1.Clinical Diseases Responding Specially to TCM Treatment: Psoriasis
Liu LIU ; Xiaoying SUN ; Mei MO ; Yaqiong ZHOU ; Bin LI ; Xiaoxiao ZHANG ; Xin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):260-268
Psoriasis is a common chronic inflammatory systemic disease in dermatology. Its high prevalence, recurrence rate, and numerous comorbidities impose a significant physical and mental burden on patients. With the continuous advancement of modern medicine, the emergence of biological agents has improved clinical efficacy, making it possible to overcome psoriasis, in addition to classical treatments. However, in clinical practice, adverse reactions, drug resistance, recurrence rates, and immune drift cannot be ignored. Traditional Chinese medicine (TCM) has a history of thousands of years in treating psoriasis, demonstrating good efficacy, high safety, and a low recurrence rate, but a standardized management system is lacking. Therefore, the 25th Clinical Diseases Responding Specially to TCM Treatment Series (Psoriasis) Youth Salon, hosted by the Chinese Association of Chinese Medicine and organized by the Youth Committee of the Chinese Association of Chinese Medicine, invited 29 experts and scholars from TCM, Western medicine, and interdisciplinary fields to actively discuss the "Advantages, Challenges, and Clinical Transformation of TCM and Western Medicine in the Diagnosis and Treatment of Psoriasis". The experts at the meeting concluded that the advantages of TCM in the treatment of psoriasis are as follows. Firstly, in the TCM-led treatment plan, TCM's understanding of psoriasis follows the principle of combining the differentiation of disease and syndrome. This approach distinguishes the basic contradiction from the current main contradiction and enables a clear grasp of the dynamic process of psoriasis development. Based on the system of syndrome differentiation and treatment, TCM intervention is applied to address the current main contradiction, and the optimal TCM treatment plan is formulated by combining internal and external treatments. Adhering to the principle of "what is visible outside must be addressed inside", TCM can prevent and treat psoriasis comorbidities early by differentiating syndrome types. Secondly, in the integrated TCM and Western medicine treatment plan, the combination of both methods not only enhances efficacy but also reduces the adverse reactions of immunosuppressants and biological agents, lowering the recurrence rate. This conference provides a reference for the diagnosis and treatment of psoriasis using TCM and integrated TCM and Western medicine, opening up new ideas for clinical and basic research and guiding future research directions.
2.Exploring Mechanism of Hei Xiaoyaosan Regulating PI3K/Akt Pathway to Improve Learning and Memory Ability of Insomnia Rats with Liver Depression Syndrome Based on Transcriptomics
Jiamin LIU ; Yale WANG ; Hai HUANG ; Yue LI ; Xin FAN ; Pengpeng LIANG ; Shizhao ZHANG ; Mei YAN ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):114-125
ObjectiveBased on transcriptomics, to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group, model group, eszopiclone group (0.09 mg·kg-1), and low, medium, and high dose groups of Hei Xiaoyaosan (3.82, 7.65, 15.30 g·kg-1), with ten rats in each group. Except for the blank group, the other groups were induced insomnia rat model with liver depression by chronic restraint, tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine (PCPA). Each treatment group received intragastric administration according to the specified dosage, once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test, open field test, and Morris water maze test were used to test the sleep quality, depressive-like behavior, and learning and memory abilities of rats. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nitric oxide (NO) in hippocampus. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of the hippocampal tissue, while terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group, as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersecting genes. Subsequently, the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to assess the mRNA expression levels of phosphatase and tensin homolog (PTEN), B-cell lymphoma-2 (Bcl-2)-like protein 11 (BCL2L11), and mitogen-activated protein kinase 1 (MAPK1) in hippocampus, and Western blot was employed to evaluate the protein expressions of PI3K, phosphorylation (p)-PI3K, Akt, p-Akt, Bcl-2, Bcl-2-associated X protein (Bax), and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group, the model group exhibited a reduction in body weight, an increase in sleep latency, and a decrease in sleep duration (P<0.01). Additionally, rats showed obvious depression-like behavior, and their learning and memory abilities decreased. Furthermore, the contents of 5-HT, GABA, NO, BDNF and GDNF in hippocampus decreased (P<0.01). Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus, characterized by irregular cell shapes, a reduced cell count, deeply stained and pyknotic nuclei, increased vacuolar degeneration, and an elevated apoptosis rate (P<0.01). Compared with the model group, the body weight of the high and medium dose groups of Hei Xiaoyaosan increased, the sleep latency shortened and the sleep time prolonged (P<0.05, P<0.01). Additionally, depression-like behavior and learning and memory abilities of rats were significantly improved, the levels of 5-HT, GABA, NO, BDNF and GDNF in the hippocampus increased (P<0.05, P<0.01). These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons (P<0.01). Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN, BCL2L11, and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group, the expression levels of PTEN, BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased (P<0.01), while the protein expression levels of p-PI3K, p-Akt and Bcl-2 were decreased (P<0.01), and the protein expression levels of PTEN, Bax and cleaved Caspase-3 were increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN, BCL2L11 and MAPK1 mRNAs (P<0.01), up-regulate the expressions of p-PI3K, p-Akt and Bcl-2 proteins (P<0.01), and down-regulate the protein expressions of PTEN, Bax and cleaved Caspase-3 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN, BCL2L11 and MAPK1, and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.
