Systematic review on the safety of Harpagophytum preparations for osteoarthritic and low back pain

Harpagophytum products are a treatment option for osteoarthritic and low back pain. The aim of this study was to review the safety of treatment with Harpagophytum procumbens. The databases OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for studies with Harpagophytum procumbens. Twenty-eight clinical trials were identified of which 20 stated adverse events. In none of the double-blind studies was the incidence of adverse events during treatment with Harpagophytum procumbens higher than during placebo treatment. Minor adverse events occurred in around 3% of the patients, mainly gastrointestinal adverse events. A few reports of acute toxicity were found but there were no reports on chronic toxicity.Since the dosage used in most of the studies is at the lower limit and since long-term treatment with Harpagophytum products is advisable, more safety data are urgently needed.     

Effect of the major glycosides of Harpagophytum procumbens (Devil's Claw) on epidermal cyclooxygenase-2 (COX-2) in vitro

Harpagophytum procumbens, commonly known as Devil's Claw, is indigenous to southern Africa, and extracts of the tubers have been used for centuries in the treatment of a variety of inflammatory disorders. Its major active components, harpagoside (1), harpagide (2), 8-coumaroylharpagide (3), and verbascoside (4), are believed to interact either synergistically or antagonistically in modulating the enzymes responsible for inducing inflammation, although this has not been probed hitherto. In the current work, the ability of these compounds to inhibit the expression of COX-2 following administration to freshly excised porcine skin has been investigated. An ethanol-soluble extract of H. procumbens tubers and two of the pure compounds tested showed promising activity in Western blotting and immunocytochemical assays, with harpagoside (1) and 8-coumaroylharpagide (3) exhibiting greater reductions in COX-2 expression than verbascoside (4). Harpagide (2) caused a significant increase in the levels of COX-2 expression after 6 h of topical application. The data suggest that the efficacy of H. procumbens is dependent upon the ratios of compounds 1-4 present, which is inconsistent with some current official monograph specifications based solely on harpagoside (1) content.     

Evaluation of acute and chronic treatments with Harpagophytum procumbens on Freund's adjuvant-induced arthritis in rats

The extract of Harpagophytum procumbens, widely utilized in Europe and, more recently, in other countries, is traditionally indicated to treat inflammatory processes. Harpagophytum procumbens acts by way of interleukins and leukocyte migration to the painful and inflamed joint area. Chemically, its secondary tuberous roots contains iridoid glycosides, harpagogide, procumbide, and harpagoside, as the active principle. The purpose of the present study was evaluate the therapeutic potential as anti-inflammatory and analgesic agent in rat model of Freund's adjuvant-induced arthritis both in the acute and chronic phases. The animals were injected with Freund's adjuvant in sub-plantar tissue of the right posterior paw and randomly assigned in acute (25, 50, or 100 mg/kg) or chronic (100 mg/kg) treatments with Harpagophytum procumbens solution test or vehicle. Then, submitted to behavioral test and assessment of body weight and right paw's measurements. The results show that Harpagophytum procumbens extract increased the animals 'latency of paws' withdrawal, indicating a protective effect against the pain induced by the thermal stimulus, both in acute and chronic treatments. In addition to reduction in the right paw edema in the experimental groups when compared to control group. Thus, the data showed anti-inflammatory and peripheral analgesic properties of Harpagophytum procumbens extract with all doses tested, thus confirming its indication for inflammatory processes.     

Discovering new natural products directly from crude extracts by HPLC-SPE-NMR: chinane diterpenes in Harpagophytum procumbens

HPLC-SPE-NMR experiments with crude extracts of Harpagophytum procumbens allowed the rapid identification of novel, unstable chinane-type tricyclic diterpenes (1 and 2), along with numerous other constituents. Dramatic sensitivity gains achieved with this novel hyphenated technique establish a new paradigm in natural products research: rapid and rigorous structure determination of multiple extract components, including minor components, without preparative-scale isolation.     

Analgesic, antiinflammatory and antidiabetic properties of Harpagophytum procumbens DC (Pedaliaceae) secondary root aqueous extract

South Africa is blessed with a rich floral biodiversity of medicinally useful plants. One such plant is Harpagophytum procumbens DC (Family: Pedaliaceae). H. procumbens is widely used in South African traditional medicine for the treatment, management and/or control of a variety of human ailments. In the present study, the analgesic effect of H. procumbens secondary root aqueous extract was evaluated in mice, using the 'hot-plate' and 'acetic acid' test methods; while the antiinflammatory and antidiabetic effects of the plant's secondary root extract were investigated in rats. Fresh egg albumin-induced pedal oedema and streptozotocin (STZ)-induced diabetes mellitus were used as experimental test models of inflammation and diabetes Diclofenac (DIC, 100 mg/kg i.p.) was used as a reference analgesic and antiinflammatory agent for comparison. Chlorpropamide (250 mg/kg p.o.) was used as a reference hypoglycaemic agent for comparison. H. procumbens root aqueous extract (HPE, 50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. H. procumbens root extract (HPE, 50-800 mg/kg i.p.) also produced dose-related, significant reductions (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw oedema. Furthermore, the plant extract (HPE, 50-800 mg/kg i.p.) produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. The results of this experimental animal study indicate that H. procumbens root aqueous extract possesses analgesic, antiinflammatory and hypoglycaemic properties, and lend pharmacological support to the suggested folklore uses of Harpagophytum procumbens root in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.     

