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A new cyclic diarylheptanoid (1) and a new flavone glucoside (2), along with seven known compounds, were isolated from the green peel ofJuglans mandshurica. Their structures were elucidated based on extensive spectroscopic analyses. Moreover, the cytotoxicity against NCI-H460, A549, and K562 cancer cells of compounds1–6was evaluated. The results showed that compound3exhibited moderate inhibitory potency against the growth of three cell lines. [ABSTRACT FROM PUBLISHER]

Hericium erinaceus is a well-known medicinal and edible mushroom, which is considered as a potential source to obtain antitumor candidates. In this work, five new isoindolinones, named erinaceolactams A-E ( 1 – 5 ), along with five known compounds ( 6 – 10 ), were isolated from 70% ethanol extract of the fruiting bodies of H . erinaceus . The structures of new compounds were validated by HRESIMS and 1D, 2D NMR. It's worth mentioning that there are two pairs of isomers included in the new compounds. Moreover, their cytotoxicity against metastatic human hepatocellular carcinoma cell lines SMMC-7221 and MHCC-97H were evaluated. The results showed that compounds 6 and 7 exhibited promising inhibitory potency against the growth of two cell lines. [ABSTRACT FROM AUTHOR]

The most common and leading cause of cancer-related death in men is lung cancer. Despite the recent advances in chemotherapy, advanced lung cancer still remains incurable. For this, the understanding of molecular mechanisms involved in lung carcinogenesis is necessary to provide potentially effective therapeutic targets for the treatment of lung cancer, and thus the therapeutic limitations can be overcome. Cyclooxygenase-2 (COX-2) is an important inflammation factor that is reported to be up-regulated in different cancers. A number of COX-2 inhibitors have been developed, but most of them are restricted due to the different risk factors. Currently, the FDA has allowed celecoxib to remain on the market but advised physicians to apply this drug with alternative therapies or to use at a low dosage. Some other COX-2 inhibitors, such as, apricoxib and etoricoxib are under critical investigation currently. Celecoxib is being tested in clinical trials against lung cancer, as a single agent or in combination with other agents. Recent studies have suggested celecoxib as a feasible and clinically active regimen in the treatment of patients with lung cancer. However, more clinical trials are necessary for the better understanding of the role of selective COX-2 inhibitors in the prevention and treatment of lung cancer along with their assessment of toxicity. In this review, we have discussed the mechanism of actions of COX-2 in cancer progression and the therapeutic use of COX-2 inhibitors in the treatment of lung cancer with subsequent clinical studies and future management. [ABSTRACT FROM AUTHOR]

Two new selaginellin derivatives selaginellin P (1) and selaginellin Q (2) were isolated fromSelaginella tamariscina. The structures of1and2were established as 2,4′-dihydroxy-4-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene (1) and 2,4′-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene (2) on the basis of spectroscopic means including HR-ESI-MS, 1D, and 2D NMR experiments. [ABSTRACT FROM PUBLISHER]

Six new flavonoids, unciflavones A–F ( 1 – 6 ), have been isolated from medicinal plant Selaginella uncinata (Desv.) Spring. Their structures were established on the basis of extensive NMR analysis including 1D NMR ( 1 H, 13 C and DEPT) and 2D NMR (COSY, HSQC, HMBC) experiments as well as HRESIMS analysis. All compounds possess exceptional structural features with an aryl substituent at the C-8 position, which are uncommonly encountered in natural resources and firstly reported in genus Selaginella . [ABSTRACT FROM AUTHOR]

Published in Khimiya Prirodnykh Soedinenii, No. 1, January-February, 2021, pp. 168-169 I Selaginella i is the sole genus of the Selaginellaceae, which consists of about 700 species and widely distributed in the world. By using extensive spectroscopic data, including UV I vis i , IR, HR-ESI-MS, and 1D/2D NMR and comparing the spectroscopic data with the reported literature, compounds B 1-18 b have been identified. Subfraction F7 was directly purified by semi-preparative HPLC (ACN-H SB 2 sb O, 45:55, 3.0 mL/min) to yield compounds B 1 b (2.3 mg), B 2 b (3.5 mg), B 3 b (3.3 mg), B 4 b (3.0 mg), B 5 b (2.4 mg), B 6 b (4.1 mg), B 9 b (2.1 mg), B 10 b (2.3 mg), B 11 b (5.1 mg), and B 12 b (5.3 mg). Fraction H was chromatographed over silica gel repeatedly and then subjected to Sephadex LH-20 with MeOH-H SB 2 sb O (60:40, isocratic elution) to afford six subfractions (Subfrs. [Extracted from the article]

