Bioactive Secondary Metabolites Research Articles

Assessment of antimicrobial activity and GC-MS using culture filtrate of local marine Bacillus strains

Secondary metabolites produced by Bacillus species from marine sources encompass a variety of compounds such as lipopeptides, isocoumarins, polyketides, macrolactones, polypeptides and fatty acids. These bioactive substances exhibit various biological activities, including antibiotic, antifungal, antiviral, and antitumor properties. This study aimed to isolate and identify a particular species of Bacillus from marine water and organisms that can produce bioactive secondary metabolites. Among the 73 Bacillus isolates collected, only 5 exhibited antagonistic activity against various viral and bacterial pathogens. The active isolates were subjected to 16S rRNA sequencing to determine their taxonomical affiliation. Among them, Bacillus tequilensis CCASU-2024-66 strain no. 42, with the accession number ON 054302 in GenBank, exhibited the highest inhibitory potential. It displayed an inhibition zone of 21 mm against Bacillus cereus while showing a minimum zone of inhibition of 9 mm against Escherichia coli and gave different inhibition against pathogenic fungi, the highest inhibition zone 15 mm against Candida albicans but the lowest inhibition zone 10 mm was against Botrytis cinerea, Fusarium oxysporum. Furthermore, it demonstrated the highest percentage of virucidal effect against the Newcastle virus and influenza virus, with rates of 98.6% and 98.1%, respectively. Furthermore, GC-MS analysis was employed to examine the bioactive substance components, specifically focusing on volatile and polysaccharide compounds. Based on these results, Bacillus tequilensis strain 42 may have the potential to be employed as an antiviral agent in poultry cultures to combat Newcastle and influenza, two extremely destructive viruses, thus reducing economic losses in the poultry production sector. Bacteria can be harnessed for the purpose of preserving food and controlling pathogenic fungi in both human and plant environments. Molecular docking for the three highly active derivatives 2,3-Butanediol, 2TMS, D-Xylopyranose, 4TMS, and Glucofuranoside, methyl 2,3,5,6-tetrakis-O-(trimethylsilyl) was carried out against the active sites of Bacillus cereus, Listeria monocytogenes, Candida albicans, Newcastle virus and influenza virus. The data obtained from molecular docking is highly correlated with that obtained from biology. Moreover, these highly active compounds exhibited excellent proposed ADMET profile.

Whole-genome sequencing of marine water-derived Curvularia verruculosa KHW-7: a pioneering study

Marine microorganisms are renowned for being a rich source of new secondary metabolites that are significant to humans. The fungi strain KHW-7 was isolated from the seawater collected from the Gulf of Khambhat, India, and identified as Curvularia verruculosa KHW-7. On a next-generation sequencing platform, C. verruculosa KHW-7’s whole-genome sequencing (WGS) and gene annotation were carried out using several bioinformatic methods. The 31.59 MB genome size, 52.3% GC, and 158 bp mean read length were discovered using WGS. This genome also contained 9,745 protein-coding genes, including 852 secreted proteins and 2048 transmembrane proteins. The antiSMASH algorithm used to analyze genomes found 25 secondary metabolite biosynthetic gene clusters (BGCs) that are abundant in terpene, non-ribosomal peptide synthetase (NRPS), and polyketides type 1 (T1PKS). To our knowledge, this is the first whole-genome sequence report of C. verruculosa. The WGS analysis of C. verruculosa KHW-7 indicated that this marine-derived fungus could be an efficient generator of bioactive secondary metabolites and an important industrial enzyme, both of which demand further investigation and development.

Analysis of Bioactive Secondary Metabolites Produced by Endophytic Bacillus amyloliquefaciens against Rice Sheath Blight Pathogen Rhizoctonia solani

