Chinese Medicine最新文献

Epilepsy, one of the most common neurological diseases, affects more than 70 million people worldwide. Anti-seizure drugs targeting membrane ion channels or GABAergic neurotransmission are the first choices for controlling seizures, whereas the high incidence of pharmacoresistance and adverse effects largely restrict the availability of current anti-seizure drugs (ASDs). Traditional Chinese Medicine (TCM) has shown historical evidence-based therapeutic effects for neurological diseases including epilepsy. But until the late 1990s, great efforts in both clinical and experimental fields advanced TCM interventions for epilepsy from evidence-based practices to more systematic neuropharmacological significance, and show new lights on preferable management of epilepsy in the last decade. This review summarized the advances of applying TCM interventions (ranging from herbal medicines and their active ingredients to other strategies such as acupuncture) for epilepsy, followed by associated mechanism theories. The therapeutic potential of TCM interventions for epilepsy as well as its comorbidities turns from somehow debatable to hopeful. Finally, some prospects and directions were proposed to drive further clinical translational research. The future directions of TCM should aim at not only deriving specific anti-epileptic molecules but also illustrating more precise mechanisms with the assistance of advanced multifaceted experimental tools.

Classical prescriptions of Chinese medicine represent the crystallized wisdom of millennia of clinical practice, enduring as cornerstones of therapeutic intervention due to their demonstrated efficacy across generations. Their evolving role in modern healthcare systems reflects shifting disease patterns, scientific advancements, and global health priorities. Banxia Xiexin Decoction (BXD), formulated by Zhang Zhongjing in the Treatise on Febrile and Miscellaneous Diseases (Shanghanlun), is a time-honored classical prescription renowned for its therapeutic versatility in managing gastrointestinal disorders, both in China and internationally. Recent advancements in clinical research and pharmacological studies on BXD underscore the necessity for a comprehensive bibliometric analysis to summarize and elucidate its specific clinical benefits. Through an extensive literature review of publications from the Web of Science, PubMed, Scopus, and the China National Knowledge Infrastructure (CNKI) between 1997 and 2024, 11 major categories of clinical applications for BXD were identified, along with an analysis of the potential pharmacological mechanisms, such as chronic gastritis, functional dyspepsia, and inflammatory bowel disease. We believe this review will provide new insights into the understanding of clinical value of BXD and identify potential future perspectives for its research and development.

Background: Liver fibrosis is a representative scarring response that can ultimately lead to liver cancer. However, relevant antifibrotic drugs for the effective treatment of liver fibrosis in humans have not yet been identified. Chikusetsusaponin IVa (CS-IVa) is derived from natural products and exhibits multiple biological activities; however, its efficacy and potential mechanism of action against liver fibrosis remains unclear.

Purpose: This study aimed to examine the antifibrotic properties and potential mechanisms of action of CS-IVa.

Methods: We constructed two mature mouse models (CCl₄ challenge and bile duct ligation) to evaluate the antifibrotic properties of CS-IVa in vivo. Proteomics analysis and transforming growth factor β1 (TGF-β1)-activated LX-2 cells were used to elucidate the potential effects and mechanisms. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to detect the affinity and binding between CS-IVa and its target.

Results: We found that CS-IVa significantly alleviated liver fibrosis and injury by downregulating yes-associated protein (YAP) and tafazzin (TAZ) expression. In an in vitro model, CS-IVa suppressed TGF-β1-induced hepatic stellate cell (HSC) activation, as well as the mRNA and protein expression of COL1A1, α-SMA, YAP, and TAZ. Moreover, specific knockdown or inhibition of YAP did not enhance the suppressive effect of CS-IVa on HSC activation or fibrosis-associated protein expression. Molecular docking, SPR, and CETSA showed that CS-IVa could directly bind to YAP.

Conclusion: These findings demonstrated that the administration of CS-IVa effectively alleviated liver fibrosis by suppressing the YAP/TAZ pathways. In addition, CS-IVa could directly bind to YAP and act as a YAP inhibitor.

Background: Castration-resistant prostate cancer (CRPC) has been a major cause of tumor-associated death among men worldwide. The discovery of novel therapeutic medicines for CRPC remains imperative. Atractylenolide I (ATR-I), a prominent bioactive component from Atractylodes macrocephala, exhibits powerful anticancer potentials in various malignancies. Nevertheless, the ATR-I's activity on CRPC has not been reported.

Methods: An enzalutamide-resistant (EnzR) cell line was successfully constructed. CCK-8, EdU, wound healing, Transwell assays, flow cytometry, and xenograft tumor models were applied to investigate the antitumor activity of ATR-I against CRPC. The changes in the gene expression profiles after ATR-I treatment were analyzed using RNA sequencing.

