Objective To investigate the dynamic changes of volatile and water-soluble constituents in Schizonepetae Herba and Cinnamomi Cortex decoctions at different boiling durations, reveal the characteristics of constituent dissolution, volatilization, and degradation during decoction from the material basis, and provide a scientific basis for rational determination of decoction time and different administration routes (e.g., decoction, powder infusion) in clinical practice. Methods Decoctions of JIngjie (Schizonepetae Herba) and Rougui (Cinnamomi Cortex) were prepared at different boiling times. A headspace GC-MS/MS method was established and validated for pulegone, menthone, o-methoxycinnamaldehyde, and cinnamaldehyde, and their content changes at different decoction times were compared. UPLC-Q-TOF MS/MS was employed to characterize and semi-quantify water-soluble constituents. Normalized ion intensities and clustering analysis were used to assess the impact of boiling duration on the overall chemical profile. Results The four volatile compounds exhibited distinct time-dependent patterns.Pulegone, menthone, and cinnamaldehyde increased rapidly at early stages and declined thereafter, whereas o-methoxycinnamaldehyde increased continuously. A total of 139 water-soluble constituents were identified by UPLC‑Q‑TOF MS/MS, many of which showed reduced abundance with prolonged boiling, indicating potential heat degradation. Integrated analysis suggested that approximately 7.5 min represents an optimal decoction time for Schizonepetae Herba. For Cinnamomi Cortex, prolonged decoction is not suitable when emphasizing the effects of warming yang and reinforcing fire, whereas appropriate prolonged decoction or alternative administration such as powder infusion can be used when emphasizing warming and unblocking to relieve pain. Conclusion Schizonepetae Herba and Cinnamomi Cortex exhibit clear time-dependent chemical changes during decoction. Boiling time critically influences the retention of volatile and water-soluble constituents. The results provide a reference for selecting decoction time and optimizing administration routes of the two herbs under different clinical applications, and offer an experimental basis for the standardization and modernization of traditional Chinese medicine decoctions.

Objective To address the issues of poor flowability and high hygroscopicity of fermented Cordyceps powder, the particle size gradation strategy and investigates the relationship between flowability parameters, particle size, and particle size distribution, so as to provide theoretical support and technical guidance for enhancing powder performance and optimizing processing strategies. Methods A laser particle size analyzer, powder characteristics tester, and powder rheometer were employed to systematically characterize the particle size distribution, static flowability parameters (angle of repose, Hausner ratio, and flat plate angle, etc.), and rheological properties (flow energy, aeration, permeability, and shear behavior) of the fermented Cordyceps powder. The effects of different particle size ratios on powder packing behavior and hygroscopicity were analyzed. Results Particle size is a critical factor affecting powder flowability. A particle size ratio of 24-80 (95:5) mesh yielded optimal packing performance. Hygroscopic kinetics modeling showed that both the double exponential and Weibull models provided good fits for describing the moisture absorption behavior of powders with different particle sizes, offering quantitative indicators of hygroscopicity. Conclusion Particle size gradation design provides a new strategy for improving the flowability and stability of fermented Cordyceps powder.

Objective To establish the pressing process of the Fujv decoction pieces of Daqingye (Isatidis Folium, IF), and determine the optimal process parameters. Methods The contents of indirubin, isovitexin and tryptanthrin in IF were determined by HPLC. The paste yield was determined by hot maceration. The analytic hierarchy process (AHP)-entropy weight method was used to determine the weight coefficients of each index and calculate the comprehensive score. Pressure, compression time, drying temperature and drying time were investigated as single factors. The AHP-entropy weight method combined with the Box-Behnken design-response surface methodoly (BBD-RSM) was used to optimize the pressing process of the decoction pieces of the Fujv decoction pieces of IF. Results The optimal parameters of the initial pressing process of the decoction pieces of the Fujv decoction pieces are as follows: After moistening, the medicinal materials were cut into 5—7 mm pieces, pressed at 4 MPa for 60 s, and baked at 60 ℃ for 4 h. Under these conditions, the overall desirability (OD) value of the validation tests was 94.12%, which is close to the predicted OD value of 93.30%. Conclusion The compression process for IF Fujv decoction pieces is practically feasible, providing a reference for the development and utilization of such pieces.

