Chinese Medicine最新文献

Background: The no-reflow (NR) phenomenon remains a challenge in the treatment of acute myocardial infarction. This study aimed to explore the therapeutic potential and underlying mechanism of a combination of ferulic acid (FA) and ginsenoside Rb1 (Rb1), active components of the traditional Chinese herbal pair of Ligusticum chuanxiong Hort. and Panax ginseng C. A. Mey., respectively, in alleviating myocardial ischemia-reperfusion injury (MIRI) and NR.

Methods: A rat model of MIRI was established to evaluate the effects of FA and Rb1 on cardiac function, infarction/NR area, microthrombi formation, and serum biomarkers. An integrated strategy combining network pharmacology, molecular docking, and molecular dynamics simulations was employed to predict key pathways and targets. Platelet HMGB1 release and neutrophil extracellular trap (NET) formation were investigated both in vitro and vivo.

Results: MIRI induced obvious NR, accompanied by enhanced platelet HMGB1 release, increased NET formation and microthrombi accumulation. Bioinformatical analyses confirmed that FA and Rb1 stably interacts with HMGB1 and PAD4. Experimentally, FA predominantly inhibited platelet HMGB1 release, with IC₅₀ of 19.28 µM, by suppressing the p38/ERK1/2 pathway. Rb1 exhibited stronger efficacy in inhibiting PAD4 enzyme activity. The FA-Rb1 combination demonstrated superior effects compared to either agent alone, effectively suppressing NET formation, improving cardiac function, and reducing both NR area and microthrombi burden.

Conclusions: The combination of FA and Rb1 not only inhibits platelet HMGB1 release but also reduces NETs, thereby enhancing anti-NR efficacy. These findings propose a novel therapeutic approach involving FA-Rb1 combination therapy for alleviating myocardial NR.

Background: The integration of artificial intelligence (AI) into traditional Chinese medicine (TCM) research and development offers promising solutions to longstanding challenges in the field. These challenges include the complexity of TCM formulations, variability in quality control, and hurdles in global market acceptance. The unique synergy between AI technologies and TCM principles creates opportunities to enhance research efficiency, standardization, and innovation.

Aim of review: This review aims to explore the applications and impact of AI across three critical stages of TCM development: drug design, pharmaceutical manufacturing, and market access. By summarizing the advancements and limitations in these areas, the review identifies the transformative potential of AI and proposes future directions for integrating AI with emerging technologies to advance TCM research and development (R&D).

Key scientific concepts of review: AI has transformative potential in TCM development, addressing key challenges across various stages. In drug design, AI accelerates the identification of active compounds, optimizes formula composition, and models pharmacodynamic relationships to enhance innovation efficiency and precision. During pharmaceutical manufacturing, AI contributes to process optimization, quality control, and the standardization of TCM products, ensuring stable and scalable production. For market access, although no TCM developed by AI has entered the clinic, AI has played a role in comprehensive safety and efficacy assessments and simplified regulatory compliance in other drugs. By leveraging these advances and reviewing limitations, AI promotes the need to develop more integrated, more efficient, and more utilized methods in TCM R&D.

Traditional Chinese medicine, with millennia of history, demonstrates significant therapeutic efficacy against diverse diseases. A key characteristic of traditional Chinese medicine lies in the use of compound formulas-multi-herb concoctions that enhance efficacy and mitigate toxicity. The synergy within these formulas arises fundamentally from interactions among multiple active components. Recently, growing experimental studies have aimed to elucidate the scientific principles underlying synergy in traditional Chinese medicine. By reviewing literature over the past 30 years, this review summarizes that traditional Chinese medicine synergy manifests primarily through three key mechanisms: physicochemical interactions, pharmacokinetic processes, and pharmacodynamic effects. Furthermore, it provides an overview of methodological advances for studying these mechanisms, including HPLC fingerprinting, network pharmacology, and metabolomics, among others. Finally, it highlights current research limitations as well as challenges in traditional Chinese medicine modernization. This review systematically synthesizes current knowledge on traditional Chinese medicine synergy to establish a foundation for compatibility research and promote evidence-based clinical application.

Background: Electroacupuncture (EA) has demonstrated efficacy in ameliorating obesity through its marked appetite-suppressing effects. This study aims to elucidate the peripheral-central communication mechanism underlying EA's appetite inhibition mediated by the "vagal afferent fiber-nucleus tractus solitarius (NTS)-hypothalamic arcuate nucleus (ARC)" neural circuit.

Methods: High-fat diet-induced obese rats received EA or transcutaneous auricular vagus nerve stimulation (taVNS) for 8 weeks. Furthermore, we employed chemogenetic approaches to activate NTS glucagon-like peptide-1 (GLP-1) neurons (NTS^GLP-1) and utilized capsaicin for gastric vagal deafferentation (GVND). Outcomes included metabolic profiles, vagal electrophysiology, expression of NTS^GLP-1 and hypothalamic appetite-regulating neuropeptides, and neuronal activation markers.

