Anti-arthritic effects of yucca

Yucca products have been used for many years for reputed anti-arthritic effects, both by Native Americans and more recently by the nutraceutical industry. Whole yucca plant powder in tablet form is a common nutraceutical. The only direct studies of anti-arthritic effects of yucca are those of Bingham [22-24], who reported that symptoms of pain and swelling in arthritic human patients were relieved by consumption of yucca tablets. Bingham's work was reported in an obscure journal, and has apparently not been recognized as valid by the arthritis research community. Nevertheless, Bingham's reports have led to the widespread use of yucca products for treatment and prevention of arthritis not only in humans but also in horses and dogs.

Bingham [22] proposed that yucca saponins have anti-protozoal activity, which suppresses protozoal infection of the intestine. Bingham [22] reported that R. Wyburn-Mason had observed a free-living protozoan, Naegleria, universally present in the joints of arthritic patients [25]. Tropozoites of the organism reportedly were found in the intestine. Support for this theory was provided by the effectiveness of metronidazole, an anti-protozoal drug, in arthritis treatment. Saponins are also effective anti-protozoal agents. Yucca saponins are as effective as metronidazole in killing giardia tropozoites in the intestine [14]. Thus, if the protozoal theory of causation of arthritis has any merit, a role of yucca in arthritis treatment can be advanced on the basis of the anti-protozoal activity of yucca saponins.

There are well-known interactions between rheumatoid arthritis, chronic inflammatory disease, and food and nutrition [26,27]. Of particular importance are nutrients that stimulate the formation of oxidants and peroxides (e.g. unsaturated fatty acids, iron), which promote inflammatory disease, and antioxidants (e.g. vitamin E) and omega-3 fatty acids, which protect against auto-oxidation. Yucca compounds may have roles in these effects. Yucca polyphenols are potent antioxidants [18,21,28]. Yucca saponins are known to reduce iron absorption [29] and may reduce fatty acid absorption by sequestering bile acids necessary for micelle formation and fat absorption [4].

Cordain [30] stated, "Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice-versa, the nature of the relationship remains elusive." These authors reported that arthritis is associated with intestinal bacterial overgrowth of Escherichia coli and Lactobacillus lactis. Yucca saponins have antibacterial properties [31,32], although Lactobacillus spp. and E. coli may be tolerant of yucca extract and yucca saponins [31]. Thus, a beneficial effect of yucca on arthritis could involve anti-protozoal, anti-oxidant and anti-bacterial activities. As previously mentioned, the drug metronidazole attenuates gastrointestinal inflammation and can prevent activation of arthritis in animal models [30]. Yucca saponins are as effective as metronidazole in control of intestinal protozoa [14].

Recent research suggests another possible mode of action of yucca in preventing arthritis by anti-inflammatory activity. Yucca contains anti-inflammatory polyphenolics such as resveratrol and yuccaols A, B, C, D and E [18,19]. Yucca bark and whole yucca plant powder contain resveratrol (Table 1), well known for its anti-inflammatory activity [20,33]. Marzocco [34] demonstrated that yuccaols inhibit inducible nitric oxide synthase (iNOS) expression (Fig. 3). Nitric oxide is an inflammatory agent, and its content in tissues increases during inflammatory responses. The expression of iNOS is controlled by NFkappaB (NFkB), a transcription factor that regulates gene expression. Resveratrol and yucca phenolics strongly inhibit NFkB [34]. Yuccaol C is particularly effective (Fig. 3 and 4). Thus, whole plant yucca powder has powerful anti-inflammatory activity, mediated via inhibition of NFkB activation.

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models [35]. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes, giving rise to the highly toxic radical peroxynitrite [35]. The study of experimental arthritis in animals has demonstrated an increased activity of iNOS [36,37]. Thus the NFkB inhibitory and anti-oxidant effects of yucca polyphenolics may aid in prevention of reactive oxygen species (ROS) induction of arthritis by inhibiting the induction of iNOS.

Platelet aggregation is characteristic of inflammation. Yucca phenolics have inhibitory activity against platelet aggregation [38-40]. Yucca phenolics also have antioxidant activity [19] and free-radical scavenging effects [18]. Blood platelets participate in allergic inflammation responses [41]. Yuccaols inhibit the generation of free radicals in blood platelets [39]. One of the yucca phenolics, trans-3,3',5,5'-tetrahydroxy-4-methoxystilbene, showed the highest anti-platelet action.

Another botanical product with anti-inflammatory activity is cat's claw [42]. As reviewed by Miller et al. [42], cat's claw (Uncaria guianensis) "is a remarkably potent inhibitor of NFkB activity and tumor necrosis factor production." Evaluation of the anti-inflammatory activity of a combination of yucca and cat's claw would be of interest.

The evidence presented in this review indicates that yucca has potential in vivo anti-inflammatory activity, and warrants more in-depth investigation.