A drug used in traditional medicine: Harpagophytum procumbens DC. IV. Effects on some isolated muscle preparations

Effects of the crude methanolic extract of Harpagophytum procumbens secondary roots and two of its active principles, harpagoside and harpagide, on some smooth muscle in vitro have been studied. The results obtained show how the action of H. procumbens is due to a complex interaction between the various active principles contained in the drug and suggest that they, especially harpagoside, interfere with the mechanisms that regulate the influx of calcium in the cells.     

Cholinesterases inhibitory and antioxidant activities of Harpagophytum procumbens from in vitro systems

A previous report showed that extracts of cell suspension and transformed root cultures of Harpagophytum procumbens (commonly known as Devil's claw), an African plant with high medicinal value, exhibit strong antiinflammatory characteristics. The present work tests the ability of extracts, phenylethanoid-containing fractions and the major phenylethanoid glycoside isolated from the Devil's claw cultures, to inhibit acetylcholinesterase and butyrylcholinesterase, and the antioxidant activity in iron-related systems (e.g. ferric-reducing antioxidant power and ferrous ion-chelating capacity). The results indicated that the phenylethanoid fractions may be attractive for various commercial purposes since they displayed significant cholinesterase inhibitory activity (even higher than that of pure galanthamine in the case of butyrylcholinesterase inhibition assay). Crude methanolic extracts from cell and hairy root cultures of Devil's claw exhibited strong ferrous ion-chelating capacity (1.5-2 times higher than pure butylated hydroxyanisole, used as positive standard).     

A drug used in traditional medicine. Harpagophytum procumbens DC. I. Scanning electron microscope observations

Histological characteristics, as observed by scanning electron microscope, of the secondary roots of Harpagophytum procumbens DC. (Pedaliaceae), a drug widely used in South African traditional medicine, specially by Bushmen, Hottentots and Bantu, are described in detail. It has been possible to reveal some morphological elements that, together with superficial granular material containing harpagoside and harpagide, allow drug identification.     

A drug used in traditional medicine: Harpagophytum procumbens DC. III. Effects on hyperkinetic ventricular arrhythmias by reperfusion

In Langendorff preparations of rat heart, hyperkinetic ventricular arrhythmias (HVA) have been induced by an ischaemic perfusion (coronary flux 0.5 ml/min; pressure 8 mmHg) and following reperfusion at basal conditions (coronary flux 8 ml/min; pressure 50 mmHg). Crude methanolic extracts of Harpagophytum procumbens secondary roots and harpagoside showed a significant, dose-dependent, protective action toward HVA induced by reperfusion.     

Potent cytotoxic lignans from Justicia procumbens and their effects on nitric oxide and tumor necrosis factor-alpha production in mouse macrophages

A new lignan glycoside, 4-O-alpha-L-arabinopyranosyl-(1' "-->2' ')-beta-D-apiofuranosyldiphyllin (2), named procumbenoside A, and 11 known compounds were isolated from the whole plant of Justicia procumbens. The structure of 2 was established by spectral analysis and chemical methods. The known compounds justicidin A (1), diphyllin (3), and tuberculatin (4) showed potent cytotoxic effects against a number of cancer cells in vitro. Compounds 1 and 4 also strongly enhanced tumor-necrosis factor-alpha (TNF-alpha) generation from mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS).     

Identification of major and minor constituents of Harpagophytum procumbens (Devil's claw) using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS

The HPLC-SPE-NMR technique, supported by HPLC-MS measurements, was used to determine structures of major as well as some minor constituents of ethanol and petroleum ether extracts of Harpagophytum procumbens (Devil's claw) roots. This method was also shown to be applicable for rapid and precise on-line identification of secondary metabolites present in commercial herbal products of H. procumbens. A total of 15 compounds (1-14 and 17) were identified from the ethanol and petroleum ether extracts, including a novel Diels-Alder dimer 14. Optimization of the HPLC-SPE-NMR experiments included quantitative (1)H NMR measurements, determination of trapping and elution efficiency, effect of multiple trapping of analytes, use of various deuterated solvents for SPE cartridge elution, and effect of post-column dilution ratio of eluent with water. Linear accumulation of apolar and relatively polar analytes was demonstrated for at least 8-10 repeated trappings, resulting in greatly improved signal-to-noise ratios in NMR spectra and reduced acquisition times. Thus, the HPLC-SPE-NMR technique provides an efficient means of identification of multiple components of crude extracts. By allowing on-line generation of high-quality 2D NMR data without traditional purification of extract components, the HPLC-SPE-NMR methodology represents a paradigm shift in natural products research with respect to structure elucidation.     

