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Citrus hystrix essential oil (CHEO) have shown various pharmacological properties including antibacterial activity. This EO also possessed antibacterial effect against foodborne pathogens. There is less information available about the synergy interaction between CHEO and tetracycline, as well as their mechanism of action. Therefore, this study was conducted to evaluate the synergistic effect of CHEO and tetracycline against clinical isolate of Escherichia coli. Antibiofilm, bacteriolytic, and efflux pump inhibitor activities were also performed. The chemical composition of CHEO was analysed using GC-MS. Three major compounds, D-limonene (25.02%), ß-pinene (23.37%), and ß-sabinene (22.20%) were identified. CHEO exhibited moderate antibacterial activity with MIC value of 250 µg/mL. The combination of CHEO (7.8 µg/mL) and tetracycline (62.5 µg/mL) produced a synergistic effect on E. coli with fractional inhibitory concentration index of 0.5. This mixture inhibited biofilm formation in E. coli. The combination of 7.8 µg/mL CHEO and 62.5 µg/mL tetracycline demonstrated bacteriolytic activity. In addition, the CHEO at 250 µg/mL showed a significant effect in inhibiting efflux pump. D-limonene has a binding free energy value of -20.13 kcal/mol with ompA transmembrane domain of E. coli. This finding indicates that CHEO has a potency to be developed as natural antibacterial against E. coli.
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BACKGROUND: Malaria is a major global health concern, particularly in tropical and subtropical countries. With growing resistance to first-line treatment with artemisinin, there is an urgent need to discover novel antimalarial drugs. Mesua ferrea Linn., a plant used in traditional medicine for various purposes, has previously been investigated by our research group for its cytotoxic properties. The objective of this study was to explore the compounds isolated from M. ferrea with regards to their potential antiplasmodial activity, their interaction with Plasmodium falciparum lactate dehydrogenase (PfLDH), a crucial enzyme for parasite survival, and their pharmacokinetic and toxicity profiles. METHODS: The isolated compounds were assessed for in vitro antiplasmodial activity against a multidrug-resistant strain of P. falciparum K1 using a parasite lactate dehydrogenase (pLDH) assay. In vitro cytotoxicity against Vero cells was determined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The interactions between the isolated compounds and the target enzyme PfLDH were investigated using molecular docking. Additionally, pharmacokinetic and toxicity properties were estimated using online web tools SwissADME and ProTox-II, respectively. RESULTS: Among the seven compounds isolated from M. ferrea roots, rheediachromenoxanthone (5), which belongs to the pyranoxanthone class, demonstrated good in vitro antiplasmodial activity, with the IC50 being 19.93 µM. Additionally, there was no toxicity towards Vero cells (CC50 = 112.34 µM) and a selectivity index (SI) of 5.64. Molecular docking analysis revealed that compound (5) exhibited a strong binding affinity of - 8.6 kcal/mol towards PfLDH and was stabilized by forming hydrogen bonds with key amino acid residues, including ASP53, TYR85, and GLU122. Pharmacokinetic predictions indicated that compound (5) possessed favorable drug-like properties and desired pharmacokinetic characteristics. These include high absorption in the gastrointestinal tract, classification as a non-substrate of permeability glycoprotein (P-gp), non-inhibition of CYP2C19, ease of synthesis, a high predicted LD50 value of 4,000 mg/kg, and importantly, non-hepatotoxic, non-carcinogenic, and non-cytotoxic effects. CONCLUSIONS: This study demonstrated that compounds isolated from M. ferrea exhibit activity against P. falciparum. Rheediachromenoxanthone has significant potential as a scaffold for the development of potent antimalarial drugs.
