Search

Foodborne illness caused by pathogens has been a major health problem. Antibacterial resistance renders therapeutic options for treating the condition more limited, hence there is a growing interest in finding novel antibacterial alternatives. Zanthoxylum acanthopodium (Rutaceae) essential oil (ZAEO) has a substantial potential to suppress the growth of bacterial infections. This study was conducted to evaluate antibacterial activity of ZAEO against four species of foodborne pathogens that cause potential infections. The checkerboard assay was used to identify synergistic effect of ZAEO and tetracycline, while bacteriolysis test was applied to evaluate the ability of ZAEO releasing material genetics of bacteria, inhibiting biofilm formation, and suppressing efflux pump. The oils of Z. acanthopodium was evaluated and showed that the highest constituents were limonene and geranyl acetate at 47.13 % and 23.84 %, respectively. These oils have the strongest ability to inhibit Escherichia coli compared to other pathogens with MIC value of 62.5 μg/mL. ZAEO and tetracycline also presented a synergistic effect against E. coli with FICI value of 0.37. Moreover, this combination of ZAEO and antibiotic shown as potential antibacterial agent by several mechanisms such as, decreasing biofilm formation, releasing ions, rupturing membrane cells, and suppressing the efflux pump of E. coli. It can be concluded that ZAEO and tetracycline presented a promising antibacterial activity, which can be explored further to develops antibacterial agents against foodborne pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quercetin is abundant in plants and has notable pharmacological properties for skin health. This review aims to comprehensively evaluate the effects of quercetin on skin-related issues, adhering to the PRISMA guidelines and analyzing studies from ScienceDirect, Web of Science, Scopus, and PubMed. Of the 1,398 studies identified, 65 studies met the criteria for meta-analysis. The meta-analysis indicated that quercetin had powerful antioxidant properties, protecting against oxidative stress by significantly lowering levels of MDA (Z-score, 2.51), ROS (Z-score, 3.81), and LPO (Z-score, 4.46), and enhancing enzymes of GSH (Z-score, 5.46), CAT (Z-score, 5.20), and SOD (Z-score, 4.37). Quercetin acted as an anti-inflammatory by significantly suppressing protein regulators such as NF-κβ, AP-1, and MAPKs (ERK and JNK), cytokines of TNFα, IL-6, IL-1β, IL-8, and MCP-1, and enzymes of COX-2, iNOS, and MPO, while upregulating the cytokine IL-10. Additionally, quercetin significantly suppressed IL-4 (Z-score, 3.16) and IFNγ (Z-score, 3.76) cytokines involved in chronic inflammation of atopic dermatitis. Quercetin also supported wound healing by significantly decreasing inflammatory cells (Z-score, 5.60) and enhancing fibroblast distribution (Z-score, 5.98), epithelialization (Z-score, 8.57), collagen production (Z-score, 4.20), and angiogenesis factors of MVD (Z-score, 5.66) and VEGF (Z-score, 3.86). Furthermore, quercetin significantly inhibited tyrosinase activity (Z-score, 1.95), resulting in a significantly reduced melanin content (Z-score, 2.56). A significant reduction in DNA damage (Z-score, 3.27), melanoma cell viability (Z-score, 2.97), and tumor formation was also observed to ensure the promising activity of quercetin for skin issues. This review highlights quercetin's potential as a multifaceted agent in skin care and treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The increased resistance of Plasmodium falciparum to artemisinin and its partner drugs poses a serious challenge to global malaria control and elimination programs. This study aimed to investigate the therapeutic potential of Mesua ferrea Linn., a medicinal plant, as a source for novel antimalarial compounds. In this study, we conducted in vitro assays to evaluate the antimalarial activity and cytotoxicity of crude extracts derived from M. ferrea L. leaves and branches. Subsequently, the most promising extracts were subjected to assessments of their antimalarial efficacy and acute oral toxicity tests in mouse models. Furthermore, selected crude extracts underwent gas chromatography-mass spectrometry (GC-MS) analysis to identify their phytochemical