Isolation, Identification, Anti-Inflammatory, and In Silico Analysis of New Lignans from the Resin of Ferula sinkiangensis.

Ferula sinkiangensis K. M. Shen (Apiaceae) is distributed in arid desert areas of Xinjiang, and its resin is a traditional Chinese medicine to treat gastrointestinal digestive diseases. To explore bioactive components from F. sinkiangensis, three new lignans and thirteen known components were isolated. The structural elucidation of the components was established utilizing spectroscopic analyses together with ECD calculations. Griess reaction results indicated new compounds 1 and 2 significantly decreased NO production in LPS-stimulated RAW 264.7 macrophages, and ELISA results indicated that they effectively attenuated LPS-induced inflammation by inhibiting TNF-α, IL-1ß, and IL-6 expressions. The in silico approach confirmed that compound 1 docked into the receptors with strong binding energies of -5.84~-10.79 kcal/mol. In addition, compound 6 inhibited the proliferation of AGS gastric cancer cells with IC50 values of 15.2 µM by suppressing the cell migration and invasion. This study disclosed that F. sinkiangensis might be a promising potential resource for bioactive components.

Undescribed sesquiterpene coumarins from the aerial parts of Ferula sinkiangensis and their anti-inflammatory activities in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Eight undescribed sesquiterpene coumarins (1-8) and twenty known ones (9-28), were isolated from the aerial parts of Ferula sinkiangensis K. M. Shen. Their structures were elucidated based on the comprehensive analysis of UV, IR, HRESIMS, 1D, and 2D NMR data. The absolute configuration of 1 was determined by single crystal X-Ray diffraction, while the absolute configurations of 2-8 were determined by comparisons of experimental and calculated electrostatic circular dichroism spectra. Compound 2 is the first hydroperoxy sesquiterpene coumarin from the genus Ferula, while compound 8 has an unusual 5',8'-peroxo bridge. Griess reaction results indicated compound 18 significantly decreased nitric oxide production of the lipopolysaccharide-stimulated RAW 264.7 macrophages with an IC50 value of 2.3 µM, and ELISA results revealed that compound 18 effectively inhibited tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 expressions.

Sesquiterpenes and Sesquiterpene Derivatives from Ferula: Their Chemical Structures, Biosynthetic Pathways, and Biological Properties.

Ferula is a genus of flowering plants known for its edible and medicinal properties. Since ancient times, many species of Ferula have been used in traditional medicine to treat various health issues across countries, such as digestive disorders, respiratory problems, and even as a remedy for headaches and toothaches. In addition, they are also used as a flavoring agent in various cuisines. As the main active ingredients in Ferula, sesquiterpenes and their derivatives, especially sesquiterpene coumarins, sesquiterpene phenylpropanoids, and sesquiterpene chromones, have attracted the attention of scientists due to the diversity of their chemical structures, as well as their extensive and promising biological properties, such as antioxidative, anti-inflammatory, antibacterial properties. However, there has not been a comprehensive review of sesquiterpenes and their derivatives from this plant. This review aims to provide an overview of the chemical structures, biosynthetic pathways, and biological properties of sesquiterpenes and sesquiterpene derivatives from Ferula, which may help guide future research directions and possible application methods for this valuable edible and medicinal plant.

Stereochemical insights into neuroprotective alkaloids from the aerial parts of Emilia sonchifolia.

A new alkaloid featured with a dibenz[c,e]azepin-5-one scaffold, namely emililactam A (3), together with a known pyrrolidine alkaloid (emilisonchine, 1) and a known flavonoid alkaloid [8-(2″-pyrrolidinone-5″-yl)-quercetin, 2] were isolated from the aerial parts of Emilia sonchifolia. Compounds 1 and 2 were isolated as racemic forms which were further separated, for the first time, to their corresponding enantiomers [(+)-1/(-)-1 and (+)-2/(-)-2], respectively, by using chiral-phase HPLC. The structure of new compound 3 was elucidated by extensive spectroscopic analysis. In addition, the absolute configurations of optically pure (+)-1/(-)-1 and (+)-2/(-)-2 were determined by the time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. In an in vitro bioassay, compounds (+)-1, (-)-1, (±)-1, and 3 exhibited moderate neuroprotective effects against corticosterone-induced injuries of PC12 cells.

