Six novel compounds, comprising three quinolones (1a, 1b, and 2) and three flavanones (3-5), along with seven known analogs (6-13), were isolated from the 95% EtOH extract of the stems and leaves of Glycosmis craibii var. glabra. The structures of the new compounds were elucidated using HR-ESI-MS, UV, and 1D and 2D nuclear magnetic resonance (NMR) data analysis. The absolute configurations were determined through Mosher ester and electronic circular dichroism (ECD) spectral analysis. Compounds 2, 6, 9, and 10 demonstrated inhibition of nitric oxide (NO) production stimulated by lipopolysaccharide in BV-2 microglial cells, with IC values ranging from 13.5 to 20.1 μmol·L, comparable to the positive control, dexamethasone.

A novel amide alkaloid, bursatamide A (1), featuring an unprecedented propyl-hexahydronaphthalene carbon framework, was isolated from the infrequently studied sea hare Bursatella leachi, alongside a new 3-phenoxypropanenitrile alkaloid, bursatellin B (2), and twelve known compounds. The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses, while their relative and absolute configurations (ACs) were established through total synthesis and a series of quantum chemical calculations, including calculated electronic circular dichroism (ECD) spectra, optical rotatory dispersion (ORD) methods, and DP4+ probability analyses. Bursatamide A (1) demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocytogenes and Vibrio cholerae. Erythro-bursatellin B (21), a diastereoisomer of 2, exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28, with an MIC value of 0.0472 μg·mL.

Seven novel linear polyketides, talaketides A-G (1-7), were isolated from the rice media cultures of the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Among these, talaketides A-E (1-5) represented unprecedented unsaturated linear polyketides with an epoxy ring structure. The structures, including absolute configurations of these compounds, were elucidated through detailed analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS) data, as well as electronic custom distributors (ECD) calculations. In the cytotoxicity screening against prostate cancer cell lines, talaketide E (5) demonstrated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines, with an IC value of 14.44 μmol·L . Moreover, compound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase, ultimately inducing apoptosis. These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treatment for prostate cancer.

Three novel, highly oxygenated polyketides, multioketides A-C (1-3), and three previously described multioxidized aromatic polyketides (4-6), were isolated from an endophytic Penicillium sp. YUD17006 associated with Gastrodia elata. Their chemical structures were elucidated using extensive spectroscopic data, electronic circular dichroism calculations, and single X-ray diffraction analysis. All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation. Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core. Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities. Plausible biosynthetic pathways for 1-6 were proposed. Additionally, compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyrosine phosphatase 1B.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, with only one Food and Drug Administration (FDA)-approved drug for its treatment. Given MASLD's complex pathophysiology, therapies that simultaneously target multiple pathways are highly desirable. One promising approach is dual-modulation of the farnesoid X receptor (FXR), which regulates lipid and bile acid metabolism. However, FXR agonists alone are insufficient due to their limited anti-inflammatory effects. This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD. Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger (2018) for molecular docking. Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance (SPR) binding assay, reporter gene analysis, and reverse transcription-polymerase chain reaction (RT-PCR). The anti-inflammatory properties of these compounds were evaluated in AML12 cells treated with tumor necrosis factor-alpha (TNF-α). Dual-function compounds with FXR agonism and inflammation inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α. The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid. Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists, with 15 exhibiting a strong affinity for FXR recombinant protein. Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb. Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones. Three compounds (2, 6, and 8) were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors, while one compound (12) acted as an FXR agonist to inhibit inflammation. These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and inflammation. In conclusion, compounds 2, 6, and 8 (genistein, biochanin A, and 7-methoxyisoflavone, respectively) were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation, serving as potential candidates or lead compounds for MASLD therapy.

A phytochemical investigation of the whole plant of Parasenecio rubescens (S. Moore) Y. L. Chen yielded 14 previously undescribed, highly oxidized bisabolane-type sesquiterpenoids, named pararunines L-Y, along with one known oplopane-type sesquiterpenoid. The structural elucidation of these compounds was accomplished through comprehensive spectroscopic analysis, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques. Motivated by traditional uses and previous studies on this genus, all isolated compounds were subjected to in vitro cytotoxicity assays against four human cancer cell lines (MCF-7, Hela, HCT116, and HT-29). Considering that the reported chemical constituents of numerous other species within this genus primarily consist of eremophilane-type sesquiterpenoids, our findings not only expand the structural diversity of bisabolane-type sesquiterpenoids but also contribute valuable scientific evidence to the chemotaxonomy of this genus.

