Swieteliacates S-U, phragmalin limonoids, from the leaves of Swietenia macrophylla.

Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.

Limonoids from Swietenia macrophylla and their antitumor activities in A375 human malignant melanoma cells.

Swietelinins A - C (1-3) and swieteliacates F - R (4-16), sixteen new limonoids and 18 known limonoids (17-34) were isolated from Swietenia macrophylla. The absolute configurations of these compounds were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. Swieteliacate J (10) is the first limonoid possessing an unusual 8ß, 9ß-epoxy ring system. All of the compounds were tested for cytotoxicity against four human tumor cell lines (SMMC-7721, SW620, A549, and A375). Compounds 10, 11, and 19 exhibited selectively moderate cytotoxicity against four tumor cell lines, especially 19 exhibited significant cytotoxic effects against A375 with IC50 an value of 9.8 µM and was more active than the positive control, dacarbazine with an IC50 value of 22.4 µM. Compound 19 effectively induced apoptosis of A375, which was associated with G2/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 19 significantly induced A375 cell apoptosis in a dose-dependent manner.

Cloning and Functional Characterization of Two Germacrene A Oxidases Isolated from Xanthium sibiricum.

Sesquiterpene lactones (STLs) from the cocklebur Xanthium sibiricum exhibit significant anti-tumor activity. Although germacrene A oxidase (GAO), which catalyzes the production of Germacrene A acid (GAA) from germacrene A, an important precursor of germacrene-type STLs, has been reported, the remaining GAOs corresponding to various STLs' biosynthesis pathways remain unidentified. In this study, 68,199 unigenes were studied in a de novo transcriptome assembly of X. sibiricum fruits. By comparison with previously published GAO sequences, two candidate X. sibiricum GAO gene sequences, XsGAO1 (1467 bp) and XsGAO2 (1527 bp), were identified, cloned, and predicted to encode 488 and 508 amino acids, respectively. Their protein structure, motifs, sequence similarity, and phylogenetic position were similar to those of other GAO proteins. They were most strongly expressed in fruits, according to a quantitative real-time polymerase chain reaction (qRT-PCR), and both XsGAO proteins were localized in the mitochondria of tobacco leaf epidermal cells. The two XsGAO genes were cloned into the expression vector for eukaryotic expression in Saccharomyces cerevisiae, and the enzyme reaction products were detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods. The results indicated that both XsGAO1 and XsGAO2 catalyzed the two-step conversion of germacrene A (GA) to GAA, meaning they are unlike classical GAO enzymes, which catalyze a three-step conversion of GA to GAA. This cloning and functional study of two GAO genes from X. sibiricum provides a useful basis for further elucidation of the STL biosynthesis pathway in X. sibiricum.

[Germacrene-derived sesquiterpene lactones:opportunities and challenges for biosynthesis].

Sesquiterpene lactones are a kind of widely distributed natural organic compounds with anti-tumor, anti-malarial and other significant biological activities. Based on their carbocylic skeletons, sesquiterpene lactones are classified into germacranolide, guaia-nolide, xanthanolide, pseudo-guaianolide, elemonolide and eudesmanolide, etc. In recent years, with the development of various omics and synthetic biology technologies, the biosynthetic pathways of sesquiterpene lactone compounds of different structural types have gradually been resolved. Among them, the researches on germacrene-derived sesquiterpene lactones are relatively more than others. Therefore, this article focused on the germacrene-derived sesquiterpene lactone biosynthesis pathways and their key enzyme genes, which can lay the foundation for in-depth analysis of sesquiterpene lactone biosynthetic pathways, functional gene mining and heterologous synthesis of active ingredients.

[Review of chemical composition, pharmacological effects, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma and prediction of its Q-markers].

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.

Kalshiolin A, new lignan from Kalimeris shimadai.

The Asian plant Kalimeris shimadai has been used as food and ethnologic medicine for over a thousand years. In this study, we isolated and identified one new lignan, kalshiolin A (1), and 12 known lignans (2-13). The structures were characterized by the comprehensive analyses of spectroscopic data (HR-ESI-MS, IR, 1D, and 2D-NMR) and the absolute configuration of 1 was determined from ECD calculations. The new compound 1 was also screened for cytotoxic activity but did not show significant potency (IC50 35.9-43.3 µM) against A549, MDA-MB-231, MCF7, KB, and KB-VIN cell lines.

Kalshinoids A-F, Anti-inflammatory Sesquiterpenes from Kalimeris shimadae.

