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.

Mona Abdel-Tawab

doi:10.3390/ph14050437

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 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.

Highlights

Chronic inflammation is associated with many chronic diseases like arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, allergy, cancer, and conditions of aging [1]. it has been recognized as the greatest threat to human health, with more than50% of all deaths being attributable to inflammation-related diseases such as ischemic heart disease, stroke, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease (NAFLD) and autoimmune and neurodegenerative conditions [2]
Possible role of boswellic acids with too high IC50 values that are not achieved in vivo in providing therapeutic effects pharmacokinetic properties of other promising frankincense ingredients i.e., tirucallic, lupeolic and roburic acid the influence of other extract ingredients on the pharmacological activity and efficacy effect of the pharmacological assays applied and experimental conditions on the outcoming results with regard to pharmacological activity and bioavailability the need for more well designed and high quality clinical trials to better underline positive/negative effects already observed
While a lot of data exist on possible molecular targets and pharmacologically relevant concentrations in vitro mostly for purified and isolated phytoconstituents, much less information is available on the pharmacokinetics of the tentative active ingredients of medicinal plants and even less information on clinical efficacy and the translation of in vitro data to the clinic

Summary

Introduction

Chronic inflammation is associated with many chronic diseases like arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, allergy, cancer, and conditions of aging [1]. it has been recognized as the greatest threat to human health, with more than50% of all deaths being attributable to inflammation-related diseases such as ischemic heart disease, stroke, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease (NAFLD) and autoimmune and neurodegenerative conditions [2]. Chronic inflammation is associated with many chronic diseases like arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, allergy, cancer, and conditions of aging [1]. In spite of extensive research activities devoted to the discovery of new anti-inflammatory drugs evidence based anti-inflammatory therapies are still restricted to the administration of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and recently cytokine blocking biologicals. These existing anti-inflammatory treatment options are associated with a lot of side effects [3]. A large portion of research activities in academia and industry is still devoted to the discovery of new anti-inflammatory compounds that are urgently needed [4].

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