A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent pathways.

Neuronal differentiation is a critical developmental process that determines accurate synaptic connection and circuit wiring. A wide variety of naturally occurring compounds have been shown as promising drug leads for the generation and differentiation of neurons. Here we report that a diarylheptanoid from the plant Alpinia officinarum, 7-(4-hydroxyphenyl)-1-phenyl-4E-hepten-3-one (Cpd 1), exhibited potent activities in neuronal differentiation and neurite outgrowth. Cpd 1 induced differentiation of neuroblastoma Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of cultured hippocampal neurons. Moreover, Cpd 1 promoted neurite extension in both Neuro-2a cells and neurons. We showed that the effects of Cpd 1 on neuronal differentiation and neurite growth were specifically dependent on the activation of extracellular signal-regulated kinases (ERKs) and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways. Importantly, intraperitoneal administration of Cpd 1 promoted the differentiation of new-born progenitor cells into mature neurons in the adult hippocampal dentate gyrus. Collectively, this study identifies a naturally occurring diarylheptanoid with beneficial effects on neuronal differentiation and neurite outgrowth in vitro and in vivo.

Polyphenols from Parabarium huaitingii and their positive inotropic and anti-myocardial infarction effects in rats.

Eight phenolic compounds, including (-)-epicatechin (1) and seven proanthocyanidins (2-8), were obtained from the butanol extract of Parabarium huaitingii (PHB). Their chemical structures were identified based on analyses of mass spectra (MS), NMR, CD spectra, and partial acid catalyzed thiolytic degradation. The observation made by laser scanning confocal microscope found a significant increase of the concentration of intracellular Ca²+ ([Ca²+](i)) in single myocytes when the PHB was added, while compounds 1 and 3 had the same physiological effect. Further investigations showed PHB had a dose-dependent positive inotropic effect on isolated right atria and papillary muscle of left ventricle of the rat, while having no significant influence on the spontaneous beating rate of the isolated right atria. The inotropic effect of PHB could be greatly abolished by pretreating the myocardium in Ca²+-free solution. These findings indicated that PHB could significantly increase [Ca²+](i) in myocytes, which was greatly dependent on the influx of extracellular Ca²+. Compounds 1 and 3 might be the effective ingredients of the inotropic effect of PHB. In addition, PHB could also significantly decrease the infarct size of the heart on acute myocardial infarction (AMI) model rats, which suggested its myocardial protective effect on ischemic myocardium. The positive inotropic effect of PHB, together with its myocardial protective effect on AMI, suggested that PHB had a promising potential for the prevention and treatment of heart failure, especially the one that was caused by AMI.

New triterpenoid from Stellaria media (L.) Cyr.

One new triterpenoid, 3beta, 16beta, 23, 28-tetrahydroxy oleana-11, 13(18)-dien-3-O-beta-D-glucopyranosyl(1 --> 3) [beta-D-glucopyranosyl(1 --> 2)]-beta-D-fucopyranoside (1), together with two known flavonoids, were isolated from Stellaria media (L.) Cyr. The structure elucidation of the new compound was primarily based on HREIMS, EIMS, UV, IR, 1D- and 2D-NMR analyses, including COSY, HMQC and HMBC correlations.

A new sesquiterpenoid from rhizomes of Homalomena occulta.

A new sesquiterpeniod, 6alpha, 7alpha, 10alpha-trihydroxyisoducane (1), together with two known sesquiterpenoids, oplodiol (2) and oplopanone (3), were isolated from the chloroform extract of the rhizomes of Homalomena occulta. Their structures were elucidated by 1D and 2D NMR spectral interpretation.

Ginsenoside Re attenuate beta-amyloid and serum-free induced neurotoxicity in PC12 cells.

AIM: To study the effect of ginsenoside Re on PC12 cell damage induced by serum deprivation and beta-amyloid peptide. METHODS: PC 12 cell survival was measured by MTT and lactate dehydrogenase (LDH) assay. Results Serum-free medium and beta-amyloid peptide (10-100 microM) induced cytotoxicity in PC 12 cells. Ginsenoside Re (0.1-100 microM) attenuated the cytotoxic effects of serum-free medium and beta-amyloid peptide (50 microM) in a concentration-dependent manner. CONCLUSION: Ginsenoside Re prevented PC 12 cells from lesion induced by serum-free medium and beta-amyloid peptide.

Antipruritic and antinociceptive effects of Chenopodium album L in mice.