Results: We observed reduced expression of GLP-1 in the NTS of obese rats. Chemogenetic activation of NTS^GLP-1 significantly suppressed appetite, mitigated obesity, and modulated hypothalamic pro-opiomelanocortin (POMC) and neuropeptide Y (NPY). Following EA intervention in obese rats, concurrent activation of NTS^GLP-1 and vagal afferent fibers was observed. Similar to chemogenetic NTS^GLP-1 activation, EA upregulated the anorexigenic peptide POMC while downregulating the orexigenic peptide NPY in the ARC. Chemogenetic inhibition of GLP-1 neurons during EA application partially inhibited its anti-obesity and anorectic effects. Further investigations revealed that both EA and taVNS effectively reduced food intake and alleviated obesity. While both interventions activated vagal pathways and NTS^GLP-1, EA induced a significantly stronger activation of vagal afferent fibers compared to taVNS. Critically, GVND prior to EA application attenuated its anti-obesity effects.

Conclusion: The therapeutic benefits of EA in appetite suppression and obesity mitigation are mediated by selective regulation of the "vagal-GLP-1-ARC" neural circuit.

Background: Psoriasis-associated dyslipidemia presents as a critical comorbidity characterized by a self-perpetuating cycle of metabolic dysfunction and chronic inflammation. Current treatment paradigms lack the capacity to simultaneously modulate these interconnected pathological axes. Here we investigated the efficacy and mechanisms of brusatol (a natural quassinoid derived from Bruceae Fructus) against psoriatic dyslipidemia from the insight of restoring lipid homeostasis.

Methods: The in vitro efficacy of brusatol was assessed in TNF-α-stimulated HaCaT keratinocytes by evaluating proliferation, apoptosis, and inflammatory responses. In vivo, its therapeutic activity and systemic toxicity were examined in an imiquimod-induced psoriatic mouse model using PASI scoring, histopathological analysis, serum biochemical markers (TC, TG, ALT, AST, Cre), inflammatory cytokines (TNF-α, IL-1β, IL-17A), and BBB-chip analysis. Integrated proteomics and lipidomics of skin tissue and serum revealed dysregulated pathways, and subsequent target engagement was confirmed via molecular docking, CETSA, and DARTS. Mechanistic investigations included IL-1β overexpression, Co-IP, GST pull-down and AMPK pathway analysis (Western blot, qPCR) was explored to delineate the regulatory mechanisms.

Results: Brusatol dose-dependently suppresses proliferation and inflammatory mediator expression in TNF-α-induced HaCaT keratinocytes, ameliorates skin lesions and systemic dyslipidemia in mice, effectively normalizing serum TC and TG levels without inducing visceral organ toxicity. Further integrated omic analyses and subsequent target validation identified IL-1β as the direct target linking inflammatory signaling and lipid dysregulation. Mechanistic studies uncovered a novel IL-1β-AMPK physical interaction that sequesters AMPK in the cytoplasm. Brusatol disrupts this complex, facilitating AMPK nuclear translocation to suppress lipogenic regulators (SREBP-1c/FASN/ACC1) and potentiate β-oxidation pathways (PPARα/CPT1A), thereby restoring lipid homeostasis.

Conclusion: Our findings not only establish brusatol as an effective agent for ameliorating psoriatic dyslipidemia, but also unveil a fundamental IL-1β-AMPK interaction that orchestrates inflammation-metabolism crosstalk.

Background: Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical pathological mechanism in acute kidney injury (AKI). While pharmacologic targeting of ferroptosis holds therapeutic potential, clinically applicable inhibitors remain elusive, with even the classical inhibitor ferrostatin-1 (Fer-1) demonstrating limitations. Ginsenoside Rb1 (Rb1), a major active component of Panax ginseng, has recently been shown to inhibit ferroptosis in non-renal tissues. This study aimed to investigate the role and mechanism of Rb1 in treating AKI.

Methods: The protective and anti-ferroptotic effects of Rb1 on AKI were evaluated by assessing renal function, tissue damage, inflammation, ferrous iron, glutathione, malondialdehyde, and ferroptosis markers in C57BL/6 mice, as well as cell viability and ferroptosis-related indicators in HK-2 cells. Network pharmacology and molecular docking were employed to identify Rb1's target proteins. Transcriptome sequencing predicted further mechanisms underlying its anti-ferroptotic effects, which were subsequently validated through in vivo and in vitro experiments.

