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Oleandrin: A Systematic Review of its Natural Sources, Structural Properties, Detection Methods, Pharmacokinetics and Toxicology

Zhai, Jinxiao, Dong, Xiaoru, Yan, Fenglian, Guo, Hongsong, Yang, Jinling·2022·Frontiers in Pharmacology
DOI 10.3389/fphar.2022.822726PMC PMC8902680
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Abstract

Oleandrin is a highly lipid-soluble cardiac glycoside isolated from the plant Nerium oleander (Apocynaceae) and is used as a traditional herbal medicine due to its excellent pharmacological properties. It is widely applied for various disease treatments, such as congestive heart failure. Recently, oleandrin has attracted widespread attention due to its extensive anti-cancer and novel anti-viral effects. However, oleandrin has a narrow therapeutic window and exhibits various toxicities, especially typical cardiotoxicity, which is often fatal. This severe toxicity and low polarity have significantly hindered its application in the clinic. This review describes natural sources, structural properties, and detection methods of oleandrin. Based on reported poisoning cases and sporadic animal experiments, the pharmacokinetic characteristics of oleandrin are summarized, so as to infer some possible phenomena, such as enterohepatic circulation. Moreover, the relevant factors affecting the pharmacokinetics of oleandrin are analyzed, and some research approaches that may ameliorate the pharmacokinetic behavior of oleandrin are proposed. With the toxicology of oleandrin being thoroughly reviewed, the development of safe clinical applications of oleandrin may be possible given potential research strategies to decrease toxicity.

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FIGURE 1 Natural sources and structural properties of oleandrin. (A) Categories of plants commonly known as “oleander.” (B) The main sources of oleandrin: Nerium oleander. (C) Classification of cardiac glycosides (CGs). (D) The chemical structure of oleandrin and its hydrolysate oleandrigenin and other structure of typical CGs.
FIGURE 1 Natural sources and structural properties of oleandrin. (A) Categories of plants commonly known as “oleander.” (B) The main sources of oleandrin: Nerium oleander. (C) Classification of cardiac glycosides (CGs). (D) The chemical structure of oleandrin and its hydrolysate oleandrigenin and other structure of typical CGs.CC BY · PubMed Central
FIGURE 2 Pharmacokinetic characteristics and influencing factors of oleandrin.
FIGURE 2 Pharmacokinetic characteristics and influencing factors of oleandrin.CC BY · PubMed Central
FIGURE 3 The absorption, distribution, metabolism, and excretion (ADME) process of oleandrin. (A) Pharmacological properties of oleandrin. (B) Detailed ADME process of oleandrin in vivo. (C) The possibility of bile excretion and enterohepatic circulation (EHC) of oleandrin in vivo. (D) The possible first-pass effect.
FIGURE 3 The absorption, distribution, metabolism, and excretion (ADME) process of oleandrin. (A) Pharmacological properties of oleandrin. (B) Detailed ADME process of oleandrin in vivo. (C) The possibility of bile excretion and enterohepatic circulation (EHC) of oleandrin in vivo. (D) The possible first-pass effect.CC BY · PubMed Central
FIGURE 4 Overview of literature data of the poisoning cases caused by Nerium Oleander. (A) Species involved in oleander poisoning cases. (B) Summary of oleandrin tissue distribution concentration in reported fatal cases of oleander in humans (ng/mL or ng/g).
FIGURE 4 Overview of literature data of the poisoning cases caused by Nerium Oleander. (A) Species involved in oleander poisoning cases. (B) Summary of oleandrin tissue distribution concentration in reported fatal cases of oleander in humans (ng/mL or ng/g).CC BY · PubMed Central
FIGURE 5 The toxicity of oleandrin and its typical toxicity mechanism. (A) Summary of the toxicity of oleandrin. (B) Schematic representation of oleandrin-mediated inhibition of Na/K-ATPase in cardiac myocytes.
FIGURE 5 The toxicity of oleandrin and its typical toxicity mechanism. (A) Summary of the toxicity of oleandrin. (B) Schematic representation of oleandrin-mediated inhibition of Na/K-ATPase in cardiac myocytes.CC BY · PubMed Central

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Metadata

Authors
Zhai, J., Dong, X., Yan, F., Guo, H., & Yang, J.
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2022-02-21
Volume
13
ISSN
1663-9812
DOI
10.3389/fphar.2022.822726
PMC
PMC8902680
Cited by
45
References
3
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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