Natural components are crucial sources for drug discovery. Based on the central dogma of molecular biology, we proposed a novel paradigm for classifying natural products by categorizing natural components into "direct gene-encoded components" (including nucleic acids and peptides) and "indirect gene-encoded components" (encompassing primary metabolites and secondary metabolites). Utilizing multi-omics and artificial intelligence technologies, we systematically analyzed the nuclear and organellar genomes of 1 037 medicinal species sourced from eight authoritative global pharmacopeias, integrating multidimensional data resources to establish the gene-encoded natural diversity components repository (GNDC). This paper comprehensively describes: (1) The construction methodology of GNDC, including data integration strategies, standardized annotation pipelines, and rigorous quality control; (2) Core features and data scale: GNDC is currently the world's largest repository of medicinal natural products, housing over 234 million gene-encoded (directly or indirectly) natural components. It encompassed four specialized sub-databases: HerbalMDB for 2.32 million secondary metabolites, HerbalPDB for 229 million small peptides, HerbalRDB for 2.38 million small RNAs, and HerbalCDB for 0.26 million carbohydrates; (3) Exploring the application prospects of GNDC in the modernization of traditional medicine research. GNDC will provide an unprecedented expansive "chemical space" for drug discovery. It will powerfully drive a paradigm shift in drug development from "experience-oriented" to "big data-driven" approaches, offering a transformative framework for traditional medicine research.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with metabolic syndrome, and its animal models are essential for investigating the pathological mechanisms and disease progression of NAFLD. Currently, the most commonly used NAFLD animal models include the high-fat, methionine- and choline-deficient diet (HFMCD) and the high-fat diet (HFD)-induced mouse models. In this study, we compared NAFLD mouse models established by an 8-week HFMCD diet and a 12-week HFD, systematically evaluating differences in liver weight, histological alterations, lipid metabolism, and inflammation-related gene expression. The experimental results showed that, compared with the normal chow diet (NCD) group, mice in the HFMCD group exhibited significant reductions in body weight and blood glucose levels, whereas those in the HFD group exhibited significant increases. Both dietary models led to an increase in liver weight; however, hematoxylin and eosin (H&E) staining revealed more severe liver damage in the HFMCD group. Oil red O staining indicated a significantly greater degree of hepatic lipid accumulation in the HFMCD group than in the HFD group. Quantitative PCR (qPCR) analysis demonstrated that, compared with the NCD group, both the HFMCD and HFD groups exhibited significantly elevated hepatic expression of inflammatory cytokines. Sirius red staining demonstrated pronounced hepatic fibrosis in the HFMCD group, accompanied by a significant upregulation of genes associated with collagen synthesis, whereas the HFD group exhibited no evident fibrotic alterations. F4/80 immunohistochemical staining showed increased hepatic macrophage infiltration in both models, with a significantly higher number of F4/80-positive macrophages in the HFMCD group than in the HFD group. In conclusion, the HFMCD and HFD-induced NAFLD models exhibit distinct pathological characteristics and molecular mechanisms. The HFMCD model is more suitable for studying the progression of NAFLD to non-alcoholic steatohepatitis (NASH), whereas the HFD model is more appropriate for investigating the metabolic mechanisms of simple steatosis. This study provides experimental evidence for NAFLD research and offers guidance for selecting appropriate animal models based on specific research objectives. All experimental animals used in this study were approved by the Animal Care and Use Committee of Nanjing University and were handled in strict accordance with the guidelines and recommendations provided by the Nanjing University's Animal Ethics Committee.

Breast cancer bone metastasis disrupts bone metabolism, enhancing osteogenic differentiation can improve the metastatic microenvironment and treatment outcomes. Thus, developing agents that inhibit breast cancer and promote osteogenesis may offer new strategies. Tripterygium wilfordii possesses antitumor and bone-regulating properties, but its toxicity limits clinical application. Here, a carbon dot was synthesized from Tripterygium wilfordii (Tripterygium wilfordii carbon dots, T-CDs) and characterized by spectral analysis, dynamic light scattering, and transmission electron microscopy. T-CDs exhibited a near-spherical morphology with a lattice spacing of 0.20 nm, an average size of 5.38 nm, and a ζ potential of -8.46 mV. The surface was rich in -OH, C=O, and C=C groups, with ultraviolet absorption at 280 nm. T-CDs disrupted redox homeostasis in breast cancer cells, inducing ferroptosis and immunogenic cell death. Moreover, T-CDs modulated cytokine secretion and promoted osteogenic differentiation, offering potential for the treatment of breast cancer and its bone metastasis.

