Infections caused by antibiotic-drug-resistant microorganisms are a major global health concern, and they result in millions of deaths every year. Methicillin-resistant Staphylococcus aureus (MRSA) is one of such drug-resistant microbial strains, and new and effective antimicrobial agents are desperately needed to combat infections caused by MRSA. In the search for effective anti-MRSA agents, the leaves of Citrus grandis (Rutaceae), also known as C. maxima, were investigated. Implementing a bioassay-guided approach, sinensetin (2), which is a polymethoxyflavone, was isolated as a promising anti-MRSA compound, showing inhibitory activity against three (EMRSA-15, MRSA340802 and MRSA274819; MIC values 128-256 μg/mL) of five MRSA strains tested in the present study. Five other flavonoids 6,7,8,3',4'-pentamethoxyflavone (1), cirsilineol (3), nobiletin (4), 5-desmethylsinensetin (5) and hesperidin (6) were isolated from the dichloromethane extract of this plant. They displayed varied levels of antimicrobial activities against the tested microbial strains, Micrococcus luteus NCTC 7508, Escherichia coli NCTC 12241 and Pseudomonas aeruginosa NCTC 12903, and a fungal strain, Candida albicans ATCC 90028, but not against Staphylococcus aureus NCTC 12981. Sinensetin (2) also exhibited strong antimicrobial activity against the fungal strain C. albicans with an MIC value of 0.0625 mg/mL. The chemical structures of all isolated compounds were unequivocally elucidated by spectroscopic means (1D and 2D NMR and HR-ESIMS). The present study revealed sinensetin (2) as a potential structural template for generating structural analogues and developing anti-MRSA agents and provided scientific evidence supporting the traditional uses of C. grandis in the treatment of microbial infections.
- Klíčová slova
- Citrus grandis, MRSA, Polymethoxyflavonoids, Rutaceae, Sinensetin, Staphylococcus aureus,
- MeSH
- antibakteriální látky farmakologie izolace a purifikace chemie MeSH
- Candida albicans účinky léků MeSH
- Citrus * chemie MeSH
- flavonoidy * farmakologie izolace a purifikace MeSH
- fytonutrienty farmakologie izolace a purifikace MeSH
- listy rostlin * chemie MeSH
- methicilin rezistentní Staphylococcus aureus * účinky léků MeSH
- mikrobiální testy citlivosti * MeSH
- molekulární struktura MeSH
- rostlinné extrakty farmakologie chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- flavonoidy * MeSH
- fytonutrienty MeSH
- rostlinné extrakty MeSH
- sinensetin MeSH Prohlížeč
Cancer kills about 10 million people every year. Medicinal plants remain a major source in the global search for anticancer drugs. In this study, 3,4,3'-tri-O-methylflavellagic acid (MFA) was isolated from the methanol root extract of Anogeissus leiocarpus. The structure was determined by 1D- and 2D-NMR data. The cytotoxic effects of MFA were evaluated against human breast (MCF-7), colorectal (Caco-2), and cervical (HeLa) cancer cell lines using the 3-[4,5-dimethylthiazole-2-yl] 3,5-diphenyltetrazolium bromide assay. A multi-protein target screening via molecular docking was conducted against ten cancer-related proteins, and ADMET properties were evaluated. MFA exhibited the most potent activity against Caco-2 (IC50: 46.75 ± 13.00 µM). Molecular docking analysis showed that MFA had a strong binding affinity for the colchicine-binding site of αβ-tubulin and polo-like kinase-1 (binding energies: -8.5 and -8.4 kcal/mol, respectively). MFA also satisfied the Lipinski's Rule of Five. MFA could, therefore, potentially serve as a scaffold for developing new anticancer molecules.