The ethanolic extract from the fruits of Chenopodium album L. (FCAL), orally administered at doses of 100-400 mg/kg, dose-dependently inhibited scratching behavior induced by 5-HT (10 micro g per mouse, s.c.) or compound 48/80 (50 micro g per mouse, s.c.) in mice. But it failed to affect hind paw swelling induced by 5-HT or compound 48/80 in mice at doses of 100 and 200 mg/kg and only showed a relatively weak inhibition on the swelling at a higher dose of 400 mg/kg. In addition, FCAL (200 and 400 mg/kg) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and the inflammatory pain response induced by an intraplantar injection of formalin in mice. At a dose of 400 mg/kg, it also inhibited the neurogenic pain response of formalin test. In conclusion, FCAL possesses antipruritic and antinociceptive activities and the antinociceptive effects are not secondary to anti-inflammatory effects. The findings support evidence for the clinical use of FCAL to treat cutaneous pruritus.

Cycloartane glycosides from Cimicifuga dahurica.

A new cycloartane bisdesmoside and two new trinorcycloartane glycosides, along with four known cycloartane compounds, were isolated from the rhizomes of Cimicifuga dahurica (Ranunculaceae). The structures of the new compounds were elucidated as 3-O-alpha-L-arabinopyranosyl cimigenol 15-O-beta-D-glucopyranoside, 24-hydroxy-12beta-acetoxy-25,26,27-trinorcycloartan-16,23-dione 3beta-O-alpha-L-arabinopyranoside, and 16alpha,24alpha-dihydroxy-12beta acetoxy-25,26,27-trinor-16,24-cyclocycloartan-23-one 3beta-O-alpha-L-arabinopyranoside by extensive NMR methods, FAB-MS, and hydrolysis.

Four new oleanane saponins from Anemone anhuiensis.

Four new oleanane triterpene saponins, anhuienosides C-F, together with three known saponins, were isolated from the rhizomes of Anemone anhuiensis (Ranunculaceae). The structures of anhuienosides C-F were elucidated as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, respectively.

Inhibition of xanthine and monoamine oxidases by stilbenoids from Veratrum taliense.

The bioassay guided refractionation of the methanol extract of roots and rhizomes of Veratrum taliense (Liliaceae) yielded five stilbenoids: veraphenol, resveratrol, piceid, isorhapontin, and mulberroside E, all inhibiting xanthine oxidase (XO, EC 1.2.3.2.) in vitro in a dose-dependent manner with IC50 values of 11.0, 96.7, 66.1, 70.0, and 78.4 microM, respectively. Veraphenol and mulberroside E were found to be mixed XO inhibitors with the Ki and Ki data of the former being 32.8 and 239.3 microM, and those of latter 32.5 and 13.8 microM, respectively. However, the inhibition on the enzyme by resveratrol, isorhapontin, and piceid was shown to be competitive with their Ki values of 9.7, 19.1, and 14.3 microM, respectively. Among the five stilbenoids, veraphenol and resveratrol were also revealed to inhibit competitively monoamine oxidase A (MAO, EC 1.4.3.4) with IC50 values at 38.0 and 26.6 microM, and Ki data 36.4 and 47.3 microM, respectively. However, none of the stilbenoids was inhibitory on MAO B in our assay. The structure-activity relationship examination showed that glycosylation of the stilbenoids could reduce the inhibition on XO and diminish the activity against MAO A, indicating that the free phenolic hydroxy group of the compounds was most likely essential for these bioactivities.

Secoiridoid constituents from the fruits of Ligustrum lucidum.

Two secoiridoid glucosides, lucidumosides A and B, as well as six known glucosides, oleoside dimethyl ester, ligustroside, oleuropein, nuezhenide, isonuezhenide, and neonuezhenide, were isolated from the fruits of Ligustrum lucidum. Their structures were elucidated by spectroscopic methods.

[Studies on chemical constituents from Anemone anhuiensis Y. K. Yang N. Wang et W. C. Ye].

OBJECTIVE: To investigate the constituents from the roots of Anemone anhuiensis. METHOD: To isolate chemical constituents, using solvent extraction together with column chromatography, FAB-MS and NMR methods were employed for strutural elucidation. RESULT AND CONCLUSION: Three compounds were isolated and elucidated as oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)- beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyransyl ester (cussonoside B), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- xylopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D- glucopyranosyl-(1-->6)-beta-D-glucopyransyl ester (flaccidoside II) and 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl- (1-->6)-beta-D-glucopyransyl ester (flaccidoside III), respectively. All of them were isolated from the plant for the first time.

