As the primary form and means of clinical treatment, traditional Chinese medicine formulas (TCM formulas) embody the core of TCM’s syndrome differentiation and treatment approach and serve as a bridge between TCM theory and clinical practice. Exploring the relationship between the chemical constituents of TCM formulas and the body’s vital activities, along with their complex interactive mechanisms, represents one of the key scientific challenges in modern TCM research. However, due to the complexity of TCM chemical constituents and the inherent vast systemic nature of the human body, coupled with the fragmented, experiential, and semi-quantitative nature of TCM formulas pharmacology research, bottlenecks such as complex composition, unclear mechanisms, and insufficient standardization and refinement constrain its in-depth development. Technical guidelines for non-clinical pharmacology research of traditional Chinese medicine formulas systematically review and summarize the research content and relevant advances in non-clinical pharmacology of TCM formulas, integrate multidisciplinary technical approaches, and establish research standards, providing practical standards for systematically elucidating the integrated mechanisms of action between multi-component drugs and the body. This article interprets the core content of the technical guidelines, thereby initiating the following discussion on TCM formulas pharmacology: analyzing critical points, elucidating the complete evidence chain, and describing research content and application scenarios, which aims to enhance the scientization and reliability of TCM formulas pharmacology and to facilitate the research and development of new TCM drugs.
Given that the immunity imbalance in patients with Long COVID-19 (LC) may pose a significant global health and economic post-pandemic burden, there is an emergent need to identify therapeutic targets and treatment options. Traditional Chinese medicine (TCM), as an evidence-based therapeutic approach, can effectively improve the sequelae of LC patients by eliminating pathogenic factors. The purpose of this paper is to discuss how immune remodeling contributes to the pathogenesis of LC, the clinical evidence supporting TCM’s treatment of LC, and the mechanism of TCM modulating immune remodeling and relieving chronic inflammation to develop new ideas for the treatment of LC as well as the development of drugs. Data were retrieved using appropriate keywords from a variety of internet databases, including PubMed and Web of Science. Current evidence shows that LC can affect multiple organ systems, and its prominent manifestations include respiratory complications, neurological symptoms and cardiovascular dysfunction. Immunoassay showed a characteristic increase in interleukin 6 (IL-6), interferon gamma (IFN-γ), and T helper (Th)17/regulatory T (Treg) imbalance. TCM interventions have shown great therapeutic potential, with active compounds such as baicalin reducing lung inflammation and ginsenosides improving heart function. Clinical research reports that Qingfei Paidu decoction (QFPD) can effectively alleviate respiratory symptoms, and Sini powder (SNP) has antidepressant effects. TCM interventions can be tailored based on the specific clinical symptoms of individual patients. This article elucidates the crucial role of inflammation and immune dysfunction in alleviating multiple organ symptoms of LC. TCM used in LC treatment is an important source of new molecules. These new molecules may act synergistically to combat adverse effects such as COVID-19 infection-induced inflammation and oxidative stress.
Chronic fatigue syndrome (CFS), a complex, debilitating disorder that significantly challenges global health systems, is characterized by unrelenting fatigue, cognitive disturbances, and a series of other symptoms that do not improve with rest. While the etiology of CFS remains unclear, emerging research underscores the involvement of neuroendocrine-immune network disruption, metabolic irregularities, and gut microbiota dysbiosis. Current treatments for CFS range from pharmacological interventions, such as anti-depressant and immunosuppressant therapies, to non-pharmacological therapies like cognitive behavioral therapy and graded exercise, but these approaches often fall short in fully alleviating symptoms due to various side effects and limited efficacy. Traditional Chinese medicine (TCM), with its unique therapeutic approach involving herbal medicines, acupuncture, and massage, presents a promising alternative by addressing underlying imbalances, enhancing quality of life, and potentially mitigating fatigue symptoms. This review delves into the efficacy of TCM in managing CFS and the possible underlying mechanisms, highlights recent advancements, and advocates for rigorous clinical trials to help solidify its role in integrative healthcare. By bridging contemporary research with traditional modalities, this paper aims to expand the therapeutic strategies against CFS, offering new hope for comprehensive, effective management.
Objective: To investigate the protective effect and underlying mechanism of Eleutheroside E (EE), derived from Acanthopanax senticosus, against γ-ray radiation-induced splenic injury.