Effectiveness of Harpagophytum extracts and clinical efficacy

Various preparations from Harpagophytum procumbens are used for the treatment of pain in the joints and lower back. Studies published in peer reviewed journals were examined for their clinical evidence. The studies offering preparations with 50-60 mg harpagoside in the daily dosage are of better quality and provide more reliable evidence on efficacy than a proprietary ethanol extract with half the amount of harpagoside per day. However, confirmatory studies are required for all extracts before they can gain a place in treatment guidelines.     

羽芒菊化学成分研究

目的 研究羽芒菊Tridax procumbens的化学成分.方法 利用Diaion HP-20、MCI-Gel CHP-20、Sepha-dex LH-20及硅胶等柱色谱法对羽芒菊中的化学成分进行分离纯化,根据理化性质和波谱技术(1H-NMR、13C-NMR、DEPT、1H-1H COSY、HSQC、HMBC、ESI-MS、IR)鉴定化合物的结构.结果 从中分离鉴定了5个化合物:8,3'-二羟基-3,7,4'-三甲氧基-6-O-β-D-葡萄糖黄酮苷-6"-乙酸酯(Ⅰ)、豆甾醇(Ⅱ)、β-谷甾醇(Ⅲ)、邻苯二甲酸二-(2-乙基)己酯(Ⅳ)、芹菜素-7-O-β-D-葡萄糖苷(Ⅴ).结论 化合物Ⅰ为新化合物,命名为羽芒菊苷A(trid-proeumoside A).化合物Ⅱ～Ⅴ为首次从该植物中分离得到.     

A broad review of commercially important southern African medicinal plants

Aims of the study

Commercially important indigenous medicinal plants of southern Africa are reviewed in the context of fundamental knowledge about their ethnobotany, phylogeny, genetics, taxonomy, biochemistry, chemical variation, reproductive biology and horticulture. The aim is to explore the rapidly increasing number of scientific publications and to investigate the need for further research.

Materials and methods

The Scopus (Elsevier) reference system was used to investigate trends in the number of scientific publications and patents in 38 medicinal plant species. Fifteen species of special commercial interest were chosen for more detailed reviews: Agathosma betulina, Aloe ferox, Artemisia afra, Aspalathus linearis, Cyclopia genistoides, Harpagophytum procumbens, Hoodia gordonii, Hypoxis hemerocallidea, Lippia javanica, Mesembryanthemum tortuosum, Pelargonium sidoides, Siphonochilus aethiopicus, Sutherlandia frutescens, Warburgia salutaris and Xysmalobium undulatum.

Results

In recent years there has been an upsurge in research and development of new medicinal products and new medicinal crops, as is shown by a rapid increase in the number of scientific publications and patents. Despite the fact that an estimated 10% of the plant species of the world is found in southern Africa, only a few have been fully commercialized and basic scientific information is often not available.

Conclusions

The limited available information indicates that some of the plants display remarkable regional variation in morphological, genetic and chemical characters that should be more thoroughly investigated. Basic biological information is needed to guide the rapidly accelerating commercialization process, especially the selection of superior clones, the development of new cultivars and the standardization of raw materials.     

The inhibition of free radical generation by preparations of Harpagophytum procumbens in vitro

Harpagophytum procumbens (Hp), commonly known as Devil's Claw has been used as a traditional treatment for a variety of illnesses for centuries. Since the early twentieth century, it has become a popular antiinflammatory and analgesic preparation amongst European herbalists for supportive or adjuvant treatment of degenerative joint diseases. Extracts of Hp tubers have demonstrated antiinflammatory and analgesic effects in animal models of inflammation and in human trials. The mechanism(s) of action responsible for these attributes, however, remain to be elucidated. Reactive oxygen species generated in acute and chronic inflammatory diseases are known to be cytotoxic and can cause tissue damage. In this study, a root tuber extract (Hp extract) and commercially available tincture (Hp tincture) were investigated for antioxidant characteristics using in vitro test systems. Both preparations were found to effectively scavenge DPPH radical, inhibit nitrite levels in supernatants harvested from LPS-stimulated RAW 264.7 macrophages, and cause dose-dependent suppressions in the detection of fMLP- and AA-induced neutrophil MPO. The antioxidant effects demonstrated for both preparations of Hp may contribute to the antiinflammatory and analgesic properties observed for the plant.     

