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Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic., (© 2020 John Wiley & Sons Ltd.)

Spiroconyone A (1), the first rearranged phytosterol featuring an unusual spiro [5,6] ring system, and nine known compounds (2-10) were isolated from the aerial parts of Conyza japonica. The structure of 1 was elucidated through spectroscopic methods, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Enzyme-based assay revealed that spiroconyone A showed weak TDP1 inhibition and compounds 7 and 10 showed TDP1 inhibition with IC50 values of 36 μM and 16 μM, respectively. MTT assay indicated that 7 and 10 showed a strong synergistic effect with the clinical TOP1 inhibitor topotecan in MCF-7 cells. Compound 5 displayed the most potent cytotoxicity against MCF-7 cells with a GI50 value of 3.3 μM. Furthermore, a hypothetical biosynthetic pathway for 1 was proposed. This work provides valuable information that the secondary metabolites from Conyza japonica could be developed as anticancer agents.

Crotonpenoids A ( 1 ) and B ( 2 ), two highly modified clerodane diterpenoids featuring a new 10-(butan-2-yl)-1,6,12-trimethyltricyclo[7.2.1.0 2,7 ]dodecane skeleton, were isolated from the leaves and twigs of Croton yanhuii . Their structures including the absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, and biomimetic semisynthesis. Compounds 1 and 2 exhibited an agonistic effect on pregnane X receptor at 10 μM.

Phytochemical investigation on the leaves and twigs of Toona ciliata has led to the isolation of four new polyynes ( 1 - 4 ) and two knowns ( 5 and 6 ). Their structures were determined by extensive spectroscopic analysis (MS, UV, IR, and NMR) and Mosher's method. All compounds were evaluated for their inhibitory activities against HepG2 human tumor cell line but were inactive.

Mannosylxylarinolide ( 1 ), a new 3,4- seco -ergostane-type steroidal saponin featuring a β -d-mannose moiety, was isolated from the culture of the endophytic fungus Xylaria sp. that had been isolated from an ornamental plant of Hoya sp. The gross structure was determined by spectroscopic data, and the absolute configuration of the new 3,4- seco -ergostane-type steroidal saponin ( 1 ) was determined by X-ray diffraction analysis.

The phytochemical investigation of the roots of Croton crassifolius led to the isolation of 16 new halimane furanoditerpenoids, crohalifuranes A-P ( 1 - 16 ), along with 15 known analogues, 17 - 31 . The new structures including their absolute configurations were elucidated by NMR and MS data analysis, comparison of experimental and calculated electronic circular dichroism data, single-crystal X-ray diffraction data, and chemical methods. Crohalifuranes A ( 1 ) and B ( 2 ) are tetranor - and 19- nor -halimane diterpenoids featuring a rare decahydroacenaphthene core, respectively, which might be derived from the accompanying crassifoliusin A by loss of the furan ring or the C-19 substituent. Crohalifurane C ( 3 ) represents the first example of a 20- nor -halimane diterpenoid, and crohalifurane D ( 4 ) is characterized by an unusual 6,20-δ-lactone moiety. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and 2 and 23 exhibited moderate inhibition on NO production with IC 50 values of 17.2 ± 1.3 and 23.7 ± 1.4 μM, respectively.

A germacrane sesquiterpenoid library containing 30 compounds ( 2 - 31 ) was constructed by structural modification of a major component aristolactone ( 1 ) from the traditional Chinese medicine Aristolochia yunnanensis . Compound 11 was identified as a promising anticardiac fibrosis agent by systematic screening of this library. 11 could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor β 1 (TGFβ1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose. Mechanistic study revealed that 11 inhibited the TGFβ/small mother against decapentaplegic (Smad) signaling pathway by targeting TGFβ type I receptor (IC 50 = 14.9 ± 1.6 nM). The structure-activity relationships (SARs) study indicated that the unsaturated γ-lactone ring and oxidation of C-1 were important to the activity. These findings may provide a new type of structural motif for future anticardiac fibrosis drug development.

