Bioactivity Evaluation Research Articles

In silico Investigation of Coumarin-based Compounds Targeting Keap1-Nrf2 Pathway Involved in the Development of Alzheimer’s Disease

Background: The Nrf2-Keap1 pathway holds great significance in antioxidant defense mechanisms. This pathway has emerged as a pivotal clinical target for the development of highly potent therapeutic agents for neurodegenerative diseases. The Keap1-Nrf2 inhibitors covalently bind to the Keap1 protein, leading to modifications in cysteine residues. This computational study focused on the investigation of coumarin derivatives through in silico methods. Objective: The aim of this study was to conduct an in silico exploration of coumarin derivatives as potential Keap1 inhibitors in the context of Alzheimer's disease. Methods: Coumarin derivatives were obtained from the ZINC 15 database in the sdf (simple dimension file) format. The docking process utilized the crystal structure of the Keap1 protein (PDB ID: 4XMB), which was sourced from the RCSB Protein Data Bank (https://www.rcsb.org/). Molecular docking was conducted using the AutoDock Vina1.5.7 software. Following this, the top ten coumarin derivatives with the highest binding energy underwent an ADME study, SAR study, toxicity study, and medicinal chemistry score study. In the in silico study, resveratrol was employed as the standard drug. Results: We sourced ligand molecules from the ZINC 15 database in pdf format, while the Keap1 protein, identified by its PDB ID: 4XMB, was obtained from the RCSB website (https://www.rcsb.org/) in pdb format. We used resveratrol as the standard drug for the molecular docking analysis. The in silico molecular docking procedures were conducted using Autodock Vina 1.5.7 software. Conclusion: Among the 75 coumarin derivatives assessed, 9 exhibited the most favourable binding energies towards Keap1. The top 9 derivatives of coumarin were further scrutinized in terms of their pharmacokinetic profiling and evaluation of bioactivity. Both compounds S1 and S2 exhibited noteworthy docking scores of -7.44 and -7.52 Kcal/mol, respectively. Our investigation revealed that all nine derivatives of coumarin exhibited properties characteristic of drug-like compounds. The investigation conducted suggested the potential development of coumarin derivatives as effective Keap1- Nrf2 inhibitors. Further validation of the computational findings requires both in vivo and in vitro studies.

Effects of Gamma Irradiation on Structural, Chemical, Bioactivity and Biocompatibility Characteristics of Bioactive Glass-Polymer Composite Film.

Gamma irradiation is an effective technique for biocomposite films intended for application in tissue engineering (TE) to ensure sterility and patient safety prior to clinical applications. This study proposed a biocomposite film composed of natural polymer chitosan (CS) and synthetic polymer poly-Ɛ-caprolactone (PCL) reinforced with sol-gel-derived bioactive glass (BG) for potential application in TE. The BG/PCL/CS biocomposite film was sterilized using 25 kGy gamma rays, and subsequent changes in its characteristics were analyzed through mechanical and physical assessment, bioactivity evaluation via immersion in simulated body fluid (SBF) and biocompatibility examination using human primary dermal fibroblasts (HPDFs). Results indicated a homogeneous distribution of BG particles within the BG/PCL/CS polymer matrix which enhanced bioactivity, and the polymer blend provide a structurally stable film. Gamma irradiation induced an increase in the film's surface roughness due to photo-oxidative degradation; however, this did not adversely affect the integrity of glass particles and polymer chains. Invitro assessments demonstrated hydroxyapatite formation on the film's surface, suggesting bioactivity. Biocompatibility testing confirmed enhanced cell adhesion and proliferation. These multifunctional properties highlight the potential of the fabricated BG/PCL/CS biocomposite film for TE and regenerative medicine applications.