compositions. Our findings revealed that the ethanolic extract of M. ferrea L. branches (EMFB) exhibited high antimalarial activity, with an IC50 value of 4.54 μg/mL, closely followed by the ethanolic extract of M. ferrea L. leaves (EMFL), with an IC50 value of 6.76 μg/mL. Conversely, the aqueous extracts of M. ferrea L. branches (AMFB) and leaves (AMFL) exhibited weak and inactive activity, respectively. The selected extracts, EMFB and EMFL, demonstrated significant dose-dependent parasitemia suppression, reaching a maximum of 62.61% and 54.48% at 600 mg/kg body weight, respectively. Furthermore, the acute oral toxicity test indicated no observable toxicity at a dosage of 2,000 mg/kg body weight for both extracts. GC-MS analysis revealed abundant compounds in the EMFB, such as oleamide, cis-β-farnesene, alloaromadendrene, physcion, palmitic acid, 5-hydroxymethylfurfural, and 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, while the EMFL contained friedelin, friedelinol, betulin, β-caryophyllene, oleamide, and 5-hydroxymethylfurfural. Notably, both extracts shared several phytochemical compounds, including 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, 5-hydroxymethylfurfural, α-copaene, cyperene, β-caryophyllene, alloaromadendrene, palmitic acid, ethyl palmitate, and oleamide. Additionally, further study is needed to isolate and characterize these bioactive compounds from M. ferrea L. leaves and branches for their potential utilization as scaffolds in the development of novel antimalarial drugs., Competing Interests: The authors declare no competing interests regarding the publication of this study., (Copyright: © 2024 Konyanee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Development of novel inhibitors is necessary to counteract the rising prevalence of breast cancer (BC) in women in recent years, as evidenced by the side-effect profiles of a few clinically approved inhibitors. In this study, the usnic acid derivative (UA1) was synthesized due to the effectiveness of usnic acid (UA) against BC cell line. Furthermore, the structure of synthesized compound was determined using FT-IR, 1 H NMR, 13 C NMR, HSQC, and HMBC spectroscopic techniques. The anticancer potential of UA1 was assessed using the MTT assay on two different cell lines of BC including MCF7 and T47D. To ascertain the binding affinity and stability of the docking complex, further procedures included the in silico molecular docking, molecular dynamic simulation, principal component analysis, and binding free energy experiments. The cytotoxicity results show that the UA1 exhibits strong antitumor activities and comparable effects against BC cell lines with the IC 50 values of 9.21 µM for MCF7 cell and 14.8 µM for T47D cell, respectively, where the positive control cisplatin showed the IC 50 values of 8.95 µM for MCF7 cell and 10.9 µM for T47D cell. Additionally, the molecular docking results of UA1 showed that it interacts strongly into the active site of target protein. Molecular dynamics simulation results also revealed that the docking complex was formed stability with the RMSD and RMSF values of 0.50 nm and 0.19 nm, respectively. According to the PCA analysis, the target protein displays good conformational space behaviour when bound with UA1. Furthermore, the UA1 showed the free binding energy value of -18.52 kcal/mol with the target protein, which indicating that UA1 may prevent BC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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, β-turmerone, α-zingiberene, α-terpinolene, 1,8-cineole, and camphor. CHEO exhibited the strongest antibacterial activity against E. coli with a MIC of 3.9 µg/mL, which is comparable to that of tetracycline. The combination of CHEO (0.97 µg/mL) and tetracycline (0.48 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 6.8 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 ., Competing Interests: DECLARATION OF CONFLICTING INTERESTSThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 IC 50 being 19.93 µM. Additionally, there was no toxicity towards Vero cells (CC 50 = 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 LD 50 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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

