Reuma / Artrose / Gewrichtspijnen
fytoschema uit de cursus fytotherapie van de Herboristen opleiding 'Dodonaeus'
Zie ook artrose
Ontsteking en degeneratie (slijtage) van de gewrichten en de weefsels rond gewrichten (bindweefsel, kraakbeen). Artritis, osteoartritis, artrose.
- Aanleg, slechte opname van mineralen (invloed kalk, magnesium, kiezelzuur)
- Overbelasting en slijtage van de gewrichten, leeftijd
- Voeding: stofwisseling (slakken), urinezuren
- Auto-immuunziekte, verkeerde ontstekingsreacties (leukotriënen, prostaglandinen)
Planten met een specifieke farmacologische werking:
Bloedzuiverend (celstofwisseling), urinedrijvend: brandnetel, paardebloem, berk
Ontstekingswerend (cortisone-like): duivelsklauw, zwarte bes (gemmo), brandnetel, gember, ananas
Pijnstillend en ontstekingswerend (salycilhoudende planten): moerasspirea, wilg, berk, populier, gaultheria (e.o. uitwendig), ook voedings suplementen zoals gammalinoleenzuur (teunisbloemolie) en eicosapentaenzuur (visolie), verder S-adenosyl-methionine (zaden, noten, vooral zonnebloemzaad)
Mineraalaanvullend, demineralisatie tegengaan: heermoes, brandnetel, paardebloem
Antioxydanten: vooral lipbloemigen met rozemarijnzuur zoals rozemarijn, oregano, ook uitwendig als etherische olie (massage) en preventief in de voeding (soep, thee)
Verse bladknoppen in glycerine en alcohol gemacereerd 1:10
Ribes nigrum 1D smorgens 50 dr.
Pinus montana 1D smiddags 50dr.
Vitis vinifera 1D savonds 50dr.
Kuurmatig innemen gedurende 3 tot 6 weken
Alfabetische lijst van reumaplanten
Ananas comosus: vermindert gewrichtszwelling (bromelaine)
Betula alba / Berk: sap als kuur, zuiverend, uitscheiding urinezuren
Capsicum sp. / Rode pepers: uitwendig kompres, bevordert aanmaak endorfinen
Equisetum arvensis / Heermoes: remineraliserend (silicium) invloed bindweefsel
Filipendula ulmaria / Moerasspirea: ontstekingswerend en pijnstillend (salicylaten)
Fraxinus excelsior / Es: blad als thee, knoppen als glycerinemaceraat
Gaultheria procumbens / Bergthee: etherische olie, uitwendig massage, pijnstillend
Harpagophytum procumbens / Duivelsklauw: anti-inflammatoir
Juniperus communis / Jeneverbes: inwendig drainage, uitwendig e.o.
Ribes nigrum / Zwarte bes: vooral knoppen, cortisone-like bij artrose
Salix species / Wilg: pijnstillend (decoct + zoethout + kweekgras)
Urtica dioica / Brandnetel: urticatie, inwrijven met verse netel ontzwellend effect, inwendig als thee(extract) remmende werking op ontstekingsfactoren (TNF, IL-1)
Zingiber officinale / Gember: remmende werking op ontstekingsfactoren (leukotriënen)
glucosaminesulfaat: belangrijk bestanddeel van het kraakbeen
chondroïtinesulfaat (runderkraakbeen): bouwstof voor beenderweefsel, anti-inflammatoir
MSM (methyl-sulfonyl-methaan): zwavelverbinding komt veel voor in beenderweefsel, organische zwavel heeft anti-inflammatoire en pijnstillende werking
SAMe (S-adenosyl-methionine): in granen, zaden, waar vit. B (methionine) in zit, heeft analgetische en anti-inflammatoire werking (bvb. zonnebloemzaad en Brasilnoten)
vitamine D, vitamine B, silicium, mangaan e.a.
Omega-3-vetzuren (o.a. EPA) vooral in vette visolie (zalm, haring) en lijnzaadolie, ook wal- en andere noten.
Omega-6-vetzuren (o.a. GLA) vooral in zaden (teunisbloem en bernagie), is nodig voor de aanmaak van PGE1 (anti-inflammatoir prostaglandine)
Soep tegen reuma: Brandnetel, zevenblad en selder laten koken in water, daarna peterselie, gember, knoflook, oregano en rozemarijn toevoegen, kort koken en laten trekken.
Broodsmeersel: Hazelnoten of Paranoten (Bertholettia) en zonnebloempitten fijn wrijven, mengen met honing (noten bevatten veel S-adenosyl-methionine, een stof met ontstekingswerende en pijnstillende werking)
Regelmatig vette vis eten (zalm, haring, vetzuren)
Veel rauwkost (zuur-base evenwicht)
Regelmatig bewegen (zwemmen, wandelen) zonder overbelasting heeft een ‘smerend’ effect op de gewrichten.
Böhmig U. – Reumatische aandoeningen en jicht.
Boneprotect / Glucosamine-500. Productinformatie Orthica
Brennessel: Schutz von destruktiven Zytokinen bei Rheuma (Rheuma-Hek)
Dualisme: nieuwe inzichten met betrekking tot Phytodolor (Populus tremula, Solidago virgaurea, Fraxinus excelsior). VNT 8 (1992)
Duke J. Le Pouvoir des plantes. Marabout
GLA proven effective for rheumatoid arthritis. Herbalgram 31 (1993)
Halkes – Moerasspiraea / Filipendula ulmaria (L.) Maxim. Ned.Tijdschr. Fyto 6 (1993)
Huibers J. – Voorkom en behandel reuma. Anckertje.
