Silibinin and Naringenin against Bisphenol A-Induced Neurotoxicity in Zebrafish Model—Potential Flavonoid Molecules for New Drug Design, Development, and Therapy for Neurological Disorders

Abstract

Bisphenol A (BPA), a well-known xenoestrogen, is commonly utilised in the production of polycarbonate plastics. Based on the existing evidence, BPA is known to induce neurotoxicity and behavioural issues. Flavonoids such as silibinin and naringenin have been shown to have biological activity against a variety of illnesses. The current research evaluates the neuropharmacological effects of silibinin and naringenin in a zebrafish model against neurotoxicity and oxidative stress caused by Bisphenol A. In this study, a novel tank diving test (NTDT) and light–dark preference test (LDPT) were used in neurobehavioural investigations. The experimental protocol was planned to last 21 days. The neuroprotective effects of silibinin (10 μM) and naringenin (10 μM) in zebrafish (Danio rerio) induced by BPA (17.52 μM) were investigated. In the brine shrimp lethality assay, the 50% fatal concentrations (LC50) were 34.10 μg/mL (silibinin) and 91.33 μg/mL (naringenin) compared to the standard potassium dichromate (13.15 μg/mL). The acute toxicity investigation found no mortality or visible abnormalities in the silibinin- and naringenin-treated groups (LC50 > 100 mg/L). The altered scototaxis behaviour in LDPT caused by BPA was reversed by co-supplementation with silibinin and naringenin, as shown by decreases in the number of transitions to the light zone and the duration spent in the light zone. Our findings point to BPA’s neurotoxic potential in causing altered scototaxis and bottom-dwelling behaviour in zebrafish, as well as the usage of silibinin and naringenin as potential neuroprotectants.

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

“…[20,[37][38][39] Studies are increasing day by day to reduce these negative effects of BPA. [26,40] GA has important antioxidant, anticancer, anti-inflammatory, and antiapoptotic properties. [41] As the ameliorative effects of GA on BPA-caused cardiotoxicity had not been previously studied, this study demonstrated cardioprotective effects of GA on several antioxidant and antiapoptotic signaling pathways.…”

The Multifaceted Effects of Flavonoids on Neuroplasticity

“…Quercetin and rutin Prevention of scopolamine-induced memory impairment [101] Danio rerio Silibinin and Naringenin Prevention of Bisphenol A-induced neurotoxicity [102] As reported in Table 2, most of the studies on 326 the multifaceted effects of bioactive compounds Therefore, the administration of dietary bioactive compounds and/or food and beverage rich in them in transgenic flies and worms allowed the characterization of the multifaceted effects of bioactive compounds on brain plasticity and functionality.…”

Flight for fish in drug discovery: a review of zebrafish-based screening of molecules

“…Reverse genetics is well established in the zebrafish model for precise exploration of behaviours, such as gene knockdown using antisense morpholino oligos for blocking locations on RNA, or genome-editing technologies like the CRISPR/Cas9 system [1,2]. Humans and zebrafish have been found to have organ-specific structural, physiological and functional features in common, the zebrafish genome has been completely sequenced, and over 80% of human disease-associated genes have been linked to the zebrafish genome [3][4][5]. Using several high-throughput approaches, researchers are now screening a considerable number of compounds for a variety of toxicological endpoints in zebrafish [6].…”