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., (© 2024 John Wiley & Sons Ltd.)

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 (C max ) of 94.02 ng/mL, time to attain C max (T max ) 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., (© 2024. The Author(s).)

Methicillin-Resistant Staphylococcus Aureus (MRSA) is a worldwide major pathogenic bacteria that has emerged over the past three decades as the leading cause of nosocomial and community-acquired infections. Biosensors can provide rapid, sensitive, and selective detection of the presence and number of bacteria in various environments. Herein, a novel fluorescence nanoprobe was designed as a biosensor for MRSA detection using dye-incorporated silica nanoparticles (FSiNP). Based on the results of specific surface area analysis using the Brauner Emmett-Teller (BET) method, the surface area of the nanoparticles was obtained at 377.127 m 2 /g, and the X-ray diffraction (XRD) analysis confirmed that it was in the amorphous phase. Vancomycin, as the bioreceptor, was immobilized on the silica surface through a hydrosilylation reaction, generating the biosensing platform FSiNP-Van. Each modification step was corroborated by the Fourier Transform Infra-Red (FTIR) spectroscopy. The sensing principle was based on the fluorescence-quenching mechanism of FSiNP-Van at 515 nm obtaining a rapid response time of 20 min. The FSiNP-Van nanoprobe provided a wide linear concentration range of 10-10 6 CFU/mL with a limit of MRSA detection calculated at 1 CFU/mL. The fluorescent nanoprobe demonstrated here is expected to find applications in point-of-care (POC) diagnostics to detect the presence of MRSA bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chaniad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

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., (© 2023 Wiley-VCH GmbH.)

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-1β, 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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Arisara Phuwajaroanpong et al.)

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.

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuandani, Jantan, Haque, Rohani, Nugraha, Salim, Septama, Juwita, Khairunnisa, Nasution, Utami and Ibrahim.)

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., (© 2023. The Author(s).)

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.

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 IC 50 value of 1.32 ± 0.66 µg/ml, followed by ethanolic extracts of Formulation 4 and Formulation 6 with an IC 50 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., (© 2023. The Author(s).)

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., (© 2022 John Wiley & Sons Ltd.)

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  μ g/mL. Tetracycline showed antibacterial activity against MRSA and P. aeruginosa with MIC values of 15.62 and 31.25  μ g/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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Denny Satria et al.)

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 (IC 50  <  10 μg/ml) and 9 extracts (18.75%) were moderately active (IC 50  = 11-50 μg/ml). Additionally, the ethanolic extract of Prabchompoothaweep remedy showed moderate antimalarial activity against the K1 strain of P. falciparum (IC 50  = 14.13 μg/ml). Based on in vitro antimalarial and toxicity results, antimalarial activity of the aqueous fruit extract of Terminalia arjuna (IC 50  = 4.05 μg/ml and CC 50  = 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., (© 2023. The Author(s).)

This study evaluated the in vitro and in vivo antiplasmodial efficacy and toxicity of aqueous and ethanolic extracts from traditional recipes used in Thailand. The aqueous and ethanolic extracts of ten traditional recipes were tested for in vitro antiplasmodial activity (parasite lactate dehydrogenase assay), cytotoxicity (MTT assay), and hemolysis). Oxidant levels were measured using cell-permeable probe 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate fluorescent dye-based assays. The best candidate was chosen for testing in mouse models using 4-day suppressive and acute toxicity assays. An in vitro study showed that ethanolic extracts and three aqueous extracts exhibited antiplasmodial activity, with an IC 50 in the range of 2.8-15.5 µg/mL. All extracts showed high CC 50 values, except for ethanolic extracts from Benjakul, Benjalotiga, and Trikatuk in HepG2 and Benjalotiga and aqueous extract from Chan-tang-ha in a Vero cell. Based on the results of the in vitro antiplasmodial activity, an aqueous extract of Triphala was chosen for testing in mouse models. The aqueous extract of Triphala exhibited good antiplasmodial activity, was safe at an oral dose of 2 g/kg, and is a potential candidate as a new source for the development of antimalarial drugs.

