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15 pages, 4096 KB  
Article
Metabolomics Reveals the Dynamic Characteristics of Flavonoids During the Different Developmental Stages of Citrus reticulata ‘Shiyue Ju’ and Its Mutant C. reticulata ‘Denglong Ju’
by Qin Guan, Doudou Huang, Lan Zhang and Zongyou Lv
Curr. Issues Mol. Biol. 2026, 48(8), 774; https://doi.org/10.3390/cimb48080774 - 29 Jul 2026
Viewed by 323
Abstract
Flavonoids, prominent bioactive compounds in citrus fruits, exhibit diverse health-promoting properties. However, the dynamic compositional changes in flavonoids during fruit development remain insufficiently characterized in Citrus reticulata ‘Shiyue Ju’ (STJ) and C. reticulata ‘Denglong Ju’ (DLJ). In this study, a comprehensive untargeted metabolomics [...] Read more.
Flavonoids, prominent bioactive compounds in citrus fruits, exhibit diverse health-promoting properties. However, the dynamic compositional changes in flavonoids during fruit development remain insufficiently characterized in Citrus reticulata ‘Shiyue Ju’ (STJ) and C. reticulata ‘Denglong Ju’ (DLJ). In this study, a comprehensive untargeted metabolomics approach was employed to systematically analyze the flavonoid profiles in both peel and flesh tissues across six key developmental stages, leading to the putative annotation of 205 flavonoids. Heatmap analysis revealed higher flavonoid levels in SP-4 (STJ peel in stage 4) compared to DP-4 (DLJ peel in stage 4), potentially resulting from the substantial upregulation of genes involved in flavonoid biosynthesis during this period. Furthermore, S-plot analysis identified salvigenin, demethylnobiletin, and nobiletin as key discriminators in the peel of STJ (SP), whereas sinensetin, tangeretin, and 3′,4′,5,7-tetramethoxyflavone were predominant in the peel of DLJ (DP). These compounds could represent potential biochemical markers for varietal differentiation. Notably, SP exhibited higher levels of neohesperidin, hesperidin, naringin, and naringenin, suggesting enhanced health-promoting properties. The results enhance our understanding of flavonoid dynamics during citrus development and provide valuable implications for quality-oriented cultivation and genetic improvement. Full article
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21 pages, 2992 KB  
Article
Effects of Basil (Ocimum basilicum L.) Leaf Extracts on Gastrointestinal Smooth Muscle Spasms: An In Vitro Study on Rat Ileum
by Milica Randjelović, Nebojša Simić, Suzana Branković, Maja Koraćević, Miloš Jovanović, Nemanja Kitić, Bojana Miladinović, Milica Milutinović and Dušanka Kitić
Plants 2026, 15(7), 1079; https://doi.org/10.3390/plants15071079 - 1 Apr 2026
Viewed by 838
Abstract
The present study was designed to evaluate the effects of eighteen different extracts derived from basil (Ocimum basilicum L.) leaves on spontaneous contractions, as well as contractions induced by potassium chloride (KCl) and acetylcholine in the ileum of rats, under in vitro [...] Read more.
The present study was designed to evaluate the effects of eighteen different extracts derived from basil (Ocimum basilicum L.) leaves on spontaneous contractions, as well as contractions induced by potassium chloride (KCl) and acetylcholine in the ileum of rats, under in vitro conditions. The extracts were prepared with 96% v/v, 80% v/v, and 60% v/v ethanol, and absolute (100%) v/v, 80% v/v, and 60% v/v methanol, employing extraction techniques that included maceration, digestion, and sonication-assisted methods. Chemical characterization of the extracts revealed the presence of various phenolic acids, including rosmarinic, chlorogenic, caftaric, salvianolic acid B, cinnamic, caffeic, and chicoric acid, as well as flavonoids such as rutin and salvigenin. The evaluated extracts produced significant, concentration-dependent inhibitory effects on rat ileal contractions. Notably, the extract obtained via maceration with 80% methanol exhibited the most pronounced relaxant effects on spontaneous muscle contractions, achieving a maximum reduction of 46.16 ± 2.11%. Furthermore, the extract prepared with the same solvent using sonication-assisted extraction demonstrated superior efficacy in diminishing both the frequency and amplitude of KCl-induced ileal contractions, reducing contraction intensity caused by elevated potassium ion levels to 59.48 ± 3.34% at a maximum concentration of 1.5 mg/mL, thereby indicating its potential as a potent calcium channel blocker. Additionally, the extract prepared with 60% methanol through sonication-assisted extraction resulted in the most substantial reduction of acetylcholine-induced ileal contractions, decreasing contraction intensity to 35.74 ± 1.54% at the maximum concentration of 1.5 mg/mL, which suggests a high level of neurophysiological activity. By comparing extracts with different phytochemical profiles, this study provides additional insight into how variations in phenolic composition may influence different mechanisms of smooth muscle relaxation. This study affirms the significant spasmolytic properties of basil leaf extracts, thereby supporting their potential application in the management of gastrointestinal motility disorders. Full article
(This article belongs to the Special Issue Efficacy, Safety and Phytochemistry of Medicinal Plants)
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23 pages, 3705 KB  
Article
Revealing the Multi-Target Mechanisms of Fespixon Cream in Diabetic Foot Ulcer Healing: Integrated Network Pharmacology, Molecular Docking, and Clinical RT-qPCR Validation
by Tianbo Li, Dehua Wei, Jiangning Wang and Lei Gao
Curr. Issues Mol. Biol. 2025, 47(7), 485; https://doi.org/10.3390/cimb47070485 - 25 Jun 2025
Cited by 4 | Viewed by 3520
Abstract
Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese [...] Read more.
Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and relevant literature, and their corresponding targets were standardized using the Universal Protein Resource (UniProt) database. Diabetic foot ulcer (DFU)-related targets were retrieved and filtered from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug and disease targets was identified, and a protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The interaction network was visualized using Cytoscape version 3.7.2 software. The potential mechanisms of the shared targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using R software packages, and results were visualized through Bioinformatics online tools. Molecular docking was performed to validate the binding between key active compounds of Fespixon cream and core DFU targets using AutoDock Vina version 1.1.2 and PyMOL software. Furthermore, RT-qPCR analysis was performed on wound edge tissue samples from DFU patients treated with Fespixon cream to experimentally verify the mRNA expression levels of predicted hub genes. Results: Network pharmacology analysis identified eight active compounds in Fespixon cream, along with 153 potential therapeutic targets related to diabetic foot ulcer (DFU). Among these, 21 were determined as core targets, with the top five ranked by degree value being RAC-αserine/threonine-protein kinase (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Interleukin-6 (IL6), and Mitogen-activated protein kinase 1 (MAPK1). GO enrichment analysis indicated that the targets of Fespixon cream were primarily involved in various biological processes related to cellular stress responses. KEGG pathway enrichment revealed that these targets were significantly enriched in pathways associated with diabetic complications, atherosclerosis, inflammation, and cancer. Molecular docking confirmed stable binding interactions between the five major active compounds—quercetin, apigenin, rosmarinic acid, salvigenin, and cirsimaritin—and the five core targets (AKT1, TP53, TNF, IL6, MAPK1). Among them, quercetin exhibited the strongest binding affinity with AKT1. RT-qPCR validation in clinical DFU tissue samples demonstrated consistent expression trends with computational predictions: AKT1 was significantly upregulated, while TP53, TNF, IL6, and MAPK1 were markedly downregulated in the Fespixon-treated group compared to controls (p < 0.001), supporting the proposed multi-target therapeutic mechanism. Conclusions: Our study reveals the potential mechanisms by which Fespixon cream exerts therapeutic effects on DFUs. The efficacy of Fespixon cream in treating DFUs is attributed to the synergistic actions of its bioactive components through multiple targets and multiple signaling pathways. Full article
(This article belongs to the Section Molecular Pharmacology)
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24 pages, 18947 KB  
Article
Mechanistic Insights into Salvigenin for Glucocorticoid-Induced Femoral Head Osteonecrosis: A Network Pharmacology and Experimental Study
by Zhengjie Zhu, Yujian Zhong, Ruyuan He, Changheng Zhong, Junwen Chen and Hao Peng
Biomedicines 2025, 13(3), 614; https://doi.org/10.3390/biomedicines13030614 - 3 Mar 2025
Cited by 4 | Viewed by 2229
Abstract
Background/Objectives: Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is a debilitating condition resulting from impaired bone metabolism and vascular disruption due to prolonged glucocorticoid use. This study aimed to explore the therapeutic potential of salvigenin, a flavonoid with antioxidative and estrogen-like properties, in [...] Read more.