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Antimaláricos , Simulación del Acoplamiento Molecular , Extractos Vegetales , Raíces de Plantas , Plasmodium falciparum , Xantonas , Antimaláricos/farmacología , Antimaláricos/farmacocinética , Antimaláricos/química , Antimaláricos/toxicidad , Plasmodium falciparum/efectos de los fármacos , Xantonas/farmacología , Xantonas/química , Xantonas/farmacocinética , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Chlorocebus aethiops , Células VeroRESUMEN
Staphylococcus haemolyticus is a cause of bovine mastitis, leading to inflammation in the mammary gland. This bacterial infection adversely affects animal health, reducing milk quality and yield. Its emergence has been widely reported, representing a significant economic loss for dairy farms. Interestingly, S. haemolyticus exhibits higher levels of antimicrobial resistance than other coagulase-negative Staphylococci. In this study, we synthesized silver/silver chloride nanoparticles (Ag/AgCl-NPs) using Solanum lasiocarpum root extract and evaluated their antibacterial and antibiofilm activities against S. haemolyticus. The formation of the Ag/AgCl-NPs was confirmed using UV-visible spectroscopy, which revealed maximum absorption at 419 nm. X-ray diffraction (XRD) analysis demonstrated the crystalline nature of the Ag/AgCl-NPs, exhibiting a face-centered cubic lattice. Fourier transform infrared (FT-IR) spectroscopy elucidated the functional groups potentially involved in the Ag/AgCl-NPs synthesis. Transmission electron microscopy (TEM) analysis revealed that the average particle size of the Ag/AgCl-NPs was 10 nm. Antimicrobial activity results indicated that the minimum inhibitory concentration (MIC) and maximum bactericidal concentration (MBC) of the Ag/AgCl-NPs treatment were 7.82-15.63 µg/mL towards S. haemolyticus. Morphological changes in bacterial cells treated with the Ag/AgCl-NPs were observed under scanning electron microscopy (SEM). The Ag/AgCl-NPs reduced both the biomass of biofilm formation and preformed biofilm by approximately 20.24-94.66 % and 13.67-88.48 %. Bacterial viability within biofilm formation and preformed biofilm was reduced by approximately 21.56-77.54 % and 18.9-71.48 %, respectively. This study provides evidence of the potential of the synthesized Ag/AgCl-NPs as an antibacterial and antibiofilm agent against S. haemolyticus.
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Antibacterianos , Biopelículas , Mastitis Bovina , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Raíces de Plantas , Compuestos de Plata , Plata , Solanum , Staphylococcus haemolyticus , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antibacterianos/farmacología , Antibacterianos/química , Plata/farmacología , Plata/química , Biopelículas/efectos de los fármacos , Compuestos de Plata/farmacología , Compuestos de Plata/química , Bovinos , Mastitis Bovina/microbiología , Mastitis Bovina/tratamiento farmacológico , Raíces de Plantas/química , Nanopartículas del Metal/química , Staphylococcus haemolyticus/efectos de los fármacos , Femenino , Solanum/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Microscopía Electrónica de TransmisiónRESUMEN
Bacterial contamination and infection widely affect the food, pharmaceutical and biomedical industries. Additionally, these bacteria developed resistance to synthetic antibiotics causing public health danger, globally. Natural plant extracts (NPE) are suitable alternatives to synthetic antibiotics to tackle antimicrobial resistance problems. Furthermore, a blend or combination of different NPEs exerts a wide spectrum of antimicrobial activity. Therefore, the combined effect of brazilin-rich extract (BRE) and lawsome methyl ether (LME) against infection-causing common bacteria were evaluated. BRE had a lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against most of the Gram-negative bacteria (Salmonella typhi, Salmonella typhimurium and Pseudomonas aeruginosa) while LME was active against most of the Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, and Staphylococcus epidermidis). The combination of BRE and LME at 2:1 and 1:1 concentration significantly reduced the MIC value of each compound as compared to either BRE or LME concentration alone (P < 0.05). Further time-kill kinetics revealed a 3.0-3.5 log reduction in Gram-positive bacteria and a 2.5-3.0 log reduction in Gram-negative bacteria during 120 min of incubation, respectively. Therefore, a combination of BRE and LME was recommended as natural antibacterial to synthetic antibiotics for food and pharmaceutical applications.
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The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.
