Maackiain: A comprehensive review of its pharmacology, synthesis, pharmacokinetics and toxicity

Maackiain is an important component of some herbs in traditional Chinese medicine (TCM), such as Sophora flavescens Aiton, Spatholobus suberectus Dunn and Paeonia lactiflora Pall. Maackiain belongs to the second largest group of isoflavonoids the pterocarpans that is widespread in several plant genera, for example Maackia, Sophora, Caragana, Trifolium and Millettia. Recently, maackiain has attracting more attention because of its numerous pharmacological properties. This review offers the first extensive overview of maackiain natural isolation sources, pharmacological activities, synthesis, toxicity, and pharmacokinetic properties. The literature search published between 1962 and 2023 were reported by collecting the data from Google Scholar, Science Direct, SpringerLink, Web of Science, PubMed, Wiley Online, China National Knowledge Infrastructure, Scopus and structure search in SciFinder. Finding reveals the broad range of pharmacological activities of maackiain, such as anti-inflammatory, sepsis prevention, anti-cancer, anti-allergic, anti-osteolytic, anti-obesity, nephroprotective, antifungal, neuroprotective, anti-leukemic, antimalarial and inflammasome activation. Based on findings of pharmacokinetic studies, it is observed that maackiain possesses a low level of bioavailability and absorption and a rapid rate of elimination, but maackiain absorption rates in the extract were comparatively much higher than pure forms because of higher solubility and may reduce the metabolism by other ingredients present in the extract. Toxicity investigations revealed that maackiain is non-toxic to the majority of cells and selectively cytotoxic. After witnessing the beneficial pharmacological properties of maackiain, it is believed to be an emerging drug candidate for the treatment of inflammation, allergic, nephroprotection in T2D, depression, or Alzheimer's disease and obesity. However, future research topics should likely to include that elucidates its mechanism of toxicity and in vivo proper tracking of its conducts in drug delivery system. Integrating toxicity and efficiency, as well as structure modification, are critical approaches to enhancing its pharmacological properties and oral bioavailability.