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Background: The MYB superfamily (v-myb avian myeloblastosis viral oncogene homolog) plays a role in plant growth and development, environmental stress defense, and synthesis of secondary metabolites. Little is known about the regulatory function of MYB genes in Peucedanum praeruptorum Dunn, although many MYB family members, especially R2R3-MYB genes, have been extensively studied in model plants., Results: A total of 157 R2R3-MYB transcription factors from P. praeruptorum were identified using bioinformatics analysis. Comprehensive analyses including chromosome location, microsynteny, gene structure, conserved motif, phylogenetic tree, and conserved domain were further performed. The length of the 157 transcription factors ranged from 120 to 1,688 amino acids (molecular weight between 14.21 and 182.69 kDa). All proteins were hydrophilic. Subcellular localization predictions showed that 155 PpMYB proteins were localized in the nucleus, with PpMYB12 and PpMYB157 localized in the chloroplasts and mitochondria, respectively. Ten conserved motifs were identified in the PpMYBs, all of which contained typical MYB domains. Transcriptome analysis identified 47,902 unigenes. Kyoto Encyclopedia of Genes and Genomes analysis revealed 136 pathways, of which 524 genes were associated with the phenylpropanoid pathway. Differential expressed genes (DEGs) before and after bolting showed that 11 genes were enriched in the phenylpropanoid pathway. Moreover, the expression patterns of transcription genes were further verified by qRT-PCR. With high-performance liquid chromatography (HPLC), 8 coumarins were quantified from the root, stem, and leaf tissue samples of P. praeruptorum at different stages. Praeruptorin A was found in both roots and leaves before bolting, whereas praeruptorin B was mainly concentrated in the roots, and the content of both decreased in the roots and stems after bolting. Praeruptorin E content was highest in the leaves and increased with plant growth. The correlation analysis between transcription factors and coumarin content showed that the expression patterns of PpMYB3 and PpMYB103 in roots align with the accumulation trends of praeruptorin A, praeruptorin B, praeruptorin E, scopoletin, and isoscopoletin, which declined in content after bolting, suggesting that these genes may positively regulate the biosynthesis of coumarins. Eleven distinct metabolites and 48 DEGs were identified. Correlation analysis revealed that the expression of all DEGs were significantly related to the accumulation of coumarin metabolites, indicating that these genes are involved in the regulation of coumarin biosynthesis., Conclusions: R2R3-MYB transcription factors may be involved in the synthesis of coumarin. Our findings provide basic data and a rationale for future an in-depth studies on the role of R2R3-MYB transcription factors in the growth and regulation of coumarin synthesis., Competing Interests: Declarations. Ethics approval and consent to participate: The samples were collected from the Botanical Garden growing in West Anhui University. The voucher specimens were deposited in the herbarium of West Anhui University and identified by Prof. Bangxing Han. This study complies with relevant institutional, national, and international guidelines and legislation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Complex coumarins (CCs) represent characteristic metabolites found in Apiaceae plants, possessing significant medical value. Their essential functional role is likely as protectants against pathogens and regulators responding to environmental stimuli. Utilizing genomes and transcriptomes from 34 Apiaceae plants, including our recently sequenced Peucedanum praeruptorum, we conduct comprehensive phylogenetic analyses to reconstruct the detailed evolutionary process of the CC biosynthetic pathway in Apiaceae. Our results show that three key enzymes - p-coumaroyl CoA 2'-hydroxylase (C2'H), C-prenyltransferase (C-PT), and cyclase - originated successively at different evolutionary nodes within Apiaceae through various means of gene duplications: ectopic and tandem duplications. Neofunctionalization endows these enzymes with novel functions necessary for CC biosynthesis, thus completing the pathway. Candidate genes are cloned for heterologous expression and subjected to in vitro enzymatic assays to test our hypothesis regarding the origins of the key enzymes, and the results precisely validate our evolutionary inferences. Among the three enzymes, C-PTs are likely the primary determinant of the structural diversity of CCs (linear/angular), due to divergent activities evolved to target different positions (C-6 or C-8) of umbelliferone. A key amino acid variation (Ala161/Thr161) is identified and proven to play a crucial role in the alteration of enzymatic activity, possibly resulting in distinct binding forms between enzymes and substrates, thereby leading to different products. In conclusion, this study provides a detailed trajectory for the establishment and evolution of the CC biosynthetic pathway in Apiaceae. It explains why only a portion, not all, of Apiaceae plants can produce CCs and reveals the mechanisms of CC structural diversity among different Apiaceae plants., (© 2024. The Author(s).)

The present investigation explored the antifungal effectiveness of Trachyspermum ammi essential oil (TAEO) against Aspergillus flavus, aflatoxin B 1 (AFB 1 ) contamination, and its mechanism of action using biochemical and computational approaches. The GC-MS result revealed the chemical diversity of TAEO with the highest percentage of γ-terpinene (39 %). The TAEO exhibited minimum inhibitory concentration against A. flavus growth (0.5 µL/mL) and AFB 1 (0.4 µL/mL) with radical scavenging activity (IC 50  = 2.13 µL/mL). The mechanism of action of TAEO was associated with the alteration in plasma membrane functioning, antioxidative defense, and carbon source catabolism. The molecular dynamic result shows the multi-regime binding of γ-terpinene with the target proteins (Nor1, Omt1, and Vbs) of AFB 1 biosynthesis. Furthermore, TAEO exhibited remarkable in-situ protection of Sorghum bicolor seed samples against A. flavus and AFB 1 contamination and protected the nutritional deterioration. Hence, the study recommends TAEO as a natural antifungal agent for food protection against A. flavus mediated biodeterioration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Powdery mildew, caused by Eeysiphe heraclei, seriously threatens Heracleum moellendorffii Hance. Plant secondary metabolites are essential to many activities and are necessary for defense against biotic stress. In order to clarify the functions of these metabolites in response to the pathogen, our work concentrated on the variations in the accumulation of secondary metabolites in H. moellendorffii during E. heraclei infection., Results: Following E. heraclei infection, a significant upregulation of coumarin metabolites-particularly simple coumarins and associated genes was detected by RNA-seq and UPLC-MS/MS association analysis. Identifying HmF6'H1, a Feruloyl CoA 6'-hydroxylase pivotal in the biosynthesis of the coumarin basic skeleton through ortho-hydroxylation, was a significant outcome. The cytoplasmic HmF6'H1 protein was shown to be able to catalyze the ortho-hydroxylation of p-coumaroyl-CoA and caffeoyl-CoA, resulting in the formation of umbelliferone and esculetin, respectively. Over-expression of the HmF6'H1 gene resulted in increased levels of simple coumarins, inhibiting the biosynthesis of furanocoumarins and pyranocoumarins by suppressing PT gene expression, enhancing H. moellendorffii resistance to powdery mildew., Conclusions: These results established HmF6'H1 as a resistance gene aiding H. moellendorffii in combatting E. heraclei infection, offering additional evidence of feruloyl-CoA 6'-hydroxylase role in catalyzing various types of simple coumarins. Therefore, this work contributes to our understanding of the function of simple coumarins in plants' defense against powdery mildew infection., (© 2024. The Author(s).)

Cryptotaenia japonica, a traditional medicinal and edible vegetable crops, is well-known for its attractive flavors and health care functions. As a member of the Apiaceae family, the evolutionary trajectory and biological properties of C. japonica are not clearly understood. Here, we first reported a high-quality genome of C. japonica with a total length of 427 Mb and N50 length 50.76 Mb, was anchored into 10 chromosomes, which confirmed by chromosome (cytogenetic) analysis. Comparative genomic analysis revealed C. japonica exhibited low genetic redundancy, contained a higher percentage of single-cope gene families. The homoeologous blocks, K s , and collinearity were analyzed among Apiaceae species contributed to the evidence that C. japonica lacked recent species-specific WGD. Through comparative genomic and transcriptomic analyses of Apiaceae species, we revealed the genetic basis of the production of anthocyanins. Several structural genes encoding enzymes and transcription factor genes of the anthocyanin biosynthesis pathway in different species were also identified. The CjANSa, CjDFRb, and CjF3H gene might be the target of Cjaponica_2.2062 (bHLH) and Cjaponica_1.3743 (MYB). Our findings provided a high-quality reference genome of C. japonica and offered new insights into Apiaceae evolution and biology., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Traditional Chinese medicine has used Peucedanum praeruptorum Dunn (Apiaceae) for a long time. Various coumarins, including the significant constituents praeruptorin (A-E), are the active constituents in the dried roots of P. praeruptorum. Previous transcriptomic and metabolomic studies have attempted to elucidate the distribution and biosynthetic network of these medicinal-valuable compounds. However, the lack of a high-quality reference genome impedes an in-depth understanding of genetic traits and thus the development of better breeding strategies., Results: A telomere-to-telomere (T2T) genome was assembled for P. praeruptorum by combining PacBio HiFi, ONT ultra-long, and Hi-C data. The final genome assembly was approximately 1.798 Gb, assigned to 11 chromosomes with genome completeness >98%. Comparative genomic analysis suggested that P. praeruptorum experienced 2 whole-genome duplication events. By the transcriptomic and metabolomic analysis of the coumarin metabolic pathway, we presented coumarins' spatial and temporal distribution and the expression patterns of critical genes for its biosynthesis. Notably, the COSY and cytochrome P450 genes showed tandem duplications on several chromosomes, which may be responsible for the high accumulation of coumarins., Conclusions: A T2T genome for P. praeruptorum was obtained, providing molecular insights into the chromosomal distribution of the coumarin biosynthetic genes. This high-quality genome is an essential resource for designing engineering strategies for improving the production of these valuable compounds., (© The Author(s) 2024. Published by Oxford University Press GigaScience.)

