Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant fibroblast proliferation and excessive expression and deposition of extracellular matrix (ECM) by myofibroblasts, ultimately resulting in progressive and irreversible disorder or even loss of the pulmonary function. IPF is incurable with limited therapeutic options and low survival rate, thus the discovery of the therapeutic potential agents for IPF is in urgent need. Here, we identified isopropyl 9-ethyl-1-(naphthalen-1-yl)-9H-pyrido[3,4-b] indole-3-carboxylate (Z86) as a promising bioactive agent against Bleomycin (BLM) induced pulmonary fibrotic mice with the lung abnormalities including histological alteration, accumulation of ECM, as well as markers of EMT (epithelial-mesenchymal transition) were all relieved upon Z86 treatment in C57BL/6 mice. Consistent to the activity in vivo, Z86 decreased TGF-β induced cell migration, fibrotic marker expression, and myofibroblast activation in A549 and HFL1 cells. In further mechanism of action study of Z86 against IPF, we found TGF-β (transforming growth factor β) /Smad2/3 signaling pathway was substantially attenuated in TGF-β treated A549 and HFL1 cells, with remarkably decreased protein level of Smad2/3. Further, we identified Z86 as a novel USP15 inhibitor. Correspondingly, Z86 interacted with USP15, promoted the ubiquitination and degradation of Smad2/3 and disrupted TGF-β/Smad2/3 signaling pathway. Taken together, our findings demonstrated that Z86 suppressed TGF-β induced pulmonary fibrosis in A549 and HFL cells and BLM induced pulmonary fibrotic mice through inhibiting TGF-β/Smad2/3 signaling, and provided the possibility of USP15 inhibitors as the potential drug candidates for idiopathic pulmonary fibrosis.
Three pairs of new furo[3,2-c]pyridone derivative racemates, named (±)-phaeopyridones A–C (1–3), together with two new compounds, berkeleyamide E (4), and phaeopyranone (5), were isolated from the endophytic fungus Phaeobotryon negundinis 12020, along with three known compounds, (8S,9S)-dihydroisoflavipucine (6), (8S,9R)-dihydroisoflavipucine (7), and sapinopyridione (8), guided by bioinformatics and feature-based molecular networking and fragment-based LC-MS/MS analysis. The chemical structures of these compounds were elucidated by comprehensive spectroscopic analyses and single-crystal X-ray diffraction. Furthermore, a biosynthetic pathway for compounds 1–3 was proposed, indicating the unique furo[3,2-c]pyridone moiety may be generated by a non-enzymatic intermolecular hemiketal formation reaction. Our research expands the known range of flavipucine alkaloids and highlights the unexplored biosynthetic potential of natural products derived from endophytic fungi.
Plant diseases caused by fungal pathogens severely threaten crop yields and food security, driving the need for new, environmentally friendly fungicides. In this study, thirty-six alkaloids, including seven novel ones (1–4, 23, 29, and 30), were isolated from the fruits of Tetradium ruticarpum, and their structures were elucidated by extensive spectroscopic analyses. The antifungal potential of compounds obtained with sufficient quantities was evaluated using the mycelial growth rate method against three phytopathogens (Alternaria solani, Bipolaris sorokiniana, and Fusarium odoratissimum). Compounds 16 and 24 showed notable activity against A. solani, exhibiting approximately 80
Objective: To design and synthesize a series of tetrahydrocurcumin (THC) derivatives bearing α, β-unsaturated carbonyl moieties, evaluate their anticancer activities, screen potential candidates for colorectal cancer (CRC) therapy, and assess their biological activities. Methods: THC derivatives were synthesized in high yield via Knoevenagel condensation reaction, and their anticancer activities were evaluated in HCT116, SW480, SW620, HeLa, A549 and HepG2 cell lines. The in vitro and in vivo anti-CRC activities of the target compound were subsequently investigated. Results: Most compounds displayed potent antiproliferative activity against multiple tumor cell lines, with notably enhanced sensitivity in CRC cells. The fluorinated derivative 5 (C5) exhibited superior anti-CRC activity (IC50 = 2.66 ± 0.82 μM) relative to the positive control 5-fluorouracil (5-FU). By contrast, its reduced product compound H5 showed a 13-fold decline in potency (IC50 = 35.74 ± 1.40 μM), validating that the α, β-unsaturated carbonyl moiety represents the critical pharmacophore. Furthermore, C5 induced S-phase cell cycle arrest in HCT116 cells, triggered apoptosis via modulation of Bcl-2 family proteins, and suppressed cell migration. Mechanistically, it exerted its anticancer effects by inhibiting the PI3K/AKT/mTOR signaling pathway through downregulating p-AKT and p-mTOR. In vivo, C5 effectively inhibited tumor growth and cancer cell proliferation in HCT116 xenograft models, with higher efficacy and lower toxicity than 5-FU. Conclusions: These THC derivatives exhibited selective targeting toward CRC cells and suppressed the PI3K/AKT/mTOR signaling pathway, exerting significant anti-CRC efficacy both in vitro and in vivo, and thus held promise as potential lead compounds for CRC therapy.
