ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

Objective: To analyze the epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors, so as to provide a scientific basis for the targeted prevention and control of infectious diseases for children and adolescents. Methods: Using data from the "Infectious Disease Reporting Information Management System" of the "China Disease Prevention and Control Information System" covering the period from January 1, 2012 to December 31, 2024, the study analyzed clinical and confirmed cases of hand, foot, and mouth disease, other infectious diarrhea, and acute hemorrhagic conjunctivitis among individuals aged 6-19 years old to describe demographic and temporal characteristics. It used Joinpoint regression to calculate the average annual percent change (AAPC) and annual percent change (APC) to analyze incidence trends, and Spearman s correlation was combined to generalize linear models so as to assess the association between category C intestinal infectious diseases and meteorological factors. Results: From 2012 to 2024, a cumulative total of 61 019 cases of hand, foot, and mouth disease among children and adolescents, 58 498 cases of other infectious diarrhea, and 6 377 cases of acute hemorrhagic conjunctivitis were reported. The AAPC in the incidence rates of these three diseases was 19.19%, 31.03% and 31.48 %, respectively(all P <0.05). Notably, the incidence of hand, foot, and mouth disease increased significantly after 2022 (APC= 133.66 %, P <0.01). The temporal distribution showed that hand,foot,and mouth disease was most prevalent in May,June and July (seasonal index of 2.39,3.64,1.97), other infectious diarrhea was most prevalent in February,March and December (seasonal index of 1.22,1.25,1.47), and acute hemorrhagic conjunctivitis peaked in September and October (seasonal index of 4.22,2.16). Monthly average temperature could increase the risk of hand,foot,and mouth disease( β = 0.18 ,95% CI =0.11-0.25); as monthly average wind speed increased, the incidence of other infectious diarrhea ( β =-0.86, 95% CI = -1.50 to -0.22) and acute hemorrhagic conjunctivitis ( β =-1.32, 95% CI =-2.60 to -0.05) both decreased (all P < 0.05 ). Conclusions Among children and adolescents in Shenzhen, category C intestinal infectious diseases remain prevalent throughout the year；the number of reported hand, foot, and mouth disease cases has shown an upward trend in recent years.Temperature and wind speed significantly affect the number of reported cases of three types with category C intestinal infectious diseases.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and abnormal accumulation of α‑synuclein. Its pathogenesis involves multiple interconnected processes, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation, and impaired protein homeostasis. Extracellular signal-regulated kinase 1/2 (ERK1/2), a major component of the mitogen-activated protein kinase signaling network, plays an important role in neuronal survival, synaptic plasticity, stress responses, and cell death. However, accumulating evidence indicates that ERK signaling in PD is not unidirectional, as both insufficient activity and sustained overactivation have been associated with neuronal dysfunction and disease progression. In this review, we systematically summarize the evidence for the pathological and protective roles of ERK signaling in PD. Insufficient ERK activity may impair neurotrophic support, synaptic plasticity, mitochondrial homeostasis, and neuronal adaptation to stress, thereby increasing the vulnerability of dopaminergic neurons. In contrast, persistent and excessive ERK activation may promote neuroinflammation, oxidative stress, mitochondrial dysfunction, apoptosis, autophagy-lysosomal impairment, and abnormal α-synuclein accumulation. Conversely, moderate and transient ERK activation induced by neurotrophic factors, bioactive compounds, or exercise may enhance neuronal survival, antioxidant defense, synaptic plasticity, and functional recovery. These apparently contradictory findings suggest that ERK activation itself cannot be simply classified as either neuroprotective or neurotoxic. Based on the available evidence, we propose the concept of an “ERK activity window” to explain the context-dependent effects of ERK signaling in PD. This hypothesis suggests that ERK activity needs to remain within an appropriate dynamic range to maintain neuronal homeostasis and adaptive responses. ERK activity below this range may weaken neurotrophic support and stress resistance, whereas prolonged and high-intensity activation may exceed the adaptive capacity of neurons and glial cells, thereby promoting inflammatory and degenerative processes. Importantly, this functional window should not be regarded as a fixed threshold. Its biological effects are likely determined by the intensity and duration of activation, cell type, subcellular localization, upstream stimuli, interaction with other signaling pathways, and disease stage. This framework may therefore help reconcile the apparently inconsistent findings among different PD models and experimental conditions. From a therapeutic perspective, these findings indicate that ERK should not necessarily be considered a target for simple activation or inhibition. Instead, restoring ERK signaling toward an appropriate functional state may represent a more rational strategy. Exercise is of particular interest because it can simultaneously influence neurotrophic signaling, oxidative stress, inflammation, synaptic plasticity, and ERK activity, potentially promoting adaptive remodeling of ERK signaling according to pathological conditions. Nevertheless, current evidence is predominantly derived from cellular and animal studies, and the dynamic, cell-specific, and spatial characteristics of ERK signaling remain insufficiently defined. Blood-brain barrier penetration, long-term safety, preservation of physiological ERK functions, and the lack of reliable biomarkers for monitoring brain ERK activity also limit clinical translation. Importantly, the “ERK activity window” remains a theoretical framework, and direct clinical evidence that ERK modulation can alter the progression of human PD is currently lacking. Future studies should therefore integrate longitudinal analysis, cell-specific and spatial approaches, and clinical biomarker validation to determine whether precise regulation of ERK signaling can provide a viable strategy for disease-modifying intervention in PD.

AIM To explore the differential metabolites of different aged Citrus reticulate'Chachi'and their processed cakes.METHODS Non-targeted metabolomics technology of GC-TOF-MS was used to analyze the chemical constituents.The data was processed by principal component analysis and orthogonal partial least squares discriminant analysis,and the differential metabolites were identified.RESULTS A total of 74 differential metabolites were identified,including 16 glycosides,14 organic acids and their derivatives,11 amino acids and their derivatives,and 4 flavonoids.Comparative analysis revealed 40 and 30 differential metabolites between fresh C.reticulate'℃hachi'and 3-year or 5-year aged samples,respectively.Furthermore,27 and 34 differential metabolites were identified between the 3-year or 5-year aged samples and their corresponding processed cakes,respectively.Differential metabolites among fresh,aged C.reticulate'Chachi',and processed cakes were predominantly enriched in 6 metabolic pathways,including the biosynthesis of secondary metabolites.Specifically,differential metabolites between 3-year aged C.reticulate'Chachi'and its processed cake were significantly enriched in 4 pathways,such as ABC transporters.Differential metabolites between 5-year aged C.reticulate'Chachi'and its processed cake were mainly enriched in 5 pathways,including carbon metabolism.CONCLUSION Non-targeted metabolomics technology can elucidate the chemical compositional differences among fresh/aged and processed cakes of C.reticulate'Chachi',laying a foundation for the research into C.reticulate'Chachi'aging processing techniques and the development of processed products.

AIM To investigate the clinical effects of Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment on patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency.METHODS Sixty patients were randomly assigned into control group(30 cases)for 24-week intervention of non-immunosuppressive treatment,and observation group(30 cases)for 24-week intervention of both Mahuang Fuzi Xixin Decoction and non-immunosuppressive treatment.The changes in clinical effects,TCM syndrome effects,TCM syndrome score,24 h UTP,ALB,eGFR,Nephrin,Podocin and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate and TCM syndrome effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,24 h UTP,Nephrin,Podocin(P＜0.05),and increased ALB(P＜0.05),especially for the observation group(P＜0.05).No obvious adverse reactions occured in the two groups.CONCLUSION For the patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency,Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment can improve TCM syndromes,whose action mechanism may be contribute to the alleviation of podocyte injury.

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*