Chinese Traditional and Herbal Drugs

Study on in vitro release and pharmacokinetic of different phases of co-decoction of Scutellariae Radix and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle

ZHANG Shuangchen, HE Yican, ZHANG Nianzhan, CHEN Fangwen, WEI Xinling, SHEN Chengying, YUE Pengfei, SHEN Baode

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3720-3729.

Objective To investigate the compositional distribution, in vitro release, and pharmacokinetic behavior of different phases in the Huangqin (Scutellariae Radix, SR)-Zhigancao (Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, GRRPM) decoction, and to elucidate the physical structural basis for the delayed and enhanced efficacy mediated by herb compatibility. Methods The decoction was separated into nanoparticulate, true solution, and precipitate phases by centrifugation combined with dialysis. The particle size and morphology of these phases were characterized. The contents of major active components baicalin, wogonoside, liquiritin apioside, glycyrrhizic acid, and others were determined by HPLC, and their in vitro release profiles were evaluated. The plasma concentration of baicalin in rats after oral administration of different phases was measured using LC-MS/MS, and pharmacokinetic parameters were calculated. Results Significant differences in particle size and morphology were observed among the phases. The mass fractions of liquiritin apioside, baicalin, wogonoside, and glycyrrhizic acid in each phase decreased in the order: nanoparticulate phase > true solution phase > precipitate phase. All four components showed the highest release from the nanoparticulate phase, followed by the true solution phase, and the lowest release from the precipitate phase. After oral administration of the whole extract and the different phases, the C_max and AUC_0-t of baicalin ranked as follows: nanoparticulate phase > whole extract > true solution phase > precipitate phase. Conclusion The formation of a complex multiphase system in the SR-GRRPM decoction significantly affects the spatial distribution, in vitro release, and pharmacokinetic behavior of the active constituents. This may represent the physical structural basis underlying the delayed and enhanced efficacy resulting from the combination of the two herbs.

Effects of different vinegar processing methods on major constituents and antioxidant activity of Citri Reticulatae Pericarpium Viride

LI Xinyue, ZHANG Lei, YANG Chunguo, XU Lili, WANG Bing, ZHANG Ziru, CUI Weiliang, LI Huifen

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3730-3740.

Objective To investigate the effects of different types of vinegar as processing excipients on the main components and antioxidant activity of Qingpi (Citri Reticulatae Pericarpium Viride, CRPV), aiming to provide a basis for optimizing the vinegar stir-frying processing technology and establishing quality standards for vinegar used as a processing excipient in traditional Chinese medicine. Methods The influence of 20 batches of vinegar as processing excipients on the main components of CRPV was studied using HPLC combined with chemical pattern recognition. The antioxidant activity of CRPV processed with different vinegars was determined by DPPH and ABTS assays. A comprehensive score was calculated by weighting averaging of principal component scores based on their contribution rates. Orthogonal partial least squares-discrimination analysis (OPLS-DA) was employed to identify differential markers for distinguishing different vinegar-processed products. Results A total of 15 common peaks were calibrated in the HPLC of vinegar-processed CRPV, and six flavonoids, including narirutin, hesperidin, didymin, hesperetin, sinensetin, and nobiletin, were identified. Principal component analysis (PCA) indicated that CRPV processed with mature vinegar achieved the highest comprehensive score, followed by those processed with white vinegar, rice vinegar, and balsamic vinegar, respectively. Hesperetin and hesperidin can serve as differential markers to distinguish the different vinegar-processed CRPV products. In vitro antioxidant assays showed that CRPV processed with white vinegar exhibited the strongest DPPH radical scavenging ability, while raw CRPV possessed the optimal ABTS radical scavenging capacity. The antioxidant potency composite (APC) index was highest for the white vinegar-processed product ranked the highest, followed by those processed with aromatic vinegar, rice vinegar, and aged vinegar. Conclusions The type of vinegar excert selective effects on the dissolution and transformation of flavonoid components in CRPV and modulate its antioxidant activity. Mature vinegar is more conducive to the retention of flavonoid components, while white vinegar can significantly enhance its antioxidant capacity. In practical applications, the selection should be tailored according to specific therapeutic objectives.

Optimization of ginger-steamed Amomi Fructus kernels process based on AHP-entropy weight method combined with Box-Behnken response surface methodology and fingerprint study before and after ginger processing

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3741-3752.

