Chromanes and chromenes with various biological activities are widespread in nature and have now been found in a variety of plants, fungi and marine organisms. To date, 79 previously undescribed chromanes and 161 previously undescribed chromenes have been isolated and identified. The chromanes were further classified into four skeleton types, and the chromenes were further classified into five skeleton types. In this review, natural chromanes and chromenes were classified according to their skeleton types, and their biological activities and biosynthetic pathways were also summarized. Pharmacological research has demonstrated that chromanes and chromenes possess a range of biological activities, including antimicrobial, anti-inflammatory, anticancer, antidiabetic, and insecticidal properties. This review provides an important reference for structural analysis, pharmacological activity studies, and biosynthetic pathways of chromanes and chromenes.

Salvianolic acid A (SAA), a major water-soluble bioactive compound extracted from Salvia miltiorrhiza, has been extensively studied for its diverse pharmacological properties in cerebrovascular diseases. However, its immunomodulatory effects on lymphocytes in stroke remain incompletely understood. This study systematically investigated the therapeutic efficacy and underlying mechanisms of SAA in a murine model of transient middle cerebral artery occlusion (tMCAO). Early administration of SAA (20 mg/kg) to ischemic stroke (IS) mice demonstrated neuroprotective effects, characterized by reduced infarct volume and improved behavioral outcomes, alongside creating a T-favorable environment in the spleen. In T cells differentiation assays and a luciferase reporter gene system, SAA was further identified as the primary active component in Salvia miltiorrhiza extract responsible for promoting in vitro T differentiation. Flow cytometry analysis revealed that SAA treatment significantly enhanced the accumulation of T cells in the brain after tMCAO, potentiated the immunosuppressive profile of the cerebral microenvironment, alleviated inflammatory responses, and avoided inducing systemic immunosuppression, ultimately leading to substantial neurological improvement. T depletion abolished SAA-induced neuroprotection. Mechanistically, SAA appeared to regulate T differentiation through the RUNX1/CBFβ/FOXP3 axis independent of TGF-β signaling. In summary, these findings suggest that SAA improved stroke outcomes via upregulation of cerebral Treg cells abundance, a process linked to the RUNX1/CBFβ/FOXP3 pathway. Collectively, this study offers new perspectives on the therapeutic potential of SAA in ischemic stroke management.

We previously developed LJ-4378, a dual ligand for A and A adenosine receptors, as a potential anti-obesity agent. In this study, we compared the anti-obesity effects of LJ-4378 with those of tirzepatide (TZP), a dual agonist of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, and one of the most potent FDA-approved obesity therapeutics. Using a mouse model of diet-induced obesity, we assessed the effects of LJ-4378 and TZP on body weight loss, metabolic parameters, and post-treatment weight rebound. Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days. Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure. To assess the durability of the treatment effects, drug administration was discontinued after 14 days, and the mice remained on the HFD for an additional 4 weeks. Notably, LJ-4378-treated mice exhibited attenuated body weight regain, stable food intake, persistent metabolic benefits, and sustained enhancement of energy metabolism, compared to TZP-treated mice. These findings highlight LJ-4378 as an anti-obesity agent that functions independently of appetite suppression and may offer superior long-term benefits by limiting post-treatment weight rebound and preserving metabolic improvements.

Osteoarthritis (OA) is characterized by oxidative stress, inflammation, and apoptosis, leading to an imbalance between cartilage extracellular matrix (ECM) synthesis and degradation. Gingerols can regulate multiple biological activities, indicating their therapeutic potential for OA. The present study investigated the feasibility, efficacy, and mechanism of gingerols for OA therapy. Regarding feasibility, gingerol exhibited antioxidant, anti-inflammatory, and antiapoptotic activities for OA therapy, while 10-G exhibited most potent effects among the three gingerols. Regarding efficacy, 10-G upregulated the expression of genes associated with ECM assembly and downregulated the expression of genes involved in ECM disassembly. Mechanistically, 10-G promoted NRF2 nuclear translocation; enhanced antioxidant gene expression; inhibited the phosphorylation of ERK, JNK, P38, RELA, and IKBA; and reduced the expression levels of TP53 and CDKN1A, thereby decreasing the production of inflammatory cytokines and apoptotic regulators. Furthermore, KEAP1 was identified as the direct target of 10-G, with NRF2 confirmed as the key regulatory target. This study demonstrates that 10-G mitigates oxidative stress, inflammation, and apoptosis through the KEAP1-NRF2-ARE axis and simultaneously restores ECM balance to promote cartilage regeneration, establishing its potential as a novel candidate for OA therapy.

