Traditional Medicine (TM) plays an important role in the healthcare system and is increasingly used worldwide for managing various chronic diseases and promoting well-being. Although huge progresses have been achieved to dereplicate major compounds in well-known botanical drugs, such as
Ginkgo biloba,
Salvia miltiorrhiza, and
Panax ginseng, the identification of major active constituents remains extremely challenging due to the complexity of chemical composition and the elusive mechanisms of action. One major barrier to solving such problems is the lack of feasible methodology to distinguish those active compounds from ones which make no or only a minor contribution to the activity of a TM.
In the past three decades, bioactivity-guided screening has become a mainstream workflow for lead discovery from traditional medicine. With the aid of modern analytical approaches such as LC-MS, GC-MS, and NMR, it allows us to identify multiple constituents in active components found by phenotypic or target-based assays. However, synergistic effects among multiple compounds of TMs are difficult to recognize during conventional phytochemical isolation, which requires repeated purification step to obtain single compound from mixtures of TM. Often unsubstantiated claims about such synergistic effects are made, which are misleading scientifically and also in terms of the practical application of such ethnopharmacological studies. Often ubiquitous or widely distributed compounds are then claimed to be ‘actives’ for major disease conditions. Moreover, it is difficult to judge whether certain components or compounds identified by specific cellular model or target-based assays can exert a pharmacological effect
in vivo in the context of biological network or in a real life clinical setting. Therefore, it is time to dedicate greater efforts in either improving the capability of bioassays or developing novel paradigms to refresh our toolbox for dissecting TMs.
Multiple novel pharmacological techniques, e.g. high-throughput screening and high-content screening provide opportunities to compare the efficacy of components singularly and as a whole on a larger scale. The screening models are shifting from conventional biochemical and cellular assay to co-culture models, 3D cultured organoid, organ-on-a-chip, as well as
in vivo zebrafish model. Meanwhile, innovative strategies including component-knockout/knock-in and ligand fishing that can directly identify active compounds from complex mixture of TMs have been proposed. It can be expected that the combined use of these new methods and strategies will allow scalability of targets-based assays, which were rarely used previously. Therefore, the discovery of active compounds in TM will move further away from systematic isolation and bioassay-guided isolation to programmed/targeted isolation to find those parts with equivalent effects of the whole, improving our pharmacological understanding of complex mixtures.
The aim of this Research Topic is to improve the quality of such studies, accelerate the pace of screening and identification of active compounds from TMs, as well as to facilitate the expansion of screening assays from cellular, tissue levels to organ and
in vivo models. We invite submissions of original research papers, which will focus on the identification of active compounds that elicit pharmacological effects by analytical approaches coupled with advanced bioassays. We also encourage submissions with advanced methodological procedure that can lift the efficiency of lead discovery. Original Research articles and Review articles on all subtopics in this research field are invited.
We invite submissions of original research papers that report the identification of active compounds with similar pharmacological effects or targets by analytical approaches coupled with advanced bioassays. We also encourage submissions with advanced methodological procedure that can lift the efficiency of lead discovery. Original Research articles and Review articles on all subtopics in this research field are invited.
This Research Topic will cover the following subtopics:
1. Screening active compounds of TMs by advanced genetic or genetic screening approaches
Studies focusing on searching of active TM compounds based on advanced cell or animal models with specific readouts of biologically significance are all suitable for this subtopic. Screenings using genetically modified cell or animal models (e.g. transgenic reporter lines of downstream targets, knock in/out mutants with relevant phenotypic defects) are preferred.
2. Novel strategies to investigate potential synergistic effects of multiple active compounds of TMs
Studies investigating the effects of a combinations of novel or known active components of TMs are anticipated in this subtopic. We look forward to see experiments tackling the problem of acclaimed synergistic effects of TMs, which may include but not limit to
in silico studies (e.g. how to efficiently arrange and prioritize the combinations to be tested), high-content/high-throughput assays.
3. Novel and improved assays for screening bioactive compounds from TMs
Studies using novel techniques or assays for the evaluation of TM bioactive compounds are all welcomed in this subtopic. Some possible directions could be computer aided compound screening, high throughput image processing, artificial intelligence aided screening design and processing, the application of novel fluorescence probes or cell/animal models, etc. It will be essential to demonstrate how such new models will improve the investigation of TMs
All manuscripts must comply with the four pillars of best practice in Ethnopharmacology.
1) Pharmacological Requirements:a)
Traditional context - The traditional context must be described in the introduction.
b)
Credible experimental models - methods must be state of the art, or a credible alternative. The following have specific requirements:
Antioxidant:
- FRAP, ABTS, DPPH, and Trolox equivalent antioxidant capacity assays are not accepted.
-
in silico studies are not accepted as a main method.
Antimicrobial:
- Disc diffusion experiments must be followed by
in vitro or
in vivo experiments.
- Specificity must be assessed to rule out general toxic effects, e.g. by including parallel cytotoxicity testing (
cf. Cos et al. 2006)
- The mechanism of action must be assessed in sufficient detail (for crude extracts, the effects of contaminants should also be addressed).