Results: ATR-I suppressed the proliferative and migratory abilities of AR⁺ and AR^- CRPC cells, while triggering cell cycle arrest and apoptosis. ATR-I also exerted anti-cancer activity on EnzR cell lines. Intriguingly, a combination of ATR-I with enzalutamide synergistically induced more apoptosis of tumor cells. RNA-sequencing identified kinesin family member 15 (KIF15) as a potential target of ATR-I. KIF15 was up-regulated in prostate cancer (PCa), and its higher level was associated with poorer clinical outcomes. Further investigation showed that ATR-I mediated ubiquitin-proteasomal degradation of AR/AR-V7 through targeting KIF15, resulting in CRPC repression. Finally, our in vivo experiment verified that ATR-I alone or in combination with enzalutamide retarded the growth of EnzR xenograft tumors.

Conclusions: These findings identified ATR-I as a promising therapeutic drug for overcoming enzalutamide resistance in CRPC patients and increased our understanding about its antitumor mechanisms.

Background: Pyrrolizidine alkaloids (PAs), recognized globally for their hepatotoxic properties, significantly contribute to liver damage through an imbalance in bile acid homeostasis. Addressing this imbalance is crucial for therapeutic interventions in PA-related liver injuries. Chlorogenic acid (Cga), a phenolic compound derived from medicinal plants, has demonstrated hepato-protective effects across a spectrum of liver disorders. The specific influence and underlying mechanisms by which Cga mitigates PA-induced liver damage have not been clearly defined.

Materials and methods: To explore the protective effects of Cga against acute PA toxicity, a murine model was established. The influence of Cga on bile acid metabolism was confirmed through a variety of molecular biology techniques. These included RNA sequencing, western blotting, and immunoprecipitation, along with quantitative analyses of bile acid concentrations.

Results: Our findings indicate that Cga enhances sirtuin 1 (SIRT1) activation and increases farnesoid X receptor (FXR) signaling, which are crucial for maintaining bile acid balance in PA-induced hepatic injury. When mice subjected to PA-induced hepatic injury were treated with SIRT1 inhibitors alongside Cga, the hepatoprotective effects of Cga were significantly reduced. In Fxr-KO mice, the ability of Cga to mitigate liver damage induced by PAs was substantially reduced, which underscores the role of the SIRT1/FXR signaling axis in mediating the protective effects of Cga.

Conclusion: Our research suggests that Cga can serve as an effective treatment for PA-mediated hepatotoxicity. It appears that influencing the SIRT1/FXR signaling pathway might provide an innovative pharmacological approach to address liver damage caused by PAs.

Background: Shi Zheng (SZ, syndrome of dampness) is a major syndrome type in traditional Chinese Medicine (TCM), the ambiguity of its pathomechanism and the lack of blood diagnostic indicators have limited the understanding of the development of SZ.

Purpose: To explore the pathological mechanism of SZ and establish a symptom-centered diagnosis and treatment model.

Methods: We recruited 250 participants, including healthy individuals and patients diagnosed with SZ. Serum metabolomics and proteomics analyses were performed to screen common pathways. Along with the biological significance of common pathways, a common pathway-symptom correlation diagram was constructed to elucidate the pathological mechanism underlying the occurrence and development of SZ. The enrichment score and correlations with SZ main symptom was used to screen the key common pathways. The key common pathways related to differential metabolites and proteins were used to establish a multi-index diagnostic model and protein therapy target group.

Results: Joint metabolomics and proteomics analyses revealed 18 common pathways associated with symptoms. Six key pathways, such as pathogenic Escherichia coli infection, rheumatoid arthritis, PPAR signaling pathway, bile secretion, GnRH signaling pathway, and fat digestion and absorption were correlated with the main symptoms of SZ. These symptoms included greasy/thick/slippery tongue coating, heavy head, heavy body, heavy limbs, heavy joints, greasy hair, sticky mouth, sticky stool, and damp scrotum. Moreover, seven differential metabolites related to the key pathways were identified: LysoPA (20:3(5Z,8Z,11Z)/0:0), prostaglandin E2, leukotriene B4, lithocholate 3-O-glucuronide, 3-hydroxyquinine, lithocholic acid glycine conjugate, and PA(18:0/22:6(5Z,8E,10Z,13Z,15E,19Z)-2OH(7S, 17S)), and the combined diagnostic value of the seven indicators was the highest (discovery cohort: AUC = 0.90; validation cohort: AUC = 0.99). There were 23 differential proteins related to the key pathways, and six protein targets were identified, including RHOA, TNFSF13, PRKCD, APOA2, ATP1A1, and FABP1.

Conclusion: The combined analysis of metabolomics and proteomics established a symptom-centered diagnosis and treatment model of Shi Zheng.

