A new cycloartane saponin from Cimicifuga acerina

A new cycloartane saponin along with two known compounds, cimigenol and cimigenol 3-O-β-D-xyloside, was isolated from the rhizomes of Cimicifuga acerina (Sieb. et Zucc.) Tanaka (Ranunculaceae). The structure of the new compound was elucidated as 3'-O-acetyl cimigenol 3-O-β-D-xyloside on the basis of chemical and spectral evidence.     

Further flavonol and iridoid glycosides from Ajuga remota aerial parts

Five new iridoid glycosides characterised as 6-keto-8-acetylharpagide (1), 6,7-dehydro-8-acetylharpagide (2), 7,8-dehydroharpagide (3), 8-acetylharpagide-6-O-β-glucoside (4), harpagide-6-O-β-glucoside (5) together with three flavonol glycosides, myricetin 3-O-rutinoside-4'-O-rutinoside (6), myricetin 3-O-rutinoside-3'-O-rutinoside (7) and isorhamnetin 3-O-rutinoside-7-O-rutinoside-4'-O-β-glucoside (8) have been isolated from the aerial parts of Ajuga remota. Also isolated were two known compounds ajugarin IV and ajugarin V. Their structures were established using spectroscopic methods including UV, IR, FAB-MS, HR-MS, 1D and 2D NMR techniques.     

A new dicoumarinoid glycoside from Daphne giraldii

A new dicoumarinoid glycoside, named giraldoid A (1), has been isolated from Daphne giraldii Nitsche. The structure of 1 was determined as 7-O-β-glucosyl-8-(7-hydroxy-2H-1-benzopyran-2-one-8-)yl-2H-1-benzopyran-2-one on the basis of chemical reactions and spectroscopic methods.     

Stilbene C-glucosides from Cissus repens

Four new stilbene C-glucosides, namely trans-3-O-methyl-resveratrol-2-C-β-glucoside (1), cis-3-O-methyl-resveratrol-2-C-β-glucoside (2), trans-3-O-methyl-resveratrol-2-(2-p-coumaric)-C-β-glucoside (cissuside A) (3), and trans-3-O-methyl-resveratrol-2-(3-p-coumaric)-C-β-glucoside (cissuside B) (4), were isolated from the aerial parts of Cissus repens, along with known trans-resveratrol (5), trans-resveratrol-2-C-β-glucoside (6) and cis-resveratrol-2-C-β-glucoside (7). Their structures were established by spectroscopic methods. Stilbene C-glucosides were found in the genus Cissus for the first time.     

A new iridoid diglycoside from Clerodendrum chinense

A new iridoid diglucoside, 5-O-β-glucopyranosyl-harpagide, has been isolated from the aerial part of Clerodendrum chinense together with three known iridoid glucosides and six known cyclohexylethanoids. Their structures have been determined by analyses of spectroscopic data.     

Glycosyl flavonoids from the roots and rhizomes of Asarum longerhizomatosum

Two new glycosyl flavonoids including a glycosyl aurone, together with six known flavonoids were isolated from the roots and rhizomes of Asarum longerhizomatosum. The structures of the two new compounds were elucidated as 4,6,4'-trihydroxy-aurone-4,6-di-O-β-D-glucopyranoside (7, caulesauroneside) and naringenin-7,4'-di-O-β-D-glucopyranoside (8, caulesnarinside). The six known flavonoids were identified as naringenin (1), naringenin-5-O-β-D-glucopyranoside (2), naringenin-7-O- β-D-glucopyranoside (3), chalcononaringenin-2'-O-β-D-glucopyranoside (4), naringenin-5,7-di-O-β-D-glucopyranoside (5), chalcononaringenin-2',4'-di-O-β-D-glucopyranoside (6), respectively. This is the first report of the isolation of aurones in the family Aristolochiaceae.     

Arylglycerol glucosides from Dracocephalum forrestii

Three new arylglycerol glucosides, threo-guaiacylglycerol 3-O-(6-O-p-hydroxybenzoyl)-β-D-glucopyranoside (1), threo-guaiacylglycerol 3-O-[6-O-(E)-p-coumaroyl]-β-D-glucopyranoside (2) and threo-guaiacylglycerol 3-O-[6-O-(Z)-p-coumaroyl]-β-D-glucopyranoside (3), together with seven known compounds were isolated from the whole plants of Dracocephalum forrestii and their structures were determined on the basis of spectroscopic evidences.     

