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.     

Kujigamberol, a new dinorlabdane diterpenoid isolated from 85million years old Kuji amber using a biotechnological assay

A new compound, 15,20-dinor-5,7,9-labdatriene-18-ol (1), named kujigamberol, was isolated from amber, fossilized tree resin from the Kuji area in Japan, has been dated as being 85 million years old (late Cretaceous). Kujigamberol was identified using the hypersensitive mutant yeast (zds1? erg3? pdr1? pdr3?) with respect to Ca²⁺-signal transduction. The structure was elucidated on the basis of spectroscopic analysis including 1D NMR, 2D NMR and HR-EI-MS. It was different from known diterpenoids with a similar activity isolated from Baltic amber (agathic acid 15-monomethyl ester (2), dehydroabietic acid (3) and pimaric acid (4)). Kujigamberol showed glycogen synthase kinase-3β (GSK-3β) inhibition activity involving the growth restored activity against the mutant yeast and was cytotoxic to HL60 cells (IC₅₀ = 19.6 μM).     

泡桐丛枝植原体胸苷酸激酶的原核表达、纯化及酶活性测定

胸苷酸激酶是d TTP从头合成和补救途径的关键酶,催化d TMP形成d TDP,在DNA复制和生物的生存中发挥着必不可少的作用。本文在前期研究的基础上,对从泡桐丛枝(Pa WB)植原体中获得的的3个同源蛋白TMK-a-1、TMK-a-2及TMK-b与已报道的小麦蓝矮(WBD)、洋葱黄化(OY-W)植原体的TMK-a、TMK-b的氨基酸序列进行了比对和相似性分析,结果显示Pa WBPS TMK-b与WBD TMK-2和OY-W TMK-b之间的相似性分别为95.65%和99.03%;Pa WBPS TMK-a-1与Pa WBPS TMK-a-2的相似性为90.57%,且二者与WBD TMK-1和OY-W TMK-a之间的相似性为87.32%-94.26%;而Pa WBPS、WBD、OY-W三种植原体的TMK-a与TMK-b之间的相似性仅为22.22%-25.95%。构建了Pa WBPS TMK-b、TMK-a-1、TMK-a-2的p ET28a原核表达载体,对Pa WBPS TMK-b、TMK-a-1、TMK-a-2 3种蛋白进行了原核表达,经Ni-NTA柱纯化后,利用双酶法进行了胸苷酸激酶催化活性测定,结果表明,Pa WBPS TMK-b具有较高的胸苷酸激酶活性,为85.96±0.74 U·mg-1,而Pa WBPS TMK-a-1和TMK-a-2几乎没有胸苷酸激酶活性。本文为进一步研究胸苷酸激酶在植原体繁殖过程中的作用机理奠定了基础。     

Identification of chicoric acid as a hypoglycemic agent from Ocimum gratissimum leaf extract in a biomonitoring in vivo study

Ocimum gratissimum L. is popularly used to treat diabetes mellitus. The hypoglycemic activity of this medicinal species has been confirmed by in vivo studies. The present study conducted a chemical investigation of a leaf decoction (10% p/v) of O. gratissimum monitored by in vivo hypoglycemic activity assays. Four phenolic substances were identified: l-caftaric acid (1), l-chicoric acid (2), eugenyl-β-d-glucopyranoside (3) and vicenin-2 (4). The acute hypoglycemic activity of the O. gratissimum decoction fractions Og1-S (300 mg/kg), Og1-A (240 mg/kg) and Og1-B (80 mg/kg) was evaluated intraperitoneally in normal and streptozotocin-induced diabetic mice. They reduced glycemia by 63%, 76% and 60% (in 120 min), respectively, in the diabetic mice. Subfractions of Og1-A were also evaluated under the same conditions: Og1-AS (200 mg/kg) and Og1-AP (40 mg/kg) produced a decrease of only 37% and 39%, respectively. Among the major phenolic substances, only chicoric acid (2; 3 mg/kg) reduced significantly the glycemic levels of diabetic mice by 53%, 120 min after treatment. This is the first study describing the hypoglycemic activity of chicoric acid in an animal model of diabetes mellitus. In addition, we suggest that there may be other substances contributing to this activity. Thus, for the first time, a correlation is established between the hypoglycemic activity of O. gratissimum and its chemical composition.     

Five new triterpenoidal saponins from the roots of Ilex cornuta and their protective effects against H2O2-induced cardiomyocytes injury

Five new ursane-type triterpenoidal saponins (1–5), together with five known ones (6–10), were isolated from the EtOH extract of the roots of Ilex cornuta. The structures of saponins 1–5 were elucidated as 19α-hydroxyurs-12-en-28-oic acid 3β-O-β-D-glucuronopyranoside (1), 19α-hydroxyurs-12-en-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-ethyl ester (2), 19α-hydroxyurs-12-en-28-oic acid 3β-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucuronopyranoside (3), 3β-O-[α-L-arabinopyranosyl-(1 → 2)-β-D-glucuronopyranosyl]-19α-hydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranosyl ester (4) and 3β-O-[α-L-arabinopyranosyl-(1 → 2)-β-D-glucuronopyranoside-6-O-methyl ester]-19α-hydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranosyl ester (5), on the basis of spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR) and chemical reactions. Protective effects of compounds 1–10 against H₂O₂-induced H9c2 cardiomyocyte injury were tested. Compounds 1–5, 7, and 10 showed cell-protective effects. Among them compound 5 exhibited the highest activity. No significant DPPH radical scavenging activity was observed for compounds 1–10.     

