Quality control of traditional Chinese medicines (TCM) has progressively evolved from empirical identification and component testing toward multicomponent and holistic control. With advances in modern pharmaceutical quality science, analytical technologies, manufacturing methods, and data environment, the central question is shifting from “what can be measured” to “what truly matters to product quality and therefore needs to be assured.” Centered on critical quality attributes (CQA), this article proposes a methodological framework that starts from clinical positioning and product understanding and proceeds through “a product quality profile-candidate quality attributes-CQA identification-investigation of materials, processes, and intermediate materials-identification of critical material attributes (CMAs)/critical process parameters (CPPs)-quality formation laws-quality state evaluation-continuous lifecycle confirmation”. CQA criticality should be supported by product-specific quality risks and corresponding evidence. CMAs and CPPs should be identified through whole-process investigation guided by CQAs, and whole-process investigation should serve targeted control rather than expansion of control items. The article further discusses the non-compensatory boundary of holistic evaluation, reliable measurement, complementary retrospective and prospective studies, and the role of real-world manufacturing data in continual confirmation. A shift from a component-oriented to a quality attribute-oriented approach does not negate established analytical technologies or quality standards. Rather, it relocates the starting point of quality research from “what can be found and measured” to “what truly matters, why it matters, how it is formed, and how it can be continuously assured.” This paradigm transformation requires further validation and refinement across different types of traditional Chinese medicine products and real-world commercial manufacturing data.

Objective To investigate the chemical composition of the rhizome of Dalbergia pinnata. Methods Separation and purification were performed using silica gel, RP-C₁₈, MCI, Sephadex LH-20 column chromatography, semi-preparative high-performance liquid chromatography and recrystallization; compound structures were identified based on spectroscopic techniques, including NMR spectroscopy; and the anti-complement activity of selected isolated monomeric compounds was screened using an in vitro erythrocyte hemolysis assay. Results Fifteen compounds were isolated and identified from the ethyl acetate fraction of D. pinnata, including 5,7,4′-trihydroxy-6,2′,5′-trimethoxyisoflavone (1), 7,3 ¢-dihydroxy-8,4 ¢-dimethoxyisoflavone (2), (&8722;)-vestitol (3), 3-O-acetyloleanolic acid (4), (&8722;)-hydroxymedioresinol (5), (&8722;)-episyringaresinol (6), (&8722;)-liquiritigenin (7), butein (8), (&8722;)- isolariciresinol (9), (＋)-lyoniresinol (10), (2R)-3-(3 ¢,4¢-dimethoxyphenyl)-1,2-propanediol (11), (2R)-3-(3 ¢,4 ¢,5 ¢-trimethoxyphenyl)-1,2-propanediol (12), 3,3 ¢,4,4 ¢-tetrahydroxybiphenyl (13), vanillicvanillyric acid (14), cinnamtannin B1 (15). In vitro anti-complement activity assays demonstrated that compounds 1, 3, 7 and 8 exhibited distinct in vitro complement inhibitory activities, with their half-maximal hemolysis-inhibitory concentrations (CH₅₀) measuring (1.21 ± 0.07), (0.57 ± 0.03), (0.12 ± 0.13) and (0.17 ± 0.04) mg/mL respectively. Conclusion Compound 1 is a new compound, designated as dalbergiaisoflavone A, obtained from D. pinnata; compounds 2—6 and 8—15 were obtained from this species for the first time, and compound 7 exhibits significant in vitro anti-complement activity.

Objective To investigate the chemical constituents of the leaves of Tectona grandis, and search for antifungal active ingredients. Methods The compounds were obtained by silica gel, MCI, and prep-HPLC column chromatography. Their structures were identified by HRESIMS, IR, 1D- and 2D NMR analysis. The isolates were tested for their antifungal activity by 96 well plate microbroth dilution method. Results Two new naphthoquinones, (E)-2,5,8-trihydroxy-3-(4-acetoxy-3-methylbut-2-en-1-yl)-1,4-naphthoquinone (1) and (E)-2,5,8-trihydroxy-3-(4-hydroxy-3-methylbut-2-en-1-yl)-1,4-naphthoquinone (2), were isolated from the 90% MeOH extract of the leaves of T. grandis. Compounds 1 and 2 exhibited significant antifungal activity when combined with fluconazole, against fluconazole-resistant Candida albicans with MIC₅₀ values of 3.28 and 5.32 μg/mL, respectively. Conclusion Compounds 1 and 2, named tectonagrandiones A and B, were two new naphthoquinones, and the naphthoquinones might be the active antifungal constituents from T. grandis.

Objective To isolate structurally defined bioactive oligosaccharide fractions from Prunella vulgaris (PV) polysaccharides and evaluate their in vitro antioxidant activity and intestinal microbiota-modulating effects. Methods Total polysaccharides were extracted via water extraction and alcohol precipitation, followed by deproteinization using the Sevag method. Partial acid hydrolysis was performed under two conditions (80 ℃ and 100 ℃, 0.5 mol/L trifluoroacetic acid). The hydrolysates were fractionated and purified by hydrophilic interaction chromatography (HILIC). Structural characterization of the dominant components in each fraction was performed using HILIC/IM-QTOF-HDMSE, UHPLC-UV and 1D/2D-NMR (1H/13C-NMR, COSY, HSQC, HMBC). Antioxidant activity of three oligosaccharide components was assessed via a DPPH free radical scavenging assay, while their modulatory effects on gut microbial abundance were evaluated using an in vitro anaerobic co-culture model of mouse fecal microbiota coupled with real-time quantitative PCR. Results Three oligosaccharide fractions with degrees of polymerization (DP) of 2, 3, and 5 were obtained, namely DP2 (yield: 5.60%), DP3 (1.19%), and DP5 (1.70%). The dominant structural features of three fractions were elucidated as follows: DP2 is mainly composed of a disaccharide composed of 3-O-methyl-α-glucuronic acid linked to xylose, with α/β anomerism at the xylose terminus; DP3 mainly contains a trisaccharide consisting of xylose-arabinose-uronic acid, terminating in either 4-O-methyl-β-glucuronic acid or α-galacturonic acid; DP5 is primarily a linear pentasaccharide starting with 2-O-methyl-α-glucuronic acid, linked through three xylose units, and ending with 3-O-methyl-glucuronic acid existing in both α- and β-forms. Antioxidant assessment revealed that all three fractions exhibited significant DPPH radical-scavenging activity, with DP5 being the most potent (IC₅₀ = 0.36 μg/mL). At 0.1 mg/mL, both DP3 and DP5 showed scavenging rates exceeding 84%, comparable to the positive control VC (IC₅₀ = 0.11 μg/mL, P > 0.05). Microbiota analysis indicated that all three fractions modulated the intestinal flora: DP2 significantly promoted the growth of the probiotic genus Lactobacillus; DP3 increased the abundance of the beneficial phylum Bacteroidetes while suppressing the potentially pathogenic phylum Actinobacteria; DP5 primarily exerted inhibitory effects on Actinobacteria. Conclusion This study successfully isolated three oligosaccharide fractions (DP2, DP3, and DP5) from the PV polysaccharides and characterized their predominant structural features, revealing the antioxidant and gut microbiota-regulating activities.

Objective To systematically characterize the metabolites of polygala oligosaccharide esters (PROEs) in rats, thereby providing evidence for elucidating the pharmacodynamic material basis of Polygala tenuifolia. Method Plasma samples from rats after oral administration of PROEs were analyzed using UPLC-QTOF-MS/MS. Feature-based molecular networking (FBMN) was employed to visually cluster and screen for potential metabolites. The identities of predicted metabolites were further confirmed by comparison with reference standards prepared via in vitro enzymatic incubation and chemical isomerization synthesis. Results FBMN effectively clustered structurally similar metabolites, such as glucuronidated and sulfated products, from the mass spectrometry data. A total of 59 metabolites were identified in rat plasma, including 14 free phenolic acids, 21 sulfated organic acids, 17 glucuronidated organic acids, and seven other compounds. No intact PROEs were detected. The metabolic pathway analysis revealed that PROEs were rapidly hydrolyzed in vivo to generate various phenolic acids (e.g., sinapic acid, ferulic acid, syringic acid), which subsequently underwent extensive phase I metabolism (reduction, demethylation, dehydroxylation) and predominantly phase II metabolism (sulfation and glucuronidation). Conclusion Following oral administration, PROEs enter the systemic circulation primarily as hydrolyzed organic acids and their extensive phase II conjugates. This study demonstrates that the combination of UPLC-Qtof-MS/MS and FBMN provides an efficient and comprehensive strategy for identifying the in vivo metabolites of PROEs. This approach offers a basis for revealing the active constituents of P. tenuifolia and serves as an effective method for elucidating the metabolic profiles of traditional Chinese medicines.