Tetrahydrofuran ring formation from dibenzylbutyrolactone lignans is a key step in the biosynthesis of aryltetralin lignans including deoxypodophyllotoxin and podophyllotoxin. Previously, Fe(II)- and 2-oxoglutarate-dependent dioxygenase (2-ODD) from Podophyllum hexandrum (Himalayan mayapple, Berberidaceae) was found to catalyze the cyclization of a dibenzylbutyrolactone lignan, yatein, to give deoxypodophyllotoxin and designated as deoxypodophyllotoxin synthase (DPS). Recently, we reported that the biosynthesis of deoxypodophyllotoxin and podophyllotoxin evolved in a lineage-specific manner in phylogenetically unrelated plant species such as P. hexandrum and Anthriscus sylvestris (cow parsley, Apiaceae). Therefore, a comprehensive understanding of the characteristics of DPSs that catalyze the cyclization of yatein to deoxypodophyllotoxin in various plant species is important. However, for plant species other than P. hexandrum, the isolation of the DPS enzyme gene and the type of the enzyme, e.g. whether it is 2-ODD or another type of enzyme such as cytochrome P-450, have not been reported. In this study, we report the identification and characterization of A. sylvestris DPS (AsDPS). Phylogenetic analysis showed that AsDPS belonged to the 2-ODD superfamily and shared moderate amino acid sequence identity (40.8%) with P. hexandrum deoxypodophyllotoxin synthase (PhDPS). Recombinant protein assay indicated that AsDPS and PhDPS differ in terms of the selectivity of substrate enantiomers. Protein modeling using AlphaFold2 and site-directed mutagenesis indicated that the Tyr305 residue of AsDPS probably contributes to substrate recognition. This study advances our understanding of the podophyllotoxin biosynthetic pathway in A. sylvestris and provides new insight into 2-ODD involved in plant secondary (specialized) metabolism., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ammi visnaga L. is an enriched medicinal plant with medicinally important compounds. Two types of nanoparticles (NPs) including silica (SiO 2 ) and graphene oxide bound with SiO 2 (GO-SiO 2 ) NPs at different concentrations (0, 15, 25 mg L -1 ) were used as elicitors to investigate their effects on callus morphology, H 2 O 2 content, total phenolic content (TPC), total flavonoids content (TFC), ferric reducing/antioxidant power (FRAP), and few antioxidant enzymes such as catalase (CAT), guaiacol peroxidase (GPX), superoxide dismutase (SOD), ascorbate peroxidase (APX), and polyphenol oxidase (PPO) in the callus cultures of A. visnaga. The effects of elicitation of both NPs on calli were observed using a scanning electron microscope (SEM). The 15 mg L -1 concentration of GO-SiO 2 NPs produced the highest TPC (193.3 mg GAE g -1 FW), CAT (13.1 U mg -1 Protein), GPX (0.0089 U mg -1 Protein), and APX (0.079 U mg -1 Protein). Whereas, the maximum content of H 2 O 2 (0.68 μmol g -1 FW), FRAP (0.0092 μmol mg -1 ), and TFC (62.27 mg QE g -1 FW) was observed at 25 mg L -1 and 15 mg L -1 of SiO 2 NPs, respectively. Conclusively, in the callus culture of A. visnaga, the 15 mg L -1 concentration of GO-SiO 2 NPs was the most suitable dosage for enhancing the enzymatic antioxidant activities (CAT, GPX, APX) and TPC, rather than SiO 2 NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Lung cancer is one of the deadliest cancers in the world. Introducing new promising agents can help the chemotherapeutic management of cancer. In the knowledge of oncology, plants are of special interest as a rich source of new antineoplastic and chemotherapeutic agents. Grandivittin (GRA) is one of the main constituents of Ferulago trifida Boiss. with established medicinal, phytochemical, and pharmacological properties. This study aimed to isolate and evaluate the antineoplastic potential of grandivittin and its underlying mechanisms in human lung cancer A549 cells. The viability of the A549 cells after being treated with 0.1, 0.4, 0.7, 1, and 1.3 mM of GRA for three following days was measured using the MTT method. The early apoptosis and late apoptosis were assessed by fluorescence-activated cell sorter analysis through annexin V/PI staining. The expression of apoptotic agents' genes (caspase 3, caspase 9, Bcl2, Bax, and P53) was evaluated by the RT-PCR method. GRA increased apoptotic cells and decreased cell viability in a dose- and time-dependent manner, in which only 50% of cells survived at a dose of 0.7 mM. The expression of Bax, P53, caspase 3, and caspase 9 genes in the A549 cells was significantly upregulated after GRA treatment compared to control cells (P < 0.05). On the other hand, Bcl2 was significantly downregulated after GRA treatment (P < 0.05). The results indicated that GRA can activate cell death in A549 lung carcinoma cells by inducing both DNA toxicity p53 and cascade-dependent pathways. Therefore, GRA may be a potential new therapeutic agent for the treatment of lung cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The dried root of Saposhnikovia divaricata (Turcz.) Schischk. is popular as a good medicinal material, however the abundant aerial part is often discarded, which caused the waste of resources. In order to exploit resources, the essential oils of the plant aerial part and root were extracted, separately called as VOA and VOR, their chemicals were identified. The tumor necrosis factor-α, interleukin-6, nitric oxide and interleukin-1β were detected to evaluate the oils anti-inflammatory activities. Then, the oils free radical scavenging rates were measured with DPPH, ABTS and hydroxyl free radical. The oils antitumor activities were evaluated with HeLa and HCT-8 cancer cell lines. The results showed the concentrations of VOA and VOR were separately 0.261% and 0.475%. Seventeen components of VOA were identified, accounting for 80.48% of VOA, including phytol, spathulenol, phytone, 4(15),5,10(14)-Germacratrien-1-ol, neophytadiene, etc. Seven components of VOR were determined, representing 90.73% of VOR, consisted of panaxynol, β-bisabolene, etc. VOA and VOR significantly inhibited the secretion of nitric oxide, interleukin-1β, interleukin-6 and tumor necrosis factor-α, effectively scavenged the DPPH, ABTS and hydroxyl free radicals, and showed significant antiproliferative activity against HeLa and HCT-8. The two oils presented important biological activity, which provided a hopeful utilized basis, and helped to reduce the waste of the aerial non-medicinal resources of S. divaricata., (© 2023. The Author(s).)