Objective This study aimed to establish an evaluation system for screening transdermal penetration enhancers suitable for traditional Chinese medicine (TCM) compound formulations and to apply it to the optimization of a composite penetration enhancer for Erxian Decoction (EXD, 二仙汤). Methods Menthol, azone, and borneol were selected as penetration enhancers, and an L₉(3³) orthogonal design was employed. The 48 h cumulative permeation per unit area (Q₄₈), steady-state flux (J_ss), and enhancement ratio (ER) of ten marker components (phellodendrine, mangiferin, ferulic acid, berberine, curculigine, epimedin A1, epimedin A, epimedin B, epimedin C, icariin) were measured. Principal component analysis (PCA) was performed separately for Q₄₈ and J_ss datasets to reduce dimensionality, while fingerprint similarity (S) was incorporated as a quality constraint. The PCA scores and S were weighted and integrated via the satisfaction function to calculate the comprehensive satisfaction (D). With D as the response value, range analysis and analysis of variance were performed to screen the optimal formulation of penetration enhancers. Results The optimal compound penetration enhancer formulation was identified as 2% menthol combined with 1% azone. Validation studies showed that this formulation exhibited excellent penetration-enhancing effect, while the fingerprint similarity S remained above 0.9, achieving both “high-efficiency penetration enhancement” and “quality fidelity”. Conclusion The constructed “PCA dimension reduction-fingerprint constraint-satisfaction function integration” system can effectively solve the problems of information redundancy and decision contradiction in multi-index optimization, providing a referable research paradigm for screening composite penetration enhancers of TCM compound prescriptions.

Objective In order to demonstrate the feasibility of microwave processing as an alternative to traditional methods, the study aimed to systematically compare that different processing methods affect on the appearance, active components, toxicity and efficacy of Banxia (Pinelliae Rhizoma, PR). Methods This study systematically compares the active components of different processed PR using extract yield determination, UV spectrophotometry, and HPLC. The irritancy of various processed products of PR was assessed through scanning electron microscopy (SEM)/X-ray diffraction (XRD) characterization, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and slug irritation tests. Additionally, mouse ammonia-induced cough suppression and tracheal phenol red secretion assays were employed to evaluate the antitussive and expectorant effects of the different processed products of PR. Results The experimental results indicate that the water-soluble extract and alkaloid content of microwave-processed PR are significantly higher than those of traditionally processed products (P < 0.01). However, the total nucleoside content is lower than that of raw PR, Jiangbanxia (Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine, PRPZA), and Qingbanxia (Pinelliae Rhizoma Praeparatum cum Alumine, PRPA), but higher than that of Fabanxia (Pinelliae Rhizoma Praeparatum, PRP) (P < 0.01). Compared to raw PR and traditionally processed products, the content of calcium oxalate raphides in microwave-processed PR is significantly reduced (P < 0.01), and the lectin protein structure is disrupted. The mucosal irritation was in the order: raw PR > PRPA > PRP > PRP > microwave-processed PR, and microwave-processed product showed almost no mucosal irritation. Pharmacological experiments indicated that the cough-suppressing and expectorant effects of microwave-processed PR were comparable to those of raw PR and significantly superior to those of traditionally processed products. Conclusion Microwave processing retains active components of PR while rapidly reducing its irritancy, with antitussive and expectorant activities comparable to those of raw PR. This study demonstrates the feasibility of microwave technology for PR, providing scientific evidence for its industrial-scale production and clinical applications.

Objective To compare the composition and content differences of volatile components in Liushenqu (六神曲, Massa Medicata Fermentata, MMF) samples with different fermentation times, clarify the material basis of the unique aroma of MMF, and identify the key components that give it its main characteristic aroma. Methods Taking MMF fermented for different durations as the research object, and electronic nose was used to characterize its overall odor profile, and gas chromatography-mass spectrometry (GC-MS) was combined to analyze the specific volatile components. Chemometrics was applied to screen the differential components at different fermentation stages, and the relative odor activity value (ROAV) was used to reveal the odor differences of MMF and the material basis for its odor formation. Results Based on the detection results of the W5S, W1W, and W2W sensors of the electronic nose, the fermentation process of MMF was clearly divided into three stages: T1—T4 (initial fermentation), T5—T8 (middle fermentation), and T9—T12 (late fermentation). A total of 120 volatile components were identified by GC-MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) confirmed that there were significant differences in the volatile components of MMF at different fermentation times. A total of 49 differential components were screened out according to the criteria of variable importance in projection (VIP) > 1 and P < 0.05. Combined with the relative odor activity value method, 5-hydroxymethylfurfural was identified as the component contributing the most to the characteristic aroma of the main body. 2-Hexene, pentyl (9E)-octadec-9-enoate, 3,5-dihydroxy-1-nonadecylbenzene, and methyl 2-methoxy-5-hexadecenoate played important modifying roles in the characteristic aroma. Conclusion The differences in volatile components during the fermentation of MMF can be effectively analyzed by electronic nose, GC-MS, combined with the relative odor activity value method, which provides a scientific basis for the identification and quality evaluation of MMF.