Kongress der IASP Special Intertest Group on Rheumatic Pain. Ztschr. Phytoth. 20, 1999
Meier B. und Liebi M. – Salicinhaltige pflanzliche Arzneimittel. Ztschr. Phytoth. 11 (1990)
Speight Ph. – Reuma & gewrichtsontsteking.
Wagner H. – Zum Wirknachweis antiphlogistisch wirksamer Arzneidrogen. Ztschr. Phytoth. 8 (1987)
Werbach - Nutritional influences on Illness. Keats.
Voor een cursus over fytotherapie: Herboristen Opleiding ‘Dodonaeus’ Maurice Godefridi
Wien Med Wochenschr. 2002;152(7-8):198-203.
[Pain management with herbal antirheumatic drugs].
Chrubasik S1, Pollak S.
Herbal antirheumatics are indicated in painful inflammatory and degenerative rheumatic diseases. Their mechanism of action is broader than that of synthetic antirheumatics. Particular preparations from Devils's Claw with 50 to 100 mg of harpagoside in the daily dosage as well as a particular willow bark extract with 120 to 240 mg salicin in the daily dosage proved efficacy in a number of clinical studies including confirmatory ones. Exploratory studies indicate that these herbal antirheumatics were not inferior to the selective COX-2 inhibitor rofecoxib when treating acute exacerbations of chronic low back pain. For the proprietary nettle root extract IDS23 promising in vitro/in vivo results indicate an anti-inflammatory effect, however there are only 2 open uncontrolled clinical studies available and the proof of efficacy is still missing. Safety data in order to recommend use during pregnancy and lactation are only available for the herbal combination product Phytodolor prepared from aspen, ash and goldenrod. In principle, blackcurrent leaf with not less than 1.5% flavonoids may be an appropriate antirheumatic. Likewise, the seed oils of blackcurrent, evening primrose and borage offering at least 1 to 3 g gammalinolenic acid/day are recommendable. In case superiority versus placebo has been established, proprietary herbal antirheumatics should be administered before the conventional analgesics due to the lower incidence of adverse events.
Wien Med Wochenschr. 2007;157(13-14):343-7.
Phytodolor--effects and efficacy of a herbal medicine.
Gundermann KJ1, Müller J.
Herbal antirheumatics are successfully used in painful inflammatory or degenerative rheumatic diseases. One of these herbal medicines is Phytodolor (STW 1), a fixed combination of extracts from aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and golden rod herb (Solidago virgaurea). Its effects as well as those of its components have been verified in experimental and human pharmacological investigations. The mode of action of STW 1 includes antiinflammatory, antioedematous, antioxidative and analgesic properties, and it is considered to be broader than that of synthetic antirheumatics. Open clinical studies and randomised, placebo- or verum-controlled double-blind trials, performed in different subtypes of rheumatic diseases, confirm the pharmacological evidence of efficacy, such as by reducing the intake of non-steroidal antiinflammatory drugs (NSAIDs). STW 1 has a high drug safety.
Phytodolor (STW 1) is a reasonable alternative to NSAIDs and to cyclooxygenase(COX)-2-inhibitors such as rofecoxib.
Phytother Res. 2009 Jul;23(7):897-900. doi: 10.1002/ptr.2747.
A systematic review on the effectiveness of willow bark for musculoskeletal pain.
Vlachojannis JE1, Cameron M, Chrubasik S.
Since ancient times preparations from Salix species have been used to alleviate pain. The aim of this study was to update the evidence of the effectiveness of willow bark products in the treatment of musculoskeletal pain. OVID(MEDLINE), PUBMED, Silverplatter, and CENTRAL and manual searches were used to identify clinical trials investigating Salix preparations. Authors SC and JEV extracted the data independently and discussed disagreements. Seven manuscripts were identified, reporting four trials with confirmatory and four with exploratory study designs. Three manuscripts presented the same trial data: repetitious reports were excluded. One confirmatory and two exploratory studies indicate a dose-dependent analgesic effect not inferior to rofecoxib in patients with low back pain. In one exploratory and one confirmatory study conflicting results were achieved in participants with osteoarthritis. No significant effect was seen in a confirmatory study in patients with rheumatoid arthritis, but this study was grossly underpowered. All studies investigated ethanolic extracts with daily doses up to 240 mg salicin over periods of up to six weeks. Minor adverse events occurred during treatment. The review provides moderate evidence of effectiveness for the use of ethanolic willow bark extract in low back pain. Further studies are required to find out if treatment of osteoarthritis and rheumatoid arthritis requires extract with higher doses than 240 mg salicin per day.
Special Arnica Gel as Effective as Ibuprofen Gel in Osteoarthritis of the Hands
HerbalGram. 2007; 76:28 American Botanical Council
Reviewed: Widrig R, Suter A, Saller R, Melzer J. Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomized, double-blind study. Rheumatol Int. 2007;27:585-591.