Abstract Bletilla striata is highly regarded in traditional Chinese medicine and has also gained widespread attention as a valuable medicinal plant resource. However, the molecular composition and bioactive potential of its polysaccharides present a significant knowledge gap. Herein, a specific glucomannan fraction, designated as BSP60, was purified from Bletilla striata tubers and subsequently subjected to structural, rheological, and biological evaluations. Comprehensive characterization via methylation-GC–MS, monosaccharide composition analysis, and 1D and 2D NMR techniques demonstrated that BSP60 possesses a β-(1 → 4)-linked backbone featuring alternating mannosyl and glucosyl units, with the mannose moieties exhibiting partial O-acetylation at their C-2 or C-3 positions (with an acetylation rate of 23.54%). Rheological studies showed that BSP60 aqueous solutions exhibit shear-thinning behavior and form an elastic-dominated viscoelastic network, with higher viscosity and storage modulus than dextran of comparable molecular weight, indicating enhanced intermolecular interactions. Biological assays revealed that the BSP60 effectively decreased the level of NO, IL-6, and TNF-α in LPS-triggered macrophages (RAW264.7). Furthermore, the scavenge ability of BSP60 to superoxide anion (O2 •−) and ABTS⁺• radicals are significantly higher than that of hyaluronic acid. This study systematically characterizes the structural features of glucomannan derived from Bletilla striata, thereby establishing a robust scientific basis for its expanded utilization in the development of biomedical materials and functional cosmetic ingredients.
Marine-derived Penicillium fungus gained significant attention in recent years due to their potential as a valuable source of unique natural compounds with a wide range of chemical structures and bioactive capabilities. The primary origins of marine-derived Penicillium fungi are mangroves, sediments, marine shrimps, corals, starfish, algae, and sponges. A total of 390 unique natural compounds were extracted from Penicillium fungi which were found in marine environments. These compounds primarily consist of polyketides, alkaloids, terpenoids, chromone derivatives, anthraquinones, citrinins, steroids, azaphilones, and macrolides. Biological studies demonstrated that these compounds exhibit antimicrobial, anti-inflammatory, cytotoxic, pesticide development, neuroprotective, anti-glioma, anti-proliferative, α-glucosidase inhibitory activities, anti-allergic, photo-protective, anti-angiogenic effect, larvicidal activity, antiviral, anti-diabetic activity, and other activities that could be useful in the development of new drugs. This study shed the light on the recent discovery of bioactive MNPs (marine-derived Penicillium; natural products) derived from Penicillium fungi found in marine environments in the last five years from 2020 to 2025, classified the MNPs based on the sources of the fungi and their specific biological activities. Besides, the results of molecular docking studies recently performed on Penicillium metabolites referring to various biological activities were also compiled in this review. Thus, this review highlighted that Penicillium species obtained from marine organisms act as an everlasting mine of bioactive novel metabolites combating various ailments.
