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. 2025 May 14;26(10):4712.
doi: 10.3390/ijms26104712.

Multitargeted Effects of Plantago ovata Ethanol Extract in Experimental Rat Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome

Lia-Oxana Usatiuc  1 , Raluca Maria Pop  2 , Surd Adrian  3 , Marcel Pârvu  4 , Mădălina Țicolea  1 , Ana Uifălean  1 , Dan Vălean  5 , Laura-Ioana Gavrilaș  6 , Szabo Csilla-Enikő  7 , Loredana Florina Leopold  8 , Floricuța Ranga  8 , Florinela Adriana Cătoi  1 , Alina Elena Pârvu  1
Affiliations

Multitargeted Effects of Plantago ovata Ethanol Extract in Experimental Rat Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome

Lia-Oxana Usatiuc et al. Int J Mol Sci. .

Abstract

Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE's antioxidant activity was evaluated in vitro through DPPH, H2O2, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride-Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment.

Keywords: Plantago ovata; diabetes mellitus; inflammation; oxidative stress; polycystic ovary syndrome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The HPLC chromatogram of phenolic content from P. ovata ethanolic extract at 340 nm.
Figure 2
Figure 2
The FTIR analysis of phenolic content from P. ovata ethanolic extract at 340 nm.
Figure 3
Figure 3
OS and inflammatory markers PCA results: (A) STZ group; (B) POEE100%; group; (C) POEE50% group; and (D) POEE25% group.
Figure 4
Figure 4
OS, metabolic, and liver injury marker PCA results in STZ-induced DM in rats: (A) STZ group; (B) POEE100% group; (C)POEE50% group; and (D) POEE25%.
Figure 5
Figure 5
OS and inflammatory markers PCA result in LET-induced PCOS in rats: (A) LET group and (B) POEE100% group.
Figure 6
Figure 6
Hormonal and inflammatory markers PCA results in LET-induced PCOS in rats: (A) LET group and (B) POEE100% group.
Figure 7
Figure 7
Effect of POEE treatment on histology of LET-induced ovary. (A) LET group, (B) LET + POEE100% group, and (C) LET + M group. AF, antral follicle; CL, corpus luteum; CF, cystic follicle.
Figure 8
Figure 8
Ultrasound images of ovaries of PCOS animals: bilateral enlarged ovaries with oblonged multiple cystic follicles.
See this image and copyright information in PMC

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