Characterizing the human equivalent dose of herbal medicines in animal toxicity studies

Abstract

Ethnopharmacological relevance: Herbal medicines have been generally believed to be safe. With the increasing use of herbal medicine worldwide, however, the safety of traditional herbal drugs frequently becomes a medical issue.

Aim of the study: This study was aimed to characterize the safe dose of herbal medicines through the systematic review for "human equivalent dose (HED)" from animal-based toxicity studies.

Methods and materials: A literature search for animal-based toxicity studies of herbal medicines in eight databases, including PubMed and Embase, was performed without language restriction. From the "no observed adverse effect level (NOAEL)" of each animal study, HED values were then calculated according to the composition (single or multiple herbs) and indication of the medicines.

Results: Among 729 relevant articles identified in the initial screening, 112 (233 studies comprising 105 single-herb and 128 multiple-herb studies) that met our inclusion criteria were finally reviewed. The total average HED value (from mouse, rat, rabbit and dog) was 278.1±358.0 mg/kg, and the values for single- and multiple-herb studies were 322.7±488.4 mg/kg and 241.5±189.2 mg/kg, respectively. When the studies were analyzed according to herbal drug indication, drugs used for revitalization had the highest HED value (433.0±265.2 mg/kg), while those for infectious diseases had the lowest (110.6±118.6 mg/kg).

Conclusions: Our results provide important information regarding the safe dose of herbal medicines; thus, these data offer researchers and practitioners information critical for drug development or clinical application.

Keywords: Adverse drug reaction; HED; Herbal medicine; NOAEL safety.