Inflammation:
- Experiments on the rat hind paw oedema model are not acceptable unless they are part of a larger pharmacological – phytochemical study.
Docking studies:
- These will not be accepted unless followed by benchwork confirming affinity.
- A proposed mechanism of action is required.
in silico network pharmacology studies
-Network pharmacology studies must critically assess the evidence to evaluate the potential pharmacological effects of a preparation / herbal (medical) product.
- The identification of the compounds must be sound. This information may be derived from the existing literature or from benchwork. It is essential that the quantities of the compounds in the preparation or plant are stated and are high enough to be of pharmacological relevance.
- The bioavailability of the compounds must be assessed.
- Ubiquitous or very widely known compounds are highly unlikely to be ‘active’.
- Transcriptomic data need to be validated using RT-PCR, and proteomic data with Western blots.
Single dose studies:
- These are not accepted unless they focus on a species / compound not yet studied in detail, and can be justified on specific ethical grounds
c)
Dose - ranges must be therapeutically relevant:
- Implausibly high doses will not be considered.
- Both positive and negative controls are essential.
- Multiple doses are strongly recommended, as single dose studies are rarely accepted - only in some specific complex models.
2. Composition Requirements:Whether the material under investigation is a crude plant extract, a multi-herbal preparation, a single compound from a commercial source or extracted from plant, chemical and botanical composition must be explicitly stated.
a) Chemical:
- The concentrations of the dominating compounds must be listed, including dominant impurities if these compounds have been identified in previous studies. Stating the class of compounds present (such as “alkaloids”) is insufficient. We will usually ask for a HPLC or UPLC to establish the compounds present to ensure replicability, if this is not possible a credible alternative can be used.
- Referring to a previously used preparation in the literature is not acceptable, unless it has come from the same preparation or has the same batch number.
- For purchased compounds, purity (%) and the supplier name must be included.
- For extracted compounds, purity (%) and the method used to determine the purity must be stated.
- The structure of active compounds should be included as figures.
b) Botanical:
- Species names must be fully validated and should be described in their full taxonomy, using the
Kew Medicinal plant names service.
- Samples must be deposited in a recognised herbarium, and accessible if necessary. To find out if your institution is indexed, please use the
NYBG Steere Herbarium Search tool- Voucher numbers from the herbarium must be included in the Methods.
- Coordinates of plant picking should also be included, or the commercial source of a preparation, which must include a batch number and details on the preparation’s composition.
3. Basic Experimental and Ethical Requirements:a)
The study must contribute substantially to the existing literature. How it does so must be explicitly stated. The most up-to-date surrounding literature should be discussed, including related compounds, to demonstrate the contribution of the study to the field.
b)
Compliance with all international ethical standards is essential.
The Convention on Biological Diversity and the Nagoya Protocol are of particular relevance. This includes that research in the field should benefit the original users and consider their traditions.
c)
The use of animals must be justified. If a material is well-characterised, and its properties well-known, performing another in vivo study is considered an unethical use of animals. A thorough knowledge of the literature is essential to avoid this mistake. Conversely, if a material is not well characterised, initial experiments in cell-based models are necessary to justify moving onto animal experiments.
d)
The effects of traditional medicinal preparations must be testable in scientific terms. We acknowledge the importance of the understanding of medicinal preparations in their cultural context, and it may be that the treatment of symptoms as defined by traditional practices forms a basis for such investigations. However, pharmacological studies generally do not provide evidence for such uses, but rather for the established therapeutic targets of the model. Experimental outcomes should be linked to and described in these terms. For example, a series of in vitro tests will not demonstrate relevant evidence that will contribute to a physiological understanding of traditional therapeutic concepts, e.g. “dispelling wind” or “dampness” in Traditional Chinese Medicine. A justification must therefore be given for choosing a certain model to test a certain preparation.
4. Article-type Specific Requirements:a) FIELD STUDIES
- Data must be substantial and original.
- The study must be discussed in the context of previous studies carried out in the region. How the study contributes to the development of the field must be made explicit.
- Must comply to the
ConsEFS standards, including any updates.
b) REVIEWS
- The objective of the review must be clearly defined.
- They must provide a specific, critical assessment of the literature. The scientific quality of the original articles must be critically assessed. This includes the experimental design, and reliability of the studies.
- The traditional use must be linked to scientific evidence.
- Future needs and priorities must be clearly defined.
c) SYSTEMATIC REVIEWS & META ANALYSES
- To assure the quality of the studies included, we ask for the inclusion of a summary table (templates available on the
Ethnopharmacology About page).
- We ask that a chemical analysis is included, taken from one of the included studies. The chemical composition of the study material must be well defined. If the composition is poorly characterised, this must be highlighted.
- Quality control measures taken, as defined by a pharmacopoeia, must also be included.
- If the included studies do not use full botanical taxonomic names, this should be highlighted, as must any naming inconsistency between studies.