Hindawi Publishing Corporation
Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 519652, 7 pages
doi:10.1155/2011/519652
Research Article
DLBS1033, A Protein Extract from Lumbricus rubellus,
Possesses Antithrombotic and Thrombolytic Activities
Jessica Trisina,
1
Febrina Sunardi,
1
Maggy T. Suhartono,
1, 2
and Raymond R. Tjandrawinata
1
1
Division of Protein Biochemistry and Molecular Pharmacology, Dexa Laboratories of Biomolecular Sciences, PT Dexa Medica,
Industri Selatan V Block PP no. 7, Kawasan Industri Jababeka II, Cikarang 17550, Indonesia
2
Department of Food Science and Technology, Bogor Agricultural University, Fateta Building Kampus IPB Darmaga,
Bogor 16680, Indonesia
Correspondence should be addressed to Raymond R. Tjandrawinata, raymond@dexa-medica.com
Received 9 November 2010; Revised 17 December 2010; Accepted 15 January 2011
Academic Editor: Michael Kalafatis
Copyright © 2011 Jessica Trisina et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The medicinal value of earthworm has been widely known since the history of Asian ancient medicine. This present study aims
to determine the mechanism of action and effect of a standardized extract of Lumbricus rubellus named as DLBS1033. The
fibrinogen degradation, antiplatelet aggregation, and ex vivo antithrombotic assay using human blood were performed to study
antithrombotic activity. Fibrin plate and clot lysis assay were also done to examine thrombolytic properties. DLBS1033 was found
to possess fibrinogenolytic activity on α-, β-, and γ-chain of fibrinogen. It also induced antiplatelet aggregation and prolonged
blood clotting time, which further confirmed its antithrombotic properties. In addition, thrombolytic properties of DLBS1033
were shown with its fast and long-acting fibrinolytic activity, as well as its effective blood clot lysis activities. In conclusion,
DLBS1033 conferred antithrombotic and thrombolytic action which could be used as a safe and promising oral thrombolytic
drug.
1. Introduction
For several years, earthworms have been widely used in
Indonesia, China, Japan, and the Far East to treat vari-
ous chronic diseases. Deep exploration has been made to
reveal the use of earthworms as antimicrobial [1], anti-
inflammatory [2], and anticancer [3] agents.
In 1991, Mihara et al. found that the earthworm from
Lumbricidae family could directly dissolve fibrin and activate
plasminogen [4]. The active constituents of earthworm have
been characterized and known to have fibrinolytic enzymes,
a group of serine protease enzymes. Earthworm fibrinolytic
enzymes (EFEs) are composed of several isozymes which
can be transported into blood through intestinal epithelium
[5–7]. It confers fibrinolytic and fibrinogenolytic properties,
lowers blood viscosity, markedly reduces platelet aggrega-
tion, and promotes thrombus degradation in blood [8–
10]. Due to those properties, earthworm fibrinolytic enzyme
has been extensively studied as an oral thrombolytic drug
[10, 11].
The most common sources of earthworm fibrinolytic
enzymes are Lumbricus rubellus, Eisenia foetida, and Phere-
tima sp. Each earthworm has different isozyme constituents
depending on the species and living environment [12] that
may lead to differences in their activities. Recently, research
progress has been made using earthworm as one of its natural
resources in developing medicines to treat thrombosis-
related diseases. It is one of the most widely occurring
diseases in modern life, which often cause disability and
death. This present study was intended to explore the
characterization, activity, and mechanism of actions of
DLBS1033, earthworm extract prepared from Lumbricus
rubellus originated from Indonesia, with regards to its
antithrombotic and thrombolytic activities as a promising
therapeutic agent for thrombosis-associated diseases.
2. Materials and Methods
DLBS1033 was prepared in Dexa Laboratories of Biomolec-
ular Sciences (Cikarang, Indonesia). Lumbricus rubellus