Understanding the interactions between numerous chemical compounds of herbs or herbal formulae and complex biological systems related with diseases or traditional Chinese medicine (TCM) syndromes is one of great dilemmas in current studies on TCM. To address such a difficult issue, we propose a novel concept and methodology of "Network Target" based on our previous works and from the perspective of network pharmacology as well as systems biology. The network target treats a disease-specific biomolecular network as a target to help design and predict the best possible treatments. Focused on mapping disease phenotypes and herbal compounds into biomolecular networks and then calculating, analyzing and predicting the mechanism of their mutual interactions, the network target approaches will facilitate discovery of effective compounds and their combinations, elucidation of mechanistic relationships between herbal formulae and diseases or TCM syndromes, and development of rational drug designs for TCM. In this paper, our recent progresses on the methodology of Network Target and its applications in herbal medicine are reviewed to provide reference for the coming TCM network pharmacology.
Chemistry, Pharmaceutical ; Drug Design ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Medicine, Chinese Traditional ; trends ; Metabolic Networks and Pathways ; drug effects ; genetics ; Pharmacogenetics

Pharmacological activity and druggability are two pivotal factors in drug innovation, which are respectively determined by the microscopic structure and macroscopic property of a molecule. Since structural optimization consists in a molecular operation in the space with multi-dimensions, and there exists a body of uncertainties for transduction from in vitro activity into in vivo pharmacological response. It is necessary for early stage in lead optimization to evaluate compound quality or efficiency using a kind of metrics containing multi-parameters. On the basis of the describing parameters of activity and druggability, this overview deals with the roles of thermodynamic signatures and binding kinetics of drug-receptor interactions in optimizing quality of compounds, signifying the significance in optimization of microscopic structures for drug discovery.
Drug Design ; Drug Discovery ; methods ; Ligands ; Molecular Structure ; Pharmaceutical Preparations ; chemical synthesis ; chemistry ; Pharmacokinetics ; Pharmacology ; Protein Binding ; Receptors, Drug ; chemistry ; Structure-Activity Relationship ; Thermodynamics

While hormonal changes during the ovulatory cycles affect multiple body systems, medical management, including medication dosing remains largely uniform between the sexes. Little is known about sex-specific pharmacology in women. Although hormonal fluctuations of the normal menstruating process alters women's physiology and brain biochemistry, medication dosing does not consider such cyclical changes. Using schizophrenia as an example, this paper illustrates how a woman's clinical symptoms can change throughout the ovulatory cycle, leading to fluctuations in medication responses. Effects of sex steroids on the brain, clinical pharmacology are discussed. Effective medication dose may be different at different phases of the menstrual cycle. Further research is needed to better understand optimal treatment strategies in reproductive women; we present a potential clinical trial design for examining optimal medication dosing strategies for conditions that have menstruation related clinical fluctuations.
Biochemistry ; Brain ; Clothing ; Female ; Humans ; Male ; Menstrual Cycle ; Menstruation ; Pharmacology ; Pharmacology, Clinical ; Physiology ; Psychopharmacology ; Schizophrenia ; Steroids

OBJECTIVETo investigate and arrange the ethno-pharmacological information of Schisandraceae plants in China.

METHODThe information was obtained by literature search, specimen inspection, field resource investigation and samples collection.

RESULTTwenty-six Schisandraece plants (inlcuding 4 varieties) have been used as folk medicines in different regions of China, the identical medicinal parts of different species in one genus show the similar usage, action and indications, and different medicinal parts with different administrated ways show different action and indications.

CONCLUSIONThe results provide reliable information for resource development and comprehensive utilization of Schisandraece plant resource in China.