Uncinataflavone (1), a new flavonoid, together with four known compounds (2–5), was isolated from Selaginella uncinata (Desv.) Spring. Compounds 2 and 3 were isolated from the genus selaginella for the first time. The structure of the new compound was determined as methyl 3-(5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate by means of spectroscopic evidence, including UV, IR, 1D and 2D NMR analyses as well as HR-ESI-MS. These compounds (1–5) were evaluated for the antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl assay system. [ABSTRACT FROM AUTHOR]

A new flavonoid, 6-(5-acetyl-2-methoxyphenyl)-apigenin (1), together with nine known compounds (2–10), was isolated from Selaginella uncinata (Desv.) Spring. This is the first report of the spectroscopic data of compound 3. Compound 2 was first reported from this species. The structure of the new compound was elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR as well as HR-EI-MS analysis. [ABSTRACT FROM AUTHOR]

A new selaginellin derivative, selaginellin M (1), together with one known compound, selaginellin E (2), was isolated from Selaginella pulvinata. The structure of the new compound was elucidated and named as (R,S)-4-((4′-hydroxy-4-((2-hydroxyethoxy)methyl))-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone on the basis of the spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS analysis. [ABSTRACT FROM PUBLISHER]

Two new selaginellin derivatives, selaginellins K (1) and L (2), were isolated from Selaginella tamariscina (Beauv.) Spring and characterized as 2-formyl-4,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene and 4,4'-dihydroxy-2-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene on the basis of their spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS spectroscopic analysis. [ABSTRACT FROM AUTHOR]

Selaginellins I (1) and J (2), two new compounds, were isolated from Selaginella tamariscina (Beauv.) Spring and were characterized as (R,S)-4-((2',4'-dihydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone (1) and (R,S)-4-((3-((3,4-dihydroxyphenyl)ethynyl)-4'-hydroxy-4-(hydroxymethyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone (2) on the basis of UV, IR, 1D and 2D NMR, and HR-ESI-MS spectroscopic analysis. [ABSTRACT FROM AUTHOR]

A novel compound, selaginellin C (1), was isolated from Selaginella pulvinata Maxim (Hook et Grev.) as (R,S)-4-((1,2-dihydroxyethyl)-2',4'-dihydroxy-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)((4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone, along with two known compounds, selaginellin (2) and selaginellin A (3). The structure of the new compound was elucidated on the basis of 1D and 2D NMR as well as HR-ESI-MS spectroscopic analysis. [ABSTRACT FROM AUTHOR]

The article focuses on the study regarding the isolation of compounds from Selaginella delicatula. The study has employed air-dried S. delicatula extraction with ethanol by heat, its crude oil extract is subjected to polyamide column chromatography with EtOH-H 2O (v/v) elution, and recrystallization. The study has yielded compounds including heveaflavone, amentoflavone, and emodin-8-O-Β-D-glucopyranoside.

A new abietane diterpenoid, 1β, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2–4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [ABSTRACT FROM AUTHOR]

Regorafenib is a novel tyrosine kinase inhibitor, which has been approved by the United States Food and Drug Administration for the treatment of various tumors. The purpose of the present study was to describe the metabolic map of regorafenib, and investigate its effect on liver function. Mass spectrometry-based metabolomics approach integrated with multiple mass defect filter was used to determine the metabolites of regorafenib in vitro incubation mixtures (human liver microsomes and mouse liver microsomes), serum, urine and feces samples from mice treated with 80 mg/kg regorafenib. Eleven metabolites including four novel metabolites were identified in the present investigation. As halogen substituted drug, reductive defluorination and oxidative dechlorination metabolites of regorafenib were firstly report in present study. By screening using recombinant cytochrome P450 s (CYPs), CYP3A4 was found to be the principal isoforms involved in regorafenib metabolism. The predication with a molecular docking model confirmed that regorafenib had potential to interact with the active sites of CYP3A4, CYP3A5 and CYP2D6. Serum chemistry analysis revealed no evidence of hepatic damage from regorafenib exposure. This study provided a global view of regorafenib metabolism and its potential side-effects. [ABSTRACT FROM AUTHOR]

