Analgesic Effects of Methanol Leaf Extracts from Datura alba ness in Male Wistar Rats through Reduction of C-reactive Protein Levels

Abstract

Introduction: The increasing interest in utilizing natural products from medicinal plants for pain management stems from their wide availability and minimal side effects. This study aims to evaluate the toxicity profile of Datura alba ness (DAN) extracts and assess their potential analgesic activity through preventive and therapeutic analgesia models in Wistar rats, as well as to investigate the possible mechanisms of action using molecular docking. Materials and Methods: Fresh leaves of DAN were collected from a garden in the Abua/Odua Local Government Area of Rivers State, Nigeria. The leaves were extracted using cold maceration to obtain ethanolic extracts of Datura alba ness (MEDAN). Twelve mice (19-30g) were used for toxicity study, while sixty Wistar rats (140-180g) were used for analgesic studies. Serum C-reactive protein levels were determined using ELISA methods, and molecular docking simulations were conducted using AutoDock and Discovery Studio Visualizer. Results: The results indicated that MEDAN was very safe, with an LD50 of 5000 mg/kg. The findings demonstrate that MEDAN significantly increased the pain threshold in male Wistar rats after three weeks of administration in a dose-dependent manner during the preemptive analgesia study, while pain thresholds increased within one hour but decreased over time in the therapeutic analgesia study. The combination of MEDAN with a standard drug (Flexicam) resulted in improved analgesic effects at the 500 mg/kg dose. Additionally, the study revealed that MEDAN significantly reduced serum C-reactive protein levels after three weeks of oral administration. Molecular docking studies indicated that stigmasterol, gamma-sitosterol, and cholest-5-en-3-ol, 24-propylidene-(3β) from MEDAN demonstrated binding affinity to C-reactive protein receptors, mimicking the effects of the reference drug, celecoxib. Conclusion: This study concludes that ethanolic extracts of Datura alba ness exhibited significant efficacy in pain reduction by lowering C-reactive protein levels. This effect was especially enhanced when the 500 mg/kg dose of MEDAN was combined with the standard drug, Flexicam. The findings provide a scientific basis supporting the traditional medicinal use of Datura alba ness for pain management.