Anti-cancer labdane diterpenoids from adventitious roots of Andrographis paniculata: augmentation of production prospect endowed with pathway gene expression

Abstract

Andrographolide (AD) is the time-honoured pharmacologically active constituent of the traditionally renowned medicinal plant-Andrographis paniculata. Advancements in the target-oriented drug discovery process have further unravelled the immense therapeutic credibility of another unique molecule-neoandrographolide (NAD). The escalated market demand of these anti-cancer diterpenes is increasingly facing unrelenting hurdles of demand and supply disparity, attributable to their limited yield. Callus and adventitious root cultures were generated to explore their biosynthetic potentials which first time revealed NAD production along with AD. Optimization of the types and concentrations of auxins along with media form and cultivation time led to the successful tuning towards establishing adventitious roots as a superior production alternative for both AD/NAD. Supplementation of IBA to the NAA + Kn-containing MS medium boosted the overall growth and AD/NAD synthesis in the adventitious roots. Compared to control leaves, the adventitious root exhibited about 2.61- and 8.8-fold higher contents of AD and NAD, respectively. The qRT-PCR involving nine key pathway genes was studied, which revealed upregulation of GGPS1 and HMGR1/2 genes and downregulation of DXS1/2 and HDR1/2 genes in the adventitious root as compared to that in the control leaves. Such observations highlight that in vitro cultures can serve as efficient production alternatives for AD/NAD as the cytosolic genes (HMGR1/2 of MVA pathway) are competent enough to take over from the plastidial genes (DXS1/2 and HDR1/2 of MEP pathway), provided the accredited first branch-point regulatory gene (GGPS) expression and the culture requirements are optimally fulfilled.

The influence of cultivation conditions on the formation of psychoactive salvinorin A, salvinorin B, rosmarinic acid and caffeic acid in Coleus scutellarioides

“…6-benzyloaminopurine reduce the amount of compounds witch are biosynthesized on the MEP pathway 48 , similar as in our case. The other studies indicate the influence of NAA on the MEP pathway 49 , 50 . Our results indicate that this plant growth regulator stimulated the biosynthesis of identificed secondary metabolites.…”

Antitumor effects of Andrographis via ferroptosis‑associated genes in gastric cancer

“…Accumulating evidence has shown that dietary botanical compounds, such as herbal medicines, have increasingly important roles in the field of cancer treatment, both as therapeutic agents and adjunctive treatments to traditional therapies (10,47). Andrographolide is a C20 labdane diterpenoid derived from the traditional Chinese medicine Andrographis paniculate (12)(13)(14), which has been found to have cytotoxic/anti-tumorigenic potential in various malignancies (14,20,22,(24)(25)(26)28). Intriguingly, Andrographolide was demonstrated to alter multiple cancer-associated signaling pathways, such as BAX-dependent apoptotic signaling in breast cancer (22), PI3K/AKT/mTOR-dependent signaling in leukemia (20) and glioblastoma (24), p38 signaling in melanoma ( 14), STAT3/AKT activation in pancreatic cancer (28), and the Src/MAPKs/AP-1 axis (25) and TLR4/NF-kB/MMP-9 pathway (32) in colorectal cancer.…”

“…Interestingly, most of these dietary botanicals function by targeting multiple cancer-associated pathways to exert anti-tumorigenic effects on cancer progression (11). Andrographolide is a C20 diterpenoid lactone, which is an active ingredient derived from the traditional Chinese herbal medicine Andrographis paniculate (12)(13)(14). Because of its ability to circulate in the bloodstream (15)(16)(17), Andrographis…”

Molecular Cloning and Differential Gene Expression Analysis of 1-Deoxy-D-xylulose 5-Phosphate Synthase (DXS) in Andrographis paniculata (Burm. f) Nees

“…Evidently, the higher expressions of ApDXS and ApHMGR genes at 25 µM and 50 µM with higher andrographolide synthesis indicated the crucial role of these two genes and the synergy between MVA/MEP pathways. Singh et al [48] reported that untreated control, in vitro adventitious root cultures of A. paniculata have shown high-expression levels of MVA pathway genes (HMGR1/2) and low expression of MEP pathway genes (DXS1/2 and HDR1/2). However, in our study, an external stimulus JA not only enhanced the MEP pathway-related gene expression, but also significantly influenced MVA pathway genetic.…”