Holothurins B(2), B(3), and B(4), new triterpene glycosides from mediterranean sea cucumbers of the genus holothuria

Triterpene glycosides of three species of the Mediterranean sea cucumbers Holothuria polii, Holothuria tubulosa, and Holothuria sp. were studied. Three new monosulfated biosides, holothurins B(2) (1), B(3) (2), and B(4) (3), along with the previously known holothurins A (4) and B (5) were isolated from the sea cucumber H. polii. Triterpene glycosides belonging to holothurin A and B groups were found in H. tubulosa, while only one individual glycoside, holothurin A (4), was isolated from Holothuria sp. Structures of new substances were elucidated on the basis of spectral data (2D NMR and MS). The significance of holothurins as chemotaxonomic markers of the animals belonging to the genus Holothuria and taxonomic status of some representatives of the holothurians studied are discussed.     

Optimization of Aqueous Extraction and Biological Activity of Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model

Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave‐assisted aqueous Harpagophytum extract (1–1000 μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis. In this context, we evaluated the effects on C2C12 and HCT116 viability, and on LPS‐induced production of serotonin (5‐HT), tumor necrosis factor (TNF)‐α, prostaglandin (PG)E₂ and 8‐iso‐prostaglandin (8‐iso‐PG)F_2α. Harpagophytum extract was well tolerated by C2C12 cells, while reduced HCT116 colon cancer cell viability. On the other hand, Harpagophytum extract reduced H₂O₂‐induced (1 mM) reactive oxygen species (ROS) production, in both cell lines, and inhibited LPS‐induced colon production of PGE₂, 8‐iso‐PGF_2α, 5‐HT and TNFα. Concluding, we demonstrated the efficacy of a microwave‐assisted Harpagophytum aqueous extract in modulating the inflammatory, oxidative stress and immune response in an experimental model of inflammatory bowel diseases (IBD), thus suggesting a rational use of Harpagophytum in the management and prevention of ulcerative colitis in humans. Copyright © 2017 John Wiley & Sons, Ltd.     

A review of the biological and potential therapeutic actions of Harpagophytum procumbens

Harpagophytum procumbens (Hp), commonly known as Devil's Claw is a perennial plant which thrives in arid conditions. For centuries, it has been used as a traditional treatment for a variety of illnesses, including fevers, skin complaints, arthritis and diseases of the digestive tract as well as an appetite stimulant. Since its introduction to Europe in the early twentieth century, it has become a popular antiinflammatory and analgesic preparation amongst herbalists for supportive or adjuvant treatment of degenerative joint diseases, tendonitis, headache, backache and menstrual pain. The validity of Hp as an effective antiinflammatory and analgesic preparation, particularly in the relief of arthritic symptoms, has been investigated in numerous animal, clinical and in vitro studies. Although some contradictory evidence exists, the majority of animal studies appear to indicate Hp as an effective antiinflammatory and analgesic preparation in the treatment of acute and subacute inflammation. Clinical trials support Hp as a beneficial treatment for the alleviation of pain and improvement of mobility in a variety of musculoskeletal conditions. Analysis of the in vitro and ex vivo studies that currently exist, indicate that Hp has significant effects on numerous proinflammatory markers. However, the exact mechanism(s) by which Hp may reduce inflammation remain to be elucidated.     

Saponins of Allium elburzense

A phytochemical investigation of the bulbs of Allium elburzense has been undertaken, leading to the isolation of 13 furostanol and spirostanol saponins, eight of which are new, namely, elburzensosides A1/A2 (1a/1b), B1/B2 (2a/2b), C1/C2 (3a/3b), and D1/D2 (4a/4b). On the basis of spectroscopic analysis, mainly 2D NMR and mass spectrometry, and chemical methods, the structures of the new compounds were determined as furost-2alpha,3beta,5alpha,6beta,22alpha-pentol 3-O-beta-D-glucopyranosyl 26-O-beta-D-glucopyranoside (1a), furost-2alpha,3beta,5alpha,6beta,22alpha-pentol 3-O-[beta-D-glucopyranosyl-(1-->4)-O-beta-D-glucopyranosyl] 26-O-beta-D-glucopyranoside (2a), furost-2alpha,3beta,5alpha,22alpha-tetrol 3-O-beta-D-glucopyranosyl 26-O-beta-D-glucopyranoside (3a), and furost-2alpha,3beta,5alpha,22alpha-tetrol 3-O-[beta-D-xylopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-galactopyranosyl] 26-O-beta-D-glucopyranoside (4a), and the corresponding epimers at position 22 (1b-4b). Along with these compounds we have isolated the corresponding 22-O-methyl derivatives that we consider extraction artifacts. All the new elburzensosides A1/A2-D1/D2 possess as a common structural feature an OH-5alphathat is rare among furostanol saponins. The reported compounds have been isolated in large amounts, and this makes A. elburzense a prolific producer of saponins of the furostanol and spirostanol types.