Potential Biological Activity Research Articles

Exploration and evaluation of antioxidant activity in isolated phenolics from Jasminum scandens (retz) vahl

Given the widespread and established use of Jasminum scandens (Retz) Vahl, a member of the Oleacea family, this study aimed to identify and characterise secondary metabolites derived from the plant, with the objective of evaluating their potential biological activities. Using chromatographic separations techniques based on molecular weight and polarity, various VLC fractions of the plant were purified. These fractions yielded seven compounds- 2-(4-hydroxyphenyl)-ethanol (1), 2-(4-hydroxy-3-methoxy-phenyl)-ethanol (2), 1-(4-hydroxy-3-methoxy-phenyl)-1,2,3-propanetriol (3), 1-(4-hydroxy-3,5-dimethoxy-phenyl)-1,2,3-propanetriol (4), lupeol (5), β-sitosterol (6), and methyl linoleate (7), which have never been previously reported in this plant. Out of the seven identified compounds, compounds 3 and 4 had the greatest capacity to scavenge free radicals with IC50 values of 3.81 µg/ml and 4.08 µg/ml, respectively when compared to the standard Butylated Hydroxy Toluene (BHT) with IC50 value of 6.54 µg/ml.

Phytochemical Profiling and Biological Activities of Rhododendron Subsect. Ledum: Discovering the Medicinal Potential of Labrador Tea Species in the Northern Hemisphere.

Rhododendron subsect. Ledum is a distinct taxonomic subdivision within the genus Rhododendron, comprising a group of evergreen shrubs and small trees. This review will comprehensively analyse the phytochemical profiles and biological properties of the Rhododendron subsect. Ledum species subsect. Ledum consists of eight plant species indigenous to temperate and subarctic regions of the Northern Hemisphere, collectively known as Labrador tea. Recent investigations have concentrated on the phytochemical constituents of these plants due to limited data, emphasizing their evergreen nature and potential industrial significance. This review summarizes their major phytochemical constituents, including flavonoids, phenolic acids, and terpenoids, and discusses their potential biological activities, such as antioxidant, anti-inflammatory, antimicrobial, antitumor, hypoglycemic, hepatoprotective, neuroprotective, and cardioprotective effects. Traditional uses of these plant species align with scientific findings, emphasizing the significance of these plants in traditional medicine. However, despite promising results, gaps exist in our understanding of specific compounds' therapeutic effects, necessitating further research for comprehensive validation. This review serves as a valuable resource for researchers, identifying current knowledge, uncertainties, and emerging trends in the study of the Rhododendron subsect. Ledum species.

General characteristics of lavender biomass (Lavandula angustifolia Mill.) before and after industrial distillation

The aim of the present study was to evaluate and compare three types of lavender (Lavandula angustifolia Mill.) biomasses for their content of biologically active substances and potential application. The first one was from unprocessed lavender (L-UNTR22_Z) and the other two were industrial steam-distilled lavender solid residues (L-SD22_Z and L-SD22_M). Ash, protein, polyuronide content and the degree of esterification of the pectic substances in the biomass were investigated. 70% ethanolic extracts of the residues were prepared and their total polyphenol content and antioxidant activity were evaluated by four methods. Individual phenolic acids, flavonoids, polar non-volatile compounds and polar volatile compounds were also determined by chromatographic analyses. The highest degree of esterification (83.9±0.5%) and protein content (8.15±1.6%) were found in L-SD22_Z extract. L-SD22_M extract demonstrated the highest polyphenolic content and antioxidant activity. Six phenolic acids (protocatehuic, syringic, p-coumaric, ferulic, salicylic, and gallic acid) and five flavonoids ((+)-catechin, (-)-epicatechin, rutin, hesperidin, and quercetin) were detected by HPLC analyses. The detail information about amino acids, sugars, organic and phenolic acids, as well as polar volatile compounds was obtained by GC-MS. The results suggested that the lavender (untreated and residual biomass) are a good source of dietary antioxidants and compounds with potent biological activity.