In a study of the potential anti-inflammatory constituents from Kalimeris shimadae, six new sesquiterpenes, kalshinoids A-F (1-6), together with 21 known compounds (7-27), were isolated. The structures and absolute configurations of the new compounds were discerned from extensive spectroscopic analysis, and the absolute configurations of kalshinoids A, B, E, and F were established by ECD calculations. Furthermore, the identified compounds were tested for anti-inflammatory activity as assessed by inhibition of tumor necrosis factor-alpha (TNF-α) in THP-1 cells. Three sesquiterpenes [kalshinoid F, 4(15)-eudesmen-1ß,7,11-triol, and 4α,10α,11-trihydroxy-1ßH,5ßH-guai-7(8)-ene] reduced levels of TNF-α in lipopolysaccharide-stimulated THP-1 cells in a concentration-dependent manner and were more potent than dexamethasone. These natural sesquiterpenes merit further investigation as possible anti-inflammatory agents.

Analysis of Chuanxiong Rhizoma substrate on production of ligustrazine in endophytic Bacillus subtilis by ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Ligustrazine was the active ingredient of the traditional Chinese medicine Chuanxiong Rhizoma. However, the content of ligustrazine is very low. We proposed a hypothesis that ligustrazine was produced by the mutual effects between endophytic Bacillus subtilis and the Ligusticum chuanxiong Hort. This study aimed to explore whether the endophytic B. subtilis LB5 could make use of Chuanxiong Rhizoma fermentation matrix to produce ligustrazine and clarify the mechanisms of action preliminarily. Ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry analysis showed the content of ligustrazine in Chuanxiong Rhizoma was below the detection limit (0.1 ng/mL), while B. subtilis LB5 produced ligustrazine at the yield of 1.0268 mg/mL in the Chuanxiong Rhizoma-ammonium sulfate fermentation medium. In the fermented matrix, the reducing sugar had a significant reduction from 12.034 to 2.424 mg/mL, and rough protein content increased from 2.239 to 4.361 mg/mL. Acetoin, the biosynthetic precursor of ligustrazine, was generated in the Chuanxiong Rhizoma-Ammonium sulfate (151.2 mg/mL) fermentation medium. This result showed that the endophytic bacteria B. subtilis LB5 metabolized Chuanxiong Rhizoma via secreted protein to consume the sugar in Chuanxiong Rhizoma to produce a considerable amount of ligustrazine. Collectively, our preliminary research suggested that ligustrazine was the interaction product of endophyte, but not the secondary metabolite of Chuanxiong Rhizoma itself.

Anti-inflammatory lupane triterpenoids from Menyanthes trifoliata.

A new lupane triterpenoid, 23-O-trans-feruloylcylicodiscic acid (1), as well as four known analogues (2‒5), was isolated from the EtOAc fraction of Menyanthes trefoliata. The structure of compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 2D NMR data. The structures of the known compounds were established by comparison of their spectroscopic data with that in the literature. Compounds 1, 2, and 4 exhibited certain anti-NO production activities.

Chemical Structures and Biological Activities of Limonoids from the Genus Swietenia (Meliaceae).

Swietenia is a genus in the plant family Meliaceae. This genus contains seven to eight known species, found in the tropical and subtropical regions of the Americas and West Africa. Thus far, more than 160 limonoids have been isolated from four species of the genus Swietenia. Limonoids are rich in structure type and biological activity, and these compounds are the main active components in the Swietenia species. This paper will give a comprehensive overview of the recent phytochemical and pharmacological research on the terpenes from Swietenia plants and encourage further drug discovery research.

[Chemical constituents from fresh tubers of Dioscorea bulbifera].

Eighteen compounds were isolated from the 95% ethanol extract of fresh tubers of Dioscorea bulbifera by column chromatography over silica gel,Sephadex LH-20, and ODS. Their structures were elucidated by spectroscopic data analysis as 6-hydroxy-2,10,10-trimethoxy-anthracen-9-one(1), diosgenin (2), stigmasterol(3), 3, 7-dimethoxy-5, 3', 4'-trihydroxyflavone(4), 2, 7-dihydroxy-3, 4-dimethoxyphenanthrene(5), 3, 7-dihydroxy-2, 4-dimethoxy phenanthrene(6), 2, 7-dihydroxy-4-methoxyphenanthrene (7), 2, 7-dihydroxy-3, 4-dimethoxy-9, 10-dihydroxy phenanthrene(8), azelaic acid (9), 8-epidiosbulbin E acetate (10), 1, 7-bis-(4-hydroxyphenyl)-4E, 6E-heptadien-3-one(11), diosbulbin B(12), pentacosanoic acid 2', 3'-dihydroxypropyl ester(13), 2, 7-dihydroxy-4-methoxy-9, 10-dihydroxy-phenanthrene (14), 1, 7-bis-(4-hydroxyphenyl)-1E, 4E, 6E-heptatrien-3-one (15), 6-ethoxy-1H-pyrimidine-2, 4-dione (16), 3, 5, 4'-trihydroxy-bibenzyl (17), and diosbulbin F (18). Compound 1 is a new compound, and compounds 7, 9, 13, and 16 were isolated from this plant for the first time.