Results: The experimental results demonstrated that Rb1 administration significantly ameliorated renal dysfunction, attenuated tubular necrosis and inflammatory responses, while markedly suppressing ferroptosis-related indicators. Strikingly, Rb1 exhibited superior efficacy to Fer-1 in preventing ferroptosis in proximal tubular epithelial cells (PTECs) in vitro. Nuclear factor erythroid 2-related factor 2 (NRF2) was verified as a direct target for Rb1's ferroptosis-inhibitory effect. Mechanistic studies revealed that Rb1 selectively inhibits lipid peroxidation-the biochemical hallmark of ferroptosis-by activating the NRF2-PPARγ-ACSL4 axis.  CONCLUSION: Given its established safety profile in human use, Rb1 represents a potential therapeutic agent for preventing and treating AKI, providing scientific evidence for its application in anti-ferroptosis therapy..

Background: Boesenbergia rotunda (fingerroot) is widely used in traditional medicine, and its bioactive compound panduratin A has demonstrated potent antiviral properties. However, the mechanistic basis underlying its anti-hepatitis B virus (HBV) activity remains to be fully elucidated.

Methods: HBV-infected human hepatocytes (imHCs) were treated with B. rotunda extract, panduratin A, or pinostrobin. Intracellular HBV DNA, secreted HBsAg and HBeAg, and pregenomic RNA (pgRNA) were quantified in dose- and time-dependent experiments. Luciferase reporter assays were used to assess HBV promoter activity. The roles of HNF1α and HNF4α were evaluated by siRNA-mediated knockdown and ectopic gene expression. Drug interaction studies were performed using the KDM5 inhibitor GS-5801 and the capsid assembly modulator NVR-3778. A 3D liver spheroid model was used to validate antiviral effects on HBV DNA and cccDNA. Gene interaction network analysis was conducted to identify central regulatory pathways.

Results: B. rotunda extract, panduratin A, and pinostrobin significantly suppressed intracellular HBV DNA, HBsAg, HBeAg, and pgRNA. Panduratin A exhibited the strongest antiviral activity and inhibited preS1, preS2, and core promoter activities. Panduratin A markedly downregulated HNF1α expression, with only modest effects on HNF4α. Knockdown of HNF1α significantly reduced the antiviral efficacy of panduratin A, whereas ectopic HNF1α expression rescued its inhibitory effects. Co-treatment with GS-5801 produced synergistic activity, and combination with NVR-3778 yielded additive antiviral effects. In 3D liver spheroids, panduratin A reduced intracellular HBV DNA and cccDNA with minimal cytotoxicity. Network analysis further identified HNF1α as a key regulatory node modulated by panduratin A.

Conclusion: Panduratin A is a potent anti-HBV compound that acts primarily through HNF1α-dependent suppression of HBV transcription and replication. Its efficacy in combination therapy and in 3D liver models highlights its potential as a promising candidate for future HBV treatment strategies.

Traditional Chinese medicine (TCM) decoctions represent a complex system comprising multiple phases, and their therapeutic effects cannot be fully elucidated solely at the molecular level. The nanophase within TCM decoctions plays a significant role in mediating their pharmacological activities. Zhimu and Huangbai herbal decoction (ZBD), traditionally used to treat type 2 diabetes mellitus (T2DM), is a formulation combining Rhizoma Anemarrhenae and Cortex phellodendri chinensis. Our prior research identified natural nanoparticles (N-ZBD) within ZBD. However, the role of these nanoparticles in ZBD's anti-T2DM effects and their potential impact on the oral bioavailability of its active components remain unclear. Therefore, this study aimed to examine the anti-T2DM effects of N-ZBD and to assess whether N-ZBD could enhance the bioavailability of its primary active compounds. Initially, we employed a dialysis centrifugation method to isolate the N-ZBD (nanoparticles derived from Zhimu-Baihu Decoction) from ZBD. The separated N-ZBD exhibited an average particle size of 234.4 ± 1.04 nm, a polydispersity index (PDI) of 0.56 ± 0.06, and a zeta potential of - 12 .97 ± 1.46 mV. Then, a type 2 diabetes mellitus (T2DM) rat model was created by administering a low dose of streptozotocin (35 mg/kg) intraperitoneally following 4 weeks on a high-fat diet. After a 7-week treatment period, compared with the model group, the levels of FBG, TC, TG and LDL in MET group, N-ZBD group and ZBD group were significantly reduced, and the morphology of islets was significantly improved. In all phases state of ZBD, N-ZBD had a significant therapeutic effect on T2DM rats, which was comparable to that of ZBD. In order to explore whether N-ZBD has the effect of promoting absorption, we assessed the intestinal absorption properties of N-ZBD, ZBD, and free drugs (mangiferin, timosaponin BII, berberine, phellodendrine, neomangiferin and jatrorrhizine) utilizing a single-pass intestinal perfusion (SPIP) model. Compared to free drugs, N-ZBD enhanced the absorption of active ingredients in the jejunum and ileum. In order to explore whether N-ZBD can improve the bioavailability of active ingredients, a method using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was also established to compare the pharmacokinetic profiles of six primary active compounds in plasma after the oral administration of ZBD, N-ZBD and free drugs. The pharmacokinetic profiles of N-ZBD and ZBD in rats were comparable. Notably, N-ZBD exhibited higher C_max, AUC_0-t, and T_1/2 values for the index compounds compared to free drugs and a reduced plasma clearance rate. In conclusion, N-ZBD is primarily responsible for ZBD's anti-T2DM effects and significantly enhances the bioavailability of active ingredients, highlighting the essential role of natural nanoparticles in the therapeutic effectiveness of decoctions.

