A triterpene glucosyl ester from the roots ofRubus crataegifolius

Along with five known triterpene glycosides, a new triterpene glucosyl ester, named crataegioside, was isolated from the roots of Rubus crataegifolius Bunge. The structure was established as ilexosapogenin A 28-O-beta-D-glucopyranosyl ester by chemical and spectroscopic methods.     

Triterpenoids from Rubi Fructus (Bogbunja)

The dried unripe fruits ofRubus sp. (Rubi Fructus, Bogbunja) have yielded β-sitosterol glucoside and four urs-12-en-28-oic acid derivatives, three of which were as their glucosides. They were identified as 23-hydroxytormentic acid, rosamultin, niga-ichigosides F₁ and F₂ on the basis of spectral data.     

A new triterpene lactone from the roots ofPatrinia scabiosaefolia

A new triterpene lactone named patrinolide A (1) has been isolated from the roots of Patrinia scabiosaefolia (Valerianaceae). Its structure was determined to be 11beta,21beta-dihydroxy-3-oxooleanan-28,13beta-olide on the basis of spectral analysis, including 2D-NMR techniques. Key words: Patrinia scabiosaefolia, Valerianaceae, Lactone, Patrinolide, 11beta,21beta-dihydroxy-3-oxooleanan-28,13beta-olide.     

Antiviral triterpenes fromPrunella vulgaris

Two triterpenes 1 and 2 with antiviral activity againstHerpes simplex virus type 1in vitro were isolated fromPrunella vulgaris. Each compound caused a significant reduction in viral cytopathic effect whenvero cells were exposed to them for 72 hours after viral challenge. They were identified asbetulinic acid(1) and 2α, 3α-dihydroxyurs-12-en-28-oic acid(2) on the basis of their spectroscopic properties. The antiviral activity of them was estimated as EC₅₀=30 μg/ml(1) and 8 μg/ml(2), respectively by plaque reduction assay.     

Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior

Rationale and objectives  The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs). Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, α-conotoxin MII (αCtxMII, α₃β₂*, β₃*, α₆*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-β-erythroidine (DHβE, α₄β₂*), and methyllycaconitine (MLA, α₇*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats. Methods  The effects of drugs were studied in rats trained for operant oral self-administration of ethanol (FR = 1). For ethanol deprivation, trained animals were subjected to a period of alcohol deprivation for 10 days. αCtxMII was given directly into the VTA through implanted permanent intracranial cannulae, whereas MEC, DHβE, and MLA were administered systemically. Results  αCtxMII reduced operant ethanol self-administration and blocked the deprivation-induced relapse-like ethanol consumption. MEC reduced operant ethanol self-administration and inhibited the deprivation-induced increase in alcohol consumption. DHβE did not alter ethanol self-administration in the lower-dose range but inhibited ethanol intake at a higher dose (4 mg/kg), although this effect might have been nonspecific. MLA failed to block self-administration of ethanol and relapse-like drinking after deprivation. Conclusions  Our results indicate that nAChRs are involved in the modulation of operant alcohol self-administration and relapse-like alcohol drinking behavior in rats. Our observations support the working hypothesis that systemically active selective ligands for nAChR α₃β₂*, β₃, and/or α₆* receptor subunits might be of therapeutic value for the treatment of alcoholism.     

Two new coumarin glucosides from the roots of<Emphasis Type="Italic">angelica apaensis</Emphasis> and their anti-platelet aggregation activity

Two new coumarin glucosides, 11-O-beta-D-glucopyranosyl thamnosmonin (1) and 12-O-beta-D-glucopyranosyl gosferol (2), were isolated from the roots of Angelica apaensis. Their structures were elucidated spectroscopically. Both compounds showed weak inhibitory effects on rabbit platelet aggregation induced by PAF, AA and APD.     

A new stilbene glucoside gallate from the roots of Polygonum multiflorum

A new stilbenoid (1) was isolated from the root extract of Polygonum multiflorum together with eight known constituents (2∼9). The chemical structure of 1 was established as the 6″-O-monogalloyl ester of (E)-2,3,4′,5-β-tetrahydroxystilbene-2-β-D-glucopyranoside based on physicochemical and spectroscopic analyses, particularly by NMR spectroscopic data, i.e., COSY, HMQC and HMBC. Compound 1 weakly inhibited acetylcholinesterase in vitro.     