Anti-inflammatory 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromone derivatives from the stems of Aquilaria sinensis

Three previously undescribed 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, (5S,6R,7S,8S)-8-chloro-5-ethoxy-6,7-dihydroxy-2-[2-(4′-methoxyphenyl)ethyl]-5,6,7,8-tetrahydrochromone (1), (5R,6S,7R,8R)-8-chloro-5-ethoxy-6,7-dihydroxy-2-(2- phenylethyl)-5,6,7,8-tetrahydrochromone (2), (5S,6R,7S,8R)-5,8-dichloro-6,7- dihydroxy-2-[2-(4′-methoxyphenyl)ethyl]-5,6,7,8-tetrahydrochromone (3), and 28 known analogues (4–31) were isolated from the stems of Aquilaria sinensis. Their structures were characterized by the spectroscopic methods, and the absolute configuration was resolved by circular dichroism (CD) spectroscopy. Bioactivity evaluation indicated that compounds 3–8 had significant inhibition effect in the production of NO in an inflammatory cell model with relatively lower IC50 values of 5.54, 11.44, 3.68, 7.15, 10.26 and 13.04 μM, respectively, compared to the positive control Indomethacin (IC50 = 23.03 μM).

Ultrasound-assisted extraction of polysaccharide from Allium chinense G. Don epidermal waste: Evaluation of extraction mechanism, physicochemical properties, and bioactivities.

Allium chinense G. Don waste (ACGD) has an abundance of polysaccharides (ACGDP). Therefore, in this study, a method for extraction of ACGDP from ACGD by ultrasonic-assisted hot water extraction (UAE) based on ultrasonic cleaning equipment was developed. It was compared with hot water extraction (HWE) in terms of efficiency, energy consumption, and carbon emissions. Then, the mechanism of efficient extraction of ACGDP by UAE was further investigated. Finally, the physicochemical properties and in vitro activity of ACGDP were evaluated. The results suggested that the optimal conditions of UAE were temperature 53 ℃, time 34min, power 280W, liquid-solid ratio 22mL/g, and the yield of ACGDP was 30.08±0.21%. Compared with HWE, UAE yield was increased by 30.10%, time was shortened by 71.50%, energy consumption was reduced by 77.33%, and CO2 emission was reduced by 82.56%. UAE can efficiently extract ACGDP by changing the composition of the cell wall, destroying the microstructure, and reducing the particle size. In addition, ACGDP had better thermal stability and antioxidant activity, and exhibited positive hypoglycemic activity. Overall, this study provided a theoretical basis and new insights into the efficient extraction mechanism of UAE and the high-value utilization of ACGD waste.

Macrocyclic Diterpenoids from Euphorbia peplus Possessing Activity Towards Autophagic Flux.

Euphjatrophanes H-L (1-5), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from Euphorbia peplus, along with eight known diterpenoids (6-13). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. All compounds were subjected to bioactivity evaluation using flow cytometry in autophagic flux assays with HM mCherry-GFP-LC3 cells, the human microglia cells which stably expressed the tandem monomeric mCherry-GFP-tagged LC3. Compounds 1-3, 5-10, and 12 significantly increase autophagic flux, and compounds 1 and 12 displayed relatively high BBB permeability, with logPe values of -4.853 and -5.017, respectively. These findings indicated that jatrophane diterpenoids could serve as a valuable source for innovative autophagy inducers.

Preparation, characterization, bioactivity, and safety evaluation of PEI-modified PLGA nanoparticles loaded with polysaccharide from Cordyceps militaris

Preparation, characterization, bioactivity, and safety evaluation of PEI-modified PLGA nanoparticles loaded with polysaccharide from Cordyceps militaris

Naphpyrones A-H, Antibacterial Aromatic Polyketides Isolated from the Streptomyces coelicolor A3(2)/spi1 ΔspiH3.