Osteoarthritis (OA) is a common joint disorder, but current treatments only help the symptoms and do not reverse or halt its progression. Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen) are typical treatments. Topical and oral treatments are used. Topical treatments have the advantage of preventing systemic side effects. Extracts of arnica (Arnica montana, Asteraceae) are also used topically to treat symptoms associated with OA. The purpose of this randomized, double-blind, reference-controlled study was to compare the efficacy of a specific commercial arnica gel with an NSAID gel.
Patients (n=204) from 20 general practice clinics in Switzerland, diagnosed with radiologically confirmed and symptomatically active OA of interphalangeal joints (fingers) of the hands participated. Patients received either ibuprofen gel 5% (Optifen Gel, Spirig Pharma Ltd; Egerkingen, Switzerland) or arnica gel (A. Vogel Arnica Gel; A. montana fresh herbal tincture 50 g/100 g gel; drug-to-extract ratio of the tincture 1:20, Bioforce AG; Roggwil, Switzerland). This arnica preparation was chosen because (1) it has published evidence from preclinical studies of some anti-inflammatory action, (2) the preparation has published evidence of skin penetration, and (3) it is available as a gel that is similar to the ibuprofen gel, so it could be blinded with the control ibuprofen gel during the study.
Patients were instructed to rub in a 4 cm strip of gel to the affected joints 3 times daily for 3 weeks. They were told not to wash their hands for 1 hour after applying the treatment. Patients were dispensed a preset number of 500 mg paracetamol tablets (acetaminophen) as “escape treatment,” often referred to as a “rescue treatment” (i.e., the patients were allowed to use the acetaminophen for pain that was not bearable and for which the tested treatment may not provide adequate pain relief). Subjects were not allowed to use the rescue medication within 24 hours prior to the final evaluation and were asked to return any unused tablets at the end of the treatment course. Pain and functional capacity were assessed.
The results demonstrate that the arnica gel was “non-inferior” and similar to ibuprofen gel in terms of hand functional capacity, pain intensity, number of painful joints, duration and severity of morning stiffness, or acetaminophen consumption. When blinded to treatment, neither patients nor doctors could distinguish between the effects of the 2 treatments. Global efficacy evaluation by physicians was rated very good or good in 56.5% of the subjects using the ibuprofen gel and 64.0% of those using the arnica gel, while patients rated efficacy very good or good in 58.8% (ibuprofen) and 64.1% (arnica) of cases. Patients’ acceptance of the gel treatment was 76.5% and 78.7% (very satisfied or satisfied; ibuprofen and arnica, respectively). In these secondary measures the arnica gel was rated slightly better than the ibuprofen gel.
Both treatments were well tolerated. Adverse events were reported by 6 patients (6.1%) on ibuprofen and by 5 patients (4.8%) on arnica.
The authors conclude that short-term use (up to 3 weeks) of arnica gel improves pain and function in OA of the hand and that the effects were indistinguishable from those of ibuprofen gel. According to the data of this well-designed study, the arnica gel preparation used in the study can be used as an alternative to ibuprofen gel when treating OA of the hand joints. It is important to emphasize that these clinical findings may not be extended to other topical arnica preparations, which may contain a different extract and concentration. Likewise, similar benefits may not be obtained unless the specific arnica product evaluated in this trial is used as described in this protocol.
Rheumatismus und Arthritis uit http://www.drugbase.de/de/datenbanken/arzneipflanzen
Zu den Störungen des Bewegungsapparates, die mittels Phytopharmaka therapiert werden können, zählen Weichteilrheumatismus, Polyarthritis, Spondylitis, Arthrose und Gicht. Diese Erkrankungen sind komplexer Natur und schließen Entzündungen und Degeneration der Skelettmuskeln, Knochen und Gelenke ein; sie sind meist von anhaltenden Schmerzen begleitet.
Da Schmerz und Entzündung vorherrschen, steht deren symptomatische Behandlung im Vordergrund. Dazu werden die Enzyme der Prostaglandin- und Leukotrienbildung (Cyclooxygenase bzw. 5-Lipoxygenase) durch Wirkstoffe (z. B. Salicylsäure, Iridoidglykoside oder ihre Metabolite) gehemmt. Alternativ setzt man corticomimetische Wirkstoffe (möglicherweise Triterpene, Steroide und andere Sekundärstoffe) ein, die die Produktion von endogenem Cortison anregen oder direkt die Phospholipase A2 und damit die Freisetzung der Arachidonsäure hemmen. Eine immunmodulierende Therapie kann ebenfalls sinnvoll sein. In der Volksmedizin werden häufig Hautreizmittel (Counterirritantien), Drogen gegen Dyskrasie („fehlerhafte Blutzusammensetzung”) und hydrolytische Enzyme eingesetzt, wie z. B. Papain, Bromelain, Ficin, Pepsin, Trypsin, Amylasen und Lipasen. Kontrollierte klinische Studien belegen die Wirksamkeit von Harpagophytum, Salix und Urtica bei der Behandlung rheumatischer Störungen.
Wichtige Arzneipflanzen und Pflanzen der Volksmedizin
Drogen mit Inhibitoren der Prostaglandinsynthese: Arnica montana, Boswellia sacra, Chrysanthemum parthenium, Filipendula ulmaria, Gaultheria procumbens, Harpagophytum procumbens, Matricaria recutita, Populus tremula, Primula elatior, P. veris, Salix alba, S. purpurea, Solidago virgaurea, Urtica dioica, Viola tricolor.
