The aim of this study is to conduct research about the phytochemical composition and neuroprotective potential of Encephalartos kisambo leaves. LC-ESI-MS/MS profiling of the methanolic extract putatively annotated 56 different compounds. Six compounds, namely β-sitosterol, 7,4',7'',4'''-tetra-O-methyl amentoflavone, kayaflavone, isoginkgetin, bilobetin, and amentoflavone were isolated and characterized by spectroscopical investigations using UV, 1D- and 2D-NMR, HPLC-ESI-MS, and HR-ESI-MS. The neuroprotective efficacy of the ethyl acetate and n-butanol fractions was evaluated in vivo using an aluminum chloride-induced neurodegeneration model. The ethyl acetate and n-butanol fractions exihibted significant cognitive improvement in the Morris water maze test. These fractions also enhanced catalase activity while markedly reducing malondialdehyde levels, indicating their ability to alleviate oxidative stress associated with dementia. Furthermore, treatment with the n-butanol fraction downregulated the expression of lnc-MALAT1 and vimentin while upregulating SIRT1, suggesting modulation of neuroinflammatory and apoptotic pathways. Histopathological examination revealed that co-administration of the n-butanol fraction with AlCl₃ preserved the neuronal architecture in the cerebral cortex and CA2 region of the hippocampus. These findings highlighted E. kisambo as a promising source of neuroprotective agents with potential therapeutic relevance to help prevent Alzheimer's disease and manage its development.

Antimicrobial resistance remains a significant global threat, leading to a high mortality rate and the need for alternative treatments. This study aimed to determine the antimicrobial and antioxidant properties of liquid-liquid fractions from Terminalia mantaly stem bark extract and to investigate their potential multi-target interactions using in silico approaches. DPPH, ABTS, and FRAP assays, and cytotoxicity on Vero cells, were performed. The most active fractions were further evaluated for time-kill kinetics, antibiofilm activities, scanning electron microscopy (SEM), and liquid chromatography-mass spectrometry profiling, followed by molecular docking, molecular dynamics (MD) simulations, quantum-chemical calculations, and pharmacokinetics and toxicity profiling. Five fractions (F1-F5) showed minimum inhibitory concentrations ranging from 62.5 to 1000 μg/mL. Staphylococcus aureus ATCC43300 and Candida albicans ATCC14516 were the most susceptible strains, with F4 and F5 showing the highest activity against bacteria and F1 and F3 against yeast. The highest antioxidant activity was obtained with F1 against DPPH (IC50 of 237.4 μg/mL), F4 against FRAP (IC50 of 22.69 μg/mL), and F5 against ABTS radicals (IC50 of 23.46 μg/mL). SEM analysis indicated that the fractions disrupted the membrane and caused lysis of S. aureus. LC-MS profiling revealed 26 metabolites, with CNP0326236 and 6DTA identified as leads against AgrA, CrtM, and SarA. These findings suggest that modulation of quorum sensing, virulence factor expression, and cellular integrity may contribute to the observed antibacterial activity; however, these proposed mechanisms require experimental validation. Further studies, including mechanistic investigations and in vivo validation, are necessary to establish the antimicrobial potential of the identified lead compounds.

Rhododendron anthopogonoides, an important medicinal plant, has been historically used in both traditional Chinese medicine and Tibetan folk medicine. The first phytochemical investigation on the water-soluble fraction of its leaves and twigs led to the isolation of seven new aromatic glycosides, named anthopogosides A-G (1-7), together with 15 known compounds (8-22). Their chemical structures and absolute configurations were unambiguously elucidated by comprehensive spectroscopic analysis (NMR and HRMS) and quantum chemical calculations (NMR and ECD). Compounds 3-5, 15, 16, and 21 showed significant anti-inflammatory activity at the concentration of 40 μM. Compound 10 exhibited the most potent DPPH and ABTS free radical scavenging capacities with IC50 values 29.46 ± 0.07 and 79.10 ± 1.07 μM, respectively. In addition, flavonoid trimers 20 and 22 displayed outstanding α-glucosidase inhibitory activity with IC50 values of 0.48 ± 0.02 and 0.47 ± 0.02 μM, which were 700-fold higher than that of the positive control acarbose. These findings could greatly enrich the chemical diversity of water-soluble constituents from Rhododendron species and highlighted their potential applications.

