• Clinical data 90%
  • Efficacy 80%
  • Security 70%
  • Toxicity 30%

Harpagophytum procumbens
Radix Harpagophyti

Synonyms

Harpagophytum burcherllii Decne.

General appearance

Irregular thick, fan-shaped or rounded slices or roughly crushed discs of tuber, 2–4 cm and sometimes up to 6 cm in diameter, 2–5 mm thick, greyish-brown to dark brown. Darker outer surface traversed by tortuous longitudinal wrinkles. Paler cut surface shows a dark cambial zone and xylem bundles distinctly aligned in radial rows. Central cylinder shows fi ne concentric striations. Seen under a lens, the cut surface presents yellow to brownish-red granules, longitudinally wrinkled; transverse surface yellowish-brown to brown, central region raised, fracture short.

Major chemical constituents

The major active constituents are harpagoside and the related iridoid glycosides, harpagide and procumbide, which occur in lesser amounts. Total iridoid glycoside content 0.5–3.3%.

Medicinal uses

Uses supported by clinical data
Harpagophytum procumbens treatment of pain associated with rheumatic conditions.
Uses described in pharmacopoeias and well established documents
Treatment of loss of appetite and dyspeptic complaints; supportive treatment of degenerative rheumatism, painful arthrosis and tendonitis.
Uses described in traditional medicine
Treatment of allergies, boils, diabetes, liver disorders and sores.

Pharmacology

Experimental pharmacology

Anti-infl ammatory and analgesic activity

A 60% ethanol extract of Radix Harpagophyti, 100.0 μg/ml, standardized to contain 2.9% harpagoside, inhibited the release of tumour necrosis factor-α (TNF-α) induced by the treatment of human monocytes with lipopolysaccharide (LPS) in vitro. However, treatment of the monocytes with harpagoside and harpagide, 10.0 μg/ml, isolated from the roots, had no effect on LPS-induced TNF-α release. Harpagoside, 10.0–100.0 μmol/ l, reduced the synthesis of thromboxane B2 in cells treated with calcium ionophore A23187. The results of studies assessing the anti-infl ammatory activity of Radix Harpagophyti in animal models are confl icting. Intragastric administration of 20.0 mg/kg body weight (bw) of an aqueous or methanol extract of the root to rats inhibited oedema and infl ammation in the granuloma pouch and carrageenan-induced footpad oedema tests. Intragastric administration of 20 mg/kg bw of a methanol extract of the root inhibited erythema induced by ultraviolet light in rats. Intragastric administration of 20.0 mg/kg bw of the same methanol extract to mice exhibited analgesic activity in the hot-plate test, but did not inhibit benzoquinoneinduced writhing. Intraperitoneal pretreatment of rats with an aqueous extract of the roots reduced carrageenan-induced footpad oedema in a dose dependent manner. Doses of 400 mg/kg bw and 1200 mg/kg bw reduced oedema by 43% and 64%, respectively, 3 hours after administration. The effi cacy of the higher dose was similar to that of indometacin, 10 mg/kg bw. Intraperitoneal administration of 400.0 mg/kg bw of a chloroform extract of the roots to mice with carrageenan induced footpad oedema and infl ammation reduced infl ammation by 60.3% 5 hours after treatment. Intraperitoneal administration of 200–400 mg/kg bw of an aqueous extract of the roots reduced carrageenan-induced footpad oedema in rats, but did not increase the reaction time of mice in the tail-fl ick hot-plate test. The anti-infl ammatory activity of the highest dose was more effi cient in rats than indometacin, 10.0 mg/kg bw. Treatment of the aqueous extract with 0.1 mol/l hydrochloric acid dramatically decreased the activity, suggesting that oral dosage forms should be enteric coated to protect the active principles from stomach acid. In the same study, harpagoside did not appear to be involved in the anti-infl ammatory activity. Intraperitoneal administration of 20.0 mg/kg bw of an aqueous extract of the roots to rats reduced formalin induced arthritis. The effectiveness was comparable to that of phenylbutazone, 50.0 mg/kg bw. This study also demonstrated that intraperitoneal administration of 10–50 mg/kg bw of harpagoside to rats inhibits both formalin- and albumin-induced footpad oedema and formalin-induced arthritis. Intragastric administration of 200.0 mg of an aqueous extract of the roots to rats inhibited formalin-induced footpad oedema. However, another study showed that intragastric administration of 1.0 g/kg bw of the powdered roots to rats did not inhibit carrageenan-induced footpad oedema or adjuvant-induced arthritis, as compared with other antiinfl ammatory agents such as indometacin or acetylsalicyclic acid. Investigations of the antiphlogistic activity of harpagoside, harpagide and an aqueous extract of Radix Harpagophyti (doses not specifi ed) indicated that all three substances had anti-infl ammatory activity similar to that of phenylbutazone. In mice, intragastric administration of 100.0 mg/kg bw of harpagoside inhibited carrageenan-induced footpad oedema, and external application of 1.0 mg/ear reduced ear oedema induced by phorbol ester. Intragastric administration of up to 100 times the recommended daily dose of powdered roots (6.0 g/kg bw) to rats did not reduce footpad oedema induced by carrageenan or Mycobacterium butyricum. Furthermore, the root preparation, 100.0 mg/ml, failed to inhibit prostaglandin synthase activity in vitro.