Abstract Background The gut-lung axis is a bidirectional communication network linking intestinal and pulmonary homeostasis through shared immunological and molecular mechanisms, conceptually consistent with the traditional Chinese medicine theory of “lung-intestine combined treatment.” Polygonatum cyrtonema Hua is an edible medicinal plant with reported anti-inflammatory and antioxidant properties, yet its role in intestinal inflammation-associated lung injury remains unclear. Materials and methods Dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced lung injury models were established in vivo, while LPS-stimulated A549 lung epithelial cells were used in vitro. The protective effects of Polygonatum cyrtonema oligosaccharides (PFOS) were evaluated, with particular focus on NF-κB and Nrf2 signaling pathways. The Nrf2 inhibitor ML385 was applied in vitro to verify pathway involvement. Non-targeted fecal metabolomics was conducted to assess PFOS-mediated metabolic modulation. Results PFOS significantly alleviated DSS-associated lung histopathological damage, reduced inflammatory cell infiltration, and improved epithelial barrier integrity. PFOS suppressed pulmonary proinflammatory cytokines, including TNF-α and IL-6, decreased myeloperoxidase activity, and attenuated oxidative stress by lowering malondialdehyde levels while enhancing antioxidant enzymes such as superoxide dismutase and HO-1. Mechanistically, PFOS inhibited NF-κB activation and promoted Nrf2/HO-1 signaling in lung tissues and LPS-stimulated A549 cells, effects that were partially reversed by ML385. Metabolomics analysis revealed that PFOS corrected DSS-induced disturbances in amino acid and lipid metabolism, with enrichment in cAMP, PPAR, and tryptophan-related pathways. Conclusions PFOS protects against colitis-associated lung injury by modulating the gut-lung axis through coordinated anti-inflammatory and antioxidant mechanisms involving NF-κB inhibition and Nrf2 activation, supporting its potential therapeutic application in gut-lung axis-related diseases.
In the search for natural products with potent activity against plant diseases, we employed the one strain–many compounds (OSMAC) strategy to the marine-derived fungus Trichoderma virens B211 by supplementing cultures with halogen salts such as sodium bromide (NaBr). Both solid and liquid cultures grown under NaBr-supplemented conditions exhibited markedly darker pigmentation of B211, a diversified secondary metabolite profile, and enhanced antibacterial activity against Erwinia amylovora. Bioassay-guided fractionation of these extracts led to the isolation of fourteen compounds (1–14), including two new polycyclic aromatic terpenoids (1 and 5) belonging to the viridin family. In vitro antimicrobial assays demonstrated that viridin (3) and β-viridin (4), together with gliotoxin (8), displayed broad-spectrum activity against diverse plant pathogenic fungi and bacteria. Notably, viridin derivatives 1 and 2, which are structural isomers, exhibited distinct bioactivity profiles: compound 1 exhibited antifungal activity, whereas compound 2 showed antibacterial activity. Among the isolated metabolites, only gliotoxin (8) and bisdethiobis(methylthio)gliotoxin (9) exhibited direct antibacterial activity against E. amylovora. Furthermore, NaBr-induced crude extracts in which compounds 8 and 9 were the major constituents, as well as the purified compounds themselves, effectively suppressed fire blight symptoms. Collectively, these findings highlight the effectiveness of the OSMAC approach in expanding the chemical diversity of metabolites produced by T. virens B211 and enhancing its potential as a biocontrol agent for plant disease management.
