Elsevier

Phytochemistry

Volume 92, August 2013, Pages 8-15
Phytochemistry

Molecules of Interest
Harpagoside: from Kalahari Desert to pharmacy shelf

https://doi.org/10.1016/j.phytochem.2013.04.009Get rights and content

Highlights

  • Harpagoside is an iridoid glycoside isolated from several plant species.

  • Harpagoside possesses remarkable biological properties.

  • The biosynthetic pathway of harpagoside is not yet unraveled.

  • Engineering harpagoside biosynthesis would allow development of cell factories.

Abstract

Harpagoside is an iridoid glycoside that was first isolated from Harpagophytum procumbens (devil’s claw, Pedaliaceae), a medicinal plant in which it is the major constituent of the iridoid pool. Both the pure compound and devil’s claw extracts have potent anti-rheumatic, anti-inflammatory and analgesic effects. According to the European Pharmacopoeia commercial devil’s claw products should contain at least 1.2% harpagoside. However, the compound has also been isolated from several other plant species and in vitro plant culture systems. Recent advances in knowledge of harpagoside distribution, biosynthesis/accumulation and pharmacology are summarized in this review. We also discuss the possible synergism and/or antagonism between major constituents in harpagoside-containing phytopharmaceutical products. Finally, future perspectives for its potential application are highlighted.

Graphical abstract

Harpagoside is an iridoid glycoside with highly attractive pharmaceutical properties. It is the major constituent of the iridoid pool in Harpagophytum procumbens and is used for standardization of pharmaceutical products and botanical supplements. The compound has also been isolated from several other plant species and in vitro plant systems.

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Section snippets

Power from the Kalahari Desert: the discovery of harpagoside and related iridoid glycosides

Deep in the Kalahari Desert grows a herbaceous plant with high medicinal value called devil’s claw, Harpagophytum procumbens subsp. procumbens (Burch.) de Candolle ex Meissner, Pedaliaceae (Fig. 1A and B). Harpagophytum plants have been used for centuries by the Khoisan people of southern Africa to treat diverse health disorders, including fever, gastrointestinal problems diabetes, hypertension and blood diseases (Stewart and Cole, 2005). In the middle of the last century several systematic

The occurrence and distribution of harpagoside

A search of the SCOPUS database (accessed February 2013) identified 240 articles and 14 patents in which the word “harpagoside” appeared, mostly published after 2000 and mainly concerned with harpagoside isolated from devil’s claw. Knowledge of its occurrence and distribution in other plants is still limited. It has been detected mainly in the Lamiaceae, Pedaliaceae, Plantaginaceae and Scrophulariaceae families of the Lamiales order of dicotyledonous angiosperms (Table 1). However, Yuan et al.

The (bio)production and biosynthesis of harpagoside

It is important to develop sustainable biotechnological methods to produce devil’s claw products (particularly the valuable harpagoside) for pharmaceutical applications due to the restricted availability of plant material. In early studies, callus cultures were induced from fresh root tubers of H. procumbens, but they failed to produce harpagoside (Abou-Mandour, 1977, Franz et al., 1982). This is not surprising, since callus cultures consist of undifferentiated cells, in which gene expression

Pharmacology and applications of harpagoside

Arthritis is a common, chronic (long lasting), progressive and disabling autoimmune disease that causes inflammation and pain in the joints (usually in the hands and feet first, but any joint may become affected), tissues around the joints, and other organs in the human body (Firestein, 2003, Luyten et al., 2006). Current drugs have severe limitations for treating this crippling disease: thus there are urgent needs for new leads (Breedveld and Combe, 2011). Devil’s claw offers attractive

Future perspectives

Fifty years after the discovery of harpagoside, very little is still known about its biosynthetic pathway. Several key enzymes, and the genes encoding them, remain to be discovered. Thus, better understanding of harpagoside biosynthesis is required to identify means to boost its biosynthesis (and that of putative synergists) by metabolic engineering and subsequently to develop efficient cell factories for its mass-production. Recent advances in deep sequencing and metabolomic technologies are

Acknowledgements

Financial support from the Marie Curie programme of the European Community (Grant PIEF-GA-2009-252558) and the National Science Fund of Bulgaria (Grant DO-02-261/2008) is greatly appreciated. The authors express their thanks to Dr. Ilze Vermaak (Tshwane University of Technology, RSA) for kindly providing the devil’s claw photos.

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