Pflanzen mit hautreizenden und entzündungshemmenden ätherischen Ölen: Arnica montana, Brassica nigra, Bryonia dioica, Capsicum annuum, C. frutescens, Cinnamomum camphora, C. verum, Croton tiglium, Eucalyptus globulus, Juniperus communis, Pinus mugo, P. sylvestris, Rhododendron tomentosum (= Ledum palustre), Rosmarinus officinalis, Spilanthes acmella, Syzygium aromaticum, Taraxacum officinale, Thymus vulgaris, Verbena officinalis, Viscum album.
Drogen mit Corticomimetischen Eigenschaften: Boswellia serrata, Bryonia dioica, Calendula officinalis, Glycyrrhiza glabra, Phytolacca americana, Smilax regelii, Solanum dulcamara, Withania somnifera.
Immunstimulantien: Echinacea angustifolia und verwandte Arten, Viscum album. Enzymquellen: Ananas comosus, Carica papaya, Ficus carica;
weitere Pflanzen: Aconitum napellus, Cardiospermum halicacabum, Commiphora mukul, Gelsemium sempervirens, Gnaphalium polycephalum, Lachnanthes tinctoria, Ruta graveolens, Symphytum officinale.
Eine Störung des Harnsäuregleichgewichts, als Hyperurikämie (>6.5 mg Harnsäure/ 100 ml Serum) bezeichnet, wird durch eine Störung des Purinstoffwechsels hervorgerufen. Sie führt zum Ausfallen von Harnsäurekristallen in der Gelenksflüssigkeit des großen Zehs, weniger häufig im Knie-, Fuß-, Hand- und Fingergelenk. Die Kristalle verursachen Entzündungen und locken Leukozyten und Makrophagen an. Sobald die Makrophagen die Harnsäurekristalle aufnehmen, werden die Zellen lysiert und setzen lysosomale Enzyme frei, die den Entzündungsprozess weiter stimulieren. Zusätzlich wird bei der Zelllyse Milchsäure freigesetzt, die die lokale Wasserstoffionen-Konzentration erhöht und die Löslichkeit der freien Harnsäure weiter senkt und somit ihre Auskristallisation fördert. Dies lockt dann noch mehr Makrophagen an und der Circulus vitiosus setzt sich fort.
Colchicin wird eingesetzt, um diesen Circulus vitiosus zu unterbrechen. Colchicin bindet an Tubulin und verhindert so die Ausbildung von Mikrotubuli. In Konsequenz wird die Fortbewegung der Makrophagen gehemmt, die sich nicht länger am Entzündungsort versammeln können. Zusätzlich weist Colchicin schmerzstillende Wirkung auf, indem es die Freisetzung von entzündungsfördernden Prostaglandinen hemmt. Da Colchicin sehr giftig ist (letale Dosis 20 mg), dürfen nicht mehr als 8 mg bei einem akutem Gichtanfall eingenommen werden.
Osteoarthritis (OA) of the knee and hip is a debilitating disease and the risk increases precipitously with aging. The severity of OA varies from person to person, but the consonant clinical signs include pain, reduced range of motion, inflammation and deformity (1,2). OA and other rheumatic diseases currently affect >43 million Americans with the number expected to increase to an estimated 60 million by the year 2020 (3,4). The high prevalence of OA with its associated loss of joint function results in expensive and long-term conventional therapies that poses a significant socioeconomic burden. This fact alone makes OA a significant health and economic challenge. When clinically evident, OA is characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion and variable degrees of inflammation without systemic effects. Although not a traditional inflammatory disease, symptoms of local inflammation and synovitis are present in many patients of OA and also seen in animal models of OA [reviewed in (5)]. The presence of elevated levels of proinflammatory cytokines IL-1 and TNF-α has been demonstrated in OA synovial fluid and it has been shown that proinflammatory cytokines can stimulate the expression of inflammatory mediators and matrix degrading metalloproteinases in an arthritic joint [(6,7) and references therein]. Pharmacological management of OA includes the administration of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), but their use does not provide adequate pain relief in some patients.
Inflammatory joint diseases, of which rheumatoid arthritis (RA) represents the most common form, is a chronic and systemic inflammatory disease of unknown etiology and is marked by synovial hyperplasia with local invasion of bone and cartilage leading to joint destruction (8,9). RA affects ∼1% of the adult population with more women being afflicted than men [(3,10) and references therein]. Recent reports suggest that patients with RA not only have a higher chronic disease burden [(11,12) and references therein] but may also have increased morbidity and mortality from cardiovascular disease compared with persons without RA (13). RA pathogenesis is regulated by proinflammatory cytokines such as IL-1 and TNF-α that activate a broad array of intracellular signal transduction mechanisms (14–16). In RA, migration of leukocytes into the synovial tissue (ST) occurs. These leukocytes and other cells in the ST, particularly RA ST fibroblasts, produce several mediators of inflammation, including chemokines—chemotactic cytokines that recruit leukocytes to the inflamed joint and also play a role in angiogenesis [(17) and references therein].