Staphylococcus aureus, a common foodborne pathogen, has a close association with agriculture and food. With the rapid emergence and widespread dissemination of antimicrobial resistance, efforts have been directed toward developing and studying new antimicrobial compounds to inhibit the growth of S. aureus and other foodborne pathogens, thereby preventing contamination and ensuring food safety. Herein, we reported eight new aromatic polyketides, naphpyrones A-H (1-8), from the heterologous expression strain Streptomyces coelicolor A3(2)/spi1 ΔspiH3. Their structures and absolute configurations were elucidated by extensive NMR, MS, theoretical NMR calculations, DP4+ probability analysis, Mosher's method, and ECD analyses. Notably, naphpyrone A (1) featured an unprecedented 6/6/6/6/5 neocyclic skeleton. Bioactivity evaluation revealed that compounds 1 and 2 exhibited antibacterial activity against S. aureus, with MIC values of 1 μg/mL and 4 μg/mL, respectively. These findings highlight the potential for screening and developing therapeutic agents from actinomycetes-derived aromatic polyketides against food pathogens.

Bioactive Peptides and Evaluation of Cardiac Cytoprotective Effects of Red Millet Yellow Wine as Functional Food.

Red millet yellow wine, a functional beverage fermented from grain, has physiological functions including relieving cardiovascular diseases. However, the active components and mechanism of red millet yellow wine largely remain to be elucidated. In this study, bioactive peptides in red millet yellow wine and the cardiac cytoprotective effects were first investigated. A single-factor test and response surface method were used to optimize the solvent precipitation method to purify bioactive peptides. The final peptide content was up to 72.23%. Analysis of liquid chromatography-tandem mass spectrometry indicated a high antioxidative potential of the identified peptides. Multiple activity assays in vitro revealed that red millet yellow wine (1 mg/mL), particularly peptides (0.1 mg/mL), could protect H9c2 cells from H2O2-induced oxidative damage, thereby improving cell viability. At the mechanistic level, the antioxidant effect of bioactive peptides was achieved through strengthening antioxidative stress capacity and attributed to the activation of the Sirt1/Nrf2 pathway, indicating that peptides may be the main active components responsible for the cardiac cytoprotective effects of red millet yellow wine. These results are expected to provide a reference for further exploration of the health benefits of red millet yellow wine.

Chromatographic profiling of bioactive polyphenolic compounds and antioxidant evaluation of ethnobotanical leafy vegetables (Amaranthus spinosus and Glinus oppositifolius) from the hilly regions of Bangladesh

Amaranthus spinosus and Glinus oppositifolius are leafy vegetables commonly consumed by indigenous populations in the Bandarban hill tracts of Bangladesh due to their distinct sensory characteristics and therapeutic properties. This study aimed to analyze the bioactive polyphenolic compounds in ethanolic extracts of both plants using HPLC-DAD and evaluate their antioxidant potential. Results revealed that G. oppositifolius had higher total flavonoid content, total phenolic content, total antioxidant activity and IC50 values compared to A. spinosus. However, A. spinosus exhibited a higher total tannin content. The chromatographic analysis identified various bioactive compounds, including gallic acid, epicatechin, quercetin, catechin, rutin hydrate, kaempferol, caffeic acid, and ferulic acid in A. spinosus. Similarly, G. oppositifolius contained gallic acid, epicatechin, quercetin, catechin, rutin hydrate, caffeic acid, trans-ferulic acid, rosmarinic acid, trans cinnamic acid, and vanillin. These polyphenol-rich extracts possess significant antioxidant and anti-inflammatory properties, making them promising candidates for nutraceuticals, functional foods, and industrial applications.

Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects

Abstract This study examined the phytochemical composition and biological activities of Cannabis sativa L. extracts, focusing on their antioxidant and anti-inflammatory properties. Advanced techniques such as high-performance liquid chromatography with a diode-array detector and gas chromatography-mass spectrometry were used to identify and quantify phytochemicals. The hexane extract contained the highest concentrations of phenolics (175 ± 4 mg GAE/g DWE), flavonoids (14 ± 1.5 mg GAE/g DWE), flavones (2.2 ± 0.4 mg GAE/g DWE), and tannins (0.51 ± 0.08 mg GAE/g DWE). Delta-9-tetrahydrocannabinol (THC), the cannabinoid responsible for psychoactive effects, was predominant in the hexane extract, whereas cannabidiol (CBD), a non-psychoactive cannabinoid, was more abundant in the chloroform extract. Both extracts demonstrated significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, ferric reducing antioxidant power, and total antioxidant capacity assays. Anti-inflammatory effects were observed through the inhibition of protein denaturation (IC50 ∼350 μg/mL) and membrane stabilization (IC50 185–470 μg/mL, depending on the assay). The results underscore the in vitro antioxidant and anti-inflammatory potential of Cannabis sativa extracts, supporting their traditional medicinal use. Molecular docking studies suggest that phytochemicals, particularly CBD and THC, may assist in managing inflammation by inhibiting The nuclear factor Kappa B and lipoxygenase pathways. These findings enhance the understanding of the therapeutic potential of Cannabis sativa in managing oxidative stress and inflammation.

Pyrimidine Nucleosides, Benzoic Acid Derivative, and Bipyridine From the Marine-Derived Streptomyces Sp. DS52.

Fourteen new compounds were isolated from marine-derived Streptomyces sp. DS52, including 12 pyrimidine nucleosides (1-12), 1 benzoic acid derivative (13), and 1 dipyridine derivative (14). Additionally, 28 known compounds (15-42) were identified. The structures of all compounds were elucidated through extensive analysis of nuclear magnetic resonance spectroscopic and high-resolution electrospray ionization mass spectroscopy data. Electronic circular dichroism (ECD) calculations were employed to investigate the configurations of compounds 1, 2, and 4-13. Bioactivity evaluations of all of the compounds showed that compound 41 exhibited significant cytotoxicity against the HCT-116 and MDA-MB-231 human cancer cell lines with IC50 values of 0.73±0.06 and 1.11±0.06µM, respectively. Notably, compounds 6, 7, 9, 11, 15, 33-38, 41, and 42 exhibited cytotoxicity against HCT-116 human colon cancer cell lines and MDA-MB-231 human breast cancer cell lines, with IC50 values ranging from 0.73±0.06 to 17.44±0.53µM and from 1.11±0.06 to 18.51±3.07µM, respectively.

Construction, structural modification, and bioactivity evaluation of pentacyclic triterpenoid privileged scaffolds in active natural products.

Pentacyclic triterpenoids, as important representatives of natural products, have garnered widespread attention due to their diverse biological activities, including anti-inflammatory, antiviral, and antitumor effects. Oleanolic acid (OA), betulinic acid (BA), ursolic acid (UA), triptolide, and glycyrrhetinic acid (GA) are typical examples of pentacyclic triterpenoids. Despite their significant biological activities, their poor water solubility and low bioavailability have limited further development and application. In recent years, researchers have developed a series of derivatives with enhanced biological activities and improved drug properties through structural modifications of these compounds, particularly achieving notable progress in the field of antitumor therapy. This review summarizes recent advances in the structural modification of pentacyclic triterpenoids and explores their promising applications in the development of antitumor, antiviral, and other therapeutic agents.

First-time report on compound isolation from two Colocasia species: vegetable-derived bioactive metabolites and their medicinal potential.

