Effect of Hautriwaic Acid Isolated from Dodonaea viscosa in a Model of Kaolin/Carrageenan-Induced Monoarthritis

Abstract

In the present work, the antiarthritic activity of hautriwaic acid is reported. This ent-clerodane diterpene isolated from Dodonaea viscosa was evaluated in mice using a kaolin/carrageenan-induced monoarthritis model. The inflammation observed in the joint (knee) on days 1-8 ranged from 50-70 %. After 10 days of treatment with different doses of hautriwaic acid (5, 10, 20 mg/kg), a decrease in knee inflammation was detected. This recovery was observed with both reference drugs, methotrexate (1 mg/kg) and diclofenac (0.75 mg/kg). In these groups of mice, the concentration of proinflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the joint was significantly lower than that of the negative control group (animals with damage without any treatment). The negative control group presented a decrease in the concentration of interleukin-10, while the groups that received hautriwaic acid at different dose exhibited an increase in this interleukin. This anti-inflammatory cytokine was not modified in the joint of mice with diclofenac, but in mice that received methotrexate, a significant decrease was observed. Hautriwaic acid isolated from D. viscosa diminished the joint edema induced by this mixture of polysaccharides (carrageenan), possibly by acting as immunomodulator of the inflammatory response.

Effect of Dichloromethane-Methanol Extract and Tomentin Obtained from Sphaeralcea angustifolia Cell Suspensions in a Model of Kaolin/Carrageenan-Induced Arthritis

“…The administration of this substance resulted in localized inflammation associated with the production of a number of mediators such as TNF-α and IL-1β [22]. In a study in our laboratory, it has been shown that the intra-articular administration of carrageenan, as an experimental procedure, induced an important local increment of TNF-α and IL-1β [23]. It has been demonstrated that TNF-α induces cartilage and bone degradation, and the penetration of lymphocytes, macrophages, and neutrophils to the joint cavity.…”

Terpenes from Natural Products with Potential Anti-Inflammatory Activity

“…In both models, the compound diminished the edema [19]. Hawtriwaic acid at doses of 5, 10, and 20 mg/kg decreased knee inflammation in a murine model of monoarthritis induced with kaolin/carrageenan, by the reduction of serum levels of the pro-inflammatory interleukins Il-1β, IL-6, and TNF-α, and the increase in the serum levels of the anti-inflammatory interleukin IL-10 [20]. Ursolic acid, a pentacyclic triterpene found in many plant species, was identified for the first time in 1920 in the epicuticular waxes of apples.…”

Terpenes as possible drugs for the mitigation of arthritic symptoms – A systematic review

“…The use of substances able to induce anti-inflammatory or reduce proinflammatory cytokines can represent an important advance in the therapeutic treatment of a range of diseases. In this respect, terpenes stand out as an interesting option for the discovery of new bioactive molecules for arthritis injury, especially as an alternative to reduce the inflammatory process (Barreto et al, 2016, Brito et al, 2015, de Santana Souza et al, 2014, Salinas-Sánchez et al, 2015 . Our review highlighted 14 terpenes (Table 1) that are able to modulate the levels of cytokines in different models of arthritic diseases, and thereby contribute to improving the clinical profile by reducing the inflammatory process and pain.…”