Like OA, current treatment modalities for RA are mostly symptomatic although recently it has been suggested that use of disease-modifying antirheumatic drugs (DMARDs) has led to important gains in our overall ability to treat RA patients, resulting in a better health status for patients with RA (18). The value of DMARDs for treating OA or RA is also limited by their side effects and the fact that they are more expensive to use than traditional NSAIDs. The major side effects of NSAIDs are their propensity to cause stomach ulcers, GI bleeding and perforations. Although a new class of NSAIDs—the specific inhibitors of COX-2—was developed, these drugs have similar efficacy as the general NSAIDs but are safer with respect to gastrointestinal toxicity. However, some of these COX-2 inhibitors were recently withdrawn from the market or ordered by the United States Food and Drug Administration (FDA) to have a black box warning on the label because of concerns that their long-term use may increase the risk of stroke and heart attack.
However, despite optimal use of currently available antirheumatic agents, most RA patients live with chronic pain and severe functional decline because these therapies focus primarily on preventing joint inflammation and soft tissue swelling, but are not effective in preventing cartilage breakdown and the joint destruction associated with RA.
Recently, efforts have been focused on using the class of drugs called biologics (antibodies or soluble receptors for IL-1, IL-6 and TNF-α) for the treatment of OA and RA. Although these agents reduce inflammation and joint destruction, their long-term risks and benefits are not yet clear. Additionally, higher costs and the findings that they are not effective universally and severe side effects such as life-threatening infections and increased risk of malignancies limit the use of such agents in many populations (19–23). Thus, a final assessment on the use of biologics for the treatment of RA or OA, particularly with regard to risk of infections, malignancies and autoantibody production has to be carefully monitored.
Because of these and other limitations, the use of complementary and alternative medicine (CAM) therapies, such as acupuncture and extracts of medicinal herbs, is on the rise and according to reports ∼60–90% of dissatisfied arthritis patients are likely to seek the option of CAM therapy (24,25). While most of the rheumatologists and other clinicians are skeptical of CAM therapies, patients who use CAM appear to be satisfied with the self-care approach. This self-satisfaction is mostly based on the notion that since these herbs and plants are found in nature, remedies derived from them must be safe. However, the long-term safety and efficacy of most of the herbal preparations commonly promoted as antiarthritic have not been established by placebo-controlled randomized trials either in OA or RA patients and indeed some of these may even interfere with the ongoing treatments. Therefore, it is imperative that scientific evidence regarding the safety and efficacy of herbal preparations commonly used by arthritis patients be presented to both the physicians and the patients helping them in making informed decisions. The objective of this review is to summarize the currently available information on selective herbal preparations that are commonly consumed by arthritis patients.
Herbal medicine is the root of various traditional medicine systems around the world. Botanicals are a chemical source that directly provides ∼25% of currently used crude drugs, with another 25% derived from chemically altered natural products (26). Various traditional medicine systems around the world, including ancient Chinese medicinal system, Indian medicinal system (composed of two major branches—Unani and Ayurveda) and Amazonian ethnomedicine, rely heavily on herbs for health preservation and healing. Herbal medicines have been described in traditional texts and used as antimicrobial, anti-inflammatory and antiviral medicine for the cure of allergies, RA, infections, wound healing and fever (27). Arthritis (both OA and RA) is one of the foremost diseases for which patient seeks the CAM option (28,29). Because there is little evidence about the long-term effects of currently available traditional medicines and its associated adverse effects, the American College of Rheumatology recommends the careful use of dietary supplements and herbal medicines during early stages of treatment or disease development to limit the degree of joint destruction.
It is no surprise, then, that the use of alternative medicine, such as botanicals and nutritional supplements, has become popular with arthritis patients and is on the rise. An increasing number of people in the United States, as many as 42% use complementary or alternative medicine approaches to help meet their personal health problems (29,30). This review describes the currently available scientific evidence that regarding the efficacy and toxic effects, if known, of Camellia sinensis (green tea) (Fig. 1A), Uncaria tomentosa (cat's claw) (Fig. 1B), Tripterygium wilfordii Hook F (Fig. 1C), Curcuma longa (turmeric) (Fig. 1D) and Zingiber officinale (ginger) (Fig. 1E) since these are most commonly used as therapeutic agents for the treatment of RA and OA.
Plants and herbs most commonly used in CAM practices for the treatment of rheumatic diseases. [Images courtesy of Dr Hasan Mukhtar, University of Wisconsin-Madison (A); Rainforest Nutrition, Inc., (B.1 and B.2); Dr Xullien Tao, NIAMS/NIH (C); Dr V. A. ...
C. sinensis (green tea)
Green tea (Fig. 1A) is one of the most commonly consumed beverages in the world with no reported side effects. The established pharmacological properties of green tea are attributed to its high content of polyphenols/catechins, mainly epigallocatechin-3-gallate (EGCG) (31). The potential disease-modifying effect of green tea on arthritis came to light when it was shown that collagen type II-induced arthritis (CIA) in mice, an animal model of inflammatory polyarthritis, was ameliorated by prophylactic administration of green tea polyphenols (GTPs) in drinking water (32). The reduced CIA incidence and severity was reflected in a marked inhibition of the inflammatory mediators COX2, interferon-γ and TNF-α in arthritic joints of green tea-fed mice. The activity of neutral endopeptidase, an enzyme capable of breaking peptides at neutral pH to block their biological actions, was found to be ∼7-fold higher in arthritic joints of non-GTP-fed mice in comparison to non-arthritic joints of unimmunized mice, but only 2-fold higher in the arthritic joints of GTP-fed mice. Additionally, total immunoglobulins (IgG) and type II collagen-specific IgG levels were found to be lower in serum and arthritic joints of GTP-fed mice. The reduction in biochemical markers correlated with the marked reduction of inflammation in the synovium seen on histopathology.
