Anatabine Ameliorates Experimental Autoimmune Thyroiditis

Abstract

Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile.

Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice

“…We have shown that anatabine lowers Aβ production and neuroinflammation both in vitro and in vivo suggesting it could be a useful therapeutic compound against AD, particularly as it readily crosses the blood-brain barrier [21][22][23]. Other studies have revealed that anatabine suppresses the induction of cycloxygenase-2 and inducible nitric oxide synthase in macrophage and reduces the incidence of tyroiditis in mice [24] further supporting an anti-inflammatory activity of anatabine in vivo. A randomized controlled clinical trial has shown that anatabine supplementation can reduce thyroglobulin antibodies in patients with Hashimoto's thyroiditis [25] whereas a survey of people using a dietary supplementation of anatabine has shown a beneficial effect on joint pain and stiffness [26] suggesting that anatabine exerts an anti-inflammatory activity also in humans.…”

Patterns of Interferon-Alpha–Induced Thyroid Dysfunction Vary with Ethnicity, Sex, Smoking Status, and Pretreatment Thyrotropin in an International Cohort of Patients Treated for Hepatitis C

“…Several other studies have suggested a protective effect of smoking against autoimmune hypothyroidism (33)(34)(35), and a recent report found that smoking was associated with a lower risk of papillary thyroid cancer (36). One group has recently reported that anatabine, a minor nicotinic alkaloid in the tobacco leaf, can decrease disease prevalence and severity in a mouse model of autoimmune thyroiditis (37).…”

Effects of a Facial Cream Containing the Minor Alkaloid Anatabine on Improving the Appearance of the Skin in Mild to Moderate Rosacea: An Open-Label Case Series Study

“…Anatabine has been shown in multiple in vitro and in vivo models of excessive inflammation to attenuate the production of proinflammatory mediators through a reduction in the activation of the transcription factors NF-κB and STAT3 [9, 10, 11, 13]. Research has shown that NF-κB is involved in the upregulation of the antimicrobial peptides (cathelicidins) and other proinflammatory mediators believed to be involved in the progression and severity of rosacea [14, 15].…”

“…Anatabine has also been shown to block the production of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α in the blood and tissues of mice injected with lipopolysaccharide by blocking the activation of the transcription factors NF-κB and STAT3 [10]. Caturegli et al [11] investigated the effects of anatabine in a mouse model of autoimmune thyroiditis and found that anatabine significantly reduced several markers of systemic inflammation.…”