3.Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultra-sound irradiation on M109 cells in vitro and in vivo
Hailiang ZHANG ; Xiaoyu ZHAO ; Jiahua MEI ; Rui PAN ; Junze TANG ; Kun YU ; Rui XUE ; Xiaofei LI ; Xin CHENG
China Pharmacy 2025;36(14):1730-1736
OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles (FA-Cre@PEG- PLGA NPs, hereinafter referred to as “NPs”) combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration, and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells, and the best ultrasound time was selected. Using human lung cancer A549 cells as a control, the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration, invasion, apoptosis, cell cycle and reactive oxygen species (ROS) levels of M109 cells were detected by cell scratch test, Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration; the changes of mitochondrial membrane potential (MMP) were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed, and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells, and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells, and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells, the uptake rate of NPs in M109 cells was significantly higher (P<0.01), and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group, the apoptosis rate of M109 cells and ROS level were increased significantly (P<0.01), while the MMP decreased significantly (P<0.01) in the different concentration (100, 200, 300 μg/mL) groups of M109 cells. Compared with the mice in non-ultrasound group, the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced (P<0.05 or P<0.01). CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo, the anti-tumor mechanism includes inhibiting cell migration and invasion, blocking cell cycle, and inducing apoptosis.
4.Analysis and application thinking of standards for 500 kinds of traditional Chinese medicine formula granules on base of industrial practice.
Yong LIU ; Jun ZHANG ; Xin-Hai DONG ; Lin ZHOU ; Dong-Mei SUN ; Fu-Lin MAO ; Zhen-Yu LI ; Lei HUANG ; Jin-Lai LIU
China Journal of Chinese Materia Medica 2025;50(5):1427-1436
Following the release of the Technical Requirements on Quality Control and Standard Establishment of Traditional Chinese Medicine Formula Granules by the National Medical Products Administration in 2021, Chinese Pharmacopoeia Commission has promulgated 296 national drug standards so far, and most provinces have started the work of establishing provincial standards as supplements. The promulgation of standards fostered high-quality development of the industry. Since the implementation of national and provincial standards for more than three years, enterprises have gained deep understanding and hands-on experiences on the characteristics, technical requirements, production process, and quality control of traditional Chinese medicine(TCM) formula granules. Meanwhile, challenges have emerged restricting the high-quality development of this industry, including how to formulate quality control strategies for medicinal materials and decoction pieces, how to reduce manufacturing costs, and how to improve the pass rate and product stability under high standards. Based on the work experiences from standard management and process research, this article analyzed the distribution of sources, processing methods, dry extract rate ranges, process requirements for volatile oil-containing decoction pieces, control measures of safety indices, characteristics and trends of setting characteristic chromatograms or fingerprints, characteristics and trends of setting content ranges, and main differences between national standards and provincial standards. On the one hand, this article aims to present main characteristics for deeply understanding different indicators in standards and provide basic ideas for establishing quality and process control systems. On the other hand, from the perspective of industrial practice, suggestions are put forward on the important aspects that need to be focused on in the quality and process control of TCM formula granules.
