Research Topic

Medicinal Plants for Managing HIV/AIDS in Africa: From Ethnobotany to Reverse Pharmacology

About this Research Topic

Globally, around 36.9 million people are living with human immunodeficiency virus (HIV). In Africa alone, 25.7 million people are living with HIV, and in 2018, 1.1 million Africans were infected with HIV and 470,000 Africans died from AIDS-related disease. By the end of 2017, only 15.3 million people infected with HIV in Africa were accessing life-saving antiretroviral drugs.

In African countries such as Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe, the overall prevalence of HIV resistance is 5.6%; this includes 3.3% associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). People living with HIV who develop drug-resistant HIV have few other treatment options except regimens based on ritonavir-boosted protease inhibitors.

Still, protease and integrase inhibitors result in inferior virological outcomes, more HIV resistance, and are less likely to be recommended within current treatment protocols. Severe liver toxicity affects 8–23% of HIV-infected patients receiving indinavir and tenofovir, and combination antiretroviral therapy (cART) is associated with nephrotoxicity. Development of HIV-resistance and toxicity subtract from the efficacy of and adherence to cART. Against this backdrop, use of anti-HIV/AIDS medicinal plants provides a complementary treatment option that might significantly improve the quality of life for patients. This potential use to complement existing therapies and the search for new anti-HIV medications are the two foci of this Research Topic.

However, in the management of HIV/AIDS, as in many other diseases, medicinal plants have been misunderstood by patients, medical doctors, and the general public. However, as natural remedies continue to make a dramatic comeback, it is important to evaluate which medicinal plants have the potential to specifically work against which HIV-linked opportunistic disease and in what setting or provide support during the course of the disease.

Of course, medicinal plants are not a silver-bullet solution to HIV/AIDS. They do not replace the need for antiretroviral drugs but they do increase the options available to many HIV/AIDS patients in Africa’s resource-limited settings, especially those faced by side-effects, drug resistance and treatment failure. For example, patients with HIV drug resistance or those suffering from liver and kidney toxicity tend to use medicinal plants improve their health.
Several plants are known to inhibit HIV-1 reverse transcriptase: Adansonia digitata L. , Terminalia sericea Burch. ex DC. , Hypoxis hemerocallidea Fisch. , C.A.Mey. & Avé-Lall. , and Moringa oleifera Lam. While these plants are used by patients as complementary therapy, public health systems in Africa have not yet accepted the efficacy and safety of these herbal anti-HIV/AIDS preparations obtained from in vitro studies, more so because challenges of adverse interactions with synthetic antiretroviral drugs have not yet investigated in any detail. Despite these challenges, ethnopharmacology has an important role to play because the structure of several active anti-HIV-1 reverse transcriptase compounds from African plants mimics known nucleoside analogues found in synthetic antiretrovirals.

If it is well used, phytotherapy, especially in the context of African medicinal plants, may soon result in the discovery of novel antiretrovirals that could be developed for stubborn and drug-resistant HIV-1 and AIDS-related opportunistic diseases including cancer, tuberculosis, malaria, and skin, oral or sexually transmitted infections. As synthetic antiretroviral drugs begin to flounder, there is a real sense of expectation for finding and testing novel antiretroviral drugs from African plants used in traditional medicine.

Working at the crossroads of indigenous knowledge of medicinal plants and HIV/AIDS, in the field known as Reverse Pharmacology, African scientists hope to shorten the classical route of antiretroviral drug discovery. The focus of this Research Topic is to demystify the use of natural remedies from plants and to bring the efficacy and safety of medicinal plants that are used to manage HIV/AIDS in Africa to the forefront of current knowledge in antimicrobial and pharmacological research.

Several drug discovery efforts in Africa are inconclusive because many studies only start and end with the description of ethnobotanical data. Therefore, although the first part of the topic (Medicinal Plants for Managing HIV/AIDS in Africa) is broadly important, we are particularly interested in manuscripts targeting the second part of the topic, from Ethnobotany to Reverse Pharmacology.

Authors should focus on those medicinal plants that are used as herbal remedies for HIV/AIDS (including the treatment of secondary symptoms) and plants at various stages of the drug discovery pipeline whose selection or starting point is based on indigenous knowledge. Stated differently, rather than just presenting a description of ethnobotanical survey data, preference will be given to manuscripts that present the use of plants as supportive therapy for HIV/AIDS and ethnobotanically-selected plants that are at high-end stages of the drug discovery pipeline.

We invite Original Research and Review manuscripts that detail the indigenous knowledge associated with the use of medicinal plants used to treat HIV infections and HIV/AIDS opportunistic diseases. We are particularly interested in manuscripts that present data related to the following in the context of African Medicinal plants or the treatment of HIV/AIDS:

• Posology and ethnopharmacology
• Screening for efficacy and in vitro activity
• Toxicity testing and clinical studies
• Characterization of active ingredients, structure elucidation and progress towards drug development
• Interactions of herbal and synthetic drugs



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.


Keywords: Ethnobotany, indigenous knowledge, ethnopharmacology, drug discovery


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.