Medicinal plants have long served as an important asset in the treatment of diseases. Recent developments in computer science have enabled the rise of specialized databases cataloging medicinal plant knowledge. However, a systematic comparison of available region-specific medicinal plant databases is lacking. This review summarizes globally available medicinal plant databases that focus on specific geographical regions, aiming to inspire and guide people from specialists to the general public toward fostering innovation and making informed decisions. Through a systematic search of literature and digital resources, 81 regional medicinal plant databases established or updated between 2013 and 2025 were identified. From this pool, 40 core platforms were subjected to detailed statistical characterization regarding their data categories and volume. Our analysis reveals a geographical concentration in Asia (48.1
Pestalotiopsis sp. and Colletotrichum camelliae are two devastating fungal pathogens that cause significant yield losses and quality degradation in tea plants (Camellia sinensis). The increasing resistance of these pathogens to commercial fungicides necessitates the development of novel fungicidal agents with distinct modes of action. In this study, A series of novel sesamol derivatives incorporating a quinazolin moiety were synthesized and structurally validated by 1H NMR, 13C NMR, and HRMS. In vitro bioassays demonstrated that these derivatives exhibited potent antifungal activity, with compounds 4g and 4i standing out: against Pestalotiopsis sp., their inhibition rates reached 76.4
Plants of Salvia are frequently used for treatment infections of boils and sores in Traditional Chinese medicine, which might inhibit microbial. In this work, the chemical constituents of the effective fractions were analyzed using UPLC-Q-TOF-MS, and multivariate analysis and network pharmacology were used to predict potential antibacterial substances and their mechanism. Moreover, against methicillin-resistant Staphylococcus aureus (MRSA) effect and pathway of bioactive compounds were validated by experiments in vitro and in vivo. Two unreported anti-MRSA compounds, miltirone and przewaquinone A were proposed and then validated by serial experiments. They acted as bactericides and biofilm scavengers, respectively, and both targeted on the cell membrane, causing leakage of contents and affecting intracellular metabolism, leading to bacterial death without significant toxicity. Furthermore, miltirone ameliorated skin wound infection caused by MRSA in mice, roughly equal to vancomycin. The research supported the traditional use of Salvia plants, and presented two potent bactericidal agents for further investigation.
Abstract Naringin and phloridzin are structurally similar flavonoids with anti-inflammatory, antioxidant, and antimicrobial properties, showing considerable potential as natural therapeutic agents. This study demonstrated that naringin and phloridzin exert anti-inflammatory effects and preserve normal intestinal function in UC mice. This protective effect is mediated by inhibition of the NF-κB signalling pathway. To investigate metabolic differences, we employed UPLC-MS/MS-based widely targeted metabolomics alongside targeted analyses of tryptophan (Trp) and short-chain fatty acids (SCFAs). Comparative analysis of metabolic profiles, differential metabolites, and associated pathways revealed regulatory effects on Trp and SCFAs. However, naringin demonstrated superior regulation of Trp metabolism and SCFA levels compared to phloridzin, resulting in more pronounced improvement of gut homeostasis. These findings elucidate the metabolic mechanisms underlying both flavonoid treatments and underscore their potential as complementary therapies for UC. Graphical abstract Naringin and phloridzin exert protective effects against DSS-induced ulcerative colitis by modulating tryptophan metabolism and suppressing inflammation through inhibition of the NF-κB signaling pathway
Tirucallane-type triterpenoids are one of the most structurally diverse classes of secondary metabolites in Meliaceae family, which is predominantly distributed across tropical and subtropical regions. A total of 373 tirucallane derivatives have been reported between 1967 and 2025, from 48 species belonging to 17 genera. These compounds were isolated from different plant parts, including bark, stem bark, roots, leaves, fruits, twigs, seeds, and aerial tissues. Therefore, this review aims to integrate current reports on tirucallane-type triterpenoids from 17 Meliaceae genera, emphasizing structural complexity, taxonomic occurrence, and pharmacological relevance to guide future chemotaxonomic and drug discovery efforts. Literature collection was performed through Google Scholar, Reaxys, PubMed, and SciFinder. The results showed that based on the structural characteristics, tirucallane derivatives were categorized into intact, seco, heteroatom-substituted, degraded, and highly rearranged, with the intact subgroup being the most abundant. Furthermore, tirucallane derivatives have a broad spectrum of biological properties, including cytotoxic, antimicrobial, antiplasmodial, antidiabetic, anti-inflammatory, immunomodulatory, FXR agonistic, and insecticidal effects, indicating significant potential therapeutic value. Among the reported compounds, laxiracemosin E (361) showed the strongest anticancer potential with IC50 = 1.5 µM, while aphanamgrandin C (372), aphanamgrandin D (373), and dubione B (227) demonstrated potent antibacterial activity (MIC = 1.57–3.13 µg/mL). Hispidol A (2) indicated remarkable antiplasmodial activity (IC50 = 2.45 µM), while meliasenin G (64), phellochin (66), and methyl angolensate (343) were identified as promising α-glucosidase inhibitors (IC50 = 6.1 µM). In conclusion, tirucallane triterpenoids from Meliaceae offer an outstanding structural platform for future drug discovery and bioactivity optimization.
