Antithyroid and Goitrogenic Effects of Millet: Role of C-Glycosylflavones*

Abstract

Pearl millet [Pennisetum millet (L.) leeke] is the main source of food energy for the rural poor in many areas of the semiarid tropics. Epidemiological evidence suggests that millet may play a role in the genesis of endemic goiter in these areas, and sparse experimental data in rats support this suspicion. This study was undertaken to determine in vivo in rats and in vitro using porcine thyroid slices and a thyroid peroxidase (TPO) assay the goitrogenic and antithyroid effects of millet diets, extracts of millet, and certain pure compounds contained therein. For use in these studies, whole grain millet was progressively dehulled to yield successively four bran and four flour fractions in which direct analyses revealed progressively lower concentrations of C-glycosylflavones. In vivo feeding of bran fraction 1, that richest in C-glycosylflavones, led to a significant increase in thyroid weight and antithyroid effects. Feeding of bran fraction 2, the next richest in C-glycosylflavones, produced similar, but less marked, changes. In vitro studies of 125I metabolism using porcine thyroid slices indicated that extracts of bran fractions 1 and 2 were most potent, producing changes similar to those produced by methimazole (MMI). At a concentration of 60 mumol/L, glucosylvitexin, the major C-glycosylflavone present in millet, had effects comparable to those of 1 mumol/L MMI. Similarly, in studies of porcine TPO, extracts of bran fraction 1 caused pronounced (85%) inhibition of enzyme activity, and progressively less inhibition was induced by extracts of bran fractions 2, 3, and 4. Overall, the TPO-inhibiting activities of the various millet fractions closely correlated with their C-glycosylflavone concentrations. Three C-glycosylflavones present concentrations. Three C-glycosylflavones present in millet, glucosylvitexin, glycosylorientin, and vitexin, also inhibited TPO activity. Thus, in vivo and in vitro studies revealed that millet diets rich in C-glycosylflavones produce goitrogenic and antithyroid effects similar to those of certain other antithyroid agents and small doses of MMI. We conclude that in areas of iodine deficiency in which millet is a major component of the diet, its ingestion may contribute to the genesis of endemic goiter.

Goitrogenic activity of p‐coumaric acid in rats

“…Our results of the goitrogenic effects of p-coumaric acid are in harmony with previous reports for p-coumaric acid-related compounds. Certain flavonoids (hesperidin, hesperetin, catechin, and phloretin) are known to have intrinsic antithyroid activity [6,16]. Moreover, flavonoid metabolites such as resorcinol, phloroglucinol, and dihydroxybenzoic acid have antithyroid activity [16,17].…”

Traditional Fermentation Increases Goitrogenic Activity in Pearl Millet

“…They reported that feeding of both unfermented and fermented millet to rats were associated with similar changes on thyroid follicles size or on thyroid hormone profile. On the contrary, we [4] recently showed in rats that traditional fermentation of one millet cultivar (Balady) clearly potentiated its goitrogenicity and induced an increase in serum T 3 , whereas traditional fermentation of another millet cultivar (Bayoda) caused an increase in both serum T 4 and T 3 .…”

“…Subsequent investigations have shown that feeding of millet diets to rats resulted in an enlargement of the thyroid gland and/or distortion of thyroid hormone profile [2][3][4].…”

Impact of Soy Bean on Thyroid Hormones of Albino Rats

“…The thyroid gland is responsible for the production of hormones involved in regulating metabolism, body weight and oxygen requirement as well as normal growth and development during childhood. The thyroid hormones (tri-iodothyronine (T 3 ) and thyroxine (T 4 ) are synthesized in the gland from iodine and the amino acid tyrosine [4][5][6]. At the molecular and biochemical levels, isoflavones have the ability to change thyroid cell events in at least two ways.…”

“…Secondly, by interaction with thyroid binding globulin (TBG). This is a plasma protein involved in the inactivation and transport of T 3 and T 4 . It has been hypothesized that phytoestrogens could potentially increase TBG concentrations.…”