Anti-Inflammatory and Antioxidant Effects of Gundelia tournefortii Aqueous Extract on the Liver and Kidney of PCOS Mice

Abstract

Background: Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder associated with increased risk of kidney and liver damage. Current treatments have shown contradictory outcomes, and their long-term use causes unwanted side effects. G. tournefortii could serve as a complementary medicine to current PCOS treatments.

Purpose: This study evaluates the effect of G. tournefortii in alleviating liver and kidney damage induced by PCOS via the regulation of oxidative stress pathways.

Study design: PCOS was induced in female Balb/c mice using dehydroepiandrosterone over 21 days. They included a Sham group, a Vehicle group, a group treated with the extract only, and an untreated PCOS mice group. Positive Controls were treated with Metformin. The other PCOS groups were either co-treated while inducing PCOS or treated with the extract post-disease induction.

Methods: Histological analysis was performed. Serum liver and kidney biochemical markers, levels of oxidative stress, and two pro-inflammatory markers were measured. NLRP3 and its associated genes (caspase-1 and ASC) gene expression was assessed.

Results: The extract restored normal kidney and liver histology post-PCOS induction. It decreased ALT and AST levels by 50% and the oxidant marker malondialdehyde (MDA) by 65% (P < .05). Superoxide dismutase (SOD)/catalase (CAT) activities were normalized in PCOS treated group. IL-1β/TNF-α significantly decreased (80% and 68%, respectively, P < .05) in the post-treated group. NLRP3 genes decreased in kidney tissues post-treatment with G. tournefortii extract.

Conclusion: G. tournefortii reduced oxidative stress by modifying the ASC/caspase-1/IL-1β signaling pathway, thus protecting livers and kidneys highlighting the herb as a potential preventative and complementary agent in mitigating PCOS associated damage.

Keywords: DHEA-induced mice; Gundelia tournefortii; kidney injury; liver injury; polycystic ovarian syndrome; polyphenols.

Figure 1.

Hematoxylin and eosin-stained section of livers from all the groups. The livers from control (A), Vehicle (B), and G. tournefortti (C), PCOS (D), Preco (E), Post (F), and Metformin (G) were examined under light microscope (10x) and compared to PCOS mice. Black triangles in “D” point to degenerated and swollen hepatocytes.

Figure 2.

Effect of G. tournefortii on AST and ALT serum levels. Serum levels of (A) AST and (B) ALT. Data are expressed as the mean ± SD (n = 3). ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 3.

Effects of G. tournefortii on oxidative stress in livers of PCOS mice GSH level (A), MDA levels (B) SOD activity (C), and CAT activity (D), and were measured in liver tissues. The data are presented as the means ± SD. ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 4.

Effects of G. tournefortii on the pro inflammatory markers in liver of PCOS mice. Levels of IL-1β (A) and TNF-α (B) were measured in liver homogenates. The data are presented as the means ± SD (n = 3 per group). ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 5.

Effect of G. tournefortii extract on NLRP3 expression and expression of NLRP3- associated genes in liver of PCOS mice. (A), (B), and (C) show mRNA fold change for NLRP3, capsase-1, and ASC respectively. Data are mean ± SEM of 3 mice per group. ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 6.

Hematoxylin and eosin-stained section of kidneys from all the groups. The kidneys from control (A), Vehicle (B), and G. tournefortti (C) PCOS(D), Preco (E), Post (F), and Metformin (G) were examined under light microscope (40x) and compared to PCOS mice. Blue arrow: interstitial lymphocyte infiltration; thick arrow: casts and shedding cell in tubules; star: areas of dilated tubules and tubular necrosis. Normal glomeruli (G) and normal renal tubules (RT).

Figure 7.

Effect of G. tournefortii on urea and BUN serum levels. Serum levels of (A) urea and (B) BUN. Data are expressed as the mean ± SD (n = 3). ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 9.

Effects of G. tournefortii on the pro inflammatory markers in kidney of PCOS mice. Levels of TNF-α (A) and IL-1β (B) were measured in kidney homogenates. The data are presented as the means ± SD (n = 3 per group). ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 10.

Effect of G. tournefortii extract on NLRP3 expression and its associated genes in kidneys of all groups. (A), (B), and (C) show mRNA fold change for NLRP3, capsase-1, and ASC respectively. Data are mean ± SEM of 3 mice per group. ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.

Figure 8.

Effects of G. tournefortii on oxidative stress in kidneys of PCOS mice. GSH level (A), MDA levels (B) SOD activity (C), and CAT activity (D), and were measured in Kidney tissues. The data are presented as the means ± SD. ^aP < .05 versus the Vehicle group and ^bP < .05 versus the PCOS group.