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.

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.

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.

This study investigated the toxicological mechanisms of different processed products of Strychnos nux-vomica seeds using serum metabolomics analysis. Seventy-two female KM mice were randomly divided into six groups (n = 12 per group): control, raw seeds, vinegar-processed seeds, urine-soaked seeds, sand-roasted seeds, and oil-fried seeds. Each processed preparation group received an aqueous decoction of the original herb at the same concentration for 7 days. Hepatic and renal coefficients were measured in each group, and the levels of hepatic and renal injury markers, including aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and creatinine (CRE) were determined using a fully automated biochemical analyzer. Hematoxylin-eosin (HE) staining was used for histopathological examination of the liver and kidney. Liquid chromatography-mass spectrometry (LC-MS/MS) combined with multivariate statistical analysis was employed to screen for differential serum metabolites across groups. Metabolic pathway enrichment analysis of the selected differential markers was performed using the Human Metabolome Database (HMDB) and MetaboAnalyst 6.0. All processed S. nux-vomica seed products increased hepatic and renal coefficients and elevated hepatic and renal injury markers (AST, ALT, BUN, CRE), although these effects were reduced to varying degrees compared to the raw product. Overall, vinegar processing exhibited the most significant detoxification effect, followed by oil-fried>sand-roasted≈urine-soaked > raw seeds. Metabolomic analysis identified 14 differential metabolites across the groups, primarily including sphingolipids, glycerophospholipids, and vitamin-related compounds. Five significantly perturbed metabolic pathways were identified: sphingolipid metabolism, glycerophospholipid metabolism, α-linolenic acid metabolism, lipoic acid metabolism, and linoleic acid metabolism, with sphingolipid and glycerophospholipid metabolism common to all groups. In conclusion, processing of S. nux-vomica seeds reduced hepatorenal toxicity to varying degrees, and its toxic mechanisms may primarily involve disturbances in sphingolipid and glycerophospholipid metabolism.

This study investigated the effects and molecular mechanisms of sarsasapogenin (SSG) on colorectal cancer (CRC). After HRT-18 and HCT116 cells were treated with varying concentrations of SSG, the effect of SSG on CRC cell proliferation, migration, and glycolysis was assessed by cell counting kit-8 (CCK-8), real-time cellular analysis (RTCA), colony formation assay, high-content imaging analysis, and Seahorse glycolysis stress test. Changes in intracellular lactate release and adenosine triphosphate (ATP) levels under SSG treatment were measured by lactate and ATP detection kits, respectively. The effects of SSG on the transcription level and protein expression of the key glycolytic gene hypoxia-inducible factor 1α (HIF1α) were evaluated via quantitative polymerase chain reaction (qPCR) and Western blot. Direct binding between SSG and HIF1α was identified by drug affinity responsive target stability (DARTS). The UbiBrowser database, microscale thermophoresis (MST), and molecular docking simulations were employed to screen and validate the E3 ubiquitin ligase mediating HIF1α degradation. The results showed that SSG significantly inhibited CRC cell proliferation and colony formation in a dose-dependent manner. The 24-hour half-maximal inhibitory concentrations (IC₅₀) of SSG for HRT-18 and HCT116 cells were 6.275 μmol·L^-1 and 7.029 μmol·L^-1, respectively. After 24 hours of treatment with SSG at concentrations of 2.0, 4.0, and 6.0 μmol·L^-1, the HRT-18 and HCT116 clone formation rate was significantly reduced. High-content imaging results showed that SSG significantly inhibited the migration ability of CRC cells. Seahorse glycolysis stress test, along with lactate and ATP measurements, demonstrated that SSG suppressed basal glycolysis, glycolytic capacity, glycolytic reserve, lactate release, and ATP content in CRC cells. The qPCR and Western blot results showed that SSG had no significant effect on HIF1α mRNA expression, and the HIF1α protein expression was downregulated. DARTS confirmed the direct binding of SSG to HIF1α. UbiBrowser analysis identified five E3 ubiquitin ligases potentially targeting HIF1α. Molecular docking and MST results indicated that the F-box/WD repeat-containing protein 7 (FBXW7) exhibited strong binding affinity to HIF1α in the presence of SSG. In summary, SSG exerts its anti-cancer effects in CRC by targeting HIF1α to promote its FBXW7-mediated proteasomal degradation and consequently inhibiting glycolytic reprogramming.

