Promising Anti-inflammatory Medicinal Plants—An Assessment of Bioavailability, Pharmacokinetics, Clinical Efficacy and Overview of New Methodological Approaches

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 37496

Special Issue Editor


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Guest Editor
Central Laboratory of German Pharmacists, Deputy Scientific Management and Goethe University Frankfurt Institute of Pharmaceutical Chemistry, 60323 Frankfurt, Germany
Interests: medicinal plants; inflammation; bioavailability; personalized medicine; pharmaceutical analysis, pharmaceutical quality

Special Issue Information

Dear Colleagues,

Even though monoclonal antibodies and next-gen therapeutics form a major part of new pharmaceutical developments, the great interest in medicinal plants remains unbroken. This is for good reason, because the complex herbal composition allows for multicomponent and multi-target synergistic effects that can rarely be achieved by a single synthetic or biological drug.

Nevertheless, many promising pharmacological effects revealed for medicinal plants and extracts in in vitro assays fail in vivo. This is due to several factors, ranging from not knowing the pharmacologically active ingredients in a complex composition to not achieving in vivo the high concentrations applied in vitro because of poor absorption following oral administration. The only way to break this vicious circle is to close the gap between the data obtained from pharmacological assays and clinical reality by a good pharmacokinetic understanding of the active components and their final concentrations in the body at the site of action.

This Special Issue aims to summarize the state-of-the-art and the latest findings as well as to elucidate future developments in analytical methods and predictive models that can help us to bridge the gap between proven pharmacological in vitro actions and possible resulting clinical effects. In contrast to previous Special Issues dealing generally with medicinal plants (https://www.mdpi.com/journal/pharmaceuticals/special_issues/med_plants_2020) and bioactive compounds from plants and foods of pharmaceutical interest (https://www.mdpi.com/journal/pharmaceuticals/special_issues/bio_pharmaceutical), this Special Issue focuses on recent pharmacokinetic- and bioavailability-related insights gained into medicinal plants with anti-inflammatory effects while also taking into consideration future analytical and predictive developments.

Interested experts in this field are invited to promote the research on and clinical use of promising anti-inflammatory medicinal plants by submitting a research manuscript, short communication, or review article addressing:

  • the pharmacokinetics and bioavailability of potential anti-inflammatory herbal agents;
  • promising clinical trials supporting the use of medicinal plants in clinical practice for treating inflammatory diseases;
  • clinically relevant pharmacokinetic drug interactions with medicinal plants;
  • new insights into clinically relevant mechanistic actions of promising anti-inflammatory herbal ingredients;
  • approaches to enhancing the bioavailability of poorly soluble herbal ingredients;
  • physiologically relevant predictive in vitro systems for better simulation of the absorption process;
  • untargeted metabolomic profiling for the identification of the absorbed components from medicinal plants; or
  • future analytical tools and models to better characterize active herbal ingredients in vitro and in vivo.

By your contribution, you pave the way to greater evidence-based use of anti-inflammatory medicinal plants in clinical practice.  I look forward to your participation in this mission.

Prof. Dr. Mona Abdel-Tawab
Guest Editor

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Keywords

  • inflammation
  • medicinal plants
  • bioavailability
  • clinical trials
  • metabolomics profiling
  • predictive absorption models

Published Papers (7 papers)