Biosynthesis of gold nanoparticles mediated by Curcuma longa extract: Evaluation of its catalytic activity for the degradation of environmental pollutants and study of anti-lung adenocarcinoma effects

It is essential to recognize efficient heterogeneous catalysts for environmental remediation that can eliminate organic contaminants or transform them into beneficial byproducts. Herein, we have designed and developed a gold nanoparticle based green nanocomposite material templated over the Curcuma longa extract. The Au NPs/C. longa nanomaterial was thoroughly characterized by FT-IR and UV–Vis spectroscopy followed by FE-SEM, EDX, TEM and XRD analysis. Subsequently, towards the wastewater treatment, it demonstrated excellent potential in the reduction of water contaminant toxic organic dyes like methylene blue (MB), methyl orange (MO), and 4-nitrophenol (4-NP) following excellent kinetics, as monitored by UV–Vis spectrophotometer. The reaction followed a pseudo-first order kinetics. The robustness of the nanocatalyst was justified by reusability studies, and hot filtration test and the catalytic activity did not substantially decline over the course of seven cycles. Towards the assessment of biological activity of Au NPs/C. longa nanocomposite antioxidant capacity was evaluated first using the DPPH radical scavenging method. Further, the study was extended in the investigation of anti-lung cancer properties against a number of standard lung cancer cell lines, viz., NCI-H661, NCI-H1975, NCI-H1573, and NCI-H1563 following MTT colorimetric in vitro studies. Curcuma longa-modified Au NPs are thought to have potential biological activities because of their exceptional capacity to produce reactive oxygen species (ROS).

Brain-Derived Neurotrophic Factor (BDNF) Enhances Osteogenesis and May Improve Bone Microarchitecture in an Ovariectomized Rat Model.

Brain-derived neurotrophic factor (BDNF) has gained attention as a therapeutic agent due to its potential biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully understood. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. In addition, to evaluate the clinical efficacy, an in vivo animal study was performed. Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. For the animal study, we used ovariectomized Sprague-Dawley rats and divided them into BDNF and normal saline injection groups. MicroCT, hematoxylin and eosin (H&E), and tartrate-resistant acid phosphatase (TRAP) stain were performed for analysis. BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc., in both ST-2 and the MC3T3-E1 and ST-2 co-culture systems. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B, as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Although the animal study results including bone density and histology showed increased osteoblastic and decreased osteoclastic activity, only a portion of parameters reached statistical significance. Our study results showed that BDNF affects osteoblast differentiation through TrkB receptor, and JNK and p38 MAPK signal pathways. Although not statistically significant, the trend of such effects was observed in the animal experiment.

Characterization of Seven New Steroidal Saponins from Korean Oat Cultivars by UPLC-QTOF-MS and UPLC-MS/MS.

Oat saponins are composed of triterpenoid and steroidal saponins, and their potential biological activities, such as antibacterial, antifungicidal, osteogenic, and anticancer activities, have been reported. In this study, qualitative and quantitative analyses of oat saponins were conducted by using UPLC-QToF-MS and UPLC-Triple Q-MS/MS. A total of 22 saponins were analyzed in seven Korean oat cultivars. Among them, 7 saponins were identified as new compounds in this source, which were tentatively confirmed as nuatigenin-type saponins with 26-O-diglucoside and 3-O-malonylglucoside forms and (25S)-furost-5-en-3β,22,26-triol-type saponins. In addition, the total content of these saponins ranged from 70.61 to 141.38 mg/100 g dry weight, and it was affected by the type of oat cultivar and the presence or absence of hulling. These detailed profiles will be suggested as fundamental data for breeding superior oat cultivars, evaluating of related products, and various industries.

Phytochemicals, antioxidant and antibacterial activity of crude extract of Sargassum polycystum collected from Bangladesh

Marine seaweed species have been extensively studied in recent decades due to their potential biological activities, such as antioxidant and antibacterial characteristics. This study investigates the phytochemicals, total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and antibacterial properties of Sargassum polycystum extracts collected from Bangladesh and crude extracts were prepared using methanol, ethanol, and water as extraction solvents. Phytochemical analysis revealed the presence of terpenoids, saponins, phlobatannins, and cardiac glycosides. Fourier-transform infrared spectroscopy (FT-IR) identified functional groups, including phenols, carboxylic acids, ketones, ethers, aromatics, alkanes, and ethers. The methanol extract exhibited the highest TPC (95.34 ± 1.21 mg of GAE/g) and TFC (51.48 ± 0.92 mg of QE/g). Methanol extracts displayed superior antioxidant activity in the Phosphomolybdenum assay (1.96 ± 0.08), DPPH assay (81.33 ± 5.60%, IC50 = 1.17 mg/mL), ABTS assay (71.65 ± 4.10%, IC50 = 2.54 mg/mL), and Nitric oxide scavenging assay (67.64 ± 4.10%, IC50 = 3.81 mg/mL). Ethanol extract demonstrated the highest antibacterial activity against Escherichia coli (16.50 ± 0.13 mm), while the methanol extract excelled against Salmonella typhimurium (14.6 ± 0.18 mm) at 7 mg/mL dosage. A positive correlation was found among TPC, TFC, and different antioxidant assays.