Succinimide motifs are recognized as privileged cores in anticonvulsants and antipsychotics such as phensuximide, ethosuximide, and lurasidone. These succinimides can be readily converted into pharmaceutically important pyrrolidines and γ-lactam scaffolds, making them highly promising compounds in drug discovery. Nitroarenes are also important chemical feedstocks and have attracted increased attention owing to their versatile applications in pharmaceuticals, functional materials, and agricultural pharmacology. Therefore, directly combining succinimides with nitroarenes is a valuable approach for efficiently constructing novel succinimide-linked nitroarene frameworks. We herein report the site-selective addition of the succinimide scaffold to various nitroarenes via nitro-directed ortho-C-H alkylation using maleimides under rhodium(III) catalysis. The versatility of the developed protocol is demonstrated through nitro-group reduction, reductive cyclization of the synthesized products, and selective modifications of the succinimide framework. Mechanistic studies, including deuterium-labeling and kinetic isotope effect experiments, helped elucidate a plausible reaction mechanism.

Glioblastoma (GBM) is the most aggressive and deadliest type of primary brain tumor, treated with temozolomide (TMZ) as first-line chemotherapy. However, temozolomide resistance remains a critical therapeutic hurdle in GBM, often resulting in treatment failure and tumor recurrence. Here, we aimed to identify an epigenetic target to overcome TMZ resistance in GBM. We established TMZ-resistant GBM cell lines, which exhibited increased expression of resistance markers such as E2F6, ABCG2, and phosphorylated STAT3, and decreased Bax expression. Through KDM inhibitor screening with these cells, we identified KDM4C as a key therapeutic target. Pharmacological inhibition of KDM4C via SD70 significantly reduced the viability, proliferation, and stem-like properties of TMZ-resistant GBM cells. Notably, combination treatment with SD70 and TMZ showed a synergistic effect, restoring TMZ sensitivity. Mechanistically, KDM4C directly bound to the promoter of E2F6, a transcription factor associated with poor prognosis and chemoresistance of GBM. Moreover, genetic and pharmacological inhibition of KDM4C reduced E2F6 expression. Collectively, our findings reveal that KDM4C drives TMZ resistance in GBM by epigenetically upregulating E2F6, and suggest that targeting KDM4C may be a potential approach to overcome TMZ resistance in GBM.

The present study aimed to isolate compounds from Caragana jubata (Pall.) Poir. and evaluate their in vitro neuroprotective effects. The compounds were isolated by various column chromatographic techniques and semipreparative HPLC. The structures of the new compounds were elucidated using HR‒ESI‒MS, UV, IR, 1D and 2D NMR, and single X-ray diffraction data analysis. Furthermore, their absolute configurations were determined through ECD spectroscopic data analysis. An oxygen‒glucose deprivation/reperfusion (OGD/R)-induced PC12 cell model and LPS-induced NO release from a BV2 cell model were established to evaluate their in vitro neuroprotective effects. Four undescribed compounds (1‒4), comprising one rare rearranged isoflavanone derivative with a 6/6/6/6 four-ring system, one isoflavanone, and two isoflavones, together with 21 known compounds, were isolated from C. jubata. The steric configurations of compound 5 were determined for the first time. Compounds 1‒5, 7‒9, 11‒12, 14‒15, and 17‒21 showed protective effects against OGD/R-induced PC12 cells in a range of 3.125 to 25 µM. (‒)-Caraflavonoid B (2b) displayed the most prominent protective activity. In addition, compound 2b had antineuroinflammatory activity. Results of network pharmacology indicate compound 2b may exert anti-ischemic stroke (anti-IS) effect by modulating multiple targets and pathways.

