Leucosceptoside A from Devil’s Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes

Psoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil’s claw (Harpagophytum procumbens (Burch.) DC. ex Meisn.) tubers extract has been used both systemically and topically for treatment of chronic inflammatory diseases such as arthritis, osteoporosis, inflammatory bowel disease, among others. However, its potential mechanisms of action against psoriasis remains poorly investigated. The human keratinocyte HaCaT cell line is a well-accepted in vitro model system for inflammatory skin disorders such as psoriasis. The present study involved an exploration of the effect of biotechnologically produced H. procumbens (HP) cell suspension extract and pure phenylethanoid glycosides verbascoside (VER) and leucosceptoside A (LEU) in interferon (IFN)-γ/interleukin (IL)-17A/IL-22-stimulated HaCaT cells as a model of psoriasis-like inflammation. Changes in key inflammatory signaling pathways related to psoriasis development were detected by reverse transcription polymerase chain reaction and western blotting. Treatment with LEU, but not VER and HP extract improved psoriasis-related inflammation via suppression of the PI3K/AKT signaling in IFN-γ/IL-17A/IL-22-stimulated HaCaT cells. Our results suggest that LEU may exhibit therapeutic potential against psoriasis by regulating keratinocyte differentiation through inhibition of the PI3K/AKT pathway.

DNA Barcode Authentication of Devil’s Claw Herbal Dietary Supplements

Devil’s claw is the vernacular name for a genus of medicinal plants that occur in the Kalahari Desert and Namibia Steppes. The genus comprises two distinct species: Harpagophytum procumbens and H. zeyheri. Although the European pharmacopeia considers the species interchangeable, recent studies have demonstrated that H. procumbens and H. zeyheri are chemically distinct and should not be treated as the same species. Further, the sale of H. zeyheri as an herbal supplement is not legal in the United States. Four markers were tested for their ability to distinguish H. procumbens from H. zeyheri: rbcL, matK, nrITS2, and psbA-trnH. Of these, only psbA-trnH was successful. A novel DNA mini-barcode assay that produces a 178-base amplicon in Harpagophytum (specificity = 1.00 [95% confidence interval = 0.80–1.00]; sensitivity = 1.00 [95% confidence interval = 0.75–1.00]) was used to estimate mislabeling frequency in a sample of 23 devil’s claw supplements purchased in the United States. PCR amplification failed in 13% of cases. Among the 20 fully-analyzable supplements: H. procumbens was not detected in 75%; 25% contained both H. procumbens and H. zeyheri; none contained only H. procumbens. We recommend this novel mini-barcode region as a standard method of quality control in the manufacture of devil’s claw supplements.

The effect of complex herbal extract and methotrexate on suppressing adjuvant arthritis in rats

The present study evaluated the therapeutic benefits of complex herbal preparation named CBMDS, consisting of turmeric (Curcuma longa), Boswellia (Boswellia serrata), Methylsulphonylmethane, Devil’s Claw (Harpagophytum procumbens) and Silymarin, using it in combination with methotrexate, in order to suppress adjuvant arthritis in rats, and to attenuate methotrexate-induced liver damage. Adjuvant arthritis was induced in 28 rats by a single subplantar injection of complete Freund’s adjuvant (0.1 mL) into the left hind paw. The animals were divided into four groups (with seven animals in each). Group I received CBMDS, Group II - CBMDS in combination with methotrexate, and Group III just methotrexate. The treatment lasted from day 0 to day 17 (CBMDS was given daily except weekends in a dose of 160 mg/kg, methotrexate - 2 mg/kg once a week). Group IV was the control group. Clinical (body weight, hind paw volume, erythrocyte sedimentation rate, leukocyte count), biochemical (serum pro-/antioxidant activity markers), immunological (serum interleukin levels) and histological changes in joint and liver tissues were evaluated. CBMDS significantly alleviated arthritis and reduced hepatic damage, which was more evident in the methotrexate group. The combined treatment also markedly reduced arthritic symptoms and levels of malondialdehyde. Antioxidant activity was significantly higher in treated Groups I and II. CBMDS and its combination with methotrexate promoted anti-arthritic action, reduced histological changes in the joint tissues, and minimized methotrexate-induced liver toxicity.

