Triterpenoids of Chrysosplenium carnosum

A phytochemical study of the ethanolic extract of Chrysosplenium carnosum Hook. f. et Thoms. led to the isolation of two new oleanane-type triterpenoids, 6β-hydroxy-3-oxoolean-12-en-27-oic acid (1) and 3β, 21α-dihydroxyolean-12-en-27-oic acid (2), along with fourteen known compounds (3–16), all of which were isolated from this plant for the first time. The structures of these compounds were established on the basis of spectroscopic methods. Compounds 1–4 were evaluated for their in vitro anti-tumor activities on B16F10, SP2/0 and Hep-G2 cells lines. Compounds 1, 3 and 4 exhibited strong inhibitory activity against B16F10 and SP2/0 cells' growth, compared with moderate cytotoxic activity against Hep-G2 cells. However, compound 2 showed to be inactive against these tumor cells.     

The biological activities of cardenolide triglycosides from stems, twigs, and leaves of Nerium oleander

Sixteen cardenolide triglycosides (1?C16) were isolated from stems, twigs, and leaves of Nerium oleander. Among them, 3??-O-(4-O-gentiobiosyl-d-diginosyl)-7??,8-epoxy-14-hydroxy-5??,14??-card-20(22)-enolide, named cardenolide B-3 (16), was isolated from natural sources for the first time. The in vitro anti-inflammatory activities of compounds 1?C16 were examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1). Compounds 1?C5 were active at an IC50 value of less than 7 ??M. The cytotoxic activity of isolated compounds was evaluated against three human cell lines: normal human fibroblast cells (W-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 1?C5 were active toward WI-38 cells; compounds 1, 3, and 5 were active toward VA-13 cells; and compounds 1?C5 were active toward HepG2 cells at IC₅₀ values of less than 10 ??M. The multidrug-resistant (MDR) cancer-reversal activity of compounds 1?C16 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 13 and 14 showed significant effects on calcein accumulation.     

Coniochaetones E–I,new 4H-chromen-4-one derivatives from the Cordyceps-colonizing fungus Fimetariella sp.

Five new 4H-chromen-4-one derivatives coniochaetones E–I (1–5), along with the known compounds coniochaetones B (6) and A (7) have been isolated from solid cultures of the Cordyceps-colonizing fungus Fimetariella sp. Their structures were elucidated primarily by NMR spectroscopy and the absolute configurations of compounds 1–3 were assigned using the modified Mosher's method. Compound 4 showed weak cytotoxic activity against HeLa cells with IC₅₀ values of 72.8 μM. The co-isolated known compound 6 showed modest inhibitory effects against Aspergilus fumigates, Fusarium oxysporum and Fusarium nivale.     

Biflavanones with anti-proliferative activity against eight human solid tumor cell lines from Stellera chamaejasme

Six 3,3″-biflavanones, including a new compound isochamaejasmenin C (1), were isolated from EtOH extracts of the roots of Stellera chamaejasme L. Their structures were elucidated on the basis of spectroscopic methods, including HR-ESI-MS and 2D NMR techniques. The absolute configurations on 2, 3, 3″, and 2″ of compounds 1, 3, and 6, which represent three geometry types of these compounds, were determined by TDDFT quantum chemical calculations of their ECD spectra. All compounds were evaluated for their cytotoxicities against eight human solid tumor cell lines and compounds 2, 4, and 6 showed strong anti-proliferative effects against all these cell lines with IC₅₀ values ranging from 1.08 to 15.97 μM, which were in the same range as the positive control paclitaxel.     

Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica

Fourteen sterols (1–14), including two new sterols, trihydroxysitosterol (2) and 5α,6β,7α-7α-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L. The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay. Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC₅₀ of 5.10 μmol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4.42.     

Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis

The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF). By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time. The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60. Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4.2 at 4 μg/ml. So it can be concluded that tea seed especially the compound 1 (theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer. The preliminary structure–activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly.     