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Antiinflamatorios , Artritis Reumatoide , Inmunosupresores , Fitoquímicos , Artritis Reumatoide/tratamiento farmacológico , Humanos , Antiinflamatorios/farmacología , Fitoquímicos/farmacología , Animales , Inmunosupresores/farmacología , FitoterapiaRESUMEN
BACKGROUND: The potent antiplasmodial activity of 1-hydroxy-5,6,7-trimethoxyxanthone (HTX), isolated from Mammea siamensis T. Anders. flowers, has previously been demonstrated in vitro. However, its in vivo activity has not been reported. Therefore, this study aimed to investigate the antimalarial activity and acute toxicity of HTX in a mouse model and to evaluate the pharmacokinetic profile of HTX following a single intraperitoneal administration. METHODS: The in vivo antimalarial activity of HTX was evaluated using a 4-day suppressive test. Mice were intraperitoneally injected with Plasmodium berghei ANKA strain and given HTX daily for 4 days. To detect acute toxicity, mice received a single dose of HTX and were observed for 14 days. Additionally, the biochemical parameters of the liver and kidney functions as well as the histopathology of liver and kidney tissues were examined. HTX pharmacokinetics after intraperitoneal administration was also investigated in a mouse model. Liquid chromatography triple quadrupole mass spectrometry was used to quantify plasma HTX and calculate pharmacokinetic parameters with the PKSolver software. RESULTS: HTX at 10 mg/kg body weight significantly suppressed parasitemia in malaria-infected mice by 74.26%. Mice treated with 3 mg/kg HTX showed 46.88% suppression, whereas mice treated with 1 mg/kg displayed 34.56% suppression. Additionally, no symptoms of acute toxicity were observed in the HTX-treated groups. There were no significant alterations in the biochemical parameters of the liver and kidney functions and no histological changes in liver or kidney tissues. Following intraperitoneal HTX administration, the pharmacokinetic profile exhibited a maximum concentration (Cmax) of 94.02 ng/mL, time to attain Cmax (Tmax) of 0.5 h, mean resident time of 14.80 h, and elimination half-life of 13.88 h. CONCLUSIONS: HTX has in vivo antimalarial properties against P. berghei infection. Acute toxicity studies of HTX did not show behavioral changes or mortality. The median lethal dose was greater than 50 mg/kg body weight. Pharmacokinetic studies showed that HTX has a long elimination half-life; hence, shortening the duration of malaria treatment may be required to minimize toxicity.
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Antimaláricos , Malaria , Mammea , Ratones , Animales , Antimaláricos/toxicidad , Extractos Vegetales/toxicidad , Malaria/tratamiento farmacológico , Flores , Peso CorporalRESUMEN
The emergence and spread of antimalarial drug resistance have become a significant problem worldwide. The search for natural products to develop novel antimalarial drugs is challenging. Therefore, this study aimed to assess the antimalarial and toxicological effects of Chan-Ta-Lee-La (CTLL) and Pra-Sa-Chan-Dang (PSCD) formulations and their plant ingredients. The crude extracts of CTLL and PSCD formulations and their plant ingredients were evaluated for in vitro antimalarial activity using Plasmodium lactate dehydrogenase enzyme and toxicity to Vero and HepG2 cells using the tetrazolium salt method. An extract from the CTLL and PSCD formulations exhibiting the highest selectivity index value was selected for further investigation using Peter's 4-day suppressive test, curative test, prophylactic test, and acute oral toxicity in mice. The phytochemical constituents were characterized using gas chromatography-mass spectrometry (GC-MS). Results showed that ethanolic extracts of CTLL and PSCD formulations possessed high antimalarial activity (half maximal inhibitory concentration = 4.88, and 4.19 g/mL, respectively) with low cytotoxicity. Ethanolic extracts of the CTLL and PSCD formulations demonstrated a significant dose-dependent decrease in parasitemia in mice. The ethanolic CTLL extract showed the greatest suppressive effect after 4 days of suppressive (89.80%) and curative (35.94%) testing at a dose of 600 mg/kg. Moreover, ethanolic PSCD extract showed the highest suppressive effect in the prophylactic test (65.82%) at a dose of 600 mg/kg. There was no acute toxicity in mice treated with ethanolic CTLL and PSCD extracts at 2,000 mg/kg bodyweight. GC-MS analysis revealed that the most abundant compounds in the ethanolic CTLL extract were linderol, isoborneol, eudesmol, linoleic acid, and oleic acid, whereas ethyl 4-methoxycinnamate was the most commonly found compound in the ethanolic PSCD extract, followed by 3-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one, flamenol, oleic acid amide, linoleic acid, and oleic acid. In conclusions, ethanolic CTLL and PSCD extracts exhibited high antimalarial efficacy in vitro. The ethanolic CTLL extract at a dose of 600 mg/kg exhibited the highest antimalarial activity in the 4-day suppressive and curative tests, whereas the ethanolic PSCD extract at a dose of 600 mg/kg showed the highest antimalarial activity in the prophylactic test.