- Klíčová slova
- 3,4,3’-tri-O-methylflavellagic acid, Anogeissus leiocarpus, cancer, molecular docking,
- Publikační typ
- časopisecké články MeSH
Diospyros discolor Willd., commonly known as velvet apple or Mabolo, is an underutilized fruit. Traditionally, various parts of D. discolor have been used in medicine for treating dysentery, diarrhea, and respiratory issues. Pharmacologically, the plant has exhibited diverse effects, including anti-acetylcholinesterase, anti-asthmatic, antiaging, antimicrobial, antioxidant, cytotoxic, and thrombolytic activities. These findings substantiate its traditional uses, particularly its potential as an antidiabetic, antidiarrheal, analgesic, anti-inflammatory, and vasorelaxant agent. This plant is notable for its rich aromatic profile, containing 39 volatile compounds in the fruit and peel, with esters and α-farnesene being the predominant compounds. Volatile esters such as methyl butyrate and ethyl dominate the aroma. Nutritionally, the fruit contains dietary fiber, malic acid, vitamins, essential fatty acids, flavonoids, and triterpenes. Additionally, bioactive compounds, including flavonoids, triterpenes, and dimeric naphthoquinones (e.g., diospyrin), have been isolated from the plant. The essential oil derived from its flowers further enhances its bioeconomic and health benefits. Moreover, D. discolor holds bioeconomic potential as a biosorbent, a source of timber and edible fruits, and a material for synthesizing silver nanoparticles. This review consolidates current knowledge on the traditional uses, phytometabolites, pharmacological properties, and bioeconomic potential of D. discolor. The potential toxicity of this plant and its components has also been reviewed.
- Klíčová slova
- Diospyros blancoi, Diospyros discolor, Diospyros mabolo, bioeconomy, ethnomedicine, pharmacological properties, phytometabolites, velvet apple,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cancer is a leading cause of global death. Medicinal plants have gained increasing attention in cancer drug discovery. In this study, the stem bark extract of Olax subscorpioidea, which is used in ethnomedicine to treat cancer, was subjected to phytochemical investigation leading to the isolation of oleanolic acid (OA). The structure was elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic (NMR) data, and by comparing its data with previously reported data. Molecular docking was used to investigate the interactions of OA with nine selected cancer-related protein targets. OA docked well with human 17β-hydroxysteroid dehydrogenase type-1 (17βHSD1), caspase-3, and epidermal growth factor receptor tyrosine kinase (binding affinities: -9.8, -9.3, and -9.1 kcal/mol, respectively). OA is a triterpenoid compound with structural similarity to steroids. This similarity with the substrates of 17βHSD1 gives the inhibitor candidate an excellent opportunity to bind to 17βHSD1. The structural and functional dynamics of OA-17βHSD1 were investigated by molecular dynamics simulations at 240 ns. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (-52.76, and -63.56 kcal/mol, respectively). The average C-α root mean square of deviation (RMSD) value of OA (1.69 Å) compared with the unbound protein (2.01 Å) indicated its high stability at the protein's active site. The binding energy and stability at the active site of 17βHSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.
Oleanolic acid has been isolated from the cytotoxic fraction of Olax subscorpioidea stem back extract. Its structure was deduced by 1D- and 2D-NMR analyses.The compound has strong interaction with human 17β-hydroxysteroid dehydrogenase-1 (PDB: 1FDW), caspase-3 (PDB: 1GFW), epidermal growth factor receptor tyrosine kinase (PDB: 5JEB), and poly(ADP-ribose) polymerase-1 (PDB: 5DS3), with binding affinities of –9.8, –9.3, –9.1, and –8.9 kcal/mol, respectively.MMPBSA studies, C-α RMSD and other MD parameters supported the inhibitory potential of oleanolic acid against critical residues involved in the catalysis of 17β-hydroxysteroid dehydrogenase-1.
- Klíčová slova
- 17β-hydroxysteroid dehydrogenase-1, Olax subscorpioidea, breast cancer, molecular docking, molecular dynamics simulations, nuclear magnetic resonance, oleanolic acid,
- Publikační typ
- časopisecké články MeSH
The present study aimed to assess the antioxidant and anti-inflammatory activities of polyphenol-rich extracts of seedless variety of Ziziphus mauritiana (SZM). Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis of SZM leaves and fruit extracts in ethanol revealed the presence of sixteen phenolics including chlorogenic acid, p-coumeric acid, gallic acid, kaempferol, rutin and quercetin. Leaf extract showed higher total phenolic and total flavonoid contents (177.6 mg/100 g and 46.2 mg/100 g) than in fruit extract (137.8 mg/100 g and 14.1 mg/100 g). The leaf extract exhibited higher DPPH radical-scavenging activity (63.5 %) than the fruit extract (58.2 %). The anti-inflammatory activity was evaluated on carrageenan-induced rat model and suppression of inflammatory biomarkers (Interleukin-6, Tumor necrosis factor-α and CRP) were studied. The fruit extract exhibited remarkable inhibition (98.1 %) at the dose level of 500 mg/kg body weight (BW), comparable to the standard drug indomethacin (98.4 %). Both extracts suppressed the inflammatory biomarkers and more pronounced results showed by the fruit extract including CRP, IL-6, and TNF-α. The leaf extract demonstrated the higher antioxidant potential as evident from the superoxide dismutase, catalase, malondialdehyde, glutathione peroxidase and glutathione levels. These findings suggest that SZM leaf and fruit extracts possess potential antioxidant and remarkable anti-inflammatory properties and can play a significant role in mitigating oxidative stress.
