Antibacterial and antibiofilm efficacy of Solanum lasiocarpum root extract synthesized silver/silver chloride nanoparticles against Staphylococcus haemolyticus associated with bovine mastitis.

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.

Mechanistic insights into anti-inflammatory and immunosuppressive effects of plant secondary metabolites and their therapeutic potential for rheumatoid arthritis.

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.

A synergistic interaction between Citrus hystrix peel essential oil and tetracycline and evaluation of their antibacterial mechanism of action in vitro and in silico against Escherichia coli.

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.

Antibacterial, bacteriolytic, antibiofilm, and synergistic effects of the peel oils of Citrus microcarpa and Citrus x amblycarpa with tetracycline against foodborne Escherichia coli.

Citrus essential oils (EOs) have shown significant antibacterial activity. The present study was undertaken to evaluate the antibacterial activity of the peel oils of Citrus microcarpa and C. x amblycarpa against Escherichia coli. The minimum inhibition concentration (MIC) was determined by using the broth microdilution assay. The checkerboard method was used to identify synergistic effects of the EOs with tetracycline, while bacteriolysis was assessed by calculating the optical density of the bacterial supernatant, crystal violet assay was used to assess their antibiofilm. Ethidium bromide accumulation test was employed to assess efflux pump inhibition. Electron microscope analysis was performed to observe its morphological changes. The EOs of C. microcarpa and C. x amblycarpa were found to contain D-limonene major compound at 55.78% and 46.7%, respectively. Citrus microcarpa EOs exhibited moderate antibacterial against E. coli with a MIC value of 200 µg/mL. The combination of C. microcarpa oil (7.8 µg/mL) and tetracycline (62.5 µg/mL) exhibited a synergy with FICI of 0.5. This combination inhibited biofilm formation and disrupt bacterial cell membranes. Citrus microcarpa EOs blocked the efflux pumps in E. coli. Citrus microcarpa EOs demonstrated promising antibacterial activity, which can be further explored for the development of drugs to combat E. coli.

Antiviral effects of phytochemicals against severe acute respiratory syndrome coronavirus 2 and their mechanisms of action: A review.

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.

Essential Oil of Zingiber cassumunar Roxb. and Zingiber officinale Rosc.: A Comparative Study on Chemical Constituents, Antibacterial Activity, Biofilm Formation, and Inhibition of Pseudomonas aeruginosa Quorum Sensing System.

Pseudomonas aeruginosa can regulate its pathogenicity via quorum sensing (QS) system. Zingiber cassumunar and Z. officinale have been used for the treatment of infectious diseases. The study aimed to evaluate and compare the chemical constituents, antibacterial, and QS inhibitor of Z. cassumunar essential oils (ZCEO) and Z. officinale essential oils (ZOEO). The chemical constituent was analysed using GC/MS. Broth microdilution and spectrophotometry analysis were used to evaluate their antibacterial and QS inhibitor activities. The main constituent of ZOEO with percent composition above 6 % (α-curcumene, α-zingiberene, ß-sesquiphellandrene, and ß-bisabolene, α-citral, and α-farnesene) were exist in a very minimal percentage less than 0.7 % in Z. cassumunar. All major components of ZCEO with percentages higher than 5 % (terpinen-4-ol, sabinene, γ-terpinene) were present in low proportion (<1.18 %) in Z. officinale. ZCEO demonstrated moderate antibacterial activity against P. aeruginosa. The combination of ZCEO and tetracycline showed a synergistic effect (FICI of 0.5). ZCEO exhibited strong activity in inhibiting biofilm formation. ZCEO at 1 / 2 ${{ 1/2 }}$ MIC (62.5 µg/mL) was able to reduce pyoverdine, pyocyanin, and proteolytic activity. This is the first report on the activity of ZCEO in the inhibition of P. aeruginosa QS system and it may be used to control the pathogenicity of P. aeruginosa.

Hepatoprotective and toxicological evaluation of tropical Sargassum polycystum C. Agardh collected from Sumbawa coast Indonesia, against carbon tetrachloride-induced liver damage in rats.