To explore the mechanism of Lvjiaobuxue Granule (LBG) in improving postpartum Qi and blood deficiency in rats through milk metabolomics combined with biological target network analysis, the model of postpartum Qi and blood deficiency in rats was established by "orbital bloodletting combined with exhaustive swimming under negative gravity". The behavioral indexes, blood routine parameters, immune organ index and changes of immunoglobulin G (IgG) in milk of rats were detected to evaluate the improvement effect of LBG on postpartum Qi and blood deficiency in rats. LC-MS milk metabolomics was applied to find the differential metabolites in the milk of rats with postpartum Qi and blood deficiency model regulated by LBG. Combined with biological target network analysis, the material basis of the efficacy, action targets and signaling pathways of LBG in improving postpartum Qi and blood deficiency were predicted, and molecular docking was used for verification. The animal experiments in this study were conducted in compliance with the regulations of the Scientific Research Ethics Committee of Shanxi University and approved by the Animal Experimentation Ethics Review (approval No.: SXULL2023022). LBG significantly improved the abnormal behavior, decreased blood routine parameters, immune organ damage and decreased IgG in milk of rats with postpartum Qi and blood deficiency model (P < 0.05, P < 0.01). Twenty endogenous metabolites were found to be differential in milk, serving as potential biomarkers for LBG to improve postpartum Qi and blood deficiency in rats, and these metabolites mainly included amino acids, fatty acids and nucleotides, etc. Biological target network analysis showed that its potential mechanism might be related to the signaling pathway of steroid hormone biosynthesis. The key components in LBG, luteolin, caffeic acid and ferulic acid, might respectively regulate the core targets of CYP19A1, CYP1A1, CYP1A2 and CYP3A4, affect the changes of linoleic acid endogenous metabolites in milk, and regulate the biosynthesis of steroid hormones to play its role in improving postpartum Qi and blood deficiency. In addition, the results of molecular docking showed that the three key components in LBG had significant binding effects with their core targets. LBG may affect the linoleic acid level in milk by regulating CYP19A1, CYP1A1, CYP1A2 and CYP3A4 with luteolin, ferulic acid and caffeic acid respectively, and then regulate the signaling pathway of steroid hormone biosynthesis to improve postpartum Qi and blood deficiency in rats.

Right ventricular (RV) dysfunction is a pivotal prognostic determinant in patients with pulmonary arterial hypertension (PAH). Hypoxic stimulation induces hypoxic pulmonary vasoconstriction (HPV) and exerts cardiotoxic effects, thereby accelerating RV remodeling in PAH. Previous in vitro vascular ring experiments demonstrated that α-phellandrene (PE) exhibits vasodilatory effects, but its impact on hypoxia-induced RV structural and functional alterations and underlying mechanisms remain unclear. To address this, we established a hypoxia-induced pulmonary arterial hypertension (HPH) rats model and comprehensively evaluated the therapeutic effects of PE on multi-scale RV pathological remodeling through echocardiography, histomorphometric analyses, and Western blot. Additionally, the molecular mechanisms underlying PE-mediated modulation of the nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway were investigated using H9C2 cardiomyocytes. Results demonstrated that compared with the model group, PE treatment significantly improved RV systolic function in HPH rats, as evidenced by increased tricuspid annular plane systolic excursion, pulmonary artery acceleration time, fractional area change, and RV ejection fraction. Concurrently, PE reduced RV free wall thickness in diastole and RV inner diameter, effectively attenuating hypoxia-induced RV remodeling. PE administration also markedly decreased mean pulmonary artery pressure and RV hypertrophy index compared to the model group. Histomorphological analysis demonstrated that PE treatment significantly reduced collagen deposition in RV tissues and downregulated expression of fibrotic markers, including α-smooth muscle actin, collagen Ⅰ and collagen Ⅲ. Mechanistic investigations revealed that PE upregulated endothelial nitric oxide synthase expression in both rats RV tissues and H9C2 cardiomyocytes, enhanced NO bioavailability, and activated sGC- cGMP signaling axis. These molecular effects collectively ameliorated hypoxia-induced oxidative damage and attenuated fibrotic progression. This study reveals that PE ameliorates hypoxia-induced RV remodeling and dysfunction by modulating the NO-sGC-cGMP signaling pathway to reduce oxidative damage and fibrotic remodeling in hypoxic conditions. These findings provide experimental evidence for developing RV-targeted therapeutic strategies against HPH. All animal experiments were approved by the Institutional Animal Care and Use Committee of Qinghai University (approval No: PJ-202302-01).

