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aiman,3 Dhuha N Boumarah,4 Aldana M Almubireek,2 Gaeda K Alkaltham,2 Hussain A Alhawaj,5 Taleb Alkhamis,5 Nazish Rafique,1 Ahmed Alsunni,1 Rabia Latif,1 Seham Alsaif,1 Dana Almohazey,6 Sayed AbdulAzeez,7 J Francis Borgio71Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2King Fahd hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Department of Internal Medicine, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Department of Surgery, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 5Animal House, Environmental Health Department, Institute for Research and Medical Consultation, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 6Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 7Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Lubna Al Asoom, Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O Box 2004, Dammam, 31541, Saudi Arabia, Tel +966505846344, Email [email protected] Background: Obesity is a global pandemic that is associated with high morbidity and mortality. Natural herbs are commonly used for weight reduction and appetite suppression. Therefore, we aim to investigate the role and mechanism of Nigella sativa (NS) and ginger on weight reduction and appetite regulation. Methods: This experimental study was performed at Imam Abdulrahman Bin Faisal University. Twenty-five female rats were distributed into 5 groups: NS (oral 1000mg/kg), Ginger (500 mg/kg), NS-ginger (both interventions), a positive control (intraperitoneal 50 μg/kg Liraglutide), and a negative control. Each intervention was given for  9 weeks. Food intake and body weight were assessed weekly. Serum lipid profile and peptides involved in appetite control (cholecystokinin (CCK), glucagon-like peptide 1(GLP-1), gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, and orexin) were assayed at the end of the experiment. Results: None of the interventions showed a statistically significant difference regarding food consumption or weight gain (p > 0.05). However, the three interventions significantly reduced total cholesterol (TC), NS and NS-ginger significantly increased HDL, NS increased ghrelin and ginger increased orexin. Conclusion: The present dose and duration of NS, ginger, or in combination did not demonstrate a significant change in body weight or food consumption in comparison to the negative or positive controls. However, NS or ginger has improved the lipid profile by reducing TC and increasing HDL. In addition, NS or ginger can influence some of the peptides involved in appetite regulation such as the increase in ghrelin induced by NS and the reduction of orexin induced by ginger. We believe that these latter effects are novel and might indicate a promising effect of these natural products on appetite regulation. [ABSTRACT FROM AUTHOR]