# Untargeted Metabolomic Profiling of _Fructus Chebulae_ and _Fructus Terminaliae Billericae_
## 4 Discussion  
The study conducted a comparative analysis of the metabolic profiles of FC and FTB, revealing that flavonoids, phenolic acids, and alkaloids were the most abundant differentially expressed metabolites. Flavonoids, which are commonly present in plants and are abundant in various TCM herbs, are a group of natural organic compounds characterized by a fundamental C15 benzene ring structure of C6-C3-C6. For example, liquiritigenin (flavonoid) in FC and FTB have antioxidant and anti-inflammatory activities and can prevent arsenic trioxide (ATO)-induced hepatotoxicity [27]. Phenolic acids are a class of natural active products in plants with anti-inflammatory, antioxidant, antitumor, and antibacterial properties. Their biosynthesis mainly involves the shikimic acid and phenyl-propionic acid metabolic pathways. Studies have shown that both FC and FTB have high levels of protocatechuric acid, gallic acid, and shikimic acid. Protocatechuric acid, a type of phenolic acid found in fruits and vegetables, has the ability to efficiently eliminate and decrease the amounts of reactive oxygen species (ROS) within cells, leading to a decrease in cell damage and apoptosis. Furthermore, protocatechuric acid has the ability to reduce inflammation by decreasing the production of cancer-causing substances like tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) and interleukin-\(\beta\), as well as easing inflammation. Gallic acid exists as a free lipid or lipid compound in FC and has been reported to exhibit antioxidant, anticancer, hypoglycemic, hypolipidemic, antibacterial, antiviral, and anti-inflammatory activities [28]. The gallic acid in FC fruit extract can reduce the number of immortalized and cancerous cells by inhibiting the rate of cell proliferation [29]. Additionally, gallic acid exhibits strong inhibitory properties against \(\alpha\)-amylase and \(\alpha\)-glucosidase, making it a potential hypoglycemic treatment. Oxalic acid is an organic compound that can inhibit platelet aggregation and arterial, venous, and cerebral thrombosis by modulating the metabolism of arachidonic acid. Due to its anti-inflammatory and analgesic properties, oxalic acid has been utilized as a precursor in the development of antiviral and anticancer medications [30]. FC and FTB are rich in alkaloids such as nuciferine, betaine, and cephalotaxine. Nuciferine is an aporphine alkaloid with diverse pharmacological and therapeutic effects. It not only lowers blood lipid levels, scavenges free radicals, and prevents hypercholesterolemia and atherosclerosis, but also exhibits antimitotic and potent antibacterial activities [31]. Betaine, also known as N, N, N-trimethylglycine, is an alkaloid that has been shown to inhibit tumor growth, lower blood pressure, prevent peptic ulcer and gastrointestinal dysfunction, and ameliorate liver diseases [32]. Cephalotaxine is an alkaloid extracted from _Cephalotaxine fortunei_ or other plants of the Cephalotaxaceae family. The alkaloid has the ability to block protein production in eukaryotic cells, break down polyribosomes, and act as an anticancer drug by disrupting protein synthesis. Clinically, it is utilized for treating acute promyelocytic leukemia, acute monocytic leukemia, acute granulocyte leukemia, and malignant lymphomas [33]. By performing KEGG pathway analysis on the compounds, we identified 22 signaling pathways, and most of the differentially expressed metabolites are present in metabolic pathways and in the biosynthesis of secondary metabolites, which may account for the differences in metabolites between FC and FTB. Citrate, Shikimate, Mannitol, L-Gulutamate, Maleic acid, Threonine, etc., are mainly related to the metabolic pathway of secondary metabolites. L-Tryptophan, D-Glycerate, Glutathione, Mannitol, Sallcylate, and Linoleate are mainly related to metabolic pathways.