Objective To optimize the processing technology for ginger-steamed Sharen (Amomi Fructus, AF) kernels and establish UPLC fingerprints before and after ginger-steaming. Methods Using the contents of volatile oil, bornyl acetate, extracts, 6-gingerol, vanillic acid, epicatechin, and quercitrin as evaluation indicators, the combined AHP-entropy weight method composite weighting method was employed to determine the weight coefficients of each indicator. Combined with the Box-Behnken design-response surface methodology (BBD-RSM), the effects of ginger juice dosage, moistening duration, steaming duration, and drying temperature on the ginger-steaming process of AF kernels were investigated to determine the optimal process parameters. UPLC fingerprints of AF kernels and ginger-steamed AF kernels were established and imported into the “Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System” (2012 edition) for pattern analysis. Chemometrics was used to compare the differences before and after processing. Results The optimal processing conditions for ginger-steamed AF kernels were determined as follows: ginger juice dosage 15%, moistening duration 3 h, steaming duration 38 min, drying temperature 60 ℃. Comparative analysis of the fingerprints before and after processing identified two differential components, which were ranked by variable importance projection (VIP) value as peak 6 (vanillic acid) > peak 8. Conclusion The optimized processing technology of ginger-steamed AF kernels is stable, reliable and reproducible. The method of UPLC fingerprint combined with chemometrics to screen quality difference markers before and after processing is simple and convenient, which can provide a scientific reference for the quality control and evaluation of ginger-steamed AF kernels.

Optimization of processing technology for Mume Fructus flesh based on entropy weight method combined with analytic hierarchy process and back propagation neural network

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3753-3763.

Objective To optimize the best processing technology of Wumei (Mume Fructus, MF) flesh and determine the best processing parameters. Methods The contents of 5-hydroxymethylfurfural (5-HMF), neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and caffeic acid were determined by HPLC. The content of polysaccharide in MF flesh was determined by ultraviolet-visible spectrophotometer. The content of each chemical component, the content of water-soluble extracts and the appearance traits were selected as the evaluation indexes, and the weight coefficient of each evaluation index was determined by analytic hierarchy process (AHP)-entropy weight method hybrid weighting method. The L₉(3⁴) orthogonal test was carried out with water addition, moistening time and steaming time as factors. Back propagation neural network (BPNN) was used to predict and verify the optimal processing parameters of MF flesh. Results The BPNN optimization process was superior to the orthogonal screening process, and the prediction results were stable and reliable. The composite score was the highest, which was 83.26. The best steaming process of MF flesh was 22.5 kg of water per 100 kg of MF flesh, moistening for 60 min, and steaming for 30 min. Conclusion The determined processing technology of MF flesh is scientific and feasible, which can provide scientific data support for the industrial production of decoction pieces, and also provide a theoretical basis for ensuring the quality and clinical application of MF flesh.

Optimization of extraction process for classical prescription Xuefu Zhuyu Decoction based on standard relation and entropy weight-TOPSIS method

HUANG Yan, LUO Fei, HE Zhoufeng, FU Wenrui, HUANG Xueyan, PENG Qian, GUO Yinyin, WEI Shuchang

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3764-3777.

Objective To select the optimal alcohol extraction process for the classic prescription Xuefu Zhuyu Decoction (XZD, 血府逐瘀汤), enabling the retention of small-molecule substances in traditional aqueous extracts, thereby providing experimental basis for the development of transdermal formulations. Methods The contents of 12 active components (adenosine, catalpol, amygdalin, hydroxysafflor yellow A, paeoniflorin, ferulic acid, liquiritin, narirutin, naringin, hesperidin, neohesperidin, glycyrrhizic acid) in XZD, the extract yield, and the fingerprint similarity were used as critical quality attributes (CQAs). Ethanol concentration, extraction time, and solvent ratio were selected as critical process parameters (CPPs), and experiments were conducted using a Box-Behnken design-response surface methodology (BBD-RSM). The benchmark correlation degree of each experimental sample index was calculated, and the weights of each CQA were determined using the entropy weight method to compute a comprehensive score. The TOPSIS model was applied to calculate the relative closeness of each sample to the benchmark sample and rank them, with the optimal alcohol extraction process screened based on the comprehensive score. Additionally, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was used to description the chemical components of the benchmark sample and the optimal alcohol extraction process sample, further verifying retention effect of small-molecule components.. Results Analysis using the entropy weight-TOPSIS model determined the optimal alcohol extraction process for XZD as follows: ten times the amount of 60% ethanol, with each extraction lastin 3 h. The average comprehensive score of three validation samples reached 0.501, with RSD of 0.75%, which met the requirements and confirmed that the process was stable and the method was applicable. Meanwhile, UPLC-Q-TOF-MS/MS analysis showed that the main chemical composition of the optimal process sample were similar to those of the benchmark sample. Conclusion The comprehensive screening strategy based on the benchmark correlation degree and entropy weight-TOPSIS model is feasible and effective. The obtained XZD alcohol extraction process parameters are robust and reliable, and the small molecule substances of the benchmark decoction can be effectively retained. The chemical substance basis is similar to that of the benchmark decoction. This study can provide a reference for the research and development of XZD transdermal formulations.