- Klíčová slova
- CRP, IL-6, and TNF-α, Carrageenan, Chlorogenic acid, DPPH radical scavenging, HPLC analysis, Inflammation, Oxidative stress,
- Publikační typ
- časopisecké články MeSH
Galangal (Alpinia galanga (L.) Willd) and bitter ginger (Zingiber zerumbet (L.) Roscoe) are aromatic rhizomatous plants that are typically used for culinary purposes. These rhizomatous plants have many biological properties and the potential to be beneficial for pharmaceutics. In this study, we evaluated the antioxidant and antimicrobial activities, with a specific focus on acne-causing bacteria, as well as the phytochemical constituents, of different parts of galangal and bitter ginger. The rhizomes, stems, and leaves of galangal and bitter ginger were separately dried for absolute ethanol and methanol extractions. The extracts were used to evaluate the antioxidant activity using a DPPH radical scavenging assay (0.005-5000 μg/mL), antimicrobial activity against acne-causing bacteria (0.50-31.68 mg/mL), and in vitro cytotoxicity toward human keratinocytes and fibroblasts (62.5-1000 μg/mL), as well as analyses of bioactive phytochemicals via GC-MS and LC-MS/MS (500 ppm). The ethanol and methanol extracts of bitter ginger and galangal's rhizomes (BRhE, BRhM, GRhE, and GRhM), stems (BStE, BStM, GRhE, and GRhM), and leaves (BLeE, BLeM, GLeE, and GLeM), respectively, showed antioxidant and antimicrobial activities. The extracts of all parts of bitter ginger and galangal were greatly antioxidative with 0.06-1.42 mg/mL for the IC50 values, while most of the extracts were strongly antimicrobial against C. acnes DMST 14916, particularly BRhM, BRhE, GRhM, and GRhE (MICs: 3.96-7.92 mg/mL). These rhizome extracts had also antimicrobial activities against S. aureus TISTR 746 (MICs: 7.92-31.68 mg/mL) and S. epidermidis TISTR 518 (MICs: 7.92-15.84 mg/mL). The extracts of bitter ginger and galangal rhizomes were not toxic to HaCaT and MRC-5 even at the highest concentrations. Through GC-MS and LC-MS/MS analysis, phytochemicals in bitter ginger rhizome extracts, including zerumbone, tectorigenin, piperic acid, demethoxycurcumin, and cirsimaritin, and galangal rhizome extracts, including sweroside and neobavaisoflavone, were expected to provide the antioxidant and anti-microbial activities. Therefore, the results suggest that the bitter ginger and galangal extracts could be natural anti-acne compounds with potential for pharmaceutic, cosmetic, and aesthetic applications.