Background: Drought is one of the crucial constraints limiting horticultural plant's production and development around the world. Pugionium cornutum is an annual or biennial xerophyte with strong environmental adaptability and drought resistance; however, the mechanisms with respect to response to drought stress remain largely unclear., Methods: After seedling emergence, the gravimetric method was used to control soil relative water content (SRWC). Drought stress was applied to the six-leaf stage P. cornutum seedlings. The soil water content of different drought stress levels (L) was controlled by gravimetric method as follows: control (L1): 70-75% SRWC; moderate drought level (L2): 40-45% SRWC; severe drought level (L3): 30-35% SRWC, and the water was added to different drought stress levels at about 18:00 p.m. every day. The experiment ended when the leaves of P. cornutum showed severe wilting (10-leaf stage). Samples were harvested and stored at -80 °C for physiological determination, and transcriptomic and proteomic sequencing., Results: Compared with L1, the leaves of P. cornutum seedlings were increasingly wilted after drought treatment; the SRWC of the drought-stress leaves decreased notably while the leaf water potential was rose; the proline, malondialdehyde (MDA) content increased with the continuous drought treatment but peroxidase (POD) activity decreased. Besides, 3,027 differential genes (DGs) and 196 differential proteins (DPs), along with 1,943 DGs and 489 DPs were identified in L2-L1 and L3-L1, respectively. The transcriptome and proteome integrated analysis manifested that only 30 and 70 were commonly regulated both in L2-L1 and L3-L1, respectively. Of which, 24 and 61 DGs or DPs showed the same trend including sHSPs, APX2, GSTU4, CML42, and POD, etc . However, most of DGs or DPs were regulated only at the transcriptome or proteome level mainly including genes encoding signal pathway (PYR1, PYLs, SnRK2J, PLC2, CDPK9/16/29, CML9, MAPKs), transcription factors (WRKYs, DREB2A, NAC055, NAC072, MYB and, HB7) and ion channel transporters (ALMT4, NHX1, NHX2 and TPK2). These genes or proteins were involved in multiple signaling pathways and some important metabolism processes, which offers valuable information on drought-responsive genes and proteins for further study in P. cornutum ., Competing Interests: The authors declare that they have no competing interests., (© 2023 Wang et al.)

Edible plants are gaining importance as an integrative therapy for many chronic diseases, including cancer. We first reported that the edible wild plant Crithmum maritimum L. inhibits the growth of hepatocellular carcinoma (HCC) cells by exerting a multitarget action on cellular metabolism and bioenergetic profile. Here, we show that Crithmum maritimum ethyl acetate extract significantly increases the responsiveness of HCC cells to the chemotherapeutic drug sorafenib by reducing lactic acid fermentation and inducing a pro-hepatocyte biomarker profile. Our findings strengthen the role of Crithmum maritimum L. as a valuable nutraceutical tool to support pharmacological therapeutic interventions in HCC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Early bolting of Peucedanum praeruptorum Dunn severely affects its quality. In this study, we compared with the root structure of P. praeruptorum and its four coumarins content between early bolting (CT) and unbolting (WT) at different growth stages. We found that the proportion of area outside the root cambium (Rs) was higher in the WT plants than in the CT plants and correlated positively with the proximity to the root tip. Furthermore, the content of all four coumarins was also higher in the WT plants relative to the CT plants. In addition, we identified 15,524 differentially expressed genes (DEGs) between the two plant varieties. 11 DEGs are involved in the photoperiod and gibberellin pathways that regulate early bolting and 24 genes involved in coumarins biosynthesis were also identified. Nevertheless, early bolting of P. praeruptorum does affect its quality formation, and further studies are needed to confirm its mechanism., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ducrosia anethifolia Boiss is a medicinal and aromatic plant that is used as a food additive and drug in the areas of natural distribution. In this study, eight populations from different geographical regions of Iran were evaluated for their essential oil composition, total phenolics and flavonoids as well as for free radical scavenging activity during two consecutive years under water deficit. Analysis of variance was performed using a randomized block design at three levels of irrigation and 2 years, using the GLM procedure of SAS software and cluster analysis was used according to Ward's method using squared Euclidean dissimilarity. The highest essential oil and total phenolics/flavonoids content were obtained in the second year. GC-MS analysis was used to analyze the essential oil components. In normal conditions, cis-chrysanthenyl acetate (39.1-66.4%) and α-pinene (1.02-4.7%) were recognized as major compounds. The essential oil components were elevated under water stress. The highest increase in cis-chrysanthenyl acetate (21.32%) in response to water stress was observed in Abarkuh1. Elevation in total phenolic, flavonoid and antioxidant activity was also observed in plants subjected to water deficit. The highest content of phenolic acids was measured in Semirom (136.74 mg TAE/g DW), while the highest flavonoid content was in Kerman (6.05 mg QUE/g DW) in severe water stress condition. Finally, a high diversity in the studied populations can be used to select advantageous populations for other pharmaceutical and food purposes., (© 2022. The Author(s).)

Rhizosphere soil microbial community and its diversity are important for the structure and functions of medicinal plant ecosystem. In this study, based on high-throughput sequencing, rhizosphere soil microbial diversity, and yield and quality of rhizome and root of Notopterygium incisum cultivated alone(control, CK) and intercropped with Vicia faba(QH) were analyzed, which is expected to lay a basis for optimization of the cultivation mode and ecological production of N. incisum. RESULTS:: showed that the rhizosphere soil bacteria of N. incisum were dominated by Proteobacteria and Bacteroides, with the relative abundance of 50.38%-51.95% and 16.36%-17.02%, respectively. Soil bacterial community at the phylum level was not significantly different between CK and QH. At the genus level, the relative abundance of MND1(3.54%), Spinstomonas(3.50%), Nitrospira(1.53%), and Rhizobacter(1.05%) was significantly higher and that of Gemmatimonas, Candidatus＿Solibacter, and Bryophytes was lower in QH treatment than in the CK. The plant height, leaf length, leaf width, and petiole length of N. incisum in QH treatment was significantly increased and the underground biomass rose by 71.43% compared with those in the CK. Thus, intercropping with V. faba promoted the aboveground growth of N. incisum and improved the yield of root and rhizome. Moreover, the content of notopterol and isoimperatorin increased by 37.96% and 4.09% in QH treatment, respectively, indicating that the intercropping with V. faba boosted the accumulation of secondary metabolites in N. incisum. Pearson's correlation analysis showed that the soil bacterial community was mainly influenced by the soil factors including the content of soil available nutrients, soil organic matter, pH value, and soil water. The influence was in the order: total potassium&gt;total nitrogen&gt;pH&gt;organic matter&gt;available potassium&gt;soil water content&gt;available nitrogen&gt;available phosphorus. In conclusion, the intercropping with V. faba altered soil microenvironment and also increased the yield and accumulation of secondary metabolites of N. incisum, which is a promising ecological planting model for N. incisum.

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

Introduction: Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells are exposed to ionizing radiation, they generate free radicals and reactive oxygen species that can cause damage in DNA, which leads to cellular dysfunction or even cell death. However, it is necessary to identify new radioprotective agents to protect normal cells. Ferulago angulata (F. angulata), a medicinal plant, can be used as a new radioprotective agent., Purpose: In this study, the radioprotective effect of F. angulata was evaluated against genotoxicity and oxidative stress induced by ionizing radiation in human blood lymphocytes., Methods: The antioxidant activity of F. angulata was assayed using FRAP and DPPH methods. Then, the human blood samples were incubated with F. angulata at different concentrations (25, 50, 100, and 200 μM) and subsequently exposed to IR at a dose of 2Gy. The radioprotective effect of F. angulata on the exposed cells was assessed by the micronucleus (MN) method. Also, biomarkers of oxidative stress in the exposed cells were evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) methods., Results: Our findings showed that F. angulata reduced the frequency of MN induced by IR in exposed cells. At a 200 μM concentration of F. angulata, the maximum reduction in the frequency of MN (63.11%) was observed that demonstrated a high degree of radioprotection. Afterward, pretreatment at 200 μM concentration of F. angulata inhibited oxidative stress in irradiated lymphocytes, leading to a reduction in MN frequency and MDA levels while SOD activity was enhanced in the exposed cells., Conclusion: F. angulata as a natural radioprotective agent can protect normal cells against reactive oxygen species and genetic damage induced by IR., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the present study, the phytochemical features of the essential oils from leaves, flowers, and fruits in three Ferulago species including F. angulata, F. carduchorum, and F. contracta was investigated. The essential oils were extracted using the hydrodistillation method and analyzed by GC-FID and GC/MS. The essential oil content varied between 0.46 to 2.65 % (v/w) among the various parts of the studied species. Monoterpene hydrocarbons (leaves: 34.80-78.76 %, flowers: 88.67-94.26 %, fruits: 89.54-94.21 %) constituted the main fraction of three Ferulago species. The major compounds of the essential oil among the species were α-pinene (15.01-22.16 %), β-phellandrene (2.48-14.73 %), α-phellandrene (0.52-13.8 %), and germacrene B (0.11-13.28 %) in leaves; (Z)-β-ocimene (38.46-47.21 %), α-pinene (10.25-18.32 %), and α-phellandrene (5.07-9.44 %) in flowers; (Z)-β-ocimene (10.21-41.19 %), α-phellandrene (7.51-31.89 %), α-pinene (8.96-17.71 %), β-phellandrene (7.24-17.44 %), terpinolene (2.90-7.77 %), and δ-3-carene (1.57-7.66 %) in fruits. The classical antioxidant activity of the essential oils was assessed using the DPPH method. The fruit essential oils of the studied species induced a significant level of antioxidant activity compared to ascorbic acid (EC 50 =50.24 μg/mL). The highest level of antioxidant activity was found in F. carduchorum (EC 50 =68.75 μg/mL) fruits essential oil. Ferulago species, therefore, have the potential to be utilized as natural antioxidants in the pharmaceutical, food or cosmetic industries owing to their high level of antioxidant activity., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