This article aims to investigate the inhibitory effect and molecular mechanism of sculponeatin A (STA) on triple negative breast cancer (TNBC). MDA-MB-436 and MDA-MB-468 were selected as cell models. The MTT assay, real-time cell analysis (RTCA), and colony formation assay were used to evaluate the effects of different concentrations of STA on the proliferation of TNBC cells. JC-1 staining and Annexin V-FITC/PI double staining combined with flow cytometry were used to measure the effect of STA on the apoptosis of TNBC cells. Western blot was employed to determine the expression changes of apoptosis-related proteins [cysteinyl aspartate-specific proteinase (caspase)-9, caspase-3, and poly-ADP-ribose polymerase (PARP)] and cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein kinase B (AKT) signaling pathway proteins [CIP2A, AKT, phosphorylated (p)-AKT] in TNBC cells after STA treatment. To clarify the function of CIP2A in the action of STA, a CIP2A overexpression or CIP2A knockdown plasmid was transfected into cells, which were then treated with STA. Cell proliferation, apoptosis, and protein expression changes were evaluated by CCK-8, flow cytometry, and Western blot. Further, RT-qPCR and Western blot both showed that STA significantly downregulated the mRNA and protein levels of CIP2A and the protein level of c-Myc. The overexpression of c-Myc antagonized the downregulating effects of STA on the protein and mRNA levels of CIP2A, while the knockdown of c-Myc enhanced this effect. The drug affinity-responsive target stability (DARTS) assay and microscale thermophoresis (MST) assay confirmed the existence of direct binding between STA and c-Myc protein. The results indicated that STA significantly inhibited the proliferation and colony formation and induced the apoptosis of TNBC cells, manifested by an increased apoptosis rate, downregulated precursor protein expression of caspase-9 and caspase-3, and increased PARP cleavage. STA treatment reduced the p-AKT level but did not affect total AKT. Functionally, the knockdown of CIP2A enhanced the STA effects of inhibiting proliferation and inducing apoptosis, while the overexpression of CIP2A produced antagonistic effects. From a mechanism perspective, STA directly targets and binds to c-Myc to downregulate its expression, thereby inhibiting the transcription and translation of CIP2A and ultimately blocking the c-Myc/CIP2A signaling pathway. In conclusion, STA inhibits the malignant progression of TNBC by targeting the c-Myc/CIP2A signaling axis.

The stem bark of Aquilaria yunnanensis (Thymelaeaceae) is traditionally used to treat cough and asthma in folk medicine. However, its active components have not been reported. In the present study, the chemical constituents of A. yunnanensis stem bark were isolated and identified, and their inhibitory activities against nitric oxide (NO) production in RAW264.7 cells induced by lipopolysaccharide (LPS) were evaluated to clarify the anti-inflammatory components in the stem bark of A. yunnanensis. A total of 22 compounds, including a new norlignan [(±)-1], were isolated from the ethanolic extract of A. yunnanensis stem bark by column chromatography, high-performance liquid chromatography (HPLC), recrystallization, etc. Through chiral separation of (±)-1, (-)-1 and (+)-1 were obtained. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of (-)-1 and (+)-1 were determined to be (-)-(7R, 8S, 8′S)-4-O- (1, 3-dihydroxypropan-2-yl) zhebeiresinol and (+)-(7S, 8R, 8′R)-4-O- (1, 3-dihydroxypropan-2-yl) zhebeiresinol. The known compounds included (±)-zhebeiresinol (2), (+)-syringaresinol (3), (+)-episyringaresinol (4), orcinol (5), orsellinic acid (6), methyl orsellinate (7), 3, 4-dihydroxybenzoic acid (8), lecanoric acid (9), barbatic acid (10), 7β-hydroxy-β-sitosterol (11), β-sitosterol (12), stigmasterol (13), ergosterol peroxide (14), genkwanin (15), pilloin (16), 5-hydroxy-3′, 4′, 7-trimethoxyflavone (17), (-)-epicatechin (18), (-)-epicatechin gallate (19), tectorigenin 2-O-α-L-rhamnopyranoside (20), 2, 3-dihydroxypropyl docosanoate (21), and 1-O-linolenoylglycerol (22). According to the bioassay testing results, compounds 4 and 22 which inhibited NO production with IC₅₀ values of (32.82±1.04) and (18.50±0.95) μmol·L^-1, respectively, exhibited anti-inflammatory activities.