Terpinen-4-ol (T4O) is a bioactive monoterpenoid with significant cardiovascular pharmacological activity. This study investigated T4O's protective effects against high glucose (HG) induced injury in rat cardiomyocytes (H9C2) and its impact on silencing the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-γ (PPARγ) signaling pathway. In the experiment, H9C2 cells were pre-incubated with different doses of T4O for 2 h, followed by co-incubation with HG for 48 h to create an injury model. Cell survival was determined using the MTT assay. Intracellular reactive oxygen species (ROS) levels were detected using the fluorescent probe DCFH-DA. Apoptosis rates were detected using flow cytometry. Mitochondrial membrane potentials were observed using JC-1 staining. Western blot was used to detect the expression levels of the apoptosis-related proteins Bcl-2, Bax, Caspase-9, and Caspase-3, as well as SIRT1 and PPARγ. Immunofluorescence was used to observe the localization and expression of SIRT1 and PPARγ. Silencing SIRT1 expression in H9C2 cells was achieved by SIRT1 siRNA transfection. The effects of T4O on ROS content, apoptosis rate, mitochondrial membrane potential, and expression of the aforementioned proteins in HG-induced H9C2 cells were then observed. Compared to the HG group, T4O significantly improved HG-induced injury to H9C2 cells. It decreased ROS levels and the apoptosis rate, increased the mitochondrial membrane potential, and down-regulated the expression levels of the Caspase-9 and Caspase-3 proteins induced by HG. Meanwhile, it increased the Bcl-2/Bax ratio and SIRT1 and PPARγ expression levels (P < 0.05, P < 0.01). After SIRT1 was silenced, compared with the negative control + HG group, the SIRT1 siRNA + HG group exhibited significantly increased intracellular ROS levels and apoptosis rates, reduced mitochondrial membrane potential, and upregulated of Caspase-9 and Caspase-3 protein expression. while the Bcl-2/Bax ratio and expression levels of SIRT1 and PPARγ were further downregulated (P < 0.05, P < 0.01). Co-treatment with SIRT1 silencing and T4O reversed the protective effect of T4O against H9C2 cells damage. In conclusion, T4O ameliorates HG-induced injury to H9C2 cells by activating the SIRT1/PPARγ signaling pathway. This provides a new idea and potential target for developing anti-myocardial injury drugs.

Urtica fissa, a commonly used traditional Chinese herb, frequently causes contact dermatitis during application. However, the inflammatory components have not been reported. In this study, RAW264.7 cell model was employed first to identify the dichloromethane fraction as the primary inflammatory fraction. Then, using chromatographic techniques such as silica gel column chromatography and preparative HPLC, combined with HR-MS, NMR, and UPLC-IM-Q-TOF-MS analysis, 44 compounds, including nettlol, cinnamic acid, and salicylic acid, were identified from the dichloromethane fraction. Subsequently, the potential inflammatory components were confirmed by transcriptomic analysis and molecular docking. Finally, the inflammatory effects of these candidates were evaluated by an open topical application test on mouse skin. The results showed that cinnamic acid and salicylic acid significantly induced skin erythema and ear swelling in mice, and markedly elevated histamine and NO levels in serum and skin, confirming them as the key inflammatory constituents. All animal experiments were reviewed and approved by the Ethics Committee of Shanghai Jiao Tong University Laboratory Center (A2025060-001). The findings of this study provided a scientific basis for further research and application of U. fissa.