Objective: Vascular dementia (VaD) is a neurodegenerative disease primarily characterized by white matter injury and myelin degeneration, and currently, there is a lack of effective treatment options. This study aims to investigate the effects of the traditional Chinese medicine formula Danggui Shaoyao San (DSS) on cognitive function and myelin repair in VaD rats and to elucidate its underlying mechanisms.

Methods: The VaD rat model was established using the bilateral common carotid artery ligation (2VO) method. The effects of DSS on cognitive function, myelin regeneration, sphingolipid metabolism, and SPHK2/S1P/S1PR5 pathway was conducted using behavioral tests, histological staining, Western blot, lipidomics, qPCR, immunofluorescence, LC-MS/MS, and 16S rRNA sequencing. Besides, molecular docking and molecular dynamics simulation were carried out.

Results: DSS treatment significantly improved learning and memory abilities in VaD rats, reduced structural damage in the hippocampus and white matter, and promoted the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). Lipidomics and molecular biological experiments indicated that DSS activated the SPHK2/S1P/S1PR5 pathway, ameliorated sphingolipid metabolic disorders and increased S1P levels, thereby promoting myelin repair. The specific SPHK2 inhibitor ABC294640 significantly weakened the neuroprotective effects of DSS, further confirming the central role of SPHK2/S1P/S1PR5 pathway. Antibiotic depletion experiments confirmed that the gut microbiota was not a key mediator of the therapeutic effects of DSS. Finally, molecular docking and molecular dynamics simulations indicated that the DSS components Albiflorin and Gallic acid form tighter and more stable interactions with SPHK2.

Conclusion: DSS improved VaD cognitive impairment by modulating sphingolipid metabolism and promote myelin regeneration via activating the SPHK2/S1P/S1PR5 signaling pathway. This study provides important experimental evidence for the clinical application of DSS in VaD.

Background: Anal fistula is one of the most common and frequently occurring diseases in the anorectal department. Calvatia lilacina spore (CLS) has been applied for wound treatment with a long history as a traditional Chinese medicine (TCM). However, the mechanism of CLS to treat postoperative wound of anal fistula remains unclear. The present study aims to investigate the efficacy and mechanism of CLS in promoting anal fistula wound healing from the perspective of regulating the interaction between macrophages and fibroblasts.

Methods: Twenty patients who received anal surgery were recruited in Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. We presented a single-cell atlas of granulation tissue, comparing samples with and without CLS treatment, utilizing single-cell RNA sequencing. The pharmacological effects and mechanism of CLS on anal fistula wound were assessed using elisa, Immunohistochemistry (IHC) staining, western blot, Immunofluorescence (IF) staining, flow cytometry assays and cell co-culture.

Results: The CLS had a uniform particle size and contained components mainly including proteins, steroids, polysaccharides and polyphenols. CLS reduced the expression levels of Tumor Necrosis Factor-alpha (TNF-α) and increased the expression levels of Vascular Endothelial Growth Factor (VEGF) and Collagen Type I Alpha 1 (COL1A1) in the granulation tissue. The single-cell sequencing revealed that the expression level of interleukin 6 (IL-6) and C-X-C Motif Chemokine Ligand 8 (CXCL-8) was increased in the IL-6⁺ macrophages that promoted the expression of Wiskott-Aldrich syndrome protein family member 3 (WASF3) in fibroblasts and further recruited Actin-Related Protein 2 (ACTR2), Actin-Related Protein 3 (ACTR3). Finally, CLS enhanced intercellular communication between macrophages and fibroblasts by activating the Janus Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway, thereby promoting mouse skin fibroblasts (MSF) migration ability.

Conclusion: Our study objectively demonstrated the pharmacological effects of CLS in promoting the wound healing of anal fistula and investigated its mechanisms in terms of regulating the immune inflammatory process of macrophages increases signal communication with fibroblasts while promoting fibroblast transformation.