We aimed to explore and compare new insights on the pharmacological potential of Oliveria decumbence essential oil (OEO) and its main components highlighting their antioxidant activity in-vitro, in-vivo, and in-silico and also cytotoxic effects of OEO against A549 lung cancer cells. At first, based on GC-MS analysis, thymol, carvacrol, p-cymene, and γ-terpinene were introduced as basic ingredients of OEO and their in-vitro antioxidant capacity was considered by standard methods. Collectively, OEO exhibited strong antioxidant properties even more than its components. In LPS-stimulated macrophages treated with OEO, the reduction of ROS (Reactive-oxygen-species) and NO (nitric-oxide) and down-regulation of iNOS (inducible nitric-oxide-synthase) and NOX (NADPH-oxidase) mRNA expression was observed and compared with that of OEO components. According to the results, OEO, thymol, and carvacrol exhibited the highest radical scavenging potency compared to p-cymene, and γ-terpinene. In-silico Molecular-Docking and Molecular-Dynamics simulation indicated that thymol and carvacrol but no p-cymene and γ-terpinene may establish coordinative bonds in iNOS active site and thereby inhibit iNOS. However, they did not show any evidence for NOX inhibition. In the following, MTT assay showed that OEO induces cytotoxicity in A549 cancer cells despite having a limited effect on L929 normal cells. Apoptotic death and its dependence on caspase-3 activity and Bax/Bcl2 ratio in OEO-treated cells were established by fluorescence microscopy, flow cytometry, colorimetric assay, and western blot analysis. Additionally, flow cytometry studies demonstrated increased levels of ROS in OEO-treated cells. Therefore, OEO, despite showing antioxidant properties, induces apoptosis in cancer cells by increasing ROS levels. Collectively, our results provided new insight into the usage of OEO and main components, thymol, and carvacrol, into the development of novel antioxidant and anti-cancer agents., (© 2021. The Author(s).)

Objective: Alzheimer's disease is a progressive, age-related, and neurodegenerative disease characterized by mental decline. The exact cause of Alzheimer's disease is unclear, but cholinergic dysfunction, protein accumulation, and oxidative stress are among the most important hypotheses. The main purpose of our study was to investigate the effects of aqueous and hydroalcoholic extract combination of these two medicinal plants, black pepper and cumin (as a related formulation in traditional Persian medicine), on memory and learning of an immobilized stress animal model., Methods: In this study, hydroalcoholic and aqueous extracts of cumin and black pepper fruits were prepared. Six groups of mice were treated orally for 2 weeks: control group, immobility stress, and stress-induced immobility mice received different doses of the hydroalcoholic extract (100 and 200 mg/kg) and aqueous extract (100 and 200 mg/kg). The shuttle box, novel object detection, and rotarod test were used to evaluate memory and learning. The activities of acetylcholinesterase, catalase (CAT), and superoxide dismutase (SOD) and the level of reduced glutathione (GSH) and malondialdehyde (MDA) were measured in the brain tissue., Results: Immobility stress significantly reduced learning and motor coordination. Furthermore, MDA levels and acetylcholinesterase activity were significantly increased, while CAT and SOD activities were significantly reduced in the brain of immobility-induced stress mice. Other findings indicated that hydroalcoholic and aqueous extracts (100 and 200 mg/kg) of cumin and black pepper fruits have an improving effect on animal motor coordination and learning ability, GSH content, and CAT, SOD, and acetylcholinesterase enzyme function in comparison with stress groups ( p < 0.05)., Conclusion: The hydroalcoholic and aqueous extracts of cumin and black pepper fruits have protective effects against stress-induced memory deficit and oxidative stress and may have beneficial therapeutic effect in the treatment of neurodegenerative diseases., Competing Interests: The authors declare that there are no conflicts of interest in this research project., (Copyright © 2021 Marzieh Rashedinia et al.)

Key Message: Salicylic acid and iron-oxide nanoparticles alleviated salt toxicity and improved plant growth by stimulating the activities of H + -ATPase and H + -PPase and preventing nutrient imbalance. Two factorial experiments were undertaken in a greenhouse during 2018 and 2019, to evaluate the impacts of SA (1 mM) and nano-Fe 2 O 3 (3 mM) sprays at 7 leaves and flowering stages on vacuolar H + -pumps, growth and essential oil of salt-subjected (0, 4, 8 and 12 dS m -1 NaCl) ajowan plants. Measurements of plant traits were started at about 12 days after the last foliar spray and continued up to maturity. The H + -ATPase and H + -PPase activities and root ATP content were enhanced under low salinity, but higher salinities reduced these parameters. Rising salinity enhanced Na uptake and translocation, endogenous SA and DPPH activity, while reduced K + /Na + ratio and nutrients uptake, leading to a reduction in plant biomass. Treatment with SA, nano-Fe 2 O 3 and their combination improved H + -pumps activities and ATP content in roots and leaves. The SA-related treatments caused the highest activities of H + -pumps in roots, but Fe-related treatments resulted in the highest activities of these pumps in leaves. Increasing H + -pumps activities reduced sodium uptake and translocation and enhanced nutrients uptake. Foliar treatments, especially SA + nano-Fe 2 O 3 augmented endogenous SA, DPPH activity, and plant growth in salt-stressed plants. Essential oil contents of vegetative and inflorescence organs under severe salinity and seeds under moderate and severe salinities were enhanced. Maximum essential oil was obtained from seeds of SA + nano-Fe 2 O 3 -treated plants, which was strongly correlated with endogenous SA and DPPH. Nevertheless, the SA + nano-Fe 2 O 3 was the best treatment for diminishing salt toxicity and improving ajowan plant growth and essential oil production.

A novel stability-enhanced graphene quantum dot (GQD)-decorated epidermal growth factor receptor (EGFR) cell membrane chromatography was constructed to study the potential application of GQDs in bioaffinity chromatography, and to screen active components acting on EGFR from traditional Chinese medicine (TCM). The carboxyl groups on the surface of GQDs reacted with the amino groups of the amino-silica gel (SiO 2 -NH 2 ) to form a covalent bond, thereby preparing the GQD-decorated silica gel (SiO 2 -GQDs). The EGFR cell membrane was further immobilized on the SiO 2 -GQDs through the same covalent binding method to obtain the GQD-decorated cell membrane stationary phase (SiO 2 -GQDs-CMSP). In this way, the cell membrane was firmly immobilized on the decorated silica carrier. The life span and stability of the GQD-decorated cell membrane chromatographic (SiO 2 -GQDs-CMC) column were both enhanced, and the optimal immobilization conditions of the EGFR cell membrane were also determined. This model was then verified by establishing a SiO 2 -GQDs-CMC online liquid chromatography-ion trap-time-of-flight (LC-IT-TOF) system to screen possible active components in Peucedanum praeruptorum Dunn. As a result, praeruptorin B (Pra-B) was screened out, and its inhibitory effect against EGFR cell growth was evaluated by the cell counting kit-8 (CCK-8) assay. Molecular docking assay was also conducted to further estimate the interaction between Pra-B and EGFR. Overall, this research indicated that GQDs may be a promising nanomaterial to be used in prolonging the life span of the CMC column, and Pra-B could be a potential EGFR inhibitor so as to treat cancer.

Green synthesis of metal nanoparticles using plant extracts as capping and reducing agents for the biomedical applications has received considerable attention. Moreover, emergence and spread of multidrug resistance among bacterial pathogens has become a major health concern and lookout for novel alternative effective drugs has gained momentum. In current study, we synthesized gold nanoparticles using the seed extract of Trachyspermum ammi (TA-AuNPs), assessed its efficacy against drug resistant biofilms of Listeria monocytogenes and Serratia marcescens , and evaluated its anticancer potential against HepG2 cancer cell lines. Microwave-assisted green synthesis of gold nanoparticles was carried out and characterization was done using UV-vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Most nanoparticles were observed as spherical and spheroidal with few anisotropies with an average crystalline size of 16.63 nm. Synthesized TA-AuNPs demonstrated significant biofilm inhibitory activity against L. monocytogenes (73%) as well as S. marcescens (81%). Exopolysaccharide (EPS), motility, and CSH, key elements that facilitate the formation and maintenance of biofilm were also inhibited significantly at the tested sub-minimum inhibitory concentrations (sub-MICs). Further, TA-AuNPs effectively obliterated preformed mature biofilms of S. marcescens and L. monocytogenes by 64% and 58%, respectively. Induction of intracellular ROS production in TA-AuNPs treated bacterial cells could be the plausible mechanism for the reduced biofilm formation in test pathogens. Administration of TA-AuNPs resulted in the arrest of cellular proliferation in a concentration-dependent manner. TA-AuNPs decrease the intracellular GSH in HepG2 cancer cell lines, cells become more prone to ROS generation, hence induce apoptosis. Thus, this work proposes a new eco-friendly and rapid approach for fabricating NPs which can be exploited for multifarious biomedical applications.

