[A new phenylethanol glycoside from Baphicacanthis Cusiae Rhizoma et Radix].

The 95% ethanol extract of Baphicacanthis Cusiae Rhizoma et Radix was purified by multi-chromatographic methods including microporous resin, silica gel, Sephadex LH-20, and C_(18) reversed-phase column chromatography. Fourteen compounds were isolated and structurally identified, including five phenylethanoid glycosides, five phenylpropanoids, one lupinane triterpene, two alkaloids, and one flavonoid, listed as follows: 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol B(1), threo-2,3-bis-(4-hydroxy-3-methoxybenzene)-3-methoxypropanol(2), 2-(3-hydroxy-4-methoxyphenyl)-ethanol-1-O-[3,4-O-di-acetyl-(1→3)-O-α-L-rhamnopyranosyl]-ß-D-glucopyranoside(3), verbascoside(4), 2″,3″-di-O-acetyl martynoside(5),(+)-pinore-sinol(6), diospyrosin(7), daidzein(8), wiedemannioside B(9), buddlenol A(10), 2″-O-acetyl martyonside(11), lupeol(12), indirubin(13), and tryptanthrin(14). Compound 3 was a new phenylethanoid glycoside, and the other 10 compounds were isolated for the first time from Baphicacanthis Cusiae Rhizoma et Radix except compounds 12, 13, and 14.

An Efficient Regioselective Synthesis of 8-Formylhomoisoflavonoids with Neuroprotective Activity by Enhancing Autophagy.

6-Formylisoophiopogonone B (7a) and 8-formylophiopogonone B (7b), two natural products isolated from Ophiopogon japonicus, represent a subgroup of rare 6/8-formyl/methyl-homoisoflavonoid skeletons. Herein we report an efficient method for the synthesis of these formyl/methyl-homoisoflavonoids. The synthesized compounds were evaluated for their neuroprotective effects on the MPP+-induced SH-SY5Y cell injury model and showed marked activity. Exploration of the neuroprotective mechanisms of compound 7b led to an increased expression of autophagy marker LC3-II and down-regulation of autophagy substrate p62/SQSTM1. Molecular docking studies showed that 7b may prevent the inhibition of the classic PI3K-AKT-mTOR signaling pathway by interfering with the human HSP90AA1.

[A new spirocyclic cycloartane triterpenoid from Souliea vaginata].

The 70% ethanol extract of the whole plant of Souliea vaginata was purified by multi-chromatographic methods including macroporous resin,silica gel,Sephadex LH-20,and C18-reversed-phase column chromatography. A new spirocyclic cycloartane triterpenoid was isolated and identified as( 16 R*,20 R*,23 S*,24 R*,25 S*)-16,23: 23,26-diepoxy-15α,24,25-trihydroxy-9,19-cycloart-3ß-O-ß-D-xylopyranoside( 1),and named as soulieoside S. Its planar structure and relative configuration were determined by spectroscopic techniques including 2 D NMR and HRESI-MS. As one of the main components of S. vaginata,compound 1 was evaluated for its anti-inflammatory activity by a lipopolysaccharide( LPS)-stimulated NO production model in RAW264. 7 macrophages,but it didn't show NO production inhibitory effect.

Tautomerism and bioactivities of curcumenol, a common sesquiterpenoid widely existing in edible plants.

Curcumenol was firstly revealed as a pair of hemiacetal-ketone tautomers in solutions by using temperature variation 1H-NMR experiments, 2D NMR, and chemical methods. Quantum chemical calculation allowed the explanation of its spectroscopic behavior. An antioxidative SAR study on its derivatives verified the tautomeric bio-significance. Curcumenol also remarkably enhanced myogenic differentiation and mitochondrial function.

Benzofurans from Eupatorium chinense enhance insulin-stimulated glucose uptake in C2C12 myotubes and suppress inflammatory response in RAW264.7 macrophages.

