The 2027 BCPT Perspectives on Studies Involving Natural Products, Traditional Chinese Medicine and Systems Pharmacology

ABSTRACT

Natural products, including isolated compounds, complex extracts, traditional medicinal preparations and marine, microbial, fungal and animal‐derived materials, remain important sources of therapeutic agents and pharmacological discovery. However, variation in biological source materials, preparation methods, chemical composition and experimental design may compromise reproducibility and interpretation. This guideline presents the requirements of Basic & Clinical Pharmacology & Toxicology for studies involving natural products and their semisynthetic or biotransformed derivatives. It provides recommendations for documenting scientific and ethnopharmacological rationale, taxonomy, authentication, provenance, sustainable and lawful sourcing, extraction, chemical characterisation, dosing, bioactivity, safety and data accessibility. Particular emphasis is placed on studying the preparation actually administered, using pharmacologically relevant concentrations and doses, controlling vehicle effects and assay interference and aligning mechanistic and therapeutic claims with the supporting evidence. Complex mixtures do not necessarily need to be reduced to a single active constituent; however, their composition must be adequately characterised, and claims concerning individual constituents, additivity, synergy or antagonism require experimental substantiation. Computational, network and systems‐pharmacology analyses should be transparent and reproducible, with experimental validation of central predictions. These recommendations apply equivalent standards to natural products and other interventions while recognising the additional information required to define complex biological materials and improve overall translational relevance.

1. Introduction

Natural products (NPs)—bioactive compounds derived from living organisms such as plants, fungi, bacteria and other microorganisms and animals, from terrestrial as well as marine sources, together with extracts and derivatives—have been a principal source of treatment modalities throughout the history of medicine. In many ways, NPs are the foundation of modern‐day pharmacology and toxicology. Isolated NPs and biological extracts are still the main treatment option for millions of people across the world and remain a pivotal resource in the identification and exploration of novel drug candidates [1, 2]. In this continuously expanding field, NP‐derived therapies include discoveries in Traditional Chinese medicine (TCM), marine species and microbial synthesis, adding further to the diverse and vast pharmacological resources originating from the biological systems that surround us [1, 3]. The present paper is an update of the journals original policy paper on NPs, TCM and systems pharamcology from 2024 [4].

2. Challenges Associated With NP Studies

Several serious issues may challenge the accurate assessment of NP‐derived effects and hamper the evaluation of their pharmacological properties. These include the often highly complex composition of biological extracts, where several active molecular components may be part of the NP, but with varying concentrations, bioavailability, potency and efficacy, rendering it difficult, laborious and technically challenging to identify and convincingly correlate a single substance to an observed pharmacological effect [5, 6]. Contents may also vary because of environmental factors such as seasonal and subspecies variation, time and method of harvesting and extraction and across soil types and cultivation conditions. Together, this may compromise transparency and insights into the mechanisms of action tied to specific NP constituents and in turn limit targeted investigations of biological pathways following exposure. Moreover, NP‐derived therapies or supplements are typically not subjected to the same stringent regulation as synthetically produced pharmaceuticals, hereby increasing variability and affecting the robustness of findings [7]. This may result in incomplete documentation of toxicological characterisation of NPs and weaken the basis for adequate safety assessments ultimately raising concerns for public health.

3. Network and Systems Pharmacology

Despite these challenges NPs hold extensive promise for drug discovery [2]. Advances in artificial intelligence (AI) and machine learning enable rapid and systematic mining of large and diverse datasets to identify NP‐derived compounds, structural features and previously unrecognised relationships across data resources, thereby increasing the rate of candidate discovery and facilitating the identification of compounds with potential therapeutic value. In this light, advances in integrated data analysis represent a promising opportunity to disclose complex response patterns and compound interactions. Network pharmacology and systems pharmacology [8, 9, 10, 11] apply network‐based data exploration combined with computerised modelling and AI in an integrative manner to disclose and predict interconnected pathways and biological effects of multitarget therapies in whole biological systems [12, 13, 14, 15]. In addition, computational and mathematical analysis and modelling should provide high reproducibility compared to other forms of preclinical research, although some concerns regarding transparency and reproducibility remain [16, 17, 18, 19].