Background: Bacterial endophytes live inside the plant tissues and are known to play a crucial role in the functioning of host plants by influencing their physiology and development. Moreover, this group of bacteria could produce secondary metabolites to suppress plant pathogens and also produce compounds to promote plant growth. Methods: In this present study, Bacillus amyloliquefaciens was isolated from Oryzae officinalis and screened for antifungal activity against rice sheath blight pathogen, Rhizoctonia solani by dual culture assay. The secondary metabolites produced during the interaction of B. amyloliquefaciens with R. solani were characterized with pathogen-inoculated control and antagonist inoculated control through Gas Chromatography-Mass Spectrophotometry (GC-MS). Result: The isolated Bacillus amyloliqufaciens displayed antagonistic activity against Rhizoctonia solani which showed a 63% inhibiton in the mycelial growth of R. solani over control. Analysis of secondary metabolites from the zone of inhibition, confirmed the presence of unique biomolecules including -Propanamine, N,N,2-trimethyl, 1(2H)-Naphthalenone, 3,4-dihydro-6,7-dimethyl, Diethyl Phthalate, Dichloroacetic acid tridecyl ester, Hexadecen-1-ol trans-9, Glycine N-(N-glycyl-L-leucyl) and 2,6,10-Dodecatrien-1-ol, 3,7,11-trimethyl of antifungal and antimicrobial nature.

Leprosy: Comprehensive insights into pathology, immunology, and cutting-edge treatment strategies, integrating nanoparticles and ethnomedicinal plants

Mycobacterium leprae is the causative agent responsible for the chronic disease known as leprosy. This condition is characterized by dermal involvement, often leading to peripheral nerve damage, sensory-motor loss, and related abnormalities. Both innate and acquired immunological responses play a role in the disease, and even in individuals with lepromatous leprosy, there can be a transient increase in T cell immunity during lepromatous reactions. Diagnosing of early-stage leprosy poses significant challenges. In this context, nanoparticles have emerged as a promising avenue for addressing various crucial issues related to leprosy. These include combatting drug resistance, mitigating adverse effects of conventional medications, and enhancing targeted drug delivery. This review serves as a comprehensive compilation, encompassing aspects of pathology, immunology, and adverse effects of multidrug delivery systems in the context of leprosy treatment. Furthermore, the review underscores the significance of ethnomedicinal plants, bioactive secondary metabolites, and nanotherapeutics in the management of leprosy. It emphasizes the potential to bridge the gap between existing literature and ongoing research efforts, with a profound scope for validating traditional claims, developing herbal medicines, and formulating nanoscale drug delivery systems that are safe, effective, and widely accepted.

Genomic Analysis of Kitasatospora setae to Explore Its Biosynthetic Potential Regarding Secondary Metabolites.

Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their natural products has led to a diminished probability of discovering novel bioactive compounds from this group. Consequently, our research focus has shifted towards less explored actinomycetes, beyond Streptomyces, with particular emphasis on Kitasatospora setae (K. setae). The genome of K. setae was annotated and analyzed through whole-genome sequencing using multiple bio-informatics tools, revealing an 8.6 Mbp genome with a 74.42% G + C content. AntiSMASH analysis identified 40 putative biosynthetic gene clusters (BGCs), approximately half of which were recessive and unknown. Additionally, metabolomic mining utilizing mass spectrometry demonstrated the potential for this rare actinomycete to generate numerous bioactive compounds such as glycosides and macrolides, with bafilomycin being the major compound produced. Collectively, genomics- and metabolomics-based techniques confirmed K. setae's potential as a bioactive secondary metabolite producer that is worthy of further exploration.

Important antiviral properties of Streptomyces species compounds

species, a subgroup of Actinomycetes bacteria, have been analysed for their antiviral properties. These bioactive secondary metabolites, which have a broad spectrum of chemical structures and strong biological activity, offer a promising opportunity for new antiviral therapeutics against various viral infections. These metabolites target different stages of viral replication or interactions with host cells, making them important for biological research and pharmaceutical development. bacteria contain numerous antiviral mechanisms that inhibit viral infections at different stages of the viral life cycle. and other actinomycetes can improve the health of people with viruses, and recent research suggests that combining with other bacterial species could improve overall health and regulate infections. This emphasises the importance of comprehensive approaches to combating viral infections and research into natural products. Further research into multispecies combinations of and other bacterial species is needed to fully utilise their therapeutic potential against viral diseases.

Kaempferol derivatives from Hippophae rhamnoides Linn. ameliorate H2O2-induced oxidative stress in SH-SY5Y cells by upregulating Nrf2.

