Traditional Chinese medicine（TCM） and ethnic medicine, as integral components of traditional medicine, exhibit diverse therapeutic effects, complex chemical compositions, intricate physiological processes, and multifaceted mechanisms of action. This makes elucidating the pharmacological basis and mechanisms of action of TCM and ethnic medicine a key research direction in the modernization of TCM. However, challenges such as incomplete pharmacological evaluation models, low correlation with clinical efficacy, and low screening efficiency and throughput remain core obstacles. Artificial intelligence-driven organoid and organ-on-achip technologies offer an innovative research paradigm for the screening of bioactive compounds and the discovery of target mechanisms in TCM and ethnic medicines. By constructing highly biomimetic human organoids/organ-on-a-chip models that precisely simulate the microenvironment and pathological states of human organs, combined with artificial intelligence technologies for in-depth analysis of high-throughput pharmacodynamic data, it is possible to elucidate the synergistic effects of multi-component, multi-target interactions. Systematically screening groups of active components in TCM, quantifying their metabolic kinetic processes, and revealing potential target points and molecular pathways significantly enhances the precision and efficiency of bioactive substance identification. The deep integration strategy of organoids/organ-on-a-chip technology with artificial intelligence provides new technical support for accelerating the modernization of TCM and ethnic medicine research and promoting innovative drug development.

Objective To investigate the effect of Dendrobium officinale polysaccharide (DOP) on prediabetes (PDM) and explore its mechanism in improving PDMs through the gut short-chain fatty acids (SCFAs)-G protein-coupled receptor 43 (GPR43)-glucagon-like peptide 1 (GLP1) pathway. Methods SD Rats were randomly divided into control group, model group and DOP low-, high-dose (0.1, 0.2 g/kg) groups, with 10 rats in each group. Except for the control group, the remaining rats were fed a high-sugar and high-fat diet for six weeks to establish a PDM model. During the modeling period, the corresponding drugs were administered intravenously, and the control group and model group were given distilled water of equal volume. Changes in general physiological indicators, glucose/lipid levels, glucose regulation function, intestinal/pancreatic histopathology, fecal SCFAs contents, expressions of GPR43 and GLP1 and its receptor in intestinal/pancreatic were analyzed. Results Compared with model group, DOP significantly increased tail microcirculatory blood flow in PDM rats (P < 0.01) and decreased anal temperature (P < 0.01), significantly reduced levels of total cholesterol and low-density lipoprotein cholesterol in serum (P < 0.05, 0.01), significantly decreased the oral glucose tolerance test results, fasting blood glucose, 2 h postprandial glucose, homeostasis model assessment-insulin resistance index, and C-peptide levels in PDM rats (P < 0.05, 0.01), increased the insulin sensitivity index (P < 0.05), and alleviated the pathological damage of pancreas, ileum and colon. Gas chromatography results showed that DOP administration could significantly increase the levels of acetic acid, butyric acid, isovaleric acid and SCFAs in feces (P < 0.05, 0.01). ELISA, Western blotting and qRT-PCR results showed that DOP administration could significantly increase the plasma GLP1 level, as well as the mRNA and protein expressions of GPR43 and GLP1 receptor in ileum and pancreas (P < 0.05, 0.01). Conclusion DOP could improve PDM, and its effect may be related to enhancing gut-derived SCFA production, up-regulating GPR43 expressions in intestine and pancreas, subsequent promoting GLP1 secretion, restoring β-cell function and improving glucose regulation.

Objective To study the chemical constituents fromdried whole plant of alpine herb Gentiana nanobella, and to conduct preliminary screening for antimalarial activity of the isolated constituents. Methods Ethyl acetate and n-butanol fractions of 75% ethanol extract of the whole plant of G. nanobella were isolated and purified by repeated column chromatography padded with silica gel, RP-18 and Sephadex LH-20, respectively. The structures of the isolated compounds were identified based on their physicochemical properties and spectral data. The in vitro inhibitory activity of the testing compound against human Plasmodium falciparum 3D7 strain was achieved with the SYBR Green I method. Results A total of 11 phenol compounds were obtained and identified as 2,3-dihydroxy benzoic acid methyl ester-3-O-β-L-rhamnosyl-(1''→2')-b-D-glucopyranoside (1), 2,3-dihydroxy benzoic acid-3-O-β-L-rhamnosyl-(1''→2')-b-D-glucopyranoside (2), 2,3-dihydroxy benzoic acid methyl ester-3-O-β-D-glucopyranosyl-(1''→6')-β-D-glucopyranoside (3), benzyl β-D-xylopyranosyl-(1''→6')-β-D-glucopyranoside (4), apigenin 5-O-β-D-glucopyranoside (5), salcolin B (6), apigenin-7-O-β-D-glucopyranoside (7), benzoic acid (8), p-hydroxybenzoic acid (9), 3-hydroxy-2-methoxybenzoic acid (10), and isovanillic acid (11). Compound 6 exhibited an in vitro antimalarial activity against Plasmodium falciparum 3D7 strain with IC₅₀ 18.50 μmol/L and inhibition rate of 98.48% at a concentration of 50 μmol/L. Conclusion Compounds 1 and 2 are new compounds, named gentinanoside A and gentinanoside B. Compounds 1—11 were isolated from G. nanobella for the first time. G. nanobella is abundant in phenolic compounds, and some compounds had certain antimalarial activity.