Stilbenes and flavonoids from Artocarpus nitidus subsp. lingnanensis

The first stilbene possessing a γ-aminobutyric acid lactam function, artocarpene (1), and a new flavanone, 2-hydroxynaringenin 4′-O-β-d-glucopyranoside (2), were isolated from the stems of Artocarpus nitidus subsp. lingnanensis along with four known compounds, 2-hydroxynaringenin (3), oxyresveratrol (4), 3,4′,5-trihydroxy-3′-prenylstilbene (5) and norartocarpetin (6). Their structures were elucidated on the basis of spectroscopic data. Compounds 1 exhibited weak antioxidant activity and 2 displayed weak cytotoxicity against human lung cancer A549 cell line.     

Bioactive phenolics from the fruits of Livistona chinensis

This study investigated the antioxidant and cytotoxic activity of the phenolics isolated from the fruits of Livistona chinensis. Four new compounds, 1-{ω-isoferul[6- (4-hydroxybutyl)pentadecanoic acid]}-glycerol (1), E-[6′-(5″-hydroxypentyl)tricosyl]-4-hydroxy-3-methoxycinnamate (2), 2-(3′-hydroxy-5′-methoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5- carboxylic acid (3), 7-hydroxy-5,4′-dimethoxy-2-arylbenzofuran (4), together with eleven known phenolics (5-15), were isolated and identified. Among these compounds, 1-4, 5-O-caffeoylshikimic acid (5), caffeic acid (7), and 3-O-caffeoylshikimic acid (8) showed potent antioxidant activity. 1-5, and 8 showed potent antiproliferative activities with IC₅₀ values among 5-150 μM against HepG2 human liver cancer, HL-60 human myeloid leukemia, K562 human myeloid leukemia, and CNE-1 human nasopharyngeal carcinoma cell lines. On the basis of these findings, it could be proposed that the fruits of L. chinensis may serve as attractive mines of powerful anticancer and antioxidant agents for various purposes.     

Topical anti-inflammatory activity of Gentianella achalensis

The anti-inflammatory activity of the petrol, dichloromethane and methanol extracts from Gentianella achalensis flowering plant were studied using 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice and carrageenan-induced paw edema in rats. Only the dichloromethane extract and its F2 fraction (at 1 mg/ear) showed marked anti-inflammatory activity in TPA-induced ear edema test. No effects were seen on carrageenan-induced edema. Oleanolic and ursolic acid, isolated from F2, may account for the observed topical anti-inflammatory effects.     

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.     

Ganoderic acid Df,a new triterpenoid with aldose reductase inhibitory activity from the fruiting body of Ganoderma lucidum

Ganoderic acid Df, a new lanostane-type triterpenoid, was isolated from the fruiting body of Ganoderma lucidum. Its structure was characterized as 7β, 11β-dihydroxy-3, 15, 23-trioxo-5α-lanosta-8-en-26-oic acid by 1D- and 2D-NMR spectra. This compound exhibited potent human aldose reductase inhibitory activity, with an IC₅₀ of 22.8 μM in vitro. A carboxyl group of this compound's side chain is essential for eliciting inhibitory activity because its methyl ester is much less active.     

A new cytotoxic cembrane diterpene from the roots of Euphorbia pekinensis Rupr

A new cembrane diterpene, named (−)-(1S)-15-hydroxy-18-carboxycembrene, was isolated from petroleum ether extract of the roots of the Euphorbia pekinensis Rupr. To our knowledge, this compound is the first cembrane-type diterpenoid to be found in the family Euphorbiaceae. The structure was elucidated as (−)-(1S)-15-hydroxy-cembra -2E, 4Z, 7E, 11E-tetraen-18-oic acid by a combination of IR, HR-ESIMS, 1D- and 2D-NMR techniques. (−)-(1S)-15-hydroxy-18-carboxycembrene showed cytotoxic activity against all five human cancer cell lines tested.     

Biotransformation of ursolic acid by Syncephalastrum racemosum CGMCC 3.2500 and anti-HCV activity

Microbial transformation of ursolic acid (UA, 3β-hydroxy-urs-12-en-28-oic acid, 1) by filamentous fungus Syncephalastrum racemosum CGMCC 3.2500 was conducted. Five metabolites 3β, 7β, 21β-trihydroxy-urs-12-en-28-oic acid (2); 3β, 21β-dihydroxy-urs-11-en-28-oic acid-13-lactone (3); 1β, 3β, 21β-trihydroxy-urs-12-en-28-oic acid (4); 3β, 7β, 21β-trihydroxy-urs-1-en-28-oic acid-13-lactone (5); and 21-oxo-1β, 3β-dihydroxy-urs-12-en-28-oic acid (6) were afforded. Elucidation of the structures of these metabolites was primarily based on 1D and 2D NMR and HR-MS data. Metabolite 2 was a new compound. In addition, the anti-HCV activity of compounds 1–6 was evaluated.     