Background/Objectives: Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is a debilitating condition resulting from impaired bone metabolism and vascular disruption due to prolonged glucocorticoid use. This study aimed to explore the therapeutic potential of salvigenin, a flavonoid with antioxidative and estrogen-like properties, in alleviating GIOFH by modulating estrogen receptor alpha (ESR1) pathways. Methods: A network pharmacology approach was utilized to identify salvigenin’s potential targets and their association with GIOFH. Protein–protein interaction networks, along with Gene Ontology and KEGG pathway analyses, were conducted to clarify salvigenin’s multi-target mechanisms. Molecular docking and dynamics simulations assessed the interaction between salvigenin and ESR1. Experimental validation included in vitro assays on MG63 cells treated with dexamethasone (Dex) to mimic GIOFH, evaluating oxidative stress, apoptosis, osteogenic differentiation, and ESR1 expression. Results: Network analysis identified ESR1, NOS3, and MMP9 as key hub targets of salvigenin. Molecular docking and dynamics simulations confirmed stable binding of salvigenin to ESR1. Salvigenin significantly reduced Dex-induced oxidative stress and apoptosis in osteoblasts while restoring osteogenic differentiation and ESR1 expression. Functional assays showed improved mineralized nodule formation, ALP activity, and mitochondrial integrity in salvigenin-treated cells. Conclusions: Salvigenin exhibits significant therapeutic potential in addressing GIOFH through ESR1-mediated pathways. These results offer a strong foundation for future translational studies and the development of salvigenin-based therapies for glucocorticoid-induced bone disorders. Full article
(This article belongs to the Special Issue New Insights into Bone and Cartilage Biology)
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32 pages, 9739 KB  
Article
Exploring Ocimum basilicum’s Secondary Metabolites: Inhibition and Molecular Docking against Rhynchophorus ferrugineus for Optimal Action
by Hossam Moustafa Darrag, Hesham S. Ghazzawy, Mashail Nasser Alzain, Emadaldeen Hamad Hakami, Hani Taher Almuhanna and Nashi K. Alqahtani
Plants 2024, 13(4), 491; https://doi.org/10.3390/plants13040491 - 8 Feb 2024
Cited by 5 | Viewed by 3249
Abstract
The objective of our work is to create a practical procedure to produce in vitro cell suspensions of O. basilicum and to ascertain the factors that encourage enhanced secondary metabolite production. We investigated the impact of these metabolites on Rhynchophorus ferrugineus’s adult [...] Read more.
The objective of our work is to create a practical procedure to produce in vitro cell suspensions of O. basilicum and to ascertain the factors that encourage enhanced secondary metabolite production. We investigated the impact of these metabolites on Rhynchophorus ferrugineus’s adult and larval target enzymes. The explants were cultivated on Murashige and Skoog (MS) media with 0.1 to 1 mg/L plant growth regulators (PGRs) to create calluses. 2,4-Dichlorophenoxyacetic acid (2,4-D), kinetin, 1-naphthylacetic acid (NAA), and indole-3-butryic acid (IBA) at 0.5, 0.5, 0.1, and 1 mg/L, respectively, with 3% sucrose led to the highest biomass accumulation. In cell suspensions, the total phenolic content (TPC) and total flavonoid content (TFC) were 39.68 and 5.49 mg/g DW, respectively, with abiotic Verticillium dahliae as an activator. Rosmarinic acid, ursolic acid, nepetoidin A and B, salvigenin, and quercetin-3-O-rutinoside as flavonoids and phenolics were analyzed using UPLC-I TQD MS, with the highest concentrations reached after 40 days. The extract demonstrates insecticidal activity against the fourth-instar larvae of R. ferrugineus, with adults at 1197 µg/mL and 12.5 µg/larvae as LC50 and LD50 values. The extract inhibited acetylcholine esterase (AChE), acid phosphatases (ACPs), alkaline phosphatases (ALPs), and gamma-aminobutyric acid-transaminase (GABA-T) in larval tissue in vitro, with IC50 values of 124.2, 149.3, 157.8, and 204.8 µg/mL, and in vivo, with IC50 values of 157.2, 179.4, 185.3, and 241.6 µg/mL, after 24 h. Pure compounds identified the activity of the extract, showing the inhibition of AChE, ACPs, ALPs, and GABA-T with IC50 values ˂ 200 µg/mL (in vitro). The ABMET examination revealed good oral permeability, and docking tests showed that the compounds bind AChE, ACPs, ALPs, and GABA-T. These findings show that a green bioprocessing method such as an O. basilicum cell suspension is a quick and straightforward technique for producing phenolic compounds, and it may be used to develop sustainable bio-insecticides and new green procedures. Full article
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28 pages, 5236 KB  
Article
Primary Determination of the Composition of Secondary Metabolites in the Wild and Introduced Artemisia martjanovii Krasch: Samples from Yakutia
by Zhanna M. Okhlopkova, Sezai Ercisli, Mayya P. Razgonova, Natalia S. Ivanova, Elena E. Antonova, Yury A. Egorov, Elena V. Kucharova and Kirill S. Golokhvast
Horticulturae 2023, 9(12), 1329; https://doi.org/10.3390/horticulturae9121329 - 11 Dec 2023
Cited by 11 | Viewed by 3052
Abstract
Artemisia martjanovii Krasch is a rare representative of the genus Artemisia in Siberia and the Far East. The phytochemical composition of this endangered species is essential for its potential use in medicine. We used tandem mass spectrometry and HPLC-MS/MS methods to describe the [...] Read more.