Boron, a versatile element historically underexplored in medicinal chemistry, has recently garnered prominence for its unique chemical properties that enable the design of innovative therapeutic compounds. The success of boron-containing drugs such as Bortezomib has spurred interest in developing boron-based compounds targeting a variety of tumor-related proteins. This review provides the first target-centric synthesis of boron-containing anticancer agents, integrating structure-activity relationships, binding mode visualizations, and clinical pipeline status across enzyme and receptor targets. Unlike prior reviews focused on chemistry or individual compound classes, it highlights how boron enables reversible covalent inhibition, prodrug activation, and bioisosteric replacement to overcome resistance and selectivity barriers in oncology. This review highlights the current advancements in boron-containing therapeutics, emphasizing their applications in cancer treatment. The ability to form reversible covalent bonds and interact selectively with biomolecules makes it particularly valuable for enzyme and receptor targeting. Moreover, recent developments have introduced boron-based compounds capable of overcoming drug resistance, enhancing selectivity, and minimizing side effects. This review categorizes boron-containing therapeutics into enzyme-targeting and receptor-targeting categories, discussing their mechanisms of action, preclinical and clinical advancements, and future potential. These advancements establish boron-based chemistry as a powerful tool for overcoming limitations of conventional cancer drugs, paving the way for next-generation oncologic therapies with improved specificity and reduced side effects.

Estrogen receptors (ERs) are expressed in approximately 70% of breast cancer patients and serve as pivotal therapeutic targets. ER-targeting agents like selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) have harvested encouraging clinical outcomes. However, the expansion of their clinical utility remains limited by adverse effects, acquired resistance, and suboptimal pharmacokinetic properties. Recent advancements in ER biology have driven the development of novel ER-targeted agents, including third-generation SERMs, oral SERDs, complete ER antagonists, selective ER covalent antagonists, SERM/SERD hybrids, selective human ER partial agonists, and dual-mechanism ER inhibitors. Moreover, innovative technologies, such as proteolysis-targeting chimeras, molecular glue degraders, and lysosome-targeting chimeras have revolutionized ER degradation strategies, offering possibilities to circumvent drug resistance and enhance therapeutic efficacy. Despite these advances, only two ER-targeted drugs have been officially approved to date, indicating the barriers on the road to clinical translation. This review summarizes the recent progresses and challenges in the development of ER-targeted drugs, aiming to offer a perspective into the future of anti-ER therapies in breast cancer management.

Resveratrol has been shown to mitigate liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs). However, the precise mechanisms remain incompletely understood. Resveratrol demonstrates therapeutic potential in alleviating liver fibrosis by promoting HSC ferroptosis through the dual regulation of endoplasmic reticulum stress (ERS) and glutamine metabolism, as shown by in vivo and in vitro investigations. In carbon tetrachloride (CCl) induced fibrotic mice, resveratrol significantly attenuated liver injury, extracellular matrix (ECM) deposition, and collagen synthesis. Cellular experiments revealed its dose-dependent inhibition of HSC activation via glutathione (GSH) depletion, iron accumulation, and downregulation of GSH peroxidase 4 (GPX4), with ferroptosis inhibitor Ferrostatin-1 (Fer-1) reversing these effects. Mechanistically, resveratrol suppressed activating transcription factor 4 (ATF4) -mediated ERS signaling, subsequently reducing alanine-serine-cysteine transporter 2 (ASCT2) dependent glutamine uptake essential for GSH biosynthesis. Genetic manipulation experiments confirmed the central regulatory role of ATF4, whose overexpression counteracted resveratrol's effects, while ATF4 knockdown or Jumonji domain-containing protein D3 (JMJD3) inhibition epigenetically silenced ASCT2 transcription through enhanced trimethylation of histone H3 at lysine 27 (H3K27me3). These findings revealed a novel pathway by which resveratrol induces HSC ferroptosis through metabolic and epigenetic regulation, offering a multi-targeted strategy against hepatic fibrosis that bridges amino acid metabolism, redox homeostasis, and chromatin remodeling processes.

Cytochrome P450 (CYP) enzymes are crucial for metabolizing various compounds, including therapeutic drugs. Metabolites generated through CYP-mediated pathways have been increasingly recognized as key contributors to the pathogenesis and progression of diverse diseases, particularly cancer. Consequently, ongoing research is examining Food and Drug Administration-approved drugs as potential inhibitors of specific CYP isoforms and characterizing their underlying mechanisms of action. These studies are essential for clarifying how approved drugs alter the metabolic pathways of co-administered agents, thereby influencing therapeutic efficacy and safety outcomes. CYP inhibitors significantly alter substrate metabolism, thereby increasing the risk of drug-drug interactions (DDIs). These interactions pose crucial challenges in clinical practice, necessitating careful evaluation when co-administering medications with similar metabolic pathways. Therefore, this review aims to examine the complex interplay among CYP inhibitors, their substrates, and DDIs in both cancers and non-neoplastic diseases, including allergies, depression, and stroke. The review seeks to minimize adverse outcomes and enhance therapeutic effectiveness by offering a comprehensive understanding of CYP inhibitors.