As a medicinal and edible food, Hippophae rhamnoides Linn. subsp. sinensis Rousi is plenty of bioactive secondary metabolites including flavonoids and their derivatives, which have a certain protective effect on oxidative damage. The present study isolated three new kaempferol derivatives (compound 1-3), named Hippophandine A-C, from H. rhamnoides seed residue. The structures of Hippophandine A-C were explicated by HR-ESI-MS, NMR, and chemical analyses. Hippophandine A-C (1, 5, and 10 µM) were used to attenuate H2O2-induced cell death in SH-SY5Y and explore the mechanism in oxidative damage. The results elucidated that Hippophandine A-C reduced MDA, and increased the relative SOD, GSH, CAT contents, Nrf2 and HO-1 expression in H2O2-induced SH-SY5Y.

Activation of secondary metabolite gene clusters in Chaetomium olivaceum via the deletion of a histone deacetylase

Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1–A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1–A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources.Key points• Deletion of a class I histone deacetylase activated secondary metabolite gene clusters.• Three polyketides and one asterriquinone were isolated from HDAC deleted strain.• Two different PKSs were reported in C. olivaceum SD-80A.

Mass spectrometry and Nuclear magnetic resonance spectroscopy profiles of red and pink Rhododendron flower petals establish them as rich sources of bioactive secondary metabolites

AbstractRhododendron petals are considered high‐value owing to their commercial utility, national/state flower status in certain countries, and bioactive potential from recent studies. Profiling and quantitative analysis of the bioactive metabolites would evaluate if they can be natural sources. This study is focused on the comprehensive profiling of secondary metabolites in the hot aqueous petal extracts of Red and Pink Rhododendron flowers (Rhododendron arboreum and Rhododendron campanulatum) using separation and fragmentation patterns from mass spectrometry (MS) (gas chromatography‐MS and liquid chromatography‐tandem MS) and chemical shifts from proton‐nuclear magnetic resonance spectroscopy. The complementary analytical platforms highlighted the petals to be rich in promising bioactive molecules such as quinic acid, chlorogenic acid (caffeoyl quinic acid), protocatechuic acid, coumaroyl quinic acids, catechin, epigallocatechin, and shikimic acid. The analysis also reflected the activity of shikimic acid, phenolic acid, and flavonoid biosynthetic pathways in Rhododendron flowers. These metabolites are well reported for their bioactive potential as anti‐oxidative, anti‐viral, anti‐cancerous, anti‐diabetic, anti‐inflammatory, etc. While the quantitative and multivariate analysis showed variations in the levels of phenolic acids and flavonoids, it is established that red and pink Rhododendron flower petals are a rich source of bioactive phytochemicals of interest to the phytochemical Industry.

Comprehensive analysis of genomic variation, pan-genome and biosynthetic potential of Corynebacterium glutamicum strains.

Corynebacterium glutamicum is a non-pathogenic species of the Corynebacteriaceae family. It has been broadly used in industrial biotechnology for the production of valuable products. Though it is widely accepted at the industrial level, knowledge about the genomic diversity of the strains is limited. Here, we investigated the comparative genomic features of the strains and pan-genomic characteristics. We also observed phylogenetic relationships among the strains based on average nucleotide identity (ANI). We found diversity between strains at the genomic and pan-genomic levels. Less than one-third of the C. glutamicum pan-genome consists of core genes and soft-core genes. Whereas, a large number of strain-specific genes covered about half of the total pan-genome. Besides, C. glutamicum pan-genome is open and expanding, which indicates the possible addition of new gene families to the pan-genome. We also investigated the distribution of biosynthetic gene clusters (BGCs) among the strains. We discovered slight variations of BGCs at the strain level. Several BGCs with the potential to express novel bioactive secondary metabolites have been identified. Therefore, by utilizing the characteristic advantages of C. glutamicum, different strains can be potential applicants for natural drug discovery.

Aspergillus clavatonanicus HSF015 possesses the talent in producing bioactive secondary metabolites

Mangrove-associated fungi are excellent sources of bioactive natural products. To explore the value of producing bioactive secondary, the genome and transcriptome of mangrove-associated fungus named A. clavatonanicus HSF015 are sequenced for the first time. According to the genome (8737 function gene), A. clavatonanicus HSF015 with 58.05 % genes expressing shows high performance in metabolism and secondary metabolism. Forty secondary metabolite biosynthesis gene clusters are successfully annotated from 13 contigs in the genome. Thereinto, ten biosynthesis gene clusters can synthesize 17 known compounds with various activities and application values. The remaining 30 gene clusters are unknown secondary metabolite synthesis gene clusters, which are worth exploring. In addition, three known compounds with antioxidant and antibacterial activities were isolated from the broth of A. clavatonanicus HSF015. Hence, A. clavatonanicus HSF015 with the great talent in producing bioactive secondary metabolites is worth further study.

