Immunomodulatory Activities of Thai Herbs and the Druggability of Their Bioactive Constituents: A Comprehensive Review for Potential Phytopharmaceutical Product Development

Abstract

Background: Thai herbs have been studied and developed as alternative or complementary medicines for several diseases. Some Thai herbs show immunomodulatory activities and might be beneficial for the development of novel phytopharmaceutical products. Purpose: This study aimed to review the immunomodulatory activities of Thai herbs to determine the druggability of the major bioactive components of these herbs. Materials and Methods: A list of 129 monographs (88 herbs) in the Thai Herbal Pharmacopoeia 2021 and its supplement from 2022 was used to review the immunomodulatory activities from various records and bibliological evidence. The potential bioactive components of these herbs were analyzed, and we determined druggability in compliance with Lipinski’s rule of five. Results: Among the 74/88 (84%) herbs with immunomodulatory activity, 35 were studied in vitro and ex vivo and 39 were studied in vivo. The major immunomodulatory activity was decreased tumor necrosis factor-α (20%), interleukin-6 (15%), interleukin-1β (12%), interferon-γ (8%), and interleukin-10 (7%). Only 43/74 (58%) showed an association between their immunomodulatory activity and their major bioactive compounds. We excluded 18/43 (42%) of herbs because their bioactive compound concentration exceeded the cut-off of 10 µM, and Simplified Molecular Input Line Entry System format data were lacking. The remaining 25/43 (58%) contained 32 bioactive compounds, of which 17 were potential bioactive compounds that complied with all the criteria of Lipinski’s rule of five. However, most of these potential bioactive compounds showed limitations in water solubility, and some compounds were reported to be extensively biotransformed in vivo. Conclusion: Some phytoconstituents of Thai herbs showed potential druggability as immunomodulatory agents in compliance with Lipinski’s rule of five, the criteria for drug discovery. However, limitations in water solubility and metabolic stability mean these potential bioactive compounds might need some modifications for drug development. Addition of solubilizers, bioenhancers, and other drug delivery systems to improve pharmacokinetic profiles might be appropriate strategies to develop these bioactive compounds for future clinical applications.