Objective Hesperetin and palmatine hydrochloride co-amorphous system (Hes-PH CAS) was prepared to develop new solid forms and improve the solubility and dissolution of hesperetin. Methods Hes-PH CAS was obtained via the rotary evaporation method. The solid-state characteristics were characterized by powder X-ray diffraction, differential scanning calorimetry, dynamic vapor sorption and solid-state nuclear magnetic resonance, respectively. The solubility and dissolution behavior were investigated by high-performance liquid chromatography. Furthermore, the antioxidant and antitumor activities were analyzed through radical scavenging assay and cell proliferation studies. Results Hes-PH CAS possessed a single glass transition temperature (T_g = 104.5 ℃) and exhibited intermolecular interactions. The co-amorphous simultaneously influenced the solubility and dissolution of both drugs, increasing hesperetin solubility while decreasing palmatine hydrochloride solubility, and promoting hesperetin release while delaying palmatine hydrochloride release. The antioxidant and anti-tumor results demonstrated that the free radical scavenging rate and HT-29/HCT 116 cell inhibition rate of Hes-PH CAS were higher than those of the individual raw materials, indicating a synergistic effect between the two drugs in terms of both free radical scavenging and cell inhibition. Conclusion The prepared Hes-PH CAS improved the solubility and dissolution of hesperetin, with two pharmaceutical components exhibiting good antioxidant and antitumor effects.

Objective To investigate the molecular mechanisms by which ginsenoside Rb₃ (Rb₃) inhibits lipid accumulation in macrophages. Methods Oxidized low-density lipoprotein (ox-LDL) was used to induce lipid-associated macrophages (LAMs) model in murine RAW264.7 macrophages. After Rb₃ intervention, intracellular lipid accumulation was evaluated by oil red O staining and BODIPY-based neutral lipid fluorescence staining. Changes in lipid composition were analyzed using untargeted lipidomics. Transcriptomic and proteomic analyses were performed in parallel, followed by integrative multi-omics bioinformatic analysis. Molecular docking was conducted using Autodock to predict the binding potential between Rb₃ and candidate target molecules identified from multi-omics intersections. The expression levels of key genes and proteins were validated by qRT-PCR and Western blotting. Cell thermal shift assay (CETSA) was employed to evaluate the binding of Rb₃ to complement component 5a receptor 1 (C5ar1) and cluster of differentiation 36 antigen (Cd36) targets. Results A lipid-enriched LAMs model was successfully established. Within a non-cytotoxic concentration range, Rb₃ dose-dependently suppressed intracellular lipid accumulation (P < 0.05, 0.01, 0.001). Lipidomics revealed a marked elevation of triglycerides accompanied by a reduction in glycerophospholipids in model group, whereas Rb₃ treatment significantly reduced triglyceride levels and restored glycerophospholipids, with pathway enrichment mainly involving glycerophospholipid metabolism. Transcriptomic analysis identified 1 291 differentially expressed genes, which were significantly enriched in peroxisome proliferator-activated receptor (PPAR) signaling pathway. Proteomic analysis detected 254 differentially expressed proteins, with enrichment in pathways including amyotrophic lateral sclerosis-related signaling. Integrative multi-omics analysis identified six overlapping target molecules, including Cd36, C5ar1 and adenosine triphosphate binding cassette transporter G1 (Abcg1). Molecular docking predicted favorable binding affinities between Rb₃ and Cd36, C5ar1, Abcg1. CETSA results demonstrated that Rb₃ significantly protected Cd36 and C5ar1 proteins from temperature-dependent degradation, providing further evidence of direct binding between Rb₃ and these targets. qRT-PCR and Western blotting results showed that Rb₃ significantly down-regulated the expressions of Cd36 and C5ar1 in LAMs (P < 0.05, 0.01, 0.001), while up-regulated the expressions of PPARγ, Abca1 and Abcg1 (P < 0.05). Conclusion Rb₃ activates PPAR signaling pathway and regulates glycerophospholipid metabolism, targeting Cd36 and C5ar1 to inhibit their mediated lipid uptake and promote Abca1 and Abcg1 mediated lipid efflux, regulating the intracellular levels of triglycerides and glycerophospholipids, thereby exerting an inhibitory effect on lipid accumulation in macrophages.