Marine seaweed endophytic fungi-derived active metabolites promote reactive oxygen species-induced cell cycle arrest and apoptosis in human breast cancer cells.

Endophytic fungi have an abundant sources rich source of rich bioactive molecules with pivotal pharmacological properties. Several studies have found that endophytic fungi-derived bioactive secondary metabolites have antiproliferative, anti-oxidant, and anti-inflammatory properties, but the molecular mechanism by which they induce cell cycle arrest and apoptosis pathways is unknown. This study aimed to determine the molecular mechanism underlying the anticancer property of the endophytic fungi derived active secondary metabolites on human breast cancer cells. In this study, we identified four endophytic fungi from marine seaweeds and partially screened its phytochemical properties by Chromatography-Mass Spectrometry (GC-MS) analysis. Moreover, the molecular mechanism underlying the anticancer property of these active secondary metabolites (FA, FB, FC and FE) on human breast cancer cells were examined on MCF-7 cells by TT assay, Apoptotic assay by Acridine orang/Ethidium Bromide (Dual Staining), DNA Fragmentation by DAPI Staining, reactive oxygen species (ROS) determination by DCFH-DA assay, Cell cycle analysis was conducted Flow cytometry and the apoptotic signalling pathway was evaluated by westernblot analysis. Doxorubicin was used as a positive control drug for this experiment. The GC-MS analysis of ethyl acetate extract of endophytic fungi from the marine macro-algae revealed the different functional groups and bioactive secondary metabolites. From the library, we observed the FC (76%), FB (75%), FA (73%) and FE (71%) have high level of antioxidant activity which was assessed by DPPH scavenging assay. Further, we evaluated the cytotoxic potentials of these secondary metabolites on human breast cancer MCF-7 cells for 24h and the IC50 value were calculated (FA:28.62 ± 0.3µg/ml, FB:49.81 ± 2.5µg/ml, FC:139.42 ± µg/ml and FE:22.47 ± 0.5µg/ul) along with positive control Doxorubicin 15.64 ± 0.8µg/ml respectively by MTT assay. The molecular mechanism by which the four active compound induced apoptosis via reactive oxygen species (ROS) and cell cycle arrest in MCF-7 cells was determined H2DCFDA staining, DAPI staining, Acridine orange and ethidium bromide (AO/EtBr) dual staining, flowcytometry analysis with PI staining and apoptotic key regulatory proteins expression levels measured by westernblot analysis. Our findings, revealed the anticancer potential of endophytic fungi from marine seaweed as a valuable source of bioactive compounds with anticancer properties and underscore the significance of exploring marine-derived endophytic fungi as a promising avenue for the development of novel anticancer agents. Further investigations are necessary to isolate and characterize specific bioactive compounds responsible for these effects and to validate their therapeutic potential in preclinical and clinical settings.

Terpenes as Potential Anti-Alzheimer’s Disease Agents

Alzheimer’s disease (AD), a slowly progressive neurodegenerative disorder, is the main cause of dementia worldwide. However, currently, the approved drugs to combat AD are effective only in treating its symptoms. In fact, an efficacious treatment for this complex and multifactorial disorder remains to be discovered, demanding the urgent development of new therapeutic approaches for the disease, such as the use of bioactive secondary metabolites (SMs) from natural sources. Sessile organisms, like plants, are unable to escape from adverse environmental conditions and must therefore create their own defense. Their main defense strategy is chemical defense that includes the production of an enormously diverse array of bioactive SMs, such as terpenes and their derivatives. This largest and most diverse group of plant SMs also provide the treatment of several diseases due to their broad-spectrum bioactivities, for example, anticancer, antioxidant, and anti-inflammatory properties. Thus, the evaluation of the neuroprotective potential of terpenes is imperative. It is known that the major AD clinical indications (CIs) are extracellular senile plaques of amyloid-β (Aβ) protein, intracellular hyperphosphorylated tau (τ) neurofibrillary tangles (NFTs), uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. Therefore, terpenes that may decrease these CIs might be used for AD treatment. Surely, terpenes targeting more than one AD pathogenic mechanism, multi-target drug ligands (MTDLs), have the potential to become a leading AD treatment. Thus, this review analyzes, for each CI, the scaffolds of the selected terpenes leading to the highest activity.