Objective To optimize the preparation process of nitidine chloride liposomes (NC-Lips), characterize their physicochemical properties, and evaluate their in vitro anti-cholangiocarcinoma activity. Methods NC-Lips were prepared by the thin-film dispersion method. Three key formulation variables, namely DSPE-mPEG₂₀₀₀ dosage, drug-to-lipid ratio, and phospholipid-to-cholesterol ratio, were selected. The formulation was optimized via single-factor experiments combined with Box-Behnken design-response surface methodology (BBD-RSM), with encapsulation efficiency, drug loading, PDI, and ζ potential as the evaluation indices. The drug content was determined by HPLC. The physicochemical properties of NC-Lips were characterized using a particle size analyzer and transmission electron microscopy. The in vitro drug release profile was investigated by the dialysis bag method. CCK-8 assay, flow cytometry, and cell cycle analysis were employed to evaluate the proliferation inhibition, apoptosis induction, and cell cycle arrest effects of NC-Lips on cholangiocarcinoma TFK-1 cells. Results The optimal formulation was as follows: DSPE-mPEG₂₀₀₀ dosage of 34.79 mg, drug-to-lipid ratio of 1:15.15, and phospholipid-to-cholesterol ratio of 17.88. The prepared NC-Lips exhibited typical liposomal vesicular morphology, with an average particle size of (77.67 ± 0.75) nm, PDI of 0.212 ± 0.01, ζ potential of (&8722;11.43 ± 0.12) mV, encapsulation efficiency of (85.96 ± 0.61)%, and drug loading of (4.37 ± 0.03)%. Among the in vitro drug release models, the Ritger-Peppas model showed the highest goodness of fit, indicating that NC-Lips had obvious sustained-release characteristics. The liposomes remained stable during 30 d storage at 4 ℃, with a drug leakage percentage of < 30%. In vitro cell experiments demonstrated that NC-Lips exerted significantly better effects on proliferation inhibition, apoptosis induction, and G₂/M phase arrest in TFK-1 cells than free nitidine chloride (P < 0.01). At a concentration of 12 μmol/L, the cell viability was only (8.17 ± 1.90)% after 48 h of treatment; at the same concentration, the apoptosis rate reached (28.90 ± 2.38)% at 24 h, and the proportion of cells in the G₂/M phase increased to (66.23 ± 3.31)%. Conclusion A stable and optimized NC-Lips formulation with excellent physicochemical properties was successfully prepared. NC-Lips exerted excellent in vitro anti-cholangiocarcinoma activity by inducing apoptosis and G₂/M phase arrest. These findings provide an experimental basis for formulation optimization and subsequent mechanistic and in vivo studies of nitidine chloride.

Objective To prepare trifolin-phospholipids complex/chitosan nanoparticles (Tri-PC/CS-NPs), and investigate its in vivo pharmacokinetic behavior and protective effect on acute liver injury. Methods Trifolin-phospholipids complex (Tri-PC) was prepared by solvent evaporation method. Single factor experiments combined Box-Behnken design-response surface methodology (BBD-RSM) were used to optimize the prescriptions of Tri-PC/CS-NPs. Transmission electron microscope (TEM) was employed to observe microscopic appearance of Tri-PC/CS-NPs, X-ray powder diffraction (XRPD) was used to analyze crystal form of Tri-PC/CS-NPs. Saturated solubility, oil/water partition coefficient and drug release behavior in simulated gastrointestinal fluids of trifolin, Tri-PC and Tri-PC/CS-NPs were compared. SD rats were administered intragastrically with trifolin, Tri-PC and Tri-PC/CS-NPs, respectively. Blood drug concentration was determined, and the main pharmacokinetic parameters were calculated. The model of acute liver injury was established, and the protective effect of trifolin, Tri-PC, Tri-PC/CS-NPs on acute liver injury were compared. Results Optimal formulations of Tri-PC/CS-NPs: the volume of water phase was 20.50 mL, the mass ratio of Tri-PC to chitosan was 4.15:1, and the mass fraction of Poloxamer 188 was 0.10%. Envelopment efficiency, drug loading, particle size and ζ potential were (84.80 ± 1.21)%, (15.56 ± 0.10)%, (197.74 ± 5.58) nm and (32.69 ± 1.14) mV, respectively. The appearance of Tri-PC/CS-NPs were spherical. The state of trifolin changed into amorphous form in Tri-PC and Tri-PC/CS-NPs. Tri-PC and Tri-PC/CS-NPs significantly enhanced the saturated solubility and oil/water partition coefficient of trifolin (P < 0.01). Cumulative release rate of Tri-PC and Tri-PC/CS-NPs were 56.68% and 88.45% in 18 h, respectively. The drug release process of Tri-PC/CS-NPs conformed to the Weibull model. Compared with trifolin, the relative bioavailability of Tri-PC and Tri-PC/CS-NPs was enhanced to 2.41-fold and 5.36-fold, respectively. Tri-PC and Tri-PC/CS-NPs effectively enhanced the protective effect of trifolin against acute liver injury, and the protective effect of Tri-PC/CS-NPs was superior to that of Tri-PC. Conclusion Tri-PC/CS-NPs changed the pharmacokinetic behavior of trifolin in vivo, effectively promoted the absorption of trifolin, and enhanced the protective effect of trifolin on acute liver injury.

Objective To optimize the processing technology of Shanzhatan (Crataegi Fructus Charcoal, CFC), evaluate it objectively by electronic sensory technology, and verify its antidiarrheal efficacy. Methods TG-DTG thermal analysis was used to investigate the pyrolysis behavior of total flavonoids, total organic acids, polysaccharides, and tannins in hawthorn, and to determine the processing temperature range. With tannin content as the key index, frying temperature and time were selected as process variables, and the technology was optimized through single-factor experiments combined with central combination design-response surface methodology (CCD-RSM). An electronic eye, electronic nose, and electronic tongue were applied to quantitatively evaluate the color, odor, and taste profiles of hawthorn before and after processing. A Fanxieye (Sennae Folium)-induced mouse diarrhea model was established to validate the antidiarrheal efficacy of the CFC prepared under the optimized process, with body weight change, diarrhea index, gastrointestinal hormone (gastrin, VIP) levels, small intestinal propulsion rate, and gastric residual rate as indicators. Results Thermal analysis indicated that the optimal processing temperature range was 307.4—332.0 ℃. The optimal parameters were frying temperature 311 ℃ and frying time 3.64 min (218 s). Electronic sensory analysis showed obvious differences in lightness (L), red-green degree (a), yellow-blue degree (b), total color difference (E_ab), odor, and taste characteristics between raw and processed hawthorn. The e-nose response signals were positively correlated with e-eye chromaticity values. Compared with the model group, the CFC group attenuated the trend of body weight loss (P < 0.05), reduced diarrhea index (P < 0.05), reversed serum gastrin and vasoactive intestinal peptide (VIP) levels (P < 0.05), increased gastric residual rate (P < 0.01), and a numerically lower but statistically non-significant small intestinal propulsion rate. Conclusion The processing technology was optimized by thermal analysis and response surface methodology. Electronic sensory technology enabled objective quantification of sensory attributes, and pharmacodynamic validation further confirmed the rationality of the process. This study provides a methodological reference for parameterizing fire intensity and duration in the preparation process of hawthorn charcoal and the construction of its quality standards.

Objective To investigate the change patterns of flavonoid and saponin contents in Hongqi (Hedysari Radix, HR) before and after honey-processing, and to provide a scientific basis for quality control of the honey-processing technology and its processing mechanism. Methods UV-Vis spectrophotometry was employed to determine the contents of total flavonoids and total saponins in 10 batches of HR and Zhihongqi (Hedysari Radix Praeparata Cum Melle, HRPCM). HPLC was used to establish flavonoid-based and saponin-based fingerprints, and similarity evaluations were conducted. The contents of six marker components calycosin-7-O-β-D-glucoside, ononin, calycosin, formononetin, astragaloside IV, and isoastragaloside II were determined by HPLC. Results After honey-processing of 10 batches of HR, the total flavonoid contents were significantly decreased (P < 0.01), with an average decrease of 25.8%; the total saponin contents were significantly increased (P < 0.01), with an average increase of 37.93%. Similarity evaluation of fingerprints indicated that honey-processing did not alter the basic chemical profile of HR. HPLC content determination showed that after honey-processing, formononetin content was significantly increased in 8 out of 10 batches (P < 0.05, 0.01), with an average increase of 30.49%; astragaloside IV and isoastragaloside II contents were significantly increased in 8 and 7 batches, respectively (P < 0.05, 0.01), with average increases of 34.79% and 26.22%; calycosin-7-O-β-D-glucoside and ononin contents were mainly decreased; calycosin content was mainly increased. Conclusion Honey-processing of Hedysari Radix can alter the active flavonoid and saponin components, thereby adjusting the structure of its pharmacodynamic material basis.