Malaria remains a life-threatening health problem and encounters with the increasing of antimalarial drug resistance. Medicinal plants play a critical role in synthesizing novel and potent antimalarial agents. This study aimed to investigate the phytochemical constituents, antiplasmodial activity, and evaluate the toxicity of crude ethanolic extracts of Myristica fragrans, Atractylodes lancea, and Prabchompoothaweep remedy in a mouse model. The phytochemical constituents were characterized by liquid chromatography-mass spectrometry (LC-MS). Antimalarial efficacy against Plasmodium berghei was assessed using 4-day suppressive tests at doses of 200, 400, and 600 mg/kg body weight. Acute toxicity was assessed at a dose of 2000 mg/kg body weight of crude extracts. The 4-day suppression test showed that all crude extracts significantly suppressed parasitemia (p < 0.05) compared to the control group. Higher parasitemia suppression was observed both in Prabchompoothaweep remedy at a dose of 600 mg/kg (60.1%), and A. lancea at a dose of 400 mg/kg (60.1%). The acute oral toxicity test indicated that the LD50 values of all extracts were greater than 2000 mg/kg and that these extracts were not toxic in the mouse model. LC-MS analysis revealed several compounds in M. fragrans, A. lancea, and Prabchompoothaweep remedy. For quantitative analysis, 1,2,6,8-tetrahydroxy-3-methylanthraquinone 2-O-b-D-glucoside, chlorogenic acid, and 3-O-(beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranosyl) ethyl 3-hydroxyoctanoate were found in A. lancea, while (7′x,8′x)-4,7′-epoxy-3,8′-bilign-7-ene-3,5′-dimethoxy-4′,9,9′-triol, edulisin III, and tetra-hydrosappanone A trimethyl ether are found in M. fragrans. 6′-O-Formylmarmin was present in the Prabchompoothaweep remedy, followed by pterostilbene glycinate and amlaic acid. This study showed that the ethanolic extracts of A. lancea and Prabchompoothaweep remedy possess antimalarial activity against Plasmodium berghei. None of the extracts had toxic effects on liver and kidney function. Therefore, the ethanolic extract of A. lancea rhizome and Prabchompoothaweep remedy could be used as an alternative source of new antimalarial agents. Further studies are needed to determine the active compounds in both extracts.

Multidrug-resistant Acinetobacter baumannii (MDR A. baumannii ) is an emerging pathogen in the ESKAPE group. The global burden of antimicrobial resistance has led to renewed interest in alternative antimicrobial treatment strategies, including phage therapy. This study isolated and characterized a phage vB&#95;AbaM&#95; ABPW7 (vABPW7) specific to MDR A. baumannii . Morphological analysis showed that phage vABPW7 belongs to the Myoviridae family. Genome analysis showed that the phage DNA genome consists of 148,647 bp and that the phage is a member of the Phapecoctavirus genus of the order Caudovirales. A short latent period and a large burst size indicated that phage vABPW7 was a lytic phage that could potentially be used in phage therapy. Phage vABPW7 is a high-stability phage that has high lytic activity. Phage vABPW7 could effectively reduce biofilm formation and remove preformed biofilm. The utility of phage vABPW7 was investigated in a human A549 alveolar epithelial cell culture model. Phage vABPW7 was not cytotoxic to A549 cells, and the phage could significantly reduce planktonic MDR A. baumannii and MDR A. baumannii adhesion on A549 cells without cytotoxicity. This study suggests that phage vABPW7 has the potential to be developed further as a new antimicrobial agent against MDR A. baumannii .

