolates were evaluated for their cytotoxic activities against four human tumor cell lines A549, HCT116, MGC803, CCRF-CEM, and only alantolactone (5) showed significant inhibitions against the tumor cell lines tested.

Acylated Iridoids from the Roots of Valeriana officinalis var. latifolia

Phytochemical investigation of the roots of Valeriana officinalis var. latifolia resulted in the isolation and characterization of six new acylated iridoids, (5S,7S,8S,9S)-7-hydroxy-8-isovaleroyloxy-Δ⁴,¹¹-dihyronepetalactone (1), (5S,7S,8S,9S)-7-hydroxy-10-isovaleroyloxy-Δ⁴,¹¹-dihyronepetalactone (2), (5S,8S,9S)-10-isovaleroyloxy-Δ⁴,¹¹-dihyronepetalactone (3), (5S,6S,8S,9R)-6-isovaleroyloxy-Δ⁴,¹¹-1,3-diol (4), (5S,6S,8S,9R)-1,3-isovaleroxy-Δ4,11-1,3-diol (5), and (5S,6S,8S,9R)-3-isovaleroxy-6-isovaleroyloxy-Δ⁴,¹¹-1,3-diol (6). Their structures were determined mainly by 1D and 2D NMR spectroscopic techniques. We also report herein for the first time the single crystal X-ray structure of compound 1. In addition, the cytotoxic activities of compounds 1-6 were evaluated against A549 (human lung adenocarcinoma), HCT116 (human colon carcinoma), SK-BR-3 (human breast carcinoma), and HepG2 (human hepatoma) cell lines. Compound 6 showed weak cell growth inhibition of A549, HCT116, SK-BR-3, and HepG2 cells.

Chemical constituents of Euonymus alatus

Euonymus alatus, a Chinese folk medicine, has been widely used in traditional medicine for the treatment of tumors and stomachache, wound, and asthma [1, 2], and is also used to regulate qi (bodily energy) and blood circulation, eliminate stagnant blood, and relieve pain [3, 4] for over 2000 years. Up to now, many kinds of compounds have been isolated from this plant, including flavonoids, steroids, triterpenes, diterpenes, and sesquiterpenes [2]. The stems of Euonymus alatus were collected from Kunming, Yunnan Province in China in May 2009. Plant material was identified by Prof. Li-Shan Xie, Kunming Institute of Botany, Chinese Academy of Science. A voucher specimen (No. 200905003) was deposited in the Herbarium of the School of Pharmacy, Second Military Medical University. The dried stems of Euonymus alatus (15 kg) were extracted with 95% ethanol (50 L) at room temperature for five times. The extract was evaporated under vacuo to afford a residue (0.86 kg), which was partitioned with petroleum ether (PE) and EtOAc successively. Both the PE (328 g) and the EtOAc (43 g) extracts were purified by silica gel column chromatography, Sephadex LH-20, ODS, and prep. TLC to obtain compounds 1–21. The compounds were identified by NMR and MS spectrometry and comparison with the literature. All the 21 compounds were isolated from this plant for the first time. Grasshopper ketone (1), C13H20O3, colorless oil. ESI-MS m/z 247 [M + Na] +. 1H NMR (500 MHz, CD3OD, , ppm): 1.14 (3H, s, CH3-12), 1.32 (1H, m, H-4a), 1.36 (6H, s, CH3-11/13, each 3H), 1.37 (1H, m, H-4b), 1.90 (1H, m, H-2a), 2.17 (3H, s, CH3-10), 2.20 (1H, m, H-2b), 4.20 (1H, m, H-3), 5.81 (1H, s, H-8). 13C NMR (125 MHz, CD3OD, , ppm): 37.1 (C-1), 50.0 (C-2), 64.5 (C-3), 49.8 (C-4), 72.5 (C-5), 120.0 (C-6), 201.0 (C-7), 101.2 (C-8), 211.6 (C-9), 26.8 (C-10), 30.9 (C-11), 29.4 (C-12), 32.4 (C-13) [5]. Annuionone D (2), C13H20O3, colorless oil. ESI-MS m/z 247 [M + Na]+. 1H NMR (500 MHz, CDCl3) and 13C NMR (125 MHz, CDCl3) data matched well with those in [6]. 3 -Hydroxy-5 ,6 -epoxy-7-megastimen-9-one (3), C13H20O3, colorless oil. ESI-MS m/z 225 [M + H] +. 1H NMR (500 MHz, CDCl3, , ppm, J/Hz): 0.95 (3H, s, CH3-12), 1.16 (3H, s, CH3-13), 1.17 (3H, s, CH3-11), 1.21 (1H, dd, J = 1.5, 12.0, H-2a), 1.60 (1H, dd, J = 9.0, 12.0, H-2b), 1.62 (1H, dd, J = 7.5, 14.0, H-4a), 2.25 (3H, s, CH3-10), 2.36 (1H, dd, J = 5.0, 14.0, H-4b), 3.88 (1H, m, H-3), 6.26 (1H, d, J = 16.0, H-8), 7.00 (1H, d, J = 16.0, H-7). 13C NMR (125 MHz, CDCl3, , ppm): 35.3 (C-1), 46.8 (C-2), 64.2 (C-3), 40.8 (C-4), 67.4 (C-5), 69.6 (C-6), 142.5 (C-7), 132.8 (C-8), 197.6 (C-9), 28.5 (C-10), 20.0 (C-11), 25.2 (C-12), 29.5 (C-13) [7, 8]. (3S,5R,6R,7E,9S)-3,5,6,9-Tetrahydroxy-7-en-megastigmane (4), C13H24O4, white powder. ESI-MS m/z 267 [M + Na]+. 1H NMR (500 MHz, CD3OD) and 13C NMR (125 MHz, CD3OD) data matched well with those in [9]. 8,9-Dihydro-8,9-dihydroxymegastigmatrienone (5), C13H20O3, colorless oil. ESI-MS m/z 247 [M + Na] +. 1H NMR (500 MHz, CD3OD) and 13C NMR (125 MHz, CD3OD) data matched well with those in [10]. 9-epi-Blumenol B (6), C13H20O3, colorless oil. ESI-MS m/z 249 [M + Na]+. 1H NMR (500 MHz, CD3OD) and 13C NMR (125 MHz, CD3OD) data matched well with those in [11]. Corchoionol C (7), C13H20O3, colorless oil. ESI-MS m/z 247 [M + Na] +. 1H NMR (500 MHz, CD3OD, , ppm, J/Hz): 0.99 (3H, s, CH3-12), 1.02 (3H, s, CH3-13), 1.22 (3H, d, J = 6.5, CH3-10), 1.91 (3H, s, CH3-11), 2.14 (1H, d, J = 17.0, H-2a),