This study employed CHO-K1-FSHR-CRE-Luc transgenic cells as target cells to detect the biological activity of rhFSH-CTP using a luciferase detection system. Key parameters of the method were optimized, and its performance was validated according to the requirements of the 2020 Edition of Pharmacopoeia of the People's Republic of China (Vol IV), including relative accuracy, intermediate precision, linearity and range, and reliability results. The results showed that rhFSH-CTP conformed to the four-parameter equation: y = (A-D)/[1+(x/C)^B]+D, exhibiting an excellent dose-effect curve. The geometric means of relative biological activities (n = 8) at five titer levels (50%, 80%, 100%, 125%, and 200%) were (53.87 ± 2.47)%, (81.58 ± 1.66)%, (96.76 ± 4.64)%, (127.03 ± 8.19)%, and (207.62 ± 15.52)%, respectively. The relative bias (RB) and its 90% confidence intervals were 7.7% (4.2%, 10.8%), 2.0% (0.6%, 3.3%), -3.2% (-6.4%, -0.3%), 1.6% (-2.9%, 5.8%), and 3.8% (-1.6%, 8.9%), with absolute values of RB and confidence intervals all less than 11%. The upper limits of geometric coefficients of variation (GCV) and their confidence intervals for five titer levels were less than 20%. The linear range spanned 50%-200%, with a slope of 0.974 2 and R² = 0.994 8, meeting the criteria of General Chapter 9401 in Volume IV of the 2020 Pharmacopoeia. Additionally, the deviation parallelism and regression terms satisfied the reliability test requirements of General Chapter 1431 (biological assay statistics) in the same pharmacopoeia edition. In conclusion, this study successfully established a method for detecting the biological activity of rhFSH-CTP, which demonstrates good validity and reliability.

Baicalin eye drops have broad clinical application prospects in the treatment of ocular diseases. However, there is still a lack of qualitative and quantitative research on the related substances in them. This study first established an analytical method for related substances in baicalin eye drops, providing a scientific basis for product development and quality control. Through LC-Q/TOF-MS/MS, seven related substances were preliminarily identified in baicalin eye drops, namely scutellarin, oroxylin A-7-O-glucuronide, oroxin A, quercetin-7-O-glucuronide/quercetin 3-O-glucuronide, chrysin-7-O-glucuronide, baicalein, and scutellarein. The quantitative analysis of oroxin A, scutellarin and oroxylin A-7-O-glucuronide was carried out by HPLC. The chromatographic column was the NanoChrom AR C18 column (250 mm × 4.6 mm, 5 μm). The mobile phase was 0.1% phosphoric acid aqueous solution (A)-acetonitrile (B), with gradient elution. The column temperature was 20 ℃, the flow rate was 0.8 mL·min^-1, and the detection wavelength was 254 nm. The established method has strong specificity, high sensitivity, and good precision. In this study, a method for the qualitative and quantitative analysis of related substances in baicalin eye drops was established, providing a basis for ensuring their quality.

An UPLC-QTRAP-MS/MS analytical method for six blood components (rhein, aloeemodin, sinapic acid, liquiritin, isoliquiritin apioside, and wogonoside) in Daxiefei Decoction was established and applied to the pharmacokinetic study in normal and chronic obstructive pulmonary disease (COPD) model rats to reveal their absorption kinetics characteristics and elimination rules in vivo, in order to provide a scientific basis for the clinical application and further development of Daxiefei Decoction. The plasma concentrations of each substance at different time points were determined by ultra-performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS), and the pharmacokinetic parameters of each component were calculated by pharmacokinetic software DAS 2.0. The results showed that the linear relationship between the six components was good in their respective ranges, and the methodological investigation met the requirements. The pharmacokinetic parameters of six components, such as peak concentration (C_max), peak time (t_max), half-life (t_1/2), area under the plasma concentration-time curve (AUC_0-t), were successfully calculated by using the pharmacokinetic software DAS 2.0 non-compartmental model. There were significant differences in the pharmacokinetic characteristics of the active ingredient group between the normal group and the model group, suggesting that the body was in different physiological states, and the change of the body state would have a certain impact on the absorption and elimination of the active ingredient of Daxiefei Decoction. The experiment was approved by the Laboratory Animal Ethics Committee of Nanjing University of Chinese Medicine (No. 202406A085).