[Studies on Chemical Constituents from the Fruit of Swietenia macrophylla].

Objective: To study the chemical constituents from the fruit of Swietenia macrophylla. Methods: The chemical constituents were extracted and isolated by silica gel, Sephadex LH-20. The chemical structures of components were further elucidated by the physicochemical characters and MS,NMR spectral data. Results: 17 compounds were isolated and identified as swietenine( 1),swietenine acetate( 2),febrifugine( 3),khayasin T( 4),3-O-tigloyl-6-O-acetylswietenolide( 5),3-O-tigloylswietenolide( 6),3,6-O,O-diacetylswietenolide( 7),fissinolide( 8),3-O-acetylswietenolide( 9), proceranolide( 10),swietenolide( 11),swietemahonin E( 12),swietemahonin F( 13),7-deacetoxy-7-oxogedunin( 14),secomahoganin( 15),altissimanin B( 16),ororatone( 17). Conclusion: Compounds3,5,8 ~ 10,16,17 are isolated from this plant for the first time.

[Study on Chemical Constituents of Kalimeris indica].

OBJECTIVE: To study the chemical constituents from the active fractions of Kalimeris indica. METHODS: The chemical constituents were extracted of different concentrations and isolated by silica gel, Sephadex LH-20 column and preparative HPLC. The chemical structures were further elucidated by the physicochemical characters, MS and NMR spectral data. RESULTS: Fourteen compounds were isolated and identified as α-spinasterol(1), dibutylphthalate (2), (22E,24R)-5α,8α-epidioxy-ergosta-6,22-dien-3ß-ol(3), oleanolic acid(4), coniferyl alcohol(5), umbelliferone(6), syringaresinol(7), 15-oxo-14,16H-strictic acid(8), lariciresinol(9), (Z)-3,7,11-trimethyl-1,6-dodecadien-3,10,11-triol(10), neoechinulin A(11), pinoresinol(12), 4-allyl-3,5-dimethoxyphenol(13), and 3,4,5-tri-methoxyacetophenone (14). CONCLUSION: Except compound 1, the other compounds are isolated from this genus for the first time.

[Study on chemical constituents from leaf of Bombax ceiba (II)].

OBJECTIVE: To study the chemical constituents from the leaf of Bombax ceiba. METHODS: The compounds were isolated and purified with silica gel and Sephadex LH-20 column chromatography. Their structures were determined on the basis of physicochemical properties and spectroscopic analysis. RESULTS: Eleven compounds were isolated and identified as taraxeryl acetate (1), squalene (2), taraxerone (3), beta-sitosterol palmitate (4), taraxerol (5), 4-methyl stigmast-7-en-3-ol (6), 1H-indole-3-carboxylic acid (7), 6-O-palmitoylsitosteryl-D-glucoside (8), 12beta-hydroxyl-pregnane-4, 16-diene-3, 20-dione (9), loliolide (10) and 5-(hydroxymethyl) furfural (11). CONCLUSION: All the compounds are isolated from this genus for the first time.

[Study on chemical constituents from crop pathogenic fungus active fraction of Wisteria sinensis tumor].

OBJECTIVE: To study the chemical constituents from the crop pathogenic fungus active fraction of Wisteria sinensis tumor. METHODS: The chemical constituents were extracted of different concentrations and isolated by silica gel and Sephadex LH-20 column. The chemical structures of components were further elucidated by the physicochemical characters and MS, NMR spectral data. RESULTS: Ten compounds were isolated and identified as dibutyl phthalate (1), diacetonealcohol (2), pinoresinol (3), stellasterol (4), oleanolic acid (5), olean-12-ene-3-oxo-22,24-diol (6), betulinic acid (7), 2',4',4-hydroxy-chalcone (8), avicularin (9) and quercetin-3-O-ß-D-glucopyranoside (10). CONCLUSION: All the compounds are isolated from the genus for the first time.

Discovery of ent-labdane derivatives from Andrographis paniculata and their anti-inflammatory activity.