Two new flavonoids, uncinataflavones A (1) and B (2), along with one known compound 6-(5-carboxyl-2-methoxyphenyl)-apigenin (3), were isolated fromSelaginella uncinata(Desv.) Spring. All these compounds belong to apigenin derivatives with aryl substituents at C-6 position. The structures of new compounds were elucidated on the basis of comprehensive spectroscopic analyses (UV, IR, 1D, and 2D NMR as well as HR-ESI-MS). [ABSTRACT FROM AUTHOR]

One new pentacyclic triterpenoid, urs-12,16-dien-3-one (1), together with twelve known pentacyclic triterpenoids (2‒13), were isolated from the twigs and leaves of Melaleuca linariifolia. Their structures were characterized by their 1D- and 2 D-NMR spectra analysis and mass spectra studies. Furthermore, all isolated compounds were tested the inhibitory effect on proliferation of six human cancer cell lines in vitro, including NCI-H441, NCI-H460, A549, SKOV3, hela, and caki-1 cells. Among them, compounds 3, 5, 7, 9, 12, and 13 exhibited moderate antiproliferative activities with IC50 values ranging from 3.85 to 33.31 μM. [ABSTRACT FROM AUTHOR]

Abstract: Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Hyperglycemia induces oxidative stress to generate reactive oxygen species in diabetic neurons resulting in neuronal damage and dysfunction. Apoptosis has been proposed as a possible mechanism for high glucose-induced neural dysfunction and neuronal cell injury. High glucose per se enhances lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression via activation of NADPH oxidase/reactive oxygen species pathway in endothelial cells. Selaginellin, a component extracted from Saussurea pulvinata (Hook. et Grev.) Maxim, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by high glucose. The differentiated PC12 cells were pretreated with various concentrations (10−7, 3×10−7 or 10−6 M) of selaginellin for 1h and then co-treated with selaginellin and d-glucose (75mM) for 72h. Selaginellin was shown to protect differentiated PC12 cells against high glucose toxicity, as determined by characteristic morphological features, cell viability, and apoptosis as evaluated by Hoechst 33,258 staining assay, annexin V-propidium iodide double staining assay and caspase-3 activity. In addition, the increase in NADPH oxidase activity, mRNA expression of NADPH oxidase subunits (NOX-1 and NOX-2) and LOX-1, and reactive oxygen species production induced by high glucose were significantly inhibited by selaginellin or by anti-LOX-1 antibody. The present study demonstrated that inhibitory effect of selaginellin on high glucose-induced cell injury and apoptosis in differentiated PC12 cells is related to inhibition of LOX-1/NADPH oxidase–reactive oxygen species/caspase-3 signaling pathway. [Copyright &y& Elsevier]

Two pairs of isocoumarin derivatives, (±)-rhytidhymarins A and B (1–2), one aromatic ester, rhytidhyster A (3), together with three known compounds (4–6) were isolated from fungus Rhytidhysteron sp. BZM-9. Compounds 1 and 2 are presented as racemates and resolved into optically pure enantiomers (+)-1/(−)-1 and (+)-2/(−)-2 by chiral column separation, respectively. Their planar structures were elucidated by HRESIMS, 1D and 2D NMR data and their absolute configurations were determined by X-ray crystallographic analysis and electronic circular dichroism (ECD) calculation. Compound 5 showed significant cytotoxic activity against SMMC7721 cells with an IC50 value of 0.338 μM and exhibited moderate antimicrobial activity to MRSA with a MIC value of 6.25 μg mL−1; compound 3 showed cytotoxicity against HepG2 cells with an IC50 value of 11.46 μM. [ABSTRACT FROM AUTHOR]