Abstract Twelve new sesquiterpenoids, sanguisorbaols A–L (1–12), along with twenty-five known compounds (13–37), were isolated from the roots of Sanguisorba officinalis. Structures were determined through comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, ECD and NMR calculations, and X-ray crystallographic analysis. Among them, compounds 1–6 were identified as new patchoulol-type sesquiterpenoids bearing hydroxyl groups at different positions, the further structural elucidation revealed that compounds 5 and 6 are nor-patchoulol-type sesquiterpenoids due to the absence of the C-11 carbon atom. Compounds 7–11 were characterized as guaiane-type sesquiterpenoids incorporating a [5,7]-bicyclic framework, among which 7 and 8 constitute a pair of C-11 epimers. Notably, compound 12 possesses a rare bicyclo[4.3.1]decane core scaffold. All the patchoulol-type sesquiterpenoids reported here were obtained for the first time from the genus Sanguisorba, and a plausible biosynthetic pathway was proposed. Furthermore, the anti-melanogenic bioactivity of all isolates was assessed using IBMX-stimulated B16F10 melanoma cells. Compounds 3–5, 8–10, 12–14, 17, 19, 21, 22, 25–27, 29, 31, 32 and 34 demonstrated significant inhibitory activity against melanogenesis at concentrations ranging from 6.25 to 50 μM. These results highlighted the potential of S. officinalis as a natural anti-melanogenesis agent for skin-whitening or for the treatment of hyperpigmentation disorders. Graphical Abstract
Marine fungus-derived natural products are an important source of new drugs and lead compounds. In this study, guided by the Global Natural Products Social (GNPS) molecular networking strategy, four new cyclohexenone derivatives, aspergiflones A-D (1-4), together with three known analogues (5-7), were isolated from the coral-derived fungus Aspergillus flavus. The structures of these compounds were elucidated through extensive spectroscopic analyses, comparison with literature data, hydrolysis reactions, quantum chemical calculations, and TDDFT-ECD calculations. Structurally, aspergiflone A (1) is a novel cyclohexenone dimer featuring an unprecedented skeleton in which two cyclohexenone units are connected at C-15 via a C-C single bond. Compound 1 exhibited potent antibacterial activity against Escherichia coli. Mechanism studies revealed that compound 1 disrupts bacterial cell morphology, increases cell membrane permeability, and decreases intracellular K+ ion levels. Additionally, transcriptome analysis revealed that the differentially expressed genes (DEGs) were mainly associated with cellular process regulation, stimulus response, catalytic, and binding functions. Several pathways were also significantly affected in Escherichia coli, including ABC transporters, cofactor biosynthesis, energy metabolism, and arginine biosynthesis. The finding indicated that aspergiflone A has considerable potential in food safety.
Colorectal cancer (CRC) is the third most predominant cancer caused by genetic, environmental and nutritional factors and is the world’s second most significant cause of cancer-related mortality. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inducing autophagy and apoptosis of tumor cells, blocking the angiogenesis and inhibiting EMT outside the tumor can reduce the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Research of the anticancer effect of Polyphenolic in TCM has made considerable progress in recent years. This review explores the research achievements of Polyphenolic in TCM on CRC metastasis in the past ten years, summarizes the development direction of Polyphenolic in TCM on CRC metastasis research in the past ten years and makes a prospect for the future.