Licoflavone B, an isoprene flavonoid derived from licorice residue, relieves dextran sodium sulfate-induced ulcerative colitis by rebuilding the gut barrier and regulating intestinal microflora.

Ulcerative colitis (UC) is a major inflammatory disease worldwide. We previously demonstrated that licorice residue flavones (LFs) showed satisfactory efficacy in the treatment of UC. Therefore, research into the ingredients of LFs may lead to the discovery of novel anti-UC targets. In the current study, we separated licoflavone B (LB) from LFs and administered it to dextran sodium sulfate (DSS)-exposed C57BL/6 mice for 14 days. Our results demonstrated that high dose LB (120 mg/kg) significantly prevented DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and colonic inflammation, indicating that LB has ameliorative effects on UC. We also investigated the composition of the intestinal barrier and microflora in an attempt to explore the mechanisms of LB against UC. As a result, we found that LB preserved the integrity of the colonic barrier by inhibiting colonic cell apoptosis and protecting the expression of occludin, claudin-1, and ZO-1. Moreover, LB reshaped the microflora composition by suppressing harmful bacteria (Enterococcus et al.) and boosting beneficial microorganisms (Bacteroides et al.). Further molecular exploration implied that LB exerted anti-UC activity through blocking the MAPK pathway. Here, we explored anti-UC activity of LB for the first time and clarified its mechanisms. These results will provide valuable clues for the discovery of novel anti-UC agents.

New Sulfoxide-Containing Derivatives from the Resin of Ferula sinkiangensis.

Four undescribed sulfoxide-containing derivatives, sinkiangenoxides A and B, (2Z, 4E)-sinkiangenoxide C, and (2E, 4E)-sinkiangenoxide C (1:  - 4: ), and one known compound, 1-(methylthio)propyl (E)-1-propenyl disulfide (5: ), were isolated from the resin of Ferula sinkiangensis. Their structures were determined based on spectroscopic methods, including IR, UV, HRESIMS, NMR, and CD analysis. Compounds 2:  - 4: showed moderate cytotoxic activities against four human cancer cell lines with IC50 values ranging from 15.0 to 40.3 µM. Sinkiangenoxide B (2: ) was shown to induce apoptosis in HepG2 cells. In addition, compound 5: effectively attenuated lipopolysaccharide-induced nitric oxide release and TNF-α, IL-1ß, IL-6, and IL-10 expression.

Determination of Toxic Pyrrolizidine Alkaloids in Traditional Chinese Herbal Medicines by UPLC-MS/MS and Accompanying Risk Assessment for Human Health.

Pyrrolizidine alkaloids (PAs) are a class of natural toxins with hepatotoxicity, genotoxicity and carcinogenicity. They are endogenous and adulterated toxic components widely found in food and herbal products. In this study, a sensitive and efficient ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to detect the PAs in 386 kinds of Chinese herbal medicines recorded in the Chinese Pharmacopoeia (2020). The estimated daily intake (EDI) of 0.007 µg/kg body weight (bw)/day was adopted as the safety baseline. The margin of exposure (MOE) approach was applied to evaluate the chronic exposure risk for the genotoxic and carcinogenic potential of PAs. Results showed that PAs was detected in 271 out of 386 samples with a content of 0.1-25,567.4 µg/kg, and there were 20 samples with EDI values above the baseline, 0.007 µg/kg bw/day. Beyond that, the MOE values for 10 out of 271 positive samples were below 10,000. Considering the actual situation, Haber's rule was used to assume two weeks exposure every year during lifetime, and still the MOE values for four out of 271 positive samples were under 10,000, indicating these products may have potential health risk. The developed method was successfully applied to detect the PAs-containing Chinese herbal medicines. This study provides convincing data that can support risk management actions in China and a meaningful reference for the rational and safe use of Chinese herbal medicines.