Pseudolarenone, an unusual nortriterpenoid lactone with a fused 5/11/5/6/5 ring system featuring an unprecedented bicyclo[8.2.1]tridecane core from Pseudolarix amabilis

A phytochemical investigation of the cone of Pseudolarix amabilis led to the isolation of pseudolarenone (), a structurally novel pentacyclic (5/11/5/6/5) nortriterpenoid lactone with an unprecedented carbon skeleton featuring a unique bicyclo[8.2.1]tridecane core. Its structure and absolute configurations were elucidated by spectroscopic analysis and single crystal X-ray diffraction (CuK(α)).

Vlasouliolides A-D, four rare C17/C15 sesquiterpene lactone dimers with potential anti-inflammatory activity from Vladimiria souliei.

Vlasouliolides A-D (1–4), four rare sesquiterpene lactone dimers, were isolated from Vladimiria souliei. The common structural characteristic of 1–4 is the C32 skeleton comprising two sesquiterpene lactone units linked by a C11-C13′ single bond with one acetyl connected to the C-13 position of one of the two sesquiterpene lactone units. The stereochemistries of 1–4 were assigned by a combination of NOESY correlations and Cu-Κα X-ray crystallographic analyses. Compounds 1–4 strongly inhibited the production of NO in LPS-stimulated RAW 264.7 cells. Furthermore, 1 and 2 inhibited the activation of NF-κB in LPS-induced 293T cells.