Artemisia martjanovii Krasch is a rare representative of the genus Artemisia in Siberia and the Far East. The phytochemical composition of this endangered species is essential for its potential use in medicine. We used tandem mass spectrometry and HPLC-MS/MS methods to describe the metabolome from the stem and leaf extracts of A. martjanovii from Yakutia. The metabolome profile analysis of A. martjanovii grown in the Botanical Garden of the North-Eastern Federal University, Yakutsk, Russia, and the wild A. martjanovii from Khangalassky district, Republic of Sakha (Yakutia) differed significantly both in the polyphenol composition and other compound classes. In total, we identified 104 bioactive constituents from stem and leaf extracts, 56 compounds from the polyphenol group, and 48 from other compound classes. Twenty-seven compounds classified as polyphenol groups, i.e., flavones apigenin, trihydroxy(iso)flavone, salvigenin, cirsiliol, cirsilineol, nevadensin, syringetin, gardenin B, thymonin, and chrysoeriol C-hexoside; flavonols: taxifolin, tetrahydroxy-dimethoxyflavone-hexoside, etc.; and 26 compounds from other classes are being reported for the first time in the genus Artemisia L. Full article
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13 pages, 1677 KB  
Article
Phytochemical Composition, Bioactive Compounds, and Antioxidant Properties of Different Parts of Andrographis macrobotrys Nees
by Dayanand Dalawai, Hosakatte Niranjana Murthy, Yaser Hassan Dewir, Joseph Kadanthottu Sebastian and Anish Nag
Life 2023, 13(5), 1166; https://doi.org/10.3390/life13051166 - 11 May 2023
Cited by 17 | Viewed by 4143
Abstract
Andrographis macrobotrys Nees is an ethnomedicinal plant belonging to the family Acanthaceae, distributed in the moist deciduous and semi-evergreen forests of the southern Western Ghats of India. The objective of this research was to determine the phytochemical composition and bioactive chemical components using [...] Read more.
Andrographis macrobotrys Nees is an ethnomedicinal plant belonging to the family Acanthaceae, distributed in the moist deciduous and semi-evergreen forests of the southern Western Ghats of India. The objective of this research was to determine the phytochemical composition and bioactive chemical components using gas chromatography and mass spectrometry (GC-MS) and to check the antioxidant potential of the plant part extracts. A. macrobotrys roots, stems, and leaves were obtained from the species’ natural habitat in the Western Ghats, India. The bioactive compounds were extracted using a Soxhlet extractor at 55–60 °C for 8 h in methanol. Identification analysis of A. macrobotrys bioactive compound was performed using GC-MS. Quantitative estimation of phytochemicals was carried out, and the antioxidant capacity of the plant extracts was determined by 2,2′-diphenyl-1-picrylhydrazyl radical scavenging (DPPH) and ferric reducing assays (FRAP). A. macrobotrys has a higher concentration of phenolics in its stem extract than in its root or leaf extracts (124.28 mg and 73.01 mg, respectively), according to spectrophotometric measurements. GC-MS analysis revealed the presence of phytochemicals such as azulene, 2,4-di-tert-butylphenol, benzoic acid, 4-ethoxy-ethyl ester, eicosane, 3-heptadecanol, isopropyl myristate, hexadecanoic acid methyl ester, hexadecanoic acid, 1-butyl-cyclohexanol, 9,12-octadecadienoic acid, alpha-monostearin, and 5-hydroxy-7,8-dimethoxyflavone belonging to various classes of flavonoids, terpenoids, phenolics, fatty acids, and aromatic compounds. Significant bioactive phytochemicals include 2,4-di-tert-butylphenol, 2-methoxy-4-vinylphenol, 5-hydroxy-7,8-dimethoxyflavone, azulene, salvigenin, squalene, and tetrapentacontane. In addition, the antioxidant capability of each of the three extracts was assessed. The stem extract demonstrated impressive DPPH scavenging and ferric reduction activities, with EC50 values of 79 mg/mL and 0.537 ± 0.02 OD at 0.2 mg/mL, respectively. The results demonstrated the importance of A. macrobotrys as a source of medicine and antioxidants. Full article
(This article belongs to the Special Issue Plants as a Promising Biofactory for Bioactive Compounds)
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16 pages, 2210 KB  
Article
Bio-Guided Isolation of New Compounds from Baccharis spp. as Antifungal against Botrytis cinerea
by Ana A. Pinto, Antonio Ruano-González, Abdellah Ezzanad, Cristina Pinedo-Rivilla, Rosario Sánchez-Maestre and Juan Manuel Amaro-Luis
Metabolites 2022, 12(12), 1292; https://doi.org/10.3390/metabo12121292 - 19 Dec 2022
Cited by 1 | Viewed by 2993
Abstract
Baccharis genus Asteraceae is widely used in traditional treatment against fever, headache, hepatobiliary disorders, skin ulcers, diabetes, and rheumatism, as well as an antispasmodic and diuretic. Its phytochemistry mainly shows the presence of flavonoids and terpenoids such as monoterpenes, sesquiterpenes, diterpenes, and triterpenes. [...] Read more.
