Development of an interpretable machine learning model associated with genetic indicators to identify Yin-deficiency constitution.

BACKGROUND: Traditional Chinese Medicine (TCM) defines constitutions which are relevant to corresponding diseases among people. As one of the common constitutions, Yin-deficiency constitution influences a number of Chinese population in the disease onset. Therefore, accurate Yin-deficiency constitution identification is significant for disease prevention and treatment. METHODS: In this study, we collected participants with Yin-deficiency constitution and balanced constitution, separately. The least absolute shrinkage and selection operator (LASSO) and logistic regression were used to analyze genetic predictors. Four machine learning models for Yin-deficiency constitution classification with multiple combined genetic indicators were integrated to analyze and identify the optimal model and features. The Shapley Additive exPlanations (SHAP) interpretation was developed for model explanation. RESULTS: The results showed that, NFKBIA, BCL2A1 and CCL4 were the most associated genetic indicators with Yin-deficiency constitution. Random forest with three genetic predictors including NFKBIA, BCL2A1 and CCL4 was the optimal model, area under curve (AUC): 0.937 (95% CI 0.844-1.000), sensitivity: 0.870, specificity: 0.900. The SHAP method provided an intuitive explanation of risk leading to individual predictions. CONCLUSION: We constructed a Yin-deficiency constitution classification model based on machine learning and explained it with the SHAP method, providing an objective Yin-deficiency constitution identification system in TCM and the guidance for clinicians.

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study.

The purpose of this study is to investigate the potential mechanisms of Chinese herbs for the treatment of insomnia using a combination of data mining, network pharmacology, and molecular-docking validation. All the prescriptions for insomnia treated by the academician Qi Wang from 2020 to 2022 were collected. The Ancient and Modern Medical Case Cloud Platform v2.3 was used to identify high-frequency Chinese medicinal herbs and the core prescription. The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were utilized to predict the effective active components and targets of the core herbs. Insomnia-related targets were collected from 4 databases. The intersecting targets were utilized to build a protein-protein interaction network and conduct gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the STRING database, Cytoscape software, and clusterProfiler package. Gene chip data (GSE208668) were obtained from the Gene Expression Omnibus database. The limma package was applied to identify differentially expressed genes (DEGs) between insomnia patients and healthy controls. To create a "transcription factor (TF)-miRNA-mRNA" network, the differentially expressed miRNAs were entered into the TransmiR, FunRich, Targetscan, and miRDB databases. Subsequently, the overlapping targets were validated using the DEGs, and further validations were conducted through molecular docking and molecular dynamics simulations. Among the 117 prescriptions, 65 herbs and a core prescription were identified. Network pharmacology and bioinformatics analysis revealed that active components such as ß-sitosterol, stigmasterol, and canadine acted on hub targets, including interleukin-6, caspase-3, and hypoxia-inducible factor-1α. In GSE208668, 6417 DEGs and 7 differentially expressed miRNAs were identified. A "TF-miRNA-mRNA" network was constructed by 4 "TF-miRNA" interaction pairs and 66 "miRNA-mRNA" interaction pairs. Downstream mRNAs exert therapeutic effects on insomnia by regulating circadian rhythm. Molecular-docking analyses demonstrated good docking between core components and hub targets. Molecular dynamics simulation displayed the strong stability of the complex formed by small molecule and target. The core prescription by the academician Qi Wang for treating insomnia, which involves multiple components, targets, and pathways, showed the potential to improve sleep, providing a basis for clinical treatment of insomnia.

Investigating material basis and molecular mechanism of Qing Cuo formula in the treatment of acne based on animal experiments, UPLC-LTQ-Orbitrap-MS and network pharmacology.

CONTEXT: Qing Cuo Formula (QCF) is a traditional Chinese medicine for treating acne, but its active compounds and molecular mechanisms are unclear. OBJECTIVE: To investigate the material basis and molecular mechanism of QCF. MATERIALS AND METHODS: In vivo experiments were conducted on 60 male golden hamsters with damp-heat acne, with a blank group, a spironolactone group and 3 QCF administration groups (given high, medium and low doses) over a 30-day period. Serum androgen and inflammatory cytokine levels were tested by ELISA. In vitro, chemical compositions of QCF were investigated by UPLC-LTQ-Orbitrap-MS. Network pharmacology approaches were used to analyse the protein-protein interaction (PPI) network and QCF active compounds-intersection targets-acne network. GO enrichment and KEGG pathway analysis was conducted subsequently. RESULTS: Low-dose QCF group (11.4 g/kg/day) showed significantly reduced levels of serum T (4.94 ± 0.36; 5.51 ± 0.36 ng/mL), DHT (6.67 ± 0.61; 8.09 ± 0.59 nmol/L), E2 (209.01 ± 20.92; 237.08 ± 13.94 pg/mL), IL-1α (36.84 ± 3.23; 44.07 ± 4.00 pg/mL) and FFA (128.32 ± 10.94; 148.00 ± 12.12 µmol/L) compared to the blank group (p < 0.05). In vitro experiments identified 75 compounds in QCF decoction, with 27 active compounds absorbed in serum. Network pharmacology identified 6 active components connecting 17 targets. GO enrichment and KEGG pathway analysis indicated that QCF's anti-acne targets mainly regulate extracellular matrix function, inflammatory processes, immune response and endocrine function. CONCLUSIONS: This study provides evidence of the molecular mechanism and material basis of QCF in treating androgen-related damp-heat acne, paving the way for further research on its potential in treating other conditions related to damp-heat constitution.

Protective effects of ginsenoside Rg2 against memory impairment and neuronal death induced by Aß25-35 in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg2 is an important ingredient of Panax ginseng which often appears in ancient prescriptions for forgetfulness. Ginsenoside Rg2 exert neuroprotective effects and could be a new potential medicine to treat AD. In our previous study, we reported that ginsenoside Rg2 appears protect PC12 cells against Amyloid ß-fragment (25-35) (Aß25-35)-induced apoptosis via the PI3K/Akt pathway. However, there are no in vivo studies on the protective effects of ginsenoside Rg2 on Aß-induced neurotoxicity. AIM OF THE STUDY: The present study was performed to investigate the protective effects of ginsenoside Rg2 against Aß25-35-induced memory impairment, and its underlying mechanisms in rats. MATERIALS AND METHODS: An Alzheimer's Disease (AD) rat model was established by injecting the rats with Aß25-35 (1 µg/µl). Cognitive performance was evaluated by the Morris Water Maze test (MWM). The brain sections were processed and neuronal apoptosis in the hippocampus was evaluated by Hematoxylin and Eosin staining (H&E). To explore the anti-neuronal apoptosis mechanism of ginsenoside Rg2, we analyzed the protein expression of Bcl-2/Bax, caspase-3, and phospho-protein kinase B/protein kinase B (p-Akt/Akt) via western blot. RESULTS: A significant improvement in cognitive function was observed in administrated ginsenoside Rg2 AD rats. The histological injury in hippocampus CA1 induced by Aß25-35 was inhibited following administration of the ginsenoside Rg2. Ginsenoside Rg2 increase the Bcl-2/Bax ratio, attenuate the cleavage of caspase-3, and enhance the phosphorylation of Akt. CONCLUSIONS: These findings suggest that ginsenoside Rg2 could ameliorate Aß25-35-induced cognitive dysfunction by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.