Two neolignans, including a new compound, myrifraglin A (1), and a known analogue (2), were isolated from the leaves of Indonesian Myristica fragrans Houtt. Their structures and absolute configurations were established using spectroscopic analyses, chiroptical methods, and density functional theory calculations. Both compounds showed no substantial cytotoxicity against human breast cancer (MCF-7) and lung adenocarcinoma (A549) cells, with IC₅₀ values above 300 μM. In contrast, they exhibited weak TLR4 agonistic activity in the absence of lipopolysaccharide (LPS) and modulated cytokine production in human THP-1 monocytes and murine RAW264.7 macrophages, with only 2 enhanced LPS-induced TNF-α production. Complementary in silico studies further suggested potential interactions with proteins involved in TLR4-associated inflammatory signaling. These findings provide new insights into the immunomodulatory potential of neolignans from M. fragrans.

Moringin [4-(α-L-rhamnopyranosyloxy)benzyl isothiocyanate] is a chemically distinctive glycosylated isothiocyanate generated from glucomoringin in Moringa oleifera. This PRISMA 2020 systematic review evaluated primary mammalian studies using chemically defined moringin, moringa isothiocyanate-1 (MIC-1), or defined moringin formulations to clarify molecular targets, signalling pathways and translational evidence. PubMed/MEDLINE and Europe PMC were searched from inception to 15 September 2026, with backward and forward citation searching. Forty-one primary mechanistic studies met the prespecified criteria. The strongest recurrent evidence involved suppression of NF-κB-linked inflammatory signalling and activation of Nrf2-dependent antioxidant responses. Additional evidence implicated JAK/STAT signalling, Wnt/GSK3β/β-catenin-PPARγ and PI3K/AKT/mTOR networks, PTP1B-dependent Src/Ras/Raf/ERK signalling, mitochondrial apoptosis, TRPA1 and ion-channel modulation, autophagy/mitophagy, epigenomic regulation, and cysteine-adduct chemistry with slow hydrogen sulfide release. Causal support was strongest where genetic, pharmacological or direct functional perturbation was used, whereas many pathway associations remain inferential. No qualifying human study of isolated moringin was identified. Moringin therefore appears to act as a pleiotropic electrophilic signal modulator rather than a single-target ligand. Translation will require pharmaceutical-grade standardisation, exposure-defined pharmacokinetics, direct target-engagement studies, safety characterisation and early human biomarker trials.

Ageratina adenophora is an invasive plant known for its toxicity to livestock. Many advantageous endophytes, extracts, and metabolites with antibacterial, antioxidant, and anti-inflammatory properties have been identified from A. adenophora in recent years. However, there is little information about the antiproliferative activity of these plant resources. Therefore, this study aims to screen and identify endophytic fungi from Ageratina adenophora that show favourable antiproliferative properties in vitro. Firstly, putative strains antiproliferative activity were screened and identified using the Cell Counting Kit-8 (CCK-8) method, and the chemical constituents of the extract were characterized by LC-MS/MS analysis, then potential targets and pathways were predicted through network pharmacologyand further explored through molecular docking and in vitro experiments. Our results showed that, Alternaria alternata Y-13 endophyte exhibited potent antiproliferative activity at IC50 value of (15.90 ± 2.54) μg/mL against HeLa S3 cells. The network pharmacology identified 157 potential targets, and 10 core genes including AKT1 and CASP3; KEGG enrichment revealed pathways such as cancer, PI3K-Akt, and apoptosis; the molecular docking suggested that theputatively annotated metabolites could bound to AKT1 and EGFR. In vitro experiments showed that Y-13 ethyl acetate extracts (EAE) regulated the expression of apoptosis-related genes and proteins. This is the first study to show that extracts from endophytic fungus, Alternaria alternata Y-13 isolated from A. adenophora exerts prominent antiproliferative effects against cervical cancer cells, providing preliminary insights into its potential molecular mechanisms and a basis for further investigation of its bioactive constituents.

Six undescribed dimeric 2-(2-phenylethyl)chromone derivatives, gyrinwallachromones A-F (1-6), were isolated from Sri Lankan agarwood of Gyrinops walla. Their structures were elucidated by comprehensive spectroscopic analyses, including HRESIMS, 1D and 2D NMR, and ECD data. Compounds 1-6 were characterized as dimeric 2-(2-phenylethyl)chromone derivatives consisting of a tetrahydrochromone unit and a flindersia-type 2-(2-phenylethyl)chromone unit. Structurally, compound 1 was distinguished by a C-8-O-C-6″ ether linkage between the two chromone units, whereas compounds 2-5 were connected through a C-8-O-C-7″ and compound 6 were connected through a C-8-O-C-4‴ ether bond. Notably, compounds 4 and 5 featured a 5-OCH3 substitution pattern on the tetrahydrochromone moiety, a relatively rare structural feature among agarwood-derived chromone dimers. The isolated compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages and their antibacterial activity against Helicobacter pylori. Compounds 1-6 exhibited weak inhibitory effects on NO production at non-cytotoxic concentrations. The IC50 values of compounds 3 and 4 were 68.44 ± 2.71 and 16.34 ± 2.70 μM, respectively, whereas the positive control quercetin showed an IC50 value of 10.57 ± 0.58 μM. In the anti-H. pylori assay, compounds 1-6 showed antibacterial activity. These findings expand the chemical diversity of agarwood-derived dimeric 2-(2-phenylethyl)chromones and provide further insight into the phytochemical constituents of G. walla agarwood.