Sesquiterpene components from the flower buds ofMagnolia fargesii

From the Chinese crude drugshin-i, the flower buds ofMagnolia fargesii, four sesquiterpene, oplopanone (1), oplodiol (2), homalomenol A (3) and 1β,4β,7α-trihydroxyeudesmane (4) were isolated. These structures were elucidated and the¹³C-NMR chemical, shifts of these compounds were revised by means of various 2D-NMR techniques.     

Coumarin glycosides from the roots ofAngelica dahurica

From the roots ofAngelica dahurica Bentham et Hooker (Umbelliferae), five known coumarin glucosides together with adenosine have been isolated and identified as nodakenin, 3′-hydroxymarmesinin, tert.-O-β-D-glucopyranosyl-byakangelicin, sec.-O-β-D-glucopyranosyl-byakangelicin and scopolin. This is the first report of the occurrence of these compounds in this plant.     

Similarities and differences in the autonomic control of airway and urinary bladder smooth muscle

The airways and the urinary bladder are both hollow organs serving very different functions, i.e. air flow and urine storage, respectively. While the autonomic nervous system seems to play only a minor if any role in the physiological regulation of airway tone during normal breathing, it is important in the physiological regulation of bladder smooth muscle contraction and relaxation. While both tissues share a greater expression of M2 than of M3 muscarinic receptors, smooth muscle contraction in both is largely mediated by the smaller M3 population apparently involving phospholipase C activation to only a minor if any extent. While smooth muscle in both tissues can be relaxed by beta-adrenoceptor stimulation, this primarily involves beta2-adrenoceptors in human airways and beta3-adrenoceptors in human bladder. Despite activation of adenylyl cyclase by either subtype, cyclic adenosine monophosphate plays only a minor role in bladder relaxation by beta-agonists; an important but not exclusive function is known in airway relaxation. While airway beta2-adrenoceptors are sensitive to agonist-induced desensitization, beta3-adrenoceptors are generally considered to exhibit much less if any sensitivity to desensitization. Gene polymorphisms exist in the genes of both beta2- and beta3-adrenoceptors. Despite being not fully conclusive, the available data suggest some role of beta2-adrenoceptor polymorphisms in airway function and its treatment by receptor agonists, whereas the available data on beta3-adrenoceptor polymorphisms and bladder function are too limited to allow robust interpretation. We conclude that the distinct functions of airways and urinary bladder are reflected in a differential regulation by the autonomic nervous system. Studying these differences may be informative for a better understanding of each tissue.     

Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages

Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interleukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-alpha and IL-1beta were produced by BA in a dose dependent manner at concentration of 0.625 and 10 microg/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 microg/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 microg/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625 to approximately 5 microg/mL with or without LPS. Furthermore, BA (20 microg/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.     

Two novel dammarane-type compounds from the leaves and stems of Panax quinquefolium L.

Two new dammarane-type compounds were isolated from the leaves and stems of Panax quinquefolium L. The new compounds were named as pseudo-ginsenoside RT₆ (1) and pseudoginsengenin R₁ (2). The structures of the new compounds were elucidated by the combined analysis of NMR and HR-ESI-MS as (20S,24R)-6-O-β-d-glucopyranosyl-dammar-3-one-20,24-epoxy-6α,12β,25-triol (1) and (20S,24R)-dammar-3-one-20,24-epoxy-6α,12β,25-triol (2).     