Globally, around 36.9 million people are living with human immunodeficiency virus (HIV). In Africa alone, 25.7 million people are living with HIV, and in 2018, 1.1 million Africans were infected with HIV and 470,000 Africans died from AIDS-related disease. By the end of 2017, only 15.3 million people infected with HIV in Africa were accessing life-saving antiretroviral drugs.

In African countries such as Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe, the overall prevalence of HIV resistance is 5.6%; this includes 3.3% associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). People living with HIV who develop drug-resistant HIV have few other treatment options except regimens based on ritonavir-boosted protease inhibitors.

Still, protease and integrase inhibitors result in inferior virological outcomes, more HIV resistance, and are less likely to be recommended within current treatment protocols. Severe liver toxicity affects 8–23% of HIV-infected patients receiving indinavir and tenofovir, and combination antiretroviral therapy (cART) is associated with nephrotoxicity. Development of HIV-resistance and toxicity subtract from the efficacy of and adherence to cART. Against this backdrop, use of anti-HIV/AIDS medicinal plants provides a complementary treatment option that might significantly improve the quality of life for patients. This potential use to complement existing therapies and the search for new anti-HIV medications are the two foci of this Research Topic.

However, in the management of HIV/AIDS, as in many other diseases, medicinal plants have been misunderstood by patients, medical doctors, and the general public. However, as natural remedies continue to make a dramatic comeback, it is important to evaluate which medicinal plants have the potential to specifically work against which HIV-linked opportunistic disease and in what setting or provide support during the course of the disease.

Of course, medicinal plants are not a silver-bullet solution to HIV/AIDS. They do not replace the need for antiretroviral drugs but they do increase the options available to many HIV/AIDS patients in Africa’s resource-limited settings, especially those faced by side-effects, drug resistance and treatment failure. For example, patients with HIV drug resistance or those suffering from liver and kidney toxicity tend to use medicinal plants improve their health.
Several plants are known to inhibit HIV-1 reverse transcriptase: Adansonia digitata L. , Terminalia sericea Burch. ex DC. , Hypoxis hemerocallidea Fisch. , C.A.Mey. & Avé-Lall. , and Moringa oleifera Lam. While these plants are used by patients as complementary therapy, public health systems in Africa have not yet accepted the efficacy and safety of these herbal anti-HIV/AIDS preparations obtained from in vitro studies, more so because challenges of adverse interactions with synthetic antiretroviral drugs have not yet investigated in any detail. Despite these challenges, ethnopharmacology has an important role to play because the structure of several active anti-HIV-1 reverse transcriptase compounds from African plants mimics known nucleoside analogues found in synthetic antiretrovirals.

If it is well used, phytotherapy, especially in the context of African medicinal plants, may soon result in the discovery of novel antiretrovirals that could be developed for stubborn and drug-resistant HIV-1 and AIDS-related opportunistic diseases including cancer, tuberculosis, malaria, and skin, oral or sexually transmitted infections. As synthetic antiretroviral drugs begin to flounder, there is a real sense of expectation for finding and testing novel antiretroviral drugs from African plants used in traditional medicine.

Working at the crossroads of indigenous knowledge of medicinal plants and HIV/AIDS, in the field known as Reverse Pharmacology, African scientists hope to shorten the classical route of antiretroviral drug discovery. The focus of this Research Topic is to demystify the use of natural remedies from plants and to bring the efficacy and safety of medicinal plants that are used to manage HIV/AIDS in Africa to the forefront of current knowledge in antimicrobial and pharmacological research.

Several drug discovery efforts in Africa are inconclusive because many studies only start and end with the description of ethnobotanical data. Therefore, although the first part of the topic (Medicinal Plants for Managing HIV/AIDS in Africa) is broadly important, we are particularly interested in manuscripts targeting the second part of the topic, from Ethnobotany to Reverse Pharmacology.

Authors should focus on those medicinal plants that are used as herbal remedies for HIV/AIDS (including the treatment of secondary symptoms) and plants at various stages of the drug discovery pipeline whose selection or starting point is based on indigenous knowledge. Stated differently, rather than just presenting a description of ethnobotanical survey data, preference will be given to manuscripts that present the use of plants as supportive therapy for HIV/AIDS and ethnobotanically-selected plants that are at high-end stages of the drug discovery pipeline.

We invite Original Research and Review manuscripts that detail the indigenous knowledge associated with the use of medicinal plants used to treat HIV infections and HIV/AIDS opportunistic diseases. We are particularly interested in manuscripts that present data related to the following in the context of African Medicinal plants or the treatment of HIV/AIDS:

• Posology and ethnopharmacology
• Screening for efficacy and in vitro activity
• Toxicity testing and clinical studies
• Characterization of active ingredients, structure elucidation and progress towards drug development
• Interactions of herbal and synthetic drugs



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.


Keywords: Ethnobotany, indigenous knowledge, ethnopharmacology, drug discovery


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.

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08 June 2020 Abstract
08 October 2020 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Submission Deadlines

08 June 2020 Abstract
08 October 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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