Wedelia species: phytochemistry, pharmacology, toxicology, nanoformulation, and synthetic modification- an extensive review

Wedelia species (the Asteraceae family) are renowned for treating several inflammation-related diseases clinically, such as pertussis and pharyngitis. Plants of the genus contain diverse bioactive metabolites. The review comprehensively describes scientific investigations regarding Wedelia species, comprising phytochemical record, pharmacological value, toxicological evaluation, and nano- and semisynthetic preparations. Four online sources Web of Science, Scopus, Google Scholar, and PubMed have been extensively used in the search for English references. The phytochemical profile of Wedelia species consisted of 290 secondary metabolites, which can be classified as terpenoids, phytosterols, saponins, phenolics, and others. Sesquiterpenoids and ent-kaurane diterpenoids were the major compounds. Wedelia species are also rich in terpenic essential oils. Wedelia constituents have a broad panel of pharmacological activities, such as anticancer, anti-inflammatory, antioxidant, antimicrobial, antidiabetic, antinociceptive, and antiviral activities. It is also useful in applications that protect the neurons, liver, and bones, and aid in wound healing. Bezofuran, wedelolactone, and two major diterpenoids, kaurenoic acid and grandiflorenic acid, are likely the bioactive molecules. Various molecular mechanisms of anti-inflammatory action have been proposed, including the nuclear factor kappa B/mitogen-activated protein kinase (NF-κB/MAPK) signaling pathway. Wedelia extracts were associated with an LD₅₀ value of more than 2000 mg/kg to rats. Nanoformulation and semisynthesis would enhance the pharmacological activities of Wedelia. In vitro and in vivo pharmacological studies for a vast number of Wedelia isolates are encouraged. Developing new formulations with more therapeutic value is expected.