Lentinan-buddleoside self-assembled nanoparticles: Preparation, pharmacokinetics and acute toxicity evaluation

LI Xiaomeng, GAO Qing, WANG Gaili, CUI Xiaoge, ZHENG Wumei, WAN Yacun, FU Zhenna, LI Yangjie

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3778-3791.

Objective To prepare lentinan-buddleoside self-assembled nanoparticles (Len-Bud-SANs), and evaluate investigate its physicochemical properties, oral pharmacokinetic behavior and acute toxicity. Methods Len-Bud-SANs were prepared by self-assembled method. Envelopment efficiency, drug loading and particle size were employed as indicators, single factor experiments combined with Box-Behnken design-response surface method (BBD-RSM) were used to obtainoptimal prescriptions of Len-Bud-SANs. The appearance of Len-Bud-SANs was observed by transmission electron microscope (TEM) was, crystal form of Len-Bud-SANs powder was analyzed by X-ray powder diffraction (XRPD). Molecular simulation docking and Fourier transform infrared spectroscopy (FTIR) were used to study the binding mechanism between lentinan and buddleoside. The solubility and drug release behavior of Len-Bud-SANs were determined in phosphate buffer solution (PBS) at pH 2.0 and pH 6.8. SD rats in each group were administered intragastrically with buddleoside suspension and Len-Bud-SANs powder, then buddleoside concentration in plasma was analyzed by HPLC method, and main pharmacokinetic parameters were calculated. Safety evaluation of Len-Bud-SANs powder was performed by indicators of body weight, food intake, thymus index and spleen index. Pathological conditions of the important organs were observed by hematoxylin-eosin (HE) staining. Results Optimal formulation of Len-Bud-SANs: mass fraction of lentinan was 0.39%, preparation temperature was 65.00 ℃, and preparation time was 1.50 h. Envelopment efficiency, drug loading, particle size and ζ potential were (88.57 ±0.83)%, (8.02 ±0.11)%, (57.54 ±4.90) nm and (−32.10 ±1.36) mV, respectively. Microscopic appearance of Len-Bud-SANs was spherical, and buddleoside existed as an amorphous form in Len-Bud-SANs powder. Solubility of Len-Bud-SANs in phosphate buffer solution of pH 2.0 and pH 6.8 was increased to 59.89 times and 42.95 times, and cumulative release rate were increased to 90.80% and 91.73%, respectively. Drug release behavior of Len-Bud-SANs conformed to Weibull model. Oral pharmacokinetic results showed that t_1/2 of Len-Bud-SANs was increased to (4.45 ±0.80) h, C_max and AUC_0-t were increased to 3.00-fold and 5.60-fold. Compared with the blank group, there was no significant change in body weight, food intake, thymus index, spleen index and pathology of important organs in the Len-Bud-SANs group. Conclusion Len-Bud-SANs significantly promoted oral absorption of buddleoside effectively, and no obvious toxicity was observed, which laid the foundation for subsequent research and development.

Antidepressant mechanism of nasal inhalation of Chuanxiong Rhizoma oil in modulating BDNF/TrkB/CREB pathway and remodelling gut microbiota

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3792-3806.