Jatrophane diterpenoid esters from Euphorbia sororia serving as multidrug resistance reversal agents

Six (1-6) new jatrophane diterpenoid esters together with four known compounds (7-10) were isolated from the acetone extract of fructus Euphorbia sororia. Their structures were elucidated by the spectral technology, including the 2D NMR experiments (HMQC, HMBC and NOESY). The absolute configuration of compound 1 and compound 7 were first confirmed by X-ray crystallographic analysis. Compounds 1-7 were assayed for their antiproliferative activity in human cancer cell lines: human mammary adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549). All the compounds were inactive for the cell lines. The multidrug-resistance reversal activity was also tested on KBv200 cells and compound 2 displayed strong multidrug resistance reversal activity, outperforming verapamil at 10 μM.     

Antibacterial anthranilic acid derivatives from Geijera parviflora

Five anthranilic acid derivatives, a mixture I of three new compounds 11′-hexadecenoylanthranilic acid (1), 9′-hexadecenoylanthranilic acid (2), and 7′-hexadecenoylanthranilic acid (3), as well as a new compound 9,12,15-octadecatrienoylanthranilic acid (4) together with a new natural product, hexadecanoylanthranilic acid (5), were isolated from Geijera parviflora Lindl. (Rutaceae). Their structures were elucidated by extensive spectroscopic measurements, and the positions of the double bonds in compounds 1–3 of the mixture I were determined by tandem mass spectrometry employing ozone-induced dissociation. The mixture I and compound 5 showed good antibacterial activity against several Gram-positive strains.     

Synthesis and antimycobacterial evaluation of natural oridonin and its enmein-type derivatives

A series of enmein-type derivatives were synthesized and assayed for their antimycobacterial effects. The structures of the synthesized compounds were established by ¹H NMR, ¹³C NMR and mass spectral analysis. All the compounds were screened for their antimycobacterial properties against Mycobacterium phlei, Mycobacterium smegmatis and Mycobacterium marinum. Compounds 2, 6g and 6i were found to exhibit potent antimycobacterial activity against M. phlei at a concentration of 0.5 μg/mL, which was comparable to that of positive drug streptomycin. Furthermore, five compounds were tested against Mycobacterium tuberculosis H₃₇Rv based on the promising preliminary screening results. Among them, compound 10 showed potent activity with IC₅₀ value of 17.1 μg/mL against M. tuberculosis H₃₇Rv strain. Thus, compound 10 could emerge as a promising lead for further research work.     

New secoiridoids from the fruits of Ligustrum lucidum Ait with triglyceride accumulation inhibitory effects

Five new secoiridoids, nuzhenal C (1), 6'-O-trans-cinnamoyl iso-8-epikingisidic acid (2), ligulucidumosides A (3), B (4), and C (5), were obtained from the fruits of Ligustrum lucidum Ait. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Among them, compound 3 is the first 1-OCH₃ substituent secoiridoid obtained from plant kingdom. Furthermore, activity screening results showed that all of the isolates had triglyceride accumulation inhibitory effects in HepG2 cells.     

Antibacterial prenylbenzoic acid derivatives from Anodendron formicinum

A phytochemical investigation on the stems of Anodendron formicinum led to the isolation of eight prenylbenzoic acid derivatives. Three of these were new compounds, designated as formicinuosides A (1), B (2), and C (3). Their structures were elucidated on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. This is the first report of chemical constituents from A. formicinum and their antimicrobial activities. Among the isolated compounds, compounds 4, 6 and 8 showed significant antibacterial activities against Providensia smartii with MIC values of 0.781 μg/mL. Moreover, compound 8 showed remarkable antibacterial activity against Escherichia coli with MIC value of 0.781 μg/mL.     

Caffeoylquinic acid derivatives isolated from the aerial parts of Gynura divaricata and their yeast α-glucosidase and PTP1B inhibitory activity