7-Isopentenyloxycoumarin is among the most widespread naturally occurring prenyloxy umbelliferone derivatives. This secondary metabolite of mixed biosynthetic origin has been typically isolated from plants belonging to several genera of the Rutaceae and Apiaceae families, comprising widely used medicinal plants and in general plants with beneficial effects on human welfare, as well as edible fruits and vegetables. Although known for quite a long time (more than 50 years), only in the last two decades has this natural compound been revealed to exert powerful and promising pharmacological properties, such as active cancer chemopreventive, antibacterial, antiprotozoal, antifungal, anti-inflammatory, neuroprotective, and antioxidant properties, among the activities best outlined in the recent literature. The aim of this comprehensive miniature review article is to detail the novel natural sources and the effects described during the last decade for 7-isopentenyloxycoumarin and what has been reported on the mechanisms of action underlying the observed biological activities of this oxyprenylated secondary metabolite. In view of the herein described data, suggestions on how to address future research on the abovementioned natural product and structurally related derivatives in the best ways according to the authors will be also provided.

In spite of the impressing cytotoxicity of thapsigargin ( Tg ), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum , which contains a structurally related sesquiterpene lactone, trilobolide ( Tb ), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8- O -(12-aminododecanoyl)-8- O -debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin.

Soil contamination with toxic heavy metals [such as cadmium (Cd)] is becoming a serious global problem due to rapid development of social economy. Silicon (Si), being an important fertilizer element, has been found effective in enhancing plant tolerance against biotic and abiotic stresses. The present study investigated the extent to which different levels of Si modulated the Cd tolerance of Ajwain (Trachyspermum ammi L.) seedlings when maintained in artificially Cd spiked regimes. A pot experiment was conducted under controlled conditions for four weeks, by using sand, mixed with different levels of Cd i.e., 0, 1.5 and 3 mM together with the application of Si at 0, 1.5 and 3 mM levels to monitor different growth, gaseous exchange, oxidative stress, antioxidative responses, minerals accumulation, organic acid exudation patterns of T. ammi seedlings. Our results depicted that Cd addition to growth medium significantly decreased plant growth and biomass, gaseous exchange attributes and minerals uptake by T. ammi seedlings as compared to the plants grown without addition of Cd. However, Cd toxicity boosted the production of reactive oxygen species (ROS) by increasing the contents of malondialdehyde (MDA), which is the indication of oxidative stress in T. ammi seedlings and was also manifested by hydrogen peroxide (H 2 O 2 ) contents and electrolyte leakage to the membrane bounded organelles. Although, activities of various antioxidative enzymes like superoxidase dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) initially increased up to a Cd level of 1.5 mM but were significantly diminished at the highest Cd level of 3 mM. Results revealed that the anthocyanin and soluble proteins contents were decreased in seedlings grown under elevating Cd levels but increased the Cd accumulation of T. ammi roots and shoots. The negative impacts of Cd injury were reduced by the application of Si which increased plant growth and biomass, improved photosynthetic apparatus, antioxidant enzymes, minerals uptake together with diminished exudation of organic acids as well as oxidative stress indicators in roots and shoots of T. ammi by decreasing Cd retention in different plant parts. Research findings, therefore, suggested that Si application can ameliorate Cd toxicity in T. ammi seedlings and resulted in improved plant growth and composition under metal stress as depicted by balanced exudation of organic acids., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Key Message: Psoralen synthase and angelicin synthase responsible for the formation of psoralen and angelicin in Peucedanum praeruptorum Dunn were identified and functionally characterized, respectively. Furanocoumarins were reported to possess several activities such as anticancer, anti-inflammatory and neuroprotective, and function as phytotoxin and allelochemical in plants. Furanocoumarins are the main bioactive ingredient in P. praeruptorum which is a commonly used traditional Chinese medicine. Phenylalanine ammonia lyase (PAL), 4-coumarate: CoA ligase (4CL), p-coumaroyl CoA 2'-hyfroxylase (C2'H) were cloned previously to elucidate the biosynthetic mechanism of coumarin lactone ring. However, the genes involved in complex coumarins in P. praeruptorum have not been explored. Herein, putative psoralen synthase CYP71AJ49 and angelicin synthase CYP71AJ51 were cloned from P. praeruptorum. In vivo and in vitro yeast assays were conducted to confirm their activities. Furthermore, the results of High Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry (HPLC-ESI-MS) verified that CYP71AJ49 catalyzed the conversion of marmesin to psoralen, and CYP71AJ51 catalyzed columbianetin to angelicin. Subsequently, the expression profile showed that CYP71AJ49 and CYP71AJ51 were easily affected by environmental conditions, especially UV and temperature. The genes tissue-specific expression and compounds tissue-specific distribution pattern indicated the existence of substance transport in P. praeruptorum. Phylogenetic analysis was conducted with 27 CYP71AJs, CYP71AJ49 and CYP71AJ51 were classified in I-4 and I-2, respectively. These results provide further insight to understand the biosynthetic mechanism of complex coumarins.

Notopterol (NOT) is a major bioactive ingredient extracted from the rhizomes of either Notopterygium incisum Ting ex H. T. Chang or N. forbesii Boiss (Qianghuo in Chinese), a botanical drug that was adopted as a traditional Chinese medicine. NOT is suggested to show analgesic and anti-inflammatory effects in clinical practice. The inhibitory effects of NOT on human cytochrome P450 enzymes were investigated in the present study. Our results indicate that NOT inhibited the activity of CYP2D6 in a time-, concentration- and NADPH-dependent manner. The values of K I and k inact were 10.8 μM and 0.62 min -1 , respectively. The calculated k obs at 10 μM was 0.29 min -1 , above the 0.02 min -1 risk level. After incubation with NOT at 10 μM for 9 min, approximately 92% of CYP2D6 activity was inhibited. Such loss of enzyme activity was not restored through dialysis, which indicates that the observed enzyme inhibition was irreversible. Partition ratio of the inactivation was approximately 29. Quinidine, a competitive CYP2D6 inhibitor, demonstrated protection on enzymes against the NOT-induced inactivation, but such protection was not found in incubation systems fortified with glutathione or catalase/superoxide dismutase. Additionally, CYP3A4 was observed to function as an enzyme mainly involved in the biotransformation of NOT. Taken together, these findings indicate that NOT served as a mechanism-based inactivator of CYP2D6, meanwhile, those observed effects may induce the latent drug-drug interactions. The metabolic activation of NOT may be the key to trigger the inactivation of the enzyme., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Trachyspermum ammi is an important medicinal plant that contains a bioactive compound namely thymol. In the study, T. ammi was transformed by Agrobacterium rhizogenes strains. Seedling stem explants were inoculated with A. rhizogenes strains A4, LBA 9402, ATCC 15834, and the effect of different co-cultivation media along with incorporation of acetosyringone (100 µM) was evaluated comparatively on the frequency of hairy root induction. The polymerase chain reaction using rolB and virD specific primers was served to confirm the putative transformed hairy roots. All strains established hairy root with various frequencies, among which strain ATCC 15834 was significantly the most efficient strain for hairy root induction (84.3%). Half-strength B5 medium and incorporation of acetosiryngone (100 µM) were also significantly optimal for hairy root induction. Hairy roots culture induced by ATCC 15834 using half-strength B5 liquid medium supplemented with 30 g L -1 sucrose indicated the highest accumulation of biomass (99.05 g L -1 FW and 10.95 g L -1 DW) and thymol content (11.30 mg g -1 DM) at 20 days. Nearly 4.9-fold and 5.3-fold increment of biomass and thymol accumulation was observed, respectively, at 20 days in comparison with the untransformed control roots. The results showed the high potential of T. ammi hairy roots for the biosynthesis of thymol., (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)