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Antimaláricos , Malaria , Animales , Ratones , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Antimaláricos/química , Ácido Linoleico , Ácido Oléico/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Malaria/tratamiento farmacológico , Mezclas Complejas/farmacología , Plasmodium bergheiRESUMEN
Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.
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BACKGROUND: Cerebral malaria is one of the most serious complications of Plasmodium infection and causes behavioral changes. However, current antimalarial drugs have shown poor outcomes. Therefore, new antimalarials with neuroprotective effects are urgently needed. This study aimed to evaluate the effects of selected extracts as monotherapy or adjunctive therapy with artesunate on antimalarial, anti-inflammatory, antioxidant, and neuroprotective properties in experimental cerebral malaria (ECM). METHODS: ECM was induced in male C57BL/6 mice by infection with Plasmodium berghei ANKA (PbA). Ethanolic extracts of Atractylodes lancea (a dose of 400 mg/kg) and Prabchompoothaweep remedy (a dose of 600 mg/kg) were evaluated as monotherapy and adjunctive therapy combined with artesunate at the onset of signs of cerebral malaria and continued for 7 consecutive days. Parasitemia, clinical scores, and body weight were recorded throughout the study. At day 13 post-infection, mouse brains were dissected and processed for the study of the inflammatory response, oxidative stress, blood-brain barrier (BBB) integrity, histopathological changes, and neurocognitive impairments. RESULTS: Ethanolic extracts of A. lancea and Prabchompoothaweep remedy alone improved cerebral malaria outcome in ECM, whereas artesunate combined with extracts of A. lancea or Prabchompoothaweep remedy significantly improved the outcome of artesunate and crude extracts alone. Using real-time PCR, PbA-infected mice that had received the combination treatment showed significantly reduced gene expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10), chemokines (CXCL4 and CXCL10), and adhesion molecules (ICAM-1, VCAM1, and CD36). The PbA-infected mice that received the combination treatment showed a significantly decreased malondialdehyde level compared to the untreated group. Similarly, the Evans blue dye assay revealed significantly less dye extravasation in the brains of infected mice administered the combination treatment, indicating improved BBB integrity. Combination treatment improved survival and reduced pathology in the PbA-infected group. Additionally, combination treatment resulted in a significantly reduced level of cognitive impairment, which was analyzed using a novel object recognition test. CONCLUSIONS: This study demonstrated that artesunate combined with A. lancea or Prabchompoothaweep remedy extracts as adjunctive therapy reduced mortality, neuroinflammation, oxidative stress, BBB integrity protection, and neurocognitive impairment in the ECM.
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Antimaláricos , Atractylodes , Malaria Cerebral , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Artesunato , Malaria Cerebral/tratamiento farmacológico , Antimaláricos/farmacologíaRESUMEN
Stevens-Johnson syndrome (SJS) produces a severe hypersensitivity reaction caused by Herpes simplex virus or mycoplasma infection, vaccination, systemic disease, or other agents. Several studies have investigated the genetic susceptibility involved in SJS. To provide further genetic insights into the pathogenesis of SJS, this study prioritized high-impact, SJS-associated pathogenic variants through integrating bioinformatic and population genetic data. First, we identified SJS-associated single nucleotide polymorphisms from the genome-wide association studies catalog, followed by genome annotation with HaploReg and variant validation with Ensembl. Subsequently, expression quantitative trait locus (eQTL) from GTEx identified human genetic variants with differential gene expression across human tissues. Our results indicate that two variants, namely rs2074494 and rs5010528, which are encoded by the HLA-C (human leukocyte antigen C) gene, were found to be differentially expressed in skin. The allele frequencies for rs2074494 and rs5010528 also appear to significantly differ across continents. We highlight the utility of these population-specific HLA-C genetic variants for genetic association studies, and aid in early prognosis and disease treatment of SJS.