Baccharis genus Asteraceae is widely used in traditional treatment against fever, headache, hepatobiliary disorders, skin ulcers, diabetes, and rheumatism, as well as an antispasmodic and diuretic. Its phytochemistry mainly shows the presence of flavonoids and terpenoids such as monoterpenes, sesquiterpenes, diterpenes, and triterpenes. Some of them have been evaluated for biological activities presenting allelopathic, antimicrobial, cytotoxic, and anti-inflammatory properties. In this paper, our research group reported the isolation, characterization, and antifungal evaluation of several molecules isolated from the dichloromethane extract from Baccharis prunifolia, Baccharis trinervis, and Baccharis zumbadorensis against the phytopathogen fungus Botrytis cinerea. The isolated compounds have not previously been tested against Botrytis, revealing an important source of antifungals in the genus Baccharis. Six known flavones were isolated from B. prunifolia. The dichloromethane extracts of B. trinervis and B. zumbadorensis were subjected to a bio-guided isolation, obtaining three known flavones, an α-hydroxidihydrochalcone mixture, one labdane, one triterpene, and two norbisabolenes from the most active fractions. The compounds 4′-methoxy-α-hydroxydihydrochalcone (7A), 3β,15-dihydroxylabdan-7-en-17-al (8), and 13-nor-11,12-dihydroxybisabol-2-enone (11) are novel. The most active compounds were the Salvigenin (5) and 1,2-dihydrosenedigital-2-one (10) with an IC50 of 13.5 and 3.1 μg/mL, respectively. Full article
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25 pages, 2262 KB  
Article
Secondary Metabolites in Basil, Bio-Insecticide, Inhibition Effect, and In Silico Molecular Docking against Proteolytic Enzymes of the Red Palm Weevil (Rhynchophorus ferrugineus)
by Hossam Moustafa Darrag, Hani Taher Almuhanna and Emadaldeen Hamad Hakami
Plants 2022, 11(8), 1087; https://doi.org/10.3390/plants11081087 - 16 Apr 2022
Cited by 31 | Viewed by 5450
Abstract
The purpose of this work was to determine the secondary metabolites generated by O. basilicum cell suspensions, as well as their insecticide and inhibitory activity against R. ferrugineus. The growth kinetics with inoculation Verticillium dahliae were determined and identified using LC-MS. Determination [...] Read more.
The purpose of this work was to determine the secondary metabolites generated by O. basilicum cell suspensions, as well as their insecticide and inhibitory activity against R. ferrugineus. The growth kinetics with inoculation Verticillium dahliae were determined and identified using LC-MS. Determination of total phenolic components (TFC), flavonoids (TF), and condensed tannins (TCT) were measured. Insecticidal activity of O. basilicum extract against R. ferrugineus (larva and adult) and proteolytic enzymes activity were assessed (in vitro and in vivo). The O.basilicum extract had an LC50 of 1238 µg/mL and an LD50 of 13.4 µg/larva. The LC50 of chicoric acid, ursolic acid, salvigenin, quercetin-3-O-rutinoside, rosmarinyl glucoside, and nepetoidin B demonstrated activity at an LC50 of 1132, 1167, 1189, 1214, 1275, and 1317 µg/mL, respectively. Chicoric acid, salvigenin, nepetoidin B, and rosmarinic acid demonstrated an LD50 activity of 10.23, 11.4, 11.9, and 12.4 µg/larva, respectively. The active extract of O. basilicum inhibited total protease, trypsin-like serine proteinases, elastase, cysteine, and metalloprotease activity with an IC50 (in vitro) of 119.4, 91, 102.4, 76.4, and 52.4 µg/mL, respectively. In silico studies of compounds were conducted, such as molecular docking and ADMET analysis. The study proposes using an efficient cell suspension technique to produce O. basilicum extract containing active secondary metabolites and accessible using as bio-insecticide. Full article
(This article belongs to the Special Issue Insecticidal Activity of Plant Secondary Metabolites)
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21 pages, 4128 KB  
Article
Antifungal Activity of Isolated Compounds from the Leaves of Combretum erythrophyllum (Burch.) Sond. and Withania somnifera (L.) Dunal against Fusarium Pathogens
by Hlabana Alfred Seepe, Tselane Geneva Ramakadi, Charity Mekgwa Lebepe, Stephen O. Amoo and Winston Nxumalo
Molecules 2021, 26(16), 4732; https://doi.org/10.3390/molecules26164732 - 5 Aug 2021
Cited by 29 | Viewed by 4424
Abstract
Crop diseases caused by Fusarium pathogens, among other microorganisms, threaten crop production in both commercial and smallholder farming. There are increasing concerns about the use of conventional synthetic fungicides due to fungal resistance and the associated negative effects of these chemicals on human [...] Read more.
