ABSTRACT
La raíz de harpagofito es la droga vegetal más utilizada en terapéutica para el tratamiento de dolores asociados a artrosis, artritis, lumbalgia y otras afecciones osteoarticulares de origen reumático. Numerosos estudios preclínicos han puesto de manifiesto la actividad antiinflamatoria de su principal componente, el hapagósido, vía inhibición de la activación del factor NFkappaB. Además, recientemente se ha demostrado que el 8-p-cumaroil-harpagido y el verbascósido poseen también actividad antiinflamatoria, mientras que el harpágido se comporta como pro-inflamatorio al incrementar la expresión dela COX-2. Los metanálisis realizados concluyen que el tratamiento con preparados de raíz de harpagofito con un determinado contenido en harpagósido, es eficaz en la reducción del dolor y mejora de la movilidad en lumbalgias y osteoartritis. No obstante, sería conveniente realizar ensayos adicionales, con un mayor número de pacientes para confirmar su eficacia y seguridad a largo plazo (AU)
Devik's claw in the herbal drug most commonly used in the treatment of pain associated with osteoarthritis, arthritis, low back pain and other musculoskeletal disorders of rheumatic origin. Numerous preclinical studies have shown anti-inflamatory activity of its main constituent, harpagoside, via the inhibition of the activation of nuclear factor NF-kappaB. Recently it has been described that 8-O-p-coumaroil-harpagide and verbacoside also contribute to the anti-inflamatory activity, while harpagide seems to have a pro-inflammatory action by increasing the expression of COX-2. Meta-analyses performed concluded that the treatment with devil's claw preparations with a certain content of harpagoside is effective in reducing pain and improving mobility in osteoarthritis and back pain. Nevertheless, it would be advisable to perform additional studies, with higher number of patients, in order to confirm its efficacy and long-term safety (AU)
Subject(s)
Humans , Male , Female , Harpagophytum/chemistry , Harpagophytum/metabolism , Rheumatic Diseases/therapy , Phytotherapy/instrumentation , Phytotherapy/methods , Harpagophytum/therapeutic use , Iridoids/therapeutic use , Phytotherapy/trends , Phytotherapy , Osteoarthritis/therapy , Low Back Pain/therapyABSTRACT
In a previous report, we showed that cell cultures of Harpagophytum procumbens, a South African plant with high medicinal value, accumulate high amounts of anti-inflammatory phenylethanoid glycosides during cultivation in shake-flasks. The aim of the present study was to transfer the phenylethanoid biosynthetic process to a 3-L stirred tank reactor and a 1-L glass-column bioreactor (operated with pulsed aeration). We found that, with stepwise increases in aeration, the stirred tank reactor yielded similar productivities of verbascoside (the major phenylethanoid glycoside in the cells) to those reported for shake-flask cultures (55.68 vs. 54.78 mg verbascoside/L/day, respectively). Transfer in the pulse-aerated column reactor resulted in 165.42 mg verbascoside/L/day, one of the highest yields reported to date. Further, to evaluate the physiological status of the suspended cells in the bioreactors cultures, we examined their hormone levels and compared them to those of cells in shake-flask cultures. While indole-3-acetic acid levels did not differ significantly between the bioreactor and shake-flask cultures, there were considerable differences in their levels of abscisic, jasmonic, and salicylic acids. These results are discussed with respect to relative stress levels in the different cultivation systems.
Subject(s)
Biological Factors/metabolism , Bioreactors , Glucosides/metabolism , Harpagophytum/metabolism , Phenols/metabolism , Cells, CulturedABSTRACT
Phenylethanoids are a group of natural water-soluble compounds with high biological value, which could potentially be commercially produced by hairy root cultures. Thus, we have examined the capacity of transformed root cultures of Devil's claw (Harpagophytum procumbens) to accumulate four phenylethanoid glycosides -beta-OH-verbascoside, verbascoside, leucosceptoside A, and martynoside--in shake-flasks and a 3-L stirred tank reactor. Verbascoside was found to be the major phenylethanoid, and its maximal contents were the same (1.12 mg/g dry weight) in both kinds of culture. However, peak leucosceptoside A contents were 1.6-times higher in bioreactor cultures than in shake-flask cultures. Flow cytometry analysis revealed that G0 + G1-phase cells predominated throughout the growth of the cultures, which was in accordance with the very high proportion of quiescent cells in the transformed roots. The results provide the first demonstration of the potential utility of Devil's claw hairy roots as biofactories for producing high-value phenylethanoid glycosides.
Subject(s)
Harpagophytum/growth & development , Plant Roots/growth & development , Chromatography, High Pressure Liquid , DNA, Plant/metabolism , Flow Cytometry/methods , Harpagophytum/cytology , Harpagophytum/metabolism , Kinetics , Organ Size , Plant Roots/cytology , Plant Roots/metabolismABSTRACT
El número de pacientes que sufren de molestias en el aparato locomotor va en aumento, al tiempo que crece la desconfianza en la seguridad del uso crónico de los antirreumáticos de síntesis. Por ello asistimos a un incremento en la demanda de antirreumáticos con eficacia demostrada y bien tolerados. Aunque los extractos de raíz de harpagofito o garra del diablo han sido evaluados positivamente en las monografías y se ha podido demostrar la acción antiinflamatoria y analgésica en numerosos estudios clínicos, aún no se considera una medicación estándar contra dolores del aparato locomotor. Por esta razón se realizó este estudio que demuestra que, en todos los parámetros de eficacia, la eficacia terapéutica del extracto de harpagofito es comparable a la de los analgésicos convencionales (Voltaren®, Vioxx®), y su tolerancia es mejor (AU
The number of patients who suffer disturbances of the locomotive apparatus is increasing, and at the same time it is growing the distrust in the safety of the chronic use of synthetic antirheumatic drugs. For that reason we are facing an increase of the request of antirheumatic drugs with demonstrated efficacy and good tolerability. Although the extracts of devils claw root have been evaluated positively in the monographs and its antiinflammatory and analgesic activities have beeen demonstrated in numerous clinical studies, they are not yet considered a standard medication against pain of the locomotive apparatus. Therefore, the present study was aimed to demonstrate that, in all the efficacy parameters, devils claw root extract has similar therapeutic successes than conventional analgesic drugs (Voltaren®, Vioxx®), but its tolerability is better (AU)
Subject(s)
Humans , Low Back Pain/therapy , Harpagophytum/chemistry , Harpagophytum , Harpagophytum/metabolism , Harpagophytum/analysis , Harpagophytum/therapeutic use , Treatment Outcome , Evaluation of the Efficacy-Effectiveness of Interventions , Phytotherapy/instrumentation , Phytotherapy/methods , PhytotherapyABSTRACT
A method has been developed for the analysis and characterization in equine urine and plasma of iridoid glycosides: harpagide, harpagoside and 8-para-coumaroyl harpagide, which are the main active principles of Harpagophytum, a plant with antiinflammatory properties. The method involves liquid chromatography coupled with positive electrospray ionization mass spectrometry. The addition of sodium or lithium chloride instead of formic acid in the eluting solvent has been studied in order to enhance the signal and to modify the ion's internal energy. Fragmentation pathways and associated patterns are proposed for each analyte. A comparison of three types of mass spectrometer: a 3D ion trap, a triple quadrupole and a linear ion trap, has been conducted. The 3D ion trap was selected for drug screening analysis whereas the linear ion trap was retained for identification and quantitation analysis.