Mechanism of Action
Several studies have shown that most of the effects of green tea extract are mimicked by its constituent polyphenol EGCG (31,33). Consequently, further studies were conducted using this compound and it was found that in human chondrocytes derived from OA cartilage EGCG inhibited the transcription factor nuclear factor kappaB (NF-κB) in conjunction with IL-1β-inducible nitric oxide synthase (iNOS) and COX-2, resulting in reduction of nitric oxide (NO) and prostaglandin E2(PGE2) in vitro (34,35). It has also been shown that EGCG selectively inhibits the IL-1β-induced phosphorylation of c-Jun-N-terminal kinase (JNK) p46 isoform resulting in lower levels of phospho-c-Jun and DNA-binding activity of activation protein-1 (AP-1), a transcription factor implicated in the inflammatory response, in human OA chondrocytes (36). This is important since JNK kinase is a prime culprit in inflammatory and degenerative diseases (37–40).
Matrix metalloproteinases (MMPs) are produced by activated chondrocytes and other cell types in an arthritic joint. Physiologically, they take part in remodeling although excessive production in the joint results in cartilage degradation. Among the MMPs, MMP-1 and MMP-13 levels are found to be significantly elevated in both OA and RA arthritic joints (1,41,42). Recent studies have revealed that pretreatment of human OA chondrocytes with EGCG significantly, in a dose-dependent manner, inhibited the expression and activities of MMP-1 and MMP-13 (IC50 values 27 and 16.5 μM, respectively) in vitro (43). It has also been shown that EGCG was equally effective in inhibiting IL-1β-induced MMP-1, -3 and -13 in human tendon fibroblasts (44). Also, it was recently shown that catechins from green tea inhibited the degradation of human cartilage proteoglycan and type II collagen, and selectively inhibited the aggrecanases called a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1, -4 and -5 (45,46). Thus, there is experimental evidence to support further studies to investigate the anti-inflammatory and chondroprotective effects of green tea at the molecular level. With the global availability of green tea, its low cost and proven lack of toxicity, green tea catechins or compounds derived from them could one day be useful as a conventional medicine or as effective adjunct therapies for the treatment of both RA and OA.
Cat's Claw (U. tomentosa, U. guianensis)
Cat's claw is a Peruvian vine with medicinal properties that are well-documented in alternative medicine literature. Extract of cat's claw has been shown to possess antioxidant, anti-inflammatory and immunomodulating properties [reviewed in (47), also see (48)]. Extracts or preparations from the two species U. tomentosa (Fig. 1B.1) or U. guianensis (Fig. 1B.2) are interchangeably used to treat various inflammatory and non-inflammatory conditions in the Peruvian medicinal system. The chemical composition of the aqueous extract of U. tomentosa vine includes oxindole alkaloids (virtually absent in U. guianensis) tannins, quinovic acid, glycosides, flavonoids and sterols (49). The most investigated of the active constituents in U. tomentosa extract for immunomodulating and anti-inflammatory effects are pentacyclic oxindole alkaloids, which are reported to induce a yet unknown immune regulating factor (47). However, the antioxidant and anti-inflammatory effects of the extracts of U. tomentosa and U. guianensis appear to be independent of their alkaloid content as in several assays U. guianensis was more potent in free radical scavenging and inhibition of TNF-α production by mouse macrophages (50). In another study, Piscoya and co-workers (51) evaluated the safety and side effects of U. guianensis extract in patients with OA of the knee. Pain associated with activities of daily living was significantly reduced, although pain at rest or at night was not reduced during this 4 week trial period. In another study, the use of an extract of cat's claw from the part of the vine that is rich in pentacyclic alkaloids (roots) showed a reduction in the number of painful joints when compared to placebo in patients with RA (by 53.2 versus 24.1%; P = 0.044) (52). Since no adverse effects were reported, this small preliminary study demonstrated the relative safety and modest benefit to the tender joint count of a highly purified extract from the pentacyclic chemotype of U. tomentosa in patients with active RA taking sulfasalazine or hydroxychloroquine (52).
Several other groups have documented the safety and pharmacological profile of cat's claw in animal models and also showed that cat's claw was non-toxic in in vitro bioassays [(47,50–54) and references therein]. Several standardized extracts of cat's claw are available commercially and different dosages have been recommended for different conditions, but effectiveness of these recommended doses has not been rigorously tested. In some cases, mild nausea may occur upon ingestion of crude extracts or teas (perhaps due to micropulverized bark in some preparations), but other than diarrhea in some cases no other gastrointestinal events have been associated with these herbs (47,51,52,54). Indeed, studies in animal models have documented that cat's claw is protective to the gastrointestinal tract and suggests that the use of cat's claw extract may even protect the gut from the damaging effects of NSAIDs (55). Although, in recommended dosages use of cat's claw is considered non-toxic, and there are no known contraindications or drug interactions, this aspect has not been rigorously investigated. Until the effects of these Peruvian herbs are better known, it is advisable to avoid their use in women attempting pregnancy, during pregnancy and lactation, and for children <3 years of age (47,54).