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Drug resistance remains a significant problem that threatens antimalarial drug treatment. Hence, the challenge is to find new effective antimalarial drugs. Based on our previous study, aqueous extracts of trisamo (TSM) and jatu-phala-tiga (JPT) had good in vitro antimalarial activities, and these recipes contain multiple beneficial pharmacological effects that could be useful for malaria therapy. Therefore, this study aimed to investigate the antimalarial activity and toxicity of the aqueous extracts of TSM and JPT in mouse models. The aqueous extractions were carried out using the decoction method. Compound identification was conducted using LC-QTOF-MS analysis. The antimalarial activities of TSM and JPT at doses 200, 400, and 600 mg/kg were evaluated against Plasmodium berghei ANKA infection using a four-day suppressive test. The toxic effects of oral administration of the extracts at 2 g/kg dose were determined using an acute toxicity test. The chemical constituents of TSM contained 83 compounds, whereas JPT contained 84 compounds. All doses of the extracts exhibited a significant suppression (p < 0.05) of the parasite compared to the negative control in a four-day test. The maximum activities were observed at 600 mg/kg dose with 67.02% suppression for TSM and 79.34% for JPT, followed by 400 mg/kg dose (57.63% for TSM and 64.79% for JPT) and then 200 mg/kg dose (52.35% for TSM and 54.46% for JPT). In addition, there were no significant differences (p < 0.05) in the RBC, MCV, and MCH levels of mice receiving JPT extract compared to the uninfected control. The WBC level of mice receiving 400 and 600 mg/kg of TSM, and 200 and 400 mg/kg of JPT, was significantly (p < 0.05) lower than the infected control, and the extracts did not significantly prevent the loss of platelets. For the acute toxicity test, there were no signs of toxicity or deaths in mice, and there were no differences in the histology, weight, or enzyme biochemistry of the liver and kidney between the extract and vehicle groups. However, the platelet count in the extract-treated mice was significantly higher than that in the control group. In conclusion, this study suggests that aqueous extracts of TSM and JPT have potent antimalarial activities and could be promising as new candidates for antimalarial drug development.
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Dermatomyositis (DM) is an autoimmune disease that is classified as a type of idiopathic inflammatory myopathy, which affects human skin and muscles. The most common clinical symptoms of DM are muscle weakness, rash, and scaly skin. There is currently no cure for DM. Genetic factors are known to play a pivotal role in DM progression, but few have utilized this information geared toward drug discovery for the disease. Here, we exploited genomic variation associated with DM and integrated this with genomic and bioinformatic analyses to discover new drug candidates. We first integrated genome-wide association study (GWAS) and phenome-wide association study (PheWAS) catalogs to identify disease-associated genomic variants. Biological risk genes for DM were prioritized using strict functional annotations, further identifying candidate drug targets based on druggable genes from databases. Overall, we analyzed 1239 variants associated with DM and obtained 43 drugs that overlapped with 13 target genes (JAK2, FCGR3B, CD4, CD3D, LCK, CD2, CD3E, FCGR3A, CD3G, IFNAR1, CD247, JAK1, IFNAR2). Six drugs clinically investigated for DM, as well as eight drugs under pre-clinical investigation, are candidate drugs that could be repositioned for DM. Further studies are necessary to validate potential biomarkers for novel DM therapeutics from our findings.
