# Protective Effects of Calligonum comosum as a Natural Remedy to Counteract Pregabalin‐Induced Toxicity: Insights From Chemical Profiling, In Vivo, and In Silico Analyses

## TL;DR

This study shows that Calligonum comosum extract can protect against pregabalin-induced liver, kidney, and reproductive damage in rats.

## Contribution

The study combines in vivo, chemical, and in silico methods to demonstrate the protective effects of Calligonum comosum against pregabalin toxicity.

## Key findings

- Calligonum comosum extract reduced liver and kidney damage markers in rats exposed to pregabalin.
- In silico analysis revealed strong binding of C. comosum phytochemicals to molecular targets linked to toxicity pathways.
- Phytochemicals like quercetin and rutin showed stronger interactions than pregabalin with key proteins.

## Abstract

This study explores the therapeutic potential of Calligonum comosum extract in alleviating pregabalin (PGB)‐induced toxicity in male Wistar rats, with a focus on hepatic, renal, and reproductive health. PGB exposure led to significant biochemical disturbances, including elevated liver enzymes (AST, ALT, LDH), impaired kidney markers (urea, creatinine, uric acid), reduced reproductive hormones (testosterone, FSH, LH), and notable histopathological damage in liver, kidney, and testicular tissues. Treatment with
C. comosum
extract effectively restored liver and kidney functions and partially corrected hormonal imbalances. The extract reduced AST, ALT, and LDH levels by 18.5%, 25.2%, and 13.7%, respectively. Similarly, urea, creatinine, and uric acid decreased by 30.3%, 38.0%, and 15.2%. Testosterone and LH levels improved, suggesting enhanced reproductive recovery. Histological analyses confirmed reduced inflammation, necrosis, and congestion in treated tissues. Supporting these findings, in silico docking studies showed strong interactions between
C. comosum
phytochemicals and molecular targets linked to toxicity pathways. Quercetin demonstrated the strongest binding (−8.1 to −9.2 kcal/mol), particularly with LXR‐α and GLUT‐1. Rutin showed the highest affinity for GnRH1‐R (−10.4 kcal/mol), while caffeic acid, gallic acid, and chlorogenic acid also exhibited strong interactions, especially with β2 AR (−8.9 kcal/mol). In contrast, PGB displayed weaker binding (−6.0 kcal/mol). These results highlight the protective effects of
C. comosum
and support its potential as a natural remedy for mitigating PGB‐induced hepatorenal and reproductive toxicity.

This study highlights the significant therapeutic effects of
C. comosum
extract in counteracting PGB‐induced toxicity in the liver, kidneys, and testes. Furthermore, in silico analysis offered insights into the protective molecular mechanisms of
C. comosum
phytochemicals against PGB‐induced toxicity. The integration of these computational and experimental findings underscores the potential of
C. comosum
as a natural remedy for PGB‐induced toxicity, providing a strong basis for future studies on natural therapeutic alternatives to mitigate drug‐related adverse effects.