Since its conceptual inception in 1995, Molecular Pharmacognosy has evolved over three decades from a nascent idea into a frontier interdisciplinary discipline characterized by a comprehensive theoretical system, mature methodologies, and extensive applications. This paper systematically reviews the significant milestones of this discipline in theoretical innovation, technical standardization, industrial application, and platform construction. It highlights breakthrough achievements in areas such as technical standards for the molecular identification of crude drugs, elucidation of the formation mechanisms of Dao-di herbs, establishment of conservation models for rare and endangered resources, and biosynthesis of active compounds. The paper further elucidates the evolutionary research paradigm of Molecular Pharmacognosy. Originating from phenomena observed in both the discipline and the industry, this paradigm advances through a progressive cycle of problem derivation—hypothesis presupposition—technical innovation—theoretical enrichment, driven by the dynamic interplay between theory and practice. Furthermore, the paper analyzes current challenges regarding the precision of molecular identification, the complex mechanisms of geo-authenticity, and the sustainable utilization of resources. Molecular Pharmacognosy is poised to integrate deeply with frontier technologies such as artificial intelligence, pan-omics, quantum computing, biomanufacturing, smart breeding, and gene editing. This integration will drive a revolutionary shift in the research paradigm from recognition and revelation to prediction and design. Ultimately, these achievements will mark a new phase defined by precision, systematization, and engineering, injecting fresh momentum into the modernization of TCM.

Focused on the challenges in brain disease treatment and advancements in nose-to-brain delivery research, this article summarized current progress in nasal drug delivery research and proposed several novel evaluation models for nasal drug absorption. By reviewing five types of evaluation models-ex vivo animal tissue models, in situ perfusion models, in vivo pharmacokinetic models, in vitro cell models, and computational fluid dynamics model-it clarified the distinct advantages of nasal drug delivery compared to other administration routes. Furthermore, by outlining emerging nasal drug delivery technologies and irritation evaluation methods, it explored the cutting-edge directions of nose-to-brain delivery. This provides essential support for the selection of nose-to-brain delivery dosage forms and paves new paths for the advancement of nasal drug delivery.

Osteoarthritis (OA) is a common degenerative joint disease characterized by cartilage degeneration, synovial inflammation, osteophyte formation, and joint space narrowing, seriously impairing patients' mobility and quality of life. The pathogenesis of OA is highly complex, involving multiple cell types and signaling pathways. Key pathological processes include abnormal chondrocyte function, sustained activation of inflammatory responses, and imbalances in apoptosis and autophagy. In recent years, microRNAs (miRNAs), small non-coding RNAs, have been recognized for their crucial roles in regulating gene expression and influencing the progression of various diseases. miRNAs exhibit important regulatory functions in OA-related processes such as inflammatory regulation, chondrocyte apoptosis and autophagy, extracellular matrix metabolism, and subchondral bone remodeling. Multiple specific miRNAs have been shown to be closely associated with the onset and progression of OA, demonstrating potential diagnostic and therapeutic value. Traditional Chinese medicine (TCM) is an important treatment approach for OA, offering advantages such as multi-component, multi-target, and multi-pathway regulation. Recent studies have shown that TCM single herbs, compound prescriptions, acupuncture, and moxibustion can upregulate or downregulate the expression of specific miRNAs, thereby intervening in their downstream target genes and related signaling pathways. This leads to anti-inflammatory and analgesic effects, inhibition of chondrocyte apoptosis, promotion of matrix synthesis, and cartilage repair. This review systematically summarizes the mechanisms of miRNAs in the progression of OA, with a focus on the latest research advances in TCM regulation of miRNAs to intervene in OA. The aim is to provide a theoretical basis and new insights for the early molecular diagnosis, targeted therapy, and modern research and clinical translation of TCM in OA.

Colorectal cancer (CRC) is a highly prevalent malignant tumor worldwide, and its occurrence and development are closely related to gut microbiota disturbance. The germ-free (GF) animal model, by providing a unique environment free of indigenous microorganisms, has become a tool for precisely dissecting the causal role and mechanism of the gut microbiota in the occurrence and development of CRC and the therapeutic mechanisms of pharmaceuticals. This review aims to systematically elaborate on the application progress of GF animal models in CRC research, with a focus on the key mechanisms by which specific microorganisms promote the occurrence and development of CRC revealed by this model. Furthermore, this review focuses on the research dynamics of TCM in this field and systematically expounds the application of GF models in the research of TCM against CRC. Through in-depth analysis of the GF animal models of CRC, it is possible to develop precise diagnostic and therapeutic strategies based on TCM and the microbiome in the future, providing new directions and ideas for the prevention and treatment of CRC.

