Therapeutic effects of astragaloside IV and Astragalus spinosus saponins against bisphenol A-induced neurotoxicity and DNA damage in rats

Abstract

Background Bisphenol A (BPA) is an endocrine disruptor to which humans are often subjected during daily life. This study aimed to investigate the ameliorative effect of astragaloside IV (ASIV) or saponins extracted from Astragalus spinosus (A. spinosus) against DNA damage and neurotoxic effects induced by BPA in prefrontal cortex (PFC), hippocampal and striatal brain regions of developing male rats. Materials and Methods Juvenile PND20 (pre-weaning; age of 20 days) male Sprague Dawley rats were randomly and equally divided into four groups: control, BPA, BPA+ASIV and BPA+A. spinosus saponins groups. Bisphenol A (125 mg/kg/day) was administrated orally to male rats from day 20 (BPA group) and along with ASIV (80 mg/kg/day) (BPA+ASIV group) or A. spinosus saponin (100 mg/kg/day) (BPA+ A. spinosus saponins group) from day 50 to adult age day 117. Results Increased level of nitric oxide (NO) and decreased level of glutamate (Glu), glutamine (Gln), glutaminase (GA) and glutamine synthetase (GS) were observed in the brain regions of BPA treated rats compared with the control. On the other hand, co-administration of ASIV or A. spinosus saponin with BPA considerably improved levels of these neurochemicals. The current study also revealed restoration of the level of brain derived neurotrophic factor (BDNF) and N-methyl-D-aspartate receptors (NR2A and NR2B) gene expression in BPA+ ASIV and BPA+A. spinosus saponins groups. The co-treatment of BPA group with ASIV or A. spinosus saponin significantly reduced the values of comet parameters as well as the intensity of estrogen receptors (ERs) immunoreactive cells and improved the histological alterations induced by BPA in different brain regions. Conclusion It could be concluded that ASIV or A. spinosus saponins has a promising role in modulating the neurotoxicity and DNA damage elicited by BPA.

Natural Products in Mitigation of Bisphenol A Toxicity: Future Therapeutic Use

“… ( a ) The molecular mechanism of antioxidant effects of luteolin against BPA-induced renal toxicity through Nrf2/ARE/HO-1 pathway modulation [ 293 ]. ( b ) The molecular mechanism of lycopene [ 303 ], Astragalus spinosus saponins (ASS), and Astragaloside IV (AS IV) [ 304 ] against BPA exposure-induced neurotoxicity. Nrf2: nuclear factor-like 2; ARE: antioxidant response element; HO-1: heme oxygenase 1; BDNF: brain-derived neurotrophic factor; TrKb: tyrosine receptor kinase B; ERK: extracellular signal-regulated kinases; MAPK: mitogen-activated protein kinase; CREB: cAMP response element-binding protein.…”

“…A. spinosus has potential neuroprotective effects linked to its antioxidant, anti-depressive, and anti-apoptotic roles [ 309 ]. In rats, administration of ASIV or A. spinosus saponins prevented BPA exposure-induced neurotoxicity by reducing oxidative stress and restoring the expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptors [ 304 ]. The role of A. spinosus saponins and ASIV on brain-derived neurotrophic factor expression regulation is shown in Figure 3 .…”

“…The role of A. spinosus saponins and ASIV on brain-derived neurotrophic factor expression regulation is shown in Figure 3 . Both treatments also improved histological changes caused by BPA exposure in various regions of the brain [ 304 ]. In another study in rats, administration of AS IV and A. spinosus saponins reversed the BPA-induced anxiogenic and depressive-like behaviors [ 310 ].…”

Current Progress on Neuroprotection Induced by Artemisia, Ginseng, Astragalus, and Ginkgo Traditional Chinese Medicines for the Therapy of Alzheimer’s Disease

“…Ginsenoside Rd inhibited in vivo the hyperphosphorylation of NR2B subunit and decreased its expression levels [ 133 ]. Astragaloside IV or saponins extracted from Astragalus decreased the level of glutamate (Glu), glutamine (Gln), glutaminase (GA), and glutamine synthetase (GS) in different brain regions of male rats [ 134 ]. EGb761 and its monomer component ginkgolides inhibited the postischemic LTP, by inhibiting the EPSCs and the α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor subunit GluA1 expression on postsynaptic rat hippocampus membrane [ 135 ], and ginkgolide A inhibited NMDA receptors in mouse primary cortical neurons [ 136 ].…”

Roles and Mechanisms of Astragaloside IV in Combating Neuronal Aging

“…Astragaloside IV plays multiple roles to maintain genomic integrity. It can ameliorate DNA damage and neurotoxicity by declining the level of glutaminase (GA), glutamine (Gln), glutamate (Glu) and glutamine synthetase (GS) while enhancing the amount of NO in the brain [ 56 ]. Astragaloside IV triggers the activation of the Nrf2/Keap1 cascade to inhibit inflammation and to hinders ROS production and apoptosis.…”