Baliospermum solanifolium (Burm.) Suresh, widely reported as B. montanum, is an Asian Euphorbiaceae medicinal plant whose purgative roots and seeds also carry irritant and toxic liabilities. This critical evidence audit applies a chemistry-mechanism-liability framework to distinguish direct plant-specific findings from contextual evidence. PubMed and Crossref searches through 20 August 2026 identified 89 records; after deduplication and screening, 22 plant-specific primary studies and four Baliospermum-containing formulation studies were retained. Recent root chemistry revealed the first natural 20-nor-ent-podocarpanes, whereas classical tigliane/phorbol esters remain inseparable from both cytotoxicity and safety concerns. Baliosperoid A is the most advanced lead, with submicromolar nitric-oxide inhibition and one acute lung-injury study associated with Src homology 2 domain-containing phosphatase 2 (SHP2; encoded by PTPN11); however, direct intracellular engagement, PTPN11 dependence, selectivity, pharmacokinetic/pharmacodynamic coupling and independent replication are absent. One ethanolic-root study showed that abundant propiophenone markers were less active than the parent extract, supporting only a provisional marker-effector mismatch. Likewise, an approximately 75% decrease in a phorbol 12-myristate 13-acetate (PMA)-like signal after Ayurvedic processing establishes marker reduction, not detoxification, because residual congeners, transformation products and biological hazard were not resolved. Most other claims remain limited by weak chemical definition, high test concentrations or endpoint-only designs. The species is therefore a source of preclinical leads and a chemically hazardous botanical, not a clinically validated medicine. Translation requires organ-resolved chemotypes, paired benefit-hazard markers, causal experiments, exposure data and repeated-dose toxicology.

Nardostachys jatamansi has traditionally been used to treat gastrointestinal disorders. Although it was recently reported to have anti-inflammatory properties, the pharmacological potential of water extract of Nardostachys jatamansi (WENJ) against atopic dermatitis (AD)-like skin inflammation remains unclear. We investigated the effects of WENJ on a house dust mite-induced AD-like mouse model by assessing phenotypic severity, histopathological changes, and cytokine expression. Transcriptomic analysis of murine skin tissues was performed to identify gene expression signatures and key transcription factors contributing to the efficacy of WENJ. In addition, the role of the primary bioactive component of WENJ, desoxo-narchinol A, was examined in interleukin (IL)-4/IL-13-stimulated human keratinocytes, with a focus on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. In the AD-like mouse model, oral administration of WENJ markedly alleviated AD-like symptoms, reduced immune cell infiltration and inflammatory mediator expression, and restored the expression of skin barrier proteins such as filaggrin. The Nrf2/HO-1 pathway was identified as a key molecular pathway underlying the effects of WENJ on AD-like skin inflammation. Moreover, desoxo-narchinol A significantly increased Nrf2/HO-1 expression in keratinocytes, and exhibited the ability to bind Keap1 in molecular docking analysis. These findings demonstrate that WENJ and its active constituent desoxo-narchinol A exert anti-inflammatory and skin-protective effects through activation of the Nrf2/HO-1 pathway, highlighting their potential as promising therapeutic candidates for AD and related inflammatory skin conditions.

Plant- and fungal-derived natural products remain important sources of bioactive scaffolds for pharmacological research and lead discovery. However, their further development may be limited by poor aqueous solubility, metabolic instability, moderate potency, low bioavailability, or insufficient target selectivity. Triazole-based structural modification, particularly 1,2,3-triazole formation via click chemistry, provides a versatile strategy for diversifying natural-product scaffolds and optimizing their biological properties. This review critically summarizes studies published from June 2021 to April 2026 on the design, synthesis, biological activities, and structure-activity relationships of triazole-modified natural products and related scaffolds derived mainly from plants and fungi. Representative terpenoids, steroids, flavonoids, coumarins, chalcones, curcuminoids, lignans, alkaloids, phenolics, and fungal metabolites are comparatively discussed across anticancer, antimicrobial, anti-inflammatory, antiviral, antiparasitic, neuroprotective and alzheimer's disease-related activities, antidiabetic, and phytotoxic activities. Particular emphasis is placed on the influence of the position of triazole incorporation, substitution patterns, linker characteristics, and parent scaffolds on biological activity, together with comparisons with parent compounds and positive controls where available. Overall, triazole incorporation frequently improved biological activity within individual derivative series; however, direct cross-study comparisons remain limited by differences in biological models and assay conditions. Moreover, most reported compounds remain at the in vitro stage, with limited target validation, in vivo efficacy, pharmacokinetic, metabolic, and long-term toxicity data. This review provides a critical medicinal-chemistry perspective on recent triazole-modified natural products and highlights structural features and evidence gaps relevant to their further development as bioactive leads.

