Five new biflavonoids with acetylcholinesterase inhibitory activity from Diphylleia sinensis.

Five new biflavonoids, diphybiflavonoids A - E (1-5), were isolated from the roots and rhizomes of Diphylleia sinensis. Their structures were elucidated by extensive spectroscopic data, including UV, IR, HR-ESI-MS and 2D NMR. Their absolute configurations were determined by ECD spectra. All isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activity. Compounds 1-4 exhibited the potent AChE inhibitory activities with IC50 values of 1.62, 2.10, 2.08, and 5.15 µM, respectively. The preliminary structure-activity relationship study indicated that the connection mode (C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''') of biflavonoid subunits, and 3-hydroxy group of flavonol subunit were important structural factors for AChE inhibitory activity. Biflavonoids, containing a C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''' linkage, can be a potentially useful platform for development of cholinesterase inhibitors.

2,3-Seco and 3-nor guaianolides fromAchillea alpina with antidiabetic activity.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1ß, which was achieved through the suppression of the NLRP3 pathway.

Chemical constituents from Acorus calamus with potent anti-diabetic and hepatoprotective activities.

Three previously undescribed compounds, (+)-7S,8S-syringoylglycerol-7-O-3',4'-dihydroxylphenylethanol (1), (+)-2S,3R-piscidic acid 1-methyl-5-ethyl ester (2), and 2'S-2-acetyl-3-(2,3-dihydroxypropoxyl)furan (3), together with one new natural product, 7S,8S-4,7,8-trihydroxyl-methyl phenylpropionate (4) and a known lignan (7S,8R)-methyl-4',7-epoxy-3,3'-dimethoxy-4,9-dihydroxylignan-9'-oate (5), were isolated from the ethanol extract of Acorus calamus Linn. rhizomes. Their structures were determined based on extensive spectroscopic analyses and computational methods. All the isolated compounds were evaluated for their in vitro GK activating and hepatoprotective activities, and compound 5 exhibited significant GK activating activity at 10-5 mol/L, compound 3 exhibited moderate protective effects to APAP-induced injuries of HepG2 cells at 10-5 mol/L. Furthermore, molecular docking of compound 5 bound with GK was carried out to investigate the possible structural insights into the potential binding patterns.

[Alkaloids from fruit of Lycium chinense var. potaninii].

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 µmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Dysosmaflavonoid A-F, new flavonols with potent DPPH radical scavenging activity from Dysosma versipellis.

Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 µM, respectively, in comparison with Trolox (IC50, 15.80 µM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect.

Structural characteristics and in vitro and in vivo immunoregulatory properties of a gluco-arabinan from Angelica dahurica.

A water-soluble polysaccharide identified here as ADP80-2 was acquired from Angelica dahurica. ADP80-2 was a gluco-arabinan composed of arabinose and a trace of glucose with a molecular weight of 9950 g/mol. The backbone of ADP80-2 comprised →5)-α-L-Araf-(1→, →3, 5)-α-L-Araf-(1→, →6)-α-D-Glcp-(1→, with a terminal branch α-L-Araf-(1 → residue. In terms of immunoregulatory activity, ADP80-2 can significantly promote the phagocytosis, the production of nitric oxide (NO), and the secretion of cytokines (IL-6, IL-1ß, and TNF-α) of macrophage. In addition to the cellular immunomodulatory activities, the chemokines related to immunoregulation were significantly increased in the zebrafish model after treated with ADP80-2. These biological results indicated that ADP80-2 with immunomodulatory effects was expected to be useful for the development of new immunomodulatory agents. Simultaneously, the discovery of ADP80-2 further revealed the chemical composition of A. dahurica used as a traditional Chinese medicine and spice.

Lycibarbarines A-C, Three Tetrahydroquinoline Alkaloids Possessing a Spiro-Heterocycle Moiety from the Fruits of Lycium barbarum.

Three tetrahydroquinoline alkaloids, lycibarbarines A-C (1-3), possessing a unique tetracyclic tetrahydroquinoline-oxazine-ketohexoside fused motif, were isolated from the fruits of Lycium barbarum. Their structures were determined by spectroscopic analysis and quantum-chemical calculations. Compounds 1 and 3 exhibited neuroprotective activity when evaluated for corticosterone-induced injury by reducing the apoptosis of PC12 cells through the inhibition of caspase-3 and caspase-9.

Sesquiterpenoids from Artemisia argyi and their NO production inhibitory activity in RAW264.7 cells.

Investigation into the chemical diversity of Artemisia argyi led to the discovery of two new (1, 4) and four known (2-3, 5-6) sesquiterpenoids. The new structures were determined via extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 1.91 to 36.52 µM.

1,10-seco guaianolide-type sesquiterpenoids from Chrysanthemum indicum.