Sesquiterpene glucosides from anti-leukotriene B4 release fraction of Taraxacum officinale

Chemical examination of the MeOH extract of the root of Taraxacum officinale, which exhibited inhibitory activity on the formation of leukotriene B₄ from activated human neutrophils, has resulted in the isolation of 14-O-β-D-glucosyl-11,13-dihydro-taraxinic acid (1) and 14-O-β-D-glucosyl-taraxinic acid (2). The absolute stereostructure of 1 has been established by X-ray chrystallographic examination.     

A new diterpene from the processed roots of Euphorbia Kansui

A new diterpene has been isolated from the processed roots of Euphorbia Kansui. By means of physico-chemical evidences and spectral analysis, the structure was identified as 4-O-acetyl-5-O-benzoyl-3β-hydroxy-20-deoxyingenol (1).     

The 6-derivative of beta-cyclodextrin with succinic acid: a new chiral selector for CD-EKC

6-O-Succinil-β-cyclodextrin (CDsuc6) was synthesized with very good yield by one pot synthesis and characterized by NMR spectroscopy and ESI-MS. It was used as a chiral selector in capillary electrophoresis to resolve catecholamine racemates, namely norepinephrine, epinephrine, terbutaline and norphenilephrine.

The CE experiments at pH 5.6 show very promising selector ability by 6-O-succinil-β-cyclodextrin for the chiral recognition of all the catecholamines tested, while at pH 9.2, only racemic terbutaline was successfully separated.     

Puerarin protects rat pancreatic islets from damage by hydrogen peroxide

Periodate-oxidized 2′,3′-dialdehyde ATP (oxidized ATP) has been used extensively as a selective antagonist at P2X₇ receptors, although P2X₇-independent actions on pro-inflammatory cytokine release have also been reported. Because P2X₇ receptors in astrocytes have been suggested as potential targets of anti-inflammatory drug therapy, we examined the effect of oxidized ATP on β-actin expression and superoxide production of RBA-2 type-2 astrocytes known to possess P2X₇ receptors. Oxidized ATP per se decreased β-actin expression time and dose dependently. Treatment with oxidized ATP for 8 h caused an approximately 50% decrease in β-actin expression whereas other P2 receptor antagonists, brilliant blue G (BBG), suramin and pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), were not effective. In addition, oxidized ATP per se decreased the intracellular superoxide concentration, whereas ATP and the P2X₇ receptor-selective agonist 3′-O-(4-benzoylbenzoyl)adenosine 5′-triphosphate (BzATP) stimulated intracellular superoxide production, an effect inhibited by oxidized ATP. In addition, oxidized ATP neither affected cellular viability nor affected interleukin-1β, converting enzyme (ICE)-like protease activity in these astrocytes. To further elucidate the mechanism, the effects of oxidized ATP on intracellular superoxide concentration and β-actin expression were examined in a P2X₇ receptor-negative astrocyte cell line, IA-1g1. Oxidized ATP-induced a time-dependent decrease in intracellular superoxide concentration whereas oxidized ATP had no effect on β-actin expression. Nevertheless, oxidized ATP altered f-actin cytoskeleton arrangement in IA-1g1 astrocytes. Taken together, these results indicate that oxidized ATP per se caused a cell specific decrease in β-actin expression in RBA-2 type-2 astrocytes. In addition, oxidized ATP decreased intracellular superoxide concentrations and altered f-actin cytoskeleton arrangement in both P2X₇ receptor-positive and -negative astrocytes. Thus, we conclude from these results that the effects of oxidized ATP on actin and superoxide are mediated through mechanisms that are at least in part, independent of P2X₇ receptors.     

Absolute configuration determination of angular dihydrocoumarins from Peucedanum praeruptorum

From Peucedanum praeruptorum, one new khellactone ester (3'R)-O-acetyl-(4'S)-O-angeloylkhellactone (3), as well as four known angular dihydropyranocoumarins (1, 2, 4, 5) have been isolated. On the basis of NMR spectra and X-ray crystallography, their structures were determined. We have elucidated their absolute configuration by either chiral separation of their alkaline hydrolysis products with Rp-18 HPLC eluted with 5% hydroxypropyl-β-cyclodextrin (β-HCD) or by measurement of their CD spectra. A general rule relating the position and absolute stereochemistry of the khellactone esters to the sign of their Cotton effects in CD curves is proposed.     