Objective To investigate the chemical constituents and their myocardial cell protective activity from the fruits of Daemonorops draco. Methods Compounds were isolated and purified using a combination of silica gel, RP-C₁₈, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated through comprehensive spectroscopic analysis, UV, IR, HRESIMS and NMR. The protective effects of all isolates on the H9c2 myocardial cells injury induced by oxygen-glucose deprivation (OGD) were evaluated. Results Three pairs of new flavans were purified and elucidated as (2S)-2-ethoxy-7-hydroxy-5-methoxy-6-methylflavan (1a), (2R)-2-ethoxy-7-hydroxy-5-methoxy-6-methylflavan (1b), (2S,3S)-2-ethoxy-3,7-dihydroxy-5-methoxy-6-methylflavan (2a), (2R,3R)-2-ethoxy-3,7-dihydroxy-5-methoxy-6-methylflavan (2b), (2R,3S)-2-ethoxy-3,7-dihydroxy-5-methoxy-6-methylflavan (3a) and (2S,3R)-2-ethoxy-3,7-dihydroxy-5-methoxy-6-methylflavan (3b). Compounds 1b and 2b demonstrated protective effects against OGD-induced H9c2 cell injury, which increased cell viability by (6.36 ±1.26)% and (10.78 ±0.76)% at a concentration of 20 μmol/L, respectively. Conclusion Compounds 1a/1b, 2a/2b, and 3a/3b are three pairs of enantiomers, and they are all new compounds, named as dracoropin I₁, dracoropin I₂, dracoropin J₁, dracoropin J₂, dracoropin K₁, dracoropin K₂. Among them, compounds 1b and 2b exhibited protective effects on myocardial cells.

Objective To explore the mechanism by which Astragalus polysaccharides (APS) improves the consumption of adipose tissue in cancer cachexia (CC) using lipidomics and transcriptomics. Methods A random number table was used to divide 50 male mice into control group, model group, APS low-, medium-and high-dose (200, 400, 800 mg/kg) groups, with 10 mice in each group. CC model was constructed using abdominal sc CT-26 colorectal cancer cells. The treatment group was given 0.2 mL APS solution by ig daily, while the control group and model group were given an equal volume of physiological saline by ig for four consecutive weeks. The diameter of epididymal adipocytes was evaluated using hematoxylin-eosin (HE) staining; ELISA method was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP) in epididymal adipose tissue and level of free fatty acids (FFA) in plasma. After effectiveness and significance verification, transcriptome and lipidomics sequencing were performed on control group, model group and APS high-dose group to screen differentially expressed genes (DEGs) and differentially expressed lipids (DELs), and enrichment analysis was performed; Western blotting was used to verify the expressions of relevant proteins. Results High-dose APS significantly alleviated inflammatory infiltration in epididymal adipose tissue and reversed adipocyte atrophy (P < 0.01), significantly reduced the levels of TNF-α, IL-6, cAMP in adipose tissue and level of FFA in plasma (P < 0.01, 0.001), indicating that high-dose APS inhibits inflammation and lipolysis reactions in adipocytes. The lipidomics results showed that high-dose APS intervention reduced the expression levels of 66 DELs, including ceramides and their modifications, triacylglycerols, etc. Metabolic pathway enrichment analysis showed that these DELs mainly involved glycerophospholipid metabolism and sphingolipid metabolism pathways. The transcriptomic results showed that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway was repeatedly enriched in DEGs, indicating that this pathway may be the core pathway for APS to function. In addition, the expressions of 18 DEGs was significantly down-regulated by APS, and the gene interaction network diagram showed that these genes had complex interactions with Akt. Western blotting results confirmed that APS intervention reversed the expression levels of Tribbles homologous protein 3 (TRIB3), phosphorylated Akt (p-Akt), phosphodiesterase 3B (PDE3B), phosphorylated protein kinase A (p-PKA), phosphorylated hormone sensitive lipase (p-HSL) and adipose triglyceride lipase (ATGL) (P < 0.05, 0.01, 0.001). Conclusion APS may alleviate inflammation in adipose tissue, reduce the synthesis of sphingolipids such as ceramides, regulate TRIB3-Akt axis, restore insulin resistance to lipolysis, promote lipid signaling, and improve the consumption of CC adipose tissue.

