About this Research Topic
Integrative Pharmacology can be used to determine the multi-pharmacological effects of traditional medicines such as traditional Chinese medicine (TCM), Kampo, Sa-sang, Ayurveda, etc.). Through qualitative and quantitative pharmacokinetic-pharmacodynamic (PK-PD) correlations among multi-constituents and multi-targets, integrating chemical profiling, ADME/PK processes, molecular network calculation and resulting experimental validation, the use of Integrative Pharmacology has become widespread. The data has provided a novel paradigm to evaluate the druggability of bioactive ingredients of herbs or formulae, to decipher the pharmacological mechanisms of drug action and to screen potentially new indications for approved drugs and previously unidentified adverse events. On this basis, Integrative Pharmacology may offer an effective way to test the potential scientific basis for traditional medicines and to assess what roles of traditional medicine can and cannot play in pharmaceuticals.
Integrative Pharmacology emphasizes the integration of the multidisciplinary knowledge, different pharmacokinetic and biological processes as well as multiple computational and experimental techniques. Traditional medicine is characterized by personalized, holistic and multi-component therapy and plays a crucial role in modern health care. However, the complexity of traditional medicine provides a significant challenge for researchers to identify active compounds, to understand the pharmacological mechanisms and to clarify the roles in pharmaceuticals. This complexity has so far restricted the acceptance of traditional medicine in modern biomedical practice. Integrative pharmacology was proposed to address this problem and is regarded as a novel paradigm to promote the modernization of traditional medicine and the discovery of new drugs. This Research Topic aims to achieve the following three goals:
• Further develop and innovate the methodology, databases and algorithms associated with Integrative pharmacology of traditional medicine
• Promote the application of Integrative pharmacology in the research field of traditional medicine, which may offer a contribution to resolve the key problems in the diagnosis and treatment of traditional medicine
• Offer an effective approach to assess how traditional medicine preparations can and cannot be evaluated in the context of experimental ethnopharmacological research. All submissions should contribute to developing science-based strategies for assessing traditional medicinal preparations in bioscientific terms (See the Four Pillars of Best Practice).
We intend to publish high-quality Original Research as well as Review articles to provide an overview of the most exciting developments in the field of Integrative Pharmacology in traditional medicine. This topic "Integrative Pharmacology-based Research on Traditional Medicine: Methodologies, Medical and Pharmacological Applications", intends to focus on qualitative “PK-KD” network connections between potential active constituents of traditional medicine in vivo and the molecular networks of diseases or syndromes. Submitted Manuscripts should address the following:
• Identification of quality marker of herbs and herbal formulas
• Investigation of the pharmacological mechanisms of traditional medicine
• Screening potentially new indications for approved traditional medicine and previously unidentified adverse events
• Elucidation of the biological basis of traditional Chinese medicine syndromes (submissions which include the use of the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.ehbio.com/ETCM) and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP, http://www.tcmip.cn) are welcomed
• How traditional medicine preparations can and cannot be evaluated in the context of experimental ethnopharmacological research
These themes in integrative pharmacology-based research may offer a contribution to resolve the key problems in diagnosis and treatment using traditional medicine.
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 characterized, 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.
Integrative Pharmacology emphasizes the integration of the multidisciplinary knowledge, different pharmacokinetic and biological processes as well as multiple computational and experimental techniques. Traditional medicine is characterized by personalized, holistic and multi-component therapy and plays a crucial role in modern health care. However, the complexity of traditional medicine provides a significant challenge for researchers to identify active compounds, to understand the pharmacological mechanisms and to clarify the roles in pharmaceuticals. This complexity has so far restricted the acceptance of traditional medicine in modern biomedical practice. Integrative pharmacology was proposed to address this problem and is regarded as a novel paradigm to promote the modernization of traditional medicine and the discovery of new drugs. This Research Topic aims to achieve the following three goals:
• Further develop and innovate the methodology, databases and algorithms associated with Integrative pharmacology of traditional medicine
• Promote the application of Integrative pharmacology in the research field of traditional medicine, which may offer a contribution to resolve the key problems in the diagnosis and treatment of traditional medicine
• Offer an effective approach to assess how traditional medicine preparations can and cannot be evaluated in the context of experimental ethnopharmacological research. All submissions should contribute to developing science-based strategies for assessing traditional medicinal preparations in bioscientific terms (See the Four Pillars of Best Practice).
We intend to publish high-quality Original Research as well as Review articles to provide an overview of the most exciting developments in the field of Integrative Pharmacology in traditional medicine. This topic "Integrative Pharmacology-based Research on Traditional Medicine: Methodologies, Medical and Pharmacological Applications", intends to focus on qualitative “PK-KD” network connections between potential active constituents of traditional medicine in vivo and the molecular networks of diseases or syndromes. Submitted Manuscripts should address the following:
• Identification of quality marker of herbs and herbal formulas
• Investigation of the pharmacological mechanisms of traditional medicine
• Screening potentially new indications for approved traditional medicine and previously unidentified adverse events
• Elucidation of the biological basis of traditional Chinese medicine syndromes (submissions which include the use of the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.ehbio.com/ETCM) and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP, http://www.tcmip.cn) are welcomed
• How traditional medicine preparations can and cannot be evaluated in the context of experimental ethnopharmacological research
These themes in integrative pharmacology-based research may offer a contribution to resolve the key problems in diagnosis and treatment using traditional medicine.
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 characterized, 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.
Keywords: Integrative Pharmacology, biological network, pharmacological mechanism, Traditional Medicine, bioactive constituent
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
