Stimulatory Effects of Acibenzolar-S-Methyl on Chlorogenic Acids Biosynthesis in Centella asiatica Cells

Abstract

Centella asiatica is a perrenial herb that grows in tropical regions with numerous medicinal properties mostly attributed to the presence of pentacyclic triterpenoids. Interestingly, this plant also possess a significant amount of phenylpropanoid-derived chlorogenic acids (CGAs) that have recently been reported to confer neuroprotective properties. In a biotechnological attempt to increase the biosynthesis of CGA-derivatives in cultured Centella cells, acibenzolar-S-methyl was applied as a xenobiotic inducer in combination with quinic acid and shikimic acid as precursor molecules. Applying a semi-targeted metabolomics-based approach, time and concentration studies were undertaken to evaluate the effect of the manipulation on cellular metabolism leading to CGA production. Phytochemical extracts were prepared using methanol and analyzed using a UHPLC-qTOF-MS platform. Data was processed and analyzed using multivariate data models. A total of four CGA-derivatives, annotated as trans-5-feruloylquinic acid, 3,5 di-caffeoylquinic acid, 3,5-O-dicaffeoyl-4-O-malonylquinic acid (irbic acid) and 3-caffeoyl, 5-feruloylquinic acid, were found to be upregulated by the acibenzolar-S-methyl treatment. To the best of our knowledge, this is the first report on the induction of CGA derivatives in this species. Contrary to expectations, the effects of precursor molecules on the levels of the CGAs were insignificant. However, a total of 16 metabolites, including CGA derivatives, were up-regulated by precursor treatment. Therefore, this study shows potential to biotechnologically manipulate C. asiatica cells to increase the production of these health beneficial CGAs.

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

“…Compounds such as the phenolic ferulic acid [89,90] and the triterpene asiatic acid [2,91], induce Nrf2 and its ARE-regulated targets, exhibiting a neuroprotective effect [92][93][94][95]. Caffeoylquinic acids found in CA [28,96,97], are also known to induce Nrf2 and Ho-1 signaling, and positively impact glutathione levels [98,99].…”

Comparative Metabolic Phenotyping of Tomato (Solanum lycopersicum) for the Identification of Metabolic Signatures in Cultivars Differing in Resistance to Ralstonia solanacearum

“…Defense-related HCA-conjugates include CGAs, which have a contributing role in plant resistance [ 28 , 37 ]. CGAs belong to the family of phytochemical esters produced from the shikimate- and early phenylpropanoid pathways that have been shown to confer plant resistance proportional to their intracellular concentration [ 20 , 36 , 38 , 39 ]. CGAs are natural antimicrobial compounds, which allows them to inhibit pathogenic factors and enzymes, thus suppressing pathogen virulence [ 40 ].…”

In vitro inhibition of shikimate hydroxycinnamoyltransferase by acibenzolar acid, the first metabolite of the plant defence inducer acibenzolar-S-methyl

“…The inhibition of HST by acibenzolar acid could thus theoretically play a role in the reallocation of phenylpropanoid precursors in metabolic pathways involved in defence at the expense of growth. This mechanism could for example promote the accumulation of chlorogenic acid which has been described in ASM-treated cell suspensions (Mhlongo et al, 2016, Ncube et al, 2016 or the formation of stilbenes and anthocyanins in ASM-treated grapevine cells (Iriti et al, 2004).…”