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Research

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20 pages, 35859 KiB  
Article
Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
by Christian Lechner, Ursula Mönning, Andreas Reichel and Gert Fricker
Pharmaceuticals 2021, 14(9), 908; https://doi.org/10.3390/ph14090908 - 07 Sep 2021
Cited by 8 | Viewed by 3031
Abstract
A large number of therapeutic drugs, herbal components and their metabolites are excreted by the kidneys. Therefore, generally applied models for estimating renal excretion, including freshly isolated rat proximal tubule cells, cultured tubule cells and immortalized kidney cell lines MDCKII, NRK-52E, IHKE-1 and [...] Read more.
A large number of therapeutic drugs, herbal components and their metabolites are excreted by the kidneys. Therefore, generally applied models for estimating renal excretion, including freshly isolated rat proximal tubule cells, cultured tubule cells and immortalized kidney cell lines MDCKII, NRK-52E, IHKE-1 and Caki-1, were investigated regarding their predictive potential for active renal transport. Cultured proximal tubule cells showed an epithelial cell-like morphology and formed tight monolayers. However, mRNA expression analyses and immunohistochemical studies revealed patterns of tight junction proteins that were notably different from freshly isolated cells and distinct from those in vivo. High levels of mannitol permeation were found in NRK-52E, IHKE-1 and Caki-1 cells, suggesting that they are not suitable for bidirectional transport studies. Cultured cells and freshly isolated cells also differed in proximal tubule markers and transport proteins, indicating that cultured primary cells were in a state of dedifferentiation. Cell lines MDCKII, NRK-52E, IHKE-1 and Caki-1 did not accurately reflect the characteristics of proximal tubules. The expression patterns of marker and transport proteins differed from freshly isolated primary cells. In summary, each of these models has profound disadvantages to consider when adopting them reliable models for the in vivo situation. Thus, they should not be used alone but only in combination. Full article
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17 pages, 3567 KiB  
Article
Efficacy of an Anti-Cellulite Herbal Emgel: A Randomized Clinical Trial
by Ngamrayu Ngamdokmai, Neti Waranuch, Krongkarn Chootip, Katechan Jampachaisri, C. Norman Scholfield and Kornkanok Ingkaninan
Pharmaceuticals 2021, 14(7), 683; https://doi.org/10.3390/ph14070683 - 16 Jul 2021
Cited by 1 | Viewed by 4088
Abstract
Cellulite describes unsightly skin overlying subcutaneous fat around thighs and buttocks of post-pubescent females. A herbal ‘emgel’ containing volatile oils and extracts of A traditional Thai herbal compress was tested in a double-blind, placebo-controlled trial with 18 women aged 20–50 year with severe [...] Read more.
Cellulite describes unsightly skin overlying subcutaneous fat around thighs and buttocks of post-pubescent females. A herbal ‘emgel’ containing volatile oils and extracts of A traditional Thai herbal compress was tested in a double-blind, placebo-controlled trial with 18 women aged 20–50 year with severe cellulite. Appearance of cellulite (primary outcome), thigh circumferences, skin firmness, and cutaneous blood flow (secondary outcomes) were assessed at baseline, 2, 4, 8 and 12 weeks with a 2-week follow-up. Herbal emgel applied onto the thigh skin twice daily reduced cellulite severity scores in every time point. The score was reduced from 13.4 ± 0.3 (baseline) to 12.1 ± 0.3 (week 2) and 9.9 ± 0.6 (week 12). All secondary outcomes improved with both placebo and herbal emgels suggesting that ingredients in the base-formulation might be responsible. Querying of participants, analysis of their diaries, and physical monthly inspections found no adverse events. The herbal emgel safely improved the appearance of cellulite, while the base emgel may play a role for other endpoints. Further studies on the active constituents and their mechanism of action are needed to further explore these factors. Full article
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13 pages, 1529 KiB  
Article
Analysis of Boswellic Acid Contents and Related Pharmacological Activities of Frankincense-Based Remedies That Modulate Inflammation