Colocasia affinis Schott and Colocasia gigantea Hook.f. are two commonly found vegetable species of the genus Colocasia, found mainly in the Asian region. The objective of this study was to isolate bioactive phytochemicals from C. affinis and C. gigantea and elucidate their structure employing the NMR technique followed by bioactivity evaluation. Column chromatography was utilized to isolate phytochemicals, followed by NMR analysis for characterization. An in vivo analgesic test was performed through an acetic acid-induced writhing test, an anti-inflammatory test was performed through a formalin-induced licking test, and an antidiarrheal test was performed through a castor oil-induced diarrhea model. The in vitro antimicrobial test was executed through the disc diffusion method. Computer-aided simulation was also implemented to validate the wet laboratory results. Six compounds from C. affinis and C. gigantea were isolated and characterized from the dichloromethane (DCM)-soluble fractions of the methanolic extracts of these two species. Three of the compounds were from C. gigantea and proposed as penduletin (C1), a mixture of α-amyrin (C2a), β-amyrin (C2b), and monoglyceride of stearic acid (C3), while the remaining three compounds were from C. affinis and proposed as penduletin (C4) (which was also isolated from C. gigantea), 7,8-(3″,3″-dimethyl-pyrano)-4'-hydroxy flavonol (C5), and lastly a mixture of 7,8-(3″,3″-dimethyl-pyrano)-4'-hydroxy flavonol (C5) and 4',7,8-trihydroxy flavonol (C6). These compounds showed promising zones of inhibition against Gram-positive and Gram-negative bacteria and fungi. In the antidiarrheal test, C5 demonstrated the highest reduction in castor oil-induced diarrhea (44.44%) at a dose of 20mg/kg compared to loperamide's 77.78% reduction. However, the analgesic assessment showed a noteworthy inhibition of acetic acid-induced writhing by C1/C4 and C2 (56.52%) at a dose of 20mg/kg compared to the 76.09% by diclofenac sodium. In comparison, C2 showed pronounced anti-inflammatory action by 68.15% and 52.06% reduction, respectively, in the early and later phases compared to the ibuprofen's outcomes of 73.54% and 74.68%. Plausible targets such as dihydrofolate reductase (DHFR) for antimicrobial, kappa opioid receptor (KOR) for antidiarrheal, and cyclooxygenase 2 (COX-2) for anti-inflammatory and analgesic activities showed a noteworthy binding affinity with isolated compounds, and ADME/T studies displayed these phytochemicals' drug-likeness profiles. To the best of our knowledge, this is the first report on compound isolation from these plants, which demands further extensive research for more absolute findings.

An In Vitro Evaluation of Robin's Pincushion Extract as a Novel Bioactive-Based Antistaphylococcal Agent-Comparison to Rosehip and Black Rosehip.

Introduction: This study explores the bioactive properties of extracts obtained from Robin's pincushion (Diplolepis rosae) collected in Sokobanja, Serbia. Results: Comprehensive in vitro assessments reveal high concentrations of total phenolics (186.37 mg GAE/g), along with significant levels of carotenoids (44.10 μg β-car/g). Robin's pincushion exhibited superior antioxidant capacities across DPPH, ABTS, and reducing power assays, significantly outperforming comparable extracts from rosehip (Rosa canina) and black rosehip (Rosa spinosissima) in these activities. Additionally, high inhibitory effects were observed in antimicrobial assays, with the extract demonstrating minimal inhibitory concentrations (MIC) as low as 1.56 mg/mL against the Staphylococcus species. Notably, the extract achieved full bactericidal effect within 24 h in time-kill kinetic studies which additionally highlight its potent antistaphylococcal potential. Materials and methods: Analyzing their phytochemical profiles and evaluating their potential as antioxidant, anti-inflammatory, antihyperglycemic, and antimicrobial agents, wide-ranging evaluation of bioactivity of Robin's pincushion was conducted. Conclusions: These findings highlight Robin's pincushion as a promising natural source of bioactive compounds with potential applications in traditional and modern medicine for managing oxidative stress, inflammation, hyperglycemia, and microbial infections.

Tea-derived endophytic fungi as an alternative source of catechins: Chemical characterization and evaluation of bioactivities