Mushrooms in the genus Hericium are used as functional food and traditional medicines for a long history in East Asian countries such as China, India, Japan, and Korea. Some species of Hericium are called as monkey head mushroom (Houtougu) in China and Yamabushitake in Japan, which are traditionally considered as rare and precious health promoting food and medicinal materials for the treatment of dyspepsia, insomnia, chronic gastritis, and digestive tract tumors. This review aims to summarize the ethnopharmacology and structural diversity of secondary metabolites from Hericium species, as well as the pharmacological activities of the crude extracts and pure compounds from Hericium species in recent years. All the information was gathered by searching Scifinder, PubMed, Web of Science, ScienceDirect, Springer, Wiley, ACS, CNKI, Baidu Scholar, Google Scholar databases and other published materials (books and Ph.D. and M. Sc. Dissertations) using the keywords " Hericium ", "Traditional uses", "Chemical composition", "Quality control" and "Pharmacological activity" (1971–May 2023). The species name was checked with https://www.mycobank.org/. The traditional uses of Hericium species were summarized, and 230 secondary metabolites from Hericium species were summarized and classified into six classes, mainly focusing on their chemical diversity, biosynthesis, biological activities. The modern pharmacological experiments in vivo or in vitro on their crude and fractionated extracts showed that the chemical components from Hericium species have a broad range of bioactivities, including neuroprotective, antimicrobial, anticancer, α -glucosidase inhibitory, antioxidant, and anti-inflammatory activities. The secondary metabolites discovered from Hericium species are highly structurally diverse, and they have the potential to be rich resources of bioactive fungal natural products. Moreover, the unveiled bioactivities of their crude extracts and pure compounds are closely related to critical human health concerns, and in-depth studies on the potential lead compounds, mechanism of pharmacological effects and pharmaceutical properties are clearly warranted. [Display omitted] [ABSTRACT FROM AUTHOR]

Five previously undescribed pyridone derivatives, tolypyridones I–M, were identified from the solid rice medium fermented by Tolypocladium album dws120, along with two known compounds tolypyridone A (or trichodin A) and pyridoxatin. Their planar structures and partial relative configurations have been determined by careful interpretation of their spectroscopic data. The full assignment of the relative and absolute configurations of tolypyridones I–M was achieved by gauge-independent atomic orbital 13C NMR calculation, quantitative nuclear Overhauser effects based interatomic distance calculation, and electronic circular dichroism calculation. In addition, we have fully determined the configuration of tolypyridone A by X-ray diffraction analysis. In bioassay, tolypyridones I was able to restore cell viability and inhibit the release of alanine aminotransferase and aspartate aminotransferase for ethanol-induced LO2 cells, suggesting its potential as a liver protective agent. [Display omitted] • Seven pyridones were identified from Tolypocladium album dws120. • Relative configurations were determined by 13C NMR calculation and quantitative NOE analysis. • Tolypyridones I showed protective effects against ethanol-induced LO2 cell injury. [ABSTRACT FROM AUTHOR]

Six new neolignans, sinensiols B-G (1–6), together with three known analogues (7–9) were isolated from the whole plant of Selaginella sinensis. Their planar structures were established by comprehensive spectroscopic analyses including 1D, 2D NMR, IR and HRESIMS data. The absolute configurations of new compounds were elucidated by comparing their experimental CD spectra with known ones and using the reversed helicity rule for the 1L b band ECD of dihydrobenzofuran neolignans. Sinensiols A-D (7 , 1–3) belong to sesquilignan with a dimer of dihydrobenzo[ b ]furan moiety. The potential precursors of sinensiols A, B, D were also reported in this paper. In addition, all new compounds were screened for their cytotoxicity against A549 and HepG2 human cancer cell lines, and they didn't show inhibition on the growth of cancer cells. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract Four new trace alkaloids with lycodine-related structures, Lycocasuarinines A–D (1 – 4), together with seven known analogues (5 – 11), were isolated from the chloroform extract of Lycopodiastrum casuarinoides. The structures and stereochemistry of 1 – 4 were elucidated by spectroscopic analysis (IR, UV, MS, NMR, HRESIMS and CD) and comparison with known ones. The acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities of nine isolates were evaluated. Lycocasuarinine D (4) showed the most potent AChE inhibitory effect. In addition, a plausible biogenetic pathway of compound 4 was proposed. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Two new isobenzofuranone derivatives erinaceolactones G and H (1and2) were isolated from the ethanolic extract of fruiting bodies ofHericium erinaceus. Their structures were characterized on the basis of spectroscopic evidences. Compound2was suggested to be racemic by specific rotation, which was resolved by chiral HPLC into enantiomers. [ABSTRACT FROM PUBLISHER]

Three new neolignans, lycocernuasides B-D ( 1 – 3 ), three new serratane triterpenoids, lycernuic ketones D ( 8 ) and E ( 9 ), and lycernuic A ( 10 ), together with six known compounds, were isolated from the 75% aqueous EtOH extract of Palhinhaea cernua. Their structures and absolute configurations were established primarily by NMR, HRESIMS and circular dichroism (CD). All compounds were evaluated the inhibitory activities of xanthine oxidase. Compounds 1 – 3 displayed moderate inhibitory effects on xanthine oxidase with IC 50 values of 30.36 μM, 42.65 μM and 35.33 μM, respectively. [ABSTRACT FROM AUTHOR]