Abstract An electromediated oxidative coupling strategy for constructing spirodienone fragment has been developed and applied as the key step for the total synthesis of (±)-spirobroussonin B. This concise route was accomplished in only four steps, 41.6% overall yield and the key coupling reaction was demonstrated on a gram scale. The absolute configurations of the enantiomers were unambiguously determined by chiral resolution and ECD calculations. This work establishes a solid foundation for developing practical and efficient syntheses of spirobroussonin B and related analogues. Graphical Abstract
Abstract Iron homeostasis has recently emerged as a key determinant in the early stages of plant–pathogen interactions, particularly in phytopathogens that exploit iron-dependent cell death (known as ferroptosis) to initiate host invasion. In Pyricularia oryzae, the causal agent of rice blast disease, appressorium formation is tightly linked to ferroptotic events in germinating conidia. Accumulation of intracellular Fe3⁺ and reactive oxygen species (ROS) promotes lipid peroxidation, ultimately triggering conidial cell death and, consequently, appressorium maturation. Therefore, inhibition of ferroptosis by targeting fungal iron homeostasis represents a promising strategy to suppress appressorium development and block subsequent host infection. Rhizoferrin, an α-hydroxy carboxylate siderophore secreted by Rhizopus microspora, was identified as a suitable precursor of its ring-closed derivative glomuferrin. The obtainment of an unexpected succinimide intermediate within the synthetic pathway enabled the access to both rhizoferrin and, to our knowledge for the first time, glomuferrin. Chelation evaluation revealed that rhizoferrin exhibits significantly higher affinity for iron than glomuferrin. The effects of these siderophores on conidial germination and appressorium formation were evaluated in wild-type and strobilurin-resistant P. oryzae strains, at concentrations ranging from 5 mM to 200 μM. The promising activity observed, especially for rhizoferrin, highlights the potential of α-hydroxy carboxylate siderophores as ferroptosis inhibitors and offers new perspectives for their development in crop protection. Graphical Abstract
Ten novel trichothecene sesquiterpenoids including two new seco-trichothecenes, trichotheciumones A (1) and B (2), a new trichothecene sesquiterpenoid glycoside, trichothecinoside A (3), and seven new trichothecene sesquiterpenoids, trichothecrotocins T-Z (4-10), together with three new natural products (11-13) and thirteen known compounds (14-26), were isolated from the soil fungus Trichothecium sp. DWS815. The structures and absolute configurations of the new compounds were elucidated by extensive spectroscopic analyses and quantum chemistry ECD calculations. Given the notable anticancer properties of known trichothecenes, the isolated compounds were evaluated for the cytotoxic activities against three cancer cell lines (HCT116, 4T1, MHCC97H) and one normal cell line (GES-1). Cell cycle analysis revealed new compounds 7 and 8 induced G2/M phase arrest in HCT116 cancer cells, which resulted to cell proliferation inhibition activity.
As an important and beneficial gut commensal, Akkermansia muciniphila plays a crucial role in regulating host metabolism and immunity. Lipooligosaccharides from A. muciniphila (ALOS) show anti-obesity effects in high-fat diet-fed mice. Herein, we investigated the chemical characteristics of core oligosaccharides of ALOS and explored its anti-atherosclerotic efficacy. The LC-Q-TOF-MS analysis indicated a high structural diversity of core oligosaccharides in ALOS, comprising fourteen distinct oligosaccharide species with different degrees of phosphorylation. Functionally, administration of ALOS significantly attenuated hyperlipidemia and reduced atherosclerotic plaque burden in high-fat diet-fed ApoE-/- mice. The improvement of these metabolic symptoms was related to the restoration of intestinal barrier integrity. Mechanistically, ALOS upregulated the IL-23/IL-22 immune axis, which in turn promoted intestinal epithelial repair and modulates the microbiota. ALOS intervention reshaped the gut microbiota composition by enriching beneficial genera such as Bifidobacterium longum, Roseburia intestinalis, and Oscillibacter sp., while suppressing potential pathobionts. Our findings highlight the structural diversity and anti-atherosclerotic effect of lipooligosaccharides from A. muciniphila.