Pharmacological activities of seaweed, including its antioxidant effect, have been demonstrated and can protect macromolecules from xenobiotic-induced damage. Understanding the potency of seaweed as a hepatoprotection and its toxicity remains underexplored. The aims of this study were to investigate the antioxidant and hepatoprotective activity, as well as the toxicological potencies of S. polycystum ethyl acetate extract against carbon tetrachloride-induced liver damage in rats. Total phenolic content and total flavonoid contents were quantified using standard spectroscopy-based methods. The antioxidant activity was measured using 1,1-Diphenyl- 2-picryl Hydrazil scavenging radical, while the composition of compounds was identified by LCMS/MS. After seven days of post-administrated rats with S. polycystum ethyl acetate extract, the serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) levels were tested. Total phenolic content, total flavonoid content and IC50 of S. polycystum ethyl acetate extract were 1.28±0.04 of GAE/g, 13.32±0.48 QE/g and 744.726µg/mL, respectively. S. polycystum ethyl acetate extract 150mg/kg BW provides a hepatoprotective effect with a significant improvement in the levels of SGOT (134.845 U/l±9.645) and SGPT (60.238 U/l ± 9.645) (p<0.05). S. polycystum ethyl acetate extract potentially protected the damage induced by CCl4 in the rat's liver at a certain concentration, while a higher extract concentration requires further examination.

Development of starch/chitosan expandable films as a gastroretentive carrier for ginger extract-loaded solid dispersion.

Gastroretentive expandable films were developed to provide controlled release of ginger extract (GE) for treatment of gastric diseases. The dosage form consisted of ginger extract solid dispersion (GE-SD) loaded in a starch/chitosan composite film, which was subsequently folded and inserted into a hard gelatin capsule. GE-SD was prepared by solvent evaporation using an optimum weight ratio of 1:1 for GE and PVP K30. Expandable films containing GE-SD were prepared by solvent casting combinations of chitosan and either rice-, glutinous rice - or pregelatinized maize starch with glycerin incorporated as a plasticizer. The optimized film formulation prepared from glutinous rice starch, exhibited tensile strength of 5.4 N/cm2 and high expansion in simulated gastric fluid (SGF), resulting in a 2.8-fold increase in area. The films resulted in sustained release of up to 90% of the content of 6-gingerol during 8 h exposure to SGF. Furthermore, the 6-gingerol released from the film displayed dose-dependent cytotoxic activity against AGS human gastric adenocarcinoma cells and anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells.

Investigation of HIV-1 Viral Protein R Inhibitory Activities of Twelve Thai Medicinal Plants and Their Commercially Available Major Constituents.

Viral protein R (Vpr) is an accessory protein in Human immunodeficiency virus-1 (HIV-1) and has been suggested as an attractive target for HIV disease treatment. Investigations of the ethanolic extracts of twelve Thai herbs revealed that the extracts of the Punica granatum fruits, the Centella asiatica aerials, the Citrus hystrix fruit peels, the Caesalpinia sappan heartwoods, the Piper betel leaves, the Alpinia galangal rhizomes, the Senna tora seeds, the Zingiber cassumunar rhizomes, the Rhinacanthus nasutus leaves, and the Plumbago indica roots exhibited the anti-Vpr activity in HeLa cells harboring the TREx plasmid encoding full-length Vpr (TREx-HeLa-Vpr cells). Moreover, the investigation of the selected main constituents in Punica granatum, Centella asiatica, A. galangal, and Caesalpinia sappan indicated that punicalagin, asiaticoside, ellagic acid, madecassic acid, madecassoside, zingerone, brazilin, and asiatic acid possessed anti-Vpr activities at the 10 µM concentration. Among the tested extracts and compounds, the extracts from Centella asiatica and Citrus hystrix and the compounds, punicalagin and asiaticoside, showed the most potent anti-Vpr activities without any cytotoxicity, respectively.