Objective To investigate the effect and mechanism of Chuanxiong (Chuanxiong Rhizoma) oil inhalation via nasal administration on chronic unpredictable mild stress (CUMS)-induced depressive mice. Methods The main components of Chuanxiong Rhizoma oil were identified by gas chromatography-mass spectrometry (GC-MS). A CUMS-induced depressive mouse model was established, and after drug intervention, the pharmacological effects of Chuanxiong Rhizoma oil were evaluated through behavioral tests, hematoxylin-eosin (HE) staining and Nissl staining. Mechanistic studies were conducted using ELISA, Western blotting, qRT-PCR and 16S rRNA. Results GC-MS identified Z-ligustilide and senkyunolide A as the primary components of Chuanxiong Rhizoma oil. Nasal inhalation of Chuanxiong Rhizoma oil significantly alleviated depressive-like behaviors in CUMS mice (P < 0.05, 0.01), reduced hippocampal neuronal damage, upregulated the expressions of brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB)/cAMP-response element binding protein (CREB) signaling pathway related proteins in hippocampus (P < 0.05, 0.01), elevated levels of monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT) and norepinephrine (NE) (P < 0.05, 0.01), inhibited the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis (P < 0.05, 0.01), suppressed pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) in colon tissue (P < 0.05, 0.01), enhanced barrier function (P < 0.05, 0.01), and significantly ameliorated CUMS-induced gut microbiota dysbiosis. The CREB-specific inhibitor 666-15 significantly reversed the antidepressant effects of Chuanxiong Rhizoma oil (P < 0.01). Conclusion Nasal inhalation of Chuanxiong Rhizoma oil alleviates depression by improving gut dysfunction through BDNF/TrkB/CREB pathway.

Muscone ameliorates cisplatin-induced acute kidney injury by inhibiting apoptosis of renal tubular epithelial cells via promotion of p53 ubiquitination

ZHANG Haiyan, XUE Chen, MA Jingru, GUO Jiaqi, SHI Jianyu, SUI Yang, LIU Haijing, WANG Changhe, ZHANG Zhen

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3807-3817.

Objective To explore the mechanism by which muscone improves cisplatin-induced acute kidney injury (AKI). Methods C57BL/6J mice were randomly divided into control group, model group, dexamethasone (2 mg/kg) group, muscone low-, medium-, and high-dose (24, 36, 48 mg/kg) groups, a cisplatin-induced AKI mouse model was established. After drug intervention, renal tissue pathological changes were observed using hematoxylin-eosin (HE) staining. Immunohistochemistry was used to detect the expressions and distribution of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were detected. Immunofluorescence staining was used to detect the expression and distribution of cleaved cysteine aspartate protease-3 (cleaved Caspase-3) in renal tissue. An NRK-52E cell injury model induced by cisplatin was established, the effects of cisplatin, muscone and p53 inhibitor pifithrin-μ on cell viability were detected using MTT assay. The morphological change of cells was observed under an inverted microscope. Calcein AM/PI staining was used to observe cell death. Hoechest 33342 staining was used to observe the fragmentation of cell nuclei. Cell death types was observed using transmission electron microscopy. Immunofluorescence staining was used to detect the expression and distribution of p53. Western blotting was used to detect the expressions of Caspase-3, cleaved Caspase-3 and p53. MitoSOX staining was used to detect the levels of mitochondrial reactive oxygen species (mtROS). Immunoprecipitation was used to detect the level of p53 ubiquitination modification. Results Muscone significantly reduced the renal pathological damage caused by cisplatin, restored the morphology of renal tubules (P < 0.01), decreased the expressions and distribution of NGAL, Kim-1 and cleaved Caspase-3 in renal tissue (P < 0.01), reduced the levels of BUN and SCr (P < 0.01). Muscone and pifithrin-μ significantly inhibited cisplatin-induced apoptosis and mtROS level in NRK-52E cells (P < 0.01), upregulated Caspase-3 protein expression (P < 0.05, 0.01), downregulated cleaved Caspase-3 and p53 protein expressions (P < 0.05, 0.01), and promoted p53 ubiquitination modification (P < 0.05). Conclusion Muscone inhibits apoptosis of renal tubular epithelial cells by promoting p53 ubiquitination modification, thereby improving cisplatin-induced AKI.

Mechanism of Diterpene Ginkgolides Meglumine Injection in regulating platelet production and activation during acute phase of ischemic stroke

DAI Wenjing, LYU Wenxin, ZHAN Le, YAN Changyang, WU Ziyin, ZHAO Binjiang, CAO Liang, XIAO Wei, SUN Yuqin, WANG Zhenzhong

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3818-3830.