Fourteen acetylbenzofuran derivatives, including three undescribed carbon skeletons with a newly formed hexane or benzene ring on the other side of the benzofuran ring, (±)-eupatonin A (1), (±)-eupatonin B (2), and eupatonin C (3), two new benzofurans (-)-12ß-hydroxygynunone (4) and (+)-12-hydroxyl-13-noreuparin (5), as well as 9 known ones (6-14), were isolated from 95% ethanol extract of the roots of Eupatorium chinense. Their structures were determined by spectroscopic methods and quantum chemical DFT and TDDFT calculations of the NMR chemical shifts and ECD spectra, which helped in the determination of the relative configurations of 1 and 2 and the absolute configurations of 4 and 5, respectively. 1 and 2 were further identified to be racemic mixtures by chiral HPLC analysis. All compounds were evaluated for insulin-stimulated glucose uptake in differentiated C2C12 myotubes. Compounds 1, 3, 4, 5, 11, 12, and 13 markedly enhanced insulin-mediated glucose uptake. (±)-Eupatonin A (1) activated the IRS-1/Akt/GSK-3ß signaling pathway and enhanced insulin stimulated GLUT4 membrane translocation in C2C12 myotubes. On LPS stimulated RAW264.7 macrophages, several compounds exhibited significant inhibitory effect on NO production with IC50 values ranging from 4.94 to 9.70 µΜ. (±)-Eupatonin A (1) again dose-dependently suppressed LPS-induced NO production and decreased the expression of inducible NO synthase (iNOS), through inhibiting NF-κB activity.

Triterpenoids from Cyclocarya paliurus that Enhance Glucose Uptake in 3T3-L1 Adipocytes.

Four previously undescribed compounds, including three rarely occurring seco-dammarane triterpenoid glycosides and a pentacyclic triterpenic acid, were isolated from a 70% ethanol extract of the leaves of Cyclocarya paliurus (Juglandaceae), along with eleven known triterpenoids. Their structures were determined by spectroscopic techniques, including 2D NMR and HRESIMS, as well as chemical methods. Among them, several triterpenoids enhanced insulin stimulated glucose uptake in both 3T3-L1 adipocytes and C2C12 myotubes. Furthermore, compound 1 dose-dependently increased glucose uptake through activating AMP-activated protein kinase (AMPK)-p38 pathway. Collectively, triterpenoids from C. paliurus could be developed as insulin sensitizers, which might have therapeutic potential for insulin resistance and hyperglycemia.

Cycloartane triterpenoids from Actaea vaginata with anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages.

Five undescribed cycloartane triterpenoids, including two cycloartane trinor-triterpenoids, were isolated from a 70% ethanol extract of the whole plant of Actaea vaginata (Ranunculaceae), together with thirteen known cycloartane triterpenoids. Their structures were determined by spectroscopic techniques and quantum chemical calculations for intramolecular noncovalent interactions with reduced density gradient method. All compounds were evaluated for their anti-inflammatory effects by a lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production model in RAW264.7 macrophage cells, and some showed potent inhibitory effects with IC50 values ranging from 5.0 to 24.4 µM. Further mechanism studies showed that one compound dose-dependently suppressed LPS-induced NO production and pro-inflammatory cytokines secretion, and decreased the expression of iNOS, through inhibiting NF-κB activation.

Terpenoids from Curcuma wenyujin increased glucose consumption on HepG2 cells.

Thirty four terpenoids, including two new cadinane-type sesquiterpenoids containing conjugated aromatic-ketone moieties, curcujinone A (1) and curcujinone B (2), were isolated from 95% ethanol extract of the root tubers of Curcuma wenyujin. Their structures were determined by spectroscopic methods, especially 2D NMR and HRMS techniques. The relative and absolute configurations of 1 and 2 were identified by quantum chemical DFT and TDDFT calculations of the 13C NMR chemical shifts, ECD spectra, and specific optical rotations. All compounds and extracts were evaluated for their anti-diabetic activities with a glucose consumption model on HepG2 Cells. The petroleum fraction CWP (10µg/mL) and compounds curcumenol (4), 7α,11α-epoxy-5ß-hydroxy-9-guaiaen-8-one (5), curdione (17), (1S, 4S, 5S 10S)-germacrone (18), zederone (20), a mixture of curcumanolide A (25) and curcumanolide B (26), gajutsulactone B (27), and wenyujinin C (30) showed promising activities with over 45% increasing of glucose consumption at 10µM.

