Dahong Yao

Ethnopharmacological relevance: Dioscorea nipponica Makino is a traditional medicinal plant widely used in East Asia for the treatment of rheumatic disorders, inflammatory diseases, and cardiovascular conditions. Its rhizome has long been applied in clinical practice for relieving pain, promoting blood circulation, and reducing swelling. Aim of the study: This narrative review aims to provide a comprehensive and critical overview of the phytochemical constituents, pharmacological activities, and underlying mechanisms of D. nipponica and to identify current research gaps and future perspectives. Materials and methods: The literature was searched in PubMed, Web of Science, ScienceDirect, CNKI and Wanfang Data from database inception to December 2025. The combined retrieval keywords were set as: (Dioscorea nipponica Makino OR Chuanshanlong) AND (chemical constituents OR steroidal saponins OR flavonoids OR phenols) AND (biological activity OR anti-inflammatory OR cardioprotective OR hepatotoxicity OR clinical application). Both English and Chinese publications were retrieved, and studies written in other languages were excluded. Results: Phytochemical studies have identified diverse secondary metabolites, particularly steroidal saponins, along with diarylheptanoids and phenanthrenes. These compounds exhibit multiple pharmacological activities, including anti-inflammatory, anti-tumor, immunomodulatory, and cardioprotective effects. Mechanistic studies indicate that these activities are mediated through the modulation of key signaling pathways such as NF-κB, PI3K/Akt, AMPK, and the NLRP3 inflammasome. However, current research remains fragmented, with limited integration of chemical composition, molecular targets, and therapeutic outcomes. Conclusions: D. nipponica represents a promising source of bioactive natural products, with steroidal saponins as the major contributors to its pharmacological effects. Future studies should focus on multi-component interactions, pharmacokinetics, quality control, and clinical validation to support its rational development and sustainable utilization.

Objective: Soluble epoxide hydrolase (sEH) emerges as a target of interest for inflammatory diseases. Piperine is a natural amide alkaloid from Piper nigrum and displays an inhibitory effect toward sEH, its chemical structural transformation was carried out in order to obtain a library of sEH inhibitors based on its skeleton. Methods: Structural transformation of piperine was carried out by chemical methods, and piperine derivatives were assayed for their sEH potentials. A mouse acute lung injury model was constructed by lipopolysaccharide (LPS). Hematoxylin and eosin (H&E) staining, immunofluorescence staining, Western Blot, and enzyme-linked immunosorbent assay were used for investigating the protective potential of sEH inhibitor 11h. Results: Piperine derivatives 11e, 11h, 11j, and 11o showed inhibitory potentials toward sEH with values of half maximal inhibitory concentration (IC₅₀) from 20 to 70 nM. Compound 11h attenuated the pathological course of LPS-mediated acute lung injury (ALI) in vivo. Furthermore, levels of cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) were decreased after administration of 11h. The LPS-mediated inflammation and redox unbalance, including expressions of cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), p-p65/p65, glutamate-cysteine ligase modifier subunit (GCLM), and nuclear factor erythroid-2-related factor 2 (Nrf2), were ameliorated through nuclear factor kappa B (NF-κB) and Nrf2 pathways via enhancing levels of epoxyeicosatrienoic acids (EETs) in LPS-exposed ALI mice after compound 11h treatment. Molecular docking demonstrated that the aromatic unsaturated group of 11h occupied a hydrophobic pocket and its urea group formed three hydrogen bonds with Asp333, Tyr381, and Tyr465, which stabilized the active conformation of the ligand. Conclusions: These findings demonstrated that compound 11h may serve as a lead compound for developing sEH inhibitors and treating inflammation related to diseases, such as ALI.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, and addressing its intrinsic heterogeneity has emerged as a valuable avenue for novel clinical treatment strategy. Here, we put forward an innovative strategy for TNBC treatment by simultaneously suppressing both p21-activated kinase 1 (PAK1) and histone deacetylase (HDAC) class IIb (HDAC6/10). A series of pyrido [2,3-d]pyrimidin-7(8 H )-one moiety derivatives was successfully designed and synthesized to target PAK1/HDAC6/HDAC10 by utilizing structure-based screening and pharmacophore integration. ZMF-25 demonstrates marked inhibitory activity against PAK1, HDAC6, and HDAC10 with respective IC ₅₀ values of 33, 64, and 41 nM, remarkable selectivity over HDACs and PAKs, as well as prominent antiproliferative efficiency in MDA-MB-231 cells. Additionally, ZMF-25 effectively suppresses TNBC proliferation and migration by inhibiting PAK1/HDAC6/HDAC10. Moreover, it was found to impair glycolysis and trigger reactive oxygen species generation, resulting in autophagy-related cell death by inhibiting the AKT/mTOR/ULK1 signaling. Furthermore, ZMF-25 exhibits remarkable therapeutic potential with no obvious toxicity in vivo and good pharmacokinetics. In summary, these observations indicate that ZMF-25 is a novel and potent triple-targeting PAK1/HDAC6/HDAC10 inhibitor, which is expected to provide a novel and effective strategy for TNBC treatment.