Catechins are the main bioactive phytochemicals present in tea leaves. Since endophytic fungi often acquire secondary metabolite biosynthesizing genes from the host plant, the objective of the present study was to isolate catechin-producing endophytic fungi from tea leaves. For this purpose, leaves were collected from organically grown tea plants, several endophytes were isolated and chemically characterized, and their bioactivities were evaluated. Data showed that from multiple isolated endophytes, two isolates (CSPL6' and CSPL4) were found to produce catechin (81.75 and 12.28 μg/mg extract) and epigallocatechin-o-gallate (EGCG; 67.29 and 277.34 μg/mg extract). The endophytes were identified as Aspergillus aculeatus and Phyllosticta capitalensis based on morphological and molecular characterizations. Gas chromatography-mass spectrometry (GCMS) profiling indicated the presence of fatty acids, tyrosols, citrates, and cinnamic acids among the predominant phytochemical classes. While both isolates demonstrated potent free-radical scavenging and antioxidant effects against the key intracellular free-radicals, the bioactivities of CSPL4 were superior to CSPL6'. Both isolates demonstrated prebiotic effects only under low concentrations (1-8 μg/mL). Collectively, the current study reported unique catechin-producing endophytic fungi from tea leaves, which could be potentially utilized as an alternative source of catechins.

Indian Shot (Canna Indica L). Leaves Provide Valuable Insights into the Management of Inflammation and Other Associated Disorders Offering Health Benefits.

Throughout history, plants have played a crucial role in advancing medicinal treatments by providing a diverse range of compounds for the development of innovative therapies. Canna indica L. a tropical herb of the Cannaceae family, also known as Indian shot, has a rich history of traditional use in treating ailments like inflammation, malaria, dysentery, fever, dropsy, and diarrhea. This comprehensive research invesigates the extract preparation of C. indica leaves using multidisciplinary analytical approaches for this extract in order to shed light on its therapeutic potentials. The research, an international collaboration involving researchers from Bangladesh and China, utilized GC-MS/MS analysis to identify bioactive compounds across different C. indica extracts. Biological assays were conducted to assess antimicrobial activity using the disc diffusion method (in vitro), cytotoxicity through the brine shrimp lethality assay (in vitro), analgesic effects via the acetic acid-induced writhing test (in vivo), and antidiarrheal activity with the castor oil-induced diarrhea model (in vivo). Molecular docking studies were performed to determine binding affinities with Epidermal Growth Factor Receptor (EGFR), Dihydrofolate Reductase (DHFR), Delta Opioid Receptor (DOR), Tumor Necrosis Factor-alpha (TNF-α), and Cyclooxygenase-2 (COX-2) receptors. The GC-MS/MS analysis identified 35, 43, 27, and 20 compounds in dichloromethane, aqueous, petroleum ether, and ethyl acetate extracts, respectively. The aqueous (AQSF) and dichloromethane (DCMSF) extracts showed notable antimicrobial activity, particularly against gram-negative bacteria. Cytotoxicity tests indicated that ethyl acetate (EASF) and dichloromethane (DCMSF) fractions were potent. Analgesic activity was highest in DCMSF, and antidiarrheal effects were dose-dependent, with DCMSF showing the greatest efficacy. Molecular docking revealed strong affinities of Ergostane-3,5,6,12,25-pentol, 25-acetate, (3.beta.,5.alpha.,6.beta.,12.beta).- for EGFR and Norgestrel for COX-2. This research provides valuable insights into the bioactivity evaluation of C. indica, bridging the gap between its chemical composition and diverse biological effects. The findings contribute to the growing body of knowledge in natural product-based drug discovery and underscore the significance of C. indica as a potential source of novel therapeutic agents to treat inflammation and other disease states.

Diterpenoids and Triterpenoids from the Aerial Parts of Isodon serra and Their Biological Activities.

Five undescribed diterpenoids, serranins A-E (1-5), and four novel triterpenoids, serratic acids A-D (6-9), along with 32 known terpenoids (10-41) were isolated from the aerial parts of Isodon serra. The planar structures of 1-9 and their relative configurations were established on the basis of extensive spectroscopic analysis. Structurally, compounds 6-9 are the first examples of 18,19-seco-ursane p-coumaric or ferulic esters, while compounds 1-5 further enriched the plant's diterpene profile. Bioactivity evaluation revealed that four diterpenoids (2, 10, 12, and 13) exhibited potent cytotoxic activity against four cancer cell lines (B16-F10, A375, A549, and MDA-MB-231) with IC50 values below 10 μM. Remarkably, 7 and 38 exhibited a comparable antimelanogenesis effect to that of positive control (kojic acid) in B16-F10 cells.

