Exploring Natural Compounds of Sungihwajungtang for TRPV1 Antagonistic and Anti-inflammatory Effect using in silico Method

Background: Temporomandibular joint disorder (TMD) is a neuromusculoskeletal disorder that mainly affects the temporomandibular joint. Due to the multifactorial disease etiology inflammation and chronic pain are considered as main targets for drug design and development. Surgery and pharmacologic interventions are used to treat TMD. However, these therapies have their advantages and disadvantages and require the discovery of safer and non-invasive therapies. Natural medicinal extracts remained a last resort for treating different types of diseases and possess a wide range of pharmacobiological activities. The current study investigated the phytochemicals of the Korean oriental concoction known as Sungihwajungtang against the transient receptor potential cation channel subfamily V member 1 (TRPV1) and inflammatory targets implicated in TMD. Materials and Methods: 1,191 phytochemicals from 11 medicinal plants used in the preparation of this concoction were evaluated through a virtual screening followed by in silico gene expression and pharmacokinetic prediction. Results: Four promising phytochemicals such as Cnidimoside A, Isorhamnetin-3-mono-β-D-glucoside, Kaempferol- 7-O-α-D-glucopyranoside, and Isolaricinosinol-3-α-O-β-D-glucopyranoside formed a strong hydrogen bond with the adequate binding and ligRMSD values. Moreover, these ligands interact with the inflammatory genes by reducing the mRNA expression of CXC10, SDC4, CCR6, and IL1R1 while preventing the degeneration of the articular disc by decreasing WNT7A, MAPK8, MAP4K4 expression. The toxic effect of these ligands is cautionary as they require high doses to incite nephron- and hepatotoxicity and affect the urinary bladder, kidney, and vascular system. Conclusion: The ADMET properties of these compounds are adequate but require pharmacokinetic adjustments to be further used for TMD therapy.