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 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.

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.

[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.

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.

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.

[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.

[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.

Development of the fingerprint for the quality of Radix Linderae through ultra-pressure liquid chromatography-photodiode array detection/electrospray ionization mass spectrometry.

An ultra-pressure LC (UPLC) method has been developed and validated for the quality evaluation of a traditional Chinese medicine (Radix Linderae) by chemical fingerprint analysis with chromatograms collected at two wavelengths (260 and 320 nm). Eleven characteristic peaks in the fingerprints were identified by comparing their retention times, UV spectra and ESI-MS/MS data with those of the reference substances or the data in the literatures. Both correlation coefficient of similarities in chromatograms and relative peak areas of common peaks were calculated for quality expression of the Radix Linderae samples collected from different areas in China. The results showed high variation of relative peak area and correlation coefficients among the samples collected from various habitats, which indicated that the quality consistency of Radix Linderae is still a problem worthy of serious concern.

Protective effects of steroids from Allium chinense against H2O2-induced oxidative stress in rat cardiac H9C2 cells.

Allium chinense, a traditional herbal medicine, has been used for the treatment of cardiovascular diseases for hundreds of years. In this study, A. chinense steroids (ACSs) including three steroidal glycosides and their parent aglycones were isolated from the bulbs of A. chinense. For the first time, their cardioprotective effects were evaluated in cultured rat cardiac H9C2 cells by pretreatment with ACSs for 24 h before exposure to 0.2 mm H(2)O(2). The results showed the cell viability decreased markedly when H9C2 cells were incubated with 0.2 mm H(2)O(2) alone for 2 h, while the cell lipid peroxidation (estimated by the excessive production of nitric oxide and malondialdehyde) and intracellular free calcium concentration ([Ca(2+)](i)) increased significantly. The addition of 20 microm (below the toxic concentration) of ACSs notably attenuated the cellular injury induced by H(2)O(2). The effects of ACSs in our experiments were similar to those of nimodipine, a clinically applied calcium channel blocker. Preliminary analysis of the structure-activity relationship indicated that ACSs with a spirostane-type skeleton exhibited stronger protection than that with a furostane-type skeleton, and glycosylation of the steroids could substantially lower the protective activities. The above results suggested the protective effects of steroids originated from A. chinense on the oxidative injury of H9C2 cells and ACSs may have potential for preventing cardiac injuries induced by oxidative stress.

Sesquiterpene lactones from the root tubers of Lindera aggregata.

Phytochemical investigation of the root tubers of Lindera aggregata resulted in the isolation of five new sesquiterpene lactones, linderagalactones A-E (1-5), along with eight known sesquiterpenoids, 3-eudesmene-1beta,11-diol, hydroxylindestenolide, strychnistenolide, hydroxyisogermafurenolide, atractylenolide III, linderane, neolinderalactone, and linderalactone. The structures and relative configurations of 1-5 were determined by spectroscopic methods, especially HRESIMS and 2D NMR techniques. The absolute configurations of 1-4 were defined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Linderagalactone A (1) is a halogenated sesquiterpene lactone possessing a unique rearranged carbon skeleton. Linderagalactone E (5), linderane, hydroxylindestenolide, and linderalactone showed hepatoprotective activity against H2O2-induced oxidative damages on HepG2 cells with EC(50) values of 67.5, 167.0, 42.4, and 98.0 microM, respectively.

Cycloartane triterpenoids from Kleinhovia hospita.

Four new cycloartane triterpenoids, together with the known gardenolic acid B, were isolated from Kleinhovia hospita. The triterpenoids (1-3) contain a unique 21,23-diacetal side-chain, while compound 4 contains two alpha,beta-unsaturated ketone moieties. Their structures and relative configurations were determined by spectroscopic methods, including 2D NMR and IR. These compounds showed promising hepatoprotective effects on nitrofurantoin-induced cytotoxicity in human liver-derived Hep G2 cells.

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.

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.

A new dibenzofuran and other constituents from Ligularia caloxantha, a Chinese medicinal plant.

A new dibenzofuran named 1,2,4-trimethyl-7,8-dimethoxy-dibenzofuran (1), together with seven known compounds, euparin (2), 2,5-diacetyl-6-hydroxy-benzofuran (3), 2-acetyl-5,6-dimethoxy-benzofuran (4), gummosogenin (5), lupeol (6), stigmasterol (7) and (E)-2,5-dihydroxy-cinnamic acid (8), were isolated from the roots of Ligularia caloxantha, a Chinese medicinal plant. The structures of the compounds were elucidated by spectroscopic methods.