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Zingiber and Alpinia species (family: Zingiberaceae) are popularly used in food as spices and flavoring agents and in ethnomedicine to heal numerous diseases, including immune-related disorders. However, their ethnomedicinal uses have not been sufficiently supported by scientific investigations. Numerous studies on the modulating effects of plants and their bioactive compounds on the different steps of the immune system have been documented. This review aimed to highlight up-to-date research findings and critically analyze the modulatory effects and mechanisms of the extracts and secondary compounds of several Zingiber and Alpinia species, namely, Zingiber officinale Roscoe, Z. cassumunar Roxb., Z. zerumbet (L.) Roscoe ex Sm., Alpinia galanga Linn., A. conchigera Griff, A. katsumadai Hayata, A. oxyphylla Miq., A. officinarum Hance, A. zerumbet (Pers.) Burtt. et Smith, and A. purpurata (Viell.) K. Schum. on the immune system, particularly via the inflammation-related signaling pathways. The immunomodulating activities of the crude extracts of the plants have been reported, but the constituents contributing to the activities have mostly not been identified. Among the extracts, Z. officinale extracts were the most investigated for their in vitro, in vivo, and clinical effects on the immune system. Among the bioactive metabolites, 6-, 8-, and 10-gingerols, 6-shogaol, and zerumbone from Zingiber species and cardamomin, 1'-acetoxychavicol acetate, yakuchinone, rutin, 1,8-cineole, and lectin from Alpinia species have demonstrated strong immunomodulating effects. More experimental studies using cell and animal models of immune-related disorders are necessary to further understand the underlying mechanisms, together with elaborate preclinical pharmacokinetics, pharmacodynamics, bioavailability, and toxicity studies. Many of these extracts and secondary metabolites are potential candidates for clinical development in immunomodulating agents or functional foods to prevent and treat chronic inflammatory disorders.
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Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose existing drugs to treat DFUs based on transcriptomics analysis. A total of 31 differentially expressed genes (DEGs) were identified and used to prioritize the biological risk genes for DFUs. Further investigation using the database DGIdb revealed 12 druggable target genes among 50 biological DFU risk genes, corresponding to 31 drugs. Interestingly, we highlighted that two drugs (urokinase and lidocaine) are under clinical investigation for DFU and 29 drugs are potential candidates to be repurposed for DFU therapy. The top 5 potential biomarkers for DFU from our findings are IL6ST, CXCL9, IL1R1, CXCR2, and IL10. This study highlights IL1R1 as a highly promising biomarker for DFU due to its high systemic score in functional annotations, that can be targeted with an existing drug, Anakinra. Our study proposed that the integration of transcriptomic and bioinformatic-based approaches has the potential to drive drug repurposing for DFUs. Further research will further examine the mechanisms by which targeting IL1R1 can be used to treat DFU.
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Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/tratamiento farmacológico , Pie Diabético/genética , Reposicionamiento de Medicamentos , TranscriptomaRESUMEN
Biofilm-associated infections are a critical element in infectious diseases and play an important role in antibiotic resistance. Biosynthesized gold nanoparticles (AuNPs) using ethanolic extract of Musa sapientum unripe fruit were performed. The nanoparticles demonstrated an absorption peak at 554 nm with particle sizes ranging from 5.45 to 104.44 nm. High negative zeta potential value of -33.97 mV confirmed the high stability of AuNPs. The presence of bioconstituents responsible for capping and stabilization was indicated by intensity changes of several peaks from Fourier-transform infrared spectroscopy analysis. The minimum inhibitory concentrations (MIC) of the biosynthesized AuNPs against important pathogens ranged from 10 to 40 µg mL-1 . Synthesized nanoparticles at 0.062 to 0.5 × MIC significantly inhibited biofilm formation in all the tested microorganisms (p < 0.05). Scanning electron microscopy and confocal scanning laser microscopy images clearly illustrated in disruption and architectural changes of microbial biofilms at sub-MIC of biosynthesized AuNPs. Excellent antioxidant and antityrosinase activities of AuNPs were observed. The biosynthesized AuNPs at 20 µg mL-1 significantly inhibited nitric oxide production by 93% in lipopolysaccharide-stimulated RAW 264.7 cells, compared with control (p < 0.05). The biosynthesized AuNPs at 0.6 to 40 µg mL-1 demonstrated no toxic effects on L929 fibroblast cells.