5-Fluorouracil (5-FU) remains the most commonly used first-line chemotherapeutic agent for the treatment of esophageal cancer (EC), but its therapeutic efficacy is unsatisfactory. In this study, we found that 5% of ESCC cells survived the treatment with high doses of 5-FU for 5 days. Compared to the parental cells, the rapidly acquired drug-tolerant persister (DTP) cells showed enhanced expression of those genes associated with stemness and epithelial-mesenchymal transition. Once 5-FU was removed, the regrown cells regained their sensitivity to 5-FU. Additionally, the transcriptomic profiles analysis showed that the parental and the regrown cells had very similar gene expression profile, while DTP cells showed distinct changes. Significant changes in histone deacetylation pathway were observed in DTP cells. Knockdown of HDAC2/6/9 and BRD4 markedly reduced the formation of DTP cells. We screened our drug library and found that HDAC4/5/6/7 inhibitor TMP269 and BRD2/3/4 inhibitor ABBV-744 showed potent synergistic cytotoxic effects with 5-FU in the parental ESCC cells. Our team then synthesized a new HDAC inhibitor YFF-702 and BET inhibitor C-34, which showed synergistic effects with 5-FU in the parental ESCC cells. Moreover, ABBV-744 and YFF-702 showed synergistic cytotoxic effects with 5-FU in DTP cells. Animal experiments further demonstrated that YFF-702 significantly improved the efficacy of 5-FU in an in vivo tumor model. This current research demonstrates that combining HDAC/BET inhibition with 5-FU may be a promising therapeutic strategy for ESCC patients by targeting 5-FU indued DTP cells.

Hepatocellular carcinoma (HCC) is characterized by an immunosuppressive tumor microenvironment (TME), indicating that immune cell activation is a promising approach. The use of γ-secretase inhibitors (GSIs) to control high Notch signaling activity is currently one of the traditional methods for clinical immunotherapy of HCC. However, the lack of substrate specificity in GSIs often leads to serious side effects. In contrast, a novel small molecule compound, RBPJ inhibitor-1 (RIN1), which selectively blocks the functional interaction between RBPJ and Notch intracellular domain (NICD), has been found to inhibit CD8 T cells exhaustion in HCC effectively. However, its impact on CD4 T cells is still unknown. This study found that RIN1 stimulated T cell IL-17 and IFN-γ secretion, and drove more T cell differentiation towards Th17.1 (CD161, CD183, CD191). Furthermore, RIN1 upregulated T cell STAT3, STAT4, TBX21 protein levels, enhanced STAT3 and RORγt binding to the IL-17 promoter, and facilitated STAT4 and TBX21 enrichment on IFNG promoter. RIN1 also boosted T cell-mediated antitumor immunity and inhibited HCC cells' epithelial-mesenchymal transition. Notably, IL-17R knockdown in HCC cells partially reverted RIN1-enhanced T cell antitumor effects. In vivo, RIN1 promoted the expression of IL-17 and IFN-γ in CD4 TILs while suppressing PD-1 expression and reducing the frequency of Treg cells, exhibiting tumor growth inhibition. These findings suggested that RIN1 enhances CD4 T cell-mediated antitumor immunity in HCC by modulating gene transcription and cell subset differentiation, highlighting its potential as an immunostimulatory agent (Graphical abstract).

The genus Croton, a member of the Euphorbiaceae family, comprises nearly 1300 species globally, predominantly inhabiting tropical and subtropical regions. Certain species of Croton are renowned for their significant medicinal properties. Diterpenoids, as the principal bioactive constituents of this genus, exhibit a diverse array of biological activities. From 2013 to 2025, a total of 545 newly identified diterpenoids featuring 34 distinct skeletal types, predominantly labdane, clerodane, tigliane, and crotofolane structures, were isolated from 45 Croton species, including several novel frameworks. According to available literature, Croton diterpenoids demonstrate notable anti-inflammatory and anti-tumor properties, with clerodane and tigliane variants showing particularly promising results. Additionally, antimicrobial, anti-proliferative, anti-angiogenic, neuroprotective, insecticidal, and anti-liver fibrotic activities have been reported for various Croton diterpenoids. This review consolidates information on the distribution, chemical structures, potential biosynthetic pathways and biological activities of diterpenoids isolated from Croton species during the specified period.

