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Cleome arabica L mitigates bisphenol A-induced ovarian dysfunction and inflammation in Wistar rats: biochemical, histopathological, pharmacokinetic, and in silico studies

  • Ikram Allagui,
  • Jazia Sdayria,
  • Khaled Athmouni,
  • Nourhene Zammel,
  • Fatma Guesmi,
  • Mongi Saoudi,
  • Angelo Maria Giuffrè,
  • Mohamed Salah Allagui,
  • Saber Nahdi,
  • Abdel Halim Harrath

摘要

The present study evaluated the antioxidant and anti-inflammatory properties of Cleome arabica (CA) fruit extract against bisphenol A (BPA)-induced ovarian injury in female Wistar rats. The antioxidant activity was estimated by the total antioxidant capacity (TAC) and superoxide radical (NBT) content. For the in vivo analyses, 24 animals were divided into the following 4 groups: the control group; the BPA group (50 mg/kg BW BPA for 30 days); the BPA  + CA group (50 mg/kg BW BPA and 50 mg/kg BW CA); and the CA group (50 mg/kg BW CA). The in vitro results demonstrated that CA exhibited strong antioxidant activity and scavenged O2•− radicals. . Pharmacokinetic properties were also explored, reflecting the physiological dynamics of the five active molecules (quercetin, catechin, kaempferol, rosmarinic acid, and naringenin). The in vivo findings revealed a significant increase in body weight associated with a significant increase in plasma C-reactive protein (CRP), proinflammatory cytokines (IL-1, IL-6, and TNF-α), and testosterone levels (p < 0.01). In addition, ovarian histological disruption was observed. However, co-administration of CA extract significantly improved ovarian histological integrity and attenuated inflammatory and androgenic disturbances. Moreover, in silico investigations showed that CA compounds interacted more strongly with the active sites of IL-1β, IL-6, or TNF-α. The best binding energy was observed between catechin (five H-bonds) and IL-1β and IL-6, at −6.0 and −6.1 kcal/mol, respectively, and between rosmarinic acid (four H-bonds) and TNF-α, at −6.4 kcal/mol. The present study supports the use of Cleome arabica in the treatment of infertility for female polycystic ovary syndrome (PCOS) patients.