Bacopa monnieri, a plant of Scrophulariaceae, has a long history of medicinal use and is recognized as a traditional medicinal herb in multiple countries. Neurological disorders, due to their extensive damage to neural functions, have become a major public health challenge and garnered worldwide attention. In ancient times, B. monnieri was documented for treating cognitive and memory impairments. Recent studies have elucidated its pharmacological mechanisms and therapeutic targets underpinning the neuroprotective effect. However, the molecular mechanisms of its active ingredients have not been systematically summarized. This study is the first to integrate the target sites of its core ingredients across multiple categories of neurological disorders. It summarizes the pharmacological mechanisms of B. monnieri as well as its active ingredients and derivatives in various neurological diseases, which exert neuroprotective effects through multi-target interactions. This paper provides novel strategies for developing botanical drugs targeting diseases like Alzheimer's and epilepsy and aims to offer evidence-based guidance for the development and application of B. monnieri in functional foods, health supplements, and pharmaceuticals.

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose specific markers and acquire a mesenchymal phenotype under pathological stimulation, contributing to the occurrence and progression of atherosclerosis (AS). Recent studies have shown that TCM, with its unique advantages of holism and treatment based on syndrome differentiation, can inhibit AS by regulating EndMT-related signaling pathways at multiple levels, through multiple pathways and targets. This article systematically reviews the mechanisms of EndMT in AS, as well as the research progress of TCM monomers and compounds in counteracting AS via EndMT intervention, providing new ideas and a scientific basis for the prevention and treatment of AS with TCM.

Epilepsy is a common neurological disorder characterized by refractoriness and recurrence. In China, the prevalence rate is 0.4%-0.7%, with currently over nine million patients, among whom approximately 30% suffer from refractory epilepsy. Although antiepileptic drugs (AEDs) are the mainstay of treatment, they are associated with multi-system adverse reactions and drug resistance issues. In contrast, traditional Chinese medicine (TCM) treatment exhibits significant efficacy with lower toxicity and side effects, and integrated TCM and western medicine treatment can achieve complementary advantages. Studies have shown that integrated therapy demonstrates benefits in various types of epilepsy, including status epilepticus, post-stroke epilepsy, post-traumatic epilepsy, pediatric epilepsy, refractory epilepsy, and epilepsy comorbid with depression and anxiety. It exerts synergistic effects by enhancing AED bioavailability (borneol improves blood-brain barrier permeability), reducing seizure frequency, preventing recurrence, and minimizing western medicine toxicity (Dingxian Decoction decreases digestive/neurological adverse reactions). The underlying mechanisms involve regulating neurotransmitters (modulating glutamate and γ-aminobutyric acid levels) and ion channels (inhibiting sodium/calcium ion channels). In terms of preventive care, TCM plays an important role in preventing epileptic seizures by correcting biased constitutional states. In the future, integrated TCM and western medicine in epilepsy prevention and treatment will move toward individualized treatment, etiological treatment, preventive rehabilitation, and integration of scientific research with clinical practice, forming a three-dimensional development pattern of "technology empowerment, standard guidance, and whole-process management".