Glehnia littoralis is an important medicinal halophyte-the dried root of which is used as Chinese herbal medicine. However, the use, selection and stability of reference genes are rarely verified in studies of G. littoralis, which hampers investigation of its salt tolerance and metabolism. In this study, we selected 13 candidate reference genes from the transcriptome data of G. littoralis-serine/threonine-protein phosphatase PP2A (PP2A), polyubiquitin 10 (UBQ10), actin (ACT), elongation factor 1-α (EF1-α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-tubulin (α-TUB), β-tubulin (β-TUB), polypyrimidine tract-binding protein 1 (PTBP1), expressed protein 1 (EXP1), expressed protein 2 (EXP2), TIP41-like (TIP41), SAND family (SAND), and cyclophilin 2 (CYP2), and used qRT-PCR to analyse their expression levels in roots of G. littoralis treated with NaCl, polyethylene glycol (PEG), abscisic acid (ABA), and methyl jasmonate (MeJA), as well as in various organs of G. littoralis. The ΔCt, geNorm, NormFinder, and BestKeeper algorithms were used to assess the expression stability of the candidate reference genes and the results were then used to generate a comprehensive rank list with the RankAggreg R package. The most stable reference genes for normalisation were EXP1 and PP2A in response to NaCl, EXP2 and PP2A in response to ABA, CYP2 and α-TUB in response to MeJA, and ACT and EXP1 in the PEG and the organ subsets. GAPDH, β-TUB, and UBQ10 exhibited low stability and so were unsuitable for normalisation. This study is the first systematic analysis of candidate reference genes in G. littoralis and will facilitate further investigation of normalisation of gene expression in G. littoralis.

The endangered medicinal plant Glehnia littoralis is one of the important natural source of furanocoumarin, which has been used as mucolytic, antitussive, antitumour and antibacterial. However, the genetic information of furanocoumarin biosynthesis in G. littoralis is scarce at present. The objective of this study was to mine the putative candidate genes involved in the biosynthesis pathwayof furanocoumarin and provide references for gene identification, and functional genomics of G. littoralis . We carried out the transcriptome analysis of leaves and roots in G. littoralis , which provided a dataset for gene mining. Psoralen, imperatorin and isoimperatorin were detected in G. littoralis by high performance liquid chromatography analysis. Candidate key genes were mined based on the annotations and local BLAST with homologous sequences using BioEdit software. The relative expression of genes was analysed using quantitative real-time polymerase chain reaction. Further, the CYP450 genes were mined using phylogenetic analyses using MEGA 6.0 software. Atotal of 156,949 unigenes were generated, of which 9021 were differentially-expressed between leaves and roots. A total of 82 unigenes encoding eight enzymes in furanocoumarin biosynthetic pathway were first obtained. Seven genes that encoded key enzymes in the downstream furanocoumarin biosynthetic pathway and expressed more in roots than leaves were screened. Twenty-six candidate CYP450 unigenes expressed abundantly in roots and were chiefly concentrated in CYP71, CYP85 and CYP72 clans. Finally, we filtered 102 differentially expressed transcription factors (TFs) unigenes. The transcriptome of G. littoralis was characterized which would help to elucidate the furanocoumarin biosynthetic pathway in G. littoralis and provide an invaluable resource for further study of furanocoumarin.

Sea fennel is an herbaceous aromatic and edible halophyte, naturally occurring in coastal areas of the Mediterranean basin. Besides its scientific interest as a salt-tolerant species it exhibits considerable nutritional value and economical potential. As sea fennel is distributed in maritime areas, where natural iodine is available in high concentrations, the aim of this study was to evaluate whether sea fennel has the potential to accumulate elevated iodine concentrations under cultivation. A biofortification experiment in a hydroponic system applying two forms of iodine, KI and KIO 3 in different concentrations was set up and monitored using sophisticated targeted elementary and metabolite analysis. The biofortification potential and possible effects on nutritional value were investigated. This study revealed that both iodine forms increased the iodine content of sea fennel tissues. Nutritional and health promoting components, biomass production but also antioxidant potential were stable or even improved under the iodine treatments., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Facile green synthesis of copper nanoparticles from different biological procedures has been indicated, but among all, biosynthesis of copper nanoparticles from medicinal plants is considered as the most suitable method. The use of medicinal plant material increases the therapeutical effects of copper nanoparticles. The aim of this study was green synthesis of copper nanoparticles from aqueous extract of Falcaria vulgaris leaf (CuNPs) and assessment of their cytotoxicity, antioxidant, antifungal, antibacterial, and cutaneous wound healing properties. These nanoparticles were characterized by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), transmission electron microscopy (TEM), and field emission scanning electron microscopy (FE-SEM) analysis. The synthesized CuNPs had great cell viability dose-dependently (Investigating the effect of the CuNPs on human umbilical vein endothelial cell (HUVEC) line) and indicated this method was nontoxic. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was done to assess the antioxidant activities, which indicated similar antioxidant potentials for CuNPs and butylated hydroxytoluene. In part of cutaneous wound healing property of CuNPs, after creating the cutaneous wound, the rats were randomly divided into six groups: treatment with 0.2% CuNPs ointment, treatment with 0.2% CuSO 4 ointment, treatment with 0.2% F. vulgaris ointment, treatment with 3% tetracycline ointment, treatment with Eucerin basal ointment, and untreated control. These groups were treated for 10 days. Treatment with CuNPs ointment remarkably increased (p ≤ .01) the wound contracture, vessel, hexosamine, hydroxyl proline, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate and substantially reduced (p ≤ .01) the wound area, total cells, neutrophil, and lymphocyte compared to other groups. In antibacterial and antifungal parts of this research, the concentration of CuNPs with minimum dilution and no turbidity was considered minimum inhibitory concentration (MIC). To determine minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC), 60 μL MIC and three preceding chambers were cultured on Sabouraud Dextrose Agar and Muller Hinton Agar, respectively. The minimum concentration with no fungal and bacterial growth were considered MFC and MBC, respectively. CuNPs inhibited the growth of all fungi at 2-4 mg/mL concentrations and removed them at 4-8 mg/mL concentrations (p ≤ .01). In case of antibacterial effects of CuNPs, they inhibited the growth of all bacteria at 2-8 mg/mL concentrations and removed them at 4-16 mg/mL concentrations (p ≤ .01). The results of XRD, FT-IR, UV, TEM, and FE-SEM confirm that the aqueous extract of F. vulgaris leaf can be used to yield copper nanoparticles with notable amount of antioxidant, antifungal, antibacterial, and cutaneous wound healing potentials without any cytotoxicity. Further clinical trials are necessary for confirmation these therapeutical effects of CuNPs in human., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Prangos ferulacea (L.) Lindl. (Fam. Apiaceae), an orophilous species of eastern Mediterranean and western Asia, possesses a number of biological properties that are worthy of exploitation in different fields. Phytochemical investigations revealed the presence of coumarins, prenyl-coumarins, and furano-coumarins as the main constituents of this species, as well as several flavonoids. Among prenyl-coumarins, osthol is a promising apoptotic agent quite selective toward cancer cells. In addition, the essential oils have been extensively investigated, and several chemotypes have been identified. This work reviews the literature on this species published between 1965 and 2018, describes its volatile and nonvolatile metabolites, and outlines its pharmacological effects., Competing Interests: The authors declare no conflicts of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

The purpose of this study was to investigate the effects of tocopherol, rosemary essential oil and ferulago on oxidative stability of mayonnaise during storage. Their efficacy was also compared with tertiary butylhydroquinone (TBHQ) and the control group. During the primary oxidation stage, tocopherol was more efficient than TBHQ, while in the secondary oxidation stage it was the same as other antioxidants. At end of storage, samples with added rosemary essential oil and ferulago extract showed peroxide value (2.29 and 2.80 meq O 2 /kg oil), anisidine value (11.83 and 12.23), hexanal and heptanal concentration (510.2, 589.9 and 76.6, 75.2 ng/g), respectively, which were meaningfully less than those of the control sample (10.44 meq O 2 /kg, 18.32, 1339.8 ng/g, and 225.5 ng/g, respectively). Based on the overall results, tocopherol and rosemary essential oil can be recommended as replacement for TBHQ. However, further evaluation needs to be performed on the organoleptic properties of Ferulago extract., (Copyright © 2019. Published by Elsevier Ltd.)

