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Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

  • Heike FrankeEmail author
  • Reinhold Scholl
  • Achim Aigner
Review
  • 99 Downloads

Abstract

While probably originating from Africa, the plant Ricinus communis is found nowadays around the world, grown for industrial use as a source of castor oil production, wildly sprouting in many regions, or used as ornamental plant. As regards its pharmacological utility, a variety of medical purposes of selected parts of the plant, e.g., as a laxative, an anti-infective, or an anti-inflammatory drug, have been described already in the sixteenth century bc in the famous Papyrus Ebers (treasured in the Library of the University of Leipzig). Quite in contrast, on the toxicological side, the native plant has become the “poisonous plant 2018” in Germany. As of today, a number of isolated components of the plant/seeds have been characterized, including, e.g., castor oil, ricin, Ricinus communis agglutinin, ricinin, nudiflorin, and several allergenic compounds. This review mainly focuses on the most toxic protein, ricin D, classified as a type 2 ribosome-inactivating protein (RIP2). Ricin is one of the most potent and lethal substances known. It has been considered as an important bioweapon (categorized as a Category B agent (second-highest priority)) and an attractive agent for bioterroristic activities. On the other hand, ricin presents great potential, e.g., as an anti-cancer agent or in cell-based research, and is even explored in the context of nanoparticle formulations in tumor therapy. This review provides a comprehensive overview of the pharmacology and toxicology-related body of knowledge on ricin. Toxicokinetic/toxicodynamic aspects of ricin poisoning and possibilities for analytical detection and therapeutic use are summarized as well.

Keywords

Ricinus communis Papyrus Ebers Ricin Castor oil Intoxication Nanoparticles Immunotoxins Tumor therapy 

Abbreviations

BC

Before Christ

BTWC

Biological and Toxin Weapons Convention

CB-1A

Castor bean allergenic fraction

CDC

Centers for Disease Control and Prevention

CEA

Carcinoembryonic antigen

CNS

Central nervous system

CWC

Chemical Weapons Convention

ELISA

Enzyme-linked immunosorbent assay

EMA

European Medicines Agency

EPR

Enhanced permeability and retention

ER

Endoplasmic reticulum

EROEI

Energy return-on-energy investment

EQuATox

Establishment of Quality Assurance for the Detection of Biological Toxins of Potential Bioterrorism Risk

FAO

Joint Food and Agriculture Organization

FDA

Food and Drug Administration

H5WYG

Histidine-rich fusogenic peptide

HBV

Hepatitis B virus

HER2/neu

Human epidermal growth factor receptor 2

IgG

Immunoglobulin G

i.m.

Intramuscular

i.v.

Intravenous

IUPAC

International Union of Pure and Applied Chemistry

LD50

Lethal dose 50%

LFA

Lateral flow assay

LC/MS

Liquid chromatography/mass spectrometry

MALDI-TOF

Matrix-assisted laser desorption/ionization time-of-flight

MR

Mannose receptor

MWNTs

Multiwalled carbon nanotubes

OPCW

Organization for the Prohibition of Chemical Weapons

PAP

Pokeweed anti-viral proteins

PCR

Polymerase chain reaction

PEG

Polyethylene glycol

ROS

Reactive oxygen species

RCA

Ricinus communis agglutinin

RIP2

Ribosome-inactivating protein type 2

RTA

Ricin A chain

RTB

Ricin B chain

RNAi

RNA interference

VLPs

Virus-like particles

VLS

Vascular lead syndrome

WHO

World Health Organization

Notes

Acknowledgments

Parts of this article on the history of the plant Ricinus communis in the Papyrus Ebers were presented at the Symposium on the Occasion of the 30. Anniversary of the Postgraduate Study Program (PGS) “Toxicology and Environmental Protection” at the University of Leipzig (March 23, 2018). PGS graduation theses by Jörg Pietsch (2004), Gabriele Baranius (2009), and Thorsten Meißner (2017) as well as a study work prepared by Avina Graefe (2012) contributed to this review article and are greatly acknowledged. The authors are grateful to Dr. Jens Grosche (Effigos AG) for providing Fig. 4. The authors also wish to thank Adelgunde Graefe (PGS “Toxicology and Environmental Protection,” University of Leipzig) and Thomas Gruner (Library of the Medical Faculty, University of Leipzig) for their support.

Author contribution statement

HF, RS, and AA wrote the manuscript. HF took the photos, HF and AA created figures and tables. All authors read and approved the manuscript.

Compliance with ethical standards

Not applicable.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

210_2019_1691_Fig5_ESM.png (7.7 mb)
Suppl. Figure 1

Examples of the world wide distribution of the plant Ricinus communis: (A) La Reunion (on a roadside, up to 10 m high); (B) La Reunion (forest landscape, accompanied by palms); (C) Namibia (Chobe National Park); (D) Madagaskar (Tulear); (E) Vietnam (Hanoi); (F) Ecuador; (G) Costa Rica (Rio Tarcoles); (H) Germany (Botanical Garden, Leipzig). (PNG 7863 kb)

210_2019_1691_MOESM1_ESM.tif (15.4 mb)
High Resolution Image (TIF 15726 kb)
210_2019_1691_MOESM2_ESM.pptx (459 kb)
Suppl. Figure 2 Amino acid sequence alignment of ricin in comparison with the type 1 RIPs Gelonin, Trichosanthin, Momordin, Bouganin, Pokeweed anti-viral protein (PAP), Saponin, and Dianthin. Alignment was performed using Clutal Omega (https://www.ebi.ac.uk/services). (PPTX 458 kb) (PPTX 458 kb)
210_2019_1691_MOESM3_ESM.pptx (235 kb)
Suppl. Figure 3 Amino acid sequence alignment of ricin and mistletoe lectin-1 from Viscum album. Colors indicate sequence domains encoding for the signal peptide, A-chain, linker, and B-chain. Alignment was performed using Clutal Omega (https://www.ebi.ac.uk/services). Asterisks indicate sequence identities. (PPTX 234 kb)
210_2019_1691_MOESM4_ESM.pptx (69 kb)
Suppl. Figure 4 Toxic effects of ricin (PPTX 69 kb)
210_2019_1691_MOESM5_ESM.pptx (69 kb)
Suppl. Figure 5 Examples of the different applications of castor oil and its derivatives today (PPTX 69 kb)
210_2019_1691_MOESM6_ESM.docx (27 kb)
Suppl. Table 1 Examples of representative LD50 values of different kinds of toxins (DOCX 26.8 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Rudolf-Boehm-Institute of Pharmacology and Toxicology, Medical FacultyUniversity of LeipzigLeipzigGermany
  2. 2.Department of HistoryUniversity of LeipzigLeipzigGermany
  3. 3.Rudolf-Boehm-Institute of Pharmacology and Toxicology, Clinical Pharmacology, Medical FacultyUniversity of LeipzigLeipzigGermany

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