ent-Kaurenoids from the roots of Cacalia pilgeriana

Two new ent-kaurenoids,19-acetoxyl-ent-3β,17-dihydroxykaur-15-ene (1), 19-acetoxyl-ent-3β-hydroxykaur-15-en-17-al (2), together with seven known ent-kaurenoids: ent-kaur-16-en-19-al (3), ent-kaur-16-en-19-oic acid (4), ent-kauran-16β,17-diol (5), ent-15β, 16β-epoxy-17-hydroxykauran-19-oic acid (6),19-acetyl-ent-3β-hydroxyl-kaur-16-ene (7), ent-3β,19-dihydroxykaur-16-ene (8), ent-17-hydroxykaur-15-ene (9), were isolated from Cacalia pilgeriana. Their structures were elucidated by spectroscopic methods including 2D NMR spectral analysis.     

Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation

Aim:

To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti-fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro.

Methods:

SHRs were orally treated with Cur (100 mg·kg⁻¹·d⁻¹) or Cur (100 mg·kg⁻¹·d⁻¹) plus the PPAR-γ antagonist GW9662 (1 mg·kg⁻¹·d⁻¹) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 μmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ) were detected using Western blotting and a DNA-binding assay, respectively.

Results:

Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-γ in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 μmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-γ. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad2/3, which were reversed by GW9662.

Conclusion:

Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR-γ and TGF-β1/Smad2/3 signaling is involved in the anti-fibrotic and anti-proliferative effects of Cur.     

Direct scavenging of nitric oxide and superoxide by green tea

In the present study, we investigated the free radical scavenging effects of green tea extract and green tea tannin mixture and its components using a nitric oxide (NO) and superoxide (O₂⁻) generating system in vitro. Green tea extract showed direct scavenging activity against NO and O₂⁻ and green tea tannin mixture, at the same concentration, showed high scavenging activity. Comparison of the activities of seven pure compounds isolated from green tea tannin mixture showed that (−)-epigallocatechin 3-O-gallate (EGCg), (−)-gallocatechin 3-O-gallate (GCg) and (−)-epicatechin 3-O-gallate (ECg) had higher scavenging activities than (−)-epigallocatechin (EGC), (+)-gallocatechin (GC), (−)-epicatechin (EC) and (+)-catechin (C), showing the importance of the structure of flavan-3-ol linked to gallic acid for this activity. Among the gallate-free tannins, EGC and GC were more effective O₂⁻ scavengers than EC and C, indicating the O-trihydroxy structure in the B ring is an important determinant of such activity. However, this structure did not affect the NO scavenging activity. These findings confirm that green tea tannin has excellent antioxidant properties, which may be involved in the beneficial effect of this compound.     

Pioglitazone improves lipid and insulin levels in overweight rats on a high cholesterol and fructose diet by decreasing hepatic inflammation

Background and purpose:

Nutrient overload leads to obesity and insulin resistance. Pioglitazone, a selective peroxisome proliferator-activated receptor (PPAR)γ agonist, is currently used to manage insulin resistance, but the specific molecular mechanisms activated by PPARγ are not yet fully understood. Recent studies suggest the involvement of suppressor of cytokine signalling (SOCS)-3 in the pathogenesis of insulin resistance. This study aimed to investigate the hepatic signalling pathway activated by PPARγ activation in a non-genetic insulin-resistant animal model.

Experimental approach:

Male Wistar rats were maintained on a high-cholesterol fructose (HCF) diet for 15 weeks. Pioglitazone (3 mg·kg⁻¹) was administered orally for the last 4 weeks of this diet. At the end of the treatment, serum was collected for biochemical analysis. Levels of PPARγ, SOCS-3, pro-inflammatory markers, insulin receptor substrate-2 and Akt/glycogen synthase kinase-3β phosphorylation were assesed in rat liver.

Key results:

Rats fed the HCF diet exhibited hyperlipidemia, hyperinsulinemia, impaired glucose tolerance and insulin resistance. Pioglitazone administration evoked a significant improvement in lipid metabolism and insulin responsiveness. This was accompanied by reduced hepatic expression of SOCS-3, interleukin-6, tumour necrosis factor-α and markers of neutrophil infiltration. Diet-induced PPARγ expression was unaffected by the pioglitazone treatment.

