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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.

Background: As one of the bioactive components in Cordyceps sinensis (CS), proteins were rarely used as index components to study the correlation between the protein components and producing areas of natural CS. Objective: Protein components of 26 natural CS samples produced in Qinghai, Tibet, and Sichuan provinces were analyzed and compared to investigate the relationship among 26 different producing areas. Materials and Methods: Proteins from 26 different producing areas were extracted by Tris-HCl buffer with Triton X-100, and separated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional electrophoresis (2-DE). Results: The SDS-PAGE results indicated that the number of protein bands and optical density curves of proteins in 26 CS samples was a bit different. However, the 2-DE results showed that the numbers and abundance of protein spots in protein profiles of 26 samples were obviously different and showed certain association with producing areas. Conclusions: Based on the expression values of matched protein spots, 26 batches of CS samples can be divided into two main categories (Tibet and Qinghai) by hierarchical cluster analysis. SUMMARY The number of protein bands and optical density curves of proteins in 26 Cordyceps sinensis samples were a bit different on the sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profilesNumbers and abundance of protein spots in protein profiles of 26 samples were obvious different on two-dimensional electrophoresis mapsTwenty-six different producing areas of natural Cordyceps sinensis samples were divided into two main categories (Tibet and Qinghai) by Hierarchical cluster analysis based on the values of matched protein spots. Abbreviations Used: SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis, 2-DE: Two-dimensional electrophoresis, Cordyceps sinensis: CS, TCMs: Traditional Chinese medicines

Background: Asini Corii Colla (ACC) (namely donkey hide gelatin, E'jiao in Chinese) was one of the most valuable tonic traditional Chinese medicines which is an infallible remedy to promote hematopoiesis. It should be produced by fresh or dried donkey hide according to Chinese Pharmacopeia (2015 edition) with a long-time decoction, while as donkey and horse (or mule) all belong to equids so their hides or their hide gelatins are share much in common, that cause the difficult in distinguishing raw materials donkey hide from horse/mule hide for manufacturer, and the challenge in the quality evaluation of ACC for regulatory authority to identify the adulterated with horse hide. Objective: To establish an effective quality evaluation methods for ACC focused on the qualitative-based identification of the raw material's authenticity, mainly to identify the species origin of the gelatins. Materials and Methods: DNA extracted from (1) Raw materials (hides of donkey, horse, mule, bovine and pig); (2) Five hide-glues (bovine, pig, donkey, horse and mule hide-glue); (3) 11 batches of ACC commercial products made by different manufactures from local drug stores. Polymerase chain reaction (PCR) method with newly designed horse-specific primers I and primer pair II. Results: Use the primer pair I, a 234 bp target product could be amplified sensitively from the DNA sample of horse/mule adulterated commercial ACC products, though the DNA in commercial products is severely degraded. A 219 bp product could be amplified specifically from the DNA sample of horse/mule hide, while the results were all negative for the DNA templates of donkey hide, its gelatin and ACC products without adulteration. Conclusion: The developed PCR method based on primer I and II provide an effective approach to identify the species origin of highly processed product ACC (primer pair I) as well as to distinguish the raw material donkey hide (primer pair II), which might enlighten a new strategy to the Quality Evaluation of ACC. SUMMARY Though the quality of commercial Asini Corii Colla (ACC) products varies greatly and produce with nondonkey hide was one the most common adulteration, the effective method to constrain such adulteration remains to be establishedThe gelatins made by donkey, horse, bovine, pig, mule shares much in common with each other, not only in contents of amino acids but also the profiles of protein in sodium dodecyl sulfate polyacrylamide gel electrophoresis, isoelectric focusing, gel filtration chromatography and two-dimensional electrophoresisThe adulteration in ACC by using horse/mule hide, which is most difficult to detect, could be identified by Polymerase chain reaction methods with newly designed horse/mule-specific primer. Abbreviations Used: ACC: Asini Corii Colla; TCMs: Traditional Chinese Medicines; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; IEF: Isoelectric focusing; GFC: Gel filtration chromatography; 2-DE: Two-dimensional electrophoresis; PCR: Polymerase chain reaction

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.