Antiarrhythmic activity

Intragastric administration of 100 mg/kg bw of an aqueous or methanol extract of the roots protected rats against ventricular arrhythmias induced by epinephrine-chloroform or calcium chloride. Intraperitoneal administration of 25 mg/kg bw of a methanol extract of the roots inhibited cardiac arrhythmias induced by aconitine, epinephrine-chloroform or calcium chloride in fasted rats. Intragastric administration of 300–400 mg/kg bw of a methanol extract of the roots to normotensive rats reduced heart rate and arterial blood pressure. Other studies have demonstrated that lower doses of the extract have slight negative chronotropic and positive inotropic effects, whereas larger doses have a marked inotropic effect, with reductions in coronary blood fl ow. The inotropic effect is attributed to harpagide.

Clinical pharmacology

Antidyspeptic activity

A decoction of Radix Harpagophyti is one of the strongest bitter tonics known. Ingestion of a tea prepared from the root (dose not specifi ed) over a period of several days led to an improvement in the symptoms of disorders of the upper part of the small intestine, which were accompanied by disturbances of choleresis and bile kinesis. It has been proposed that, because the root is very bitter, is a good stomachic and stimulates the appetite, it may also be useful for the treatment of dyspeptic complaints.

Anti-infl ammatory and analgesic activity

A randomized double-blind comparison study, involving 46 patients with active osteoarthritis of the hip, assessed the effects of oral administration of 480 ng of an ethanol extract of the roots twice daily in the successive reduction of ibuprofen use for pain and the Western Ontario and McMaster Universities (WOMAC) arthrosis index. Patients received, in conjunction with the extract or placebo, 800.0 mg of ibuprofen daily for 8 weeks, then 400.0 mg daily for 8 weeks, then no ibuprofen. After 20 weeks of treatment, the WOMAC index decreased in the treatment group, with improvements in pain, stiffness and loss of function. In a randomized, double-blind clinical trial in 122 patients suffering from osteoarthritis of the knee and hip, the effi cacy and tolerance of the roots and diacerein were compared. Patients received the roots as 6 capsules per day, each containing 435.0 mg of powdered roots or 100.0 mg of diacerein daily for 4 months. Assessments of pain and functional disability were made on a 10-cm horizontal visual analogue scale, and the severity of osteoarthritis was evaluated using the Lequesne functional index. There was a reduction in spontaneous pain and a progressive reduction in the Lequesne index in both groups. Fewer side effects were observed in the group treated with the powdered roots (8.1%) than in the group receiving diacerein (26.7%). In a double-blind, placebo-controlled clinical trial, 50 patients with various arthroses were treated with 1200.0 mg of a hydroalcoholic extract of the roots, containing 1.5% iridoid glycosides, daily for 3-week courses. The severity of pain was assessed 10 days after completion of treatment. Each patient was given one to three courses of treatment. Compared with placebo, the extract produced a decrease in the severity of pain in individuals with a moderate pain level. In an uncontrolled study involving 630 patients with arthrosis, 42–85% of the patients showed improvements after 6 months of daily oral treatment with 3.0–9.0 g of an aqueous extract of the roots containing 2.5% of iridoid glycosides. In an uncontrolled trial, the effi cacy of an orally administered aqueous extract of the roots (as tablets) was assessed in 13 patients, 11 with arthritis and two with psoriatic arthropathy. Treatment