3, 4-seco-Labdane diterpenoids from the leaves of Callicarpa nudiflora and their inhibitory effects on nitric oxide production

As a part of our ongoing search for bioactive compounds from the leaves of Callicarpa nudiflora that inhibit nitric oxide (NO) production, the 90% EtOH fraction eluted by macroporous resin adsorption was found to show significant inhibitory activity against the production of NO in RAW 264.7 stimulated by lipopolysaccharide (LPS). Bioactivity-guided isolation of the fraction yielded three new bioactive diterpenoids, named ent-3, 4-seco-14-carbonyl-15, 16-epoxy-4(18), 8(17), 13(14)-labdatrien-3-oic acid (1), syn-3, 4-seco-12R-hydroxy-15, 16-epoxy-4(18), 8(17), 13(16), 14(15)-labdatetraen-3-oic acid (2) and syn-3, 4-seco-12S-hydroxy-15, 16-epoxy-4(18), 8(17), 13(16), 14(15)-labdatetraen-3-oic acid (3). Their structures and configurations were elucidated by comprehensive spectroscopic analysis. All the three compounds exhibited potent inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells.     

New coumarin glycosides from the leaves of Diospyros crassiflora (Hiern)

Two new 5-methylcoumarin glycosides named diosfeboside A (1) and B (2) and five known compounds namely kaempferol 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranoside (3), ursolic acid (4), betulinic acid (5), stigmasterol (6) and stigmasterol 3-O-β-d-glucopyranoside (7) were isolated from the leaves of Diospyros crassiflora (Hiern). Their structures were established through interpretation of 1 and 2D NMR, mass spectra analysis and comparison with reported data. In vitro cytotoxic activity of the new compounds against human carcinoma cell lines (HL-60, Bel-7402, BGC-823, and KB) was evaluated and no cytotoxicity was observed for each of them.     

Chlorogenic acid protects paraoxonase 1 activity in high density lipoprotein from inactivation caused by physiological concentrations of hypochlorite

We hypothesized that chlorogenic acids, the main phenolics in coffee, many fruits and Ilex paraguariensis extracts, protect paraoxonase 1 activity in HDL from inactivation by chlorination at concentrations of HOCl (50 μM) and chlorogenic acid (2–10 μM) compatible with those found in humans.     

Antibacterial triterpenes from the threatened wood-decay fungus Fomitopsis rosea

From a biologically active extract from the fungus Fomitopsis rosea, two new lanostane triterpenes were isolated, 3α-(3′-butylcarboxyacetoxy)oxepanoquercinic acid C 1 and 3α-hydroxy-24-methylene-23-oxolanost-8-en-26-carboxylic acid 2, along with three known triterpenes, 3–5, and the epidioxy sterol derivative 6. The structures of the compounds were elucidated based on their spectral properties. All triterpenes demonstrated antibacterial activity against S. aureus but possessed no antiradical activity against DPPH radicals.     

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.     

Structure elucidation of two triterpenoid saponins from rhizome of Anemone raddeana Regel

Two new 27-hydroxy-oleanolic acid type triterpenoid saponins, raddeanoside 20 (1) and raddeanoside 21(2) were isolated from the rhizome of Anemone raddeana Regel. The structures of the two compounds were elucidated as 27-hydroxy-oleanolic acid 3-O-α-l-rhamnopyranosyl(1→2) [β-d-glucopyranosyl (1→4)]-α-l-arabinopyranoside (1) and 3-O-α-l-rhamnopyranosyl (1→2)-α-l-arabinopyranosyl-27-hydroxy-oleanolic acid 28-O-α-l-rhamnopyranosyl(1→4)-β-d-glucopyranosyl (1→6)-β-d-glucopyranoside (2) on the basis of chemical and spectral evidence.     

New flavane gallates isolated from the leaves of Plicosepalus curviflorus and their hypoglycemic activity

Two new flavane gallates were isolated from the leaves of Plicosepalus curviflorus. The structure of the new compounds was established as 2S,3R-3,3′,4′,5,7-pentahydroxyflavane-5-O-gallate (1) and 2S,3R-3,3′,4′,5,5′,7-hexahydroxyflavane-4′,5-di-O-gallate (2), respectively. In addition, seven known compounds (−)-catechin (3), quercetin (4), lupeol (5), β-sitosterol (6), pomolic acid (7), β-sitosterol 3-O-β-d-glucopyranoside (8) and 4-methoxycinnamic acid (9) were reported for the first time from the genus Plicosepalus. Compounds 1, 2 and 3 were investigated for their hypoglycemic activity and showed significant hypoglycemic activity in Swiss Albino mice.