by Friedemann Börner, Markus Werner, Johannes Ertelt, Jürgen Meins, Mona Abdel-Tawab and Oliver Werz
Pharmaceuticals 2021, 14(7), 660; https://doi.org/10.3390/ph14070660 - 10 Jul 2021
Cited by 11 | Viewed by 3215
Abstract
Extracts of frankincense, the gum resin of Boswellia species, have been extensively used in traditional folk medicine since ancient times and are still of great interest as promising anti-inflammatory remedies in Western countries. Despite their common therapeutic use and the intensive pharmacological research [...] Read more.
Extracts of frankincense, the gum resin of Boswellia species, have been extensively used in traditional folk medicine since ancient times and are still of great interest as promising anti-inflammatory remedies in Western countries. Despite their common therapeutic use and the intensive pharmacological research including studies on active ingredients, modes of action, bioavailability, pharmacokinetics, and clinical efficacy, frankincense preparations are available as nutraceuticals but have not yet approved as a drug on the market. A major issue of commercially available frankincense nutraceuticals is the striking differences in their composition and quality, especially related to the content of boswellic acids (BAs) as active ingredients, mainly due to the use of material from divergent Boswellia species but also because of different work-up and extraction procedures. Here, we assessed three frequently used frankincense-based preparations for their BA content and the interference with prominent pro-inflammatory actions and targets that have been proposed, that is, 5-lipoxygenase and leukotriene formation in human neutrophils, microsomal prostaglandin E2 synthase-1, and inflammatory cytokine secretion in human blood monocytes. Our data reveal striking differences in the pharmacological efficiencies of these preparations in inflammation-related bioassays which obviously correlate with the amounts of BAs they contain. In summary, high-quality frankincense extracts display powerful anti-inflammatory effectiveness against multiple targets which can be traced back to BAs as bioactive ingredients. Full article
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13 pages, 3551 KiB  
Article
Treatment of Early Allergic and Late Inflammatory Symptoms of Allergic Rhinitis with Petasites Hybridus Leaf Extract (Ze 339): Results of a Noninterventional Observational Study in Switzerland
by Maren Blosa, Julia Uricher, Sabine Nebel, Catherine Zahner, Veronika Butterweck and Jürgen Drewe
Pharmaceuticals 2021, 14(3), 180; https://doi.org/10.3390/ph14030180 - 24 Feb 2021
Cited by 9 | Viewed by 2207
Abstract
The primary objective of this noninterventional, observational study was to assess the effectiveness of the Petasites hybridus leaf extract (Ze 339) on early allergic and late inflammatory symptoms of allergic rhinitis in Swiss outpatients. This study was conducted by general practitioners and allergologists. [...] Read more.
The primary objective of this noninterventional, observational study was to assess the effectiveness of the Petasites hybridus leaf extract (Ze 339) on early allergic and late inflammatory symptoms of allergic rhinitis in Swiss outpatients. This study was conducted by general practitioners and allergologists. Data from 226 patients were collected during three documented visits. The intermediate visit was ideally made 2–4 weeks after the baseline visit, followed by the final visit approximately 2–4 months later. The mean study duration was 63 days, with 75% of patients being treated for at least 4 weeks. Of the patients, 58.5% started with Ze 339 monotherapy, and 41.5% received other antiallergic and/or sympathomimetic drugs. In both groups, the allergic total symptom score and the inflammatory total symptom scores were significantly (p < 0.001) reduced, and the scores for quality of life were improved. Both physicians and patients were very satisfied with the treatment and the concept of therapy, not only for short-term (seasonal) therapy but also for long-term therapy. The tolerability was good: only three mild gastrointestinal adverse events occurred. In summary, the effectiveness of P. hybridus leaf extract Ze 339 for the treatment of early allergic and late inflammatory symptoms of allergic rhinitis could be confirmed. Full article
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Review