Metabolically-dysfunction-associated steatohepatitis (MASH) represents one spectrum of MASLD, affecting over 5.27% of adults globally. Until the approval of resmetirom, no pharmacological therapies were available for MASH. Resmetirom is prescribed for the management of non-cirrhotic MASH in adults with moderate to advanced hepatic fibrosis, specifically at Stages F2 to F3. This drug is uniquely transported via liver-targeted transporters and exerts its effects by closely replicating the physiological actions of T3 (FT3). It exhibits a 28-fold selectivity for the thyroid hormone receptor beta (THR-β), predominant in the liver, over THR-α in functional assays. The approval of resmetirom marks a significant milestone, addressing a critical unmet need in MASH treatment while initiating a new chapter in therapeutic strategies for this complex chronic liver disease.

Cancer remains a critical global health issue, presenting multifaceted challenges in both prevention and treatment. It is characterized by uncontrolled cell proliferation, primarily driven by the dysregulation of cyclin-dependent kinases (CDKs). CDKs are the key regulators of phosphorylation, capable of phosphorylating various proteins at serine and threonine residues, thereby initiating essential cellular processes such as cell division, differentiation, and programmed cell death. Due to their significant role in cell cycle regulation, CDKs have emerged as attractive drug targets for anticancer drug design and development. Although several conventional CDK inhibitors have demonstrated efficacy, their associated toxicities and the development of resistance underscore the need for alternative, safer CDK inhibitors. Studies have shown that polyphenols can significantly inhibit CDKs and their associated cyclins, modulate key regulatory pathways, and induce the expression of tumor suppressors such as p21 and p27, ultimately affecting cancer cell cycle progression and metastasis. This review summarizes the in vitro and in vivo investigations on the CDK-inhibition-based antiproliferative activity of polyphenols against various cancer types, as well their synergistic anticancer effects observed when combined with other chemotherapeutic agents. Furthermore, bifunctional conjugates of various polyphenols have demonstrated promising anticancer potential by overcoming the pharmacokinetic limitations of their native forms. Looking ahead, polyphenols hold promise as the potential anticancer drug candidates with CDK inhibitory activity. Therefore, there is a pressing need for more in-depth investigations and the initiation of clinical trials to validate these findings.

The skin is frequently subjected to injuries and disorders encompassing both acute and chronic wounds. Chronic wounds, including diabetic wounds, pose significant clinical problems due to prolonged and ineffective healing processes. Traditional therapies are associated with many limitations. In this regard, nanoparticles (NPs)-based drug delivery systems have emerged as promising solutions for improving chronic wound healing and to overcome the drawbacks of conventional approaches. Furthermore, the functionalization of these NPs through surface modification can increase the overall therapeutic performance. Incorporating them into advanced dosage form maximizes the therapeutic impact. Although their therapeutic promise is high, clinical translation of nanoparticles is hindered by challenges such as manufacturing problems with scaling up production of lipid nanoparticles and the regulatory difficulties related to nanoparticle characterization, such as compliance with FDA criteria for size variation. The current review endeavored to explore the most recently developed nanotechnology-based therapeutic agents that are used in diabetic chronic wound healing, especially SLNs. It also discusses the various surface modification strategies that can enhance therapeutic effectiveness. Further, to maximize the overall efficacy of the drug delivery system and to improve wound healing outcomes, the incorporation of NPs into advanced dosage forms such as thermoresponsive gels has a huge impact. This review also serves as a database for the methodology of collecting the required data, screening, and selection in addition to the pathways from NPs preclinical studies to the stages of clinical approval; moreover, NPs manufacturing and scaling-up feasibility.