Objective Lappaconitine-self-micellizing solid dispersion sustained-release tablets (Lap-SMSD-SRT) was prepared, and investigated its pharmacokinetics and toxicokinetics in vivo. Methods Lap-SMSD powder was prepared by solvent evaporation method, and its basic physicochemical properties were also studied. The influence of hydroxypropyl methyl cellulose (HPMC) K4M dosage, carboxymethyl starch sodium (CMS-Na) dosage and lactose dosage on the drug release behavior of Lap-SMSD-SRT were investigated by single factor experiments. Composite score of cumulative release rate at 2, 6, 12 h was used as response value, Box-Behnken design-response surface method (BBD-RSM) was employed to optimize formulation of Lap-SMSD-SRT. The release behavior of lappaconitine hydrobromide tablets, lappaconitine tablets and Lap-SMSD-SRT were compared. Six beagle dogs were used to study the pharmacokinetic behavior by a three-period crossover trial, and the relative bioavailability of Lap-SMSD-SRT was calculated. Three level of low, medium, high (0.75, 1.50, 2.25 mg/kg) dose groups of Lap-SMSD-SRT were set up, and compared the plasma concentration of lappaconitine after the first and last administration with a 4-week dosing period and a 4-week recovery period. Then the toxicokinetic parameters were calculated. The living condition of Beagle dogs was observed, and the hematology and biochemical indexes were also examined. Results The dosage ratio of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soluplus) to lappaconitine in Lap-SMSD powder was 5:1, and quickly became into micelles with particle size of (29.44 ± 2.01) nm when dispersed in water. Optimal formulation of Lap-SMSD-SRT: HPMC K4M dosage was 19.09%, CMS-Na dosage was 15.59%, and lactose dosage was 22.63%. The cumulative release rate of Lap-SMSD-SRT at 2, 6, 12 h were 26.50%, 61.67% and 93.67%, respectively. Pharmacokinetic results showed that the peak time (t_max) of Lap-SMSD-SRT was delayed to (6.20 ± 1.61) h, the half-life (t_1/2) was prolonged to (9.13 ± 2.64) h, the peak concentration (C_max) was enhanced to (123.94 ± 46.77) ng/mL, and the relative bioavailability was enhanced to 5.21-fold. No significant accumulation of lappaconitine was observed in Beagle dogs at each dose of Lap-SMSD-SRT. There might be slight effect on the blood system and liver in the medium-dose and high-dose groups of Lap-SMSD-SRT, but these symptoms disappeared during the 4-week recovery period. Conclusion The preparation process of Lap-SMSD-SRT was reproducible, and the formulation exhibited obvious sustained-release characteristics, significantly enhanced the in vivo absorption of lappaconitine, and showed good safety.

Objective To enhance the hair follicle-targeted delivery efficiency of cedrol, a cedrol nanosuspension (Ce-NS) was prepared. The formulation and process parameters were optimized, the physicochemical properties were characterized, and its therapeutic efficacy in the treatment of androgenetic alopecia (AGA) was evaluated. Methods Ce-NS was prepared using a solvent-antisolvent precipitation method. Based on single-factor experiments, particle size and polydispersity index (PDI) were selected as evaluation parameters to optimize the formulation and process variables using the Box-Behnken design-response surface methodology (BBD-RSM). The physicochemical characteristics and storage stability of the formulation were determined by dynamic light scattering (DLS). In vitro transdermal performance was evaluated using a Franz diffusion cell system. Morphological characteristics were examined by scanning electron microscopy (SEM) to assess the accumulation of nanocrystals within hair follicles. An AGA model was established in C57BL/6 mice. Hematoxylin-eosin (HE) staining and immunohistochemical analysis of dorsal skin tissues were performed to evaluate the in vivo hair growth-promoting efficacy. Results The optimal formulation parameters were as follows: cedrol mass concentration 7.5 mg/mL, sodium dodecyl sulfate (SDS) 170 mg, hydroxypropyl methylcellulose (HPMC) 130 mg, and a polyethylene glycol (PEG) 400-to-water phase ratio of 1∶12. The process parameters included a dropping rate of 20 mL/min, stirring speed of 10 000 r/min, and shearing time of 5 min. The prepared Ce-NS exhibited a mean particle size of (434.47 ± 9.90) nm, a PDI of 0.232 ± 0.005, and a ζ potential of (&8722;15.20 ± 1.15) mV. The experimental values were in good agreement with the predicted values of the model. Ce-NS remained stable for 90 days at room temperature. In vitro transdermal studies showed that the skin retention of Ce-NS within 24 h reached (74.38 ± 3.90) μg/cm2, which was 4.1-fold higher than that of the raw drug group, while no cedrol was detected in the receptor medium. SEM observation of skin sections confirmed the accumulation of cedrol nanocrystals within hair follicles. Pharmacodynamic evaluation demonstrated that, compared with the model group, Ce-NS significantly promoted hair regeneration in AGA model mice, increased hair follicle density and hair length, decreased androgen receptor (AR) expression in dorsal skin tissue, and upregulated the expression of Ki67 and β-catenin. Conclusion Ce-NS was successfully prepared using a green preparation process and exhibited stable physicochemical properties. The formulation significantly enhanced the skin retention and follicular targeting of cedrol, demonstrating promising therapeutic potential for androgenetic alopecia. The underlying mechanism may be associated with the downregulation of androgen signaling and activation of the Wnt/β-catenin pathway.

Objective To investigate the mechanism of Buyang Huanwu Decoction (补阳还五汤) in ameliorating diabetes cognitive impairment (DCI) based on nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway. Methods A rat model of DCI was established by feeding a high-fat and high-sugar diet combined with low-dose streptozotocin (STZ) injection. The successfully modeled rats were randomly divided into model group, Buyang Huanwu Decoction low-, high-dose (7.125, 28.500 g/kg) groups and metformin (0.2 g/kg) group, control group was set up separately. After four weeks of administration, the cognitive and memory abilities of rats were evaluated by Morris water maze. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of hippocampal tissue in rats. The activities of superoxide dismutase (SOD), catalase (CAT) and levels of glutathione (GSH), malondialdehyde (MDA) in serum and ferrous ions (Fe2+) in brain tissue of rats were detected by biochemical methods. Immunohistochemistry was used to observe the expressions of Nrf2 and GPX4 proteins in CA1 region of hippocampus in rats. Western blotting was used to detect the expressions of Kelch-like ECH-associated protein 1 (Keap1), Nrf2, heme oxygenase-1 (HO-1), solute carrier family 7 member 11 (SLC7A11), GPX4, transferrin receptor (TFR), ferroportin 1 (FPN1) and ferritin heavy chain (FTH) proteins in hippocampal tissue of rats. Human neuroblastoma cells SHSY-5Y were cultured in vitro and a damage model was established by inducing with 160 mmol/L glucose. Control group, model group, Buyang Huanwu Decoction low-, high-dose drug containing serum groups and Buyang Huanwu Decoction high-dose drug containing serum + Nrf2 inhibitor ML385 (10 μmol/L) group were set up. Biochemical methods were used to detect the activities of SOD, CAT and levels of GSH, MDA in cells. JC-1 fluorescent probe was used to detect changes in mitochondrial membrane potential in cells. Western blotting was used to detect the expressions of Keap1, Nrf2, HO-1, SLC7A11 and GPX4 proteins in cells. Results The results of in vivo experiments showed that Buyang Huanwu Decoction could delay weight loss of DCI rats (P < 0.05), reduce fasting blood glucose (P < 0.05, 0.01), shorten the escape latency (P < 0.05, 0.01), increase the distance moved, dwell time and number of crossings in target quadrant (P < 0.05, 0.01), alleviate the damage of hippocampal neurons, reduce the levels of MDA in serum and Fe2+ in brain tissue (P < 0.05, 0.01), increase the activities of SOD, CAT and levels of GSH in serum (P < 0.05, 0.01), downregulate the expressions of TFR and Keap1 proteins in hippocampus (P < 0.05, 0.01), upregulate the expressions of Nrf2, HO-1, SLC7A11, GPX4, FTH and FPN1 proteins (P < 0.05, 0.01). The results of in vitro experiments showed that Buyang Huanwu Decoction drug-containing serum could significantly increase the survival rate of SHSY-5Y cells induced by high glucose (P < 0.01), reduce MDA level (P < 0.05), increase the activities of SOD, CAT and level of GSH (P < 0.05, 0.01), increase the mitochondrial membrane potential, downregulate the expression of Keap1 protein (P < 0.01), and upregulate the expressions of Nrf2, HO-1, SLC7A11 and GPX4 proteins (P < 0.05, 0.01). Compared with Buyang Huanwu Decoction high-dose drug containing serum group, the administration of ML385 significantly reversed the changes in the above indicators (P < 0.05, 0.01). Conclusion Buyang Huanwu Decoction could improve cognitive dysfunction, alleviate oxidative stress damage, and improve iron metabolism disorders in DCI rats. Its effects may be related to the activation of Nrf2/GPX4 signaling pathway and the regulation of ferroptosis processes.

