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Artemisinin and its derivatives (ARTs), due to their potent antimalarial activities, are widely used as frontline antimalarials across the world. Although the large-scale deployment of ARTs has significantly contributed to a substantial decline in malaria deaths, the global malaria burden is still high. New antimalarial treatments need to be developed to manage the growing artemisinin resistance. Understanding the status of ART development is crucial for developing strategies for new alternatives and identifying opportunities to develop ART-based treatments. This study sampled ART clinical trials from the past two decades to gain an overview of the global ART-development landscape. A total of 768 trials were collected to analyze the disease focuses, activity trends, development status, geographic distribution, and combination treatment profiles of ART trials. The findings highlighted the constant focus of ARTs on malaria, the evolving combination research focus, the distinctions between ART development preferences across global regions, the urgent demands for treatments for artemisinin-resistant malaria, and the unavoidable need to consider ART combinations in the development of new antimalarials.

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb–herb or herb–drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals’ effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

The purpose of this perspective is to provide insights into the current challenges and opportunities of applying network pharmacology (NP) to illustrate the effectiveness of traditional Chinese medicines (TCMs) against the coronavirus disease 2019 (COVID-19). Emerging studies have indicated that the progression of COVID-19 is associated with hematologic and immunologic responses in patients, and TCMs may fight against COVID-19 regarding the two aspects. However, the underlying mechanisms remain largely unclear [1]. This perspective is intended as a brief report derived from our previous experience in investigating the efficacy of TCMs, via conventional reductionism-based research methods, holistic NP, systems biology, or “omics” research, and prevailing big data analysis.

Herbal formulas from traditional Chinese medicines (TCMs) have been extensively used in clinics as effective therapies, but it is still a great challenge to demonstrate the scientific basis for their therapeutic effects at the level of molecular biology. By taking a classic herbal formula (Yu Ping Feng decoction, YPF) as an example, this study developed a novel network pharmacology based method to identify its potential therapeutic targets. First, this study constructed a “targets–(pathways)–targets” (TPT) network in which targets of YPF were connected by relevant pathways; then, this network was decomposed into separate modules with strong internal connections; lastly, the propensity of each module toward different diseases was assessed by a contribution score. On the basis of a significant association between network modules and therapeutic diseases validated by chi-square test (p-value

Thrombotic events act as a critical factor that interferes with Cardiovascular Diseases (CVDs), and antithrombotic herbal medicine is a long-standing controversial issue. Although a dispute is involved in their clinical application, all parties unanimously agree that herbal products have been widely used in folk medicine, and their interactions with conventional drugs are of high concern. This study aims to investigate how antithrombotic herbal medicines interact with Western cardiovascular drugs on the molecular level by taking an example of the most frequently used herbal pair, Danshen-Chuanxiong (DS-CX), and to discover more scientific evidence on their potential herb-drug interactions. Network pharmacology (NP), as an analytical approach of a complex system, is used to visualize and compare target profiles of DS-CX and Western cardiovascular drugs, which can be applied to predict common herb-drug targets and to construct a solid context for discussing herb-drug interactions. These interactions are further validated by in vitro assays, while in vivo zebrafish model employed for evaluating an overall pharmacological efficacy of herbal pairs in specific combination ratios. The study finds that DS could react directly to the Western cardiovascular drug targets relevant to antithrombotic pathways (i.e., thrombin, coagulation factor Xa and cyclooxygenase-1), whereas CX could not react directly and can synergistically affect antithrombotic effects with DS in specific combination ratios. Moreover, it is indicated that DS-CX may generate wide biological functions by a complicated mechanism of "neuro-immune-metabolism/endocrine" (NIM), which can further cause multiple direct and indirect interactions with Western cardiovascular drugs. From the clinical perspective, herb-drug interactions should be given high attention, especially when multiple herbs are used simultaneously.

Herbal formulae have a long history in clinical medicine in Asia. While the complexity of the formulae leads to the complex compound-target interactions and the resultant multi-target therapeutic effects, it is difficult to elucidate the molecular/therapeutic mechanism of action for the many formulae. For example, the Hua-Yu-Qiang-Shen-Tong-Bi-Fang (TBF), an herbal formula of Chinese medicine, has been used for treating rheumatoid arthritis. However, the target information of a great number of compounds from the TBF formula is missing. In this study, we predicted the targets of the compounds from the TBF formula via network analysis and in silico computing. Initially, the information of the phytochemicals contained in the plants of the herbal formula was collected, and subsequently computed to their corresponding fingerprints for the sake of structural similarity calculation. Then a compound structural similarity network infused with available target information was constructed. Five local similarity indices were used and compared for their performance on predicting the potential new targets of the compounds. Finally, the Preferential Attachment Index was selected for it having an area under curve (AUC) of 0.886, which outperforms the other four algorithms in predicting the compound-target interactions. This method could provide a promising direction for identifying the compound-target interactions of herbal formulae in silico.

Graphical abstract, Highlights • Artemisinin patents firstly appeared in 1986, have reached a preliminary scale in 2000, and have rapidly increased since 2010. • Universities and research centers are very involved in technological assignments and licensing and are collaborating intensively with industry. • New indications worth exploring for artemisinin are neoplasms, diseases affecting the immune and nervous systems, and skin diseases. Artemisinin also has the potential to reverse drug resistance in cancer. • Artemisinin-based combination therapy is currently receiving much research attention with the aim of minimizing drug resistance, reducing dose, better amenability to combination with other drugs, and superior pharmacokinetic and toxicity profiles. • Researchers continue to seek ways to facilitate an administration route that demonstrates good bioavailability regarding the rate and extent of absorption, as well as dosage forms that are active, stable, and acceptable to the patient. Sublingual, nasal, or pulmonary delivery are all potential administration routes. Lozenges or tablets, in particulate form, and liposomes and emulsions may be the future forms of artemisinin medicinal preparations., Background The isolation of artemisinin in 1971 heralded the beginning of a new era in antimalarial drug therapy, and artemisinin-based combination therapies are currently the mainstay of malaria treatment worldwide. Artemisinin-related studies have been extensively and intensively executed in the last few decades. However, although many purely technological reviews have been completed in this field, studies on artemisinin from the perspective of patents are still very limited. In terms of the importance of patents for academic research and commercial development, this study aims to reveal the overall patent landscape of artemisinin in the temporal, spatial, and technological dimensions. This work may provide a useful reference for relevant decision-making by researchers, investors, and policymakers. Methods All available patent data relevant to artemisinin derivatives and artemisinin-based drug combinations developed for use in various therapeutic areas were collected from the Derwent Innovation database. Descriptive statistics and citation analyses were used to analyze the patent landscape. Results A total of 4594 patent documents and 1450 simple patent families from 1986 to 2019 were analyzed. A comprehensive patent landscape of artemisinin is presented from the aspects of time trends, filing countries, patent ownership, co-patents, technological categories, therapeutic areas, and citation networks and pathways. Conclusions China and the United States are mainly responsible for the dramatic increase of artemisinin patents over the last three decades. From the point of view of patents, notable technological issues on artemisinin are chemical and biological synthesis, novel combinations, new formulations and administration routes, drug repositioning, and minimizing the resistance. Furthermore, a critical challenge lies in how to stimulate the industry to develop artemisinin-related drugs by government regulation and public-private partnership.