Crop diseases caused by Fusarium pathogens, among other microorganisms, threaten crop production in both commercial and smallholder farming. There are increasing concerns about the use of conventional synthetic fungicides due to fungal resistance and the associated negative effects of these chemicals on human health, livestock and the environment. This leads to the search for alternative fungicides from nature, especially from plants. The objectives of this study were to characterize isolated compounds from Combretum erythrophyllum (Burch.) Sond. and Withania somnifera (L.) Dunal leaf extracts, evaluate their antifungal activity against Fusarium pathogens, their phytotoxicity on maize seed germination and their cytotoxicity effect on Raw 264.7 macrophage cells. The investigation led to the isolation of antifungal compounds characterized as 5-hydroxy-7,4′-dimethoxyflavone, maslinic acid (21-hydroxy-3-oxo-olean-12-en-28-oic acid) and withaferin A (4β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2-24-dienolide). The structural elucidation of the isolated compounds was established using nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and, in comparison, with the available published data. These compounds showed good antifungal activity with minimum inhibitory concentrations (MIC) less than 1.0 mg/mL against one or more of the tested Fusarium pathogens (F. oxysporum, F. verticilloides, F. subglutinans, F. proliferatum, F. solani, F. graminearum, F. chlamydosporum and F. semitectum). The findings from this study indicate that medicinal plants are a good source of natural antifungals. Furthermore, the isolated antifungal compounds did not show any phytotoxic effects on maize seed germination. The toxicity of the compounds A (5-hydroxy-7,4′-dimethoxyflavone) and AI (4β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2-24-dienolide) was dose-dependent, while compound B (21-hydroxy-3-oxo-olean-12-en-28-oic acid) showed no toxicity effect against Raw 264.7 macrophage cells. Full article
(This article belongs to the Special Issue Biological Activity of Plant Compounds and Extracts)
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22 pages, 9974 KB  
Article
VEGFR-Mediated Cytotoxic Activity of Pulicaria undulata Isolated Metabolites: A Biological Evaluation and In Silico Study
by Sameh S. Elhady, Reda F. A. Abdelhameed, Salwa H. Zekry, Amany K. Ibrahim, Eman S. Habib, Khaled M. Darwish, Reem M. Hazem, Khadijah A. Mohammad, Hashim A. Hassanean and Safwat A. Ahmed
Life 2021, 11(8), 759; https://doi.org/10.3390/life11080759 - 28 Jul 2021
Cited by 12 | Viewed by 3368
Abstract
Natural products play a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of drugs and bioactive substances. Adding to the search for new sources of safe innovative antitumor drugs, here we [...] Read more.
Natural products play a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of drugs and bioactive substances. Adding to the search for new sources of safe innovative antitumor drugs, here we reported a phytochemical study on Pulicaria undulata which revealed promising antiangiogenic agents. Six compounds were isolated and identified as xanthoxyline (1), stigmasterol (2), oleanolic acid (3), salvigenin (4), rhamnetin (5) and dihydroquercetin-4′-methyl ether (6) using nuclear magnetic resonance (NMR) spectroscopic techniques. Compound 3 and 4 are first reported in Pulicaria genus. Both the extract and isolated compounds were evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7). In vivo antiproliferative activity against Ehrlich’s ascites carcinoma (EAC) were also assessed. The P. undulata extract and isolates showed significant reduction in tumor weight, decreased both serum vascular endothelial growth factor B (VEGF-B) levels and vascular endothelial growth factor receptor 2 (VEGFR-2) expression significantly compared to the control EAC group, suggesting an antiangiogenic activity through the inhibition of VEGF signaling. Besides, they displayed reduction in CD34 expression, confirming their antiangiogenic effect. Moreover, the potential affinity of isolated compounds to human estrogen nuclear receptor-alpha (hER-α), the most recognized modulator of VEGFR-2 expression, was virtually estimated through molecular modeling studies. The most promising activity profiles were assigned to the investigated flavonoids, compounds 46, as well as the alkyl-phenylketone, compound 1. Additionally, these four top active compounds showed respective high to intermediate docking scores while possessing preferential binding with hER-α critical pocket residues. Based on the provided data, these isolated compounds illustrated promising inhibitors of VEGF-stimulated angiogenesis, which could be a possible mechanism for their anticancer activity. Full article
(This article belongs to the Section Plant Science)
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18 pages, 3297 KB  
Article
Salvigenin, a Trimethoxylated Flavone from Achillea Wilhelmsii C. Koch, Exerts Combined Lipid-Lowering and Mitochondrial Stimulatory Effects
by Elena Serino, Azam Chahardoli, Nadia Badolati, Carmina Sirignano, Fereshteh Jalilian, Mahdi Mojarrab, Zahra Farhangi, Daniela Rigano, Mariano Stornaiuolo, Yalda Shokoohinia and Orazio Taglialatela-Scafati
Antioxidants 2021, 10(7), 1042; https://doi.org/10.3390/antiox10071042 - 29 Jun 2021
Cited by 28 | Viewed by 5619
Abstract
Phytochemical analysis of the Iranian plant Achillea wilhelmsii led to the isolation of 17 pure secondary metabolites belonging to the classes of sesquiterpenoids and phenolics. Two of these compounds, named wilhemsin (7) and wilhelmsolide (9), are new sesquiterpenoids, and [...] Read more.
