Estrogenic and anti-amnesic potential of Millettia griffoniana Baill. (Fabaceae) ethanolic extract on scopolamine-induced memory impairment in ovariectomized Wistar rats

Estrogens are female sex hormones produced by various tissues in the body, the main endogenous source being the ovaries (Ateba et al., 2013). They promote the growth and differentiation of the uterine lining, the vagina and mammary glands as well as the survival of cholinergic neurons through their neurotrophic and neuroprotective effects (Doty et al., 2015). They also inhibit amyloid-β accumulation, neuronal apoptosis pathways and reduce oxidative stress (Henderson, 2015). After menopause, there is a sudden drop in the estrogen production leading to numerous physiological disorders including hot flushes, sleep disturbances, vaginal dryness, moods change (Khayum et al., 2019). To overcome symptoms associated with the lack of estrogens, postmenopausal women often resort to hormone replacement therapy (HRT), which significantly reduces the frequency of hot flushes and alleviates vaginal dryness and bone density loss in a short and medium term (Ketcha Wanda et al., 2016). Unfortunately, the long-term use of HRT increases risks of endometrial and breast cancers, potentiates the appearance of Alzheimer's type dementia (Korol and Pisani, 2015).

Alzheimer's disease (AD), accounting for 60–70% dementia prevalence, remains the leading cause of dementia with 50 million sufferers worldwide (Alzheimer's Disease International, 2018). Its prevalence is two to three folds greater in women than in men of the same age (Alzheimer's Disease International, 2015). About 6.2 million people aged 65 or older AD patients in the United States, 3.8 million were women (Alzheimer’s Association, 2021). Although the main cause of AD remains the accumulation of β plaques (β-amyloid) and proteins (tau) hyperphosphorylation in neurons, many other factors such as low acetylcholine levels, oxidative stress, glutamatergic deficiency also contribute to its etiology. A high incidence of AD has been recorded in post-menopausal women due to the loss of endogenous estrogens (Harden, 2014). The available drugs used to reverse AD symptoms are donepezil, rivastigmine, galantamine and memantine, which have no beneficial effects on estrogen targets (Singh et al., 2016). Thus, numerous menopausal women resort to non-hormonal therapies and plant preparations or plant-derived compounds (phytoestrogens) which got a growing interest of scientists these last decades.

Phytoestrogens are naturally occurring compounds which are shaped as mammalian estrogens and mimic their estrogen-like effects via their estrogens receptor (ERα and ERβ) binding ability (Michel et al., 2013; Njamen et al., 2013). Main phytoestrogen sources include medicinal plants and dietary food intake. Most of the phytoestrogens discovered belong to flavonoids, chalcones, coumestanes, lignanes and erythroidine alkaloids classes (Michel et al., 2013; Njamen et al., 2013; Djiogue et al., 2014). In the framework of this research finding, attention was given to M. griffoniana, a member of the Fabaceae and Leguminosae subfamily, which contains the most potent phytoestrogens (Michel et al., 2013). This plant is utilized in traditional medicine to alleviate various ailments including menopausal-related symptoms and dementia just like Millettia macrophylla (Banzouzi et al., 2008; Lawal et al., 2010; Zingue et al., 2013, 2016). The in vitro and in vivo estrogenic effects of six isoflavones isolates from M. griffoniana were previously reported (Ketcha Wanda et al. 2006, 2010). However, the estrogenic potential of the crude extract as prescribed by the traditional healer and its potential neuroprotective benefit have not been demonstrated yet. This therefore prompted us to assess the in vitro and in vivo estrogenic effects of M. griffoniana ethanolic extract and its neuroprotective potential on scopolamine-induced memory impairment in ovariectomized Wistar rats.

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