of the patients for 6 weeks with 1.23 g daily did not reduce pain or infl ammation in 12 patients, and one patient withdrew owing to sideeffects. In an uncontrolled study, benefi cial results were reported in 80% of 60 patients with chronic polyarthritis after treatment with subcutaneous lateral and medial injections of aqueous root extracts on both sides of the knee joint. The effi cacy of a standardized hydroalcoholic extract of the roots for the treatment of chronic back pain was assessed in a double-blind, randomized, placebo-controlled trial. The 197 patients were treated orally with 600.0 mg or 1200.0 mg of the extract (standardized to contain a total of 50–100 mg of harpagoside) or placebo daily for 4 weeks. A total of 183 patients completed the trial. Three, six and ten patients in the placebo, low-dose extract and high-dose extract groups, respectively, (P = 0.027) remained pain-free without the permitted pain medication (tramadol) for 5 days in the last week. A 4-week randomized double-blind, placebocontrolled clinical trial assessed the safety and effi cacy of an ethanol extract of the roots in the treatment of acute attacks of pain in 118 patients with chronic back problems. Patients received two 400.0-mg tablets three times per day (equivalent to 6 g of roots containing 50.0 mg of harpagoside). Intake of a supplementary analgesic (tramadol) did not differ significantly between the placebo and the treatment group. However, further analysis revealed that nine out of 51 patients who received the extract were pain free at the end of the treatment period, compared to only one out of 54 in the placebo group. The effi cacy of a dried ethanol extract of the roots was investigated in a 4-week, double-blind, placebo-controlled study in 118 patients with a history of chronic lower back pain. Patients were randomly assigned to receive two tablets of the extract or placebo three times per day. After 4 weeks of treatment, a reduction in the Arhus low back pain index was observed in the treated patients compared
with those receiving placebo. A randomized, placebo-controlled, double-blind study investigated the effects of an ethanol extract of the roots on sensory, motor and vascular mechanism of muscle pain in 65 patients with mild to moderate muscle tension or mild back, shoulder or neck pain. Patients received two doses of 480.0 mg of the extract or placebo daily for 4 weeks. At the end of the treatment period, a signifi cant reduction in muscle pain as measured by a visual analogue scale (P < 0.001) was observed in the extract group. Muscle stiffness and ischaemia were also improved in this group, but no changes were found in antinociceptive muscle refl exes or surface electromyography. Oral administration of powdered roots, four 500.0-mg capsules, standardized to contain 3% total iridoids, daily for 21 days to healthy volunteers did not statistically alter eicosanoid biosynthesis by the cyclooxygenase or 5-lipoxygenase pathways. The results indicated that in healthy humans Radix Hapagophyti did not inhibit arachidonic acid metabolism.

Adverse reactions

Mild and infrequent gastrointestinal symptoms were reported in clinical trials.

Contraindications

Radix Harpagophyti is contraindicated in gastric and duodenal ulcers, and cases of known hypersensitivity to the roots. Owing to a lack of safety data, Radix Harpagophyti should not be used during pregnancy and nursing.

Warnings

No information available.

News and Journals

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