Phytochemical analysis of the Iranian plant Achillea wilhelmsii led to the isolation of 17 pure secondary metabolites belonging to the classes of sesquiterpenoids and phenolics. Two of these compounds, named wilhemsin (7) and wilhelmsolide (9), are new sesquiterpenoids, and the first shows undescribed structural features. Their structures were elucidated through extensive spectroscopic analysis, mainly based on 1D and 2D NMR, and chemical derivatization. Starting from plant traditional use and previous reports on the activity of the plant extracts, all the pure compounds were evaluated on endpoints related to the treatment of metabolic syndrome. The sesquiterpene hanphyllin (8) showed a selective cholesterol-lowering activity (−12.7% at 30 µM), santoflavone (13) stimulated glucose uptake via the GLUT transporter (+16.2% at 30 µM), while the trimethoxylated flavone salvigenin (14) showed a dual activity in decreasing lipid levels (−22.5% palmitic acid biosynthesis at 30 µM) and stimulating mitochondrial functionality (+15.4% at 30 µM). This study further confirms that, in addition to the antioxidants vitexin, isovitexin, and isoschaftoside, A. wilhelmsii extracts contain molecules that can act at different levels on the metabolic syndrome symptoms. Full article
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13 pages, 1650 KB  
Article
Phytochemical Analysis and Trypanocidal Activity of Marrubium incanum Desr.
by Claudio Frezza, Alessandro Venditti, Armandodoriano Bianco, Mauro Serafini, Massimo Pitorri, Fabio Sciubba, Maria Enrica Di Cocco, Eleonora Spinozzi, Loredana Cappellacci, Anders Hofer, Filippo Maggi and Riccardo Petrelli
Molecules 2020, 25(14), 3140; https://doi.org/10.3390/molecules25143140 - 9 Jul 2020
Cited by 8 | Viewed by 5023
Abstract
The rationale inspiring the discovery of lead compounds for the treatment of human parasitic protozoan diseases from natural sources is the well-established use of medicinal plants in various systems of traditional medicine. On this basis, we decided to select an overlooked medicinal plant [...] Read more.
The rationale inspiring the discovery of lead compounds for the treatment of human parasitic protozoan diseases from natural sources is the well-established use of medicinal plants in various systems of traditional medicine. On this basis, we decided to select an overlooked medicinal plant growing in central Italy, Marrubium incanum Desr. (Lamiaceae), which has been used as a traditional remedy against protozoan diseases, and to investigate its potential against Human African trypanosomiasis (HAT). For this purpose, we assayed three extracts of different polarities obtained from the aerial parts of M. incanum—namely, water (MarrInc-H2O), ethanol (MarrInc-EtOH) and dichloromethane (MarrInc-CH2Cl2)—against Trypanosoma brucei (TC221), with the aim to discover lead compounds for the development of antitrypanosomal drugs. Their selectivity index (SI) was determined on mammalian cells (BALB/3T3 mouse fibroblasts) as a counter-screen for toxicity. The preliminary screening selected the MarrInc-CH2Cl2 extract as the most promising candidate against HAT, showing an IC50 value of 28 μg/mL. On this basis, column chromatography coupled with the NMR spectroscopy of a MarrInc-CH2Cl2 extract led to the isolation and identification of five compounds i.e. 1-α-linolenoyl-2-palmitoyl-3-stearoyl-sn- glycerol (1), 1-linoleoyl-2-palmitoyl-3-stearoyl-sn-glycerol (2), stigmasterol (3), palmitic acid (4), and salvigenin (5). Notably, compounds 3 and 5 were tested on T. brucei, with the latter being five-fold more active than the MarrInc-CH2Cl2 extract (IC50 = 5.41 ± 0.85 and 28 ± 1.4 μg/mL, respectively). Furthermore, the SI for salvigenin was >18.5, showing a preferential effect on target cells compared with the dichloromethane extract (>3.6). Conversely, stigmasterol was found to be inactive. To complete the work, also the more polar MarrInc-EtOH extract was analyzed, giving evidence for the presence of 2″-O-allopyranosyl-cosmosiin (6), verbascoside (7), and samioside (8). Our findings shed light on the phytochemistry of this overlooked species and its antiprotozoal potential, providing evidence for the promising role of flavonoids such as salvigenin for the treatment of protozoal diseases. Full article
