Bioscience Evidence 2024, Vol.14, No.2, 56-68 http://bioscipublisher.com/index.php/be 60 5 Bioactive Compounds and Their Biosynthesis 5.1 Identification of key bioactive compounds Iridoids are a significant class of bioactive compounds found in Rehmannia glutinosa. These compounds are known for their diverse pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. Several studies have identified key iridoid glycosides in R. glutinosa, such as catalpol and ajugol, which are present in both the roots and leaves of the plant (Xu et al., 2019; Dong et al., 2022). The biosynthesis of iridoids involves the enzyme iridoid synthase (IS), which catalyzes the cyclization of 10-oxogeranial to epi-iridodial, a crucial step in the iridoid biosynthetic pathway (Yang et al., 2019). Phenylethanoids, including acteoside and other phenylethanoid glycosides, are another important group of bioactive compounds in R. glutinosa. These compounds exhibit various biological activities, such as antioxidant, anti-inflammatory, and hepatoprotective effects. The phenylpropanoid pathway, which involves enzymes like phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H), is critical for the biosynthesis of phenylethanoids (Yang et al., 2020; 2021; 2023). Polysaccharides in R. glutinosa are known for their immunomodulatory and antitumor activities. These complex carbohydrates, including acidic and neutral polysaccharides, are found in significant amounts in both the roots and leaves of the plant. The dynamic accumulation of these polysaccharides varies with the growth stages and cultivation regions of R. glutinosa(Xu et al., 2019). 5.2 Biosynthetic Pathways of Major Compounds The biosynthesis of iridoids, phenylethanoids, and polysaccharides in R. glutinosa involves several key enzymes and genes. For iridoids, enzymes such as 1-deoxy-D-xylulose 5-phosphate synthase (DXS), 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), and geranyl diphosphate synthase (GPPS) play crucial roles (Yang et al., 2019; Dong et al., 2022). In the phenylpropanoid pathway, enzymes like PAL, C4H, and p-coumarate 3-hydroxylase (C3H) are essential for the biosynthesis of phenylethanoids (Yang et al., 2020; 2021; 2023). The biosynthesis of polysaccharides involves various glycosyltransferases and other enzymes responsible for the polymerization of monosaccharides (Xu et al., 2019). The regulation of biosynthetic pathways in R. glutinosa is complex, involving multiple levels such as gene expression, enzyme activity, and epigenetic modifications. For example, Dong et al. (2022) explored the effects of 5-azacytidine (5-azaC) on the accumulation of iridoid glycosides and DNA methylation in R. glutinosa. The study showed that 5-azaC treatment significantly increased the expression levels of genes related to iridoid glycoside synthesis in Rehmannia glutinosa, including DXS, DXR, GPPS, G10H, and 10HGO. This upregulation of gene expression corresponded with the accumulation of iridoid glycosides, particularly under the treatment with 50 μM 5-azaC (Figure 2). Additionally, 5-azaC induced DNA demethylation in Rehmannia glutinosa, displaying a dose-dependent response. Similarly, the overexpression of PAL and C4H genes has been shown to enhance the production of phenylethanoids and improve the plant's tolerance to oxidative stress (Yang et al., 2020; 2021; 2023). The differential expression of homologous genes encoding key enzymes also plays a significant role in the regulation of terpenoid and phenylethanoid biosynthesis (Kang et al., 2022). 6 Pharmacological Activities and Mechanisms 6.1 Antioxidant properties Rehmannia glutinosa exhibits significant antioxidant properties, which are primarily attributed to its phenolic compounds. The cinnamate 4-hydroxylase (C4H) gene in R. glutinosa promotes phenolic accumulation, enhancing the plant's tolerance to oxidative stress by activating its antioxidant systems (Yang et al., 2021). Additionally, the antioxidant activity of R. glutinosa has been demonstrated through various assays, showing high levels of catalpol, rehmaionoside A, and rehmannioside D, which contribute to its strong antioxidant capacity (Liu et al., 2020). The antioxidant effects are further supported by the increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in treated models (Li et al., 2023).
RkJQdWJsaXNoZXIy MjQ4ODYzMg==