Devil's Claw (Harpagophytum procumbens) and Pain (general): evidence and sources

Ethnopharmacological relevance Harpagophytum procumbens subps. procumbens (Burch.) DC. ex Meisn. (Pedaliaceae) is an important traditional medicine growing in the Kalahari region of southern Africa where it is consumed as a general health tonic and for treating diverse ailments including arthritis, pain, fever, ulcers and boils. Aim of the review To provide a comprehensive overview of the ethnobotany, phytochemistry and biological activity of H. procumbens and possibly make recommendations for further research. Materials and methods Peer-reviewed articles on H. procumbens were acquired on Scopus, ScienceDirect and SciFinder, there was no specific timeline set for the search. A focus group discussion was held with different communities in Botswana to further understand ethnobotanical uses of the plant. Results Harpogophytum procumbens is used for a wide variety of health conditions in the form of infusions, decoctions, tinctures, powders and extracts. In addition to the common local use for arthritis and pain, other ethnomedicinal uses include dyspepsia, fever, blood diseases, urinary tract infections, postpartum pain, sprains, sores, ulcers and boils. Scientific studies revealed that H. procumbens exhibits analgesic, anti-oxidant, anti-diabetic, anti-epileptic, antimicrobial and antimalarial activities amongst others. Iridoid glycosides and phenylpropanoid glycosides have been the focus of phytochemical investigations as the biological activity has been ascribed to the iridoid glycosides (such as harpagoside and harpagide), which are common in nature and are known to possess anti-inflammatory activity. In addition, it has been shown that the hydrolysed products of harpagoside and harpagide have more pronounced anti-inflammatory activity when compared to the unhydrolysed compounds. Harpagophytum zeyheri is a close taxonomic ally of H. procumbens but H. procumbens is the favoured species of commerce, and contains higher levels of the pharmacologically active constituents. The two are used interchangeably and H. procumbens raw material is often intentionally adulterated with H. zeyheri and this may impact on the efficacy of inadequately controlled health products. The main exporter of this highly commercialised plant is Namibia. In 2009 alone, Harpagophytum exports were worth approximately €1.06 million. The high demand for health products based on this plant has led to over-harvesting, raising concerns about sustainability. Although only the secondary tubers are utilised commercially, the whole plant is often destroyed during harvesting. Conclusions Harpagophytum procumbens is used to treat a wide range of ailments. Some of the ethnobotanical claims have been confirmed through in vitro studies, however, when the constituents deemed to be the biologically active compounds were isolated the efficacy was lower than that of the whole extract. This necessitates the use of a different approach where all the metabolites are considered using a robust method such as spectroscopy; the phytochemical data can then be superimposed on the biological activity. Furthermore, there is a need to develop rapid and efficient quality control methods for both raw materials and products because the orthodox methods in current use are time-consuming and labour intensive.

The association of opioids and non-steroidal anti-inflammatory drugs, to enhance pain relief and reduce the development of side effects, has been demonstrated. Given many reports concerning the antinociceptive and anti-inflammatory effects of Harpagophytum procumbens extracts, the aim of our study was to investigate the advantage of a co-administration of a subanalgesic dose of morphine preceded by a low dose of H. procumbens to verify this therapeutically useful association in a neuropathic pain model. Time course, registered with the association of the natural extract, at a dose that does not induce an antinociceptive effect, followed by a subanalgesic dose of morphine showed a well-defined antiallodynic and antihyperalgesic effect, suggesting a synergism as a result of the two-drug association. H. procumbens cooperates synergistically with morphine in resolving hyperalgesia and allodynia, two typical symptoms of neuropathic pain. The results support the strategy of using an adjuvant drug to improve opioid analgesic efficacy.

Harpagophytum procumbens subsp. procumbens (Burch.) DC. ex Meisn. (Sesame seed Family-Pedaliaceae) is a popular medicinal plant known as Devil's claw. It is predominantly distributed widely over southern Africa. Its impressive reputation is embedded in its traditional uses as an indigenous herbal plant for the treatment of menstrual problems, bitter tonic, inflammation febrifuge, syphilis or even loss of appetite. A number of bioactive compounds such as terpenoids, iridoid glycosides, glycosides, and acetylated phenolic compounds have been isolated. Harpagoside and harpagide, iridoid glycosides bioactive compounds have been reported in countless phytochemical studies as potential anti-inflammatory agents as well as pain relievers. In-depth studies have associated chronic inflammation with various diseases, such as Alzheimer's disease, obesity, rheumatoid arthritis, type 2 diabetes, cancer, and cardiovascular and pulmonary diseases. In addition, 60% of chronic disorder fatalities are due to chronic inflammatory diseases worldwide. Inflammation and pain-related disorders have attracted significant attention as leading causes of global health challenges. Articles published from 2011 to the present were obtained and reviewed in-depth to determine valuable data findings as well as knowledge gaps. Various globally recognized scientific search engines/databases including Scopus, PubMed, Google Scholar, Web of Science, and ScienceDirect were utilized to collect information and deliver evidence. Based on the literature results, there was a dramatic decrease in the number of studies conducted on the anti-inflammatory and analgesic activity of Devil's claw, thereby presenting a potential research gap. It is also evident that currently in vivo clinical studies are needed to validate the prior massive in vitro studies, therefore delivering an ideal anti-inflammatory and analgesic agent in the form of H. procumbens products.