Three new isobenzofuranone derivatives erinaceolactones D-F (1–3), together with four known ones (4–7), were isolated from the fruiting bodies ofHericium erinaceus. Their structures were determined on the basis of comprehensive spectroscopic analyses including UV, 1D, 2D NMR and HR-TOF-MS. The absolute configuration of erinaceolactone D (1) and erinaceolactone E (2) were assigned by comparing their specific rotation with those of analogs in literatures. The four known compounds were isomers with each other and were isolated simultaneously for the first time. [ABSTRACT FROM PUBLISHER]

Pestalopyrones A–D are four unusual tricyclic pyrone derivatives with flexible chiral structures, isolated from the endophytic fungus Pestalotiopsis neglecta S3. The full elucidation of their structures was a challenging task, and remained unsolved in the original article. Herein, the relative configurations of pestalopyrones A and pestalopyrones B were unambiguously assigned by detailed analyses on spectroscopic data and GIAO 13C NMR calculation method with sorted training sets (STS). The planar structures of pestalopyrones C and pestalopyrones D were revised by reinterpretation of their reported spectroscopic data, and then their relative configurations were deduced by STS GIAO 13C NMR calculation and NOE analysis. The absolute configurations of all the mentioned compounds were determined by the comparison of their experimental and calculated ECD curves. [Display omitted] • The planar structures of pestalopyrones C and D were revised. • Relative configuration determined by 13C NMR calculation and NOE analysis. • The absolute configurations were elucidated by ECD calculation. [ABSTRACT FROM AUTHOR]

Six new flavonoids, involvenflavones A–F ( 1 – 6 ), were isolated from Selaginella involven . Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3′-aryl substituent. This is the first report of the apigenin derivatives with 3′-aryl substituent from nature resources. These compounds also exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro. [ABSTRACT FROM AUTHOR]

Three new compounds (I), (II), and (III) are isolated from the whole herbs of Selaginella involven Spring. [ABSTRACT FROM AUTHOR]

Six flavonoids, namely, three undescribed biflavonoids, one undescribed 8-aryl flavonoid, and two known compounds, were isolated from Selaginella tamariscina (P.Beauv.) Spring. The structures and absolute configurations of those undescribed compounds were established by NMR spectroscopy data, HRESIMS analyses and electronic circular dichroism (ECD) analyses. In addition, all the isolates were evaluated for their hypoglycemic activity in HepG2 cells. Involvenflavone H, I, and J significantly increased glucose consumption in both normal and insulin-resistant HepG2 cells. Interestingly, these three compounds can effectively upregulate the protein expression of glucokinase (GCK) and adenylate cyclases (ADCYs). These results suggested that involvenflavone H, I, and J (especially involvenflavone J) may have potent hypoglycemic activity, which also provided promising molecular targets for the treatment of diabetes. [Display omitted] • Four undescribed flavonoids were isolated from Selaginella tamariscina (P.Beauv.) Spring. • Involvenflavone H, I, and J significantly increased the glucose consumption in insulin-resistant HepG2 cells. • Involvenflavone J up-regulated the protein expression of glucokinase and adenylate cyclases effectively. [ABSTRACT FROM AUTHOR]

An unusual macrocyclic biflavone, selacyclicbiflavone A ( 1 ), have been isolated from Selaginella uncinata . The structure was elucidated on the basis of rigorous spectroscopic analysis including 1D and 2D NMR experiments as well as HRESIMS techniques. The absolute stereochemistry of compound 1 was further confirmed by comparing experimental data with calculated electronic circular dichroism (ECD) spectra. This is the first report of the macrocyclic biflavone with an unprecedented methylene bridge. A possible biosynthetic pathway was also postulated. [ABSTRACT FROM AUTHOR]

