<p>This study investigates the therapeutic potential of combining palmitoleic acid with niosomal serratiopeptidase in a rat model of insulin-resistant polycystic ovarian syndrome (PCOS). Niosomal serratiopeptidase was formulated by thin-film hydration and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Thirty prepubertal female rats were divided into six groups (<i>n</i> = 5). A negative control (Group 1); PCOS rats (Group 2); PCOS rats treated with free niosomes (0.7&#xa0;mg/kg, i.p.; Group 3); serratiopeptidase-loaded niosomes (1&#xa0;mg/kg, i.p.; Group 4); palmitoleic acid (300&#xa0;mg/kg, p.o.; Group 5); and a combination of serratiopeptidase-loaded niosomes plus palmitoleic acid (Group 6). PCOS was induced in groups 2–6 using letrozole plus a high-fat diet for 30&#xa0;days, followed by 30&#xa0;days of the respective treatments, after which body and ovarian weights, ovarian cysts, and histological and biochemical parameters were assessed. The niosomes prepared exhibited a size of 746.6 ± 54.1&#xa0;nm and a PDI of 0.389 ± 0.03. Serratiopeptidase encapsulation efficiency was found to be around 74%. Compared with controls, the PCOS group exhibited estrous cycle irregularities and significant increases in ovarian volume (<i>p</i> &lt; 0.01), ovarian index (ovarian weight/body weight × 100%; <i>p</i> &lt; 0.01), cyst number (<i>p</i> &lt; 0.01), fasting plasma glucose (<i>p</i> &lt; 0.01–0.001), fasting insulin (<i>p</i> &lt; 0.001), HOMA-IR (<i>p</i> &lt; 0.001), luteinizing hormone (<i>P</i> &lt; 0.001), and testosterone (<i>p</i> &lt; 0.001), along with decreased follicle-stimulating hormone (<i>p</i> &lt; 0.0001). While serratiopeptidase niosomes or palmitoleic acid alone partially improved PCOS parameters, including reductions in ovarian volume (<i>p</i> &lt; 0.05) and metabolic and hormonal markers (<i>p</i> &lt; 0.01–0.001), some effects did not reach statistical significance. In contrast, the combination of niosomal serratiopeptidase and palmitoleic acid produced the greatest effects, significantly improving metabolic, hormonal, and ovarian parameters toward near-normal levels (<i>p</i> &lt; 0.05–0.0001). These preclinical findings suggest that niosomal serratiopeptidase combined with palmitoleic acid may represent a potential supportive therapeutic approach for PCOS; however, further clinical validation is warranted before any translational conclusions can be drawn.</p>

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The activity of niosomal serratiopeptidase enzyme in combination with palmitoleic acid in rats with insulin-resistant polycystic ovarian syndrome

  • Alaa A. A. Aljabali,
  • Yahia Hayjneh,
  • Mohammad A. Obeid,
  • Ibrahim Albokhadaim,
  • Samir Alhojaily,
  • Sheryar Afzal,
  • Yazan Abu Haija,
  • Bahaa Al‑Trad

摘要

This study investigates the therapeutic potential of combining palmitoleic acid with niosomal serratiopeptidase in a rat model of insulin-resistant polycystic ovarian syndrome (PCOS). Niosomal serratiopeptidase was formulated by thin-film hydration and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Thirty prepubertal female rats were divided into six groups (n = 5). A negative control (Group 1); PCOS rats (Group 2); PCOS rats treated with free niosomes (0.7 mg/kg, i.p.; Group 3); serratiopeptidase-loaded niosomes (1 mg/kg, i.p.; Group 4); palmitoleic acid (300 mg/kg, p.o.; Group 5); and a combination of serratiopeptidase-loaded niosomes plus palmitoleic acid (Group 6). PCOS was induced in groups 2–6 using letrozole plus a high-fat diet for 30 days, followed by 30 days of the respective treatments, after which body and ovarian weights, ovarian cysts, and histological and biochemical parameters were assessed. The niosomes prepared exhibited a size of 746.6 ± 54.1 nm and a PDI of 0.389 ± 0.03. Serratiopeptidase encapsulation efficiency was found to be around 74%. Compared with controls, the PCOS group exhibited estrous cycle irregularities and significant increases in ovarian volume (p < 0.01), ovarian index (ovarian weight/body weight × 100%; p < 0.01), cyst number (p < 0.01), fasting plasma glucose (p < 0.01–0.001), fasting insulin (p < 0.001), HOMA-IR (p < 0.001), luteinizing hormone (P < 0.001), and testosterone (p < 0.001), along with decreased follicle-stimulating hormone (p < 0.0001). While serratiopeptidase niosomes or palmitoleic acid alone partially improved PCOS parameters, including reductions in ovarian volume (p < 0.05) and metabolic and hormonal markers (p < 0.01–0.001), some effects did not reach statistical significance. In contrast, the combination of niosomal serratiopeptidase and palmitoleic acid produced the greatest effects, significantly improving metabolic, hormonal, and ovarian parameters toward near-normal levels (p < 0.05–0.0001). These preclinical findings suggest that niosomal serratiopeptidase combined with palmitoleic acid may represent a potential supportive therapeutic approach for PCOS; however, further clinical validation is warranted before any translational conclusions can be drawn.