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases.

Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

Intramolecular Friedel-Crafts Reaction with Trifluoroacetic Acid: Synthesizing Some New Functionalized 9-Aryl/Alkyl Thioxanthenes.

In this study, a series of halogen-substituted thioxanthenes were synthesized because the most important and biologically active derivatives of xanthenes are thioxanthenes. In order to obtain new thioxanthene derivatives, first, the starting molecules were synthesized by the appropriate reaction methods in two steps. The intramolecular Friedel-Crafts alkylation (FCA) method was used to convert the prepared three aromatic substituted starting alcohol compounds to their corresponding thioxanthenes by cyclization. For the intramolecular FCA reaction of secondary alcohols, which are the starting compounds (1a-1t), organic Bro̷nsted acids, which require more innovative, easier, and suitable reaction conditions, were used instead of halide reagents with corrosive effects as classical FCA catalysts. Trifluoroacetic acid was determined to be the organocatalyst with the best yield. Therefore, some original 9-aryl/alkyl thioxanthene derivatives (2a-2t) were synthesized using the optimized FCA method. In addition, a new sulfone derivative of thioxanthene 3i was prepared by performing the oxidation reaction with one of the obtained new thioxanthene 2i. Thioxanthenes and their derivatives are important heterocyclic structures that contain pharmacologically valuable sulfur and are used in the treatment of psychotic diseases such as Alzheimer's or schizophrenia, as well as a number of potent biological activities.

Short macrocyclic peptides in sponge genomes

Sponges (Porifera) contain many peptide-specialized metabolites with potent biological activities and significant roles in shaping marine ecology. It is well established that symbiotic bacteria produce bioactive "sponge" peptides, both on the ribosome (RiPPs) and nonribosomally. Here, we demonstrate that sponges themselves also produce many bioactive macrocyclic peptides, such as phakellistatins and related proline-rich macrocyclic peptides (PRMPs). Using the Stylissa carteri sponge transcriptome, methods were developed to find sequences encoding 46 distinct RiPP-type core peptides, of which ten encoded previously identified PRMP sequences. With this basis set, the genome and transcriptome of the sponge Axinella corrugata was interrogated to find 35 PRMP precursor peptides encoding 31 unique core peptide sequences. At least 11 of these produced cyclic peptides that were present in the sponge and could be characterized by mass spectrometry, including stylissamides A-D and seven previously undescribed compounds. Precursor peptides were encoded in the A. corrugata genome, confirming their animal origin. The peptides contained signal peptide sequences and highly repetitive recognition sequence-core peptide elements with up to 25 PRMP copies in a single precursor. In comparison to sponges without PRMPs, PRMP sponges are incredibly enriched in potentially secreted polypeptides, with >23,000 individual signal peptide encoding genes found in a single transcriptome. The similarities between PRMP biosynthetic genes and neuropeptides in terms of their biosynthetic logic suggest a fundamental biology linked to circular peptides, possibly indicating a widespread and underappreciated diversity of signaling peptide post-translational modifications across the animal kingdom.

Potent biological activity of newly fabricated silver nanoparticles coated by a carbon shell synthesized by electrical arc

Highly effective AgNPs@C was efficiently synthesized by electrical arc powered by single spark unit which was sufficient to ionize the dielectric media (deionized water) through applying strong electric field between the electrodes (silver and carbon). The AgNPs@C shell was characterized in terms of stability, morphology and phase structure. All characterizations showed that the prepared silver nanoparticles were spherical with average size reached 17 nm coated with carbon shell. The antibacterial effect of the synthesized nanoparticles was tested against Pseudomonas aeruginosa in comparison to Ceftazidime (commonly used antibiotic against P. aeruginosa infections). It was revealed that AgNPs@C shell has superior activity with inhibition zone diameter reached 15 mm and minimum inhibitory concentration reached 2 µg/mL. The observed activity was further confirmed by confocal microscope which showed an increased red region, representing the dead cells, correlated with the presence of AgNPs@C. Moreover, transmission electron microscope studies implied the possible AgNPs@C antibacterial mechanism of action was the nanoparticles adherence to the bacterial membrane causing cell lysis. The molecular studies against fimH (virulence adhesion gene), rmpA (mucoid factor encoding gene), and mrkA (biofilm forming gene) proved the inhibition of their genetic expression. The cytotoxic effect of the synthesized AgNPs@C showed CC50 reached 235.5 μg/mL against normal lung cells (L929 cell line).