Systems pharmacology aims to understand how drugs affect the human body as a complex, interconnected system rather than focusing on individual drug–target interactions [10]. In this way, systems pharmacology offers a systematic approach to advance mechanistic insight, identify compound‐target associations and explore the combined effects of ‘multi‐compound‐pharmacology’ or ‘poly‐pharmacology’ of NPs [12, 20]. This includes analysis of network interactions examining not only single drug–protein interactions but also the entire network of interactions such as chemical–protein, protein–protein, genetic, signalling and physiological interactions, providing a thorough and reliable understanding of drug effects. By taking a holistic approach, integrating large datasets from genomics, proteomics, metabolomics and other high‐throughput technologies helps explain a compound's broader impact on biological systems. In accordance, applying computational and bioinformatics methods of systems pharmacology can provide valuable and extensive information for the identification and prediction of drug targets, and of adverse drug reactions by anchoring drug actions within the human interactome (a complete set of protein–protein interactions occurring within human cells).

4. BCPT Policy for Studies on NPs

Supported by advancing analytical methodologies to improve the validation of NP‐derived constituents and their pharmacological effects—including putative toxicity in complex biological systems—NPs remain a fundamental part of ongoing drug discovery. Basic & Clinical Pharmacology & Toxicology (BCPT) recognises the vast potential of NPs while also employing awareness of the challenges and potential shortcomings that may compromise the validity of findings. This concerns, for example, studies investigating complex NPs, where the molecular details of constituents are incomplete or not known—e.g., for some herbal mixtures applied in TCM. Rather than discarding findings, BCPT invites high‐quality investigations of putative effects of NPs provided that experimental methodology, scientific value and limitations are communicated clearly to ensure a high degree of transparency and reproducibility of findings [21, 22]. Accepted contributions may be published as part of ongoing special collections for example on TCM, NP pharmacology and toxicology or network and systems pharmacology.

This guideline helps authors address important aspects and limitations of studies involving NPs—including TCM, marine, microbial and fungal products—as well as their semisynthetic and biotransformed derivatives, prior to submitting a manuscript to BCPT (see Table 1 for key reporting requirements). In general, BCPT will not consider manuscripts reporting only screenings of NPs without a clear pharmacological rationale; routine compound bioassays without mechanistical or conceptual novelty; claims of therapeutic relevance without demonstrating relationship to biologically relevant function or mechanism. Specific guidelines for reporting are detailed in Table 2 and should be followed where relevant for the study and presented data. For semisynthetic and biotransformed derivatives, the identity and origin of the parent NP and the derivatisation route applied must be documented, whereas the points relating to biological source material (Table 2, points 6–12) apply only where relevant.

TABLE 1.

Key reporting requirements for studies involving natural products.

Item	Criterion	Status	Applies to
Authentication	Voucher/accession or justified alternative	Mandatory	Biological source materials
Dose–response	Required for quantitative potency/efficacy claims	Conditional	Pharmacological studies
Positive comparator	Include when scientifically informative	Recommended/conditional	Therapeutic comparisons
Raw spectral data	Deposit or provide as supplement	Mandatory for novel structures	Isolated compounds

TABLE 2.

Guideline for studies involving natural products.