Objective To study the blood-entry active components and molecular mechanisms of Ferula sinkiangensis leaf aqueous extract (FSLAE) against alcoholic gastritis (AG), so as to provide a scientific basis for its medicinal development and the utilization of characteristic medicinal plant resources in Xinjiang. Methods Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to characterize the in vitro chemical constituents of FSLAE and the blood-entry constituents of rats. The intersecting targets between blood-entry components of FSLAE and AG were screened by network pharmacology. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were applied to predict the core pathways, and molecular docking was performed to verify the binding activity of core components to key targets. The AG rat model was induced by 70% ethanol, control group, model group, FSLAE high-, medium-, low dose (150, 100, 50 mg/kg) groups and magnesium aluminum carbonate (31.5 mg/kg) group were set up, with 10 rats in each group, drugs were continuously given for 7 d. Pathological changes of gastric mucosa were observed by hematoxylin-eosin (HE) staining. Levels of tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and IL-6 in serum were detected by ELISA. Hepatic and pancreatic function as well as nutrition-related indicators were measured using an automatic biochemical analyzer. The expression of proteins related to the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway in gastric tissue was determined by Western blotting. Results A total of 191 in vitro chemical constituents were identified from FSLAE, among which 23 constituents were confirmed as blood-entry components, mainly including phenolic acids, coumarins, fatty acids, etc. The core active components were ferulic acid, isoferulic acid and 4-methylumbelliferone. Network pharmacology identified 148 intersecting targets between FSLAE and AG, which were significantly enriched in inflammation-related pathways such as TNF and JAK/STAT pathways, with STAT3, JAK2 and TNF as the core targets. Molecular docking verified that the binding energies of core components to core targets were all less than &8722;6 kcal/mol, indicating favorable binding activity. In vivo experiments results showed that FSLAE dose-dependently ameliorated gastric mucosal pathological injury and alleviated the lag in body weight gain in AG rats. FSLAE significantly downregulated levels of pro-inflammatory factors (TNF-α, IL-17A, IL-6) and abnormal hepatic and pancreatic function markers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase (AMY) and total bilirubin (TB) in serum (P < 0.05, 0.01, 0.001), upregulated levels of nutrition-related indicators such as albumin (ALB) and total protein (TP) (P < 0.05, 0.01), inhibited the phosphorylation levels of JAK2 and STAT3 in gastric tissue (P < 0.01, 0.001). Conclusion FSLAE exerts a gastroprotective effect against AG by inhibiting the excessive activation of JAK2/STAT3 signaling pathway and alleviating inflammatory responses via its blood-entry active components. Phenolic acids and coumarins serve as the core pharmacodynamic material basis.

Objective To study the protective effect and mechanism of Paeonia lactiflora polysaccharides on liver fibrosis with liver yin deficiency syndrome in rats based on mitochondrial dynamics. Methods Male SD rats were randomly divided into control group, model group, silybin (42 mg/kg) group, Zhibai Dihuang Wan (知柏地黄丸, 408 mg/kg) group and P. lactiflora polysaccharide low-, high-dose (169, 338 mg/kg) groups, with eight rats in each group. Drugs were continuously intervented for six weeks, starting from the second week of administration, except for the control group, all other rats were treated with an ip 20% carbon tetrachloride olive oil solution combined with ig thyroid tablets (30 mg/kg) to establish a liver fibrosis with liver yin deficiency syndrome model. Sign score, body weight, food intake, water intake, tongue surface moisture level and rectal temperature of rats were detected. Levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in serum were measured using ELISA, and ratio was calculated. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP) and levels of total bilirubin (TBIL), total bile acids (TBA) in serum were measured using colorimetric assays. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes and degree of liver fibrosis. Transmission electron microscopy was used to observe mitochondrial ultrastructure in liver. Immunofluorescence was used to detect reactive oxygen species (ROS) level in liver. Adenosine triphosphate (ATP) level was measured to using a kit. Western blotting was used to detect fibronectin 1 (FN1), collagen I (COL-I), α-smooth muscle actin (α-SMA), extracellular regulated protein kinases (ERK), p-ERK, p38, p-p38, fission 1 (Fis1), dynamin-related protein 1 (Drp1), p- Drp1, optic atrophy 1 (Opa1) and mitofusin 2 (Mfn2) protein expression levels in liver of rats. Results Compared with model group, the body weight, fecal consistency score and tongue surface moisture of rats in P. lactiflora polysaccharides group were significantly increased (P < 0.05, 0.01, 0.001), while mental state, coat luster, urine score, overall physical condition score, rectal temperature, food and water intake were significantly decreased (P < 0.05, 0.01, 0.001), cAMP level was decreased and cGMP level in serum was increased (P < 0.001), and cAMP/cGMP value was significantly reduced (P < 0.001), liver function related indicators were significantly reduced (P < 0.05, 0.01, 0.001), liver tissue pathological damage was improved, the collagen fiber area was significantly reduced (P < 0.001), and the expression levels of liver fibrosis proteins α-SMA, COL-I and FN1 were significantly decreased (P < 0.01, 0.001), the morphology and structure of mitochondria in liver were improved, ROS level in liver was decreased and ATP level was increased (P < 0.05, 0.01, 0.001), expression levels of p-ERK/ERK, p-p38/p38, Fis1 and p-Drp1/Drp1 proteins were significantly reduced (P < 0.05, 0.01, 0.001), while the expression levels of Opa1 and Mfn2 proteins were significantly increased (P < 0.01, 0.001). Conclusion P. lactiflora polysaccharides have a protective effect on liver fibrosis in rats with liver yin deficiency syndrome, and its mechanism may be related to the inhibition of ERK/p38 MAPK pathway to regulate mitochondrial dynamic homeostasis.

Objective To investigate the therapeutic effect and mechanism of Zhizhu Kuanzhong Capsule (枳术宽中胶囊, ZZKZ) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and associated depressive-like behaviors. Methods The main components in ZZKZ were analyzed using UPLC-LTQ/Orbitrap-MS. UC model was established by freely drinking 3.5% DSS solution in mice, and drug intervention was given for 7 d. Hematoxylin-eosin (HE) and Alcian blue-periodic acid Schiff (AB-PAS) staining were used to evaluate the pathological damage and mucus secretion of colon tissue. Depressive like behavior was evaluated using open field experiments and sugar water preference experiments. 16S rRNA sequencing and serum untargeted metabolomics were used to analyze changes in gut microbiota and serum metabolites. Network pharmacology was used to predict targets and pathways, which were validated through molecular docking, molecular dynamics simulation, qRT-PCR and Western blotting experiments. Results Compared with model group, ZZKZ significantly reduced colon shortening in UC mice (P < 0.05, 0.01), decreased disease activity index (DAI) score (P < 0.01), increased total distance, average exercise speed in open field experiments and sugar preference index (P < 0.05, 0.01), reduced the expressions of inflammatory factors in colon and brain tissues (P < 0.05, 0.01), and alleviated intestinal tissue pathological damage and hippocampal neuron damage (P < 0.01). 16S rRNA sequencing results showed that ZZKZ could reduce the abundance of harmful bacteria, increase the abundance of beneficial bacteria, and reverse the imbalance of gut microbiota. The results of serum non-targeted metabolomics analysis showed that ZZKZ could regulate metabolic pathways, reverse lipid, tryptophan and bile acid metabolism disorders. Network pharmacology analysis predicted that Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was related pathway, ursolic acid, atractylenolide I, hesperetin and isorhamnetin in ZZKZ showed significant binding affinity with their target proteins, which may be the main active ingredients for their therapeutic effects. Western blotting results showed that compared with model group, ZZKZ significantly upregulated the expressions of zonula occludin-1 (ZO-1), Occludin and Claudin-1 in colon of UC mice (P < 0.05, 0.01), and inhibited the phosphorylation of JAK2 and STAT3 (P < 0.05). Conclusion ZZKZ may alleviate UC and associated depressive like behavior by regulating gut microbiota, metabolic pathways and inhibiting JAK2/STAT3 pathway.