Potential biological active bacteriocin production by Bifidobacterium via eco‐friendly, low‐cost solid state fermentation principle

AbstractThe present study is undertaken to evaluate the potential biological activities of bacteriocin produced by the Lactic acid bacteria Bifidobacterium sp. adopting solid state fermentation. Bifidobacterium was isolated from cooked fermented rice water. Isolated bacterial strain was identified by morphological, biochemical, and molecular characteristics. Sterilized cooked rice was inoculated with bacterial inoculum followed by extraction of bacteriocin under aseptic condition. Extracted bacteriocin was screened for antibacterial, antioxidant, and anti‐inflammatory activities under invitro condition. Cooked fermentation rice medium used for solid state fermentation (SSF) supported growth and bacteriocin production by Bifidobacterium longum. Potential antibacterial activity of the extracted bacteriocin was confirmed by growth inhibition of Bacillus subtilis, and Escherichia coli strain. Notable free radical scavenging activity at 120 μg/mL concentration of bacteriocin clearly indicated antioxidant activity. Anti‐inflammatory activity of the bacteriocin was determined which showed maximum inhibition at 120 μg/mL concentration. All these finding suggest the possible utilization of bacteriocin extraction from Bifidobacterium as an effective, safe bioactive agent.

Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management.

This paper delves into the diverse and significant roles of curcumin, a polyphenolic compound from the Curcuma longa plant, in the context of cancer and inflammatory diseases. Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research comprehensively investigates curcumin's molecular interactions with key proteins involved in cancer progression and the inflammatory response, primarily through molecular docking studies. In cancer, curcumin's effectiveness is determined by examining its interaction with pivotal proteins like CDK2, CK2α, GSK3β, DYRK2, and EGFR, among others. These interactions suggest curcumin's potential role in impeding cancer cell proliferation and survival. Additionally, the paper highlights curcumin's impact on inflammation by examining its influence on proteins such as COX-2, CRP, PDE4, and MD-2, which are central to the inflammatory pathway. In vitro and clinical studies are extensively reviewed, shedding light on curcumin's binding mechanisms, pharmacological impacts, and therapeutic application in various cancers and inflammatory conditions. These studies are pivotal in understanding curcumin's functionality and its potential as a therapeutic agent. Conclusively, this review emphasizes the therapeutic promise of curcumin in treating a wide range of health issues, attributed to its complex chemistry and broad pharmacological properties. The research points towards curcumin's growing importance as a multi-faceted natural compound in the medical and scientific community.

Machine learning and genetic algorithm-guided directed evolution for the development of antimicrobial peptides

IntroductionAntimicrobial peptides (AMPs) are valuable alternatives to traditional antibiotics, possess a variety of potent biological activities and exhibit immunomodulatory effects that alleviate difficult-to-treat infections. Clarifying the structure-activity relationships of AMPs can direct the synthesis of desirable peptide therapeutics. ObjectivesIn this study, the lipopolysaccharide-binding domain (LBD) was identified through machine learning-guided directed evolution, which acts as a functional domain of the anti-lipopolysaccharide factor family of AMPs identified from Marsupenaeus japonicus. MethodsLBDA-D was identified as an output of this algorithm, in which the original LBDMj sequence was the input, and the three-dimensional solution structure of LBDB was determined using nuclear magnetic resonance. Furthermore, our study involved a comprehensive series of experiments, including morphological studies and in vitro and in vivo antibacterial tests. ResultsThe NMR solution structure showed that LBDB possesses a circular extended structure with a disulfide crosslink at the terminus and two 310-helices and exhibits a broad antimicrobial spectrum. In addition, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that LBDB induced the formation of a cluster of bacteria wrapped in a flexible coating that ruptured and consequently killed the bacteria. Finally, coinjection of LBDB, Vibrio alginolyticus and Staphylococcus aureus in vivo improved the survival of M. japonicus, demonstrating the promising therapeutic role of LBDB for treating infectious disease. ConclusionsThe findings of this study pave the way for the rational drug design of activity-enhanced peptide antibiotics.

