In VitroAntiplasmodial Activity of Abietane and Totarane Diterpenes Isolated fromHarpagophytum procumbens(Devil’s Claw)

Abstract

The development of drug resistance and resurgence of malaria has highlighted the need for new chemically diverse antimalarial drugs. This study investigates Harpagophytum procumbens DC. as a source of antiplasmodial hit compounds. The roots of wild harvested plants as well as the aerial sections, seeds and roots of cultivated H. procumbens were evaluated for in vitro antiplasmodial activity. Bioassay-guided fractionation of the petroleum ether root extract yielded two diterpenes, (+)-8,11,13-totaratriene-12,13-diol (1) and (+)-8,11,13-abietatrien-12-ol (2). Compounds 1 and 2 displayed significant (IC50 < 1 microg/mL) in vitro antiplasmodial activity against a chloroquine-resistant (K1) and -sensitive (D10) strain of Plasmodium falciparum, and low cytotoxicity (SI > 65) against two mammalian cell lines (CHO and HepG2). It was found that 1 and 2 did not modify the erythrocyte shape, which in conjunction with the cytotoxicity results, indicates selective antiplasmodial activity.

Identification of Major and Minor Constituents of Harpagophytum procumbens (Devil's Claw) Using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS

“…Although these were diterpenoids, as shown by the observation of methyl and isopropyl 1 H resonances, the compounds were present in very small amounts, and full structural elucidation was not conducted. While compounds 9 and 10 have previously been isolated from the PE extract of H. procumbens in 0.03% and 0.02% yields, respectively (by dry weight of the root material), this is the first report of 11 − 14 from this source. Considering the yield of the crude PE extract (0.6%), it can be concluded that the diterpenes are minor constituents of H. procumbens roots.…”

“…Some of the observed discrepancies could be attributed to the lack of standardization of the H. procumbens extracts and insufficient chemical profiling of the plant material. Although phytochemical investigations and bioassay-guided fractionation of the roots have led to the identification of a number of secondary metabolites, mainly phenethyl glycosides and iridoids, − the characterized compounds have typically been limited to those present in sufficient amounts for isolation of milligram quantities, necessary for structural elucidation.…”

From Bush Medicine to Modern Phytopharmaceutical: A Bibliographic Review of Devil’s Claw (Harpagophytum spp.)

“…Isolation and characterization of harpagoside [117] Stachyose, raffinose, and a further glucoside in the aqueous phase [118] Characterization of harpagoside [119] Isolation and characterization of harpagoside and harpagide [120] Characterization of harpagoside [121] Characterization of harpagide [122] Isolation of stachyose and a further glucoside [123] Characterization of harpagoside [124] Isolation of procumbide [125] Structural characterization of harpagoside [126] Characterization of procumbide and further constituents [127] Characterization of procumbide [128] Characterization of a chinone and other constituents [185] Characterization of procumbide [186] Further constituents [187] Elucidation of triterpene esters [188] Overview of known mono-, di-, and sesquiterpenoids with pharmacological activity [189] Elucidation of a resin, an essential oil, and a mucilaginous fraction [190] Structural characterization of procumbide [191] Glucose, galactose, fructose, myo-inositol, sucrose, raffinose, and stachyose identified [192] Preparation and structure of harpagogenine [193] Carbohydrates and harpagoside in tissue cultures and roots of devil's claw [194] New iridoids: 8-O-(p-coumaryl)-harpagide and procumboside [195] Novel iridoid and phenolic compounds [196] Three pyridine monoterpene alkaloids from harpagoside and commercial extract [197] Review of iridoids [198] Review of composition (both species) [199] Two diterpenes, (+)-8,11,13-totaratriene-12,13-diol and ferruginol [200] New iridoid-and phenylethanoid glycosides [201] Acetylated phenolic glycosides [202] Pharmacological characterization of harpagoside [203] Chinane-type tricyclic diterpenes and other minor compounds …”

“…Carrageenan-induced back-paw edema, Freund's adjuvant-induced arthritis, cotton pellet-induced granuloma, and writhing tests in rats and mice; Harpagophytum aqueous extract (800 mg/kg bw), acetyl salicylic acid and indomethacin as controls; significant effects in all models similar to indomethacin and acetyl salicylic acid.2005Ahmed et al[319] TPA-induced COX-2 expression in mouse skin; Harpagophytum methanolic extract(200,400 µg) topically prior to TPA application; significant inhibition of COX-2 expression, COX-1 unchanged, no effect on NF-κB. Adult female white New Zealand rabbits, anterior cruciate ligament transected, and medial meniscus removed; Harpagophytum extract (150 mg/day), standard food pellets as control; outcome suggests suppression of metalloproteinase-2 production.…”

The Synthesis and Antimicrobial Activity of Heterocyclic Derivatives of Totarol

“…2 Totarol exhibits antiplasmodial activity, 3 antifungal, 4 and antimicrobial activity against several organisms, including Propionibacterium acnes 5–6 and methicillin-resistant Staphylococcus aureus (MRSA). 5, 7 The mechanism of action by which totarol derives its antimicrobial activity has not been fully elucidated.…”