Objective To investigate the subcellular distribution patterns of the combination of cantharidin (CTD) and baicalin (BA) based on cell pharmacokinetics and elucidate the synergistic mechanism against hepatocellular carcinoma. Methods Using human hepatoma HepG2 cells as the model, the dynamic concentrations of the drugs in whole cells and organelles (nucleus, mitochondria, endoplasmic reticulum, and lysosomes) over 12 h after administration of single drugs (CTD 6 μg/mL, BA 30 μg/mL) and their combination (CTD 6 μg/mL + BA 30 μg/mL) were quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated using a non-compartmental model with Phoenix WinNonlin software. Results At the whole-cell level, the combination increased the intracellular area under the curve (AUC_0—t) of CTD by 48.9% and decreased its clearance (P < 0.05), but did not significantly affect the pharmacokinetics of BA. At the subcellular level, the combination significantly increased the AUC_0—t of CTD and BA in nucleus, lysosome, mitochondria and endoplasmic reticulum by 93.5%, 46.4%, 38.3%, 52.3%, and 68.4%, 40.0%, 41.0%, and 46.7%, respectively (P < 0.05, 0.01). Furthermore, the time to reach peak concentration (t_max) for both drugs in mitochondria was earlier in the combination group, and the mean residence time (MRT_0—t) of CTD in the endoplasmic reticulum was significantly prolonged (P < 0.01), indicating a spatiotemporally synergistic drug delivery optimization. Conclusions The combination of CTD and BA could synergistically optimize the distribution of drugs in key subcellular structures such as nucleus, mitochondria, endoplasmic reticulum and lysosomes, and may enhance the anti-hepatocellular carcinoma effect by inducing DNA damage, accelerating mitochondria-mediated apoptosis and promoting endoplasmic reticulum stress, which provides a theoretical basis for the design of traditional Chinese medicine combinations based on organelle targeting.

Objective To research the chemical constituents from the fruits of Lycium barbarum. Methods Separation and purification were performed using silica gel, D-101 macroporous resin, MCI, Sephadex LH-20, and semi-preparative HPLC. The structures of the compounds were identified based on spectroscopic data and physicochemical properties. The α-glucosidase inhibitory activity of the selected compounds was evaluated using 4-nitrophenol-α-D-glucopyranoside (PNPG) assay. Results A total of 15 compounds were isolated from the fruits of L. barbarum, which were identified as methyl (2R)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-4-methylpentanoate (1), 5-epi-acortatarin A (2), 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (3), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (4), (2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl) propanoate (5), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate (6), 3-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] pentanedioic acid (7), N-trans-feruloyl-3'-O-methyldopamine (8), N-trans-feruloyl-3',4'-dihydroxyphenylethylamine (9), N-cis-p-coumaroyl tyramine (10), N-cis-feruloyl tyramine (11), bungeanoline E (12), N-malonyl-tryptophan (13), 3-hydroxy-4-ethyl ketone pyridine (14), cartorimine (15). Conclusion Compound 1 is a new pyrrole alkaloid, named lycipyrrole A. Compound 2 is a new natural product. Compounds 4, 7 and 12—15 were isolated from L. barbarum for the first time, while compounds 12, 13 and 15 were isolated from this genus for the first time. Notably, compound 9 exhibited significant inhibitory activity against α-glucosidase.