Conclusion and implications:

Chronic pioglitazone administration reduced hepatic inflammatory responses in rats fed a HCF diet. These effects were associated with changes in hepatic expression of SOCS-3, which may be a crucial link between the reduced local inflammation and the improved insulin signalling.This article is commented on by Chatterjee, pp. 1889–1891 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00739.x     

Androechin, a new chalcone glucoside from Andrographis echioides

A new chalcone glucoside, androechin, and a known flavone glucoside, echioidinin 5-O-glucoside, were isolated from the whole plant of Andrographis echioides. Androechin was characterized as 2,2',6'-trihydroxy-4'-methoxychalcone 2'-O-β-D-glucopyranoside by spectral and chemical studies.     

Atorvastatin prevents Aβ oligomer-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting Tau cleavage

Aim:

The proteolytic cleavage of Tau is involved in Aβ-induced neuronal dysfunction and cell death. In this study, we investigated whether atorvastatin could prevent Tau cleavage and hence prevent Aβ_1–42 oligomer (AβO)-induced neurotoxicity in cultured cortical neurons.

Methods:

Cultured rat hippocampal neurons were incubated in the presence of AβOs (1.25 μmol/L) with or without atorvastatin pretreatment. ATP content and LDH in the culture medium were measured to assess the neuronal viability. Caspase-3/7 and calpain protease activities were detected. The levels of phospho-Akt, phospho-Erk1/2, phospho-GSK3β, p35 and Tau proteins were measured using Western blotting.

Results:

Treatment of the neurons with AβO significantly decreased the neuronal viability, induced rapid activation of calpain and caspase-3/7 proteases, accompanied by Tau degradation and relatively stable fragments generated in the neurons. AβO also suppressed Akt and Erk1/2 kinase activity, while increased GSK3β and Cdk5 activity in the neurons. Pretreatment with atorvastatin (0.5, 1, 2.5 μmol/L) dose-dependently inhibited AβO-induced activation of calpain and caspase-3/7 proteases, and effectively diminished the generation of Tau fragments, attenuated synaptic damage and increased neuronal survival. Atorvastatin pretreatment also prevented AβO-induced decreases in Akt and Erk1/2 kinase activity and the increases in GSK3β and Cdk5 kinase activity.

Conclusion:

Atorvastatin prevents AβO-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting calpain- and caspase-mediated Tau cleavage.     

17β-Estradiol inhibition of PPARγ-induced adipogenesis and adipocyte-specific gene expression

Aim:

To investigate the molecular interaction of peroxisome proliferator-activated receptor γ (PPARγ) with 17β-estradiol (E) in the regulation of adipogenesis.

Methods:

Female ovariectomized (OVX) mice and differentiated 3T3-L1 adipocytes were treated with combinations of the PPARγ agonist troglitazone or E, and the variables and determinants of adipogenesis were measured using in vivo and in vitro approaches.

Results:

Troglitazone (250 mg·kg⁻¹·d⁻¹ for 13 weeks) decreased the size of adipocytes without the change in white adipose tissue (WAT) mass and increased the expression of adipocyte-specific genes, such as PPARγ, adipocyte fatty acid binding protein, and lipoprotein lipase, compared with OVX control mice. E (0.05 mg/pellet, sc implanted) significantly reduced WAT mass, adipocyte size, and adipose marker gene expression. When mice were concomitantly treated with troglitazone and E, E blunted the effects of troglitazone on WAT mass, adipocyte size, and adipose PPARγ target gene expression. Consistent with the in vivo data, E (10 μmol/L) treatment inhibited lipid accumulation and the expression of adipocyte-specific genes caused by troglitazone (10 μmol/L) in 3T3-L1 cells. E (10 μmol/L) also decreased troglitazone-induced PPARγ reporter activity through both estrogen receptor (ER) α and ERβ. Mechanistic studies indicated that E (0.1 μmol/L) decreased the DNA binding of PPARγ induced by troglitazone (1 μmol/L) and inhibited the recruitment of the PPARγ coactivator CREB-binding protein.

Conclusion:

These results suggest that in vivo and in vitro treatment of E interferes with the actions of PPARγ on adipogenesis by down-regulating adipogenesis-related genes, which are mediated through the inhibition of PPARγ coactivator recruitment. In addition, it is likely that the activities of PPARγ activators may be enhanced in estrogen-deficient states.