Abstract
Osteoarthritis (OA) is the most common form of arthritis, which represents a substantial economic burden for society and significantly affects patients’ quality of life. Current conventional treatments of OA may be insufficiently effective and unsafe. In an attempt to overcome these limitations, many patients use herbal medicinal products (HMPs) and dietary supplements. A considerable number of herbal drugs and preparations (e.g., willow bark, Salicis cortex; devil’s claw root, Harpagophyti radix; blackcurrant leaf, Ribis nigri folium; nettle leaf/herb, Urticae folium/herba; meadowsweet/meadowsweet flower, Filipendulae ulmariae herba/flos; rosemary leaf/oil, Rosmarini folium/aetheroleum; and juniper oil, Juniperi aetheroleum) are traditionally employed to relieve minor articular pain. Active constituents (e.g., sesquiterpene lactones, triterpenic acids, diarylheptanoids, iridoid glycosides, phenolic glycosides, procyanidins, and alkaloids) are not often fully known. Experimental studies suggest that herbal extracts/compounds are able to suppress inflammation, inhibit catabolic processes, and stimulate anabolic processes relevant to OA. Therapeutic benefit of most HMPs is expected solely from the experience of their long-standing traditional use. Efficacy and safety of several HMPs were assessed in clinical trials. The growing body of preclinical and clinical evidence provides rationale for the use of herbal products in the treatment of OA. However, at present, they cannot be recommended to patients with confidence.
Keywords
- osteoarthritis
- herbal medicinal products
- medicinal plants
- mechanism of action
- active constituents
- clinical efficacy
1. Introduction
Osteoarthritis (OA) is the most common form of arthritis and the main cause of disability in elderly. Due to the aging population and obesity (major risk factors), its prevalence increases. It is estimated that symptomatic OA of knee affects approximately 12% of the older population (≥60 years). Symptomatic OA of hand (6.8%, ≥26 years) and hip (9.2%, ≥45 years) is also frequent. OA can influence patients’ quality of life significantly, as it is usually accompanied with the pain and loss of physical function. OA often affects knees, hips, hands (distal and proximal interphalangeal joints and the base of thumb), cervical and lumbosacral spine, and feet (first metatarsal phalangeal joint). It is characterized by failure of all joint structures. Articular cartilage loss is the most prominent feature of the disease, but subchondral bone, synovial membrane, associated muscles, and ligaments are also affected. On cellular level, catabolic function of chondrocytes prevails over their anabolic activity. This imbalance is promoted by pro-inflammatory cytokines, which stimulate chondrocytes to produce enzymes (collagenases and aggrecanases) able to degrade extracellular matrix composed of collagen type II and proteoglycans. Several mediators (e.g., TNF-α, IL-1β, NO, and PGE2) play an important role in the pathogenesis and progression of OA [1, 2].
Conventional treatment of OA encompasses non-pharmacotherapeutic approach (e.g., physiotherapy, correction of malalignment, weight control, and patient education), pharmacotherapy, and surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines used most often for the relief of osteoarthritic symptoms. Although NSAIDs are relatively efficient, their prolonged use or their use in susceptible individuals can cause serious side effects such as gastrointestinal toxicity, cardiovascular events, edema development, reversible renal insufficiency, and modest increase of blood pressure. Topical formulations of NSAIDs are slightly less efficient than the oral ones, but their advantage lies in better safety profile. However, irritation of the skin often occurs at the application area [1].
Some patients experiencing unsatisfactory efficacy and side effects of conventional therapy try to overcome current treatment deficiencies by using modalities of complementary and alternative medicine. In that regard, herbal medicinal products (HMPs) and dietary supplements have become considerably popular for alleviation of OA symptoms [3]. Besides expected direct effects, important indirect benefit of their use may be the decrease of required doses of concomitantly administered conventional drugs, as this may result in reduced side effects. At present, available scientific data are insufficient to support the use of these products in clinical management of OA. The aim of this review is therefore to present current knowledge on herbal treatment options in the therapy of OA, i.e., active constituents of plants and mechanisms of their action relevant to OA, advice for patients using herbal products, and results of clinical trials, if available.
2. Herbal medicinal products for oral use in the treatment of osteoarthritis
3. Herbal medicinal products for topical use in the treatment of osteoarthritis
4. Conclusion
Osteoarthritis (OA) is a slowly developing degeneration disease affecting joint cartilage and adjacent tissues. It is one of the most prevalent diseases and most common causes of disability in the elderly, associated with worsening symptoms of joint pain, stiffness, and limitation of articular movement. Therefore, it imposes a significant functional and economic burden not only on affected patients but also on health-care systems.
Contemporary therapy protocols involve an array of non-pharmacological, pharmacological, and surgical measures. Although non-pharmacological treatments represent a basis for OA treatment, pharmacotherapy is considered to be an important adjunct. Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently a cornerstone in OA pharmacotherapy. None of the therapeutic options are curative, but the aim of treatment is to relieve the pain, improve quality of life, and reduce the loss of physical functionality.
NSAIDs often have serious adverse effects, with gastrointestinal complications as the most frequently reported. Some patients do not respond well to conventional medical therapy. Facing unsatisfactory efficacy and adverse effects of conventional therapy, they try to overcome current treatment deficiencies by using herbal medicinal products.
Preclinical studies showed that a number of herbal extracts and respective constituents exhibited pharmacological properties that could be relevant for their beneficial effect in OA. They interfered with cytokine (IL-1β, TNF-α, and IL-6), PGE2, and NO production, modulated biosynthesis and activity of collagenases and aggrecanases, stimulated formation of extracellular matrix, and inhibited activation of transcription factor NF-κB. Active constituents are not often defined satisfactorily, but it could be said that they belong to various groups of secondary metabolites such as sesquiterpene lactones, triterpenic acids, galactolipids, diarylheptanoids, iridoid glycosides, phenolic glycosides, procyanidins, and alkaloids. Trials in humans support observations from
Unfortunately, this area is still far under-researched and needs further and better attention. Existing studies were frequently based on flawed research design, unclear and incomplete selection criteria, inadequate definition of the herbal interventions, or post hoc manipulation of data to support the authors’ preferred conclusions [10]. The same authors urge on high quality and adequately powered clinical studies, advising future researchers that particular attention should be given to the detail of study design, which would ensure that participant samples are well defined according to American College of Rheumatology (ACR) criteria and that participants are recruited without bias [10]. Furthermore, herbal preparations should be reported in detail, including dose, extraction method, and chemical characterization of active principle(s). Finally, study results should be recorded using reliable, valid outcome measures that combine pain and functional impairments in the identification of treatment response (as proposed by OMERACT-OARSI initiative) for comparing the efficacy of different medicinal plant products [10].
Herbal medicines that have been shown to be effective in the treatment of pain associated with OA could help lowering or ceasing the consumption of NSAIDs, reducing at the same time the incidence and severity of their adverse effects. This would also produce necessary long-term safety data, which are needed for most of the herbal medicinal products.
Currently available data are insufficient to acknowledge their use in OA treatment as clinically proven (i.e., with demonstrated efficacy and safety). However, it could be stated that the body of evidence is growing and that expectations on arrival of reliable, efficient, and safe herbal products, fulfilling the criteria of modern medicine in the near future, seem reasonable.
Acknowledgments
This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (grant no. 173021).
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