- Klíčová slova
- Acne vulgaris, Alpinia galanga, Zingiber zerumbet, antimicrobial, cytotoxicity, phytochemicals,
- MeSH
- acne vulgaris farmakoterapie mikrobiologie MeSH
- antibakteriální látky farmakologie chemie MeSH
- antiinfekční látky farmakologie chemie MeSH
- antioxidancia * farmakologie chemie MeSH
- fibroblasty účinky léků MeSH
- fytonutrienty * farmakologie chemie MeSH
- keratinocyty * účinky léků MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- oddenek chemie MeSH
- rostlinné extrakty * farmakologie chemie MeSH
- zázvor lékařský * chemie MeSH
- zázvorníkovité chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- antiinfekční látky MeSH
- antioxidancia * MeSH
- fytonutrienty * MeSH
- rostlinné extrakty * MeSH
Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by cognitive, motor, and psychiatric symptoms. Despite significant advances in understanding the underlying molecular mechanisms of HD, there is currently no cure or disease-modifying treatment available. Emerging pharmacological approaches offer promising strategies to alleviate symptoms and slow down disease progression. This comprehensive review aims to provide a critical appraisal of the latest developments in pharmacological interventions for HD. The review begins by discussing the pathogenesis of HD, focusing on the role of mutant huntingtin protein, mitochondrial dysfunction, excitotoxicity, and neuro-inflammation. It then explores emerging therapeutic targets, including the modulation of protein homeostasis, mitochondrial function, neuro-inflammation, and neurotransmitter systems. Pharmacological agents targeting these pathways are discussed, including small molecules, gene-based therapies, and neuroprotective agents. In recent years, several clinical trials have been conducted to evaluate the safety and efficiency of novel compounds for HD. This review presents an update on the outcomes of these trials, highlighting promising results and challenges encountered. Additionally, it discusses the potential of repurposing existing drugs approved for other indications as a cost-effective approach for HD treatment. The review concludes by summarizing the current state of pharmacological approaches for HD and outlining future directions in drug development. The integration of multiple therapeutic strategies, personalized medicine approaches, and combination therapies are highlighted as potential avenues to maximize treatment effectiveness.
- Klíčová slova
- Huntington's disease, Mitochondrial dysfunction, Mutant huntingtin protein, Neurodegenerative disorders, Pharmacological approaches,
- MeSH
- genetická terapie metody MeSH
- Huntingtonova nemoc * farmakoterapie MeSH
- lidé MeSH
- mitochondrie účinky léků metabolismus MeSH
- neuroprotektivní látky * terapeutické užití farmakologie MeSH
- protein huntingtin genetika antagonisté a inhibitory metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- neuroprotektivní látky * MeSH
- protein huntingtin MeSH
Background: The research is aimed at exploring the potential of marigold petal tea (MPT), rich in polyphenol contents, against oxidative stress and obesity in a rat model following a high-fat-sugar diet (HFSD). Methods: The MPT was prepared through the customary method of decoction and was subjected to analysis for its polyphenol composition using reversed-phase high-performance liquid chromatography (RP-HPLC). Two specific doses of MPT, namely, 250 and 500 mg/kg body weight (BW), were chosen for the study-referred to as MPT-250 and MPT-500, respectively. Result: The main phenolic acids and flavonoids identified in MPT, with concentrations exceeding 10 mg/100 mL of tea, included catechin, rutin, salicylic acid, gallic acid, sinapic acid, chlorogenic acid, cinnamic acid, and ellagic acid. The total phenolic (TP) and total flavonoid (TF) contents in MPT were measured to be 5.53 and 7.73 mg/g, respectively. Additionally, MPT demonstrated a 57.2% scavenging capacity with 2,2-diphenyl-1-picrylhydrazyl radical. Notably, the administration of a higher dose (MPT-500) showed a significant reduction in body mass index (BMI) and a 51.24% reduction in the rate of increase in BW compared to the HFSD group. The findings indicated that all the treatment groups, that is, orlistat treatment (OT), MPT-250, and MPT-500 groups, experienced reduced levels of serum total cholesterol (TC), triglyceride (TG), and markers of lipoproteins in contrast to the HFSD group. Moreover, MPT helped restore the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), thereby demonstrating its potential in combating oxidative stress. The MPT-500 group also displayed decreased liver and kidney weights and an improved atherogenic index when compared to the HFSD group. Conclusion: The results clearly indicate that a high dosage of MPT showed antiobesity activity which was comparable to the same effects produced by the conventional drug orlistat.