Background: Fructus Viticis Total Flavonoids (FVTF) is a novel candidate preparation that possesses anticancer activity. However, the role and mechanism of FVTF-inhibiting human hepatocellular carcinoma (HCC) cell stem properties is unclear.

Methods: Liquid chromatography (LC) in conjugation with mass spectrometer (MS) was used to identify the compounds of FVTF. Tumorsphere and soft agar colony formation ability, cancer stem marker expression levels, CD133⁺ cell percentage, and a xenograft model were utilized to investigate the impact of FVTF on HCC cells stemness. PCR array and qRT-PCR were conducted to identify differentially expressed cancer stem-related genes and miRNAs between FVTF-treated and untreated HCC cells, respectively. Pyrosequencing was conducted to assess the DNA methylation level of the miR-34a-5p promoter. A luciferase reporter assay was performed to verify whether FoxM1 serves as a direct target of miR-34a-5p. Additionally, immunohistochemistry of an HCC tissue microarray was carried out to assess the expression levels of DNMT1, FoxM1, and miR-34a-5p.

Results: A total of 26 compounds, including 10 flavones, in FVTF were identified. FVTF significantly reduced the ability of tumorsphere and soft agar colony formation, the levels of CD44 protein and BMI1, OCT4 and SOX2 mRNAs in HCC cells, and in vivo tumor initiation ability of HCC cells. Mechanistically, FVTF inhibited HCC cell stem properties via targeting DNMT1/miR-34a-5p/FoxM1 axis. Clinically, DNMT1 expression was inversely correlated with miR-34a-5p expression, whereas a positive correlation was noted between DNMT1 and FoxM1 expression levels, and high DNMT1 levels, low miR-34a-5p levels, and high FoxM1 levels were associated with cancer recurrence. Furthermore, a combination of DNMT1, miR-34a-5p and FoxM1 served as an independent prognostic indicator influencing both DFS and OS in patients with HCC.

Conclusions: FVTF inhibits HCC cell stem properties by targeting DNMT1/miR-34a-5p/FoxM1 axis, which is associated with HCC recurrence and prognosis, and FVTF is a prospective treatment drug for human HCC.

Colorectal adenoma is a common precancerous lesion with a high risk of malignant transformation. Traditional Chinese medicine and its complex prescriptions have shown promising efficacy in the treatment of adenomas; however, there remains a lack of systematic understanding regarding the compatibility patterns within these prescriptions, as well as an effective model for predicting therapeutic outcomes. In this study, we collected numerous TCM prescriptions and their components, recommended by experts for the treatment of colorectal adenoma, and developed a heterogeneous graph neural network model to predict the compatibility strength and probability among the herbs within these prescriptions. This model delineates the complex relationships among herbs, active compounds, and molecular targets, allowing for a quantification of the interactions and compatibility potential among the herbs. Using this model, we identified high-potential therapeutic prescriptions from clinical prescription records and identified their active components through network pharmacology. Through this approach, we aim to provide a theoretical foundation for the clinical TCM treatment of colorectal adenoma, foster the discovery of new prescriptions to optimize the therapeutic efficacy of TCM, and ultimately advance the field of cancer prevention and treatment based on traditional Chinese medicine.

Objective: Electroacupuncture (EA) is commonly used for pain control in clinical practice, yet the precise mechanisms underlying its action are not fully understood. The rostral ventromedial medulla (RVM) plays a crucial role in the modulation of pain. GABAergic neurons in the RVM (GABA^RVM neurons) facilitate nociceptive transmission by inhibiting off-cells activity. This research examined the role of GABA^RVM neurons in the analgesic effects of EA.

Methods: Nociceptive behavior was evaluated using inflammatory pain models induced by complete Freund's adjuvant (CFA) and neuropathic pain models induced by chronic constrictive injury (CCI). Also, in situ hybridization, chemogenetics, in vivo mouse calcium imaging, and in vivo electrophysiological recordings were used to determine neuronal activity and neural circuitry.

Results: EA at the "Zusanli" (ST36) on the affected side produced a significant analgesic effect in both CFA and CCI models. CFA treatment and CCI elevated the calcium activity of GABA^RVM neurons. Also, EA reduced the calcium activity, neuronal firing rates, and c-Fos expression of GABA^RVM neurons in both pain models. Chemogenetic inhibition of GABA^RVM neurons increased nociceptive thresholds. Chemogenetic activation of GABA^RVM neurons caused increased pain sensitivity in control mice and negated the analgesic effects of EA in both pain models. Moreover, reducing cannabinoid CB1 receptors on GABA^RVM neurons counteracted the analgesic effects of EA in CFA and CCI-induced pain models.

Conclusions: The study indicates that the analgesic effect of EA in inflammatory and neuropathic pain is facilitated by CB1 receptor-mediated inhibition of GABA^RVM neurons.