Cimicifoetones†A and B, Dimeric Prenylindole Alkaloids as Black Pigments of Cimicifuga foetida.

Two dimeric prenylindole alkaloids with a unique indole-benzoindolequinone skeleton, cimicifoetones A (1) and B (2), were isolated as black pigments from the rhizomes of Cimicifuga foetida. The structures were elucidated by spectroscopic methods including HRMS and 2D NMR, as well as single-crystal X-ray diffraction and computational chemical modeling techniques. Cimicifoetones A and B represented the first examples of dimeric indole alkaloids generated through [4+2] Diels-Alder cycloaddition between the prenyl side chain in one 3-prenylindole and the aromatic ring in another. The two compounds showed promising anti-proliferative activity on seven tumor cell lines with IC50 values in the range of 1.36-21.09 µm. Flow cytometric and western blot analysis revealed that compound 2 induced cell apoptosis via death receptor-mediated extrinsic and mitochondrial-mediated intrinsic pathways.

New homoisoflavonoid analogues protect cells by regulating autophagy.

As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.

Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice.

BACKGROUND: Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases. HYPOTHESIS: The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling. STUDY DESIGN: SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min. METHODS: High-resolution positron emission tomography scanner (micro-PET) was used for small animal imaging to examine glucose metabolism. Rota-rod time and neurological deficit scores were calculated after 24h of reperfusion. The volume of infarction was determined by Nissl-staining. The calpain proteolytic activity and eNOS uncoupling were determined by western blot analysis. RESULTS: SAA administration increased glucose metabolism and ameliorated neuronal damage after brain ischemia, paralleled with decreased neurological deficit and volume of infarction. In addition, SAA pretreatment inhibited eNOS uncoupling and calpain proteolytic activity. Furthermore, SAA inhibited peroxynitrite (ONOO-) generation and upregulates AKT, FKHR and ERK phosphorylation. CONCLUSION: These findings strongly suggest that SAA elicits a neurovascular protective role through the inhibition of eNOS uncoupling and ONOO- formation. Moreover, SAA attenuates spectrin and calcineurin breakdown and therefore protects the brain against ischemic/reperfusion injury.

Design, synthesis, and antimicrobial activities of new tanshinone IIA esters.

Sixteen new ester derivatives with various partition coefficient (ClogP) values of tanshinone IIA (TSIIA), a major lipophilic component of Salvia miltiorrhiza, were designed and synthesised, including six aliphatic esters (3a-e, 5a), one phosphate ester (4c) and nine aromatic esters (5b-j). Their antimicrobial activities against three Gram-positive bacteria strains, Staphylococcus aureus, Bacillus subtilis, and Bacillus amyloliquefaciens, and two Gram-negative bacteria strains, Pseudomonas aeruginosa and Escherichia coli, as well as two fungi species, Candida albicans and Saccharomyces cerevisiae, were evaluated in vitro by broth microdilution susceptibility tests. The results showed that keeping ClogP values in a certain range is necessary for their antimicrobial activities. For those compounds with ClogP values between 5 and 10, their MIC values showed positive correlations with ClogP values. In particular, compound 3e exhibited fourfold and twofold higher potency than the standard drug amphotericin B against fungi C. albicans and S. cerevisiae with MIC values of 1.95 and 7.81 µg/mL, respectively.

Correlation between the expression of S100A4 and the efficacy of TAC neoadjuvant chemotherapy in breast cancer.