The plant Andrographis paniculata has a long history of cultivation in Southeast Asia, especially its extensive anti-inflammatory activity, and the famous natural antibiotic andrographolide comes from this plant. In China, A. paniculata, as the main crop, has become a major source of traditional Chinese medicine (TCM) for the clinical treatment of inflammation. To further explore the diverse diterpene lactones with better anti-inflammatory activity from A. paniculata, twenty-one ent-labdanes, including six undescribed compounds (andropanilides D-I), were isolated. Their structures with absolute configurations were thoroughly determined by comprehensive NMR spectroscopic data, HRESIMS analysis and quantum chemical calculations. All isolated compounds were evaluated for anti-inflammatory activities based on the Griess method. Meanwhile, after structure-activity relationships analysis, the anti-inflammatory activity of andropanilide D (1) (IC50 = 2.31 µM) was found to be better than that of the positive control drug (dexamethasone, IC50 = 6.52 µM) and andrographolide (IC50 = 5.89 µM). Further mechanisms of activity indicated that andropanilide D significantly reduced the secretion of TNF-α, IL-6 and IL-1ß and downregulated the protein expression of COX-2 and iNOS in LPS-induced RAW264.7 macrophages in a concentration-dependent manner based on Western blot and ELISA experiments. In conclusion, andropanilide D possesses potential medicinal value for the treatment of inflammation and further expands the material basis of the anti-inflammatory effect of A. paniculata.

Two new acorane-type sesquiterpenoids from an endophytic Trichoderma harzianum associated with Paeonia lactiflora Pall.

Two new acorane-type sesquiterpenoids, harzianes A and B (1 and 2), together with two known cyclonerodiol-type sesquiterpenoids (3-4) and four known sterols (5-8) were isolated from the endophytic Trichoderma harzianum, associated with the medicinal plant Paeonia lactiflora Pall. Compounds 1 and 2 were identified as a pair of heterotropic isomers by spectroscopic analysis (HR-ESI-MS, 1D and 2D NMR), and their absolute configurations were determined by ECD calculations. All compounds were tested for anti-inflammatory activity, however, none demonstrated such activity.

[Chemical constituents of Gentiana rhodantha].

OBJECTIVE: To determine the chemical constituents of Gentiana rhodantha. METHOD: To isolate the constituents, column chromatography over silica gel, MCI, Sephadex LH-20 and C18 reverse-phased silica gel were used. Spectroscopic methods were used to elucidate the structures of the isolated compounds. RESULT: Sixteen compounds were isolated and elucidated as ten phonemic compounds, namely 1,3,7,8-tetrahydroxylxanthone (1), rhodanthenone D (2), 1,3,6,7-tetrahydroxylxanthone (3), 1,3,7-trihydroxy-4,8-dimethoxyxanthone (4), quercetin (5), isoorientin (6), mangiferin (7), norswertianolin (8), gallic acid ethyl ester (9) and salicylic acid (10), and six triterpenes including alpha-amyrin (11), erythrodiol 3-O-palmitate (12), ursolic aldehyde (13), uvaol 3-O-acetyl (14), ursolic acid (15) and 2alpha-hydroxyursolic acid (16). CONCLUSION: Compounds 4-6, 8, 10-12, 15 and 16 were isolated from this plant for the first time. Compounds 1 and 3 were obtained firstly from the genus Gentiana and compounds 9, 13-14 were firstly from the family Gentianaceae.

[Phenolic derivatives from Wisteria sinensis sweet caulis].

OBJECTIVE: To study the phenolic derivatives from Wisteria sinensis. METHODS: From the petroleum ether extraction of 95% alcohol permeating extraction, 12 compounds were isolated and purified with silica gel and Sephadex LH-20 column chromatography. Their structures were determined on the basis of physicochemical properties and spectroscopic analysis. RESULTS: They were identified as formononetin (1), (3S)-vestitol (2), (6aS, 11aS)-medicarpin (3), (-+/-) isoduartin (4), (3S)-7,1'-dihydroxy-8,3'-dimethoxyisoflavan (5), isosakuranetin (6), p-hydroxy-benzaldehyde (7), 11b-hydroxy-11b, 1-dihydromedicarpin (8), 3-hydroxy-medicarpin (9), syringaresinol (10), 5-hydroxy-7-methoxychromone (11), vanillin (12). CONCLUSION: All the compounds are isolated from this plant for the first time.

Tricholosterols A-D, four new ergosterol derivatives from the mushroom Tricholoma terreum.

Four ergosterol derivatives, named tricholosterols A-D (1-4), have been isolated from the fruiting bodies of Tricholoma terreum. Their chemical structures have been determined using a combination of spectroscopic analysis as well as computational methods. Compound 1 possesses a rare D-ring opening ergosterol skeleton, while compounds 2-4 are rare degraded ergosterols. Compounds 1 and 4 exhibited moderate inhibitory activity against NO production with IC50 values of 27.6 and 31.8 µM, respectively. This is the first report of steroids from T. terreum.