Three novel sesquiterpenoid heterodimers, designated as auckcostusolides A-C (1-3), were isolated from Aucklandia costus leaves. The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis, with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism (ECD) calculations. Notably, compounds 1 and 2, despite sharing identical planar structures derived from two identical sesquiterpenoids, exhibited opposite configurations at C-11 and C-8'. This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers. Additionally, the cytotoxic effects of compounds 1-3 were evaluated against colorectal cancer HCT116 cells, fibrosarcoma HT1080 cells, and hepatocellular carcinoma HepG2 cells. Compounds 1-3 induced cell death was characterized by endoplasmic reticulum (ER) swelling and cytoplasmic vacuolization, typical morphological changes associated with paraptosis. Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of reactive oxygen species (ROS), activation of ER stress, and stimulation of the MAPK signaling pathway.

The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCRILC3 but the depletion of NCRILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCRILC3 to improving the depletion of NCRILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCRILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, etc., was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCRILC3, NCRMNK3 and IL-22ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be -7.5 kcal·mol in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be -6.4 kcal·mol and -7.7 kcal·mol homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCRILC3 via Notch signaling, and it provides a basis for targeting NCRILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.

Loganin (LOG), a bioactive compound derived from Cornus officinalis Siebold & Zucc, has been understudied in the context of osteoarthritis (OA) treatment. In this study, we induced an inflammatory response in chondrocytes using lipopolysaccharide (LPS) and subsequently treated these cells with LOG. We employed fluorescence analysis to quantify reactive oxygen species (ROS) levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2 (NRF2) using real-time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence (IF) techniques. Additionally, we developed an OA mouse model by performing medial meniscus destabilization (DMM) surgery and monitored disease progression through micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, safranin O and fast green (S&F) staining, and immunohistochemical (IHC) analysis. Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes, inhibited the activation of the NLRP3 inflammasome, and enhanced NRF2/heme oxygenase 1 (HO-1) signaling. In vivo, LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery, decreased NLRP3 expression, and increased NRF2 expression. These findings suggest that LOG has a protective effect against OA, potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.

Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes, designated callicaintides A-E (1-5), were isolated from Callicarpa integerrima. Compounds 1 and 2 feature a distinctive 5/6-membered ring system, while compounds 3-5 are characterized by progressively truncated carbon skeletons, containing 18, 17, and 16 carbons, respectively. In addition, four known compounds 6-9 were also identified. Their structures were elucidated using advanced spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared radiation (IR), optical rotatory dispersion (ORD), DP4 analysis and electronic circular dichroism (ECD), supported by quantum chemical calculations. Compounds 1-9 were evaluated for their anti-MRSA activity. Among them, compound 6 demonstrated significant anti-MRSA activity, with a minimum inhibitory concentration (MIC) of 16 μg·mL.

Toosendanin (TSN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN's toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras (PROTAC) technology and nanotechnology-based drug delivery systems (DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.

Natural medicines (NMs) are crucial for treating human diseases. Efficiently characterizing their bioactive components in vivo has been a key focus and challenge in NM research. High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) systems offer high sensitivity, resolution, and precision for conducting in vivo analysis of NMs. However, due to the complexity of NMs, conventional data acquisition, mining, and processing techniques often fail to meet the practical needs of in vivo NM analysis. Over the past two decades, intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for in vivo NM analysis. Consequently, improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument hardware. These improvements include enhanced instrument analysis sensitivity, expanded compound analysis coverage, intelligent identification, and characterization of nontargeted in vivo compounds, providing powerful technical means for studying the in vivo metabolism of NMs and screening for pharmacologically active components. This review summarizes the research progress on in vivo analysis strategies for NMs using intelligent MS data processing techniques reported over the past two decades. It discusses differences in compound structures, variations among biological samples, and the application of artificial intelligence (AI) neural network algorithms. Additionally, the review offers insights into the potential of in vivo tracking of NMs, including the screening of bioactive components and the identification of pharmacokinetic markers. The aim is to provide a reference for the integration and development of new technologies and strategies for future in vivo analysis of NMs.

Acute lung injury (ALI) is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide (AG), a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide (LPS)-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein (Kd value: -33.5 kcal·mol), and these interactions were further corroborated by Cellular Thermal Shift Assay (CETSA) and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

Four previously unreported diarylheptanoids (1a/1b-2a/2b), one undescribed sesquiterpenoid (8), one new diterpenoid (12), and twelve known analogs were isolated from the fruits of Alpinia oxyphylla. The structural elucidation of these compounds was achieved through a comprehensive analysis of spectroscopic data, single-crystal X-ray diffraction, electronic circular dichroism (ECD), and modified Mosher's method. Enantiomeric mixtures (1a/1b, 2a/2b, 3a/3b, 4a/4b, and 5a/5b) were separated on a chiral column using acetonitrile-water mixtures as eluents. Among them, compounds 3a/3b and 4a/4b were isolated as optically pure enantiomers in the initial chiral separation. Furthermore, most of the isolates were evaluated for their inhibitory effects against the production of nitric oxide (NO) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Interestingly, 2 and 4 showed significant inhibitory activities against NO production with IC values of 33.65 and 9.88 μmol·L (hydrocortisone: IC 34.26 μmol·L), respectively. Additionally, they also partially reduced the secretion of IL-6.