Cilostamide potentiates more the positive inotropic effects of (−)-adrenaline through β2-adrenoceptors than the effects of (−)-noradrenaline through β1-adrenoceptors in human atrial myocardium

Activation of both β₁- and β₂-adrenoceptors increases the contractility of human atrial myocardium through cyclic AMP-dependent pathways. Cyclic AMP is hydrolised by phosphodiesterases, but little is known about which isoenzymes catalyse inotropically relevant cyclic AMP accumulated upon stimulation of β-adrenoceptor subtypes. We have compared the positive inotropic effects of (−)-noradrenaline and (−)-adrenaline, mediated through β₁- and β₂-adrenoceptors, respectively, in the absence and presence of the PDE3 inhibitor cilostamide (300 nM) or PDE4 inhibitor rolipram (1 μM) on human atrial trabeculae from non-failing hearts. Cilostamide, but not rolipram, potentiated the effects of both (−)-noradrenaline and (−)-adrenaline. Cilostamide increased the −logEC₅₀M of (−)-adrenaline more than of (−)-noradrenaline (P < 0.05), regardless of whether or not the patients had been chronically treated with β-blockers. The results are consistent with a greater PDE3-catalysed hydrolysis of inotropically relevant cyclic AMP produced through β₂-adrenoceptors than β₁-adrenoceptors in human atrium.     

A new lupane-triterpene glycoside from the leaves of Acanthopanax gracilistylus

A new and two known lupane-triterpene glycosides were isolated from the hot MeOH fraction of the leaves of Acanthopanax gracilistylus W. W. Smith. Based on the physical properties and spectroscopic data, their chemical structures were determined as acankoreoside A (1), acankoreoside D (2), and 3alpha-hydroxy-lup-23-al-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (3), respectively. To our best knowledge, compound 3 appears to be novel, which was named as wujiapioside A.     

Studies on the specificity of CNF, a phospholipase A2 inhibitor isolated from the blood plasma of the South American rattlesnake (Crotalus durissus terrificus). I. Interaction with PLA2 from Lachesis muta muta snake venom

A phospholipase A₂ inhibitor has been previously purified and cloned from the blood plasma of the South American rattlesnake, Crotalus durissus terrificus. This inhibitor, named CNF for Crotalus neutralizing factor, interacts with crotoxin, the main neurotoxin from C. d. terrificus venom, abolishing its phospholipase A₂ activity. Crotoxin is a heterodimer of an acidic subunit (CA) and a basic phospholipase A₂ (CB). CNF acts by forming a stable non-toxic complex with CB, replacing CA in the toxic CA–CB of crotoxin.In the present investigation, we have shown that CNF has a broader specificity. It is able to inhibit the PLA₂ activity of the whole venom from the bushmaster snake (Lachesis muta muta), a species evolutionary related to Crotalus. Inhibition experiments have been carried out with four PLA₂ active components isolated from L. m. muta venom, one basic and three acidic ones. CNF inhibition is not restricted to the basic PLA₂, but extended to the three acidic forms as well.     

Norisoprenoids and hepatoprotective flavone glycosides from the aerial parts of<Emphasis Type="Italic">Beta vulgaris</Emphasis> var.<Emphasis Type="Italic">cicla</Emphasis>

(+)-Dehydrovomifoliol (1), 3-hydroxy-5alpha,6alpha-epoxy-beta-ionone (2), vitexin 7-O-beta-D-glucopyranoside (3), and vitexin 2'-O-beta-D-glucopyranoside (4) were isolated as new constituents from the aerial parts of Beta vulgaris var. cicla. Compounds 3 and 4 demonstrated hepatoprotective activity with values of 65.8 and 56.1%, respectively, in primary cultured rat hepatocytes with CCl4-induced cell toxicity, compared to controls. This was comparable to that of silibinin (69.8 %) which was used as a positive control.     

(-)-Adrenaline elicits positive inotropic, lusitropic, and biochemical effects through β2-adrenoceptors in human atrial myocardium from nonfailing and failing hearts, consistent with Gs coupling but not with Gi coupling