Seseli libanotis is an aromatic umbelliferous plant distributed sporadically on dry grassland edges in Europe and Western Asia. The essential oil composition in the different plant parts was studied from plants collected on nine sites in Austria and one site in Alto Adige, Italy. Monoterpenes such as α-pinene, sabinene and β-myrcene and the sesquiterpene germacrene D were present in all essential oils from the aerial parts. Inflorescences and fruits had the highest essential oil contents. These essential oils from four sites were rich in acorenone B, while from other three sites they had carotol as a major component. Osthole as furocoumarin occurred in some oils. The root essential oils were dominated by α-pinene. The essential oil variability has been studied by principal component analysis (PCA) and discriminant analysis (DA) with plant parts or sampling site as a priori groups. PCA could well separate inflorescence and fruit essential oil samples from leaf and stem essential oil samples. DA differentiated well between the plant parts and most of the sampling sites., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Conopodium majus is a geophyte with pseudomonocotyly, distributed in Atlantic Europe. It is an indicator of two declining European habitats: ancient woodland understories and oligotrophic hay meadows. Attempts to reintroduce it by seed have been hindered by scarce seedling emergence and limited knowledge of its seed biology. Micro-CT scanning was used to assess pseudomonocotyly. Embryo growth and germination were studied in the laboratory and the field, using dissection and image analysis. The effects of temperature, light, nitrate and GA 3 on germination were tested. Seed desiccation tolerance was investigated by storage at different RHs and by drying seeds at different stages of embryo growth. Seeds possess morphological but not physiological dormancy. Embryo growth and germination were promoted by temperatures between 0 and 5 °C, arrested above 10 °C, and indifferent to alternating temperatures, light, nitrate and GA 3 . Pseudomonocotyly appears to result from cotyledon fusion. While seeds tolerated drying to 15% RH and storage for 1 year at 20 °C, viability was lost when storage was at 60% RH. Seeds imbibed at 5 °C for 84 days had significant internal embryo growth but were still able to tolerate drying to 15% RH. Reproduction by seed in C. majus follows a strategy shared by geophytes adapted to deciduous temperate forests. The evolution of fused cotyledons may enable the radicle and the hypocotyl to reach deeper into the soil where a tuber can develop. The embryo is capable of growth within the seed at low temperatures so that germination is timed for early spring., (© 2018 The Authors. Plant Biology published by John Wiley & Sons Ltd on behalf of German Society for Plant Sciences, Royal Dutch Botanical Society.)

Methoxylated coumarins represent a large proportion of officinal value coumarins while only one enzyme specific to bergaptol O -methylation (BMT) has been identified to date. The multiple types of methoxylated coumarins indicate that at least one unknown enzyme participates in the O -methylation of other hydroxylated coumarins and remains to be identified. Combined transcriptome and metabonomics analysis revealed that an enzyme similar to caffeic acid O -methyltransferase (COMT-S, S is short for similar) was involved in catalyzing all the hydroxylated coumarins in Peucedanum praeruptorum . However, the precise molecular mechanism of its substrate heterozygosis remains unsolved. Pursuing this question, we determined the crystal structure of COMT-S to clarify its substrate preference. The result revealed that Asn132, Asp271, and Asn325 govern the substrate heterozygosis of COMT-S. A single mutation, such as N132A, determines the catalytic selectivity of hydroxyl groups in esculetin and also causes production differences in bergapten. Evolution-based analysis indicated that BMT was only recently derived as a paralogue of caffeic acid O -methyltransferase (COMT) via gene duplication, occurring before the Apiaceae family divergence between 37 and 100 mya. The present study identified the previously unknown O -methylation steps in coumarin biosynthesis. The crystallographic and mutational studies provided a deeper understanding of the substrate preference, which can be used for producing specific O -methylation coumarins. Moreover, the evolutionary relationship between BMT and COMT-S was clarified to facilitate understanding of evolutionary events in the Apiaceae family.

Extracts of bled resin from Azorella compacta , of the Azorelloideae family from the Andes (>4000 m), were analyzed by gas chromatography-mass spectrometry. The mass spectra of the dominant compounds of the resin and its hydrogenation products were documented. The most abundant compounds were oxygenated diterpenoids, namely mulinadien-20-oic (Δ 11,13 and Δ 11,14 ) acids, azorell-13-en-20-oic acid, 13α,14β-dihydroxymulin-11-en-20-oic acid, and azorellanol, with a group of azorellenes and mulinadienes. The mass spectra of the novel diterpenoid hydrocarbons with the azorellane and mulinane skeletons were also presented. This study documents the molecular diversity of these diterpenoid classes, and could be of great utility for future organic geochemical, environmental, archeological, pharmaceutical, and forensic chemistry studies.

Coumarins exhibit many biological activities and are the main specialised metabolites of Peucedanum praeruptorum Dunn, an important plant used in traditional Chinese medicine. In preliminary studies, we cloned several genes involved in coumarin biosynthesis in P. praeruptorum, such as 4-coumarate: CoA ligase (4CL), p-coumaroyl CoA 2'-hydroxylase (C2'H), feruloyl CoA 6'-hydroxylase (F6'H) and bergaptol O-methyltransferase (BMT). However, phenylalanine ammonia-lyase (PAL) in P. praeruptorum (PpPAL) has not yet been studied. In the present study, we cloned one novel PpPAL gene. Subsequently, the relationship between gene and compounds was studied using quantitative real-time PCR (qRT-PCR) and High Performance Liquid Chromatography (HPLC) analysis. Then, enzyme function was analyzed with L -phenylalanine ( L -Phe) as substrate. These experiments showed that the coumarin content could be upregulated by methyl jasmonate (MeJA), UV irradiation and cold, which was consistent with increased expression levels of PpPAL. In addition, correlation analysis indicated that coumarins were partially related to PpPAL. And the recombinant protein could catalyze the conversion of L -Phe to trans-cinnamic acid (t-CA) with a K m of 120 ± 33 μM and a K cat of 117 ± 32 min -1 . Besides, Tyr110, Phe116, Gly117, Ser206, Leu209, Leu259, Tyr354, Arg357, Asn387 and Phe403 were essential for enzymatic activity based on three-dimensional modeling and site-directed mutagenesis experiments. Altogether these results highlight the importance of PpPAL in abiotically induced coumarin biosynthesis and provide further insights regarding the structure-function relationships of this protein., (Copyright © 2018. Published by Elsevier Ltd.)

Traditional Mediterranean diet includes the halophyte Crithmum maritimum L. (Apiaceae) which can be found in the coastline of the Balearic Islands but also inland. Both areas differed in the environmental conditions, mainly in salinity which can affect the oxidative status of this species. The aim was to evaluate the antioxidant enzyme activities, polyphenols and the lipid peroxidation in leaves of wild C. maritimum growing in a natural coastal area influenced by marine salinity and an inland area without marine influence. The activities of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase as well as polyphenol and reduced glutathione content were significantly higher in the samples from coastline population, whereas no significant differences were found in glutathione reductase activity and in malondialdehyde levels. The production of H 2 O 2 was also significantly higher in the population from coastline. In conclusion, C. maritimum adapt their antioxidant defense machinery to the different salinity conditions, avoiding the instauration of oxidative stress., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