The Kheaw Hom remedy is a traditional Thai medicine widely used to treat fevers. Some plant ingredients in this remedy have been investigated for their antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. However, there have been no reports on the antimalarial activities of the medicinal plants in this remedy. Therefore, this study focuses on identifying potential antimalarial drug candidates from the medicinal plant ingredients of the Kheaw Hom remedy. Eighteen plants from the Kheaw Hom remedy were extracted using distilled water and ethanol. All extracts were investigated for their in vitro antimalarial activity and cytotoxicity. An extract that exhibited good in vitro antimalarial activity and low toxicity was selected for further investigation by using Peter’s 4-day suppressive test and an acute oral toxicity evaluation in mice. Based on the in vitro antimalarial activity and cytotoxicity studies, the ethanolic extract of Globba malaccensis rhizomes showed promising antimalarial activity against the Plasmodium falciparum K1 strain (IC50 = 1.50 µg/mL) with less toxicity to Vero cells (CC50 of >80 µg/mL). This extract exhibited a significant dose-dependent reduction in parasitemia in P. berghei-infected mice. The maximum suppressive effect of this extract (60.53%) was observed at the highest dose administered (600 mg/kg). In a single-dose acute toxicity test, the animals treated at 2000 mg/kg died within 48 h after extract administration. In conclusion, our study indicates that the ethanolic extract of G. malaccensis rhizomes exhibited in vitro and in vivo antimalarial activities, which could serve as a promising starting point for antimalarial drug.

Scopoletin, also known as 6-methoxy-7 hydroxycoumarin, is one of the naturally occurring coumarin commonly found in many edible plants and plays an important role in human health. Despite the various potential pharmacological properties, the biosynthesis process, method of extraction, and mechanism of action on this compound have not been documented well. In this current review, the biosynthesis pathway, distribution of scopoletin in the plant kingdom, and extraction techniques are elaborated. The in vitro , in vivo , and in silico pharmacological studies are also discussed on antioxidant, antimicrobial, anticancer, anti-inflammation, and neuroprotective aspects of scopoletin. This study may help to understand the benefit of scopoletin containing plants and would be beneficial for the prevention and treatment of diseases., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Scopoletin is regarded as a major constituent of noni (Morinda citrifolia L), which contributes to the antioxidative, anti-inflammatory, immunomodulatory, and hepatoprotective properties in noni. It is also suggested as a marker for identification and quality control of noni and its derivative products. With the increasing interest in noni due to its health benefits and therapeutic effects, it is important to establish a reliable extraction and analysis method to determine scopoletin content in noni samples. The present study proposes the use of accelerated solvent extraction (ASE) to extract scopoletin from noni, followed by detection using HPLC-DAD for rapid identification and quantification of scopoletin. The optimum operating conditions of ASE were investigated using response surface methodology (RSM), using a three factors central composite design. It was found that the optimum scopoletin yield was achieved by performing the extraction at an elevated temperature of 60 °C for 12 min, using ethanol as extraction solvent with solid to solvent ratio of 1:30 (w/v). The analytical method validation was carried out under optimum conditions. The results indicate that the proposed ASE-HPLC-DAD method was adequately sensitive for the quantification of scopoletin in extracts with limit of detection of 0.17 μg/g. The presented method also exhibits excellent linearity from 0.54 to 120.10 μg/g with R 2 0.9995, high precision with RSD lower than 2% for intra-day and inter-day replication, and good recovery (99.88%). The established method was also successfully applied for scopoletin determination in noni product samples. The developed method provides a rapid and reliable method for the identification and quantification of scopoletin in noni samples that is suitable for routine procedures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Failure in the prevention of cross-transmission from contaminated gloves has been recognized as an important factor that contributes to the spread of several healthcare-associated infections. Ex situ coating process with silver nanoparticles (AgNPs) using Eucalyptus citriodora ethanolic leaf extract as reducing and capping agents to coat glove surfaces has been developed to prevent this mode of transmission. Elemental analysis of coated gloves showed 24.8 Wt% silver densely adhere on the surface. The coated gloves fully eradicated important hospital-acquired pathogens including Gram-positive bacteria, Gram-negative bacteria, and yeasts within 1 h. The coated gloves showed significant reduction, an average of five logs when tested against all standard strains and most clinical isolates (p < 0.01). Following prolonged exposure, the coating significantly reduced the numbers of most adhered pathogenic species, compared with uncoated gloves (p < 0.0001). AgNPs-coated gloves reduced microbial adhesion of mixed-species biofilms. A series of contamination and transmission assays demonstrated no transmission of viable organisms. Biocompatibility analysis confirmed high viability of HaCaT and L929 cells at all concentrations of AgNPs tested. The coated gloves were non-toxic with direct contact with L929 cells. The highly efficacious AgNPs-coated gloves potentially provide additional protection against transmission of healthcare-associated infections., (© 2021 Wiley-VCH GmbH.)

