Harpagoside is a

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...

found in the plant ''

Harpagophytum procumbens ''Harpagophytum'' ( ), also called grapple plant, wood spider, and most commonly devil's claw, is a genus of plants in the sesame family, native to southern Africa. Plants of the genus owe their common name "devil's claw" to the peculiar appe ...

'', also known as devil's claw. It is the active chemical constituent responsible for the medicinal properties of the plant, which have been used for centuries by the

Khoisan Khoisan ( ) or () is an Hypernymy and hyponymy, umbrella term for the various Indigenous peoples of Africa, indigenous peoples of Southern Africa who traditionally speak non-Bantu languages, combining the Khoekhoen and the San people, Sān peo ...

people of southern Africa to treat diverse health disorders, including fever, diabetes, hypertension, and various blood related diseases.

Biosynthesis

Harpagoside is characterized as an

iridoid glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

, which is a product of the

mevalonate pathway The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl ...

present in the metabolism of eukaryotes, archaea and some bacteria. The iridane skeleton found in iridoids is monoterpenoid in origin and contains a cyclopentane ring fused to a six-membered oxygen heterocycle. The iridoid system arises from geraniol, which itself is synthesized from geranyl pyrophosphate (GPP) by geraniol diphosphate synthase (E1). A p450 type enzyme, geraniol 8-hydroxylase (E2), then hydroxylates geraniol at the 8 position to form 8-hydroxygeraniol. The diol then undergoes two oxidation steps catalyzed by 8-hydroxygeraniol dehydrogenase (E3) to form the dialdehyde, 8-oxogeranial. NADPH catalyzed monoterpene cyclase (E4) then forms three possible iridodial isomers. Instead of further oxidation to the iridotrial, which is the branchpoint precursor to

secologanin Secologanin is a secoiridoid monoterpene synthesized from geranyl pyrophosphate in the mevalonate pathway. Secologanin then proceeds with dopamine or tryptamine to form ipecac and terpene indole alkaloids, respectively. Biosynthesis Secologa ...

and downstream alkaloids, the keto form equilibrates into a hemiacetal and isomerizes to form 8-epi-iridodial. Carboxylation followed by glycosylation leads to the glycoside. Subsequent decarboxylation and three p450-type oxidations leads to harpagide. Cinnamoyl esterification at the 3-hydroxyl position leads to the natural product harpagoside. Natural Products- Harpagoside

Biological activity

Harpagoside is widely used as a folk remedy to treat rheumatic complaints. Subsequent studies have shown that extracts have good- anti-inflammatory and analgesic activities. An assessment of 15 studies (lesquelles) on the pharmacology of harpagoside concluded that daily doses of at least 50 mg are effective for treating arthritis. Clinical studies have confirmed an increase in pain relief for 60% of patients with an osteoarthritic hip or knee. Biochemical studies have elucidated the mechanism of action of pure harpagoside, showing that it moderately inhibited cyclooxygenases 1 and 2 of the arachidonic acid pathway ( COX – 1/2) and overall nitric oxide production in human blood. COX 1 and 2 are key enzymes of the arachidonic acid pathway and it has been shown that inhibitors of these cyclooxygenases have implications for treating rheumatoid arthritis.

References

{{reflist Iridoid glycosides Glucosides Cyclopentanes Cinnamate esters