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56 pages, 6198 KiB  
Review
From Bush Medicine to Modern Phytopharmaceutical: A Bibliographic Review of Devil’s Claw (Harpagophytum spp.)
by Thomas Brendler
Pharmaceuticals 2021, 14(8), 726; https://doi.org/10.3390/ph14080726 - 27 Jul 2021
Cited by 15 | Viewed by 9545
Abstract
Devil’s claw (Harpagophytum spp., Pedaliaceae) is one of the best-documented phytomedicines. Its mode of action is largely elucidated, and its efficacy and excellent safety profile have been demonstrated in a long list of clinical investigations. The author conducted a bibliographic review which [...] Read more.
Devil’s claw (Harpagophytum spp., Pedaliaceae) is one of the best-documented phytomedicines. Its mode of action is largely elucidated, and its efficacy and excellent safety profile have been demonstrated in a long list of clinical investigations. The author conducted a bibliographic review which not only included peer-reviewed papers published in scientific journals but also a vast amount of grey literature, such as theses and reports initiated by governmental as well as non-governmental organizations, thus allowing for a more holistic presentation of the available evidence. Close to 700 sources published over the course of two centuries were identified, confirmed, and cataloged. The purpose of the review is three-fold: to trace the historical milestones in devil’s claw becoming a modern herbal medicine, to point out gaps in the seemingly all-encompassing body of research, and to provide the reader with a reliable and comprehensive bibliography. The review covers aspects of ethnobotany, taxonomy, history of product development and commercialization, chemistry, pharmacology, toxicology, as well as clinical efficacy and safety. It is concluded that three areas stand out in need of further investigation. The taxonomical assessment of the genus is outdated and lacking. A revision is needed to account for intra- and inter-specific, geographical, and chemo-taxonomical variation, including variation in composition. Further research is needed to conclusively elucidate the active compound(s). Confounded by early substitution, intermixture, and blending, it has yet to be demonstrated beyond a reasonable doubt that both (or all) Harpagophytum spp. are equally (and interchangeably) safe and efficacious in clinical practice. Full article
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19 pages, 462 KiB  
Review
Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes
by Iris Bischoff-Kont and Robert Fürst
Pharmaceuticals 2021, 14(6), 571; https://doi.org/10.3390/ph14060571 - 15 Jun 2021
Cited by 66 | Viewed by 8416
Abstract
Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora [...] Read more.
Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora of pre-clinical studies demonstrated anti-cancer, anti-oxidative, or anti-inflammatory actions. 6-Shogaol is formed from 6-gingerol by dehydration and represents one of the main bioactive principles in dried ginger rhizomes. 6-Shogaol is characterized by a Michael acceptor moiety being reactive with nucleophiles. This review intends to compile important findings on the actions of 6-shogaol as an anti-inflammatory compound: in vivo, 6-shogaol inhibited leukocyte infiltration into inflamed tissue accompanied with reduction of edema swelling. In vitro and in vivo, 6-shogaol reduced inflammatory mediator systems such as COX-2 or iNOS, affected NFκB and MAPK signaling, and increased levels of cytoprotective HO-1. Interestingly, certain in vitro studies provided deeper mechanistic insights demonstrating the involvement of PPAR-γ, JNK/Nrf2, p38/HO-1, and NFκB in the anti-inflammatory actions of the compound. Although these studies provide promising evidence that 6-shogaol can be classified as an anti-inflammatory substance, the exact mechanism of action remains to be elucidated. Moreover, conclusive clinical data for anti-inflammatory actions of 6-shogaol are largely lacking. Full article
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34 pages, 1395 KiB  
Review
Considerations to Be Taken When Carrying Out Medicinal Plant Research—What We Learn from an Insight into the IC50 Values, Bioavailability and Clinical Efficacy of Exemplary Anti-Inflammatory Herbal Components
by Mona Abdel-Tawab
Pharmaceuticals 2021, 14(5), 437; https://doi.org/10.3390/ph14050437 - 06 May 2021
Cited by 14 | Viewed by 5489
Abstract
Medicinal plants represent a big reservoir for discovering new drugs against all kinds of diseases including inflammation. In spite the large number of promising anti-inflammatory plant extracts and isolated components, research on medicinal plants proves to be very difficult. Based on that background [...] Read more.
Medicinal plants represent a big reservoir for discovering new drugs against all kinds of diseases including inflammation. In spite the large number of promising anti-inflammatory plant extracts and isolated components, research on medicinal plants proves to be very difficult. Based on that background this review aims to provide a summarized insight into the hitherto known pharmacologically active concentrations, bioavailability, and clinical efficacy of boswellic acids, curcumin, quercetin and resveratrol. These examples have in common that the achieved plasma concentrations were found to be often far below the determined IC50 values in vitro. On the other hand demonstrated therapeutic effects suggest a necessity of rethinking our pharmacokinetic understanding. In this light this review discusses the value of plasma levels as pharmacokinetic surrogates in comparison to the more informative value of tissue concentrations. Furthermore the need for new methodological approaches is addressed like the application of combinatorial approaches for identifying and pharmacokinetic investigations of active multi-components. Also the physiological relevance of exemplary in vitro assays and absorption studies in cell-line based models is discussed. All these topics should be ideally considered to avoid inaccurate predictions for the efficacy of herbal components in vivo and to unlock the “black box” of herbal mixtures. Full article
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