Polymethoxyflavones transcends expectation, a prominent flavonoid subclass from Kaempferia parviflora: A critical review

A Thai-native herbal species, Kaempferia parviflora (K. parviflora) is a dark purple, stemless rhizome that belongs to the Zingiberaceae family with historical medicinal benefits. The rhizome has been used to treat gastrointestinal disorders, allergic, and pain relief for centuries, which gave rise to its discovery as an anti-inflammatory agent. Phytochemical investigations of K. parviflora extract (KPE) showed flavones as a major compound in the crude extract, with multiple methoxy functional groups in its chemical structure known as polymethoxyflavones (PMFs). To date, 15 PMFs with methoxy-group varied from 1 to 5 have been discovered. Furthermore, the hydroxylation of PMFs compounds further expands its promising bioactivities. The PMFs in crude extract constitute numerous biological activities, including anticancer, antidiabetic, antioxidant, antimicrobial, and more, despite its high lipophilic character and low water solubility reported that hindered its maximum potential in drug discovery. Nonetheless, the mechanism induced by the specific PMFs from crude KPE has yet to be thoroughly discussed. Thus, we aim to discuss the major biological activities of the crude KPE and its isolated PMFs, together with the mechanism of action for the respective compound. Furthermore, the phytochemical investigations and structure-activity relationship of PMFs were reviewed to provide additional evidence of the chemistry of PMFs and their reported biological activities. In addition, the toxicology reports of crude extract and PMFs were summarized to determine the optimal dosage for future studies. Therefore, this article includes advanced strategies of the crude KPE and PMFs to improve drug delivery and bioavailability through structural modification, transport vehicle, microencapsulation, nanosuspension, metal nanoparticles, and self-micro and -nano emulsifying drug delivery system (SMEDDS & SNEDDS). Overall, the reviews provide a comprehensive analysis of the current therapeutics’ potential of PMFs and crude KPE, besides its obstacles and several strategies for potential applications in future studies.