Mechanism of Action
The antioxidant and anti-inflammatory activity of cat's claw extract was characterized in studies using the murine macrophages cell line RAW 264.7. These studies showed that cat's claw extract was effective in inhibiting lipopolysaccharide (LPS)-induced free radical production and subsequent lipid peroxidation in these cell types (55). In addition, the authors also showed that TNF-α production and iNOS expression via NF-κB expression were also inhibited by the cat's claw extract. Although not yet fully elucidated, the antioxidant and immunomodulating properties of the compounds certainly appear to be important in their anti-inflammatory action. These studies are important enough to support more extensive studies before long-term controlled trials of cat's claw extracts, or active compounds therein, can be initiated in large number of human subjects to determine their long-term efficacy and safety profile.
Trypterigium wilfordii Hook F
T. wilfordii Hook F (TwHF) is a perennial vine-like plant that grows in Southern China and Taiwan and is also known as ‘Thunder God Vine’. The medicinal extract is derived from the root and has been used for the treatment of various autoimmune and inflammatory diseases including RA, systemic lupus erythematosus, nephritis, psoriasis and asthma for several centuries (56). An ethanol/ethyl acetate extract of TwHF showed therapeutic benefit in patients with treatment-refractory RA (57). At the dosages used, the TwHF extract was well tolerated by most patients in this study. A prospective, double-blind, placebo-controlled study of TwHF ethanol/ethyl acetate extracts with RA patients has also been reported (58). With a two-dose regimen, (180 and 360 mg day−1) used for 20 weeks, patients at the higher dose achieved a rapid ACR-20 response with 50% of patients improving during the first 4 weeks of treatment.
Both treatment groups showed a significant decrease in the number of tender and swollen joints and improvement in the physician's global assessment. In another phase-I study, eight out of nine patients treated with TwHF extract (>360 mg day−1) showed improvements in both clinical manifestations and laboratory findings (58). One patient met American College of Rheumatology criteria for remission. Based on these data it was concluded that the extract of TwHF at dosages up to 570 mg day−1 appeared to be safe, and doses >360 mg day−1 were associated with clinical benefit in patients with RA. In both of these studies, no toxic or adverse effects other than diarrhea were observed in patients receiving the highest dose. Topical application of TwHF was also tested in a randomized, double-blind, placebo-controlled trial using 61 patients with RA and the authors concluded that topical application of TwHF was efficacious in improving ACR-20 score (59).
In these and other studies, the most common side effects of TwHF were vomiting, hair loss, diarrhea, headaches, dryness, abdominal pain and vaginal spotting. TwHF usage can also lead to the development of amenorrhea, which is reversible if present for <2 years in patients <40 years of age but irreversible in perimenopausal women patients (56).
Mechanism of Action
The immunosuppressive and anti-inflammatory effects of TwHF are believed to be mediated by one of its biologically active constituent Triptolide (60). In animal studies, triptolide inhibited the CIA in mice and rats (61,62) and markedly suppressed the IL-1 and LPS-induced production of proMMP-1 and proMMP-3 in cultured synovial fibroblasts and mouse macrophages (63). Recent studies showed that triptolide inhibited iNOS gene expression by downregulating NF-κB DNA-binding activity and JNK pathway (64). In other studies, TwHF extract or its active constituent Triptolide were shown to inhibit LPS- and cytokine-induced expression of COX-2, MMP-3 and MMP-13 in articular chondrocytes (65). Triptolide has also recently been shown to inhibit the IL-1, IL-17 and TNF-α-induced expression of aggrecanase gene in human chondrocytes (66). An additional mechanism of its anti-inflammatory effect may be via suppression of adhesion molecules E-selectin, ICAM-1 and VCAM-1 (67). These and other studies provide strong evidence regarding the scientific basis of the known beneficial effects observed in RA patients, but the molecular mechanism by which TwHF extracts or triptolide inhibit RA disease severity is yet to be elucidated. The above in vitro and other studies support the conclusion that TwHF extract or its biologically active constituent triptolide is efficacious in RA. Its efficacy in OA has not yet been determined but data from in vitro studies (63–66) strongly suggests that TwHF should be evaluated in animal models as a first step for its possible use in the prevention or treatment of OA.
Curcuma longa (turmeric)
Turmeric is a widely used spice and coloring/flavoring agent that comes from the root of the plant C. longa (Fig. 1D), a member of the Zingaberacea family (68). The FDA classified turmeric among substances ‘generally recognized as safe'. In Ayurveda, turmeric has been used for various medicinal conditions including rhinitis, wound healing, common cold, skin infections, liver and urinary tract diseases and as a ‘blood purifier’ (68–70). Turmeric was found to be effective even when given by different routes including topical, oral or by inhalation, dependent on the intended use. The major constituent of turmeric is curcumin (diferuloylmethane), which constitutes up to ∼90% of total curcuminoid content, with demethoxycurcumin and bis-demethoxycurcumin comprising the remainder (68). In animal studies, oral administration of curcumin to rats decreased the levels of inflammatory glycoprotein, Gp A 72, with a reduction in paw inflammation (71). Curcumin has also been shown to inhibit the carrageenin-induced paw edema in mice and rats, with an ED50 dose 48 and 100.2 mg kg−1, respectively (71,72). In a double-blinded crossover clinical trial of 18 patients with RA given curcumin (1200 mg day−1) for 2 weeks followed by 300 mg day−1 of phenylbutazone for another 2 weeks, respondents showed a significant improvement in morning stiffness, walking time and reduction in joint swelling (73).