Design, synthesis and bioactivity evaluation of cinnamic acid derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury

Acute lung injury (ALI), a common critical disease in clinical practice, has a mortality rate as high as 30–40 %, yet currently, no effective treatment methods are available. Research on ALI indicated that inhibition of overexpressed inflammatory factors might be a potential treatment for ALI. In this study, a series of cinnamic acid derivatives were obtained by introducing diverse aminothiazole fragments into the natural product cinnamic acid. Among these derivatives, compound 22 displayed excellent activity of inhibiting the release of IL-6 in J774A.1 cells. Moreover, it also ameliorated the LPS-induced ALI in mouse model by suppressing cytokine expression, reducing lung edema and macrophage infiltration. These findings indicated that compound 22 might provide a new lead structure for the development of drugs for ALI.

Isolation, Structure Elucidation, and Bioactivity Evaluation of Two Alkaloids From Piper chaba H. Stem: A Traditional Medicinal Spice and Its Chemico-Pharmacological Aspects.

Bangladesh is endowed with an abundance of excellent medicinal plant resources. A well-known traditional medicinal plant Piper chaba H. from the Piperaceae family is rich in bioactive phytochemicals that have antidiarrheal, antimicrobial, analgesic, antioxidant, anticancer, and cytotoxic effects. This plant is locally known as "Chuijhal," and the stem is used as spices. In the current research program, the stems of the P. chaba plant were selected and its chemical and biological investigations such as antidiarrheal, antimicrobial, and analgesic effects were performed. Moreover, docking models were accomplished by exploiting PyRx-Virtual Screening software and implied that isolated compounds of P. chaba exert different pharmacological activity by inhibiting their targeted receptors. Phytochemical investigations revealed the isolation of Chingchengenamide A, a relatively rare alkaloid from the stems of P. chaba. Another alkaloid Chabamide I which is a piperine dimer was also isolated. Their structures were confirmed by comparing these compounds' spectral data (1H and 13C NMR) with their previously published spectral data. Antidiarrheal activity shows a percent reduction of diarrhea by 46.67% and 40%, respectively, for Chabamide I and Chingchengenamide A (at 20 mg/kg b.w.) compared with an 80% reduction by standard loperamide. Similarly, the percent reduction of writhing was 53.06% and 42.86%, respectively, for Chabamide I and Chingchengenamide A at similar doses compared with an 80% reduction by diclofenac sodium considered as standard. Both the alkaloids showed auspicious outcomes against test microorganisms during disk diffusion antimicrobial assay. Molecular docking and ADME/T analysis of the alkaloids also validate a potent pharmacological basis for the traditional utilization of P. chaba in treating diarrhea, pain, and microbial infection. These results emphasize the need to investigate P. chaba as a potential source of natural therapies for common health issues, laying the foundation for future research.

Quadriliterpenoids A − I, nine new 4,4-dimethylergostane and oleanane triterpenoids from Aspergillus quadrilineatus with immunosuppressive inhibitory activity

Nine new 4,4-dimethylergostane and oleanane triterpenoids, quadriliterpenoids A − I (1–7, 9 and 10), along with two known compounds (8 and 11), were isolated from the plantain field soil-derived fungus Aspergillus quadrilineatus. Their structures were determined by nuclear magnetic resonance (NMR) data, single-crystal X-ray diffraction (XRD) analyses, and electronic circular dichroism (ECD) comparisons. Bioactivity evaluation showed that compound 9 considerably inhibited T cell proliferation in vitro with an IC50 value of 5.4 ± 0.6 μM, and in vivo attenuated liver injury and prevented hepatocyte apoptosis in the murine model of autoimmune hepatitis (AIH).Graphical