Activation of either coexisting β₁- or β₂-adrenoceptors with noradrenaline or adrenaline, respectively, causes maximum increases of contractility of human atrial myocardium. Previous biochemical work with the β₂-selective agonist zinterol is consistent with activation of the cascade β₂-adrenoceptors→Gsα-protein→adenylyl cyclase→cAMP→protein kinase (PKA)→phosphorylation of phospholamban, troponin I, and C-protein→hastened relaxation of human atria from nonfailing hearts. However, in feline and rodent myocardium, catecholamines and zinterol usually do not hasten relaxation through activation of β₂-adrenoceptors, presumably because of coupling of the receptors to Gi protein. It is unknown whether the endogenously occurring β₂-adrenoceptor agonist adrenaline acts through the above cascade in human atrium and whether its mode of action could be changed in heart failure. We assessed the effects of (-)-adrenaline, mediated through β₂-adrenoceptors (in the presence of CGP 20712A 300 nM to block β₁-adrenoceptors), on contractility and relaxation of right atrial trabecula obtained from nonfailing and failing human hearts. Cyclic AMP levels were measured as well as phosphorylation of phospholamban, troponin I, and protein C with Western blots and the back-phosphorylation procedure. For comparison, β₁-adrenoceptor-mediated effects of (-)-noradrenaline were investigated in the presence of ICI 118,551 (50 nM to block β₂-adrenoceptors). The positive inotropic effects of both (-)-noradrenaline and (-)-adrenaline were accompanied by reductions in time to peak force and time to reach 50% relaxation. (-)-Adrenaline caused similar positive inotropic and lusitropic effects in atrial trabeculae from failing hearts. However, the inotropic potency, but not the lusitropic potency, of (-)-noradrenaline was reduced fourfold in atrial trabeculae from heart failure patients. Both (-)-adrenaline and (-)-noradrenaline enhanced cyclic AMP levels and produced phosphorylation of phospholamban, troponin I, and C-protein to a similar extent in atrial trabeculae from nonfailing hearts. The hastening of relaxation caused by (-)-adrenaline together with the PKA-catalyzed phosphorylation of the three proteins involved in relaxation, indicate coupling of β₂-adrenoceptors to Gs protein. The phosphorylation of phospholamban at serine16 and threonine17 evoked by (-)-adrenaline through β₂-adrenoceptors and by (-)-noradrenaline through β₁-adrenoceptors was not different in atria from nonfailing and failing hearts. Activation of β₂-adrenoceptors caused an increase in phosphorylase a activity in atrium from failing hearts further emphasizing the presence of the β₂-adrenoceptor–Gsα-protein pathway in human heart. The positive inotropic and lusitropic potencies of (-)-adrenaline were conserved across Arg16Gly- and Gln27Glu-β₂-adrenoceptor polymorphisms in the right atrium from patients undergoing coronary artery bypass surgery, chronically treated with β₁-selective blockers. The persistent relaxant and biochemical effects of (-)-adrenaline through β₂-adrenoceptors and of (-)-noradrenaline through β₁-adrenoceptors in heart failure are inconsistent with an important role of coupling of β₂-adrenoceptors with Giα-protein in human atrial myocardium.     

刺梨酸的分离与结构研究

从刺梨中分离出一种新的五环三萜酸,命名为刺梨酸。通过光谱分析和衍生物的制备,确定其化学结构为2β,3α,7β,19α-四羟基乌苏-12-烯-28-羧酸。     

α<Subscript>1</Subscript>-Adrenergic and α<Subscript>2</Subscript>-adrenergic balance in the dorsal pons and gross behavioral activity of mice in a novel environment

Rationale Central α₁- and α₂-adrenoceptors in a number of different brain regions are known to have opposing actions on gross behavioral activity, with the former stimulating and the latter inhibiting activity. Therefore, blockade of α₁-receptors may induce inactivity by leading to unopposed α₂ activity.Objective The aim of this study was to test if central blockade of α₂-receptor function restores behavioral activity in α₁-receptor-blocked mice.Methods Dose-response studies were undertaken on the effects of α₁- and α₂-agonists and antagonists microinjected into the dorsal pons on gross behavioral activity in a novel cage test.Results The behavioral inactivity resulting from blockade of α₁-receptors in the pons with the antagonist, terazosin, was reversed by either a low dose of an α₂-antagonist, atipamezole, or a low dose of an α₂-agonist, dexmedetomidine, but was exacerbated by a high dose of the α₂-agonist.Conclusion The results support the hypothesis that blockade of α₁-receptors in the dorsal pons of mice produces inactivity by causing unopposed activity of α₂-receptors. This condition may be relevant to inactive states seen after stress or during depressive illness.