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Review
. 2022 Oct 26;15(11):1325.
doi: 10.3390/ph15111325.

Pharmacokinetics and Biological Activity of Cucurbitacins

Eugenia Elisa Delgado-Tiburcio  1 , Jorge Cadena-Iñiguez  2 , Edelmiro Santiago-Osorio  3 , Lucero Del Mar Ruiz-Posadas  1 , Israel Castillo-Juárez  1 , Itzen Aguiñiga-Sánchez  3   4 , Marcos Soto-Hernández  1
Affiliations
Review

Pharmacokinetics and Biological Activity of Cucurbitacins

Eugenia Elisa Delgado-Tiburcio et al. Pharmaceuticals (Basel). .

Abstract

Cucurbitacins are a class of secondary metabolites initially isolated from the Cucurbitaceae family. They are important for their analgesic, anti-inflammatory, antimicrobial, antiviral, and anticancer biological actions. This review addresses pharmacokinetic parameters recently reported, including absorption, metabolism, distribution, and elimination phases of cucurbitacins. It includes recent studies of the molecular mechanisms of the biological activity of the most studied cucurbitacins and some derivatives, especially their anticancer capacity, to propose the integration of the pharmacokinetic profiles of cucurbitacins and the possibilities of their use. The main botanical genera and species of American origin that have been studied, and others whose chemo taxonomy makes them essential sources for the extraction of these metabolites, are summarized.

Keywords: absorption; cancer; cucurbitacins; distribution; excretion; metabolism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the chemical structure and biological properties of cucurbitacins. (A) The basic structure of this class of molecules is the core of cucurbitan (19-(10→β)-abeo-10α-lanost-5-ene), enumerated in the molecule’s center. Some of the main cucurbitacins in natural products are CuB, CuE, CuD, CuI, CuIIa, and CuIIb. The main differences are in the substitution pattern of ring A (C1–C5) and the side chain, where there may be unsaturation (C23–C25) and acetyl groups (C25). Additionally, alpha and beta hydroxyls are present at C2, C3, C7, C9, C16, and C20–C25. At the same time, unsaturation occurs at C23–C25, and the presence of keto groups in C2, C3, C11, C15, and C22. (B) Some derivatives important for their biological effects are shown.
Figure 2
Figure 2
The pharmacokinetic properties of cucurbitacin B.
Figure 3
Figure 3
Most important biological action mechanisms of CuB, CuD, CuE, CuI, and CuIIa, where cucurbitacins have the following effects: (A) apoptotic, (B) autophagic, (C) cell migration and invasion, (D) cell cycle arrest, (E) inhibition of cell growth and survival, and (F) anti-inflammatory.
Figure 4
Figure 4
Possible mechanism of action of cucurbitacin G2-glucoside against protease Mpro SARS-CoV-2.
Figure 5
Figure 5
Recent anticancer effects described on different cell signaling pathways by CuB. Upregulation (↑) and downregulation (↓).
See this image and copyright information in PMC

References

    1. Chen J.C., Chiu M.H., Nie R.L., Cordel G.A., Qiuz S.X. Cucurbitacins and Cucurbitane Glycosides: Structures and Biological Activities. Nat. Prod. Rep. 2005;22:386–399. doi: 10.1039/b418841c. - DOI - PubMed
    1. Soto-Hernández M., Cadena-Iñiguez J., Arévalo-Galarza L., Santiago-Osorio E., Aguiñiga-Sánchez I., Ruíz-Posadas L., del Mar Ruíz-Posadas L. Lead Compounds from Cucurbitaceae for the Treatment of Cancer. IntechOpen; London, UK: 2015. - DOI
    1. Lee D.H., Iwanski G.B., Thoennissen N.H. Cucurbitacin: Ancient Compound Shedding New Light on Cancer Treatment. Sci. World J. 2010;10:413–418. doi: 10.1100/tsw.2010.44. - DOI - PMC - PubMed
    1. Abdelwahab S.I., Hassan L.E.A., Sirat H.M., Yagi S.M.A., Koko W.S., Mohan S., Taha M.M.E., Ahmad S., Chuen C.S., Narrima P., et al. Anti-Inflammatory Activities of Cucurbitacin E Isolated from Citrullus Lanatus Var. Citroides: Role of Reactive Nitrogen Species and Cyclooxygenase Enzyme Inhibition. Fitoterapia. 2011;82:1190–1197. doi: 10.1016/j.fitote.2011.08.002. - DOI - PubMed
    1. Zhong H., Huang Y., Deng X., Liu M., Luo W. Cucurbitacin B Supplementation Reduces Inflammatory Responses and Alveolar Bone Loss via Regulating MPO, COX-2 and RANK/RANKL/OPG Signals in a Rodent Model of Ligature-Induced Periodontitis. J. King Saud Univ. Sci. 2020;32:1889–1895. doi: 10.1016/j.jksus.2020.01.028. - DOI

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