Objective To explore the key enzyme genes of the pentacyclic triterpene esters biosynthesis pathway in Balanophora subcupularis, which lays a certain research idea and theoretical foundation for its biosynthesis mechanism and the development and utilization of medicinal plant resources in the genus Balanophora. Methods Transcriptome sequencing and analysis was performed on the three tissues of the flowerstalk, rhizome and umbel of B. subcupularis, then searching the candidate enzyme genes involved in triterpene ester biosynthesis by PfamScan, constructing the yeast expression vector of BsubOSCs gene which was introduced into the Saccharomyces cerevisiae lanosterol synthase gene（erg7）-deficient mutant strain GIL77 for functional characterization. Results A total of 87 candidate genes involved in pentacyclic triterpene esters biosynthesis were identified from the transcriptome of B. subcupularis, most of them were highly expressed in umbel, suggesting that umbel may be the main site of synthesis of pentacyclic triterpene esters. The enzyme function of two BsubOSC genes were characterized, which was found that BsubOSC2 could catalyze 2, 3-oxidosqualene to form β-amyrin, but no catalytic product of BsubOSC1 was detected. Conclusion Based on transcriptome analysis, the key enzyme genes involved in pentacyclic triterpene esters biosynthesis were found in B. subcupularis, and BsubOSC2 is a β-amyrin synthetase gene, and is one of the key enzyme genes for the biosynthesis of balanophorin A. This study provides gene resources for further analysis of the biosynthesis pathway of triterpene ester compounds such as balanophorins, and facilitate the research on molecular breeding of B. subcupularis.

Objective To prepare sinomenine nanoemulsion (Sin-NE) co-stabilized by Bletilla striata polysaccharide and glycyrrhizic acid, systematically characterize its properties, investigate its stability and drug release behavior, and further evaluate its anti-inflammatory effects through in vitro experiments. Methods The Sin-NE was prepared using the ultrasonic emulsification method. Its morphology, particle size, polydispersity index (PDI), and ζ potential were observed and determined. Optimal formulation parameters were screened via single-factor and orthogonal experiments, followed by formulation validation. pH value, turbidity, viscosity, encapsulation efficiency, and drug loading capacity were measured. Stability was investigated under centrifugation, storage, dilution, and heating conditions was evaluated, and in vitro drug release behavior was investigated. A RAW264.7 cell inflammation model was established to validate the effects of the Sin-NE on nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Results The optimized formulation comprised 3% Coicis Semen oil, 0.5% combined emulsifiers, a 1∶9 mass ratio of Bletilla striata polysaccharide to glycyrrhizic acid, 10 min of ultrasonic treatment, and 325 W ultrasonic power. The resulting Sin-NE exhibited an average particle size of (145.30 ±2.35) nm, ζ potential of (-39.51 ±0.43) mV, PDI of 0.095 ±0.022, and pH value of 3.990 ±0.033. Encapsulation efficiency and drug loading capacity reached 88.78% and 26.14 mg/g, respectively. The nanoemulsion demonstrated excellent stability under centrifugation, storage, dilution, and heating conditions and displayed sustained-release characteristics. In vitro, it significantly inhibited NO release and effectively reduced IL-6 and TNF-α levels in inflamed cells. Conclusion The Sin-NE significantly enhances sinomenine’s bioavailability and anti-inflammatory activity, providing experimental evidence for developing novel traditional Chinese medicine nanoemulsion formulations.

High-altitude sleep disturbance (HASD), a common physiological disorder caused by hypobaric hypoxia, clinically manifests as insomnia, sleep apnea, and sleep fragmentation. Its pathogenesis involves hypoxia-inducible factor activation, oxidative stress, and neuroendocrine dysregulation, with severe cases potentially leading to irreversible neurological damage. The gut-brain axis, a bidirectional communication network between the central nervous system and the gastrointestinal tract, plays a key role in HASD progression. Gut microbiota, as a critical interface between intestinal and cerebral functions, may modulate sleep disorders through neurotransmitter regulation, short-chain fatty acid production, and hormonal pathway modulation. Traditional Chinese medicine (TCM) and traditional Tibetan medicine (TTM) offer unique therapeutic advantages for HASD management. TCM theory suggests that “gastric imbalance disrupts sleep”, while TTM attributes insomnia to “tri-humoral dysregulation”. Both systems align with the modern gut-brain axis theory, emphasizing sleep quality improvement through spleen-stomach system regulation. This study examines the theoretical foundations of TCM and TTM for preventing and treating HASD, summarizing relevant classical prescriptions, monomeric drugs, active ingredients, and novel formulations. Additionally, it explores the pharmacological mechanisms by which TCM and TTM improve HASD by regulating the gut-brain axis, providing safe and effective strategies for individuals entering high-altitude regions.