Abstract: Previous investigations have indicated that calcitonin gene-related peptide (CGRP), a principal transmitter in capsaicin-sensitive sensory nerves, could alleviate cardiac anaphylaxis injury. Rutaecarpine relaxes vascular smooth by stimulation of CGRP release via activation of vanilloid receptor subtype 1 (VR1). In the present study, we examined the role of capsaicin-sensitive sensory nerves in anaphylactic vessels and the effect of rutaecarpine on antigen-challenged constriction in the guinea pig isolated thoracic aorta. The aortas were challenged with 0.01 mg/ml bovine serum albumin, and the tension of aorta rings was continuously monitored. The amount of CGRP released from thoracic aortas was determined in the absence or presence of rutaecarpine. Antigen challenge caused a vasoconstrictor response concomitantly with an increase in the release of CGRP from the isolated thoracic aorta, and the vasoconstrictor responses were potentiated by CGRP8-37 (10 μM) or capsaicin (1 μM). Pretreatment with diphenhydramine (1 μM) markedly decreased antigen-challenged vasoconstriction. Acute application of capsaicin (0.03 or 0.1 μM) significantly inhibited vasoconstrictor responses. Pretreatment with rutaecarpine (10 or 30 μM) significantly increased CGRP release concomitantly with decrease in antigen-challenged vasoconstriction, which was abolished by CGRP8-37 (10 μM) or capsazepine (10 μM). The present results suggest that an increase in the release of CGRP during vascular anaphylaxis may be a beneficial compensatory response, and that rutaecarpine inhibits antigen-challenged vasoconstriction, which is related to stimulation of endogenous CGRP release via activation of VR1. [Copyright &y& Elsevier]

The present study examined the anti-oxidation and protective effects of demethylbellidifolin (DMB), a xanthone compound extracted from swertia davidi Franch, on endothelium. The relationship between the protective effects of DMB on endothelium and the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, was also determined in the present study. DMB significantly inhibited Cu2+-induced low-density lipoprotein (LDL) oxidation and scavenged DPPH radicals. DMB significantly attenuated the inhibition of endothelium-dependent vasodilator responses, induced by lysophosphatidycholine (LPC) in vitro and LDL in vivo, and increased release of lactate dehydrogenase induced by LDL in cultured endothelial cells. DMB significantly attenuated the increased concentration of malondialdehyde and ADMA, and the decreased level of nitric oxide induced by LDL in vivo and in cultured endothelial cells. DMB also significantly reduced the decreased activity of dimethylarginine dimethylaminohydrolase (DDAH) induced by LDL in cultured endothelial cells. In summary, the present results suggest that DMB protects endothelial damage induced by LPC in vitro and LDL in vivo or in endothelial cells, and the protective effect of DMB on the endothelium is related to reduction of ADMA concentration via an increase of DDAH activity by inhibition of lipid peroxidation. [Copyright &y& Elsevier]

[Display omitted] • Six C-3′-C-6″ type of biflavonoids were isolated from S. trichoclada. • RF-A showed the strongest activity against MCF-7 cells among all isolated compounds. • RF-A induced the accumulation of ROS and Lipid peroxidation in MCF-7 cells. • RF-A induced ferroptosis in MCF-7 cells via the upregulation of VDAC2 protein. Breast cancer is one of the major malignant tumors in females, and currently, recurrence and metastasis are the main obstacles preventing effective breast cancer treatment. Biflavonoids of secondary metabolites from plants are excellent anticancer agents to fight sensitive and resistant breast cancer cell lines. In this study, six C-3′-C-6″ biflavonoids, including one new robustaflavone A (1 , RF-A) and five known robustaflavone derivatives (2 – 6) , were isolated from Selaginella trichoclada for the first time. We aimed to evaluate the inhibitory effects of compounds 1 – 6 against human breast cancer MCF-7 cells. Among the six compounds, RF-A showed the strongest activity, decreasing cell viability with an IC 50 value of 11.89 μΜ. Furthermore, RF-A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways. [ABSTRACT FROM AUTHOR]