Synergistic effect of artocarpin on antibacterial activity of some antibiotics against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

CONTEXT: Antibacterial resistance has dramatically increased and resulted in serious health problems worldwide. One appealing strategy to overcome this resistance problem is the use of combinations of antibacterial compounds to increase their potency. OBJECTIVE: The objective of this study is to determine the synergistic effects of artocarpin for ampicillin, norfloxacin, and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA) as well as the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli. MATERIALS AND METHODS: A broth microdilution method (1.95-250 µg/mL) was used to determine the minimum inhibitory concentration (MIC) of artocarpin and the antibiotics. Any synergistic effects were evaluated at their own MIC using the checkerboard method and a time-kill assay at 37 °C for 24 h. RESULTS AND DISCUSSION: Artocarpin showed antibacterial activity against MRSA and E. coli with an MIC value of 62.5 µg/mL, and against P. aeruginosa with an MIC value of 250 µg/mL. The interaction of artocarpin with all tested antibiotics produced synergistic effects against MRSA with a fractional inhibitory concentration index (FICI) of 0.15-0.37. In addition, a combination of artocarpin and norfloxacin showed a synergistic effect against E. coli with an FICI value of 0.37, while the combinations of artocarpin and tetracycline as well as artocarpin and norfloxacin exhibited synergy interactions against P. aeruginosa with FICI values of 0.24 and 0.37, respectively. Time-kill assays indicated that artocarpin enhanced the antimicrobial activities of tetracycline, ampicillin, and norfloxacin against MRSA as well as Gram-negative bacteria.

Antibacterial assay-guided isolation of active compounds from Artocarpus heterophyllus heartwoods.

CONTEXT: Preparations from Artocarpus heterophyllus Lam. (Moraceae) heartwoods are used in the traditional folk medicine for the treatment of inflammation, malarial fever, and to prevent bacterial and fungal infections. OBJECTIVE: The objective of this study was to isolate pure antibacterial compounds from A. heterophyllus heartwoods. MATERIALS AND METHODS: The dried and powdered A. heterophyllus heartwoods were successively extracted with the following solvents: hexane, ethyl acetate, and methanol. Each of the extracts was screened for their antibacterial activities using a disc diffusion method (10 mg/disc). Their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using a broth microdilution method. The extract that showed the strongest antibacterial activities was fractionated to isolate the active compounds by an antibacterial assay-guided isolation process. RESULTS AND DISCUSSION: The ethyl acetate extract exhibited the strongest antibacterial activities against Streptococcus mutans, S. pyogenes, and Bacillus subtilis with MIC values of 78, 39, and 9.8 µg/mL, respectively. Based on an antibacterial assay-guided isolation, four antibacterial compounds: cycloartocarpin (1), artocarpin (2), artocarpanone (3), and cyanomaclurin (4) were purified. Among these isolated compounds, artocarpin exhibited the strongest antibacterial activity against Gram-positive bacteria, including S. mutans, S. pyogenes, B. subtilis, Staphylococcus aureus, and S. epidermidis with MICs of 4.4, 4.4, 17.8, 8.9, and 8.9 µM, respectively, and MBCs of 8.9, 8.9, 17.8, 8.9, and 8.9 µM, respectively, while artocarpanone showed the strongest activity against Escherichia coli, a Gram-negative bacteria with MIC and MBC values of 12.9 and 25.8 µM, respectively. Only artocarpin showed inhibitory activity against Pseudomonas aeruginosa with an MIC of 286.4 µM.

Combined effect of brazilin-rich extract and lawsone methyl ether against infection-causing bacteria.

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.

Assessment of antimalarial activity of crude extract of Chan-Ta-Lee-La and Pra-Sa-Chan-Dang formulations and their plant ingredients for new drug candidates of malaria treatment: In vitro and in vivo experiments.

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.

Antiplasmodial potential of isolated xanthones from Mesua ferrea Linn. roots: an in vitro and in silico molecular docking and pharmacokinetics study.

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.

In vivo antimalarial effect of 1-hydroxy-5,6,7-trimethoxyxanthone isolated from Mammea siamensis T. Anders. flowers: pharmacokinetic and acute toxicity studies.

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.

Leveraging Genomic and Bioinformatic Analysis to Enhance Drug Repositioning for Dermatomyositis.

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.

Efficacy of artesunate combined with Atractylodes lancea or Prabchompoothaweep remedy extracts as adjunctive therapy for the treatment of cerebral malaria.

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.

Phytochemical Analysis, Antimalarial Properties, and Acute Toxicity of Aqueous Extracts of Trisamo and Jatu-Phala-Tiga Recipes.

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.

Antimalarial efficacy and toxicological assessment of medicinal plant ingredients of Prabchompoothaweep remedy as a candidate for antimalarial drug development.

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.

Control of biomaterial-associated infections through biofabrication of gold nanoparticles using Musa sapientum extract.

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.