Background	1	The rationale of the therapeutic potential of the applied compound or compounds (extract, fraction, essential oil, multicomponent preparation or isolated compound, etc.) should be outlined including reference to relevant literature (if available) concerning the compound and/or individual NP constituents.
	2	If the investigation is based on traditional use, the ethnobotanical or ethnopharmacological background must be provided. This covers the reported indication, the preparation form, the route of administration, the region and community concerned and the source of this information. It is necessary that the correspondence between the traditional use and the experimental design is addressed, and that any divergence in preparation, dose or route must be explained.
	3	The relevance of the investigated NP, e.g., herbal products in a phytotherapeutic perspective should be stipulated, e.g., how is the compound intended to exert an effect, e.g., an anti‐inflammatory agent and anticancer.
	4	For products/extracts consisting of multiple components, the expected pharmacological effects of main constituents should be presented and support the stated hypotheses of the study.
	5	The scientific reasoning behind the performed study should be elaborated: how does the experiment contribute to addressing the rationale outlined above, e.g., by targeting early discovery and/or a specific problem or challenge.
NP description	6	The nature of the investigated product (e.g., extract, fraction, essential oil, multicomponent preparation or isolated compound, and whether prepared from dried or fresh material) must be disclosed.
	7	Origin of the constituents must be detailed, e.g., purchased from commercial manufacturer, harvested and collected from the wild.
	8	The crude composition of the applied NP(s) such as whole plant parts (roots, stem, leaves, flowers and fruits), active or inactivated microorganisms, must be detailed.
	9	Each (main) component must be stated using currently accepted scientific nomenclature, giving both the accepted name and any synonym used in the source literature and citing the database consulted together with the date of access. Names must be verified against the authority appropriate to the organism group: Plants of the World Online (https://powo.science.kew.org) or World Flora Online (https://www.worldfloraonline.org) for plants, with the International Plant Names Index (https://www.ipni.org) for nomenclatural and authorship detail; Index Fungorum (https://www.indexfungorum.org) for fungi; the List of Prokaryotic names with Standing in Nomenclature (https://lpsn.dsmz.de) for bacteria and archaea; and the World Register of Marine Species (https://www.marinespecies.org) for marine organisms. For medicinal plants, the Kew Medicinal Plant Names Services (https://mpns.science.kew.org/) should additionally be consulted to link pharmaceutical and trade names to accepted scientific names.
	10	The identity of the biological source material must be authenticated, either by a qualified taxonomist or by a validated molecular method (e.g., DNA barcoding), and a voucher specimen deposited in a recognised public collection (a herbarium for plants, a culture collection for microorganisms or a museum collection for animal material), with the voucher or accession number stated together with the collection locality, date and collector. Where identification is based on DNA sequence data, the sequence must be deposited in a public sequence database (e.g., GenBank, https://www.ncbi.nlm.nih.gov/genbank) and the accession number stated. Where the material is obtained commercially and deposition of a voucher is not feasible, the supplier, batch or lot number and certificate of analysis must be provided instead.
	11	The IUCN Red List status of NP‐components must be stated when available and IUCN (https://www.iucnredlist.org/) cited appropriately.
		Contents from species categorised as IUCN ‘endangered (ED)’, ‘critically endangered (CR)’, ‘regionally extinct (RE)’ or ‘extinct in the wild (EW)’ will not be accepted for publication in BCPT. In isolated cases where specific circumstances may prompt the use of a particular compound listed as endangered, for example, farmed herbs that are endangered in the wild, a valid justification must be provided. Adherence to international legislation of the protection of endangered species (https://cites.org/) must be stated separately and proof of compliance submitted to the editor
	12	In cases of rare NPs (wild plants or species that are not commonly known) pictures should be included as well as geographical information system data (GIS‐data) to identify the component and the location of origin.
	13	Studies using genetic resources or associated traditional knowledge must state compliance with the Convention on Biological Diversity and its Nagoya Protocol on Access and Benefit‐sharing (https://www.cbd.int/abs/), with the national access and benefit‐sharing legislation of the country of origin and, where applicable, with the regional legislation implementing it (e.g., Regulation [EU] No 511/2014). Where the material or the associated traditional knowledge was accessed from a country with such measures in place, evidence of prior informed consent (PIC) and mutually agreed terms (MAT) must be provided, and the permit or internationally recognised certificate of compliance (IRCC) number stated. Where the protocol does not apply, the reason must be provided.
Preparation	14	Any processing of the source material must be detailed, including drying, grinding and comminution. For extraction, the solvent(s) and their grade, the solvent‐to‐material ratio, temperature, duration, number of extraction cycles and the technique used (e.g., maceration, percolation, Soxhlet, ultrasound‐ or microwave‐assisted extraction or supercritical fluid extraction) must be stated, together with the extraction yield expressed relative to the dry weight of the starting material. Any concentration or drying of the extract (e.g., rotary evaporation and lyophilisation) and the conditions of storage prior to use must be reported.