Euphorkanlide A (1), a highly modified ingenane diterpenoid with a C 24 appendage forming an additional hexahydroisobenzofuran-fused 19-membered macrocyclic bis-lactone ring system was isolated from the roots of Euphorbia kansuensis. Its structure was determined by extensive spectroscopic analysis and quantum-chemical calculations. Compound 1 showed significant cytotoxicities against a panel of cancer cell lines (IC 50s < 5 μM). Mechanistic study revealed that 1 could induce the generation of ROS, leading to cell cycle arrest and cell apoptosis in drug-resistant cancer cell line HCT-15/5-FU.

The phytochemical study of Euphorbia prolifera led to the isolation of two tiglianes (1 and 2) and 23 mysrinanes (3-25). Most of these isolates showed significant antiadipogenic activity in 3T3-L1 adipocyte without apparent cytotoxicity. Subsequent structural modification yielded 10 derivatives, among which 1a, the 5- O-acetyl derivative of 1, turned out to be the most active compound with improved triglyceride-lowering activity (EC 50 for 1 and 1a: 0.61 and 0.32 μM, respectively) and reduced cytotoxicity (selectivity index for 1 and 1a: 28 and 312, respectively). The structure-activity relationship study revealed that the trans-fused 5/7/6 ring system in an angular shape was important to the activity. A mechanistic study indicated that 1 and 1a could inhibit the glucocorticoid receptor α-Dexras1 axis in adipocyte, leading to the retardation of cell differentiation at the early stage. These findings may provide a new type of lipid-lowering agents for future antiobesity drug development.

Chloraserrtone A (1), a new sesquiterpenoid dimer with two lindenane-type sesquiterpenoid monomers bridged by two six-membered rings, was obtained from Chloranthus serratus. A combination of UV, IR, NMR, HRESIMS, and X-ray diffraction data were used to elucidate the structure of 1. Compound 1 represents the first lindenane-type sesquiterpenoid dimer with extremely unique C-15-C-15', C-4-C-6', and C-6-C-11' linkages to form two six-membered rings between the monomeric units. A plausible biosynthesis toward chloraserrtone A is proposed. This new compound (1), together with the known lindenane dimers (2-11), were assessed for their inhibitory effects on lipopolysaccharide-induced NO production in RAW264.7 cells. Compound 6 showed activity with an IC 50 value of 3.7 μM.

Cardiac fibrosis contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Antifibrotic therapies are likely to be a crucial strategy in curbing many fibrosis-related cardiac diseases. In our previous study, an ethyl acetate extract of a traditional Chinese medicine Aristolochia yunnanensis Franch. was found to have a therapeutic effect on myocardial fibrosis in vitro and in vivo. However, the exact chemicals and their mechanisms responsible for the activity of the crude extract have not been illustrated yet. In the current study, 10 sesquiterpenoids (1-10) were isolated from the active extract, and their antifibrotic effects were systematically evaluated in transforming growth factor β 1 (TGFβ1)-stimulated cardiac fibroblasts and NIH3T3 fibrosis models. (+)-Isobicyclogermacrenal (1) and spathulenol (2) were identified as the main active components, being more potent than the well-known natural antifibrotic agent oxymatrine. Compounds 1 and 2 could inhibit the TGFβ1-induced cardiac fibroblasts proliferation and suppress the expression of the fibrosis biomarkers fibronectin and α-smooth muscle actin via down-regulation of their mRNA levels. The mechanism study revealed that 1 and 2 could inhibit the phosphorylation of TGFβ type I receptor, leading to the decrease of the phosphorylation levels of downstream Smad2/3, then consequently blocking the nuclear translocation of Smad2/3 in the TGFβ/Smad signaling pathway. These findings suggest that 1 and 2 may serve as promising natural leads for the development of anticardiac fibrosis drugs., (© 2018 John Wiley & Sons, Ltd.)

