Chemical Constituents with Anti-Proliferative Activity on Pulmonary Arterial Smooth Muscle Cells from the Roots of Anthriscus sylvestris (L.) Hoffm.

A chemical investigation of Anthriscus sylvestris roots led to the isolation and characterization of two new nitrogen-containing phenylpropanoids (1-2) and two new phenol glycosides (8-9), along with fifteen known analogues. Structure elucidation was based on HRESIMS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD). In addition, compounds 3, 6, 9-10, 12, and 17 exhibited inhibitory effects against the abnormal proliferation of pulmonary arterial smooth muscle cells with IC50 values ranging from 10.7 ± 0.6 to 57.1 ± 1.1 µM.

Chemical constituents from stipes of Lentinus edodes and their protective effects against Aß25-35-induced N9 microglia cells injury.

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.

Five new eremophilane-type sesquiterpenes from the fresh roots of Rehmannia glutinosa.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

Six New Compounds from the Herbaceous Stems of Ephedra intermedia Schrenket C. A. Meyer and Their Lung-Protective Activity.

Six new compounds, (7R,8S,8'R)-balanophorone (1), (7'S,8'R,8R)-yunnanensin A (2), (3S)-thunberginol C (3), (8R,8'R)-maninsigin B (4), (7S,8R)-4,7,8-dihydroxy-9,9-dimethyl-chroman (5), and 4-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butan-1-one (6), along with eight known compounds (7-14), were isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on their spectroscopic (MS, NMR, IR, and UV) data, and their absolute configurations were determined by comparing their calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, compounds 1 and 3-6 were evaluated for their ability to protect human pulmonary epithelial cells (BEAS-2B) from injury induced by lipopolysaccharide (LPS) in vitro. The results showed that compound 6 exhibited a significant protective effect against LPS-induced injury in BEAS-2B, and compound 5 exhibited a slightly protective effect at the concentration of 10 µM.

Diarylpentanoids and phenylpropanoids from the roots of Anthriscus sylvestris (L.) Hoffm.

Three pairs of undescribed diarylpentanoid enantiomers (1-3) and five undescribed phenylpropanoids (4-8), along with seven known compounds, were isolated from the roots of Anthriscus sylvestris. The structures of compounds (1-8) were determined by analysis of their 1D and 2D NMR spectra, HRESIMS, and electronic circular dichroism. In addition, the inhibitory activities against hypoxia-stimulated pulmonary arterial smooth muscle cells abnormal proliferation were evaluated by MTT assay. The mRNA expression levels of Bcl-2, BAX, Caspase3, and IL-6 were detected by quantitative real-time PCR. The results showed that compounds (-)-1, (+)-1, (-)-2, (+)-3, 4, 8-10, 14, and 15 inhibited the abnormal proliferation of PASMCs by regulating the levels of apoptosis and inflammatory factors.

Salviamilthone A-O, diterpenoid quinones from Salvia miltiorrhiza.

Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 µM) significantly increased cell viability and decreased the expression of IL-1ß in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.

Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities.

A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against α-glucosidase with IC50 of 1.11-33.53 µM, 5-150 times stronger than acarbose (IC50 = 169.78 µM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09-44.26 µM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 value of 47.13 µM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.

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.

Diterpenoid quinones from the Salvia miltiorrhiza and their lung protective activity.

Seven new diterpenoids quinones (1-6), together with five known ones (7-11), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated by using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by interpretations of the NOESY correlations and comparison of the experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthiza C (3), significantly increased cell viability and decreased the expression of IL-1ß in LPS-induced BEAS-2B cells.

Minor iridoid glycosides from the fruits of Cornus officinalis Sieb. et Zucc. and their anti-diabetic bioactivities.

Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 µM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 µM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.

Ionones and lignans from the fresh roots of Rehmannia glutinosa.

Nine undescribed compounds, together with 21 known components, were isolated from the fresh roots of Rehmannia glutinosa. Their structures were elucidated based on spectroscopic data analysis, and the absolute configurations of undescribed compounds were determined by comparison of their calculated and experimental electronic circular dichroic (ECD) spectra and interpretation of their optical rotation data. The α-glucosidase inhibitory effects of the isolated compounds were investigated and all of them exhibited slightly inhibitory activities.