Clarifying the two-dimensional spatial distribution and the seasonal yield dynamics of Epimedium pubescens roots in agroforestry systems can provide an ecological theoretical basis and technical support for optimizing the understory cultivation patterns of E. pubescens. E. pubescens plants cultivated in Ginkgo biloba forests (YX), Phellodendron amurense forests (HB), and monocropping fields (CK) were taken as research subjects. Stratified sampling was conducted during the summer and winter harvest seasons to analyze root spatial distribution, morphological characteristics, and biomass allocation. Additionally, high-performance liquid chromatography (HPLC) was employed to determine the total flavonol glycoside content. The results demonstrated that the spatial distribution of E. pubescens roots exhibited significant differences among planting patterns. Specifically, the HB group showed a significantly higher proportion of fine roots in the surface soil layer (0-10 cm) than the YX and CK groups, whereas the YX group displayed more extensive root distribution in deeper soil layers (30-50 cm) than the HB and CK groups. The root morphology of E. pubescens was significantly influenced by planting patterns and seasonal variations. In summer, the root length density of E. pubescens in the YX group decreased by 56%-75% (P<0.05) in the 0-20 cm soil layer compared with that in the CK group, whereas in winter, both agroforestry systems showed significantly higher root length density than the CK group. No significant difference was observed in aboveground or belowground biomass of E. pubescens among different planting patterns. However, the YX group exhibited significantly higher root biomass allocation ratio and significantly lower rhizome biomass allocation ratio than the CK and HB groups. These findings indicate that E. pubescens roots exhibit remarkable phenotypic plasticity, enabling adaptive adjustment strategies to enhance resource acquisition efficiency in agroforestry systems.

Using the whole-genome data of Atractylodes lancea, members of the auxin (Aux)/indole-3-acetic acid (IAA) gene family were identified and characterized, and the effects of 1-naphthaleneacetic acid (NAA) treatment on the expression levels of this gene family were investigated, providing a foundation for further studies on the functions of the A. lancea Aux (AlAux)/IAA gene family. Members of the AlAux/IAA gene family were identified from the A. lancea whole-genome data using TBtools-Ⅱ. Bioinformatics software was employed to analyze the physicochemical properties of the encoded proteins, construct a phylogenetic tree, and predict conserved motifs and gene structures. Tissue-cultured seedlings of A. lancea were used as experimental materials, and key genes of the AlAux/IAA gene family were screened by transcriptome sequencing. The expression of key AlAux/IAA genes was analyzed after one month of NAA treatment. A total of 53 AlAux/IAA genes were identified from the A. lancea genome. Most AlAux/IAA proteins were localized in the nucleus, lacked transmembrane domains, and exhibited negative hydrophobicity. Among them, 44 AlAux/IAA genes were predicted to encode functional Aux/IAA transport proteins. Transcriptome sequencing and RT-qPCR analyses showed that the AlAux/IAA family genes exhibited spatiotemporal expression specificity, and different members displayed varying response times and intensities to NAA treatment. Tissue-specific expression analysis revealed that the AlAux/IAA gene family was generally highly expressed in flowers. This study identified the Aux/IAA gene family members in A. lancea, preliminarily analyzed their sequence characteristics, and examined their expression features in response to Aux. It is speculated that AlAux/IAA13 and AlAux/IAA38 may be involved in rooting and bud growth and development during the subculture process of A. lancea tissue-cultured seedlings. These results provide a theoretical basis for elucidating the molecular mechanisms of AlAux/IAA gene function and Aux-mediated regulation of rhizome growth in A. lancea.

Based on supramolecular chemistry of TCM, this study investigated the interaction between Cinnamomi Cortex-Coptidis Rhizoma herb pair and compared phase states and bioactivity differences under different decoction methods (co-decoction vs individual decoction followed by mechanical mixing). Phase state variations were observed macroscopically and through turbidimetry. The herb interaction was analyzed using isothermal titration calorimetry, UV and IR spectroscopy. Particle size differences were determined by dynamic light scattering and scanning electron microscopy (SEM). Antimicrobial activity was evaluated through broth dilution, plate coating, live/dead staining, and SEM. Component analysis was conducted using UPLC-MS/MS. Results revealed distinct supramolecular structures in Cinnamomi Cortex-Coptidis Rhizoma decoctions, with co-decoction showing more stable macroscopic phase states. The interaction was a spontaneous exothermic reaction driven by both entropy and enthalpy. UV and IR spectra revealed co-decoction demonstrated more sufficient molecular interactions, more stable supramolecular structures, and smaller particle sizes with a more centralized distribution. In addition, co-decoction resulted in higher berberine and coptisine content and stronger inhibitory activity against Staphylococcus aureus compared to mechanical mixtures. These findings indicated that co-decoction produced Cinnamomi Cortex-Coptidis Rhizoma supramolecular systems with more homogeneous phase states, enhanced measurable coptisine and berberine content, and superior antibacterial efficacy.