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

Devil’s claw (Harpagophytum spp., Pedaliaceae) is one of the best-documented phytomedicines. Its mode of action is largely elucidated, and its efficacy and excellent safety profile have been demonstrated in a long list of clinical investigations. The author conducted a bibliographic review which not only included peer-reviewed papers published in scientific journals but also a vast amount of grey literature, such as theses and reports initiated by governmental as well as non-governmental organizations, thus allowing for a more holistic presentation of the available evidence. Close to 700 sources published over the course of two centuries were identified, confirmed, and cataloged. The purpose of the review is three-fold: to trace the historical milestones in devil’s claw becoming a modern herbal medicine, to point out gaps in the seemingly all-encompassing body of research, and to provide the reader with a reliable and comprehensive bibliography. The review covers aspects of ethnobotany, taxonomy, history of product development and commercialization, chemistry, pharmacology, toxicology, as well as clinical efficacy and safety. It is concluded that three areas stand out in need of further investigation. The taxonomical assessment of the genus is outdated and lacking. A revision is needed to account for intra- and inter-specific, geographical, and chemo-taxonomical variation, including variation in composition. Further research is needed to conclusively elucidate the active compound(s). Confounded by early substitution, intermixture, and blending, it has yet to be demonstrated beyond a reasonable doubt that both (or all) Harpagophytum spp. are equally (and interchangeably) safe and efficacious in clinical practice.

Formulation, Development and Assessment of Novel Phyto-Elastosomes Loaded with Devil’s Claw Extract

Background: Management of arthritis requires frequent administration of medications at high doses that may lead to unwanted side effects and diminished patient adherence to the therapy. Devil’s claw extract, a herbal medicine from the Kalahari sands possess similar therapeutic efficacy with less side effects as the commercialized NSAIDs. The objectives of this study were to formulate, develop and assess novel phyto-elastosomes loaded with Devil’s claw extract in order to combat the toxicity levels associated with Devil’s claw and enhance penetration of harpagoside to intended targeted site.Methods: Screening studies were undertaken to determine the ideal amount of Tween® 80, cholesterol, ethanol, diacetyl phosphate and the pH of the hydration medium necessary to produce stable Devil’s claw-loaded phyto-elastosomes. Parameters monitored were particle size, polydispersity index, zeta potential, entrapment efficiency and deformability index.Results: The use of 20 % v/v ethanol was sufficient to produce novel phyto-elastosomes capable of deforming with minimal size alterations. Hydration of thin films in acidic solution produced phyto-elastosomal dispersions with high entrapment efficiency. The presence of cholesterol impeded harpagoside entrapment and increased cholesterol content affected the stability of vesicles by causing agglomeration. Conversely, increasing Tween® 80 concentration promoted harpagoside entrapment. Diacetyl phosphate promoted the stability of vesicle through charge induction.Conclusions: Development of Devil’s claw loaded phyto-elastosomes is useful in ensuring harpagoside reach the target site of action in arthritis-affected patients. Incorporation of these elastic vesicles in transdermal dosage forms may significantly improve the management of arthritis in the near future.

Spices and herbs as immune enhancers and anti-inflammatory agents: A review

Spices and herbs have been used in traditional medicine for centuries, with research starting to accumulate on their beneficial properties. Of these properties, the immune-enhancing and anti-inflammatory capabilities of many spices and herbs have led to promising results. The current review article aims to explore the current research of several spices and herbs as immune-enhancers and anti-inflammatory agents. The spices and herbs examined are African potato (Hypoxis hemerocallidea), allspice (Pimenta dioica), basil (Ocimum basilicum), black pepper (Piper nigrum), chili powders (Capsicum species), clove (Syzygium aromaticum), Devil’s claw (Harpagophytem procumbens), fenugreek (Trigonella foenum-graecum), ginger (Zingiber officinale), lavender (Lavandula angustifolia), oregano (Origanum vulgare), rooibos (Aspalathus linearis), rosemary/sage (Salvia rosmarinus/officinalis), saffron (Crocus sativus), South African geranium (Pelargonium sidoides), and turmeric (Curcuma longa). All the spices and herbs exhibited immune-enhancing or immunomodulatory and anti-inflammatory capabilities through various processes. Rooibos and oregano had the most contradictory results, with some studies finding pro-inflammatory properties, especially at high doses regarding oregano. Turmeric had the most extensive research with positive results.