Objective To explore the mechanism of Diterpene Ginkgolides Meglumine Injection (银杏二萜内酯葡胺注射液, DGMI) in treatment of acute ischemic stroke (IS) based on platelet generation and activation. Methods Sham group, model group, ibrutinib (10 mg/kg) group, DGMI low-, medium- and high-dose (6.25, 12.50, 25.00 mg/kg) groups were established. A transient middle cerebral artery occlusion (tMCAO) model was prepared in C57BL/6 mice using suture method. Medication was administered continuously for 3 d starting 0.5 h after surgery. The infarct rate was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Motor and neurological function were evaluated using spinning rod experiment and Bederson score. Flow cytometry and ELISA were used to detect the whole blood platelet count and platelet factor 4 (PF4) level in serum. Bone marrow smears and immunohistochemistry were used to observe the proliferation, differentiation, apoptosis and phosphorylation levels of focal adhesion kinase (FAK) in bone marrow megakaryocytes. Immunofluorescence staining was used to detect platelet activation and FAK phosphorylation levels in brain tissue. A combination group of FAK agonist ZINC40099027 (ZIN) and medium-dose DGMI was set up to verify whether DGMI exerts a protective effect by inhibiting FAK activation. Results DGMI significantly reduced cerebral infarction and megakaryocyte generation in tMCAO mice. Among them, the inhibitory effect of medium-dose DGMI on differentiation and proliferation of bone marrow megakaryocytes in tMCAO mice, as well as the improvement of cerebral infarction area, motor coordination ability and neurological function score were the most significant (P < 0.05, 0.01, 0.001). In addition, DGMI could significantly reduce the number of platelets and PF4 level in serum of tMCAO mice (P < 0.05, 0.001), and inhibit the phosphorylation of FAK in bone marrow megakaryocytes and infiltrating platelets in brain (P < 0.01, 0.001). The FAK agonist ZIN significantly reversed the protective effects of DGMI on tMCAO mice (P < 0.05, 0.01, 0.001). Conclusion DGMI exerts neuroprotective effects by inhibiting the excessive generation of megakaryocytes during the acute phase of IS and the phosphorylation of FAK in infiltrating platelets in the brain, thereby suppressing platelet generation and activation.

Phase separation of classic prescription Baoyuan Decoction and screening of effective phases for alleviating exercise-induced fatigue in rats

Chinese Traditional and Herbal Drugs. 2026, 57(10): 3831-3847.

Objective To split the classic prescription Baoyuan Decoction (保元汤) into different phases, study the relieving effects of different phases on exercise fatigue in rats, and screen for their effective phases. Methods The gradient centrifugation dialysis method was used to separate Baoyuan Decoction into the nano phase (BD nano phase, BD-N), precipitation phase (BD-P) and solution phase (BD-S). The appearance was physically characterized and contents of main ingredients was determined. A rat swimming fatigue model was established, control group, model group, positive control (Dazhu Hongjingtian Capsule) group, Baoyuan Decoction group, BD-N group and BD-P group were set up, active phases was screened by measuring behavioral indicators, organ indices, serum biochemical indicators, and pathological changes in liver and muscle tissues. Based on combined analysis of gut microbiome, metabolomics and transcriptomics, the potential mechanism of Baoyuan Decoction and its effective phase in alleviating exercise fatigue in rats was explored. Four differentially expressed genes (Gck, Ackr3, Pde4b, Ppp1r3b) were randomly selected for qRT-PCR validation. Results The particle morphology of BD-N was spherical and Tyndall effect was significant. The particle size was in the order of BD-P > Baoyuan Decoction > BD-N. The polydispersity index (PDI) of each phase was in the order of Baoyuan Decoction > BD-N > BD-P. The absolute value of zeta potential for each phase was BD-P > BD-N > Baoyuan Decoction. Ginsenoside Rb₁, calycosin-7- O-β-D-glucoside, liquiritin, ammonium glycyrrhizinate, cinnamic acid, cinnamaldehyde and 6-gingerol were mainly distributed in BD-N. The comprehensive efficacy ranking was Baoyuan Decoction ≈ positive control drug > BD-N > BD-P. The ability of BD-N in regulating the abundance of gut microbiota, increasing the level of Lactobacillus genus and regulating 45 differential metabolites related to fatigue was similar to Baoyuan Decoction. The qRT-PCR results showed that the regulatory trends of BD-N and Baoyuan Decoction on four genes were consistent with the transcriptome sequencing results. Conclusion From the perspective of physics, chemistry and pharmacological effects, the effective phase of Baoyuan Decoction in relieving fatigue is screened, and BD-N is the effective phase of Baoyuan Decoction in relieving fatigue.