Coalescence of traditional medicine Ayurveda and in silico technology is a rigor for supplementary development of future-ready effective traditional medicine. Ayurveda is a popular traditional medicine in South Asia, emanating worldwide for the treatment of metabolic disorders and chronic illness. Techniques of in silico biology are not much explored for the investigation of a variety of bioactive phytochemicals of Ayurvedic herbs. Drug repurposing, reverse pharmacology, and polypharmacology in Ayurveda are areas in silico explorations that are needed to understand the rich repertoire of herbs, minerals, herbo-minerals, and assorted Ayurvedic formulations. This review emphasizes exploring the concept of Ayurveda with in silico approaches and the need for Ayurinformatics studies. It also provides an overview of in silico studies done on phytoconstituents of some important Ayurvedic plants, the utility of in silico studies in Ayurvedic phytoconstituents/formulations, limitations/challenges, and prospects of in silico studies in Ayurveda. This article discusses the convergence of in silico work, especially in the least explored field of Ayurveda. The focused coalesce of these two domains could present a predictive combinatorial platform to enhance translational research magnitude. In nutshell, it could provide new insight into an Ayurvedic drug discovery involving an in silico approach that could not only alleviate the process of traditional medicine research but also enhance its effectiveness in addressing health care.
Network Pharmacology ; Medicine, Traditional ; Medicine, Ayurvedic ; Drug Discovery/methods* ; Delivery of Health Care

Androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of many severe diseases such as prostate cancer, muscle atrophy, and osteoporosis. Binding of ligands to AR triggers the conformational changes in AR that may affect the recruitment of coactivators and downstream response of AR signaling pathway. Therefore, AR ligands have great potential to treat these diseases. In this study, we searched for novel AR ligands by performing a docking-based virtual screening (VS) on the basis of the crystal structure of the AR ligand binding domain (LBD) in complex with its agonist. A total of 58 structurally diverse compounds were selected and subjected to LBD affinity assay, with five of them (HBP1-3, HBP1-17, HBP1-38, HBP1-51, and HBP1-58) exhibiting strong binding to AR-LBD. The IC values of HBP1-51 and HBP1-58 are 3.96 µM and 4.92 µM, respectively, which are even lower than that of enzalutamide (Enz, IC = 13.87 µM), a marketed second-generation AR antagonist. Further bioactivity assays suggest that HBP1-51 is an AR agonist, whereas HBP1-58 is an AR antagonist. In addition, molecular dynamics (MD) simulations and principal components analysis (PCA) were carried out to reveal the binding principle of the newly-identified AR ligands toward AR. Our modeling results indicate that the conformational changes of helix 12 induced by the bindings of antagonist and agonist are visibly different. In summary, the current study provides a highly efficient way to discover novel AR ligands, which could serve as the starting point for development of new therapeutics for AR-related diseases.
Androgen Receptor Antagonists ; pharmacology ; Androgens ; metabolism ; pharmacology ; Biological Assay ; Cell Line, Tumor ; Drug Discovery ; methods ; Humans ; Ligands ; Male ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Phenylthiohydantoin ; analogs & derivatives ; pharmacology ; Principal Component Analysis ; Prostatic Neoplasms ; drug therapy ; Protein Binding ; physiology ; Protein Conformation ; drug effects ; Receptors, Androgen ; metabolism

Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.
Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Autoanalysis ; Biological Availability ; Biomarkers ; Biomarkers, Pharmacological ; Databases, Chemical ; Drug Combinations ; Drug Discovery ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Machine Learning ; Molecular Docking Simulation ; Neural Networks, Computer ; Peptide Fragments ; chemistry ; Permeability

Red blood cell (RBC) dysfunction is often associated with a pathological intervention, and it has been proposed as a critical risk factor for certain lethal diseases. Examining the cell viability of RBCs under various physiological conditions is essential and of importance for precise diagnosis and drug discovery in the field of medicine and pharmacy. In this paper, we report a new analytical method that employs dielectrophoretic (DEP) force measurements in absolute units to assess the viability, and potentially the functionality of RBCs. We precisely quantify the frequency-dependent DEP forces of the RBCs by using a micro-electrode embedded chip combined with optical tweezers. DEP characteristics are known to be well-correlated with the viability of biological cells, and DEP forces are measured in both fresh and long-term stored RBCs to investigate the effect that the storage period has on the cell viability. Moreover, we investigate the DEP behavior of RBCs when exposed to oxidative stress and verify whether EDTA protects the RBCs from an oxidant. From the experiments, it is found that the fresh RBCs without oxidative stress display very high DEP forces over the entire frequency range, exhibiting two cutoff frequencies. However, both the RBCs stored for the long-term period and exposed to oxidative stress reveals that there exist no significant DEP forces over the frequency range. The results indicate that the DEP forces can serve as a useful parameter to verify whether the RBCs in certain blood are fresh and not exposed to oxidative stress. Therefore, it is believed that our system can be applied to a diagnostic system to monitor the cell viability of the RBCs or other types of cells.
Cell Survival ; Diagnosis ; Drug Discovery ; Edetic Acid ; Erythrocytes* ; Methods ; Microfluidics* ; Optical Tweezers* ; Oxidative Stress* ; Pharmacy ; Risk Factors

Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH.
Animals ; DNA Methylation/drug effects ; Drug Discovery/methods ; *Epigenesis, Genetic/drug effects ; Genetic Therapy/methods ; Humans ; Hypertension, Pulmonary/*genetics/therapy ; MicroRNAs/*genetics

The influenza A is an acute respiratory infection persistently threatening human health and social stability, and has caused high morbidity and mortality. The development of novel anti-influenza drugs based on new targets is very significant because of high mutation and drug resistance of influenza virus. The nucleoprotein of influenza A virus identified high conservation, provides cross immune protection as a potential target of anti-influenza drugs and reports on relevant studies have been published at home and a- board. Herbal drug as a traditional Chinese medicine shows the distinct advantages in the aspect of prevention and treatment of influenza A. This paper analyzes the structure and function of influenza a virus, and reviews the advances in the research on anti-influenza targets based on the nucleoprotein of the influenza A virus.
Animals ; Drug Discovery ; methods ; Humans ; Influenza A virus ; drug effects ; metabolism ; physiology ; Influenza, Human ; drug therapy ; Molecular Targeted Therapy ; methods ; Nucleoproteins ; chemistry ; metabolism ; Virus Replication ; drug effects

High-throughput screening is a regular approach available for identitying new lead compounds for the growing validated drug targets in drug screening. However, it has also introduced a large number of peculiar molecules which interfere drug screening. Pan assay interference compounds (PAINS) interfere with the progress of drug screening in various ways, such as interfering with a biochemical assay, modifying the protein, aggregate-based inhibitors and so on. So it is of vital significance to remove them. This paper has consulted the concept, category of PAINS and reviewed the way of PAINS interfering and the countermeasures to cope with them to direct the approach of high through screening and improve the hits percent.
Drug Discovery ; High-Throughput Screening Assays ; methods

As the actual clinical reflecting of transform Chinese medicine special curative effect, Chinese medicine preparation not only satisfies the need of hospital clinic, scientific research and teaching, but also plays an important role in deepening medical and health system reform, improving people's health level and contributing to the economic growth. However, some problems about administration and approval (tending to western medicine), contraction of the scale, lack of synchronization for clinic and scientific research, and the imbalance of regional development make Chinese medicine preparation move forwards slowly in contradiction. It has not only reduced the effectiveness of the Chinese medicine preparation in hospital clinic, but also brought bad effect on modernized development of Chinese medicine preparation. Research shows that main influencing factors of status quo of Chinese medicine preparation in medical institution include imperfect laws and regulations, high cost than income, and shortage of talents in preparation research. The analysis indicated that the necessary measures to break the contradiction, improve clinical effect of Chinese medicine, and promote the modernization development of Chinese drugs preparation were as follows: government and related departments should strengthen the supporting force in policy by adjusting the examination and approval policy, speeding up dispensing use, reforming pricing system, including into medicare reimbursement, integrating advantage resources and so on; medical institution should actively carry out research and development of traditional Chinese Medicine through drawing the traditional and modern essence, reserving professional talents, and developing characteristic preparation; companies cooperate with hospitals for complementary advantages, which can rapidly transform Chinese medicine preparation into clinical practice.
Chemistry, Pharmaceutical ; economics ; methods ; trends ; China ; Drug Discovery ; economics ; trends ; Drugs, Chinese Herbal ; chemistry ; economics ; pharmacology ; Humans ; Medicine, Chinese Traditional ; economics ; trends

Rheumatoid arthritis (RA) is a kind of chronic, progressive, multiple, invasive autoimmune disease with two chief cclinical manifestations arthrosynovitis and ex-arthrosis, easy to occur in middle-aged women, also occur in children and the elderly, is characterized by progressive and break out repeatedly. RA pathogenesis is complex, there is no special treatment, used in treatment of R drug varied, new drugs and new therapies also emerge in endlessly, main including non-steroidal anti-inflammatory drugs (NSAIDs), slow action anti-rheumatism medicine (SAARDs), glucocorticoids (GCs), biological agent, traditional Chinese medicine and traditional Chinese medicine preparations, domestic market for rheumatoid main drug treatment are NSAIDs, SAARDs, GCs, traditional Chinese medicine and traditional Chinese medicine preparations. Traditional Chinese medicine and traditional Chinese medi- cine preparations for the treatment of RA have its unique advantages, show the characteristics of overall adjustment, multi-level and multiple targets, and also can alleviate and against side effects of western medicine. In recent years, more and more get people's atten- tion. This paper reviewed the research progress and treatment features of commonly used therapeutic agents for the treatment of RA in recent years, which provides reference and basis for future medicine anti-RA.
Animals ; Arthritis, Rheumatoid ; drug therapy ; Biological Factors ; adverse effects ; therapeutic use ; Drug Discovery ; methods ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; adverse effects

With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.
Drug Discovery ; methods ; Drug Therapy ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Humans ; Medicine, Chinese Traditional