The phytochemical investigation of natural products of Gynura divaricata led to the isolation of eleven caffeoylquinic acid derivatives. They were characterized by spectrometric methods as 5-O-caffeoylquinic acid (1), 5-O-p-coumaroylquinic acid (2), 5-O-feruloylquinic acid (3), methyl 5-O-caffeoylquinate (4), 3,4-dicaffeoylquinic acid (5), 3,5-dicaffeoylquinic acid (6), 4,5-dicaffeoylquinic acid (7), methyl 3,4-dicaffeoylquinate (8), methyl 3,5-dicaffeoylquinate (9), methyl 4,5-dicaffeoylquinate (10) and ethyl 4,5-dicaffeoylquinate (11). The individual compounds were screened for the inhibition of yeast α-glucosidase and Protein Tyrosine Phosphatase 1B (PTP1B) using in vitro assays. Among the isolated compounds, 3,4-dicaffeoylquinic acid (5), 4,5-dicaffeoylquinic acid (7), methyl 3,4-dicaffeoylquinate (8) and methyl 4,5-dicaffeoylquinate (10) exhibited significant inhibitory activities against α-glucosidase. In addition, 5-O-p-coumaroylquinic acid (2), 3,5-dicaffeoylquinic acid (6) and 4,5-dicaffeoylquinic acid (7) had considerable inhibitory effect against PTP1B. Based on these findings, the caffeoylquinic acid derivatives were deduced to be potentially responsible for the anti-diabetic activity of G. divaricata. The preliminary structure–activity relationship study suggests that the number and positioning of caffeoyl groups in the quinic acid derivatives are important for both α-glucosidase and PTP1B inhibitory potency. Moreover, the corresponding methyl esters of some dicaffeoylquinic acids have enhanced inhibitory activity against yeast α-glucosidase.     

One new sesquiterpene from Saussurea laniceps

One new guaiane-type sesquiterpene (1) was isolated from Saussurea laniceps. The structure of the new compound was elucidated by spectroscopic data analysis. The immunomodulatory activity of compound 1 was evaluated. It was found that compound 1 showed significant inhibition for proliferation of murine T cells in vitro.     

Flavonoids from Tetrastigma obtectum enhancing glucose consumption in insulin-resistance HepG2 cells via activating AMPK

Four new flavonoids including three C-glycosidic flavonoids, named tetrastigma A–D (1–4) and five known flavones (5–9) were isolated from the herbs of Tetrastigma obtectum (Wall.) Planch. The structures of 1–4 were elucidated by 1D- and 2D-NMR and HR mass spectrometric methods. Compound 1 caused significant enhancement in glucose consumption by insulin-resistant HepG2 cells compared with control cells. In addition, compound 1 stimulated phosphorylation of AMPK, which plays an important role in glycometabolism.     

Antioxidant xanthones from Swertia mussotii,a high altitude plant

Four new xanthones, 3,5,6,8-tetrahydroxyxanthone-1-C-β-d-glucoside (1), 7-hydroxy-3,4,8-trimethoxyxanthone-1-O-(β-d-glucoside) (2), 6-hydroxy-3,5-dimethoxyxanthone-1-O-(β-d-glucoside) (3), 3,4,7,8-tetramethoxyxanthone-1-O-(β-d-glucoside) (4), together with twenty-one known xanthones (5–25) were isolated from the ethanol aqueous extract of Swertia mussotii. Their structures were elucidated via spectroscopic analyses. Oxygen radical absorbance capacity of all the isolated xanthones was systematically evaluated by ORAC_FL assay. Results disclose that all the tested xanthones display moderate to excellent antioxidant activity, where 1 is the most active compound and 13 is the least one. A preliminary structure–activity relationship is also discussed.     

Polar cardenolide monoglycosides from stems and twigs of Nerium oleander and their biological activities

Twelve polar cardenolide monoglycosides, 1, 2, 4?C13, and oleagenin (3) were isolated from the methanol extract of stems and twigs of Nerium oleander. Among these, oleagenin (3) and cardenolide monoglycosides named cardenolide B-1 (1) and cardenolide B-2 (2) were isolated from natural sources for the first time. The in vitro antiinflammatory activity of compounds 1?C13 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 4?C7 were active at an IC₅₀ value of less than 0.4 ??M. The cytotoxic activity of compounds 1?C13 was evaluated against three human cell lines: normal human fibroblast cells (WI-38), malignant tumor cells derived from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 4, 6, and 7 were active toward these three cell lines at IC₅₀ values of less than 0.7 ??M, and compounds 5 and 8 were active toward the cell lines at IC₅₀ values of less than 1.5 ??M. The multidrug resistance (MDR) cancer-reversal activity of compounds 1?C13 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compound 1 and 12 showed significant effects on calcein accumulation.     