Secondary metabolite profiling using HR-LCMS, antioxidant and anticancer activity of Bacillus cereus PSMS6 methanolic extract: In silico and in vitro study

Novel anticancer drugs of natural origin have increased tremendously due to the resistance of multiple chemotherapeutic drugs in breast cancer therapy and their high toxicity with undesirable side effects. The study investigates the bioactivity of secondary metabolites derived from Bacillus cereus PSMS6 isolated from marine soil sediment in the Velar estuary, Parangepattai, Cuddalore district, Tamil Nadu, and India. Strains were isolated and antagonistic activity was screened using the agar well diffusion method. B. cereus PSMS6 exhibited potency, and its crude extract was tested for antioxidant, anticancer, and cytotoxic MTT assay potential. The methanolic extract of B. cereus PSMS6 was analyzed by mass spectrometry HRLC-MS and FT-IR to determine the bioactive compounds. A drug interaction study with the anti-breast cancer protein HER2 was performed by molecular docking analysis. Antioxidant activities were determined using total antioxidant scavenging assay, ABTS and DPPH free radical scavenging assays. The total antioxidant scavenging assay of the crude extract of B. cereus methanol had an IC50 value of 28.33±1.01, in ABTS IC50 value of the extract was 29.00±0.28 and in DPPH the IC50 of the extract was 34.91±0.09. The negative ion compound Palmitoylglycerone phosphate had a LibDock score of 149.487 and the positive ion compound N5-(4-Methoxybenzyl) glutamine had 120.116. These compounds show promising anticancer activity. The current study reported that the bioactive secondary metabolite of B. cereus PSMS6 retains anti-cancer, and antioxidant properties. This is the first report to show the production of the Palmitoylglycerone phosphate metabolite from B. cereus PSMS6.

Actinomycetota bioprospecting from ore-forming environments.

Natural products from Actinomycetota have served as inspiration for many clinically relevant therapeutics. Despite early triumphs in natural product discovery, the rate of unearthing new compounds has decreased, necessitating inventive approaches. One promising strategy is to explore environments where survival is challenging. These harsh environments are hypothesized to lead to bacteria developing chemical adaptations (e.g. natural products) to enable their survival. This investigation focuses on ore-forming environments, particularly fluoride mines, which typically have extreme pH, salinity and nutrient scarcity. Herein, we have utilized metagenomics, metabolomics and evolutionary genome mining to dissect the biodiversity and metabolism in these harsh environments. This work has unveiled the promising biosynthetic potential of these bacteria and has demonstrated their ability to produce bioactive secondary metabolites. This research constitutes a pioneering endeavour in bioprospection within fluoride mining regions, providing insights into uncharted microbial ecosystems and their previously unexplored natural products.

Species-level distribution of microbiota with secondary metabolic potential in Chinese Baijiu fermentation

Chinese Baijiu fermentation is a typical spontaneous fermentation with complex microbial community. However, the species-level distribution of microbiota with secondary metabolic potential in Baijiu fermentation has not been well studied so far. In this study, taking soy sauce aroma type Baijiu and light aroma type Baijiu fermentations as examples, we identified 1575 biosynthetic gene clusters (BGCs) belonging to 874 gene cluster families (GCFs) through metagenomic analysis. Bioactivity prediction analysis revealed 210 BGCs producing potential bioactive secondary metabolites (probabilities of bioactivities ≥70%). We recovered 66 bacterial metagenome-assembled genomes (MAGs) to explore distribution of bioactive secondary metabolites at a higher resolution taxonomic level. A total of 16 MAGs were identified as BGC-rich MAGs (>3 BGCs), and they belonged to 11 genera. Four MAGs, annotated to be Bacillus velezensis, Bacillus licheniformis, Kroppenstedtia eburnea and Kroppenstedtia spp., contained more than 3 BGC-producing potential bioactive secondary metabolites and had more than 1 counts per million (CPM) abundance in fermentations. They were identified as the potential producers of bioactive secondary metabolites. This study contributed to characterising the diversity and distribution of microbiota with secondary metabolic potential in Baijiu fermentation, and mining novel secondary metabolites and their producers.