- Klíčová slova
- lipid profile, marigold petal tea, obesity, oxidative stress, rutin,
- MeSH
- antioxidancia * farmakologie MeSH
- biologické markery * krev MeSH
- dieta s vysokým obsahem tuků * MeSH
- hmotnostní úbytek účinky léků MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- látky proti obezitě * farmakologie MeSH
- modely nemocí na zvířatech * MeSH
- obezita * farmakoterapie metabolismus MeSH
- oxidační stres * účinky léků MeSH
- polyfenoly * farmakologie MeSH
- potkani Sprague-Dawley MeSH
- rostlinné extrakty farmakologie izolace a purifikace MeSH
- sacharidová dieta škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia * MeSH
- biologické markery * MeSH
- látky proti obezitě * MeSH
- polyfenoly * MeSH
- rostlinné extrakty MeSH
Cancer remains a major global health concern, often challenging traditional treatments. Natural compounds like fungal polysaccharides have gained attention for their immune-modulatory properties. This study evaluates the phytochemical properties of the n-hexane fraction of Trichaptum biforme and explores its immune-enhancing effects. The study involved isolating three sterol derivatives using column chromatography and purifying polysaccharides from T. biforme (TBP) through hot aqueous extraction. TBP content was quantified via the phenol‑sulfuric acid method, and antioxidant activity was assessed using DPPH and FRAP assays. Cytotoxicity of TBP on THP-1 cells and the impact on IL-1β and TNF-α secretion were evaluated through the XTT assay. Flow cytometry and ELISA assessed cytotoxic activity and IFN-γ secretion in NK cells. The compound 9, 11-Dehydroergosterol peroxide was identified for the first time in T. biforme. The total polysaccharide content was 78.18 ± 0.81 %. The TBP significantly increased IL-1β and TNF-α secretion from THP-1 cells at concentrations of 10 and 320 μg/mL (p < 0.01). Treatment of NK cells with the extract (320 μg/mL) and IL-2 (100 units/mL) significantly enhanced cytotoxic activity and IFN-γ secretion compared to the control group (p < 0.01). These findings suggest that TBP holds promise as a candidate for bolstering anticancer immune responses.
- Klíčová slova
- Immune system, Interleukin, Mushroom, NMR, Tumor,
- Publikační typ
- časopisecké články MeSH
Diabetic nephropathy, characterized by inflammation and oxidative stress, poses a management challenge. This study investigates the effect of Polygonum hyrcanicum extract on diabetic nephropathy in alloxan-induced diabetic mice. In this experimental animal study, the P. hyrcanicum extract was prepared using continuous macerations. Thirty male Albino mice, divided into five groups, were induced with alloxan-induced diabetes. They received intraperitoneal injections of the plant extract (100 and 200 mg/kg) and metformin (300 mg/kg) for four weeks. Kidney and blood samples were collected to assess protein carbonyl, glutathione, lipid peroxidation, TNF-α and IL-6 levels. The amount of total flavonoid and phenolic content in the hydroalcoholic extract of P. hyrcanicum were 7.5 ± 0.3 mg of quercetin and 88.2 ± 1.3 mg gallic acid per gram of extract respectively. The antioxidant activity level of the hydroalcoholic extract was determined to be 1.78 ± 0.51 mM equivalent per gram of extract. Alloxan administration resulted in a significant reduction in glutathione levels and a significant increase in protein carbonyl, lipid peroxidation, TNF-α, and IL-6 levels. Hydroalcoholic extract of P. hyrcanicum effectively reduced oxidative stress markers and inflammatory cytokines (TNF-α, IL-6), indicating its potential in mitigating diabetic nephropathy. However, no significant difference in efficacy was observed between the 100 mg/kg and 200 mg/kg doses in terms of reducing these toxicities.
- Klíčová slova
- Polygonum hyrcanicum, Alloxan, Diabetes, Nephropathy, Oxidative stress,
- MeSH
- alloxan MeSH
- antioxidancia * farmakologie MeSH
- diabetické nefropatie * farmakoterapie metabolismus MeSH
- experimentální diabetes mellitus * farmakoterapie metabolismus MeSH
- glutathion metabolismus MeSH
- interleukin-6 metabolismus krev MeSH
- ledviny účinky léků metabolismus patologie MeSH
- myši MeSH
- oxidační stres * účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- Polygonum * chemie MeSH
- rostlinné extrakty * farmakologie chemie MeSH
- TNF-alfa metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alloxan MeSH
- antioxidancia * MeSH
- glutathion MeSH
- interleukin-6 MeSH
- rostlinné extrakty * MeSH
- TNF-alfa MeSH