Objective To investigate the hypolipidemic effects of gypenosides based on serum, liver and fecal metabolomics techniques. Methods A high-fat diet was used to establish a hyperlipidemia model in rats, with 32 male SD rats randomly divided into control group, model group, atorvastatin (10 mg/kg) group and gypenosides (150 mg/kg) group. After eight weeks of continuous administration, body weight and blood lipid levels were measured. Metabolites in serum, liver and feces were analyzed using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, and differential metabolites were screened through multivariate statistical analysis. Results Gypenosides significantly reduced levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in serum of hyperlipidemic rats (P < 0.05, 0.01). Metabolomics analysis revealed that gypenosides effectively normalized the endogenous metabolic profile of model rats, identifying 30, 27, 19 differential metabolites in serum, liver and feces, respectively, primarily including lysophosphatidylcholine, unsaturated fatty acids and derivatives, bile acids, and amino acids and derivatives, linked to glycerophospholipid, linoleic/arachidonic acid, unsaturated fatty acid, primary bile acid biosynthesis, and tryptophan metabolism. Except for glycoursodeoxycholic acid and glycylglycoursodeoxycholic acid in liver, which still showed an increasing trend after gypenosides intervention, all other differential metabolites returned to near-normal levels. Conclusion Gypenosides modulate blood lipids by regulating the lipid metabolism network through multiple targets, with mechanisms related to intervention in lysophosphatidylcholine metabolism, linoleic acid and arachidonic acid metabolism, bile acid metabolism and tryptophan metabolism pathways, systematically revealing the overall regulatory effect of gypenosides on endogenous metabolism of hyperlipidemic rats.

Objective To investigate the acute and chronic diuretic effects and diuretic mechanisms of Clematis hexapetala in a saline-loaded rat model. Methods Model group, furosemide (10 mg/kg) group, C. armandii (20 g/kg) group, C. hexapetala low-, medium- and high-dose (5, 10, 20 g/kg) groups, with eight rats in each group. Urine volume and electrolyte concentration in rats were measured after acute and long-term drug intervention. The activity of Na⁺-K⁺-triphosphatase (ATPase) and levels of angiotensin II (Ang II), antidiuretic hormone (ADH), aldosterone (ALD), atrial natriuretic peptide (ANP) in serum were measured. Hematoxylin-eosin (HE) staining was used to observe pathological changes in renal tissue. Network pharmacology was used to screen the active ingredients and diuretic targets of C. hexapetala, a protein-protein interaction (PPI) network was constructed to perform gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on core targets. Molecular docking validation was performed on the core components and targets, qRT-PCR and Western blotting were used to detect the expressions of genes and proteins related to aquaporin (AQP)/cyclic adenosine monophosphate (cAMP)/cAMP response element binding protein (CREB) pathway in renal tissue. Results A total of seven active compounds and 354 potential drug targets were identified for C. hexapetala from TCMSP database. A total of 1 531 disease-related targets were screened from GeneCards and OMIM databases, including 133 intersecting targets. PPI analysis revealed that the top 5 core targets were prostaglandin-endoperoxide synthase 2 (PTGS2), adrenergic receptor β1 (ADRB1), peroxisome proliferator-activated receptor α (PPARA), angiotensin II receptor type 1 (AGTR1) and PPARG. KEGG pathway enrichment analysis revealed that cAMP pathway played an important role in the process of diuresis in C. hexapetala. Animal experiment results showed that C. hexapetala significantly increased urine output and Na⁺, Cl⁻, K⁺ levels in urine of rats (P < 0.05, 0.01), significantly reduced Ca²⁺ level (P < 0.05), thereby increasing NaCl excretion. C. hexapetala significantly reduced the levels of ADH, Ang II and ALD in serum of rats (P < 0.05, 0.01), significantly increased Na⁺-K⁺-ATPase activity and ANP level (P < 0.05, 0.01), thereby inhibiting the activation of renin-angiotensin-aldosterone system (RAAS). C. hexapetala significantly inhibited the expressions of genes and proteins related to AQP/cAMP/CREB pathway (P < 0.05, 0.01, 0.001). Conclusion C. hexapetala may exert acute and long-term diuretic effects by inhibiting AQP/cAMP/CREB pathway in saline loaded rats.