In Vivo and In Silico Studies of Flavonoids Isolated from Pistacia integerrima as Potential Antidiarrheal Agents

Fahad A Alhumaydhi; Abdur Rauf; Umer Rashid; Saud Bawazeer; Khalid Khan; Mohammad S Mubarak; Abdullah S M Aljohani; Haroon Khan; Gaber El-Saber Batiha; Mohamed A El-Esawi; Abhay P Mishra

doi:10.1021/acsomega.1c00298

In Vivo and In Silico Studies of Flavonoids Isolated from Pistacia integerrima as Potential Antidiarrheal Agents

ACS Omega. 2021 Jun 14;6(24):15617-15624. doi: 10.1021/acsomega.1c00298. eCollection 2021 Jun 22.

Authors

Affiliations

¹ Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Buraydah 51452, Saudi Arabia.
² Department of Chemistry, University of Swabi, Swabi, Anbar, 23561 Khyber Pakhtunkhwa, Pakistan.
³ Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Islamabad 22060, Pakistan.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21421, P.O. Box 42, Saudi Arabia.
⁵ Directroate of Science and Technology, Peshawar, University of Peshawar, Peshawar 25120, Khyber Pakhtunkhwa, Pakistan.
⁶ Department of Chemistry, The University of Jordan, Amman 11942, Jordan.
⁷ Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia.
⁸ Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
⁹ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhou 22511, Al Beheira, Egypt.
¹⁰ Botany Department, Faculty of Science, Tanta University, Tanta 31527, Egypt.
¹¹ Department of Pharmacology, Faculty of Health Science, University of Free State, Bloemfontein 9300, South Africa.

Abstract

Pistacia integerrima leaf galls are used in several traditional medicines to cure many diseases such as diarrhea, asthma, fever, cough, vomiting, and hepatitis. The main goal of the present investigation was to assess the antidiarrheal effect of the Pistacia integerrima extracts/fractions and four isolated flavonoid compounds (1-4) on mice. An in vivo assay involving castor-oil-induced diarrhea was used to evaluate the antidiarrheal potential of extracts/fractions at 100, 200, and 400 mg/kg p.o., as well as isolated compounds at 5, 10, and 20 mg/kg p.o. Pretreatment of mice with extracts/fractions significantly attenuated castor-oil-induced diarrhea in a dose-dependent manner. Among all crude extracts and fractions, the ethyl acetate extract was the most effective with 100% protection against diarrhea followed by chloroform (75% protection) at 400 mg/kg p.o. Although all the isolated compounds exhibited strong antidiarrheal activity, isolated compounds 1 and 4 demonstrated 100% protection against diarrhea. Moreover, docking models were performed using the Molecular Operating Environment (MOE) and AutoDock software and suggested that the extracts and isolated compounds exert antidiarrheal activity by inhibiting mu-opioid and delta-opioid receptors. Therefore, our finding affords a strong pharmacological basis for the traditional use of P. integerrima galls in the treatment of diarrhea.