Synthesis of (Z)-3-Allyl-5-(4-nitrobenzylidene)-2-sulfanylidene-1,3-thiazolidin-4-one and Determination of Its Crystal Structure

To extend the existing library of arylidenerhodanines which display a potential biological activity, 3-N-allylrhodanine 1 was condensed under Knoevenagel conditions with p-nitrobenzaldehyde in acetic acid to afford the π-conjugated heterocyclic compound 3-allyl-5-(4-nitrobenzylidene)-2-sulfanylidene-1,3-thiazolidin-4-one 2. Compound 2 was characterized by IR and NMR spectroscopy, and its UV-vis spectrum was compared with that of compound 3-allyl-5-(4-methoxybenzylidene)-2-sulfanylidene-1,3-thiazolidin-4-one 3. The molecular structure is ascertained by a single-crystal X-ray diffraction study performed at 100 K.

A type III polyketide synthase cluster in the phylum Planctomycetota is involved in alkylresorcinol biosynthesis

Members of the bacterial phylum Planctomycetota have recently emerged as promising and for the most part untapped sources of novel bioactive compounds. The characterization of more than 100 novel species in the last decade stimulated recent bioprospection studies that start to unveil the chemical repertoire of the phylum. In this study, we performed systematic bioinformatic analyses based on the genomes of all 131 described members of the current phylum focusing on the identification of type III polyketide synthase (PKS) genes. Type III PKSs are versatile enzymes involved in the biosynthesis of a wide array of structurally diverse natural products with potent biological activities. We identified 96 putative type III PKS genes of which 58 are encoded in an operon with genes encoding a putative oxidoreductase and a methyltransferase. Sequence similarities on protein level and the genetic organization of the operon point towards a functional link to the structurally related hierridins recently discovered in picocyanobacteria. The heterologous expression of planctomycetal type III PKS genes from strains belonging to different families in an engineered Corynebacterium glutamicum strain led to the biosynthesis of pentadecyl- and heptadecylresorcinols. Phenotypic assays performed with the heterologous producer strains and a constructed type III PKS gene deletion mutant suggest that the natural function of the identified compounds differs from that confirmed in other bacterial alkylresorcinol producers.Key points• Planctomycetal type III polyketide synthases synthesize long-chain alkylresorcinols.• Phylogenetic analyses suggest an ecological link to picocyanobacterial hierridins.• Engineered C. glutamicum is suitable for an expression of planctomycete-derived genes.

Fabrication and characterization of CuO–SiO2/PVA polymer nanocomposite for effective wastewater treatment and prospective biological applications

ABSTRACT The quality of water significantly affects the health and walefare of all orginisms, highlighting the importance to develop low-cost and efficient wastewater treatment methods. Herein, we report the fabrication, characterization, and utilization of a polymer-based ternary nanocomposite (CuO–SiO2/PVA) for the removal of Nile Blue (NB) and Methylene Blue (MB) contaminants from wastewater, along with exploring its potential biological activities. We have successfully employed the cost-effective sol–gel and in-situ polymerization approaches to fabricate the CuO–SiO2/PVA based ternary composite, utilizing Cu(NO3)2·3H2O:Glycerol:TEOS:PVA in a ratio of 8:2:3:4. The desired fabrication of nanocomposite was confirmed through UV-Visible spectroscopy, SEM (scanning electron microscope), TEM (transmission electron microscope), EDX (energy dispersive X-ray diffraction), FTIR (Fourier transform infrared), DSC (differential scanning calorimetry), and TGA (thermogravimetric analysis). In addition to its biological potentialthe performance of the nanocomposite in catalytic / photocatalytic removal of NB and MB dyes is investigated and compared. The higher photodegradation performance of the composite for NB (85%) dye than for MB (76%) dye indicates that variables such as chemical structure, charge, molecular mass, and pH sensitivity of the dyes can influence the catalyst's removal potential. This composite is considered to have a higher capability for removing pollutants and microorganisms from wastewater.

Draft genome sequence of Bacillus sp. strain X and Salarachaeum sp. strain III isolated from Lake Karum, Danakil Depression, Ethiopia.

Here, we report the draft genome sequences of strains of Bacillus and Salarachaeum that were isolated from hypersaline water samples collected from Lake Karum, Danakil Depression, Ethiopia. The sequences pave the way for more targeted studies into the potential biological activities and secondary metabolite synthesis of these organisms.