Mechanism of Action
Curcumin is a non-toxic dietary pigment in turmeric and is potent inhibitor of the common transcription factor NF-κB in several cell types (74–76). Other studies have shown that curcumin inhibits/modulates upstream pathways of the arachidonic acid cascade (COX-2 and LOX) by inhibiting the catalytic activities of phospholipases A2, Cγ1 and D in various cell lines (77–79). In human chondrocytes, curcumin significantly inhibited MMP-3 and MMP-13 gene expression by inhibiting the JNK, AP-1 and NF-κB pathways (75). Other studies have shown that curcumin blocks LPS and interferon-γ-induced production of NO and TNF-α in vitro by inhibiting the activation of NF-κB and AP-1 [reviewed in (68)]. Curcumin also inhibited the incorporation of arachidonic acid into membrane lipids, PGE2 production, leukotriene B4 and leukotriene C4 synthesis, as well as the secretion of collagenase, elastase and hyaluronidase by macrophages (78). Furthermore, IL-1β-induced upregulation of MMP-3 was inhibited by curcumin in a time-dependent manner. In addition, IL-1β-induced decrease in type II collagen synthesis was also blocked by curcumin treatment. Based on the data obtained it was concluded that curcumin antagonizes crucial catabolic effects of IL-1β signaling that are known to contribute to the pathogenesis of OA. Although not conclusive, but these data clearly show the necessity of additional studies to develop and use optimized doses in randomized, placebo-controlled clinical trials to confirm or refute the reported efficacy of the use of curcumin in OA and RA.
Zingiber officinale (ginger)
Ginger, the rhizome of Z. officinale (Fig. 1E), is one of the most common constituents of diets worldwide and is reported to possess antioxidant, anti-inflammatory, antiseptic and carminative properties (80). In Ayurvedic and traditional Sino–Japanese medicine systems, ginger has been used for thousands of years to treat inflammatory and rheumatic diseases. The major constituents of ginger include volatile oils, oleoresin (gingerol), linoleic acid and trace elements such as magnesium, phosphorus and potassium. The pungent phenolic constituent of ginger, -gingerol, inhibited LPS-induced iNOS expression and production of NO and other RNS species in macrophages and blocked peroxynitrite-induced oxidation and nitration reactions in vitro (81). These results suggest that -gingerol is a potent inhibitor of NO synthesis and also an effective protector against peroxynitrite-mediated damage. Another in vitro study showed that ginger extract was effective in inhibiting production of PGE2 and TNF-α and COX-2 expression in human synoviocytes by regulating NF-κB activation and degradation of its inhibitor IκBα (82). Anti-inflammatory activities of silica gel chromatography fractions of ginger have also been tested using an in vitro PGE2 assay. Results showed that most of the fractions containing gingerols and/or gingerol derivatives were excellent inhibitors of LPS-induced PGE2 production (83). Ginger extract administered daily for 4 weeks, either orally or intraperitoneally caused significant reduction in PGE2 levels in rats (82).
In other studies, ginger alleviates pain and associated symptoms in patients suffering from OA. In a randomized, double-blind, placebo-controlled trial of the effects of ginger extract on knee OA, 63% of the patients in the ginger extract group experienced reduction in knee pain on standing versus 50% in the placebo group (84). It was concluded that a highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of OA of the knee. There was a good safety profile, with mostly mild GI adverse events in the ginger extract group. The beneficial effects of ginger were attributed to its ability to inhibit COX and LOX pathways resulting in the blockade of PGE2 and LTB4 production in affected joints (77,78). More recently, in a randomized, double-blind, placebo-controlled, crossover study in patients with OA, patients in the ginger extract group showed statistically significant effect in the first period of treatment before crossover (85). In a limited study with RA patients, Srivastava and Mustafa (86) reported that ginger was effective in relieving pain and swelling in the joints of seven RA patients. Based on this limited information, it is difficult to determine whether use of ginger or ginger oils will be beneficial in treating of OA or RA. However, these results are strong enough to advocate and support further studies on the effects of ginger in OA and RA in both animal models and clinical studies.
At present, the current modalities for treating arthritis are symptomatic and have not been shown to either block or reverse the cartilage degradation and joint destruction. This has resulted in heightened interest in the use of CAM therapies for the treatment of arthritis. However, much of the current research is focused on the identification, isolation and characterization of active principle(s) from crude extracts of known medicinal plants or herbs, often overlooking the fact that strong synergism of several constituents in the crude drug may prove more potent and effective than any single purified compound and this may help to nullify the toxic effects of individual constituents (24). This attractive hypothesis encourages further studies but demands rigorous experimentation. Once the underlying molecular mechanism(s) for the observed anti-inflammatory and chondroprotective effects of nutraceuticals are elucidated, their health benefits may be exploited to develop new and better modalities for treating degenerative and inflammatory joint diseases.
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