The aim of this study was to investigate the correlation between the expression of S100A4 and the efficacy of neoadjuvant chemotherapy in breast cancer. A total of 65 patients with invasive breast cancer were treated with neoadjuvant chemotherapy using the TAC regimen. The expression of S100A4 was detected by an immunohistochemical two-step method prior to treatment, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy. Pathological evaluations of the chemotherapy were performed using the Miller and Payne (MP) grading system and their correlation with the changes of S100A4 expression during and after the treatment were explored. Between pre-neoadjuvant chemotherapy and 4 cycles post-chemotherapy, there was a significant difference in the expression of S100A4 (P<0.05); S100A4 expression was associated with neoadjuvant chemotherapy. However, between pre-neoadjuvant chemotherapy and 2 cycles post-chemotherapy, there was no significant difference in the expression of S100A4 (P>0.05). The intensity and changes of S100A4 expression were positively correlated with the efficacy of neoadjuvant chemotherapy (r=0.259, P<0.05). When patients with an MP grade of I or II following the second cycle of neoadjuvant chemotherapy were continually treated with the original chemotherapy for another 2 cycles, the desired effect was generally not achieved. S100A4 may be used as a predictor of the efficacy of neoadjuvant chemotherapy in breast cancer, guiding the formulation of individualized programs to improve the effectiveness of the treatment. For patients with an MP grade level of I or II after 2 cycles of neoadjuvant chemotherapy, the use of alternative chemotherapy regimens should be considered.

Eight new cycloartane triterpenoids from Beesia calthifolia with hepatoprotective effects against D-galactosamine induced L02 cell damage.

Fourteen 20,24-epoxy-cycloartane triterpenoids, including eight new ones (1-8), were isolated from 95% ethanol extract of the rhizomes of Beesia calthifolia. Their structures were determined by spectroscopic and chemical methods, especially 2D NMR and HRMS techniques. Among them, four new compounds (1-4) possess carbonyl groups at C-16, which were rarely found in cycloartane triterpenoids from this genus. Relative configuration at C-12 in beesioside III (9) and its aglycone (10) was revised to be 12α-OH rather than the reported 12ß-OH. Some of the compounds showed potential hepatoprotective activities against human hepatic L02 cell damage induced by d-galactosamine.

Five new cycloartane triterpenoids from Beesia calthifolia.

Phytochemical study on rhizomes of Beesia calthifolia resulted in the isolation of five new (1-5) and three known (6-8) cycloartane triterpenoids possessing a hemiketal or ketal group at C-24 from the EtOAc fraction of 95% ethanol extract. Their structures were determined by spectroscopic and chemical methods, especially HRMS and 2D NMR techniques. Compounds 3 and 4 showed potential hepatoprotective activities against D-galactosamine induced human hepatic L02 cell damage.

Effects and molecular mechanisms of the antidiabetic fraction of Acorus calamus L. on GLP-1 expression and secretion in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: The radix of Acorus calamus L. (AC) is widely used in diabetes therapies in traditional folk medicine from America and Indonesia, and we have previously reported that the ethyl acetate fraction of AC (ACE) acts as an antidiabetic through insulin sensitizing, insulin releasing and alpha-glucosidase inhibitory activities. The present study is designed to investigate the effects and molecular mechanisms of ACE on glucagon-like peptide-1 (GLP-1) expression and secretion related to its hypoglycemic effects. MATERIALS AND METHODS: The hypoglycemic effect of ACE (100mg/kg, i.g.) was confirmed by testing blood glucose levels or via oral glucose tolerance test (OGTT) in streptozotocin (STZ) induced hyperglycemic mice, db/db diabetic mice and diet-induced obese (DIO) mice. Plasma insulin, GLP-1 levels and intestinal GLP-1 related gene expression were determined in STZ-induced and db/db diabetic mice. The in vitro effects of ACE (12.5µg/ml) on the expression and secretion of GLP-1 were detected in NCI-H716 intestinal L-cells, and the correlation between ACE and molecules in the Wnt signaling pathway was further explored. RESULTS: ACE (100mg/kg) significantly lowered fasting blood glucose in STZ-induced and db/db diabetic mice and improved the OGTT in DIO mice. Insulin releasing and islet protective effects, along with the increased secretion of GLP-1, were observed. The expression of proglucagon gene (gcg) and post-translational processing gene prohormone convertase 3 (pc3) and the GLP-1 content in the culture medium of L-cells notably increased after the ACE treatment (12.5µg/ml). At the same time, ß-catenin nuclear translocation occurred, and its downstream protein cyclin D1 was activated, showing the involvement of Wnt signaling. CONCLUSIONS: ACE might activate Wnt signaling to increase the gene expression of gcg and pc3 and exert incretin effects, including insulinotropic and islet protection, to lower blood glucose levels via elevated GLP-1 secretion either directly or indirectly.