The high failure rate of the reductionist approach to discover effective and safe drugs to treat chronic inflammatory diseases has led scientists to seek alternative ways. Recently, targeting cell signaling pathways has been utilized as an innovative approach to discover drug leads from natural products. Cell signaling mechanisms have been identified playing key role in diverse diseases by inducing proliferation, cell survival and apoptosis. Phytochemicals are known to be able to modulate the cellular and molecular networks which are associated to chronic diseases including cancer-associated inflammation. In this review, the roles of dietary polyphenols (apigenin, kaempferol, quercetin, curcumin, genistein, isoliquiritigenin, resveratrol and gallic acid) in modulating multiple inflammation-associated cell signaling networks are deliberated. Scientific databases on suppressive effects of the polyphenols on chronic inflammation via modulation of the pathways especially in the recent five years are gathered and critically analyzed. The polyphenols are able to modulate several inflammation-associated cell signaling pathways, namely nuclear factor-kappa β, mitogen activated protein kinases, Wnt/β-catenin and phosphatidylinositol 3-kinase and protein kinase B via selective actions on various components of the networks. The suppressive effects of the polyphenols on the multiple cell signaling pathways reveal their potential use in prevention and treatment of chronic inflammatory disorders. Understanding the mechanistic effects involved in modulation of the signaling pathways by the polyphenols is necessary for lead identification and development of future functional foods for prevention and treatment of chronic inflammatory diseases., (Copyright © 2021. Published by Elsevier Inc.)

The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is associated with nosocomial infection and difficult to control. Artocarpin, a flavonoid from Artocarpus heterophyllus Lam. exhibits several pharmacological properties including antibacterial. The study was performed to evaluate interaction between artocarpin and antibiotics including tetracycline against P. aeruginosa . Its mechanism of action on membrane permeability was also investigated. Broth microdilution was conducted for the susceptibility assay. The interaction of artocarpin and antibiotics was evaluated using checkerboard method, the effect on alteration of membrane cell was investigated using bacteriolysis and the released of 260 nm materials. Artocarpin showed moderate to weak activity against the Gram-negative bacteria including P. aeruginosa with MIC values in the range of 31.25-250 μg/mL. A synergistic effect against P. aeruginosa was produced by the combination of artocarpin (31.25 μg/mL) and tetracycline (1.95 μg/mL) with FICI of 0.37. The time-killing assay showed that artocarpin enhance the antibacterial activity of tetracycline against  P. aeruginosa by completely inhibiting the bacterial growth. Additionally, the mixture of artocarpin (31.25 μg/mL) and tetracycline (1.95 μg/mL) disrupted membrane permeability and lead to cell death. These results proposed that the combination of artocarpin and tetracycline may be used to overcome P. aeruginosa infection., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as anti-oxidant, anti-tumor, anti-microbial and anti-inflammatory activities. It is believed that the mechanisms involved in these bioactivities are due to the modulation of immune system. Recently, the pharmacological validation on immunomodulatory of pentacyclic triterpenes derived from higher plants is very limited and several existence review papers related for this group of compound have not been focused for this activity. In this review, we have highlighted several studies on immunomodulatory potential of botanical pentacyclic triterpenes isolated from wide array of different species of medicinal plants and herbs based on various preclinical in vitro and animal models. This review also attempts to discuss on bioactivities of compouns related with their structure-activity relationship. Hence, the evaluation of pentacyclic triterpenes offers a great opportunity to discover adjuvants and novel therapeutic agents that presented beneficial immunomodulatory properties., Competing Interests: The authors declared no conflict of interest., (© 2020 Tianjin Press of Chinese Herbal Medicines. Published by Elsevier B.V.)

