The chemical constituents from the stems and leaves of Clausena excavata were isolated and purified by column chromatography with silica gel, ODS, Sephadex LH-20 and RP-HPLC. The chemical structures of the isolated compounds were identified on the basis of physicochemical properties, spectroscopic analysis, as well as the comparisons with the data reported in literature. Nineteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. excavata, which were identified as methyl orsellinate(1), syringaresinol(2), lenisin A(3), scopoletin(4), osthenol(5), N-benzoyltyrarnine methyl ether(6), N-p-coumaroyltyramine(7), aurantiamide acetate(8), 1H-indole-3-carboxaldehyde(9), furostifoline(10), clausenalansine E(11), 3-formylcarbazole(12), clausine L(13), clausine E(14), methyl carbazole-3-carboxylate(15), glycosinin(16), murrayafoline A(17), clausine H(18) and 2,7-dihydroxy-3-formyl-1-(3'-methyl-2'-butenyl)carbazole(19). Among these isolated compounds, compounds 1-11 were isolated from C. excavata for the first time, and compounds 1, 2 and 10 were isolated from the genus Clausena for the first time. In addition, this study evaluated the anti-rheumatoid arthritis activities of compounds 1-19 by measuring their anti-proliferative effects on synoviocytes in vitro according to MTS method. Compounds 10-19 displayed remarkable anti-rheumatoid arthritis activities, which exhibited the inhibitory effects on the proliferation of MH7 A synovial fibroblast cells with the IC_(50) values ranging from(27.63±0.18) to(235.67±2.16) μmol·L~(-1).
Cell Proliferation ; Chromatography, Reverse-Phase ; Clausena ; Plant Leaves ; Synoviocytes

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Clausena ; chemistry ; Doxorubicin ; Humans ; Phytochemicals ; isolation & purification ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry

The present study carried out a phytochemical investigation of the methanol extract of the branches and leaves of Clausena lansium and afforded nine carbazole alkaloids (compounds 1-9) including two new carbazole alkaloids, claulansiums A and B (compounds 1 and 2). The new compounds were elucidated on the basis of extensive spectroscopic data (MS, NMR, IR, and UV) and the known compounds were identified by comparing spectroscopic data with those reported in literature. All the isolated compounds were tested for their cytotoxic activity against A549 and Hela cancer cell lines. Our results showed that compounds 2-6 exhibited varying degrees of cytotoxicity to cancer cells, with IC values ranging from 8.67 to 98.89 μmol·L.
A549 Cells ; Alkaloids ; chemistry ; isolation & purification ; toxicity ; Antineoplastic Agents ; chemistry ; isolation & purification ; toxicity ; Carbazoles ; chemistry ; isolation & purification ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Clausena ; chemistry ; HeLa Cells ; Humans ; Molecular Structure ; Plant Extracts ; chemistry ; toxicity ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena (family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.
Alkaloids ; chemistry ; pharmacology ; therapeutic use ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Carbazoles ; chemistry ; pharmacology ; therapeutic use ; Cell Cycle Checkpoints ; drug effects ; Clausena ; chemistry ; Coumarins ; chemistry ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Plants, Medicinal ; chemistry

The first study on chemical constituents and biological activities of Clausena lansium (Lour.) Skeels (Rutaceae) growing in Vietnam has been done. Phytochemical investigation of n-hexane extract led to the isolation of five compounds: dihydroindicolactone (1), 8-geranyloxy psoralen (2), imperatorin (3), heraclenol (4) and indicolactone (5), in which this is the first report on the presence of dihydroindicolactone (1). Their structures were elucidated based on LC/MS/NMR hyphenated techniques as well as comparison with those of literature data. The n-hexane extract and its subfractions, ethanol 95% extract and several isolated compounds were evaluated for antifungal activity.
Clausena* ; Ethanol ; Ficusin ; Vietnam

A new phenethanol, (2'R)-4-(2', 3'-dihydroxy-3'-methyl-butanoxy)-phenethanol (1), along with other eleven known benzene derivatives (2-12) were isolated from the roots, stems and leaves of Clausena excavata (Rutaceae). Compounds 3 and 4 are new natural products, and compounds 5-8, 10-12 were isolated from C. excavata for the first time. Their structures were elucidated on the basis of MS, 1D and 2D NMR spectroscopic analyses including HSQC, COSY and HMBC experiments. 1 was tested for its cytotoxicities against A549, HeLa and BGC-823 cancer cell lines, and antimicrobial activities against Candida albicans and Staphylococcus aureus. The results showed that 1 did not exhibit cytotoxic and antimicrobial activities.
Benzene Derivatives ; chemistry ; Candida albicans ; drug effects ; Cell Line, Tumor ; Clausena ; chemistry ; HeLa Cells ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Staphylococcus aureus ; drug effects