Objective To explore the mechanism of Lvjiao Buxue Granules (驴胶补血颗粒) in improving postpartum qi and blood deficiency model rats based on spleen transcriptomics. Methods Rats 24 h postpartum were subjected to continuous two weeks weight-bearing swimming combined with orbital bloodletting to establish a postpartum qi and blood deficiency model. After successful modeling, they were randomly divided into model group, Lvjiao Buxue Granules low-, medium-, high-dose (0.84, 1.68, 3.36 g/kg) groups and Danggui Buxue Pills (当归补血丸, 1.89 g/kg) group. Rats 24 h postpartum were also selected as the control group. After two weeks of drug intervention, the comprehensive evaluation of the improvement effect of Lvjiao Buxue Granules on postpartum qi and blood deficiency symptoms in model rats was conducted through qi deficiency score, blood deficiency score, blood routine index, immune organ index, immune inflammation index and other indicators. Through transcriptome analysis, the effects of Lvjiao Buxue Granules intervention on differentially expressed genes and related signaling pathways in spleen of rats were explored. Western blotting and qRT-PCR were used to verify the protein and gene expressions in key signaling pathways. Results Lvjiao Buxue Granules could significantly improve qi deficiency score, blood deficiency score and blood routine indicators of postpartum qi and blood deficiency model rats (P < 0.05, 0.01), reduce inflammation related indicators such as interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) levels in serum (P < 0.05, 0.01), increase immune regulation related indicators such as immunoglobulin A (IgA), IgG and IgM levels (P < 0.05, 0.01), and inhibit the expressions of mitogen-activated protein kinase (MAPK) pathway related proteins and genes in spleen tissue (P < 0.05, 0.01, 0.001). Conclusion Lvjiao Buxue Granules can improve the symptoms of postpartum qi and blood deficiency in rats by inhibiting the phosphorylation of MAPK pathway, regulating the immune function of body and reducing the occurrence of inflammatory reactions.

Objective To explore the effect and mechanism of icariin in improving knee osteoarthritis (KOA) in rats with kidney deficiency and blood stasis based on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods A total of 60 female SD rats were randomly divided into control group, model group, positive control [Xianling Gubao Capsules (仙灵骨葆胶囊, 270 mg/kg)] group and icariin low-, medium-, high-dose (40, 100, 200 mg/kg) groups, with 10 rats in each group. Except for the control group, the other groups were prepared with a combination of “ovariectomy method + hydrocortisone combined with adrenaline method + modified Hulth method” to establish a kidney deficiency and blood stasis KOA rat model. After successful modeling, each group was administered ig continuously for four weeks. The joint inflammation score and joint swelling degree of rats were measured at 0, 1, 2, 3, and 4 weeks after administration. After administration, the levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and IL-10 in serum were detected by ELISA. Hematoxylin-eosin (HE) staining was used to observe pathological changes in knee cartilage. Western blotting was used to detect the expressions of TLR4, myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB (IκB), p-IκB, NF-κB p65 and p-NF-κB p65 proteins in cartilage tissue. Results Compared with control group, the joint inflammation score and joint swelling degree of rats in model group were significantly increased (P < 0.001), the levels of IL-1β, IL-6, TNF-α in serum were significantly increased (P < 0.001), and the level of IL-10 was significantly decreased (P < 0.001). The pathological damage of cartilage tissue was obvious, and the protein expression levels of TLR4, MyD88, p-IκB, p-NF-κB p65 in cartilage tissue were significantly increased (P < 0.05, 0.01, 0.001). Compared with model group, the positive control group and icariin medium-, high-dose groups showed varying degrees of improvement in the above indicators, while some indicators in icariin low-dose group showed an improvement trend. Conclusion Icariin could improve joint inflammation and cartilage damage in KOA rats with kidney deficiency and blood stasis, and its mechanism may be related to inhibiting the activation of TLR4/NF-κB signaling pathway and regulating the balance of inflammatory cytokine network.

Objective Given the complexity of traditional Chinese medicine (TCM) formula constituents and their unclear interactions, a deep learning-based molecular interaction prediction model is constructed taking the prediction of interactions among constituents as the entry point, providing methodological support for identifying potential constituent interactions and subsequent studies on formula compatibility mechanisms. Methods We propose a molecule-molecule interaction prediction model based on molecular 3D structural features and Extended Connectivity Fingerprints, designated as 3D structure and extended connectivity fingerprints molecule-molecule interaction (3DFPMMI). The model employs the SchNet network to extract deep features from the 3D graph structure of molecules while simultaneously acquiring Extended Connectivity Fingerprints, and achieves effective fusion of multi-source features through a contrastive learning strategy. The model is trained on the DrugBank drug-drug interaction dataset, and cross&8209;domain generalization is implemented to realize the prediction of interactions among TCM constituents. Results The 3DFPMMI model achieves an accuracy of 0.921 and an area under the precision-recall curve of 0.972 on the DrugBank dataset, both outperforming other benchmark models. Ablation studies confirm that molecular 3D structural features, extended connectivity fingerprint features, and the contrastive learning-based feature fusion strategy are all core effective modules for improving model performance. When applied to predict component interactions in the classic TCM formulas Buyang Huanwu Decoction and Banxia Xiexin Decoction, some of the prediction results are highly consistent with the conclusions from existing experimental studies. Conclusion This study establishes a novel method for predicting interactions among TCM ingredients and preliminarily validates its application potential. This work offers new technical tools and methodological references for interpreting the compatibility mechanisms of TCM formulas at the molecular level.

Objective To address the challenges of difficult detection of tiny tangential defects, strong background noise interference, and the difficulties in deploying general detection models on low-computing-power edge devices in pharmaceutical capsule production lines, an improved lightweight object detection algorithm is proposed. Methods Using YOLOv8n as the baseline architecture, targeted optimizations are performed through a three-pronged strategy. A coordinate attention (CA) mechanism is embedded in the backbone network to enhance the model’s spatial perception capability for tiny tangential defects and edge micro-defects of capsules. A C2f_GhostConv module is designed to reconstruct the neck network, utilizing Ghost convolution (“primary convolution + cheap operations”) to enhance fine-grained feature representation. Depthwise separable convolution (DWConv) is comprehensively adopted to replace the standard convolution in the backbone, decoupling spatial convolution and channel fusion into two independent steps, thereby achieving deep compression of parameter count and computational load. Results On an industrial dataset containing 1 204 images of various capsule defects, DWG-CA-YOLOv8 achieves a mean Average Precision (mAP@0.5) of 90.5%, demonstrating high-precision localization and accurate classification for six defect types and normal capsules, meeting the reliability required for industrial real-time detection. The model’s parameter count is reduced to 2.10 M, and the floating-point operations (FLOPs) to 5.9 G, representing reductions of 30.2% and 28.1%, respectively, significantly improving lightweight performance. Conclusion This study successfully achieves synergistic optimization of detection accuracy and model complexity, providing a scalable and low-cost lightweight solution for real-time online quality control of pharmaceutical production lines.

Objective To analyze the research status, thematic structure and evolutionary trends of Chinese and English literature on Huangqi (Astragali Radix) using natural language processing and deep-learning-based semantic modeling, and to provide references for hotspot identification and knowledge structure mapping. Methods Literature related to Astragali Radix was retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP databases, with the retrieval fields limited to titles and keywords. After deduplication using NoteExpress and manual screening, titles, keywords and abstracts were combined to construct the analytical corpus. Natural language processing approaches including text cleaning, terminology normalization and semantic embedding were performed, and PubMedBERT combined with BERTopic was used for topic identification, visualization and subtopic analysis of Topic 0. Results A total of 12 159 Chinese publications and 1 536 English publications were included. The publication output of Chinese publications increased markedly after 2015, while English publications showed a continuous upward trend. Topic modeling identified 19 major topics in Chinese literature, mainly involving immunomodulation, diabetic nephropathy, quality control of astragaloside IV, peripheral neuropathy, tumor immunoregulation and phosphatidylinositol-3-hydroxykinase (PI3K)-protein kinase B (Akt)-related network pharmacology. In English literature, 20 major topics were identified, mainly involving formula-related mechanisms, quality analysis of Astragali Radix, network pharmacology and cancer, chemical constituents, fibrosis, ischemia-reperfusion injury, diabetes and gut microbiota. Subtopic analysis of Topic 0 suggested that the Chinese core topic showed an intertwined pattern of “components-preparations-formulas-diseases-mechanisms”, whereas the English core topic was more mechanism- and model-oriented. Conclusion Both Chinese and English Astragali Radix literature showed continuous growth and thematic diversification. Chinese studies focused more on clinical application, compound formulas, diabetic nephropathy and quality control, whereas English studies emphasized molecular mechanisms, network pharmacology, natural product chemistry and modern pharmacological validation. Natural language processing and deep-learning-based topic modeling can effectively reveal the knowledge structure and evolutionary trajectory of Astragali Radix research, providing references for subsequent research topic selection and evidence integration.

