Effects of long-term dietary administration of estrogen receptor-beta agonist diarylpropionitrile on ovariectomized female ICR (CD-1) mice

Abstract

Diarylpropionitrile (DPN) is an estrogen receptor-β-specific agonist that has been linked to neuroprotection, preserving cognitive function with age, the suppression of anxiety-like behaviors, inhibition of cancer growth, and other positive properties. We hypothesized that DPN may have pro-longevity properties. DPN was administered via feed at a dose corresponding to approximately 3 mg/kg/day to ovariectomized female mice beginning at 7 months of age. Mice were followed for the duration of their lifespans while monitoring body mass, aspects of behavior, learning, memory, and frailty. DPN-treated mice gained more body mass over the first 2 years of age (17 months of the study). A test of voluntary running behavior at 24 months of age behavior revealed no deficits in DPN-treated mice, which were as likely as control mice to engage in extended bouts of wheel running, and did so at higher average speeds. DPN administration had anxiolytic-like effects when measured using an elevated plus maze at 9 months of age. A mouse frailty index was used to assess age-related changes. The correlation between age and frailty differed between control and DPN-treated mice. Overall, dietary DPN administration had some beneficial effects on the aging phenotype of ovariectomized female mice with few significant detrimental effects.

Screening of Anxiolytic and Antidepressant of Methanolic Leaves Extract of Syzygium Cumini in Mice

“…A simple, expeditious and reliable method to evaluate the antidepressant potential of drug is tail suspension method. Sherry et al discussed the method in which immobility duration was induced by tail suspension which is an indication of a depressive state [18]. Each mouse was suspended individually 25 cm from the bottom by adhesive tape applied on the tip of tail.…”

Preclinical models of frailty: Focus on interventions and their translational impact: A review

“…Diarylpropionitrile is an estrogen receptor-␤-specific agonist that has anti-aging effects including positive effects on energy metabolism and neuroprotection [78]. Based on these observations, Said and colleagues [79] proposed that it might improve healthspan. Indeed, chronic treatment with diarylpropionitrile (3 mg/kg/day) attenuates frailty, improves spatial learning and memory and enhances running in adult, ovariectomized CD-1 female mice [79].…”

“…Based on these observations, Said and colleagues [79] proposed that it might improve healthspan. Indeed, chronic treatment with diarylpropionitrile (3 mg/kg/day) attenuates frailty, improves spatial learning and memory and enhances running in adult, ovariectomized CD-1 female mice [79].…”

“…Several other studies have looked at interventions that exacerbate frailty. One recent study showed that, although treatment with the estrogen receptor-ß agonist diarylpropionitrile attenuates frailty in young adult ovariectomized CD-1 female mice it increases frailty in older mice (17-33 months of age) [79]. The reasons for this age-specific differential effect are unclear.…”

“…The reasons for this age-specific differential effect are unclear. However, this does demonstrate the need to investigate frailty interventions across the life course and not just in younger animals [79]. Another preclinical study investigated the influence of radiation therapy on frailty.…”