Kleinhospitines A-D, new cycloartane triterpenoid alkaloids from Kleinhovia hospita.

Kleinhospitines A-D, four unprecedented cycloartane triterpenoid alkaloids possessing a spiro α,ß-unsaturated γ-lactamlactone side chain, were isolated as two mixtures of C-23 epimers from Kleinhovia hospita. Kleinhospitines C and D represent the first examples of naturally occurring cycloartane triterpenoids with a 9α,10α-cyclopropyl ring. The structures and absolute configurations were determined on the basis of spectroscopic analyses and comprehensive quantum chemical calculations. The two mixtures showed hepatoprotective activity against H2O2-induced oxidative damages on primary cultured rat hepatocytes with EC50 values of 167.0 and 126.5 µM.

Terpenoids from Cichorium intybus.

A new sesquiterpenoid, 1alpha,5alpha-epoxy-4alpha-hydroxyl-4beta,10beta-dimethyl-7alphaH,10alphaH-guaia-l1(13)-en-12-oic acid (1), and four known compounds, lactucin (2), 1beta-hydroxy-7alphaH,8,11betaH-eudesm-3-en-8,12-olide (3), 13,14-seco-stigma 9(11),14(15)-dien-3alpha-ol (4), and bacosterol-3-O-beta-D-glucopyranoside (5) were isolated from Cichorium intybus L. Their structures were determined on the basis of detailed analysis of their 1D- and 2D-NMR spectroscopic and mass spectrometric data. Compounds 2 and 4 showed strong activities against the A2780 cell line with IC50 values of 1.81 and 0.07 microM, respectively.

[Study on the chemical constituents of the roots of Dendropanax chevalieri].

OBJECTIVE: To study the chemical constituents of the roots of Dendropanax chevalieri. METHODS: The constituents were isolated by column chromatography with silica gel, Sephadex LH-20 gel and RP-18. Their structures were elucidated by analysis of spectral data and physicochemical properties. RESULTS: Eight compounds were isolated and identified as palmitic acid (1), dibutylphthalate (2), beta-sitosterol (3), coniferaldehyde (4), scopoletin (5), beta-hydroxypropiovanillone (6), (+)-pinoresinol (7), (+)-syringaresinol (8). CONCLUSION: Compounds 1-2, 4-8 are obtained from this genus for the first time.

[Chemical constituents of Acorus calamus].

OBJECTIVE: To study the chemical constituents contained in Acorus calamus. METHOD: The chemical constituents were separated and purified by various chromatographic methods including silica gel, ODS, HPLC and Sephadex LH-20, and their structures were identified on the basis of analysis on spectroscopic data. RESULT: Ten compounds were separated from A. calamus and identified as 1beta, 4beta, 7alpha-trihydroxyeudesmane (1), bullatantriol (2), teuclatriol (3), threo-1', 2'-dihydroxyasarone (4), erythro-1', 2'-dihydroxyasarone (5), (+)-de-4'-O-methyleudesmin (6), (+)-de-4'-0-methylmagnolin (7), (+)-eudesmin (8), (+)-magnolin (9) and beta-sitosterol (10), respectively. CONCLUSION: Compounds 1-2,4-9 were separated from this plant for the first time. Specifically, compounds 1-2,6-9 were obtained from Acorus genus for the first time.