This also is one of the main reasons for skepticism about CAM in the minds of both the lay public and the professionals [25, 29C31]. arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities. 1. Herbal CAM for the Treatment of Inflammatory Autoimmune Arthritis Conventional (allopathic) anti-inflammatory drugs are the mainstay of treatment for a variety of immune disorders, including rheumatoid arthritis (RA) [1C5]. The nonsteroidal anti-inflammatory drugs (NSAIDs) and biologics (e.g., antitumor necrosis factor (TNF)-antibody and the decoy TNF-receptor) represent a prominent group of such drugs. However, the usage of these drugs is associated with severe adverse effects, including gastrointestinal bleeding and cardiovascular complications [3, 5, 6]. Owing to the side effects and the high cost of conventionally used anti-inflammatory drugs, patients with arthritis are increasingly using complementary and alternative medicine (CAM) modalities of treatment [7C21]. Over 36% Americans used CAM products annually for different disorders and the trend is on the rise [11, 22C25]. Traditional Chinese medicine, Ayurvedic medicine, Kampo, and Homeopathy are among the MK-3207 major contributors to the natural products consumed by patient populations. However, despite the increasing usage and popularity of CAM products in the western world [11, 22C26], one of the main limitations of their use is the meager information about their mechanisms of action and objectivity in evaluating efficacy [27, 28]. This also is one of the main reasons for skepticism about CAM in the minds of both the lay public and the professionals [25, 29C31]. Thus, there is a need for continued MK-3207 studies on the mechanistic aspects of action of CAM products. A diverse group of diseases is characterized by inflammation that can be triggered not only by foreign microbial antigens but also by self-antigens. The response to self-antigens results in autoimmune inflammation. Therefore, like the infectious diseases, the autoimmune diseases (such as multiple sclerosis (MS), type-1 diabetes mellitus (T1D), RA, and atherosclerosis) are also associated with inflammation. Considering that autoimmune diseases result from a dysregulated immune system [36, 37], it is imperative to examine and unravel the immunological basis of the therapeutic activity of CAM products against autoimmune disorders as well as other conditions involving inflammation [27, 28, 38C42]. This paper is focused on the immunomodulation of autoimmune arthritis by herbal CAM products. We have described here in detail adjuvant arthritis (AA) (Figure 1) as a prototypic experimental model of RA. Conceptually, the main immune effector pathways in AA are broadly representative of various other animal models of arthritis, for example, collagen-induced arthritis (CIA), streptococcal cell wall-induced arthritis (SCWIA), and proteoglycan-induced arthritis. We have elaborated upon specific MK-3207 immune pathways in arthritis that are modulated by a variety of herbal preparations originating from plants native to different regions of the world (Table 1, and Figures ?Figures22 and ?and3).3). These immune mechanisms include the cellular and humoral responses, the cytokine response/balance, and the cellular migration into the target organ. Open in a separate window Figure 1 Experimentally-induced adjuvant arthritis (AA) in the Lewis rat. (a) Arthritic paws and (b) the course MK-3207 of the disease. AA is CX3CL1 induced by subcutaneous immunization with heat-killed H37Ra (1?mg/rat) [32C34]. The phases of AA are as follows: incubation, onset, peak, and recovery. The Arthritic Score represents the severity of arthritis . Each paw is graded on a scale of 0 to 4, and total score per rat is derived by adding the scores of all 4 paws of that rat [32C34]. Open.