Methods: The Cell Counting Kit-8 assay was used to determine the toxicity of the drug. Hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end-labeling, and live/dead cell double staining assays were used to evaluate the protective effects of EE on the spleen. Immunofluorescence, immunohistochemical, and enzyme-linked immunosorbent assays (ELISA) were used to investigate the underlying mechanisms of EE. Cross-talk between the absent in melanoma 2 (AIM2) inflammasome and the protein kinase A (PKA) signaling pathway was clarified using selective inhibitors.
Results: EE reduced IR-induced splenic injury—the increased apoptosis rates and the levels of γ-H2AX and inflammatory factors in splenic cells were significantly alleviated. ELISA showed that EE reduced the level of interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in irradiated tissues. The radioprotective effects of EE were mediated by inhibition of the AIM2 inflammasome and stimulation of PKA signaling, in which EE inhibited the increased levels of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved caspase-1 proteins upon ionizing radiation damage but rescued the decreased protein levels in PKA signaling. Suppression of AIM2 signaling was dependent on the activation of PKA signaling by EE treatment.
Conclusions: EE exerts a significant radioprotective effect on the spleen in vitro and in vivo. Activation of the PKA signaling pathway leads to AIM2 inflammasome inhibition, thereby attenuating radiation-induced DNA damage. This was demonstrated to be the mechanism involved in the radioprotective effects of EE. Thus, EE can be used as a potential radioprotective drug in clinical practice.
Objective: To investigate the antidepressant mechanism of Jiaotaiwan (JTW), a classic Traditional Chinese Medicine formula, by examining its effects on the gut microbiota short-chain fatty acid (SCFA) neurotransmitter/immune axis in patients with depression.
Methods: In this 8-week multicenter randomized controlled trial, 120 patients with depression were randomized to receive JTW, selective serotonin reuptake inhibitors (SSRIs), or JTW+SSRIs, and 30 healthy volunteers were enrolled as controls without intervention (healthy controls, n = 30). Gut microbiota profiling (16S ribosomal RNA [16S rDNA] gene sequencing), fecal SCFA quantification (gas chromatography-mass spectrometry), and plasma levels of neurotransmitters (5-hydroxytryptamine [5-HT], norepinephrine [NE], dopamine [DA]) and gut barrier/inflammatory markers (lipopolysaccharide [LPS], soluble zonula occludens-1 [sZO-1], high mobility group box 1 [HMGB1]) were assessed pre- and post-treatment. Correlations between brain gut peptides, gut flora, SCFAs, and gut barrier/inflammatory markers were analyzed using Spearman correlation analysis.
Results: Treatment with JTW, particularly in combination with SSRIs, significantly modulated gut microbiota composition by reducing Bacteroidetes abundance and increasing Firmicutes. It selectively ameliorated SCFA metabolic disturbances, notably elevating fecal levels of branched-chain fatty acids, including isobutyric and isovaleric acids. These changes were accompanied by increased plasma levels of 5-HT and DA, and reduced levels of LPS and HMGB1, suggesting improved gut barrier integrity and attenuated systemic inflammation. Correlation analysis revealed a positive association between Firmicutes abundance and sZO-1 levels, and overall coordination among microbial shifts, metabolic changes, and neurotransmitter improvements.
Conclusion: JTW may alleviate depressive symptoms through multitarget modulation of the microbiota-SCFA-neurotransmitter/immune axis, potentially involving the restoration of microbial composition, enhanced beneficial SCFA production, improved intestinal barrier function, reduced inflammation, and elevated monoamine neurotransmitters. Synergistic effects were observed when JTW was combined with SSRIs, thereby providing a mechanistic basis for using JTW in microbiota-directed approaches for treating depression.
Objective: Long-term methadone maintenance treatment (MMT) requires gradual dose reduction to mitigate adverse effects; prior research has shown that acupuncture facilitates dose tapering and alleviates opioid cravings. Although medication dosage parameters hold significant clinical value in addiction medicine, the impact of early outpatient dose data on therapeutic effects currently remains unclear. This study aimed to construct a methadone dose reduction prediction model and analyze the clinical value of historical dose trajectories.
Methods: Data from two randomized trials (N = 197 patients across six Chinese MMT clinics) were analyzed, with participants grouped into the acupuncture and non-acupuncture cohorts. The primary outcome was combined outcome comprising methadone dose reduction and craving score changes. Pre-intervention dose trajectories were derived via cluster analysis and merged with baseline features. Five machine learning models were trained using SHapley Additive exPlanations (SHAP) to explain the feature contributions. Subgroup analyses linking trajectories to the effects of acupuncture were conducted.
