Modulatory effect of berberine and its risk assessment during pre-natal and post-natal exposure of nicotine

Nicotine is a naturally occurring alkaloid that has deleterious effects on the female reproductive system while, berberine is an isoquinoline alkaloid reported to exhibit multiple pharmacological properties. This study was conducted to analyze the role of berberine on pre and post-natal toxic effects of nicotine on mothers and pups. Nicotine was administered subcutaneously while berberine was administered orally to adult female Wister rats. Animals were divided into seven groups, with each group containing ten females. For the pre-mating phase, treatments were given daily for 30 days; after 20 days of dosing, females were housed with males for mating, and dosing continued for the remaining 10 days. Group I served as the control and received 0.5% carboxymethylcellulose (CMC) orally. Group II received nicotine alone (1 mg/kg, subcutaneously) from gestational day 0 (GD0) to GD21. Groups III and IV received nicotine (1 mg/kg, subcutaneously) combined with berberine at 10 mg/kg and 20 mg/kg orally, respectively, from GD0 to GD21. Group V received nicotine (1 mg/kg) starting 20 days before mating and continuing through GD21. Groups VI and VII received nicotine (1 mg/kg, subcutaneously) along with berberine at 10 mg/kg and 20 mg/kg (orally), respectively, beginning 20 days before mating and continuing through gestation. Berberine showed protective effects at lower doses by normalizing key antioxidant biomarkers like superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), higher doses can exacerbate oxidative stress, as indicated by increased levels of malondialdehyde (MDA), a marker of oxidative damage. The results from the current study showed that berberine might have protective effects in other conditions but the dose-dependent toxicity highlights the potential risks of berberine, especially during pregnancy, where its ability to induce uterine contractions and teratogenic effects at higher doses poses significant concerns for fetal health.