Extracellular vesicles isolated from Arabidopsis thaliana leaves reveal characteristics of mammalian exosomes.

Plant-derived extracellular vesicles (EVs), containing a myriad of bioactive proteins, microRNAs, lipids, and secondary metabolites, have recently become the focus of rising interest due to their important roles in various applications. The widely accepted method for isolating plant EVs is differential ultracentrifugation plus density gradient centrifugation. However, the combination of differential ultracentrifugation and density gradient centrifugation for the isolation of plant EVs is time-consuming and labor-intensive. Hence, there is a need for more efficient methods to perform the separation of plant EVs. In this study, EVs were separated from Arabidopsis thaliana leaves by a cost-effective polyethylene glycol (PEG)-based precipitation approach. The mean size of purified Arabidopsis thaliana EVs determined by dynamic light scattering was 266nm, which is consistent with nanoparticle tracking analysis. The size was also confirmed via transmission electron microscopy with morphology of a cup-shaped appearance which is the typical mammalian exosome's morphology. Additionally, Western blotting of the purified Arabidopsis thaliana EVs, using commercially available mammalian exosomal kits, displayed surface marker tetraspanin proteins (CD9, CD63, and CD81), and endosomal sorting complexes required for transport (ESCRT)-associated proteins (TSG101 and ALIX). This demonstrates that the purified Arabidopsis thaliana EVs reveal the typical proteins reported in mammalian exosomes.

Pontederia crassipes Biosynthesised Silver Nanoparticles (AgNPs), Characterisation and Activity against Multidrug-Resistant Microbes

Introduction: Pontederia crassipes (water hyacinth) has been singled out as one of the major causes of enormous economic and ecological losses to tropical water systems and habitats. Almost impossible to eradicate, the ominous species is characterized by rapid multiplication, giving rapid and extensive spread that can choke entire rivers and water bodies. However, vast, diverse bioactive secondary metabolites are found in P crassipes which exhibit an expansive assortment of antibacterial properties used in traditional medicine. The rapid emergence of Multi Drug Resistant (MDR) pathogens to common drugs is a pandemic of global proportions. Global health institutions are calling for a coordinated, global action plan to develop new biomaterials to combat the rising threat by MDR strains and improve treatment outcomes and save lives. This study proposes consumption of the water hyacinth lily species through a novel, material biosynthesis approach not only to manage the aquatic infestation but to develop advanced multifunctional, anti-microbial Silver nanoparticles through bio-reduction and capping of Silver salts targeted at MDR microbes. Methodology: After screening for active phytoconstituents of P.crassipes. The Biosynthesis of Novel AgNPs mediated by phenolic, antibacterial lyophilized hydro-ethanolic extracts from P crassipes as both bioreduction and capping agents was investigated. The resultant AgNPs characteristics, toxicological profiles and the antibacterial effects on 10 common microbes including MDR bacterial strains were evaluated. Observations and Results: TEM revealed that cubic and spherical nanometric AgNPs structures were successfully synthesized with particle size range from 10-60nm. With an average zone of inhibition of 29mm and an MIC of 6.25 µg/ml .The nanoparticles were efficacious against selected MDR strains and common infectious bacterial strains tested. In-vivo acute oral toxicity evaluations confirmed the safety of P crassipes. Conclusion: Biogenic P.crassipes mediated AgNPs are feasible, safe and efficacious and have immense potential for optimization into efficient broad spectrum MDR antibacterial agents.b

Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway

Ethnopharmacological relevanceGout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. Aim of the studyThis study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. Materials and methodsUPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. ResultsOur analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. ConclusionThis study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.

Novel Bioactive Natural Products from Marine-Derived Penicillium Fungi: A Review (2021-2023).

Marine-derived Penicillium fungi are productive sources of structurally unique and diverse bioactive secondary metabolites, representing a hot topic in natural product research. This review describes structural diversity, bioactivities and statistical research of 452 new natural products from marine-derived Penicillium fungi covering 2021 to 2023. Sediments are the main sources of marine-derived Penicillium fungi for producing nearly 56% new natural products. Polyketides, alkaloids, and terpenoids displayed diverse biological activities and are the major contributors to antibacterial activity, cytotoxicity, anti-inflammatory and enzyme inhibitory capacities. Polyketides had higher proportions of new bioactive compounds in new compounds than other chemical classes. The characteristics of studies in recent years are presented.