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BACKGROUND: Kheaw Hom remedy is a traditional Thai medicine used to treat fever. Some plants used in the Kheaw Hom remedy show promising in vitro antimalarial activity. This study prepared novel formulations of plants from the Kheaw Hom remedy and evaluated their antimalarial and toxicological activities. METHODS: Seven new formulations were prepared by combining at least three herbs of six selected plants from the Kheaw Hom remedy, namely Mammea siamensis Kosterm., Mesua ferrea L., Dracaena loureiroi Gagnep., Pogostemon cablin (Blanco) Benth., Kaempferia galanga L, and Eupatorium stoechadosmum Hance. In vitro antimalarial activities of each formulation's aqueous and ethanolic extracts were evaluated using the parasite lactate dehydrogenase (pLDH) assay. Cytotoxicity in Vero and HepG2 cells was assessed using the MTT assay. An extract with good antimalarial potency and selectivity index (SI) was selected for in vivo antimalarial activity using Peter's 4-day suppressive test and acute oral toxicity test in mice. In addition, bioactive compounds were identified using Gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Among the seven new formulations, ethanolic extracts of CPF-1 (Formulation 1) showed the highest activity with an IC50 value of 1.32 ± 0.66 µg/ml, followed by ethanolic extracts of Formulation 4 and Formulation 6 with an IC50 value of 1.52 ± 0.28 µg/ml and 2.48 ± 0.34 µg/ml, respectively. The highest SI values were obtained for the ethanolic extract of CPF-1 that was selected to confirm its in vivo antimalarial activity and toxicity. The results demonstrated a significant dose-dependent reduction in parasitemia. Maximum suppressive effect of the extract (72.01%) was observed at the highest dose administered (600 mg/kg). No significant toxicity was observed after the administration of 2000 mg/kg. Using GC-MS analysis, the most abundant compound in the ethanolic extract of CPF-1 was ethyl p-methoxycinnamate (14.32%), followed by 2-propenoic acid, 3-phenyl-, ethyl ester, (E)- (2.50%), and pentadecane (1.85%). CONCLUSION: The ethanolic extract of CPF-1 showed promising in vitro and in vivo antimalarial efficacy, with no toxic effects at a dose of 2000 mg/kg, suggesting that the ethanolic extract of CPF-1 may serves as a new herbal formulation for the treatment of malaria. Additional research is required for safety and clinical pharmacology studies.
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Antimaláricos , Malaria , Animales , Ratones , Antimaláricos/toxicidad , Extractos Vegetales/química , Malaria/tratamiento farmacológico , Malaria/parasitología , Medicina TradicionalRESUMEN
Foodborne pathogens may cause foodborne illness, which is among the major health problems worldwide. Since the therapeutic options for the treatment of the disease are becoming limited as a result of antibacterial resistance, there is an increasing interest to search for new alternatives of antibacterial. Bioactive essential oils from Curcuma sp become potential sources of novel antibacterial substances. The antibacterial activity of Curcuma heyneana essential oil (CHEO) was evaluated against Escherichia coli, Salmonella typhi, Shigella sonnei, and Bacillus cereus. The principal constituents of CHEO are ar-turmerone, ß-turmerone, α-zingiberene, α-terpinolene, 1,8-cineole, and camphor. CHEO exhibited the strongest antibacterial activity against E. coli with a MIC of 3.9â µg/mL, which is comparable to that of tetracycline. The combination of CHEO (0.97â µg/mL) and tetracycline (0.48â µg/mL) produced a synergistic effect with a FICI of 0.37. Time-kill assay confirmed that CHEO enhanced the activity of tetracycline. The mixture disrupted membrane permeability of E. coli and induced cell death. CHEO at MIC of 3.9 and 6.8â µg/mL significantly reduced the formation of biofilm in E. coli. The findings suggest that CHEO has the potential to be an alternative source of antibacterial agents against foodborne pathogens, particularly E. coli.
