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.

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.

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.

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.

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.

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial-Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36.

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial-mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 µmol/L sodium oleate were given 10 µmoL/L moracin-P-2″-O-ß-d-glucopyranoside (Y-1), moracin-P-3'-O-ß-d-glucopyranoside (Y-2), moracin-P-3'-O-α-l-arabinopyranoside (Y-3), and moracin-P-3'-O-[ß-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1ß), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-ß, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-ß-d-glucopyranoside and moracin-P-3'-O-ß-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.

Iridoid glycosides and lignans from the fruits of Gardenia jasminoides Eills.

Four previously undescribed iridoid glycosides, including two bis-iridoid glycosides, and three undescribed lignans, together with 16 known analogues, were isolated from the fruits of Gardenia jasminoides Eills. Their structures were elucidated on basis of spectroscopic methods, and the absolute configurations of three of the unknown compounds were determined by interpretation of their electronic circular dichroic (ECD) and [α] [Formula: see text] data. The α-glucosidase inhibitory effects of the isolated compounds were evaluated and all the compounds exhibited slightly inhibitory activity with the values of IC50 greater than 50 µM.

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.

Geniposide in Gardenia jasminoides var. radicans Makino modulates blood pressure via inhibiting WNK pathway mediated by the estrogen receptors.

OBJECTIVES: To investigate the effects of geniposide in an iridoid found in Gardenia jasminoides var. radicans Makino (GJRM) in spontaneous hypertensive rat (SHR) and explore the possible mechanisms. METHODS: In this study, we detected the content of geniposide in GJRM by high-performance liquid chromatography (HPLC). Then, we used acute diuretic experiments to determine whether geniposide has diuretic effect. Moreover, we carried out experiments on SHR to further study the mechanism of hypertension, while real-time PCR, Western blot and immunohistochemistry were used for the experiments in vivo test. Hypotonic model was used for in vitro test. KEY FINDINGS: Our data showed that the content of geniposide in the extract of GJRM is 27.54%. Meanwhile, 50 mg/kg geniposide showed the strongest effect on promoting urine volume. Further study indicated that the extract of GJRM and geniposide could significantly reduce blood pressure and promote the excretion of urine and Na+ in SHR. In addition, geniposide significantly inhibited the activation of the with-no-lysine kinase (WNK) signalling pathway and significantly increases the protein expressions of estrogen receptor α (ERα), estrogen receptor ß (ERß) and G protein-coupled receptor 30 (GPR30) in SHR. In hypotonic model, geniposide significantly inhibits the phosphorylation of NKCC and NCC and could be antagonistic to estrogen receptor antagonists. CONCLUSIONS: Collectively, we would suggest that geniposide may potentially be utilized as an adjunct to existing thiazide and thiazide-like diuretics to control hypertension, mainly through inhibiting the activation of the WNK signalling pathway mediated by the estrogen receptor.

[Lignans from flower buds of Magnolia biondii].

The present study aims to investigate the lignans from the flower buds of Magnolia biondii. The isolation and purification of the compounds were performed by column chromatographies on Diaion HP-20, silica gel, and Sephadex LH-20, combined with semi-preparative HPLC. Their structures were elucidated on the basis of spectral data and physiochemical properties. Eighteen compounds were isolated and identified as magnolin (1), epimagnolin (2), eudesmin (3), kobusin (4), aschantin (5), lirioresinol B dimethyl ether (6), pinoresinol monomethy ether (7), (+)-de-O-methylmagnolin (8), isoeucommin A (9), syringaresinol 4-O-ß-D-glucopyranoside (10), phillygenin (11), lariciresinol-4'-O-ß-1-D-glucoside (12), conicaoside (13), (7'S, 8'R)-dihydrodehydrodiconiferylalcohol (14), 7R*, 8S*-dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (15), 7S, 8R-erythro-7, 9, 9'-trihydroxy-3, 3'-dimethoxy-8-O-4'-neolignan 4-O-ß-D-glucopyranoside (16), 7S, 8R-erythro-4, 9, 9'-trihydroxy-3, 3'-dimethoxy-8-O-4'-neolignan-7-O-ß-D-glucopyranoside (17), and (+)-isolariciresinol (18). Compounds 7-18 are isolated from this plant for the first time.

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.

Four New Monoterpenoid Glycosides from the Flower Buds of Magnolia biondii.

Four new monoterpenoid glycosides 1-4, named magnoliaterpenoid A-D, were isolated from a 50% aqueous acetone extract of flower buds of Magnolia biondii, along with one known compound, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3-O-ß-d-glucopyranoside (5). Their structures and relative configuration were identified by extensive spectroscopic analysis (IR, UV, MS, 1D and 2D NMR). The aglycones of these four new compounds possess seven-membered rings systems, which are very rare. A plausible biosynthetic route for the four new compounds was proposed via the biogenetic isoprene rule. Compounds 1, 2, 3, and 4 showed no antimicrobial activity at the concentration range of 1.95-250 µg/mL.

Extractions of oil from Descurainia sophia seed using supercritical CO2, chemical compositions by GC-MS and evaluation of the anti-tussive, expectorant and anti-asthmatic activities.

Descurainia sophia is widely distributed in China and is one of the most troublesome annual weeds. It has diverse medicinal usage. D. sophia has abundant oil, making it an important oil plant in China. The main goal of this study was to obtain the maximum yield of the oil by an optimal selection of supercritical fluid extraction parameters. According to the central composite design and response surface methodology for supercritical fluid extraction method, a quadratic polynomial model was used to predict the yield of D. sophia seed oil. A series of runs was performed to assess the optimal extraction conditions. The results indicated that the extraction pressure had the greatest impact on oil yield within the range of the operating conditions studied. A total of approximately 67 compounds were separated in D. sophia seed oil by GC-MS, of which 51 compounds represented 98.21% of the total oils, for the first time. This study was also aimed at evaluating the anti-asthmatic, anti-tussive and expectorant activities in vivo of D. sophia seed oil which supplied for further research on bioactive constituents and pharmacological mechanisms.

Three new ursane-type triterpenes from the leaves of Rehmannia glutinosa.

Three new ursane-type triterpenes, glutinosalactone A-C (1-3), were isolated from the 50% aqueous acetone extract of the leaves of Rehmannia glutinosa. Their structures were elucidated on the basis of spectral analysis (IR, NMR and MS spectroscopy). The cytotoxic effects of compounds 1-3 against three human cancer cell lines (MCF-7, MG63 and HepG2) were also evaluated. Compound 3 showed cytotoxic activities with IC50 values of 8.35-39.25 µM.