Objective Through bibliometric analysis, the relevant literature on the prevention and treatment of cognitive dysfunction in diabetes with traditional Chinese medicine from January 2001to December 2025 was analyzed, and the research status, development context, cutting-edge trends and future directions in this field were systematically revealed. Methods By searching the relevant literature in the databases of China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Web of Science (WOS) and PubMed in the past 20 years, the NoteExpress software was used to deduplicate and sort them, and CiteSpace and VOSviewer softwares were used to conduct visual analysis on the publication trends, authors, institutions, countries, keywords, etc. Results A total of 312 Chinese literature and 183 English literature were included. The number of published literature in Chinese is higher than that in English, occupying a dominant position. China and the United States ranked among the leading countries in terms of publication volume. The research teams centered on Zhan Libin have establish in both the Chinese and English literature, however, collaboration across teams and institutions remained insufficient. Beijing University of Chinese Medicine and Liaoning University of Traditional Chinese Medicine were the core institutions contributing to the Chinese literature, while Liaoning University of Traditional Chinese Medicine was the major contributor to the English literature. Overall, the research institutions were primarily concentrated among Chinese universities of traditional Chinese medicine and their affiliated hospitals. The “apoptosis” exhibited the highest burst strength in the Chinese literature, whereas “traditional Chinese medicine” exhibited the highest burst strength in the English literature. “Gut microbiota” was a sustained burst keyword in both the Chinese and English literature. Meanwhile, the “microbiota-gut-brain axis” and multi-omics integration have emerged as promising research frontiers in this field. Conclusion Research on traditional Chinese medicine for the prevention and treatment of diabetic cognitive dysfunction is currently at a critical stage of transition from phenomenological description to mechanistic elucidation, from single-pathway investigation to network-based regulation, and from basic research to clinical translation. Future research should focus on five key areas: target validation, multi-omics integration, peripheral-central interactions, metabolic reprogramming, and clinical translation, with the aim of addressing major challenges related to target validation, quality control, model relevance, blood-brain barrier assessment, and clinical trials, thereby advancing the modernization and internationalization of traditional Chinese medicine in the prevention and treatment of diabetic cognitive dysfunction.

Objective Based on the whole-genome data of Lycium ruthenicum, this study aimed to systematically identify members of the LrMATE gene family, characterize their structural features, evolutionary relationships, and expression patterns during different fruit coloration stages, and screen candidate genes potentially involved in anthocyanin transport and accumulation. Methods Members of the LrMATE gene family were identified using hidden Markov model (HMM) searches and sequence alignment with known MATE proteins. Bioinformatics approaches were then used to analyze their physicochemical properties, chromosomal location, phylogenetic relationships, gene structures, cis-acting regulatory elements, and syntenic relationships. Combined with transcriptome data from different fruit developmental stages and changes in anthocyanin content, candidate genes related to anthocyanin accumulation were screened through correlation analysis between gene expression levels and anthocyanin content, as well as weighted gene co-expression network analysis (WGCNA). Results A total of 53 LrMATE genes were identified in the L. ruthenicum genome and were unevenly distributed across 12 chromosomes. Phylogenetic analysis classified these genes into five subfamilies, among which subfamily II contained the largest number of members, with 19 genes. Some members of this subfamily clustered closely with previously reported MATE proteins involved in the transport of plant secondary metabolites. Based on the expression patterns of LrMATE genes during different fruit developmental stages, changes in anthocyanin content, and co-expression analysis, LrMATE12, LrMATE15, LrMATE23, LrMATE26, LrMATE27, LrMATE37, and LrMATE38 were predicted to be involved in anthocyanin transport and accumulation during fruit coloration in L. ruthenicum. Conclusion This study systematically characterized the LrMATE gene family in L. ruthenicum and identified seven candidate genes potentially associated with anthocyanin transport and accumulation. These findings provide important candidate gene resources for further elucidating the molecular mechanisms through which LrMATE genes mediate anthocyanin accumulation in L. ruthenicum, and offer a theoretical basis for the development of anthocyanin-related medicinal active components, fruit quality improvement, and the breeding of high-anthocyanin germplasm resources.

Objective To investigate the differential components existing in the roots of Puerariae lobata, a plant with both medicinal and edible properties, at growth stages of one-year, biennial and three-year-old. Methods By comprehensively applying metabolomics and label-free quantitative proteomics, a comparative analysis was conducted of metabolite accumulation dynamics and protein expression profiles in samples from different growth years. Results Metabolic profiling revealed significant differences in flavonoid composition across developmental stages. Comparative analysis identified 236 significantly differentially accumulated metabolites between one-year-old and two-year-old plants, of which 205 were up-accumulated and 31 down-accumulated; between two-year-old and three-year-old plants, the number decreased markedly to 25 differentially accumulated metabolites (14 up-accumulated, 11 down-accumulated); and between one-year-old and three-year-old plants, 83 differentially accumulated metabolites were detected (70 up-accumulated, 13 down-accumulated). Subsequent compound classification, correlation analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of these metabolites identified five pathways significantly enriched in flavonoid-related metabolism. Parallel proteomic profiling yielded 2 764 significantly differentially expressed proteins (FC ≥ 1.5 or ≤ 0.67, P < 0.05). Across the three pairwise comparisons, upregulated proteins numbered 1 565, 1 437, and 193, respectively, while downregulated proteins totaled 931, 817, and 260, respectively. Functional annotation via gene ontology (GO) and KEGG pathway analyses further demonstrated significant enrichment of these proteins in biological processes and pathways central to flavonoid biosynthesis, pyruvate metabolism, and amino acid biosynthesis. Conclusion Metabolite accumulation and proteomic variations across different growth years of P. lobata are predominantly enriched in the biosynthetic pathways of phenylpropanoids, flavonoids, and other plant secondary metabolites. Flavonoid constituents from P. lobata are closely associated with pharmacological activities including anti&8209;inflammatory, lipid&8209;regulating and hypoglycemic effects.This study establishes a foundational framework for both the rational development and utilization of P. lobata resources and the mechanistic understanding of its growth and developmental regulation at the molecular level.

Objective To establish the HPLC fingerprint and multi-component content determination method of Lavandula angustifolia from different origins, and to evaluate the quality of L. angustifolia medicinal materials from different origins by combining chemical pattern recognition methods, providing a basis for further research and development. Methods A Zorbax Eclipse XDB-C₁₈ column (250 mm × 4.6 mm, 5 μm) was used, with acetonitrile-0.1% phosphoric acid solution as the mobile phase, and gradient elution. The detection wavelength was 350 nm, the column temperature was 30 ℃, the flow rate was 0.6 mL/min, and the injection volume was 10 μL. The HPLC fingerprint of L. angustifolia from Xinjiang was established and the similarity was analyzed. At the same time, the chemical components were identified by comparison with reference substances and quantitatively determined. Hierarchical clustering analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed using Origin2025b, IBM SPSS Statistics 27 and SIMCA 14.1 software to evaluate the quality of L. angustifolia medicinal materials from different origins and screen the quality difference markers. Results The HPLC fingerprint chromatograms of L.angustifolia from different regions in Xinjiang were established. A total of 14 common chromatographic peaks were identified, and five components were recognized: Chlorogenic acid (peak 2), luteolin-7-O-glucoside (peak 8), rosmarinic acid (peak 12), luteolin (peak 13), and apigenin (peak 14).The similarity of 15 batches of samples was all above 0.9. HCA divided 15 batches of L. angustifolia into three categories. PCA extracted four principal components, with a cumulative contribution rate of 93.310%. PCA results showed that batch YC23072402 from Huocheng, Xinjiang, had the best quality. OPLS-DA identified seven quality difference markers, namely luteolin, rosmarinic acid and apigenin, in L. angustifolia samples. The contents of luteolin, rosmarinic acid and apigenin in L. angustifolia were 0.018—0.230, 0.380—3.095 and 0.144—0.481 mg/g respectively. Conclusion The HPLC fingerprint and multi-component content determination method for L. angustifolia from different origins is simple, accurate, and has good repeatability. It can be used for the quality evaluation of L. angustifolia from Xinjiang and provide a basis for its quality control.