Four pairs of tautomers from rhizomes of Acorus calamus and fruits of Cornus officinalis.

A pair of new guaiane-type sesquiterpene tautomers (1) was isolated from rhizomes of Acorus calamus. Meanwhile, three pairs of known compounds, including a pair of dihydroflavone glycoside tautomers (2), a pair of 4-hydroxybenzoic acid ester glycoside tautomers (3), as well as a pair of secoiridoid glycoside tautomers (4) were isolated from fruits of Cornus officinalis. Their structures were elucidated by extensive spectroscopic and computational methods. Furthermore, the tautomeric mechanisms were discussed.

Neolignans and amide alkaloids from the stems of Piper kadsura and their neuroprotective activity.

Four undescribed neolignans and three undescribed amide alkaloids, along with twelve known compounds, were isolated from the stems of Piper kadsura (Choisy) Ohwi. The structures of the new compounds were determined by spectroscopic analysis, quantum-chemical calculations, and Mo2(OAc)4-induced ECD analysis. The neuroprotective effects of these compounds against Aß25-35-induced cell damage in PC12 cells were investigated, and eight compounds exhibited significant neuroprotective effects against Aß25-35-induced PC12 cell damage, with the EC50 values of 3.06-29.3 µM. Three of these compounds were selected for further experiments, and they appear to reduce apoptosis and enhance autophagy against Aß25-35-induced PC12 cell damage.

Chemical Constituents from the Flowers of Carthamus tinctorius L. and Their Lung Protective Activity.

A new flavonoid, saffloflavanside (1), a new sesquiterpene, safflomegastigside (2), and a new amide, saffloamide (3), together with twenty-two known compounds (4-25), were isolated from the flowers of Carthamus tinctorius L. Their structures were determined based on interpretation of their spectroscopic data and comparison with those reported in the literature. The protective effects against lipopolysaccharide (LPS)-stimulated damage on human normal lung epithelial (BEAS-2B) cells of the compounds were evaluated using MTT assay and cellular immunofluorescence assay. The results showed that compounds 2-3, 8-11, and 15-19 exhibited protective effects against LPS-induced damage to BEAS-2B cells. Moreover, compounds 2-3, 8-11, and 15-19 can significantly downregulate the level of nuclear translocation of NF-κB p-p65. In summary, this study revealed chemical constituents with lung protective activity from C. tinctorius, which may be developed as a drug for the treatment of lung injury.

A new ent-clerodane diterpene from Detarium microcarpum Guill. & Perr. and its protective potential for osteoporosis.

A new clerodane diterpene, named 6α-hydroxy-3,13E-clerodien-15-oic acid (1), together with a known clerodane diterpene (2), four known labdane diterpenes (3-6), a triterpenoid (7), a known steroid (8), and two benzenoid compounds (9 and 10) were isolated from Detarium microcarpum Guill. & Perr. The structures of all obtained compounds were determined by chemical properties and spectroscopic evidence, accompanied by comparisons with data in the literature. Electronic circular dichroism (ECD) was performed for compounds 1-4 to confirm the absolute configuration. Compounds 1-3 and 8-10 were evaluated for the protective effect on osteoblasts. Compound 1 was observed to increase the proliferation of dexamethasone (DEX)-treated MC3T3-E1 cells significantly at 1 µM, which was comparable with the positive control geniposide at 10 µM. The results were further confirmed by flow cytometry analysis. In addition, compound 1 increased the level of alkaline phosphatase (ALP) and mineralization in osteoblasts inhibited by DEX. Moreover, Compound 9 (vanillic acid) showed a pronounced inhibition (IC50 6.5 ± 0.6 µM) on reactive oxygen species (ROS) production, and 10 (4-O-methyl gallic acid) showed a good inhibition with IC50 as 103.3 ± 2.2 µM, compared with the standard drug ibuprofen (IC50 54.2 ± 9.2 µM). Besides, compounds 1-3 and 8-10 were non-cytotoxic against MCF-7, NCI-H460, Hela, and BJ cell lines.

Ten undescribed diterpenoid quinones derived from the Salvia miltiorrhiza.