ABSTACTA chemical investigation of the whole plant of traditional Chinese medicine, Chrysanthemum indicum L., led to the discovery of six guaianolide-type sesquiterpenoids 1-6 with a 1,10-splited skeleton. The structure of the new compound 1 was established by extensive analysis of UV, IR, MS, NMR and ECD data. Compounds 3-6 are mutually stereoisomers with four chiral centers and their absolute configurations were determined by comparison of ECD spectra. The anti-inflammatory effects of these isolates on lipopolysaccharide (LPS)-induced nitric oxide (NO) were investigated in RAW 264.7 cells. Results showed that most of the compounds displayed NO production inhibitory activities with IC50 values ranged from 3.54 to 8.17 µM.

Solanrubiellin A, a hydroanthraquinone dimer with antibacterial and cytotoxic activity from Solanum lyratum.

A new hydroanthraquinone dimer derivative, solanrubiellin A, was isolated from the whole plants of Solanum lyratum. The structure of 1 was established through extensive NMR spectroscopy analysis, and the absolute configuration was elucidated by comparison of its experimental and calculated ECD spectra. Compound 1 showed antibacterial activity with MIC values of 2-10 µM against several Gram-positive bacteria. Compound 1 also demonstrated cytotoxic activity against human A549, HT-29 and HL-60 cell lines with IC50 values ranging from 2.06 to 9.35 µM.

Antihyperlipidemic glycosides from the root bark of Lycium chinense.

Three new glycosides (1-3), together with six known ones (4-9), were isolated from the root bark of Lycium chinense. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Five compounds (3, 5, 6, 8, and 9) exhibited potent antihyperlipidemic activities in HepG2 cells as assessed by Oil Red O staining and significant inhibition of intracellular triglyceride (TG) levels, whereas two compounds (5 and 9) significantly reduced total cholesterol (TC) levels.

Application of high-speed counter-current chromatography and HPLC to separate and purify of three polyacetylenes from Platycodon grandiflorum.

Three polyacetylenes were isolated and purified from Platycodon grandiflorum A. DC for the first time by high-speed counter-current chromatography using a two-phase solvent system composed of hexane/ethyl acetate/methanol/water (1:31:1:31, v/v/v/v) and high-performance liquid chromatography with an Agilent ZORBAX® SB-C18 column (4.6 mm × 150 mm, 5 µm). After separation by high-speed counter-current chromatography and high-performance liquid chromatography, we obtained 3.5 mg of platetyolin A, 4.1 mg of platetyolin B, and 18.1 mg of lobetyolin with purities of 97.2, 96.7, and 96.9%, respectively. The purity of each compound was assessed by high-performance liquid chromatography and the chemical structures were evaluated by high-resolution electrospray ionization time-of-flight mass spectrometry and one- and two-dimensional NMR spectroscopy. Among the isolated compounds, platetyolin A and platetyolin B are newly reported compounds.

Homoisoflavanones with estrogenic activity from the rhizomes of Polygonatum sibiricum.

A new homoisoflavanone, (3R)-5-hydroxy-7-methoxyl-3-(2'-hydroxy-4'- methoxybenzyl)-chroman-4-one (1), together with six known analogs, were isolated from the rhizomes of Polygonatum sibiricum. Their structures were elucidated on the basis of extensive spectroscopic analysis. All compounds were tested for their estrogenic activity using the MCF-7 estrogenresponsive human breast cancer cell lines. At a dose of 0.1 µmol/L, compounds 1-7 exhibited significant proliferative effects on MCF-7 cells compared with E2. The molecular docking study results indicated that the activity of compounds 3, 5, 6, and 7 may be the binding with ERR.

Lignanamides with potent antihyperlipidemic activities from the root bark of Lycium chinense.

Seven new lignanamides, lyciumamides D-J (1-4 and 9-11), together with nine known analogues (5-8 and 12-16), were isolated from the root bark of Lycium chinense. The structures of the isolated compounds were elucidated on the basis of NMR spectroscopic and HRESIMS data. All isolated compounds were evaluated for antihyperlipidemic activities in HepG2 cells. The primary structure-activity relationships were discussed.

Therapeutic effects of curcumin nanoemulsions on prostate cancer.

The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.

Therapeutic Effects of Curcumin Nanoemulsions on Prostate Cancer / 华中科技大学学报（医学）（英德文版）

The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability.The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur.Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology,droplet size and zeta potential.The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur.Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur,as assessed by apoptosis and cell cycle studies.In siru single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur.Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.

[Chemical Constituents from Eucommia ulmoides].