[Progress on antineoplastic constituents derived from polypore fungi].

Polypore fungi is a cluster of important pharmacological fungi with significant antitumor activity. In recent years, the antineoplastic constituents from polypore fungi have been comprehensively studied. Through investigating the domestic and overseas studied paper, the antitumor active constituents derived from polypore fungi including high molecular weight compounds such as polysaccharides, glycopeptides, glycoproteins, lectins, and lipid soluble low molecular weight compounds such as terpenoids, steroids, phenolics, benzopyranones, were reviewed. In addition, the significance in the exploitation of new drug for antitumor by the application of polypore fungi was discussed at the end of this paper.

[Studies on chemical constituents from herbs of Taraxacum mongolicum].

OBJECTIVE: To investigate the chemical constituents of the herbs of Taraxacum mongolicum. METHOD: The chemical constituents were isolated by various column chromatographic methods and their structures elucidated mainly by NMR and MS evidences. RESULT: Forty-four components were obtained and identified were as artemetin (1), quercetin (2), quercetin-3', 4', 7-trime-thyl ether (3), luteolin (4), luteolin-7-O-beta-D-glucopyranoside (5), luteolin-7-O-beta-D-galactopyranoside (6), genkwanin (7), isoetin (8), hesperetin (9), genkwanin-4'-O-beta-D-lutinoside (10), hesperidin (11), quercetin-7-O-[beta-D-glucopyranosyl (1-->6) -beta-D-glucopyranoside (12), quercetin-3, 7-O-beta-D-diglucopyranoside (13), isoetin-7-O-beta-D-glucopyranosyl- 2'-O-alpha-L-arabinopyranoside (14), isoetin-7-O-beta-D-glucopyranosyl-2'-O-alpha-D-glucopyranoside (15), isoetin-7- O-beta-D-glucopyranosyl-2'-O-beta-D-xyloypyranoside (16), caffeic acid (17), furulic acid (18), 3-O-caffeoylquinic acid (19), 3, 5-di-O-caffeoylquinic acid (20), 3, 4-di-O-caffeoylquinic acid (21), 4, 5-di-O-caffeoylquinic acid (22), 1-hydroxymethyl-5-hydroxy-phenyl-2-O-beta-D-glucopyranoside (23), p-hydroxybenzoic acid (24), p-coumaric acid (25), 3, 5-dihydroxylbenzoic acid (26), gallic acid (27), gallicin (28), syringic acid (29), 3, 4-dihydroxybenzoic acid (30), caffeic acid ethyl ester (31), esculetin (32), rufescidride (33), mongolicumin A [6, 9, 10-trihydroxy-benzoxanthene-1, 2-dicarboxylic acid] (34), mongolicumin B [1 l-hydroxy-2-oxo-guaia-1 (10), 3, 5-trien-8, 12-lactone] (35), isodonsesquitin A (36), taraxacin (37), sesquiterpene ketolactone (38), taraxasteryl acetate (39), phi-taraxasteryl acetate (40) and lupenol acetate (41), palmitic acid (42), beta-sitosterol (43), and stigmasterol (44). CONCLUSION: Four compounds (14, 15, 34 and 35) were new compounds, compounds 1, 3, 6-13, 20-22, 30 and 31 were isolated from this genus for the first time, while compounds 18, 23-29, 32 and 37-42 were obtained from this species for the first time.

[Studies on constitutes from Taraxacum mongolicum].

OBJECTIVE: To study the chemical constituents of Taraxacum mongolicum. METHOD: Repeated column chromatography over silica gel, C-18 and Sephadex LH-20 were used to isolate chemical constitutes and their structures were elucidated by spectroscopic methods MS, 1H-NMR, 13C-NMR including 2D-NMR techniques and by direct comparing spectral data with those reported in literatures. RESULT: Eight compounds were identified as artemetin (1), quercetin (2), luteolin (3), luteolin-7-O-beta-D-glucopyranoside (4), caffeic acid (5), esculetin (6), stigmasterol (7), taraxasteryl acetate (8), respectively. CONCLUSION: Compound 1 was obtained from this genus and compound 6, 8 from this species for the first time. Furthermore, the 13 carbon data of compound 6 from the literature were corrected with 2D-NMR techniques in this paper.

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.