Objective To establish a multi-index quantitative determination method for Limonium bicolor from different habitats, and to evaluate the quality of L. bicolor from different habitats by combining chemometrics and integratedTOPSIS-GRA method. Methods HPLC was performed on a Prep Scalar C₁₈ (250 mm × 4.6 mm, 5 μm) column. Detection wavelength: 273, 254, 360 and 210 nm; acetonitrile-0.2% phosphoric acid was used as the mobile phase for gradient elution. The injection volume was 10 μL, the flow rate was 1.0 mL/min, and the column temperature was 30 ℃. The contents of gallic acid, vanillic acid, myricitrin, eriodictyol, rutin, luteolin, quercetin, kaempferol, isorhamnetin, naringenin, β-sitosterol, daucosterol in 20 batches of L. bicolor were determined simultaneously. The extractives, total ash and acid-insoluble ash of samples were examined. Utilize SPSS 26.0 and SIMCA 14.1 statistical software to perform chemometric analysis on detection data to group 20 batches of L. bicolor from different habitats, and the quality difference markers were screened, and then the TOPSIS-GRA method fusion model was constructed to sort the quality. Results The results of the established multi-index quantitative methodology were good. Under the same chromatographic conditions, gallic acid, vanillic acid, myricitrin, eriodictyol, rutin, luteolin, quercetin, kaempferol, isorhamnetin, naringenin, β-sitosterol, daucosterol were effectively separated. There were differences in the content of each component. The results of chemometrics analysis showed that the clustering of 20 batches of L. bicolor was obvious, and luteolin, gallic acid, β-sitosterol, rutin, isorhamnetin, quercetin, eriodictyol and myricitrin were the dominant components of origin difference. The results of TOPSIS-GRA analysis showed that there were differences in the comprehensive relative closeness of 20 batches of samples, and the comprehensive relative closeness of S16, S18, S15, S17, S19, S20 was larger, which was 0.642 1, 0.634 2, 0.626 1, 0.614 8, 0.595 4 and 0.593 0, respectively. Conclusion The established multi-index quantitative method can reflect the quality differences of L. bicolor rutin from different habitats. The fusion model combining chemometrics with weighted TOPSIS and GRA comprehensively evaluated the quality characteristics of from different origins, which established a foundation for the quality analysis and evaluation of L. bicolor.

Objective To establish a method for multi-index quantitative analysis and quality difference evaluation of Bupleurum scorzonerifolium from different producing areas. Methods A UPLC-MS/MS method was developed for simultaneous determination of saikosaponin a, saikosaponin d, saikosaponin c, saikosaponin b₂, and saikosaponin f in B. scorzonerifolium. The separation was performed with a mobile phase of acetonitrile-0.1% formic acid aqueous solution at a flow rate of 0.3 mL/min under gradient elution. Alcohol-soluble extractives, total ash, and acid-insoluble ash were also determined. Cluster analysis (CA), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted using SPSS 26.0 and SIMCA 14.1 software. The variable importance in projection (VIP) was used to identify markers contributing to quality differences. The CRITIC method was employed for objective weighting of each evaluation index, and a comprehensive quality assessment model was constructed by coupling with the TOPSIS method. Results Methodological validation results demonstrated good linearity and satisfactory accuracy for all analytes. The quantitative results showed that the contents of the five components in B. scorzonerifolium from different areas were: saikosaponin a (1.916 ± 1.338) mg/g, saikosaponin c (0.753 ± 0.445) mg/g, saikosaponin d (3.442 ± 2.351) mg/g, saikosaponin b₂ (2.083 ± 1.424) mg/g, and saikosaponin f (0.463 ± 0.322) mg/g. The amounts of alcohol-soluble extractives, total ash, and acid-insoluble ash were (29.2 ± 2.1)%,( 6.0 ± 0.6)%, and (1.2 ± 0.3)%, respectively. Multivariate statistical analysis showed that the 10 batches of B. scorzonerifolium were clearly classified into two groups. Three quality difference markers with relatively high contribution were screened, and the order of contribution was saikosaponin d > saikosaponin b₂ > saikosaponin a. The results of the CRITIC-TOPSIS analysis indicated that samples S10 (from Bozhou, Anhui), S8 (from Longnan, Gansu), and S5 (from Dingxi, Gansu) possessed relatively superior overall quality. Conclusion There are quality differences among B. scorzonerifolium samples from different producing areas. The established multi-index quantitative analysis, chemometrics, and CRITIC-TOPSIS method provide an experimental basis for improving the quality evaluation system of B. scorzonerifolium.

Colorectal cancer (CRC) cachexia is a common wasting syndrome in patients with advanced CRC. It is mainly characterized by progressive skeletal muscle wasting, lipolysis, systemic inflammatory response, and metabolic and immune dysregulation, which seriously impair patients’quality of life, treatment tolerance, and prognosis. In traditional Chinese medicine (TCM), this disease is generally classified into the category of “consumptive disease”, with its core pathogenesis characterized by “deficiency in origin and excess in superficiality” and “deficiency and excess inclusiofuzhengquxie”. Reinforcing healthy qi and dispelling pathogen are regarded as the principal therapeutic principles. By retrieving relevant domestic and international literature, this review systematically summarizes the pathogenesis of CRC cachexia, the regularity of syndrome differentiation and treatment in TCM, and the characteristics of the Application of prescriptions and drugs. Furthermore, it elucidates the pharmacological mechanisms by which active ingredients and Chinese herbal formulas intervene in cachexia through regulating inflammatory networks, improving skeletal muscle and adipose tissue metabolism, protecting mitochondrial function, and reshaping the immune microenvironment. Specifically, “reinforcing healthy qi” corresponds to the improvement of nutritional metabolism, protection of skeletal muscle, and regulation of immune function, whereas “dispelling pathogen” corresponds to the inhibition of inflammation, remodeling of the tumor microenvironment, and blockade of abnormal catabolism, thereby constructing a correlation between TCM therapeutic principles and the inflammation-metabolism-immunity regulatory network.

Process scale-up is a critical step in the transition of pharmaceutical preparations from research and development to industrial production. Dry granulation, as a key technology for forming traditional Chinese medicine (TCM) solid dosage forms, offers advantages such as a short process flow, minimal impact on active ingredients, high efficiency, and energy savings. However, its process scale-up faces numerous challenges. This article reviews the key technical bottlenecks in the process scale-up of TCM dry granulation, including critical process parameters, thermodynamic effects of the feeding system and equipment, and critical material attributes. The evolution of scale-up strategies is summarized from perspectives of methodological support and strategic evolution, tracing the progression from traditional empirical scale-up to digital modeling-driven multi-scale intelligent scale-up. Among these, gray-box hybrid modeling, population balance model-based integrated process simulation, and process analytical technology-driven closed-loop feedback control offer new approaches to address nonlinear issues during scale-up. In the future, integrating physical fingerprint with digital twin technology to establish a cross-scale scale-up framework will promote the transformation of process development from “experience-driven” to “model-driven” paradigms, thereby facilitating the strategic upgrade of TCM pharmaceutical manufacturing toward intelligent manufacturing.

Shihu (Dendrobii Caulis) has the effects of nourishing the stomach, promoting fluid production, and nourishing yin to clear heat. With its significant characteristics of being both a medicinal and food resource, its industrial chain spans multiple sectors including medicinal herbs, food, health products, daily chemicals, and cultural tourism wellness. It holds important strategic value in promoting the modernization of traditional Chinese medicine, fostering regional economic development, and driving rural revitalization. Although the industry has currently reached a scale of billions, it still faces practical challenges such as an incomplete supply system for authentic medicinal herbs, a singular product structure and insufficient deep-processing capabilities, weak fundamental and applied research, limited influence of regional public brands, and inadequate cultural empowerment. This study systematically reviews the original species of Dendrobii Caulis, resource distribution patterns, industrial status, and research progress from three dimensions—historical origins, current industrial conditions, and development strategies. It conducts an in-depth analysis of developmental bottlenecks, drawing on exemplary practices such as the protection and high-end development of “Mihu” germplasm resources in Huoshan, Anhui, large-scale cultivation of “Purple-Skin Dendrobii Caulis” in Longling, Yunnan, and rock wall near-wild cultivation in Longhu mountain, Jiangxi. Based on these cases, it proposes strategies including strengthening standardized base construction, improving comprehensive quality control systems, deepening technology-driven innovation, diversifying product pathways, shaping regional specialty brands, and promoting integrated development across primary, secondary, and tertiary industries. These measures aim to achieve a win-win scenario of ecological and economic benefits for Dendrobii Caulis industry, providing theoretical references and practical pathways for serving the inheritance, innovation of traditional Chinese medicine, and comprehensive rural revitalization.