Chemical Constituents of Celastrus angulatus

Natural products from medicinal plants usually have many biological activities to help treat many diseases [1–3]. Celastrus angulatus is a Chinese folk medicine whose root, barks, and leaves have long been used to kill harmful insects and also to treat furuncles and remove heat [4, 5]. According to the previous studies, many kinds of compounds have been isolated from this plant, such as flavonoids, steroids, triterpenes, diterpenes, and sesquiterpenes [6–9]. The stems of Celastrus angulatus were collected from Kunming, Yunnan Province in China in December 2009. Plant material was identified by Prof. Li-Shan Xie, Kunming Institute of Botany, Chinese Academy of Science. A voucher specimen (No. 20091209) was deposited in the Herbarium of the School of Pharmacy, Second Military Medical University. The air-dried stems of Celastrus angulatus (40 kg) were chopped and the thermal circumfluence extracted with ethanol (75%) three times for 3 h. The extract was concentrated under reduced pressure, then diluted with water and partitioned successively with petroleum ether (PE) and EtOAc. Both PE (150 g) and EtOAc (950 g) extracts were subjected to silica gel column chromatography, Sephadex LH-20, preparative TLC, and ODS column chromatography to obtain compounds 1–21. The compounds were identified by NMR and MS spectrometry and comparison with literature data. All 21 compounds were isolated from this plant for the first time. Epigallocatechin (1), C15H14O7, white powder. ESI-MS m/z 329 [M + Na] + [10]. (–)-Epiafzelechin (2), C15H14O5, yellow powder. ESI-MS m/z 297 [M + Na]+. 1H NMR (500 MHz, CD3OD, , ppm, J/Hz): 2.77 (1H, dd, J = 4.5, 16.3, H-4a), 2.91 (1H, dd, J = 4.0, 16.3, H-4b), 4.21 (1H, s, H-3), 4.90 (1H, s, H-2), 5.95 (1H, d, J = 2.0, H-8), 5.97 (1H, d, J = 2.0, H-6), 7.35 (2H, d, J = 8.3, H-3 , 5 ), 6.81 (2H, d, J = 8.3, H-2 , 6 ). 13C NMR (125 MHz, CD3OD, , ppm): 80.1 (C-2), 67.6 (C-3), 29.5 (C-4), 158.2 (C-5), 96.5 (C-6), 158.1 (C-7), 96.0 (C-8), 157.8 (C-9), 100.2 (C-10), 131.8 (C-1 ), 129.3 (C-2 ), 115.9 (C-3 ), 157.6 (C-4 ), 115.9 (C-5 ), 129.3 (C-6 ) [11]. Quercetin (3), C15H12O7, yellow powder. ESI-MS m/z 327 [M + Na]+ [12]. Ouratea Catechin (4), C16H16O7, yellow powder. ESI-MS m/z 343 [M + Na] +. 1H NMR (500 MHz, CD3OD, , ppm, J/Hz): 2.50 (1H, dd, J = 6.5, 16.3, H-4a), 2.78 (1H, dd, J = 7.0, 16.5, H-4b), 3.95 (1H, m, H-3), 4.55 (1H, d, J = 7.0, H-2), 5.86 (1H, d, J = 2.2, H-8), 5.92 (1H, d, J = 2.2, H-6), 6.40 (1H, s, H-2 ), 6.40 (1H, s, H-6 ). 13C NMR (125 MHz, CD3OD, , ppm): 82.8 (C-2), 68.8 (C-3), 28.2 (C-4), 156.9 (C-5), 96.5 (C-6), 157.8 (C-7), 95.7 (C-8), 158.0 (C-9), 100.8 (C-10), 136.6 (C-1 ), 107.6 (C-2 ), 151.8 (C-3 ), 136.9 (C-4 ), 151.8 (C-5 ), 107.6 (C-6 ), 60.9 (4 -OCH3) [13]. Furreginol (5), C20H30O, white powder. ESI-MS m/z 309 [M + Na] +. 1H NMR (500 MHz, CD3OD, , ppm, J/Hz): 0.96 (3H, s, CH3-16), 0.99 (3H, s, CH3-15), 1.21 (3H, s, CH3-17), 1.27 (3H, d, J = 6.9, CH3-19), 1.29 (3H, d, J = 6.9, CH3-20), 1.36 (1H, m, H-1a), 1.41 (1H, dd, J = 2.4, 12.8, H-5b), 1.52 (1H, m, H-6a), 1.62 (1H, m, H-2a), 1.70 (1H, m, H-3a), 1.77 (1H, m, H-2b), 1.90 (1H, m, H-3b), 1.99 (1H, m, H-1b), 2.17 (1H, m, H-6b), 2.85 (2H, m, CH2-7), 3.18 (1H, quin, J = 6.8 (4), H-18), 6.67 (1H, s, H-14), 6.89 (1H, s, H-11). 13C NMR (125 MHz, CD3OD, , ppm): 38.8 (C-1), 19.2 (C-2), 41.7 (C-3), 33.4 (C-4), 50.3 (C-5), 19.3 (C-6), 29.7 (C-7), 127.3 (C-8), 148.6 (C-9), 37.4 (C-10), 111.0 (C-11), 150.6 (C-12), 131.4 (C-13), 126.6 (C-14), 33.3 (C-15), 21.6 (C-16), 24.8 (C-17), 26.7 (C-18), 22.6 (C-19), 22.7 (C-20) [14].

Valeriadimers A–C, three sesquiterpenoid dimers from valeriana officinalis var. latifolia

Valeriadimer A (1), formed by a C–C (4-1′) bond between a bicyclogermacrane nor-sesquiterpene moiety and a maaliane nor-sesquiterpene moiety, together with two further sesquiterpenoid dimers, valeriadimers B and C (2, 3) were isolated from the root of Valeriana officinalis var. latifolia. Their structures were elucidated by extensive analysis of spectroscopic data and confirmed by Cu-Kα X-ray diffraction experiment.