Background Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder. Conventional treatment (i.e., the use of nonsteroidal anti-inflammatory drugs-NSAIDs) is associated with well-documented adverse effects. Devil's Claw (Harpagophytum procumbens) a traditional South African herbal remedy used for rheumatic conditions, may be a safer treatment option. To date, 14 clinical trials have assessed its efficacy/ effectiveness in OA. Aim To address the two main questions of importance to clinicians: (1) Does Devil's Claw work for the treatment of OA, and (2) Is it safe? Methods A review of the literature on Devil's Claw and OA from 1966 to 2006 was performed using multiple search databases, monographs, and citation tracking. Relevant trials in all languages were identified and included. Both internal validity (i.e., adequacy of the dosage and period of treatment for this condition, reporting of randomization, rates of dropout, blinding, and statistical analysis) and external validity (i.e., inclusion/ exclusion criteria, baseline characteristics of the study populations, trial setting, and the appropriateness of the outcome measures of the trials) were assessed. Results Fourteen studies were identified: eight observational studies; 2 comparator trials (1 open, the other randomized to assess clinical effectiveness); and 4 double-blinded, placebo-controlled, randomized controlled trials to assess efficacy. Many of the published trials lacked certain important methodological quality criteria. However, the data from the higher quality studies suggest that Devil's Claw appeared effective in the reduction of the main clinical symptom of pain. The assessment of safety is limited by the small populations generally evaluated in the clinical studies. From the current data, Devil's Claw appears to be associated with minor risk (relative to NSAIDs), but further long-term assessment is required. Conclusions The methodological quality of the existing clinical trials is generally poor, and although they provide some support, there are a considerable number of methodologic caveats that make further clinical investigations warranted. The clinical evidence to date cannot provide a definitive answer to the two questions posed: (1) Does it work? And (2) is it safe? A definitive high-quality trial that addresses the necessary methodologic improvements noted is needed to answer these important clinical questions.

Spinal cord injury (SCI) is a deliberating disorder with impairments in locomotor deficits and incapacitating sensory abnormalities. Harpagophytum procumbens (Hp) is a botanical widely used for treating inflammation and pain related to various inflammatory and musculoskeletal conditions. Using a modified rodent contusion model of SCI, we explored the effects of this botanical on locomotor function and responses to mechanical stimuli, and examined possible neurochemical changes associated with SCI-induced allodynia. Following spinal cord contusion at T10 level, Hp (300 mg/kg, p.o.) or vehicle (water) was administered daily starting 24 h post-surgery, and behavioral measurements made every-other day until sacrifice (Day 21). Hp treatment markedly ameliorated the contusion-induced decrease in locomotor function and increased sensitivity to mechanical stimuli. Determination of Iba1 expression in spinal cord tissues indicated microglial infiltration starting 3 days post-injury. SCI results in increased levels of 4-hydroxynonenal, an oxidative stress product and proalgesic, which was diminished at 7 days by treatment with Hp. SCI also enhanced antioxidant heme oxygenase-1 (HO-1) expression. Concurrent studies of cultured murine BV-2 microglial cells revealed that Hp suppressed oxidative/nitrosative stress and inflammatory responses, including production of nitric oxide and reactive oxygen species, phosphorylation of cytosolic phospholipases A 2 , and upregulation of the antioxidative stress pathway involving the nuclear factor erythroid 2-related factor 2 and HO-1. These results support the use of Hp for management of allodynia by providing resilience against the neuroinflammation and pain associated with SCI and other neuropathological conditions.

The iridoids of Harpagophytum procumbens and Harpagophytum zeyheri were studied by CLHP. Harpagoside is the main iridoid for both drugs whereas 8-p-coumaroylharpagide is a representative iridoid of Harpagophytum zeyheri only. The ratio harpagoside/8-p-coumaroylharpagide can be used to distinguish chemically both species. For commercial dried aqueous extracts this ratio is intermediate because they are probably prepared from a mixture of H. procumbens and H. zeyheri drugs. The aqueous extracts of both drugs show similar analgesic and anti-inflammatory properties. Harpagophytum procumbens and Harpagophytum zeyheri should be accepted as sources for the drug Harpagophyti radix.

Harpagophytum procumbens, also known as Devil's Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesic effects in plantar incision and spared nerve injury (SNI) rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) test measured by von Frey filaments. Pain-related behavior was also determined through analysis of ultrasonic vocalization (USVs). The results of experiments showed MWT values of the group that was treated with 300 mg/kg H. procumbens extract increased significantly; on the contrary, the number of 22-27 kHz USVs of the treated group was reduced at 6 h and 24 h after plantar incision operation. After 21 days of continuous treatment with H. procumbens extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity responses by MWT, compared with the control group. These results suggest that H. procumbens extracts have potential analgesic effects in the case of acute postoperative pain and chronic neuropathic pain in rats.