Abelmoschus manihot (L.) Medik. (AM) is traditionally used for kidney-related disorders, with its flower listed as the medicinal part in the Chinese Pharmacopoeia. However, the pharmacological basis underlying the preferential use of the flower in conditions involving glucose dysregulation and renal injury remains unclear. In this study, different AM parts and solvent extracts were evaluated in independent zebrafish models of high-glucose-associated metabolic disturbance and renal injury. HPLC fingerprinting, spectrum-effect analysis, independent pharmacological evaluation, uniform design, network pharmacology, molecular docking, and qRT-PCR were integrated to identify candidate bioactive constituents, optimize their combination, and explore potential mechanisms. Among the tested parts, AM flowers (AMF) showed the most pronounced and consistent effects on high-glucose-associated and renal injury phenotypes, with the 95% ethanol extract of AMF (AMF-95) being the most effective preparation. AMF-95 enhanced 2-NBDG uptake, reduced glucose, creatinine, and kidney injury molecule-1 levels, relieved renal edema, and improved renal histopathology. Spectrum-effect analysis revealed strong associations between eight major flavonoids, and the measured pharmacological effects, and independent pharmacological evaluation supported their bioactivity, supporting their selection as a candidate bioactive flavonoid group. An optimized constituent combination, designated combination No. 6, showed the best performance and effects comparable to those of AMF-95 under the tested experimental conditions. Network pharmacology and molecular docking predicted potential involvement of inflammation, insulin resistance, AGE-RAGE, and MAPK-related processes, with preliminary transcriptional support from whole-larvae qRT-PCR. These findings support AMF as the preferential medicinal part for high-glucose-associated and renal injury phenotypes and provide candidate flavonoids and an optimized combination for further investigation.

Cordyceps is of importance in Asian medicine. Research has focused on small molecules, but little attention was given to protein-based bioactive compounds from Cordyceps despite their therapeutic promise. This study highlights the current evidence on the five major classes of protein found in Cordyceps species: proteases, cordymin, lectins, superoxide dismutases (SOD) and ribosome inactivating proteins (RIPs). The pharmacological, biochemical, functional insights and the biological importance of these proteins were highlighted and the gaps that present constrains to their clinical use. Cordymin, a low molecular weight (10.9 kDa) antifungal peptide isolated from C. militaris, exhibits HIV-1 reverse transcriptase inhibitory and antiproliferative activity, yet its three-dimensional structure, detailed pharmacokinetic profile and molecular mechanism remain largely unknown. Proteases catalyse the hydrolysis of peptides and amino acids. Although proteases have shown promising potential as a thrombolytic agent, detailed studies of substrate specificity, catalytic mechanisms and inhibitor interactions are still lacking. While Cu/Zn-SOD has successfully been cloned and expressed from C. militaris, other important isoforms such as fungal RIPs remain one of the least explored protein families of Cordyceps. Given the clinical success of plant derived RIP based immunotoxins, the development of lectin-RIP conjugates from Cordyceps for targeted cancer therapy represents a particular but underexplored research direction. This review highlighted proteins of cordycipitoid fungi as an underexplored reservoir of bioactive molecules with significant potential for therapeutic development. A more systematic and interdisciplinary research effort will be essential to unlock their value and advance this field.

Activity-guided fractionation on the EtOH extract prepared from the whole plant of Thliphthisa antalyensis (Ehrend.) P.Caputo & Del Guacchio led to the isolation and characterization of 11 secondary metabolites (1-11). Besides, nine more compounds (12-20), including a previously unreported megastigmane glycoside (12) were obtained from the less-active fractions. Their chemical structures were elucidated using 1D and 2D NMR and HRMS. The crude EtOH extract, solvent fractions, main fractions, and isolates (1-12) were evaluated for their in vitro anti-inflammatory activities in LPS-stimulated RAW 264.7 murine macrophage cells. Compounds 1, 6, 7, and 10 displayed mild to moderate nitric oxide (NO) inhibitory activity (IC50 104.53-168.49 μM). Their effects on TNF-α, IL-6, PGE2 release, and COX-2 expression were further assessed. The chemotaxonomic significance of the isolated compounds was also discussed. This is the first study of the phytochemical and anti-inflammatory activities of T. antalyensis, an endemic species to Türkiye.