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Multidrug-resistant bacteria have raised global concern about the inability to fight deadly infectious diseases. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the most common resistant bacteria that are causing hospital infections. The present study was undertaken to investigate the synergistic antibacterial effect of the ethyl acetate fraction of Vernonia amygdalina Delile leaves (EAFVA) with tetracycline against the clinical isolates MRSA and P. aeruginosa. Microdilution was used to establish the minimum inhibitory concentration (MIC). A checkerboard assay was conducted for the interaction effect. Bacteriolysis, staphyloxanthin, and a swarming motility assay were also investigated. EAFVA exhibited antibacterial activity against MRSA and P. aeruginosa with a MIC value of 125 µg/mL. Tetracycline showed antibacterial activity against MRSA and P. aeruginosa with MIC values of 15.62 and 31.25 µg/mL, respectively. The interaction between EAFVA and tetracycline showed a synergistic effect against MRSA and P. aeruginosa with a Fractional Inhibitory Concentration Index (FICI) of 0.375 and 0.31, respectively. The combination of EAFVA and tetracycline induced the alteration of MRSA and P. aeruginosa, leading to cell death. Moreover, EAFVA also inhibited the quorum sensing system in MRSA and P. aeruginosa. The results revealed that EAFVA enhanced the antibacterial activity of tetracycline against MRSA and P. aeruginosa. This extract also regulated the quorum sensing system in the tested bacteria.
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BACKGROUND: Drug resistance exists in almost all antimalarial drugs currently in use, leading to an urgent need to identify new antimalarial drugs. Medicinal plant use is an alternative approach to antimalarial chemotherapy. This study aimed to explore potent medicinal plants from Prabchompoothaweep remedy for antimalarial drug development. METHODS: Forty-eight crude extracts from Prabchompoothaweep remedy and its 23 plants ingredients were investigated in vitro for antimalarial properties using Plasmodium lactate dehydrogenase (pLDH) enzyme against Plasmodium falciparum K1 strain and toxicity effects were evaluated in Vero cells. The plant with promising antimalarial activity was further investigated using gas chromatography-mass spectrometry (GC-MS) to identify phytochemicals. Antimalarial activity in mice was evaluated using a four-day suppressive test against Plasmodium berghei ANKA at dose of 200, 400, and 600 mg/kg body weight, and acute toxicity was analyzed. RESULTS: Of the 48 crude extracts, 13 (27.08%) showed high antimalarial activity against the K1 strain of P. falciparum (IC50 < 10 µg/ml) and 9 extracts (18.75%) were moderately active (IC50 = 11-50 µg/ml). Additionally, the ethanolic extract of Prabchompoothaweep remedy showed moderate antimalarial activity against the K1 strain of P. falciparum (IC50 = 14.13 µg/ml). Based on in vitro antimalarial and toxicity results, antimalarial activity of the aqueous fruit extract of Terminalia arjuna (IC50 = 4.05 µg/ml and CC50 = 219.6 µg/ml) was further studied in mice. GC-MS analysis of T. arjuna extract identified 22 compounds. The most abundant compounds were pyrogallol, gallic acid, shikimic acid, oleamide, 5-hydroxymethylfurfural, 1,1-diethoxy-ethane, quinic acid, and furfural. Analysis of the four-day suppressive test indicated that T. arjuna extract at dose of 200, 400, and 600 mg/kg body weight significantly suppressed the Plasmodium parasites by 28.33, 45.77, and 67.95%, respectively. In the acute toxicity study, T. arjuna extract was non-toxic at 2000 mg/kg body weight. CONCLUSIONS: The aqueous fruit extract of T. arjuna exerts antimalarial activity against Plasmodium parasites found in humans (P. falciparum K1) and mice (P. berghei ANKA). Acute toxicity studies showed that T. arjuna extract did not show any lethality or adverse effects up to a dose of 2000 mg/kg.
Asunto(s)
Antimaláricos , Malaria Falciparum , Malaria , Plantas Medicinales , Humanos , Chlorocebus aethiops , Animales , Ratones , Antimaláricos/toxicidad , Antimaláricos/química , Plantas Medicinales/química , Malaria/tratamiento farmacológico , Malaria/parasitología , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Células Vero , Malaria Falciparum/tratamiento farmacológico , Peso CorporalRESUMEN
The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.