In order to determine the morphophysiological and phytochemical properties of various Ducrosia anethifolia populations, the plant samples were collected from 20 locations in native regions. Current study indicated significant differences in the morphophysiological and phytochemical characteristics of D. anethifolia populations collected from 20 locations in Sistan and Baluchestan Province, Iran. The highest value of plant height and the number of lateral stems, node per plant, umbellate per umbel, seeds per umbellate and the roots fresh and dry weight were related to the location with relatively high rainfall (130-161 mm) and low altitude (up to 1165 m) compared with others. Based on the essential oil components, D. anethifolia populations were divided into five different chemotypes. Chemotypes I, II and III were characterized by high amounts of methyl chavicol, chrysanthenyl acetate and decanal, respectively. Moreover, the populations with high amounts of decanal, anethole and dodecanal were placed in chemotype IV. Chemotype V was attributed to the Naserabad population with 1-decanol as the major compound., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan in Anthriscus sylvestris known as cow parsley or wild chervil, and has been reported to have inhibitory effects against several pathological processes including cancer, inflammation and infection. Here, we report the effects of DPT in the fatty liver induced by high fat diet in vivo as well as its regulatory mechanism related with the transcription factor for lipogenic genes such as sterol regulatory element binding protein-1c (SREBP-1c) in vitro. C57BL/6 mice were fed high fat diet for 10 weeks and also orally administrated with DPT for additional 4 weeks. 5 and 10 mg/kg of DPT decreased lipid accumulation in the liver induced by high fat diet, as indicated by histological parameters such as Oil Red O staining and hematoxylin & eosin as well as the contents of hepatic triglyceride and cholesterol. In hepatocytes, DPT inhibited the liver X receptor α-mediated SREBP-1c induction and expression of the lipogenic genes, including fatty acid synthase, acetyl-CoA carboxylase and stearoyl-CoA desaturase-1. Moreover, DPT induced AMP-activated protein kinase (AMPK) activation, which has been known to inhibit the expression of SREBP-1c in hepatocyte. Also this compound restored the dysregulation of AMPK and SREBP-1c induced by high fat diet in mice. In conclusion, we demonstrated that DPT significantly inhibited fatty liver by adjusting lipid metabolism coordinated with AMPK activation and SREBP-1c inhibition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Thymol, as a dietary monoterpene, is a phenol derivative of cymene, which is the major component of the essential oil of Trachyspermum ammi (L.). It shows multiple biological activities: antifungal, antibacterial, antivirus and anti-inflammatory. T. ammi, commonly known as ajowan, belongs to Apiaceae and is an important medicinal seed spice. To identify the putative genes involved in thymol and other monoterpene biosynthesis, we provided transcriptomes of four inflorescence tissues of two ajowan ecotypes, containing different thymol yield. This study has detected the genes encoding enzymes for the go-between stages of the terpenoid biosynthesis pathways. A large number of unigenes, differentially expressed between four inflorescence tissues of two ajowan ecotypes, was revealed by a transcriptome analysis. Furthermore, differentially expressed unigenes encoding dehydrogenases, transcription factors, and cytochrome P450s, which might be associated with terpenoid diversity in T. ammi, were identified. The sequencing data obtained in this study formed a valuable repository of genetic information for an understanding of the formation of the main constituents of ajowan essential oil and functional analysis of thymol-specific genes. Comparative transcriptome analysis led to the development of new resources for a functional breeding of ajowan.

In the search for antifungal lead compounds from natural resources, Notopterygium incisum, a medicine plant only distributed in China, showed antifungal potential against apple fruit pathogens. Based on the bioassay-guided isolation, chromatography fraction 6 of the ethyl acetate partition exhibited significant in vitro and in vivo antifungal activities against apple fruit pathogens. Furthermore, nine antifungal secondary metabolites, including five linear furocoumarins (1-5), two phenylethyl esters (6-7), one falcarindiol (8), and one sesquiterpenoid (9), were isolated and elucidated from fraction 6. Compound 5 is a new metabolite, and 9 isolated from the genus Notopterygium for the first time. The purified compounds (1-9) were firstly reported to exhibit antifungal activities against apple fruit pathogens of Colletotrichum gloeosporioides and Botryosphaeria dothidea with the MIC values ranging from 8 to 250 mg L -1 , especially 8 of 16 and 8 mg L -1 , respectively. Moreover, 8 could inhibit the spore germination and new sporulation of B. dothidea, as well as enhance the membrane permeabilization of B. dothidea spores. This was the first investigation for the antifungal components against apple fruit pathogens from Notopterygium incisum, which has great potential to be developed into bio-fungicides., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fatness is an unwanted side effect of genetic selection in broiler chickens. In this study, we introduce mountain celery powder as a feed supplement to suppress lipogenesis and improve antioxidant status in broiler chickens. Male broiler chicks (Ross 308) were fed a control diet or a diet that includes mountain celery (MC) at 7.5 gkg -1 over 42 days., Results: Body weight gain and feed conversion ratio significantly (P < 0.05) improved in chicks fed MC. A highly significant down-regulation of genes involved in hepatic lipogenesis including acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME), and lipoprotein lipase (LPL) was observed in the liver of chickens fed MC. These birds, however, had greater compensatory upregulation in antioxidative genes SOD1 and catalase in the liver compared to the birds that received the control diet. Birds received MC had significantly lower level of lipid peroxidation (1.59 μmol/L serum malondialdehyde) compared to birds from the control group (3.57 μmol/L; P = 0.0024). Birds fed MC had significantly (P < 0.05) lower circulatory concentrations of triacylglycerols, cholesterol, and LDL but higher concentrations of HDL. Relative liver weight and abdominal fat deposition were significantly reduced by feeding MC., Conclusions: It can be concluded that feeding birds MC significantly suppresses hepatic lipogenesis by down-regulating key hepatic lipogenic enzyme genes and boosts antioxidant capacity by up-regulating hepatic antioxidantive genes.

The biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2), and lecaniside C (3). The chemical structures of these metabolites were elucidated based on extensive spectral data, including 2D NMR and HRMS. The hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these metabolites were observed in the present study. In the in vitro assays, compound 1 displayed a little PTP1B inhibitory activity.

We previously showed rats fed with apiaceous vegetables, but not with their putative chemopreventive phytochemicals, reduced colonic DNA adducts formed by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary procarcinogen. We report here the effects of feeding apiaceous and cruciferous vegetables versus their purified predominant phytochemicals, either alone or combined, on prostate and pancreatic PhIP-DNA adduct formation. In experiment I, male Wistar rats received three supplemented diets: CRU (cruciferous vegetables), API (apiaceous vegetables), and CRU+API (both types of vegetables). In experiment II, rats received three diets supplemented with phytochemicals matched to their levels in the vegetables from experiment I: P + I (phenethyl isothiocyanate and indole-3-carbinol), FC (furanocoumarins; 5-methoxypsoralen, 8-methoxypsoralen, and isopimpinellin), and COMBO (P + I and FC combined). After 6 days of feeding, PhIP was injected (10 mg/kg body weight) and animals were killed on day 7. PhIP-DNA adducts were analyzed by LC-MS/MS. In prostate, PhIP-DNA adducts were reduced by API (33%, P < .05), P + I (45%, P < .001), and COMBO (30%, P < .01). There were no effects observed in pancreas. Our results suggest that fresh vegetables and purified phytochemicals lower PhIP-DNA adducts and may influence cancer risk.

Context: Changium smyrnioides Wolff (Apiaceae) is an endangered medicinal plant with numerous pharmacological uses., Objective: To investigate the effect of light intensity levels on the growth and accumulation of secondary metabolites of C. smyrnioides, cultivated seedlings were subjected to different relative light intensities via sun-shading., Materials and Methods: Changium smyrnioides seedlings were subjected to five irradiance treatments (100, 60.54, 44.84, 31.39, and 10.56% sunlight) in glasshouse for 9 months. Enzymatic and non-enzymatic antioxidants with spectrophotometric method, photosynthetic parameters with Li-6400XT, dry matter accumulation and active component contents in the root with spectrophotometric and HPLC method were analyzed., Results: With an increase in relative light intensity levels, activities of enzymatic and non-enzymatic antioxidants, and malondialdehyde (MDA) contents were increased overall, while net photosynthetic rate (P n ) and dry matter accumulation patter first increased and then declined. The highest net photosynthetic rate (30.68 μmol/m 2 ·s) and dry root weight (5.07 g) were achieved under 60.54% sunlight. Lower relative light intensity levels stimulated the accumulation levels of bioactive compounds in the roots so that the highest contents of mannitol (1.35%) and choline (405.58 μg/g) were recorded under 31.39% sunlight, and the highest polysaccharide content (10.80%) were achieved under 44.84% sunlight. With a decrease in the relative light intensity levels, the water-soluble component content increased first and then decreased., Discussion and Conclusion: The results revealed that 31.39-60.54% sunlight serve as appropriate relative light intensity conditions for cultivated C. smyrnioides.

Water celery (Helosciadium nodiflorum, Apiaceae) is a common and invasive hydrophyte occurring in rivers and slow waters of Europe. In the past, it was consumed as a vegetable and spices, but currently it has mostly been abandoned. As a result, this plant produces an unexploited biomass occluding rivers and slow waters. With the aim to valorise water celery as an important biomass source for the development of botanical insecticides, in this work, we investigated the inhibitory effects of the essential oil hydrodistilled from its aerial parts against larvae of the filariasis vector Culex quinquefasciatus, adults of the housefly Musca domestica, and larvae of the African cotton leafworm Spodoptera littoralis. The essential oil, which was characterized by the insecticidal limonene (39.8%) and myristicin (35.3%), exerted important toxic effects on 3rd instar larvae of C. quinquefasciatus and S. littoralis and on adults of M. domestica, with LD 50 of 50.4 μl l -1 , 116.7 μg larva -1 , and 45.1 (male) and 70.1 (female) μg adult -1 , respectively. The oil did not show any noticeable inhibitory activity on the acetylcholinesterase enzyme. Our findings add scientific evidences highlighting water celery as an important biomass source to be used for the control of insect pests and vectors of high economic importance., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)