Bioscience Evidence 2024, Vol.14, No.3, 98-109 http://bioscipublisher.com/index.php/be 103 5.4 Synergistic effects of combined components The combined use of different bioactive components fromRehmannia glutinosa can result in synergistic effects, enhancing their overall pharmacological activities. For example, the combination of catalpol, acteoside, and echinacoside has been shown to enhance bone formation and prevent bone loss in diabetic rats by regulating the IGF-1/PI3K/mTOR signaling pathways (Gong et al., 2019). This synergistic interaction highlights the potential of using multiple components from Rehmannia glutinosa to achieve more effective therapeutic outcomes. Additionally, the combined antioxidant and anti-inflammatory properties of these components can provide comprehensive protection against oxidative stress and inflammation-related diseases (Liu et al., 2020; Rahmat et al., 2022). In conclusion, the bioactive components of Rehmannia glutinosa, including iridoid glycosides, phenethyl alcohol glycosides, and polysaccharides, exhibit a wide range of pharmacological activities. These activities include anti-inflammatory, neuroprotective, antioxidant, hepatoprotective, immunomodulatory, and antitumor effects. The synergistic interactions between these components further enhance their therapeutic potential, making Rehmannia glutinosa a valuable medicinal plant for various health conditions. 6 Mechanisms of Action 6.1 Cellular and molecular targets Rehmannia glutinosa, a traditional Chinese medicinal herb, contains several bioactive compounds such as acteoside, catalpol, and ferulic acid, which have been shown to target various cellular and molecular components. Acteoside, for instance, is synthesized through the action of tyrosine decarboxylase (RgTyDC2), which converts tyrosine into tyramine, a precursor in acteoside biosynthesis (Li et al., 2022). Similarly, ferulic acid biosynthesis involves the enzyme caffeic acid O-methyltransferase (RgCOMT), which catalyzes the methylation of caffeic acid (Yang et al., 2023). These enzymes are crucial for the production of bioactive compounds that interact with cellular targets to exert their pharmacological effects. 6.2 Signal transduction pathways The bioactive compounds in Rehmannia glutinosa influence various signal transduction pathways. For example, phenolic compounds produced via the phenylpropanoid pathway, such as those catalyzed by cinnamate 4-hydroxylase (RgC4H), play a significant role in the plant's response to oxidative stress by activating antioxidant systems (Yang et al., 2021). The overexpression of RgC4H enhances the plant's tolerance to oxidative stress by modulating the phenolics/phenylpropanoid pathway, which in turn activates molecular networks that mitigate the effects of drought, salinity, and hydrogen peroxide-induced stress (Yang et al., 2021). Additionally, the suppression of pro-inflammatory cytokine IL-6 in lipopolysaccharide-stimulated macrophages by puffed Rehmannia glutinosa extracts indicates the involvement of anti-inflammatory pathways (Kwon et al., 2019). 6.3 Genetic and epigenetic regulation The biosynthesis of bioactive compounds in Rehmannia glutinosa is tightly regulated at the genetic and epigenetic levels. The expression of genes involved in the phenylpropanoid pathway, such as phenylalanine ammonia-lyase (RgPAL), is crucial for the production of phenolic compounds (Yang et al., 2021). Overexpression of RgPAL genes has been shown to enhance phenolic production and release, which is associated with the development of replanting disease due to autotoxic harm (Yang et al., 2021). Furthermore, the differential expression of genes in radial striation (RS) and non-radial striation (nRS) tissues of Rehmannia glutinosa tuberous roots highlights the tissue-specific regulation of catalpol and acteoside biosynthesis (Zhi et al., 2018). Transcriptome analysis has identified key genes and transcription factors that are differentially expressed in these tissues, providing insights into the genetic regulation of bioactive compound accumulation (Zhi et al., 2018) (Figure 2). In conclusion, the bioactive compounds of Rehmannia glutinosa target specific cellular and molecular components, modulate various signal transduction pathways, and are regulated by complex genetic and epigenetic mechanisms. Understanding these mechanisms is essential for harnessing the therapeutic potential of this medicinal herb.
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