Mulberry Diels-Alder-type adducts (MDAAs) are a group of structurally unique natural products biosynthetically derived from the intermolecular [4 + 2] cycloaddition of a dehydroprenylphenol and a chalcone. In the current study, ten MDAAs, including an undescribed one, inethermulberrofuran C, were isolated from the root bark of Morus alba. The anti-Alzheimer's disease (anti-AD) properties of these isolates were systematically screened for a series of potential targets (Aβ self-aggregation, tau aggregation, and ChEs) as well as the anti-neuroinflammatory and neuroprotective activities. Four compounds, mulberrofuran C, mulberrofuran K, mulberrofuran G, and isomulberrofuran G, turned out to be potent multi-targeted agents for AD. Among them, mulberrofuran K with a good blood-brain barrier (BBB) permeability (8.7 ± 0.3 × 10 -6  cm/s) was selected as a promising candidate for further mechanism study in glutamate-induced HT22 cell model, which showed its neuroprotective ability on up-regulation of the glutathione (GSH) level and suppression of the reactive oxygen species (ROS) production., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Bioassay-guided fractionation of the ethanolic extract of the roots of Euphorbia kansui led to the isolation of two new ingenane diterpenoids, euphorkans A (1: ) and B (2: ), together with 16 known analogues (3:  - 18: ). Their structures were determined by combined spectral and chemical methods. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. Compounds 1:  - 6: and 10:  - 13: exhibited pronounced inhibitory activity with IC 50 values in the range of 2.78 - 10.6 µM, and were more potent than the positive control, quercetin (IC 50  = 15.8 µM). Compounds 1: and 5: were selected for further assays toward the key inflammation mediators TNF- α and IL-6, and showed a significant inhibition in a dose-dependent manner. The preliminary mechanistic study revealed that 1: and 5: inhibited NF- κ B activity, which may exert a role in their anti-inflammatory activity., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

A pair of undescribed bicoumarin enantiomers, (P)/(M)-corinepalensin A, two undescribed prenylated coumarins, corinepalensins B and C, along with ten known coumarins were isolated from the twigs of Coriaria nepalensis. (P)/(M)-corinepalensin A feature a rare C-5C-5' axially chiral linkage between two prenylated coumarin monomers. Their structures were determined by a combination of spectroscopic methods, single crystal X-ray diffraction, and ECD calculations. All isolates were evaluated for the inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds (P)-corinepalensin A, (M)-corinepalensin A, corinepalensin B, norbraylin, braylin, and nepalin C exhibited significant inhibition with IC 50 values ranging from 0.43 to 7.15 μM., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The bioassay-guided phytochemical study of a traditional Chinese medicine Morus alba led to the isolation of 18 prenylated flavonoids (1-18), of which (±)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC 50 values ranging from 0.0054 to 0.40 μM, being more active than the positive control rolipram (IC 50  = 0.62 μM). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: To study the Amaryllidaceae alkaloids of the bulbs of Lycoris radiata., Methods: The chemical constituents were isolated and purified by various chromatographic techniques, and the chemical structures were elucidated on the basis of spectroscopic methods. In addition, the antiviral activities of alkaloids 1-10 were evaluated using flu virus A., Results: One new homolycorine-type alkaloid 2α-methoxy-6-O-ethyloduline (1), together with nine known alkaloids 2α-methoxy-6-O-methyloduline (2), trispherine (3), 8-O-demethylhomolycorine (4), homolycorine (5), 9-O-demethylhomolycorine (6), oduline (7), lycorenine (8), 6α-O-methyllycorenine (9) and O-ethyllycorenine (10) were obtained., Conclusion: Alkaloid 1 is a new compound, and 1-3 were major alkaloids in this plant. Alkaloids 1-3 showed weak antiviral activities against flu virus A with IC50 values of 2.06, 0.69, and 2.71 μg·mL-1 and CC50 values of 14.37, 4.79, and 80.12 μg·mL-1, respectively., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Five new compounds (1-5), including two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, along with nine known limonoids (6-14), were isolated from the bark of Melia azedarach. The structures of the new compounds were elucidated by 2D NMR spectroscopy and mass spectrometry. The isolated compounds as well as three acetylated derivatives of 9 were evaluated for their cytotoxicities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) by an MTT assay. Seven limonoids (1, 6, 7, 8, 9, 9b, and 9c) showed significant inhibitory activities against tested cell lines with IC50 values ranging from 0.003 to 0.555 µM, and their preliminary structure-activity relationships are also discussed., (Georg Thieme Verlag KG Stuttgart · New York.)