Drugs, Chinese Herbal/chemistry*
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Quality Control
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Medicine, Chinese Traditional/standards*
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China
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Drug Industry/standards*
5.Pharmacological effect and mechanism of tannic acids in Paeoniae Radix Alba.
Jia-Xin DIAO ; Qi-Tong ZHENG ; Meng-Yao CHEN ; Jiang-Chuan HONG ; Min HAO ; Qing-Mei FENG ; Jun-Qi HU ; Xia-Nan SANG ; Gang CAO
China Journal of Chinese Materia Medica 2025;50(6):1471-1483
The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry*
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Tannins/chemistry*
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Humans
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Drugs, Chinese Herbal/chemistry*
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Animals
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Plant Extracts
6.Phenylpropanoids from roots of Berberis polyantha.
Dong-Mei SHA ; Shuai-Cong NI ; Li-Niu SHA-MA ; Hai-Xiao-Lin-Mo MA ; Xiao-Yong HE ; Bin HE ; Shao-Shan ZHANG ; Ying LI ; Jing WEN ; Yuan LIU ; Xin-Jia YAN
China Journal of Chinese Materia Medica 2025;50(6):1564-1568
The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry*
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Animals
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Mice
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Berberis/chemistry*
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RAW 264.7 Cells
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Macrophages/immunology*
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Drugs, Chinese Herbal/isolation & purification*
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Nitric Oxide/metabolism*
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Molecular Structure
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Anti-Inflammatory Agents/isolation & purification*
7.Processing technology of calcined Magnetitum based on concept of QbD and its XRD characteristic spectra.
De-Wen ZENG ; Jing-Wei ZHOU ; Tian-Xing HE ; Yu-Mei CHEN ; Huan-Huan XU ; Jian FENG ; Yue YANG ; Xin CHEN ; Jia-Liang ZOU ; Lin CHEN ; Hong-Ping CHEN ; Shi-Lin CHEN ; Yuan HU ; You-Ping LIU
China Journal of Chinese Materia Medica 2025;50(9):2391-2403
Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods*
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Drugs, Chinese Herbal/chemistry*
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Quality Control
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Particle Size
8.Mechanism of Euphorbiae Ebracteolatae Radix processed by milk in reducing intestinal toxicity.
Chang-Li SHEN ; Hao WU ; Hong-Li YU ; Hong-Mei WEN ; Xiao-Bing CUI ; Hui-Min BIAN ; Tong-la-Ga LI ; Min ZENG ; Yan-Qing XU ; Yu-Xin GU
China Journal of Chinese Materia Medica 2025;50(12):3204-3213
This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals
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Mice
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Milk/chemistry*
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Drugs, Chinese Herbal/chemistry*
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Male
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Tumor Necrosis Factor-alpha/immunology*
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Intestines/drug effects*
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Interleukin-1beta/immunology*
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Tandem Mass Spectrometry
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Female
9.Mechanism of Maxiong Powder in inhibiting Epac1-Piezo2 signaling pathway in medial habenular nucleus-interpeduncular nucleus of rats with neuropathic pain.
Xin-Yuan WANG ; Zhi CHEN ; Ying LIU ; Jian SUN ; Ru-Jie LI ; Zhi-Guo WANG ; Mei-Yu ZHANG
China Journal of Chinese Materia Medica 2025;50(10):2719-2729
Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals
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Neuralgia/genetics*
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Rats
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Signal Transduction/drug effects*
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Male
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Rats, Sprague-Dawley
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Guanine Nucleotide Exchange Factors/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Habenula/drug effects*
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Ion Channels/genetics*
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Humans
10.Effect of Wenpi Pills on lipid metabolism in mice with non-alcoholic fatty liver disease induced by various diets.
Chen-Fang ZHANG ; Kai LIU ; Chao-Wen FAN ; Mei-Ting TAI ; Xin ZHANG ; Rong ZHANG ; Qin-Wen CHEN ; Zun-Li KE
China Journal of Chinese Materia Medica 2025;50(10):2730-2739
The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP_L), and high-dose WPP group(15.5 g·kg~(-1), WPP_H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP_H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals
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Non-alcoholic Fatty Liver Disease/genetics*
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Lipid Metabolism/drug effects*
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Mice
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Mice, Inbred C57BL
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Diet, High-Fat/adverse effects*
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Liver/drug effects*
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Humans
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Disease Models, Animal
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Methionine

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