Constructing Innovative Covalent and Noncovalent Compound Libraries: Insights from 3D Protein-Ligand Interactions.

Noncovalent interactions between small-molecule drugs and protein targets assume a pivotal role in drug design. Moreover, the design of covalent inhibitors, forming covalent bonds with amino acid residues, requires rational reactivity for their covalent warheads, presenting a key challenge as well. Understanding the intricacies of these interactions provides a more comprehensive understanding of molecular binding mechanisms, thereby guiding the rational design of potent inhibitors. In this study, we adopted the fragment-based drug design approach, introducing a novel methodology to extract noncovalent and covalent fragments according to distinct three-dimensional (3D) interaction modes from noncovalent and covalent compound libraries. Additionally, we systematically replaced existing ligands with rational fragment substitutions, based on the spatial orientation of fragments in 3D space. Furthermore, we adopted a molecular generation approach to create innovative covalent inhibitors. This process resulted in the recombination of a noncovalent compound library and several covalent compound libraries, constructed by two commonly encountered covalent amino acids: cysteine and serine. We utilized noncovalent ligands in KLIFS and covalent ligands in CovBinderInPDB as examples to recombine noncovalent and covalent libraries. These recombined compound libraries cover a substantial portion of the chemical space present in the original compound libraries and exhibit superior performance in terms of molecular scaffold diversity compared to the original compound libraries and other 11 commercial libraries. We also recombined BTK-focused libraries, and 23 compounds within our libraries have been validated by former researchers to possess potential biological activity. The establishment of these compound libraries provides valuable resources for virtual screening of covalent and noncovalent drugs targeting similar molecular targets.

Effectiveness of Ya-Samarn-Phlae in diabetic wound healing: Evidence from in vitro studies and a multicenter randomized controlled clinical trial

Ethnopharmacological relevanceYa-Samarn-Phlae (YaSP) has traditionally been widely used in southern Thailand for treating chronic and infected wounds, including diabetic foot ulcers. However, there are only a limited number of clinical studies supporting the use of this polyherbal formulation. Therefore, the present work aims to provide clinical evidence to support the application of YaSP, prepared according to a standardized traditional procedure (T-YaSP). Additionally, its potential chemical markers and wound healing-related biological activities were examined. Materials and methodsThe in vitro wound healing-related biological activities of YaSP ethanol extract and T-YaSP, including antibacterial activity against Staphylococcus epidermidis, inhibition and eradication of staphylococcal biofilm, anti-inflammatory effects, and enhancement of human dermal fibroblast migration in scratch wounds, were examined using well-established protocols. The chemical profiles of the ethanol extract of YaSP and T-YaSP were compared, and with promising chemical markers, arecoline, alpha-mangostin, and curcumin were selected and quantified using the HPLC method. A prospective, multicenter, randomized, controlled, parallel-group study was conducted over 12 weeks to evaluate the efficacy of the YaSP solution as an adjunct therapy, combined with standard wound care, for diabetic ulcers compared to standard treatment. ResultsThe YaSP extract reduces NO production and can scavenge NO radicals in LPS-induced RAW 264.7 macrophage cells. Additionally, in a scratch assay, this extract and one of its herbal components, Curcuma longa, enhance the migration of human dermal fibroblasts. T-YaSP, containing 2.412 ± 0.002 mg/g of arecoline, 2.399 ± 0.005 mg/g of curcumin, and 0.017 ± 0.000 mg/g of α-mangostin, has shown the ability to inhibit the development and eradicate the mature biofilm of S. epidermidis. The use of T-YaSP as an adjunct therapy led to a significantly higher proportion of patients achieving healing within six weeks compared to the standard treatment group (36%/9 patients vs. 4%/1 patient; p = 0.013). After 12 weeks, 19 out of 25 patients in the T-YaSP group experienced complete healing, whereas only four patients in the standard treatment group achieved complete wound healing (76% in the T-YaSP group vs. 16% in the control group; p < 0.001). ConclusionThe results presented here represent the first randomized controlled trial to demonstrate the effectiveness of the traditional polyherbal solution, T-YaSP, which exhibits a wide range of wound healing-related activities. Utilizing T-YaSP as an adjunctive treatment resulted in a significant improvement in the number of type 2 diabetic patients achieving complete healing. However, to explore and utilize YaSP further, conducting a double-blind, randomized controlled trial with a larger population is necessary.