This study aimed to report the structure elucidation of the compounds isolated from Salvia miltiorrhiza, and their biological evaluations. Ten undescribed diterpenoid quinones and 10 known analogues were isolated from the dried roots of S. miltiorrhiza. Their structures were elucidated by extensive analysis, including nuclear magnetic resonance, high-resolution mass spectra, and ultraviolet and infrared spectra. Their absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism spectra. In the evaluation of bioactivities, Salvianolactone acid I, epi-danshenspiroketallactone F, danshinspiroketallactone, grandifolia G, and 2H-Naphtho [1,8-bc]furan (10 µM) significantly increased cell viability and decreased the nuclear transport of p-P65 in lipopolysaccharide-induced bronchial epithelial cells. It was concluded that the diterpenoid quinones might belong to potent targeted lung-protective agents.

Polysubstituted Cyclopentene Benzamides and Dianthramide Alkaloids from Delphinium anthriscifolium Hance.

Thirteen new benzamide alkaloids, delphiniumines A-M (1-13), together with one known analogue (14), were isolated from Delphinium anthriscifolium Hance. All of the structures were determined by spectroscopic and spectrometric analyses. Absolute configuration for 1 was established using experimental and calculated ECD data, as well as by X-ray crystallography analysis. Compound 1 possesses a previously undescribed polysubstituted cyclopentene carbon framework. Compound 2 was isolated as an artifact from 1 during the extraction process. Compound 7 is glycosylated with a ß-D-glucose unit. Compound 13 bears a chlorine substituent. At a concentration of 10 µM, compounds 6, 8, and 10-12 suppressed LPS-induced NO production in RAW264.7 cells with inhibition rates ranging from 40.3% to 78.8%.

Hypeisoxazole A, a Racemic Pair of Tetrahydroisoxazole-Fused Benzylisoquinoline Alkaloids from Hypecoum erectum and Structural Revision of Hypecoleptopine.

(±)-Hypeisoxazole A (1), a racemic pair of rearranged benzylisoquinoline alkaloids possessing an unprecedented diindeno[2,1-c:2',1'-d] isoxazole scaffold, was isolated from the medicinal herb Hypecoum erectum, along with hypecoleptopine (2), whose structure is now revised as a novel spiro-benzylisoquinoline alkaloid with a 6/6/5/6/6 skeleton. Their structures were determined by comprehensive spectroscopic and spectrometric analyses, X-ray diffraction, and computational studies. Racemic mixture of 2 and its pure enantiomers modulated neuronal excitability activity.

Cadinane Sesquiterpenoids and Their Glycosides from Alangium chinense That Inhibit Spontaneous Calcium Oscillations.

Nine new cadinane sesquiterpenoids, alanenses A-I (1-9), were isolated from the leaves of Alangium chinense together with three previously reported analogues (10-12). The structures of these molecules were elucidated by interpretation of spectroscopic and spectrometric data. Absolute configurations were established by the comparison of experimental and calculated ECD data, chemical degradation studies for sugar moieties, and a single-crystal X-ray diffraction analysis. Compounds 1 and 2 were isolated as racemates, and enantiopurification was achieved by chiral HPLC. Compounds 3-5 are glycosylated cadinanes bearing a ß-d-glucose unit, while compounds 6-9 incorporate a hydroxymethyl group in either the free form or additional ring fusion. The structure of compound 11 was originally misassigned and later revised using additional NMR data. The corrected structure is here supported by X-ray single-crystal analysis. Compounds 1 and 2 inhibit spontaneous calcium channel oscillations at low micromolar concentrations.

Saffloflavone, a new flavonoid from the flowers of Carthamus tinctorius L. and its cardioprotective activity.

A new flavonoid, saffloflavone , along with six known compounds, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, quercetin-3-O-ß-d-glucoside, quercetin-7-O-ß-d-glucoside, luteolin-7-O-ß-d-glucoside and kaempferol 3-O-ß-d-glucoside were isolated from the flowers of Carthamus tinctorius L. All the structures were determined by interpretation of their spectroscopic data. The cardioprotective effects of all the isolates against oxidative stress of H9c2 cells induced by H2O2 were investigated. The results showed that compounds 4-6 exhibited protective effects against of H9c2 cells injury induced by H2O2.