(This article belongs to the Special Issue Bioactive Compounds against Parasite, Bacteria and Related Diseases)
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17 pages, 3152 KB  
Article
Structural Elucidation of Malonylcommunol and 6β-Hydroxy-trans-communic Acid, Two Undescribed Diterpenes from Salvia cinnabarina. First Examples of Labdane Diterpenoids from a Mexican Salvia Species
by Celia Bustos-Brito, Antonio Nieto-Camacho, Simón Hernandez-Ortega, José Rivera-Chávez, Leovigildo Quijano and Baldomero Esquivel
Molecules 2020, 25(8), 1808; https://doi.org/10.3390/molecules25081808 - 15 Apr 2020
Cited by 10 | Viewed by 4391
Abstract
The aerial parts of Salvia cinnabarina afforded two undescribed labdane diterpenoids 1 and 2 (malonylcommunol and 6β-hydroxy-trans-communic acid) along with two known labdane diterpenoids, trans-communic acid (3) and trans-communol (4). Additionally, seven known metabolites were [...] Read more.
The aerial parts of Salvia cinnabarina afforded two undescribed labdane diterpenoids 1 and 2 (malonylcommunol and 6β-hydroxy-trans-communic acid) along with two known labdane diterpenoids, trans-communic acid (3) and trans-communol (4). Additionally, seven known metabolites were also isolated; two isopimarane diterpenoids 5 and 6, two sesquiterpenoids identified as β-eudesmol (7) and cryptomeridiol (8), and three aromatic compounds identified as phthalic acid (9), a mixture of tyrosol fatty acid esters (10) and the flavone salvigenine (11). While compounds compounds 13 showed significant inhibition of yeast α-glucosidase, compounds 2, 3 and 7 had no anti-inflammatory activity in the edema model induced by TPA. This paper is not only the first report on a wild population of Salvia cinnabarina, but also of the presence of labdane-type diterpenoids in a Mexican Salvia sp. Full article
(This article belongs to the Section Natural Products Chemistry)
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19 pages, 2687 KB  
Article
Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison
by Mansour Sobeh, Samar Rezq, Mohammed Cheurfa, Mohamed A.O. Abdelfattah, Rasha M.H. Rashied, Assem M. El-Shazly, Abdelaziz Yasri, Michael Wink and Mona F. Mahmoud
Biomolecules 2020, 10(4), 599; https://doi.org/10.3390/biom10040599 - 13 Apr 2020
Cited by 44 | Viewed by 5624
Abstract
This study aimed to investigate the chemical composition, and evaluate the antioxidant, anti-inflammatory, anti-pyretic, and the analgesic properties of methanol extracts from the leaves of Thymus algeriensis and Thymus fontanesii (Lamiaceae). Thirty-five secondary metabolites were characterized in both extracts using HPLC-PDA-ESI-MS/MS. Phenolic acids, [...] Read more.
This study aimed to investigate the chemical composition, and evaluate the antioxidant, anti-inflammatory, anti-pyretic, and the analgesic properties of methanol extracts from the leaves of Thymus algeriensis and Thymus fontanesii (Lamiaceae). Thirty-five secondary metabolites were characterized in both extracts using HPLC-PDA-ESI-MS/MS. Phenolic acids, mainly rosmarinic acid and its derivatives, dominated the T. algeriensis extract, while the phenolic diterpene carnosol and the methylated flavonoid salvigenin, prevailed in T. fontanesii extract. Molecular docking study was carried out to estimate the anti-inflammatory potential and the binding affinities of some individual secondary metabolites from both extracts to the main enzymes involved in the inflammation pathway. In vitro enzyme inhibitory assays and in vivo assays were used to investigate the antioxidant and anti-inflammatory activities of the extracts. Results revealed that both studied Thymus species exhibited antioxidant, anti-inflammatory, analgesic, and antipyretic effects. They showed to be a more potent antioxidant than ascorbic acid and more selective against cyclooxygenase (COX-2) than diclofenac and indomethacin. Relatively, the T. fontanesii extract was more potent as COX-2 inhibitor than T. algeriensis. In conclusion, Thymus algeriensis and Thymus fontanesii may be interesting candidates for the treatment of inflammation and oxidative stress-related disorders. Full article
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