Pharmacodynamics, Network Pharmacology, and Pharmacokinetics of Chinese Medicine Formula 9002A in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo. Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3ß, ESR1, and AR targets based on the anti-ß-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer's disease pathway, APP and GSK3ß, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3ß protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.

Multi-omics study on biomarker and pathway discovery of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common heterogeneous respiratory disease characterized by persistent and incompletely reversible airflow limitation. Due to the heterogeneity and phenotype complexity of COPD, traditional diagnostic methods can only provide limited information on predicted results and treatment, which are not sufficient for accurate diagnosis and evaluation. With the development of omics technologies in recent years, genomics, proteomics and metabolomics are widely used in the study of COPD, providing good tools for discovering biomarkers to diagnose and elucidate the complex mechanism of COPD. In this review, we summarize the biomarkers of COPD based on metabolomic, proteomic and transcriptomic studies that have been reported in recent years. Furthermore, protein-protein interactions and multi-omics integrated analyses were carried out to explore the important metabolites and proteins that are involved in significant pathways in the progression of COPD in order to explain the pathogenesis of COPD. Finally, the prospects and challenges in the study of COPD are proposed. It is expected that this review will provide some references for the development of diagnostic methods and elucidation of the pathogenesis of COPD.

Traditional Chinese medicine for anti-Alzheimer's disease: berberine and evodiamine from Evodia rutaecarpa.

Alzheimer's disease (AD) is one of the most common diseases in elderly people with a high incidence of dementia at approximately 60-80%. The pathogenesis of AD was quite complicated and currently there is no unified conclusion in the academic community, so no efficiently clinical treatment is available. In recent years, with the development of traditional Chinese medicine (TCM), researchers have proposed the idea of relying on TCM to prevent and treat AD based on the characteristic of multiple targets of TCM. This study reviewed the pathological hypothesis of AD and the potential biomarkers found in the current researches. And the potential targets of berberine and evodiamine from Evodia rutaecarpa in AD were summarized and further analyzed. A compound-targets-pathway network was carried out to clarify the mechanism of action of berberine and evodiamine for AD. Furthermore, the limitations of current researches on the TCM and AD were discussed. It is hoped that this review will provide some references for development of TCM in the prevention and treatment of AD.

Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer's Disease.

Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer's disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein-protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.

Metabolomics workflow for lung cancer: Discovery of biomarkers.

Lung cancer is one of the most common cancers in the world. Due to the limitations of current diagnostic techniques and methods, most lung cancers are diagnosed at the advanced stage, which is not conducive to early treatment. The rise of metabolomics has provided new ideas for the early diagnosis of lung cancer. As a method for the comprehensive analysis of endogenous metabolites of the biological system, metabolomics has shown significant application potential for the early diagnosis and individualized treatment of various cancers including lung cancers. Via advanced analytical techniques and bioinformatics tools, the metabolome was excavated to find biomarkers related to cancer and its prognosis. In this review, the research methods and workflow of metabolomics are summarized, with an emphasis on the recent discovery of biomarkers and major metabolic pathways for lung cancers.