Objective: To investigate the chemical constituents from the barks of Eucommia ulmoides. Methods: After the reflux extraction of the barks of Eucommia ulmoides with 95% ethanol, and the ethyl acetate part was separated and purified by chromatographic methods, such as silica gel, Sephadex LH-20, and ODS C18. The structures of isolated compounds were elucidated with modern spectral methods. Results: Five lignanoids and three phenylpropanoids were isolated from Eucommia ulmoieds, which were confirmed as cycloolivil (1), (7R, 8S, 8'R)-4, 9, 4', 8'-tetrahydroxy-3, 3'-dimethyoxyl-7, 9'-monoepoxy lignan (2), erythro-guaiacyl-glycerol-ß-coniferyl aldehyde ether (3), pinonesinol (4), 8-hydroxypinoresinol (5), C-veratroylglycol (6), ß-hydroxyl-3-methoxyl-4-hydroxyacetophenone (7) and 3-hydroxy-4-methoxycinnamaladehyde (8). Conclusion: Compounds 5­8 are isolated from this plant for the first time.

Preparative Isolation of Two Prenylated Biflavonoids from the Roots and Rhizomes of Sinopodophyllum emodi by Sephadex LH-20 Column and High-Speed Counter-Current Chromatography.

Two prenylated biflavonoids, podoverines B-C, were isolated from the dried roots and rhizomes of Sinopodophyllum emodi using a Sephadex LH-20 column (SLHC) and high-speed counter-current chromatography (HSCCC). The 95% ethanol extract was partitioned with ethyl acetate in water. Target compounds from the ethyl acetate fraction were further enriched and purified by the combined application of SLHC and HSCCC. n-Hexane-ethyl acetate-methanol-water (3.5:5:3.5:5, v/v) was chosen as the two phase solvent system. The flow rate of mobile phase was optimized at 2.0 mL·min(-1). Finally, under optimized conditions, 13.8 mg of podoverine B and 16.2 mg of podoverine C were obtained from 200 mg of the enriched sample. The purities of podoverines B and C were 98.62% and 99.05%, respectively, as determined by HPLC. For the first time, podoverins B and C were found in the genus Sinopodophyllum. Their structures were determined by spectroscopic methods (HR-ESI-MS, ¹H-NMR, (13)C-NMR, HSQC, HMBC). Their absolute configurations were elucidated by comparison of their experimental and calculated ECD spectra. The cytotoxic activities were evaluated against MCF-7 and HepG2 cell lines. The separation procedures proved to be practical and economical, especially for trace prenylated biflavonoids from traditional Chinese medicine.

Purity Assessment of Aryltetralin Lactone Lignans by Quantitative 1H Nuclear Magnetic Resonance.

In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized, including relaxation delay (D1), scan numbers (NS), and pulse angle. 1,4-Dinitrobenzene was used as internal standard (IS), and deuterated dimethyl sulfoxide (DMSO-d6) as the NMR solvent. The purities were calculated by the area ratios of H-2,6 from target analytes vs. aromatic protons from IS. Six aryltetralin lactone lignans (deoxypodophyllotoxin, podophyllotoxin, 4-demethylpodophyllotoxin, podophyllotoxin-7'-O-ß-d-glucopyranoside, 4-demethylpodophyllotoxin-7'-O-ß-d-glucopyranoside, and 6''-acetyl-podophyllotoxin-7'-O-ß -d-glucopyranoside) were analyzed. The analytic results of qHNMR were further validated by high performance liquid chromatography (HPLC). Therefore, the qHNMR method was a rapid, accurate, reliable tool for monitoring the purity of aryltetralin lactone lignans.

Psoralen activates cartilaginous cellular functions of rat chondrocytes in vitro.

CONTEXT: Psoralen, an active ingredient from Fructus Psoraleae (FP), is used in Traditional Chinese Medicine (TCM) to treat bone diseases. However, the effect of psoralen on cartilage is unknown. OBJECTIVE: To investigate the effects of psoralen on chondrocytes isolated from rats. MATERIALS AND METHODS: Chondrocytes were treated with different concentrations of psoralen (1, 10, and 100 µM) in vitro at 3-d and 9-d intervals. MTS assay, Alcian blue colorimetry, western blotting, and qRT-PCR, respectively, were used to evaluate the effects of psoralen on cell viability, glycosaminoglycan (GAG) synthesis, collagen synthesis, and cartilage-specific gene expression. RESULTS: Psoralen dosages of 1-10 µM exhibited low cytotoxicity toward chondrocytes. However, a dosage of 100 µM suppressed the proliferation of chondrocytes. Different concentrations of psoralen treatments on chondrocytes revealed that GAG and Type II collagen synthesis increased, especially at 100 µM, by 0.39-fold and 0.48-fold, respectively, on day 3, and by 0.51-fold and 0.56-fold, respectively, on day 9. Similarly, gene expression of Type II collagen, aggrecan, and SOX-9 were all up-regulated on days 3 and 9, particularly aggrecan which increased significantly by 9.37-fold and 7.32-fold at 100 µM. Additionally, Type I collagen was inhibited both in gene expression and in protein synthesis. CONCLUSION: The results showed that psoralen promotes cartilaginous extracellular matrix (ECM) synthesis, as well as increased cartilaginous gene expression, and it may be a useful bioactive component for activating the cartilaginous cellular functions of chondrocytes.