Results: Methadone dose data were clustered into three trajectories. Model training included nine features from 11 variables. The CatBoost model achieved the best performance on the test set (area under the curve = 0.7531, accuracy = 0.8205). The SHAP summary plot revealed that the three most influential factors in methadone dose reduction were intervention type, body mass index, and dosage trajectory. Subgroup analysis showed that trajectory class 2 exhibited significantly better efficacy than class 0 at weeks 2 and 4 of acupuncture (week 2: risk difference, 20.4%, P = 0.015; week 4: risk difference, 27.5%, P = 0.013).
Conclusions: In this study, we established a trajectory-based prediction model for MMT dose reduction and demonstrated the clinical value of historical trajectories. The results suggest that acupuncture optimally supports patients with dynamic “rise-then-decline” trajectories, advancing personalized MMT strategies.
Objectives: Acute gastric distension (GD) impairs gastric motility and engages central stress circuits. We tested whether electroacupuncture (EA) at RN12/BL21 restores motility and probed mechanisms in the paraventricular nucleus (PVN), focusing on corticotropin-releasing hormone (CRH) neurons.
Methods: Rats underwent graded gastric balloon distension (20, 40, 60 mmHg). Gastric motility and electrogastrography determined the dysmotility threshold. Animals were randomized to EA at RN12, BL21, RN12 + BL21, or sham. PVN single-unit and local field potential activity were recorded at baseline, during GD, and after EA. Cellular Fos proto-oncogene (c-Fos)/CRH double labeling quantified PVN activation. To test causality, the CRH receptor antagonist Astressin was bilaterally microinjected into the PVN, alone or combined with EA.
Results: GD at 40 mmHg markedly suppressed gastric motility amplitude without altering slow-wave frequency, establishing this pressure as a reliable acute GD model. EA at RN12 and BL21 significantly enhanced gastric motility, with combined stimulation producing synergistic effects. GD robustly increased c-Fos expression in the PVN, including within CRH neurons, and elevated PVN neuronal firing rates and power spectral density. EA attenuated GD-induced PVN hyperactivity, reducing neuronal firing rates, power spectral energy, and local field potential activity. Immunofluorescence confirmed that EA suppressed GD-induced activation of PVN CRH neurons, with combined stimulation at RN12 and BL21 producing greater inhibition than either acupoint alone. PVN microinjection of Astressin restored gastric motility and reduced CRH neuronal activation, whereas the combination of EA and Astressin produced an additive effect on gastric motor function.
Conclusions: EA at RN12 and BL21 reverses GD-induced gastric dysmotility by dampening PVN hyperexcitability, particularly within CRH-expressing neurons. Dual-acupoint stimulation confers superior efficacy, and CRH blockade augments EA. These findings identify PVN CRH neurons as key substrates mediating EA’s central control of visceral function under acute stress.
Poria cocos (Fu Ling), a traditional medicinal fungus with more than two millennia of documented use, occupies a central role in East Asian medical practice. This review systematically examines its historical development as recorded in classical materia medica, emphasizing the evolution of its medicinal sources and the specific fungal parts employed. The representative chemical constituents - namely triterpenoids and polysaccharides - are thoroughly summarized with regard to their structural types and distinguishing characteristics. Building on classical therapeutic indications such as promoting diuresis, strengthening the spleen, and calming the mind, recent research is reviewed to elucidate the expanded pharmacological profile of P. cocos. A particular focus is given to its antitumor effects, immunomodulatory activity, anti-obesity properties, mitigation of metabolic dysfunction-associated steatotic liver disease, and enhancement of intestinal barrier function. Current mainstream quality evaluation methodologies are outlined, followed by an in-depth discussion of the pharmacokinetics of its principal bioactive components, with special emphasis on the microbial fermentation of polysaccharides into short-chain fatty acids by the gut microbiota. The synergistic role of P. cocos in polyherbal formulations, exemplified by Sijunzi Decoction, is analyzed to highlight its compatibility-enhancing effects. Contemporary applications in modern pharmaceuticals and functional foods are also summarized. Finally, key challenges and prospective directions for future research and industrial development are addressed. This review aimed to provide a comprehensive reference for basic research, product innovation, and clinical utilization of P. cocos.