Songhuafen (Pini Pollen), a traditional medicinal and edible material, is rich in bioactive constituents such as polysaccharides, flavonoids, sterols, and unsaturated fatty acids. It may exert potential effects on diabetes, dyslipidemia, obesity, metabolic dysfunction-associated fatty liver disease, and diabetes-related chronic wounds by regulating glucolipid metabolism, insulin signaling, chronic inflammation, oxidative stress, gut microbiota, and intestinal barrier function. Different processing methods markedly influence active component release and clinical applicability: wall-breaking improves the dissolution of internal hydrophilic and lipophilic components, fermentation treatment may alter the polyphenol and metabolite profiles through microbial transformation, sulfation can enhance the hypoglycemic and immunomodulatory activities of polysaccharides, and supercritical CO₂ extraction is more suitable for enriching lipophilic fractions. Existing clinical evidence suggests potential auxiliary benefits in glucose-reducing, lipid regulation, and wound healing related to diabetic complications. However, most studies are limited by small sample sizes, insufficient randomization, blinding, dose standardization and long-term safety evaluation, and heterogeneity caused by differences in raw materials and preparation technologies. Future studies should clarify key quality markers, standardize processing technologies, establish material basis and relationships among components, exposure, and effects, and validate clinical efficacy and safety through rigorously designed, large-scale randomized controlled trials. These efforts promote the transition of Pini Pollen from empirical use to evidence-based and precision-oriented clinical application.

Coronary heart disease (CHD) is characterized by a high incidence rate and a substantial disease burden. Although conventional Western medicine can effectively manage cardiovascular risk factors and achieve coronary revascularization, it often fails to adequately address microcirculation disturbance, residual inflammatory risk, and the lack of holistic systemic regulation. In traditional Chinese medicine (TCM), CHD falls under the categories of “Xiongbi” (chest obstruction) and “Xintong” (cardiac pain), with “qi deficiency and blood stasis” identified as the core pathogenesis. This concept aligns closely with the modern pathological network of “vascular injury-inflammatory immune response-metabolic dysregulation”. Qishen Yiqi Dripping Pills (芪参益气滴丸, QSYQ), a Chinese patent medicine composed of Huangqi (Astragali Radix), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Sanqi (Notoginseng Radix et Rhizoma), and Jiangxiang (Dalbergiae Odoriferae Lignum), strictly adheres to the therapeutic principle of supplementing qi and activating blood, offering distinct advantages in multi-target systemic regulation. Centered on the theme of systemic regulation and precise intervention, this review first elucidates the scientific connotation of qi deficiency and blood stasis and maps its correlation with modern pathological networks. It then establishes a three-tiered mechanistic framework spanning “molecular events-signaling pathways-biological effects” to systematically decode the synergistic regulatory networks of QSYQ in anti-inflammation, anti-oxidation, anti-apoptosis, angiogenesis promotion, and energy metabolism optimization. Furthermore, a hierarchical clinical evidence evaluation system is constructed to summarize the therapeutic value of QSYQ in alleviating symptoms, improving cardiac function, enhancing long-term prognosis, and managing special patient populations. Future research should leverage multi-omics technologies and real-world evidence studies to further elucidate the underlying mechanisms of action. Additionally, high-quality evidence-based studies should be conducted to standardize evaluation criteria and optimize individualized medication regimens, ultimately promoting the standardized clinical application of QSYQ in the integrative traditional Chinese and Western medicine treatment of coronary heart disease.

The phenomenon of “bidirectional regulation” in traditional Chinese medicine (TCM), as one of its characteristic therapeutic effects, embodies the treatment principle of “achieving equilibrium as the therapeutic goal”. However, the underlying dynamic mechanism governing the selection of regulatory direction cannot be adequately explained through the static “component-target” paradigm of modern pharmacology or the empirical induction of traditional “pattern-effect” relationships. To address this theoretical bottleneck, this study, grounded in the intrinsic logic of TCM thinking, introduces and elaborates on the theoretical concept of “dynamic tendency”, constructing a dynamic explanatory framework that organically integrates “body state”, “medicinal properties”, and “effect direction”. This study proposes the basic approach of “discerning the dynamic tendency to clarify the mechanism, and following the dynamic tendency to regulate accordingly”. It innovatively defines three core categories—“disease tendency”, “tendency towards homeostasis”, and “herbal tendency” and, based on the principle of “guiding according to the tendency”, constructs a ternary dynamic response model of “disease tendency-tendency towards homeostasis-herbal tendency”. This model redefines the essence of bidirectional regulation in TCM as follows: within the context of a specific “disease tendency”, the body's inherent self-balancing trend—the “homeostatic tendency” is activated yet lacks the conditions to restore equilibrium. The “herbal tendency”, as an exogenous intervention with a consistent directional property, precisely coordinates with and stimulates this “homeostatic tendency”, thereby guiding the system back to dynamic balance from various states of deviation. Furthermore, the paper analyzes the bidirectional regulatory mechanisms of single herbs (such as Dahuang-Cijili), herb pairs (such as Chaihu-Huangqin), and compound formulas (such as Guizhi Tang) through the lens of the “disease tendency-homeostatic tendency-herbal tendency” framework. Extending the “tendency” theory to the level of clinical diagnosis and treatment, this study aims to provide a new perspective and theoretical foundation for deepening TCM clinical thinking from “pattern differentiation” toward “tendency differentiation and mechanism discernment”, and from “formula selection” toward “precise tendency alignment”. This is intended to promote the modern interpretation and development of “tendency-based” theory in TCM.

Central nervous system diseases are major causes of disability and death, with persistent activation of neuroinflammation and glial functional imbalance being one of the common pathological features. As important bioactive constituents of traditional Chinese medicine (TCM), TCM polysaccharides, possess multiple biological activities, including immunomodulatory, anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-regulating effects. They have shown potential neuroprotective effects in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, depression, cerebral ischemia-reperfusion injury, and other central nervous system diseases. Current evidence indicates that TCM polysaccharides can ameliorate aberrant glial responses and glia-mediated neuroinflammatory injury by regulating microglial activation and polarization, phagocytosis and pathological clearance, and autophagy-lipid droplet metabolism, maintaining astrocyte homeostasis, and promoting oligodendrocyte lineage differentiation and remyelination. The underlying mechanisms involve multiple signaling pathways, including nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), phosphatidylinositol-3-hydroxykinase (PI3K)/protein kinase B (Akt), etc. Overall, TCM polysaccharides exert multi-target and multi-level regulatory characteristics on glial cells, which constitutes an important mechanistic basis for timproving central nervous system diseases. Future studies should further strengthen polysaccharide structural characterization, target validation, and clinical translational research to provide evidence for elucidating its neuroprotective mechanism and promoting application development.

Calcium ion (Ca²⁺), as a crucial second messenger in plant cells, plays a central role in sensing and responding to heavy metal stress. This review systematically summarizes recent advances in the dual regulatory mechanisms of Ca²⁺signaling for the uptake and tolerance of heavy metals such as cadmium and lead. On the one hand, heavy metals can trigger specific Ca²⁺ signatures-transient elevations or characteristic oscillations—through three pathways: direct activation of Ca²⁺ channels, indirect induction of reactive oxygen species (ROS)bursts, and disruption of Ca²⁺ homeostasis. On the other hand, these spatiotemporally distinct Ca²⁺ signals are decoded by sensors including calmodulin, calcium-dependent protein kinases, and calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complexes, which then precisely regulate the expression and activity of heavy metal transporters, such as CNGCs and NRAMPs, through transcriptional and post-translational modifications. This enables a dual regulatory mode-suppressing uptake, promoting efflux, or vacuolar sequestration-while concurrently activating antioxidant and chelation-based detoxification pathways to maintain ion homeostasis and redox balance. Furthermore, arbuscular mycorrhizal fungi symbiosis can synergistically modulate plant metal uptake and tolerance by reshaping the spatiotemporal patterns of host Ca²⁺ signals, altering ion transport profiles, and enhancing detoxification pathways. In conclusion, this review emphasizes that the Ca²⁺ pathway-centered “perception-decoding-execution” network is key to regulating heavy metal uptake in plants. Future research should focus on identifying metal-specific Ca²⁺ fingerprints, functionally validating key channels and decoding modules, and developing applications combined with rhizosphere microbial interventions, thereby providing theoretical and technical support for low-heavy-metal-accumulation cultivation of medicinal plants and crops, as well as for soil remediation.