Five new furofuran lignans and their derivatives, (-)-glaberide I 4-O-β-D-glucopyranoside (1a), (+)-glaberide I 4-O-β-D-glucopyranoside (1b), (+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2a), (-)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside (2b), and (-)-isoeucommin A (3b), along with fifteen known analogs were isolated from the stems of Dendrobium 'Sonia'. These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution, and their structures were determined based on extensive spectroscopic data. Their absolute configurations were determined by hydrolysis, comparison of experimental and calculated electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analysis. The isolates were evaluated for their ability to inhibit nitric oxide (NO) production in RAW264.7 cells. Among them, syringaresinol (5) exhibited prominent inhibition activity, with an IC value of 28.4 ± 3.0 μmol·L, and there was a slight difference between 5a, 5b and the racemic mixture 5.

The phytochemical investigation of the leaves and twigs of Croton yunnanensis resulted in the isolation of eight new clerodane furanoditerpenoids, named croyunfuranoids A-H (1-8), along with three known analogs (9-11). The structures of these compounds were elucidated using spectroscopic analyses, and their absolute configurations were determined through a combination of electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Notably, Croyunfuranoid D (4) is identified as a rare 18,19-dinor-clerodane diterpenoid. Additionally, the structure of a previously reported diterpenoid, crotonyunnan B, was revised. All isolated compounds were evaluated for their inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages. Among them, compounds 5 and 6 demonstrated significant inhibitory effects, with IC values of 20.33 ± 2.31 and 22.80 ± 1.31 μmol·L, respectively.

Glioblastoma (GBM) is the most common invasive malignant tumor in human brain tumors, representing the most severe grade of gliomas. Despite existing therapeutic approaches, patient prognosis remains dismal, necessitating the exploration of novel strategies to enhance treatment efficacy and extend survival. Due to the restrictive nature of the blood-brain barrier (BBB), small-molecule inhibitors are prioritized in the treatment of central nervous system tumors. Among these, DNA damage response (DDR) inhibitors have garnered significant attention due to their potent therapeutic potential across various malignancies. This review provides a detailed analysis of DDR pathways as therapeutic targets in GBM, summarizes recent advancements, therapeutic strategies, and ongoing clinical trials, and offers perspectives on future directions in this rapidly evolving field. The goal is to present a comprehensive outlook on the potential of DDR inhibitors in improving GBM management and outcomes.

Ten previously undescribed dammarane-type triterpenoid glycosides, cyclocarysaponins A-J (1-10), were isolated from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja. The structures of these compounds were characterized through detailed spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The cytotoxic activities of all isolates were assessed against five human cancer cell lines (Bel-7402, Caski, BGC-823, A2780, and HCT-116). Of the tested compounds, compounds 1, 7, and 9 exhibited selective cytotoxicity against one or more human cancer cell lines.

Four novel macrocyclic trichothecenes, termed mytoxins D-G (1-4), along with four known analogs (5-8), were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus Myrothecium verrucaria PA57. Each compound features a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core. Notably, mytoxin G (4) represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene structure. The structures of the newly identified compounds were elucidated through comprehensive spectroscopic analysis combined with quantum chemical calculations. All isolated compounds demonstrated cytotoxic activity against the CAL27 and HCT116 cell lines, which are models for human oral squamous cell carcinoma and colorectal cancer, respectively. Specifically, mytoxin D (1) and mytoxin F (3) exhibited pronounced cytotoxic effects against both cancer cell lines, with IC values ranging from 3 to 6 nmol·L. Moreover, compounds 1 and 3 were found to induce apoptosis in HCT116 cells by activating caspase-3.

Eight novel clerodane diterpenoids (1-8) were isolated from the twigs of Casearia graveolens. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. In addition to structural determination, surface plasmon resonance (SPR) assays were conducted to investigate molecular interactions, revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis. Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

Three novel sesterterpenoids glasesterterpenoids A-C (1-3), featuring an unprecedented 7-cyclohexyldecahydronaphthalene carbon skeleton, were isolated from the root of Lindera glauca (L. glauca). Their structures were elucidated by quantum chemical calculations and spectroscopic methods. The biogenetic pathway for 1-3 is proposed. In the bioassay, glasesterterpenoid C exhibited DNA topoisomerase 1 (Top1) inhibitory activity compared with the positive control, camptothecin. These findings represent the first examples of sesterterpenoids with a 7-cyclohexyldecahydronaphthalene carbon skeleton from the root of L. glauca.