	15	Where the extract has been fractionated or purified, the stationary and mobile phases, the elution or gradient programme, the criteria used to pool fractions (e.g., TLC results) and the yield of each fraction carried forward must be reported. Where fractionation was bioassay‐guided, the assay directing the selection at each step must be specified. If no fractionation or purification has been performed, this must be stated.
	16	Any use of additional substances (e.g., vehicle) as part of compound preparation, for example, to increase palatability, stability and bioavailability must be stated along with the concentration and chemical composition of the involved substance(s). Investigation of putative isolated effects of vehicles must be included in the experimental design.
	17	For semisynthetic or biotransformed derivatives, the parent natural product must be identified and documented according to points 6–12, as applicable, and the derivatisation route described (chemical modification or enzymatic/microbial biotransformation including the biocatalyst or organism used). The final compound must be characterised in accordance with point 20.
Chemical composition	18	Chemical characterisation must be performed using methods appropriate to the material and the results provided as supplemental data: chromatographic fingerprinting (e.g., HPLC‐DAD, HPTLC and LC‐MS) for extracts and fractions; GC‐MS together with GC‐FID and retention indices for essential oils and other volatile fractions; 1D/2D NMR with HR‐MS for isolated compounds; and LC‐MS/MS with sequence determination for peptide and protein natural products. If chemical characterisation has not been performed, this must be justified.
	19	For multicomponent preparations (extracts, mixtures and essential oils), the relative contribution of each main constituent must be stated, e.g., as a percentage of the total or as mg/g of dry extract, together with the reference standards used for identification and quantification.
	20	For isolated compounds, structural elucidation must be documented (1H and 13C NMR, 2D experiments where required, and HR‐MS establishing the molecular formula); the purity stated together with the method used to determine it (e.g., ≥ 95% by HPLC or qNMR). Where the structure is not fully established, this must be clearly stated.
	21	Recorded chemical identities must be reported in machine‐readable form: for each defined compound, the InChI or InChIKey together with the PubChem CID (https://pubchem.ncbi.nlm.nih.gov) and, where available, the CAS Registry Number and the ChEBI or ChEMBL accession. Molecular targets discussed in the study must be identified by their UniProt accession (https://www.uniprot.org), and any protein structure used by its Protein Data Bank entry (https://www.rcsb.org).
	22	Raw spectral data supporting structure elucidation (NMR, MS) should be provided as supplemental material or deposited in a public repository (e.g., MetaboLights and GNPS/MassIVE), with the accession link given in the data accessibility statement (point 30).
Administration	23	Applied dose regime must be justified in relation to the therapeutic applicability and translational potential (for studies involving experimental models).
	24	Route of administration must be justified. Timing and frequency of administration must be stated and the choice supported by relevant data (e.g., pilot experiments, reference to scientific findings by others).
Bioactivity	25	Bioactivity must be assessed for the preparation administered. Where the study concerns a multicomponent preparation (an extract, fraction, essential oil or a traditional formulation such as a TCM product), the activity of the whole preparation must be reported. Where individual constituents are proposed to account for the observed effect, their activity must be determined under the same experimental conditions and compared with that of the whole preparation, so that additive, synergistic or antagonistic contributions can be assessed.
	26	The concentration or dose range tested must be justified and a concentration–response (or dose–response) relationship established; activity reported at a single concentration is not acceptable. Excessively high concentrations must be avoided unless scientifically justified. Where activity is measured in cells, a viability or cytotoxicity counter‐screen must be included, and for antiproliferative or cytotoxic activity, the selectivity of the effect must be demonstrated so that general toxicity is not reported as a specific pharmacological action.
	27	Positive control(s) with a known pharmacologically active drug should preferably be included when evaluating effects of NP compounds. If this is not included, a valid justification must be provided.
Systems Pharmacology	28	Sufficient technical data (including example model code and datasets) to allow readers to replicate the key modelling and simulation steps must be included as supplementary data. Software programmes including applied version must be stated in the material and methods section, e.g., MatLab, NONMEM and SimBiology.
	29	Data supporting the presented results should be archived in an appropriate public repository. Possible scripts and other artefacts used to generate the analyses presented should also be publicly archived and available.
	30	A data accessibility statement, including a link to the specific data repository, must be included in the manuscript.
Safety	31	Evaluation of toxicity of the investigated compound should be included (e.g., through system pharmacology, in vitro or in vivo assessments) where relevant for the stated conclusions. If not performed, this should be justified and considerations regarding toxicity and safety included in the discussion, i.e., current knowledge and knowledge gaps in the toxicological profile and safety of the investigated NP(s).

In addition to the BCPT policies for experimental and clinical studies [23], authors should carefully consult the listed points of attention (Tables 1 and 2) and include the required information as well as reference when preparing a manuscript for submission.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.