Seven undescribed C 27 steroidal glycosides, Seladelicatulasine A–G, including six cholestanol glycosides and one spirostanol glycoside, were isolated from Selaginella delicatula. Their structures were elucidated by 1D/2D NMR spectra and HRESIMS analyses. The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. These cholestanol glycosides were isolated from the family Selaginellaceae for the first time. Seladelicatulasine F is characterized as a rare B-5,6-secosteroid. In addition, all the compounds were evaluated for their inhibitory activities against cholinesterase (AChE/BChE) and monoamine oxidase (MAO-A/MAO-B). These steroidal glycosides displayed selective inhibition activities on cholinesterase. Seladelicatulasine A, B and E inhibited the AChE activity with IC 50 values of 0.31, 0.09, and 0.04 μ M, respectively. Seladelicatulasine A and F showed the strongest inhibition activity on BChE with IC 50 values of 0.37 and 0.65 μ M, respectively. Image 1 • Seven undescribed C 27 steroidal glycosides were isolated from S. delicatula. • The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. • Compounds 1, 2 and 5 inhibited the AchE activity with IC 50 values of 0.31, 0.09, and 0.04 μ M, respectively. • Compounds 1 and 6 showed the strongest inhibition activity on BchE with IC 50 values of 0.37 and 0.65 μ M, respectively. [ABSTRACT FROM AUTHOR]

• Eight new and five known prenylflavonol glycosides were isolated from the leaves of Cyclocarya paliurus. • Prenylflavonol glycosides were discovered in Cyclocarya paliurus for the first time. • The compounds were evaluated for the inhibitory effects on xanthine oxidase activity. • Compounds 2 and 7 exhibited significant inhibition on xanthine oxidase activity. Eight new prenylflavonol glycosides (1 – 8), along with five known analogues (9 – 13) were isolated from the n -butanol extract of the dried leaves of Cyclocarya paliurus (family Juglandaceae) for the first time. The structures of these compounds were characterized by comprehensive analysis of 1D, 2D NMR, HRESIMS, UV data and acid hydrolysis. In bioassay, all these thirteen prenylflavonol glycosides exhibited inhibitory effects on xanthine oxidase (XOD) activity. Especially compounds 2 and 7 , showed outstanding IC 50 values of 31.81 ± 2.20 and 29.71 ± 3.69 μM, respectively. [ABSTRACT FROM AUTHOR]

• In vivo and in vitro metabolism of nintedanib was performed, nineteen metabolites were detected and 8 of them were firstly reported. • Calculated partition coefficients (Clog P) were applied to differentiate the isomeric metabolites in present study. • ADMET prediction of nintedanib was systematically evaluated, which provided a comprehensive insight of nintedanib metabolism. Nintedanib is a promising tyrosine kinase inhibitor for clinically treating idiopathic pulmonary fibrosis (IPF). Some clinical cases reported that nintedanib treatment can cause hepatotoxicity and myocardial toxicity. U. S. FDA warns the potential drug-drug interaction when it is co-administrated with other drugs. In order to understand the potential toxicity of nintedanib and avoid drug-drug interaction, the metabolism of nintedanib was systematically investigated in human liver microsomes and mice using metabolomics approach, and the toxicity of metabolites was predicted by ADMET lab. Nineteen metabolites were detected in vivo and in vitro metabolism, and 8 of them were undescribed. Calculated partition coefficients (Clog P) were used to distinguish the isomers of nintedanib metabolites in this study. The major metabolic pathways of nintedanib majorly included hydroxylation, demethylation, glucuronidation, and acetylation reactions. The ADMET prediction indicated that nintedanib was a substrate of the cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). And nintedanib and most of its metabolites might possess potential hepatotoxicity and cardiotoxicity. This study provided a global view of nintedanib metabolism, which could be used to understand the mechanism of adverse effects related to nintedanib and its potential drug-drug interaction. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the ethyl acetate extract of Lycopodiastrum casuarinoides (Spring) Holub (Lycopodiaceae) led to the isolation of nine compounds, including two new serratene triterpenoids, serrat-14-en-3α,21α-diol (1), 26-nor-8-oxo-21-one-α-onocerin (6), one new abietane diterpenoid, lycocasuarinone A (7), one new sesquiterpene acid, 7, 9-diene-1,4-epoxy-2-hydroxy-10-carboxylic acid (8) and one new chromone derivative, 5,7-dihydroxy-2-methyl esterchromone (9), together with four known serratene triterpenoids (2 – 5). Abietane diterpenoid (7) and sesquiterpene acid (8) from Lycopodiastrum casuarinoides are reported for the first time. Their structures and stereochemistry were unambiguously elucidated by spectroscopic analysis and comparison with known ones. All the compounds were tested for acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. Bioactivity assays revealed that compound 6 exhibited the most potent AChE inhibitory effect. Unlabelled Image [ABSTRACT FROM AUTHOR]

The article presents a chemical reaction of a macrocyclic biflavone Selacyclicbiflavone, from plant Selaginella uncinata.