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Review
. 2022 Jul 13;23(14):7740.
doi: 10.3390/ijms23147740.

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

Marius Mioc  1   2 , Andreea Milan  1   2 , Daniel Malița  3 , Alexandra Mioc  2   4 , Alexandra Prodea  1   2 , Roxana Racoviceanu  1   2 , Roxana Ghiulai  1   2 , Andreea Cristea  1 , Florina Căruntu  5 , Codruța Șoica  1   2
Affiliations
Review

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

Marius Mioc et al. Int J Mol Sci. .

Abstract

Triterpenic acids are phytocompounds with a widespread range of biological activities that have been the subject of numerous in vitro and in vivo studies. However, their underlying mechanisms of action in various pathologies are not completely elucidated. The current review aims to summarize the most recent literature, published in the last five years, regarding the mechanism of action of three triterpenic acids (asiatic acid, oleanolic acid, and ursolic acid), corelated with different biological activities such as anticancer, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, hepatoprotective, and antimicrobial. All three discussed compounds share several mechanisms of action, such as the targeted modulation of the PI3K/AKT, Nrf2, NF-kB, EMT, and JAK/STAT3 signaling pathways, while other mechanisms that proved to only be specific for a part of the triterpenic acids discussed, such as the modulation of Notch, Hippo, and MALAT1/miR-206/PTGS1 signaling pathway, were highlighted as well. This paper stands as the first part in our literature study on the topic, which will be followed by a second part focusing on other triterpenic acids of therapeutic value.

Keywords: asiatic acid; molecular mechanism; molecular target; oleanolic acid; triterpenic acid; ursolic acid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The chemical structures of lupane (1), oleanane (2), ursane (3), and hopane (4) scaffolds.
Figure 2
Figure 2
Flow diagram describing the data selection process.
Figure 3
Figure 3
The chemical structure of asiatic acid (5).
Figure 4
Figure 4
Biological activities of asiatic acid.
Figure 5
Figure 5
Schematic representation of the reported anticancer mechanisms of AA; key signaling pathways targeted by AA in cancer: Src/FAK/ERK signaling pathway inhibition -> inhibition of angiogenesis, cell proliferation, and migration; PI3K/Akt signaling pathway inhibition -> inhibition of angiogenesis, cell survival, and proliferation; inhibition of MEK/ERK pathway -> inhibits cell proliferation and differentiation; inhibition of TGF-β1/Smad3 signaling pathway -> inhibition of cell survival; inhibition of Wnt/β-catenin signaling pathway -> inhibition of cell proliferation and migration. Created with BioRender.com (accessed on 8 May 2022).
Figure 6
Figure 6
Schematic representation of the reported neuroprotective mechanisms of AA; key signaling pathways targeted by AA in neurodegeneration: inhibition of NF-kB/STAT3/ERK signaling pathway-> down-regulation of TNF-α, IL-1β and IL-6; up-regulation of Bcl and down-regulation of Bax -> anti-inflammatory and antiapoptotic effect; inhibition of TAK1-JNK pathway -> anti-inflammatory effect; up-regulation of Nrf2/HO-1 pathway -> reduction of ROS -> antioxidant effect. Created with BioRender.com (accessed on 8 May 2022).
Figure 7
Figure 7
Schematic representation of the reported cardioprotective mechanisms of AA; key signaling pathways targeted by AA in neurodegeneration: MAPK/mitochondria-dependent apoptotic pathway inhibition -> antioxidant effect; Akt/GSK-3β-mir-126 mediated signaling pathway activation -> reduces myocardial hypertrophy; TGF-β1/Smad2/3 phosphorylation inhibition -> reduces myocardial hypertrophy; increasing the expression of Nrf2, HO-1, and NQO-1 -> antioxidant effect; Ang II-AT1R-NADPH oxidase-NF-κB pathway inhibition -> anti-inflammatory effect. Created with BioRender.com (accessed on 8 May 2022).
Figure 8
Figure 8
The chemical structure of oleanolic acid (6).
Figure 9
Figure 9
Anticancer effect of oleanolic acid in various types of cancer.
Figure 10
Figure 10
Schematic representation of the reported anticancer mechanisms of OA; key signaling pathways targeted by OA in cancer: PI3K/Akt pathway up-regulation -> inhibition of cell migration; Notch signaling pathway inhibition -> inhibition of cell proliferation; NF-kB signaling pathway suppression -> anti-inflammatory effect; ERK/JNK/p38 pathway activation -> induction of apoptosis. Created with BioRender.com (accessed on 8 May 2022).
Figure 11
Figure 11
Schematic representation of the reported antidiabetic mechanisms of OA; key signaling pathways targeted by OA in diabetes: NF-kB signaling inhibition -> reduces IL-6 and TNF-α inflammatory cytokines -> antioxidant effect; NLRP3 inflammasome inhibition -> reduces expression of pro-inflammatory cytokines -> anti-inflammatory effect; MAPK signaling inhibition -> antioxidant effect; HO-1/Nrf2 pathway up-regulation- antioxidant effect. Created with BioRender.com (accessed on 8 May 2022).
Figure 12
Figure 12
The chemical structure of ursolic acid (7).
Figure 13
Figure 13
Biological activities of ursolic acid.
Figure 14
Figure 14
Schematic representation of the reported anticancer mechanisms of UA; key signaling pathways targeted by UA in cancer: PI3K/Akt signaling pathway inhibition -> inhibition of angiogenesis, cell survival, and proliferation; JNK signaling pathway activation-> induction of apoptosis; TGF-β1 pathway inhibition -> miR200a/b/c up-regulation -> induction of apoptosis; EGFR/JAFK2/STAT3 signaling pathway down-regulation -> G0/G1 cycle arrest -> apoptosis; ROCK1/PTEN/cytochrome c signaling pathway down-regulation-> activation of caspases -> induction of apoptosis; IKK/NF-kB pathway down-regulation -> G0/G1 cycle arrest -> apoptosis. Created with BioRender.com (accessed on 8 May 2022).
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