The efficacy and toxicity of grayanoids as analgesics: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Grayanoids are natural diterpenoids that are mostly found in the Ericaceae family, such as Rhododendron molle (Blume) G. Don (Relevant herb: nao yang hua), Rhododendron micranthum Turcz (also known as: zhao shan bai), which have traditionally been used to treat abdominal pain, cephalgia, and rheumatoid arthritis.

AIMS OF THE REVIEW: The review investigated advancements in notable anti-nociception, toxicity, and probable mechanisms of grayanoids. Meanwhile some binding sites of these compounds on voltage-gated sodium channels (VSGCs) were also analyzed and evaluated.

MATERIALS AND METHODS: The substantial grayanoids literature published before 2022, in SCI Finder, PubMed, Science Direct, Springer, Scopus, Wiley Online Library, J-Stage, and other literature databases had been exhaustively consulted and thoroughly screened.

RESULTS: More than 50 compounds in grayanoids exhibited exceptionally significant anti-nociception (intraperitoneal injection, less than 1 mg/kg), and the alteration of several substituents that were closely associated to the change in activity were investigated. Multiple possible mechanisms of analgesic action and toxicity had been proposed, with VSGCs playing a key part in both. As a result, the binding locations of these compounds on VGSCs (mostly grayanotoxin I and III) had been summarized.

CONCLUSIONS: The considerable anti-nociception, toxicity, and probable mechanisms of grayanoids, as well as the investigation of the binding sites on VSGCs, were discussed in this review. Furthermore, the homology of toxicity and anti-nociception of these substances was considered, as well as the possibility of grayanoids being developed as analgesics.