Betula alnoides is a medicinal plant in Thai traditional longevity preparations. The crude extracts of this plant possess various biological activities. However, the isolated compounds from this plant have no reports of anti-HIV-1 integrase (IN) activity. Therefore, the present study aims to investigate the anti-HIV-1 integrase and anti-inflammatory effects of isolated compounds from this plant and predict the interaction of compounds with integrase active sites. From the bioassay-guided fractionation of the ethanol extract of B. alnoides stems using chromatographic techniques, five pentacyclic triterpenoid compounds were obtained. They are betulinic acid ( 1 ), betulin ( 2 ), lupeol ( 3 ), oleanolic acid ( 4 ), and ursolic acid ( 5 ). Compound 2 exhibited the most potent inhibitory activity against HIV-1 IN, with an IC 50 value of 17.7  μ M. Potential interactions of compounds with IN active sites were investigated using computational docking. The results indicated that active compounds interacted with Asp64, a residue participating in 3'-processing, and Thr66, His67, and Lys159, residues participating in strand-transfer reactions of the integration process. Regarding anti-inflammatory activity, all compounds exerted significant inhibitory effects on LPS-induced nitric oxide production (IC 50  < 68.7  μ M). Thus, this research provides additional scientific support for the use of B. alnoides in traditional medicine for the treatment of HIV patients.

Objectives: To investigate the effects of flavonoids isolated from Artocarpus heterophyllus. heartwood on chemotaxis, phagocytosis, reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity of human phagocytes., Methods: Chemotaxis was evaluated using a modified Boyden chamber and phagocytosis was determined by flowcytometer. Respiratory burst was investigated by luminol-based chemiluminescence assay while MPO activity was determined by colorimetric assay., Key Findings: Artocarpanone and artocarpin strongly inhibited all steps of phagocytosis. Artocarpanone and artocarpin showed strong chemotactic activity with IC 50 values of 6.96 and 6.10 μm, respectively, which were lower than that of ibuprofen (7.37 μm). Artocarpanone was the most potent compound in inhibiting ROS production of polymorphonuclear leucocytes and monocytes with IC 50 values comparable to those of aspirin. Artocarpin at 100 μg/ml inhibited phagocytosis of opsonized bacteria (28.3%). It also strongly inhibited MPO release with an IC 50 value (23.3 μm) lower than that of indomethacin (69 μm). Structure-activity analysis indicated that the number of hydroxyl group, the presence of prenyl group and variation of C-2 and C-3 bonds might contribute towards their phagocytosis., Conclusions: Artocarpanone and artocarpin were able to suppress strongly the phagocytosis of human phagocytes at different steps and have potential to be developed into potent anti-inflammatory agents., (© 2018 Royal Pharmaceutical Society.)

Aim/backgrounds: Artocarpanone isolated from Artocarpus heterophyllus L. (Moraceae) exhibits antibacterial activity. The present study investigated synergistic activity between artocarpanone and tetracycline, ampicillin, and norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Escherichia coli ., Materials and Methods: A broth microdilution method was used for evaluating antibacterial susceptibility. Synergistic effects were identified using a checkerboard method, and a bacterial cell membrane disruption was investigated by assay of released 260 nm absorbing materials following bacteriolysis., Results and Discussion: Artocarpanone exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum inhibitory concentrations values of 125 and 500 μg/mL, respectively. However, the compound showed strong antibacterial activity against E. coli (7.8 μg/mL). The interaction between artocarpanone and all tested antibiotics revealed indifference and additive effects against P. aeruginosa and E. coli (fractional inhibitory concentration index [FICI] values of 0.75-1.25). The combination of artocarpanone (31.2 μg/mL) and norfloxacin (3.9 μg/mL) resulted in synergistic antibacterial activity against MRSA, with an FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, the combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA., Conclusion: These findings suggest that artocarpanone may be used to enhance the antibacterial activity of norfloxacin against MRSA., Competing Interests: Conflict of Interest: None declared.

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.

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.