Sesquiterpene coumarins from Ferula sinkiangensis K.M.Shen and their cytotoxic activities.

Five undescribed sesquiterpene coumarins, one undescribed coumarin derivative, and twenty-five known analogues, were isolated from the resin of Ferula sinkiangensis K.M.Shen. The planar structures and relative configurations of the undescribed compounds were determined by NMR experiment and HRESIMS data. The absolute configurations were established by Electrostatic Circular Dichroism method. Among these analogues, Sinkiangenol E showed the best cytotoxic activity against HeLa cervical cancer cells. Annexin V-FITC/PI staining indicated that Sinkiangenol E induced apoptosis in HeLa cells. Cell cycle analysis showed Sinkiangenol E arrested cell cycle at G0/G1 phase. Western blot results proved that Sinkiangenol E affected apoptosis-related and cell cycle regulation-related protein expression by activating the MAPK pathway.

Simultaneous Determination and Risk Assessment of Pyrrolizidine Alkaloids in Artemisia capillaris Thunb. by UPLC-MS/MS Together with Chemometrics.

Pyrrolizidine alkaloids (PAs) are natural toxins found in some genera of the family Asteraceae. However, it has not been reported whether PAs are present in the widely used Asteraceae plant Artemisia capillaris Thunb. (A. capillaris). The purpose of this study was to establish a sensitive and rapid UPLC-MS/MS method together with chemometrics analysis for simultaneous determination and risk assessment of PAs in A. capillaris. The developed UPLC-MS/MS method was validated and was confirmed to display desirable high selectivity, precision and accuracy. Risk assessment was conducted according to the European Medicines Agency (EMA) guideline. Chemometrics analysis was performed with hierarchical clustering analysis and principal component analysis to characterize the differences between PAs of A. capillaris. Finally, PAs were found in 29 out of 30 samples and at least two were detected in each sample, besides, more than half of the samples exceeded the EMA baseline. Nevertheless, the chemometrics results suggested that the PAs contents of A. capillaris from different sources varied significantly. The method was successfully applied to the detection and risk evaluation of PAs-containing A. capillaris for the first time. This study should provide a meaningful reference for the rational and safe use of A. capillaris.

An unusual sesquiterpene coumarin from the seeds of Ferula sinkiangensis.

A sesquiterpene coumarin, sinkiangenorin E, consisting of a novel bicyclo[4.3.1]decane-type sesquiterpene system, was isolated from the seeds of Ferula sinkiangensis. The structure of sinkiangenorin E including the relative stereochemistry and the absolute configuration was elucidated on the basis of spectroscopic data. The new compound showed cytotoxic activity against AGS cells (IC50, 12.7 µM) and inhibiting effect against influenza A H1N1 (IC50, 4.0 µM), which provided important clues for the study on the bioactivities of this type of sesquiterpene coumarins.

Sesquiterpene coumarins from seeds of Ferula sinkiangensis.

A new sesquiterpene coumarin with a novel sesquiterpene carbon framework, Sinkiangenorin D, and ten known sesquiterpene coumarins were isolated from the seeds of Ferula sinkiangensis. The structures of these compounds, including the relative stereochemistry, were elucidated on the basis of spectroscopic data. All of the isolated compounds were tested against the AGS, HeLa, and K562 human cancer cell lines and showed cytotoxic activities with 50% inhibitory concentration values between 12.7 and 226.6 µM.

Steroidal esters from Ferula sinkiangensis.

Two new steroidal esters with an unusual framework, Sinkiangenorin A and B, a new organic acid glycoside, Sinkiangenorin C, and four known lignin compounds were isolated from the seeds of Ferula sinkiangensis. The structures of these compounds were established by spectroscopic analysis and single-crystal X-ray diffraction. All of the isolated compounds were tested against Hela, K562 and AGS human cancer cell lines. Sinkiangenorin C showed cytotoxic activity against AGS cells with an IC50 of 36.9 µM.