Twelve isoquinoline alkaloids including two new nitro-containing tetrahydroprotoberberines, (-)-2,9-dihydroxyl-3,11-dimethoxy-1,10-dinitrotetrahydroprotoberberine (1) and (+)-4-nitroisoapocavidine (2), were isolated from the whole plant of Corydalis saxicola Bunting. The structures of the new compounds were established by spectroscopic analysis and chemical evidence. The inhibitory activity of these isolates against cholinesterase and canine parvovirus were evaluated. Compounds 1 and 1A, (+)-1-nitroapocavidine (5), berberine (8), palmatine (9), dehydrocavidine (10), and sanguinarine (11) showed potent inhibitory activity against acetylcholinesterase with IC(50) values of less than 10 µM, while only compound 1 possessed weak activity against canine parvovirus. Structure-activity studies demonstrated that the nitro substituents at ring A in the tetrahydroprotoberberines led to an increase in the anti-acetylcholinesterase activity., (© Georg Thieme Verlag KG Stuttgart · New York.)

A new dihydroflavone, 5-carboxymethyl-7,4'-dihydroxyflavonone (1), and its glucoside 5-carboxymethyl-7,4'-dihydroxyflavonone-7-O-β-D: -glucopyranoside (2), and one new monoterpene glucoside, (4Z,6E)-2,7-dimethyl-8-hydroxyocta-4,6-dienoic acid 8-O-β-D: -glucopyranoside (3), were isolated from the whole plants of Selaginella moellendorffii. Their structures were determined by spectroscopic methods and chemical transformation. Compound 2 was evaluated for the ability to enhance glucose consumption in normal and insulin-resistant L6 muscle cells induced by high concentrations of insulin and glucose. Glucose consumption in insulin-resistant cells (but not in normal cells) was increased 15.2 ± 3.3% (p < 0.01) by compound 2 at a concentration of 0.1 μM in the presence of insulin (1 nM).

Eight new amide alkaloids (1-8) and 19 known ones were isolated from the whole plant of Piper boehmeriaefolium. Their structures were determined through spectroscopic data analyses. Cytotoxic activity of these amides against human cervical carcinoma HeLa cells was evaluated, and 1-[(9E)-10-(3,4-methylenedioxyphenyl)-9-decenoyl]pyrrolidine (9) exhibited significant inhibitory activity with an IC(50) value of 2.7 μg/mL.

A new piperidine alkaloid and three known tetranortriterpenoids were isolated from the methanol extracts of the rhizomes of Arisaema decipiens Schott (Araceae) and their chemical structures were identified as (-)-(2R*,3S*,6S*)-N,2-dimethyl-3-hydroxy-6-(9-phenylnonyl) piperidine (1), 6-deacetylnimbin (2), 28-deoxonimbolide (3) and nimbin (4). The N-methylated derivative (1a) of 1 was synthesized. Compound 1 exhibited weak inhibitory activity against the MCF-7 cell line, while compound 1a showed potential inhibitory activity against the MCF-7 cell line with an IC₅₀ value of 4.6 μM and weak inhibitory activity against K562 and SK-OV-3 cells. This plant in genus Arisaema is firstly reported as the source of limonoids that are considered a natural antitumor herbal medicine.