Comparative pharmacokinetics of paclitaxel after oral administration of Taxus yunnanensis extract and pure paclitaxel to rats

Taxus yunnanensis (T. yunnanensis) is endemic to China and has been used in traditional medicine for the treatment of cancer, diabetic ailments and others. Paclitaxel is a representative antitumor compound in the Taxus species. The pharmacokinetic behavior of paclitaxel after oral administration of the crude extract of T. yunnanensis has not been investigated. This study attempts to compare the pharmacokinetics of paclitaxel after an oral administration of the crude extract of the twigs and leaves of T. yunnanensis and pure paclitaxel. A UPLC and a UPLC/MS/MS analysis method were developed for the determination of paclitaxel in T. yunnanensis extract and in the comparative pharmacokinetic study. Caco-2 cells were used to investigate the transport profile of paclitaxel in vitro. In the pharmacokinetic study, rats were randomly grouped and administered with T. yunnanensis extract or pure paclitaxel. The results showed that the AUC and C_max of paclitaxel in rats receiving the T. yunnanensis extract were significantly increased than those receiving the pure paclitaxel, and the in vitro Caco-2 cell monolayer transport study found that the coexisting constituents in the extract of T. yunnanensis could inhibit the efflux of paclitaxel. These findings suggested that the oral absorption and bioavailability of paclitaxel in T. yunnanensis extract were remarkably higher when compared with the pure paclitaxel, and the coexisting constituents in the T. yunnanensis extract might play an important role for the enhancement of the oral absorption and bioavailability of paclitaxel.     

Four new eudesmane-type sesquiterpenes from the basal leaves of Salvia plebeia R. Br.

Four new eudesmane-type sesquiterpenes, named plebeiolide A–C (1–3) and plebeiafuran (4), together with a known eudesmanolide (5), were isolated from the basal leaves of Salvia plebeia R. Br. Their structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS spectra. The absolute configuration of compound 1 was confirmed by single-crystal X-ray analysis and CD spectra. The inhibitory activity of isolated compounds toward NO production in lipopolysaccharide-induced RAW264.7 cells was evaluated and compounds 3 and 4 showed moderate inhibitory activity. In addition, the sesquiterpene lactones in Lamiaceae plants may possess some chemosystematic implications at intergeneric and intrageneric levels.     

Proton translocating ATPase mediated fungicidal activity of eugenol and thymol

Eugenol (1) and thymol (2) exhibit excellent fungicidal activity against pathogenic yeasts, including isolates resistant to azoles. The rapid irreversible action of compound-1 and compound 2 on fungal cells suggested a membrane-located target for their action. We investigated their effect on H⁺-ATPase mediated H⁺-pumping by various Candida species. Both compounds inhibit H⁺-ATPase activity at their respective MIC values — 500 and 100 μg/ml. Glucose stimulated H⁺-extrusion was also inhibited significantly by compound 1 and compound 2. Inhibition of H⁺-ATPase leads to intracellular acidification and cell death. Inhibition of cell growth and H⁺-efflux by test compounds suggests that their antifungal properties are related to their inhibitory effects on H⁺-ATPase.     

Microbial transformation of ginsenoside-Rg₁ by Absidia coerulea and the reversal activity of the metabolites towards multi-drug resistant tumor cells

Biotransformation of ginsenoside-Rg₁ (1) by the fungus Absidia coerulea AS 3.2462 yielded five metabolites (2? 6). On the basis of spectroscopic data analyses, the metabolites were identified as ginsenoside-F₁ (2), 6α,12β-dihydroxydammar-3-one-20(S)-O-β-D-glucopyranoside (3), 3-oxo-20(S)-protopanaxatriol (4), 3-oxo-7β-hydroxy-20(S)-protopanaxatriol (5), and 3-oxo-7β,15α-dihydroxy-20(S)-protopanaxatriol (6), respectively. Among them, 5 and 6 are new compounds. These results indicated that Absidia coerulea AS 3.2462 could catalyze the specific C-3 dehydrogenation of derivatives of ginsenoside-Rg₁, as well as hydroxylation at the 7β and 15α positions. Metabolites 2, 4 and 5 exhibited moderate reversal activity towards A549/taxol MDR tumor cells in vitro.