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are typical ABC efflux transporters that play important physiological and pharmacological roles. At the blood-brain barrier (BBB), P-gp and BCRP function cooperatively as the main efflux transporters, hindering the entry of drugs into the brain. Therefore, dual inhibition of P-gp and BCRP is needed to deliver drugs effectively to the brain. This study sought potential dual P-gp/BCRP inhibitors to determine their ability to enhance brain penetration of the anticancer drug mitoxantrone (MX) and thereby improve its therapeutic efficacy against brain cancer. Candidate compounds for dual P-gp/BCRP inhibitors were extracted using in silico algorithms. The dual P-gp/BCRP inhibitory activity of 75 extracted candidates was investigated through MX accumulation studies in breast cancer cell lines overexpressing P-gp (MCF-7/ADR) and BCRP (MCF-7/MX100). The 5 compounds selected as final candidates were CDK 4/6 inhibitor IV, BX795, foretinib, BI-D1870, and CGP60474. Each of these 5 candidates increased MX accumulation and reversed MX resistance in MCF-7/ADR and MCF-7/MX100 cells. Additionally, they increased MX permeability across the BBB in an in vitro model. In situ brain perfusion studies showed that CDK 4/6 inhibitor IV, BX795, and CGP60474 improved the brain delivery of MX in rats. Moreover, in a mouse brain tumor model, CDK 4/6 inhibitor IV and BX795 potentiated the anticancer effect of MX against brain cancer, leading to a considerable reduction in tumor burden. In conclusion, potential dual P-gp/BCRP inhibitors were discovered through in silico screening and verified through in vitro and in vivo studies. CDK 4/6 inhibitor IV was the most effective dual P-gp/BCRP inhibitor candidate for enhancing the brain penetration of an anticancer drug for the treatment of brain tumors.

Twenty-seven sesquiterpenes, including twenty-one new germacrane-type ones (1-5, 8-16, and 19-25) and a new humulane-type one (27), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. The structures and absolute configurations of the new compounds were elucidated using extensive spectroscopic techniques (1D and 2D NMR, and HRESIMS) and quantum chemical calculations. Structurally, compound 20 was a new germacrane-type norsesquiterpene, while compound 27 was a new humulane-type norsesquiterpene. In addition, compound 27 significantly inhibited the production of nitric oxide with an IC value of 3.65 ± 1.06 μM. It reduced the expression of cytokines such as IL-1 and IL-6, as well as inflammation-related proteins induced by LPS or influenza A virus in macrophages, thereby exhibiting significant anti-inflammatory activity. This effect may be related to blocking the formation of the inflammasome and the activation of the NF-κB signaling pathway. Furthermore, compound 10 showed anti-influenza virus activity with an EC value of 27.28 ± 5.63 µM. The study may provide a scientific basis for the development and utilization of functional foods and medicines derived from V. officinalis var. latifolia.

Extracellular matrix protein 1 (ECM1) is a multifunctional glycosylated protein associated with the cell membrane. Increasing evidence indicates that aberrant ECM1 expression in cancer cells promotes tumor growth and metastasis by regulating proliferation, invasion, migration, and drug resistance. Beyond its direct effects on cancer cells, ECM1 plays a pivotal role in shaping the tumor microenvironment by contributing to angiogenesis, inflammatory responses, and the activation of cancer-associated fibroblasts, which collectively drive malignant progression. Immunohistochemical studies have demonstrated that ECM1 is highly expressed in a wide range of invasive cancers compared with adjacent normal tissues, underscoring its potential as a diagnostic and prognostic biomarker. Moreover, elevated ECM1 expression is consistently associated with poor clinical outcomes across multiple malignancies. In this review, we comprehensively summarize research from the past decade on the role of ECM1 in cancer progression, evaluate its potential as a prognostic biomarker, and highlight recent advances in ECM1-targeted therapeutic strategies. Overall, this review provides new insights into the multifaceted roles of ECM1 in cancer biology and its promise as a molecular target for innovative cancer therapies.

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder, which is typically characterized by symptoms such as abdominal pain, diarrhea, and weight loss, significantly impairing patients' quality of life. The etiology of IBD is multifactorial, involving complex interactions among genetic predisposition, immune dysregulation, environmental influences, and gut microbiota imbalance. Curcumin (CUR), a natural polyphenolic compound derived from the traditional Chinese medicine Curcuma longa, attracted considerable interest in pharmacological research due to its potent anti-inflammatory, antioxidant, and immunomodulatory properties. In the context of IBD, CUR exerts therapeutic effects by modulating key inflammatory signaling pathways, maintaining the integrity of the intestinal mucosal barrier, and restoring microbial homeostasis. Clinical studies demonstrated that CUR can alleviate IBD symptoms, suppress inflammatory responses, and improve patients' quality of life. Nevertheless, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To address these limitations, a variety of nanodelivery systems-including polymeric nanoparticles, lipid-based carriers, and nanofibers-have been developed to enhance the solubility, stability, and targeted delivery of CUR. This review provides a comprehensive overview of recent advances in the mechanistic insights, clinical applications, and drug delivery strategies of CUR in IBD therapy, to support future research and clinical translation.