To investigate monoterpenes and sesquiterpenes of the stems and leaves of Clausena excavata, an AcOEt fraction of the methanol extract was subjected on column chromatographies including silica gel and RP-18, as well as preparative HPLC. The structures of compounds isolated were identified on the basis of spectroscopic data as excamonoterpene (1), (6R, 9S)-9, 10-dihydroxy-4-megastigmen-3-one (2), (3R, 6R, 7E) -3-hydroxy-4, 7-megastigmadien-9-one (3), (3S) -3-hydroxy-7, 8-dihydro-beta-ionone (4), (3S, 5R, 6S) -3-hydroxy-5,6-epoxy-beta-ionone (5), (6R, 9R) -9-hydroxy-4-megastigmen-3-one (6), (3S, SR) -dihydroxy-6, 7-megstigmadien-9-one(7), (-)-loliolide(8), caryolane-1, 9alpha-diol(9) and 2, 6-dihydroxyhumula-3 (12), 7 (13), 9(E)-triene (10), were isolated from the stems and leaves of C. excavata. Compound 1 is a new monoterpene, named as excamonoterpene. Compounds 2-10 were isolated from this plant for the first time.
Chromatography, High Pressure Liquid ; methods ; Clausena ; chemistry ; Magnetic Resonance Spectroscopy ; Methanol ; chemistry ; Molecular Structure ; Monoterpenes ; analysis ; chemistry ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Sesquiterpenes ; analysis ; chemistry ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo study the chemical constituents of the leaf of Clausena lansium (Lour.) Skeels.

METHODThe compounds were isolated by various chromatographic techniques and their structures were elucidated by their physicochemical properties and the analysis of their spectroscopic data.

RESULTSeven compounds were isolated and identified as corchoionoside C (1), 1'-O-beta-D-glucopyranosyl (2R,3S)-3-hydroxynodakenetin (2), quercetin-3-O-robinobioside (3), rutin (4), quercetin-3-O-scillabioside (5), keampferol-3-O-alpha-L-rhamnopyranosyl(1-->2) [alpha-L-rhamnopyranosyl(1-->6)]-beta-D-glucopyranoside (6), mauritianin (7).

CONCLUSIONCompounds 1-7 were isolated from the genus Clausena for the first time.

Chemical Phenomena ; Chromatography, High Pressure Liquid ; Clausena ; chemistry ; Organic Chemicals ; analysis ; chemistry

This study is to investigate the protective effect of (-) clausenamide against the neurotoxicity of okadaic acid in SH-SY5Y cell line, and injection beta-amyloid peptide25-35 (Abeta25-35) to the cerebral ventricle in ovariectomy (OVX) rats. MTT assay, LDH assay, and Hoechst 33258 staining were used to detect the effect of (-) clausenamide on the toxicity of okadaic acid in SH-SY5Y cell line. The animal model was induced by ovariectomized and injection of Abeta25-35 in the cerebroventricle of rats. The effect of (-) clausenamide on learning and memory deficiency was observed by step-through test. Electron microscope, Nissl body staining, and HE staining were used to examine the morphological changes in hippocampus and cerebral cortex neurons. Pretreatment of (-) clausenamide and LiCl decreased the rate of cell death from MTT, LDH release, and apoptosis from Hoechst 33258 staining in SH-SY5Y cell line. The step-through tests showed (-) clausenamide could improve the ability of learning and memory. The Nissl body staining and HE staining experiments also showed the neuroprotective effects of (-) clausenamide on the neurons of hippocampus and cerebral cortex. (-) Clausenamide has the protective effects against the neurotoxicity induced by okadaic acid and Abeta25-35.
Amyloid beta-Peptides ; antagonists & inhibitors ; toxicity ; Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cerebral Cortex ; cytology ; Clausena ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Hippocampus ; cytology ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Lactams ; isolation & purification ; pharmacology ; Learning ; drug effects ; Lignans ; isolation & purification ; pharmacology ; Memory Disorders ; physiopathology ; Neuroblastoma ; metabolism ; pathology ; Neurons ; drug effects ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Okadaic Acid ; antagonists & inhibitors ; toxicity ; Ovariectomy ; Peptide Fragments ; antagonists & inhibitors ; toxicity ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

AIMTo study the excretion of (-)-clausenamide in rats.

METHODSThe urine, feces and bile were collected at predetermined time points after (-)-clausenamide was orally administrated to 6 rats (30 mg x kg(-1)). The concentrations of (-)-clausenamide and its metabolite 6-OH-(-)-clausnamide were determined by HPLC-MS/MS method using glipzide as the internal reference, and the accumulative excretion amount of (-)-clausenamide and 6-OH-(-)-clausenamide was calculated in the urine, feces and bile, separately.

RESULTS(-)-Clausenamide was recovered mostly (44%) from feces in 112 hours, 7.1% was found from urine in 120 hours and 0.013% was detected from bile in 24 hours. The accumulative excretions of 6-OH-(-)-clausenamide were 0.92% , 0.46% and 0.0003% of the administered dose from feces, urine and bile, respectively.

CONCLUSIONThe major amount of (-)-clausenamide was recovered from feces after (-)-clausenamide was orally administrated to rats (30 mg kg(-1)).

Administration, Oral ; Animals ; Bile ; metabolism ; Chromatography, High Pressure Liquid ; Clausena ; chemistry ; Feces ; chemistry ; Female ; Lactams ; chemistry ; pharmacokinetics ; urine ; Lignans ; chemistry ; pharmacokinetics ; urine ; Male ; Mass Spectrometry ; Neuroprotective Agents ; administration & dosage ; pharmacokinetics ; urine ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Stereoisomerism