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

It is essential for a successful drug to possess two basic characteristics: satisfactory pharmacological action with sufficient potency and selectivity; good druggability with eligible physicochemical, pharmacokinetic and safety profiles, as well as structural novelty. Promiscuity is defined as the property of a drug to act with multiple molecular targets and exhibit distinct pharmacological effects. Promiscuous drugs are the basis of polypharmacology and the causes for side effects and unsuitable DMPK. Drug promiscuity originates from protein promiscuity. In order to accommodate, metabolize and excrete various endo- and exogenous substances, protein acquired the capability during evolution to adapt a wide range of structural diversity, and it is unnecessary to reserve a specific protein for every single ligand. The structures of target proteins are integration of conservativity and diversity. The former is represented by the relatively conservative domains for secondary structures folding, which leads to overlapping in ligand-binding and consequent cross-reactivity of ligands. Diversity, however, embodies the subtle difference in structures. Similar structural domain may demonstrate different functions due to alteration of amino acid sequences. The phenomenon of promiscuity may facilitate the "design in" of multi-target ligands for the treatment of complicated diseases, whereas it should be appropriately handled to improve druggability. Therefore, one of the primary goals in drug design is to scrutinize and manipulate the "merits and faults" of promiscuity. This review discusses the application of promiscuity in drug design for receptors, enzymes, ion channels and cytochrome P450. It also briefly describes the methods to predict ligand promiscuity based on either target or ligand structures.
Cytochrome P-450 Enzyme System ; chemistry ; Drug Design ; Drug Discovery ; Drug Resistance, Multiple ; Drug-Related Side Effects and Adverse Reactions ; Enzyme Inhibitors ; chemistry ; Ion Channels ; chemistry ; Ligands ; Pharmaceutical Preparations ; chemistry ; metabolism ; Pharmacokinetics ; Pharmacology ; Protein Binding ; Protein Conformation ; Receptors, G-Protein-Coupled ; chemistry ; Receptors, Steroid ; agonists ; antagonists & inhibitors

Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

Currently available drugs for complex diseases have such limitations as unsatisfactory efficacy, drug resistance, and toxic side effects. Complexity of biological systems is a determinant of drug efficacy. It is not an effective approach to find disturbance strategies for the complicated biological network for complex diseases based on the static topological structures, as biological systems undergo dynamic changes all the time. Supported by profound theoretical basis and rich clinical experience, traditional Chinese medicine(TCM) emphasizes systematic and dynamic treatment depending on changes. Guided by TCM theory in practical treatment, Chinese medicine dynamically and comprehensively regulates the overall state. Therefore, if the dynamic factors are taken into consideration in design, the resultant drugs will be more effective. This study proposes state-regulating(SR) medicine from the perspective of system dynamics, elaborating the concept in terms of the connotations and principle and verifying the feasibility of SR medicine design with the attractor method. Thus, SR medicine is a new concept for drug discovery and design from the aspect of system dynamics, which integrates the TCM focusing on holistic dynamic regulation with biomedicine that features local microscopic research such as molecular mechanisms. The attractor method is a feasible techinical way for SR medicine design.
Drug Discovery ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Research Design

Bioactive natural products of novel structural types play a highly significant role in the drug discovery and development process. Of the 1,031 new chemical entities covering all diseases in the years 1981-2002, 48% were natural product mimics, 5% were the direct utility of natural products as sources of novel structures. Up to now, the main challenges are more efficient and rapid processes for discovery and isolation of bioactive natural products of novel structural types. Therefore, new strategies and ideas for chemical study on bioactive natural products of novel structural types should be applied. In order to discover a large number of bioactive natural products of novel structural types from naturally occurring sources and elucidate the intrinsic value of natural products as leads to new structures with different activities, new, more efficient and rapid processes for study on natural products will be established by use of modern chromatographies, techniques on line identification of natural products and screening methods based on molecular targets.
Biological Products ; chemistry ; isolation & purification ; Drug Design ; Drug Evaluation, Preclinical ; Humans ; Pharmaceutical Preparations ; chemical synthesis ; isolation & purification ; Pharmacognosy ; methods ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; classification ; Structure-Activity Relationship

Rhizoma phragmitis is a common Chinese herbal medicine whose effects are defined as 'clearing heat and fire, promoting fluid production to quench thirst, eliminating irritability, stopping vomiting, and disinhibiting urine'. During the Novel Coronavirus epidemic in 2020, the Weijing Decoction and Wuye Lugen Decoction, with Rhizoma phragmitis as the main herbal component, were included in The Pneumonia Treatment Protocol for Novel Coronavirus Infection (Trial Version 5) due to remarkable antiviral effects. Modern pharmacological studies have shown that Rhizoma phragmitis has antiviral, antioxidative, anti-inflammatory, analgesic, and hypoglycemic functions, lowers blood lipids and protects the liver and kidney. This review aims to provide a systematic summary of the botany, traditional applications, phytochemistry, pharmacology and toxicology of Rhizoma phragmitis.
Humans ; Plant Extracts/pharmacology* ; Rhizome ; Drugs, Chinese Herbal/therapeutic use* ; Antioxidants/therapeutic use* ; Antiviral Agents/therapeutic use* ; Medicine, Chinese Traditional ; Phytochemicals/therapeutic use* ; Ethnopharmacology ; COVID-19 Drug Treatment