*6.3. Anti-Autoimmune Diseases*

Recent research has shown that *T. impetiginosa* has e ffects on various autoimmune diseases such as psoriasis, osteoarthritis, allergy, and inflammatory bowel disease. Suo et al. [41] found that five novel compounds isolated from the water extract of *Taheebo* had strong anti-inflammatory activity but displayed weak or no e ffect on anti-allergic and antioxidant activities. Muller et al. [64] reported that Lapacho, a common constituent in the inner bark of *T. impetiginosa*, suppressed growth of the human keratinocyte cell line (HaCaT) and could be promising as an e ffective anti-psoriatic agent. In addition, it has been reported that *T. impetiginosa* bark extracts significantly inhibited the growth of some bacterial species associated with gastrointestinal disease and diarrhea, implying their suitability for prophylactic therapeutic usage [7]. Park et al. [15] examined the e ffect of *T. avellanedae* on monoiodoacetate-induced osteoarthritis in a Sprague-Dawley rat model. They observed that *T. avellanedae* administration ameliorated osteoarthritis symptoms by decreasing the serum levels of proinflammatory cytokines and inflammatory mediators, such as PGE2, LTB4, and IL-1β [15]. De Miranda et al. [5] further investigated its e ffects using animal models and described anti-edematogenic and antinociceptive effects of *T. impetiginosa* in rat paw edema induced by carrageenan. In this study, an aqueous extract containing a 200 mg/kg dose ameliorated rat paw edema in a way similar to indomethacin, the control drug. However, at a dose of 400 mg/kg, the edema was not reduced, suggesting that the edema-reducing compounds were competing with other constituents and nullifying any edema-reducing e ffect.

Lee et al. [28] investigated the analgesic and anti-inflammatory e ffects of *T. impetiginosa*, especially with regard to osteoarthritis. In this study, the analgesic e ffects were tested using pain threshold methods assessed by a hot plate test. A *T. impetiginosa* ethanol extract-treated group showed a significant analgesic e ffect at 200 mg/kg compared with a control group treated with diclofenac. Using an acetic acid-induced writhing response, they confirmed results from previous experiments that 100–400 mg/kg of *T. impetiginosa* ethanol extract significantly inhibited the number of writhes compared to the control group. This analgesic model used acetic acid because it causes inflammatory pain by increasing capillary permeability, and the hot plate-induced pain indicated narcotic involvement. Anti-inflammatory activity was assessed using acetic acid-induced vascular permeability, 12- *O*-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema, arachidonic acid-induced mouse ear edema, and carrageenan-induced paw edema. Most of the group treated with *T. impetiginosa* exhibited reduced inflammation at a dose of 100–400 mg/kg, including suppression of ear weight and thickness, inhibition of ear inflammation, and reduction of edema in a TPA-induced ear edema test volume [28]. Byeon et al. [8] performed a similar study using a hot water extract and tested the edema model with di fferent inducers. They found that prostaglandin E2 (PGE2) production was blocked and edema symptoms were reduced when treated with *T. impetiginosa*. However, in this study, *T. impetiginosa* only a ffected arachidonic acid-induced ear edema.

Park et al. [29] investigated the e ffect of *T. impetiginosa* on a DSS-induced colitis mouse model. They discovered that *T. impetiginosa* protected the colon from inflammation by reducing mucosal edema loss, epithelial crypts, and inflammatory cell infiltration. In addition, the use of *T. impetiginosa* in traditional arthritis medicines led researchers to perform experiments in an osteoarthritis model. Park et al. [46] used an ethanol extract of *T. impetiginosa* in the form of Tabetri ™ (Ta-EE) in a monoiodoacetate-induced osteoarthritic mouse model. They compared the pain indicator of a mechanical paw withdrawal threshold to Von Frey stimuli and found that pain was significantly increased in osteoarthritic rats, which was suppressed by Ta-EE. Moreover, they also compared the results to those of methylsulfonylmethane (MSM) and Pc-LE and found that Ta-EE produced results comparable to those of these anti-inflammatory agents. Interestingly, results with Ta-EE were not dose-dependent, indicating that Ta-EE can be used in small doses. The osteoarthritic rats showed no weight loss, indicating no toxicity or side e ffects regarding weight loss or appetite caused by Ta-EE treatments. To investigate further, they measured the degradation of articular cartilage in rats administered Ta-EE and found it to be dramatically inhibited. Strangely, the chondroprotective e ffect of Ta-EE was better than that of MSM at 60 and 120 mg/kg doses in a dose-dependent manner.