[Cycloartane triterpenes and glycosides from Cimicifuga acerina].

AIM: To investigate the chemical constituents from the rhizomes of Cimicifuga acerina (Sieb. et Zucc.) Tanaka. METHODS: Column chromatgraphy (including silica gel and ODS) together with HPLC was used to separate the chemical constituents whose structures were determined by FAB-MS, NMR (1D and 2D) and hydrolysis methods. RESULTS: Five cycloartane triterpenoids were isolated and identified as: (22R)-22-hydroxycimigenol (I), (22R)-22-hydroxy-24-O-acetylhydroshengmanol 3-O-beta-D-xylopyranoside (II), dahurinol (III), 24-epi-24-O-acetyl-7,8-didehydroshengmanol 3-O-beta-D-xylopyranoside (IV), 25-O-acetyl-7,8-didehydrocimigenol 3-O-beta-D-xylopyranoside (V). CONCLUSION: Compound I is a new natural product, compound II is a new compound and compounds IV and V were isolated from this plant for the first time.

Oleanane saponins from Gymnema sylvestre.

Six oleanane-type saponins, along with two known triterpene saponins, were isolated from the leaves of Gymnema sylvestre. The structures of the oleanane triterpene glycosides were characterized as longispinogenin 3-O-beta-D-glucuronopyranoside, 21 beta-benzoylsitakisogenin 3-O-beta-D-glucuronopyranoside, 3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, oleanolic acid 3-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl(1-->6)-beta-D- glucopyranoside, 3-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester and 3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid 28-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester on the basis of hydrolysis and spectral evidence, including 1D- and 2D-NMR (TOCSY, ROESY, HMQC and HMBC) and FABMS analyses.

[Triterpene saponins from Pulsatilla cernua].

AIM: To investigate the chemical constituents of the roots of Pulsatilla cernua (Thunb.) Bercht. et Opiz. METHODS: Column chromatography (including D101 macroporous resin, silica gel and ODS) and HPLC were used to separate the chemical constituents whose structures were elucidated by FAB-MS, NMR (1D and 2D) and hydrolysis methods. RESULTS: Six compounds were isolated and established as hederagenin 3-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside (pulsatilla saponin A, 1), hederagenin 3-O-beta-D-glucopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L- arabinopyranoside (2), hederagenin' 3-O-alpha-L-rhamnopyranosyl(1-->2)[beta-D- glucopyranosyl(1-->4)]-alpha-L-arabinopyranoside (pulsatilla saponin D, 3), 3-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl ester (dipsacoside B, 4), 3-O-alpha-L-rhamnopyranosyl(1-->2) [beta-D-glucopyranosyl(1-->4)]-alpha-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl ester (cernuoside C, 5) and daucosterol (6), respectively. CONCLUSION: Compound 5 is a new compound and named as cernuoside C. Compounds 2, 4 and 6 were isolated from Pulsatilla cernua for the first time.

A new cycloartane saponin from Cimicifuga acerina.

A new cycloartane saponin along with two known compounds, cimigenol and cimigenol 3-O-beta-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-beta-D-xyloside on the basis of chemical and spectral evidence.

Triterpenoids from Pulsatilla chinensis.

A new lupane type triterpenic acid, pulsatillic acid, and two new lupane type triterpenoid glycosides, pulsatilloside A and B, along with the known 23-hydroxybetulinic acid were isolated from the roots of Pulsatilla chinensis. Their structures were characterized as 3-oxo-23-hydroxy-lup-20(29)-en-28-oic acid, 3 beta, 23-dihydroxy-lup-20(29)-en-28-oic acid 3-O-alpha-L-arabinopyranoside and 3 beta, 23-dihydroxy-lup-20(29)-en-28-oic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside on the basis of hydrolysis and spectral evidence including two-dimensional relay HOHAHA, one-dimensional multiple relay COSY and ROESY NMR techniques. Pulsatillic acid exhibited cytotoxic activities against P-388, Lewis lung carcinoma and human large-cell lung carcinoma.

Patensin, a saponin from Pulsatilla patens var. multifida.

Patensin, a new triterpenoid glycoside, was isolated from the ethanolic extraction of the roots of Pulsatilla patens var. multifida. Its structure was established as hederagenin 3-O-beta-D-galactopyranosyl-(1-->2)-beta-D- glucopyranoside on the basis of hydrolysis and spectral evidence including 1D and 2D NMR techniques.