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.

This study investigates the mechanisms and target sites of Renshen (Ginseng Radix et Rhizoma)-Danshen (Salviae Miltiorrhizae Radix et Rhizoma) (RSDS) in regulating myocardial ischemia-reperfusion injury (MIRI) via the silent information regulator 3 (SIRT3)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)/voltage-dependent anion-selective channel 1 (VDAC1) signaling pathway. A rat MIRI model was established and randomly divided into control, model, fosinopril, and low-, medium-, and high-dose RSDS groups. Cardiac function, cell apoptosis, and myocardial fibrosis were assessed using cardiac ultrasound, TUNEL staining, hematoxylin-eosin (HE) staining, and Masson staining. Serum factors and the expression of key proteins and genes, such as SIRT3, PGC-1α, and VDAC1 in myocardial tissue, were analyzed using ELISA, Western blot, and RT-qPCR to investigate the underlying mechanisms through the SIRT3/PGC-1α/VDAC1 signaling pathway. The experimental results showed that, compared with the model group, RSDS significantly improved cardiac function, with the high-dose group exhibiting the most pronounced cardioprotective effect, including increased left ventricular ejection fraction (LVEF), decreased left ventricular end-systolic diameter (LVESD), and increased left ventricular fractional shortening (LVFS). TUNEL staining demonstrated that RSDS reduced myocardial cell apoptosis, and Masson staining indicated that RSDS significantly alleviated myocardial fibrosis. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and creatine kinase-MB (CK-MB) were significantly decreased, while superoxide dismutase (SOD) levels were significantly increased, suggesting strong anti-inflammatory and antioxidant effects. Western blot and RT-qPCR analyses demonstrated that RSDS improved mitochondrial function, inhibited oxidative stress, and protected myocardial cells by regulating the SIRT3/PGC-1α/VDAC1 signaling pathway. In conclusion, RSDS significantly ameliorates cardiac dysfunction induced by MIRI through regulation of the SIRT3/PGC-1α/VDAC1 signaling pathway, reducing myocardial apoptosis, fibrosis, and inflammation.

In this study, the total alkaloids of Corydalis delicatula were isolated and purified by a combination of silica gel, aluminum oxide basic column chromatography and other chromatographic techniques. The obtained compounds were structurally identified with the help of modern spectral resolution techniques such as nuclear magnetic resonance (1D/2D NMR), high-resolution mass spectrometry (HR-ESI-MS), and single crystal X-ray diffraction. Nine alkaloids were obtained from the total alkaloids of C. delicatula, encompassing two new compounds, corlicatine (1) and N-methyl-13-oxoprotopine (2), and seven known ones: (+)-ochotensine (3), rupestrine A (4), (+)-ochotensimine (5), oxohydrastinine (6), α-magnoflorine (7), 6, 7-methylenedioxy-N-methylisoquinoline (8), and N-methyl-6, 7-dimethoxyisoquinoline (9). The inhibitory activities of the compounds against acetylcholinesterase were evaluated, with compound 4 exhibiting moderate inhibition. Molecular docking was further performed to elucidate the binding mode of this compound. The results provide a basis for elucidating the medicinal substance basis of C. delicatula.