Phytomedicine 21 (2014) 1509–1515 Contents lists available at ScienceDirect Phytomedicine jou rn al homepage: www.elsevier.de/phymed In-vivo antinociceptive, anti-inflammatory and antipyretic activity of pistagremic acid isolated from Pistacia integerrima Abdur Rauf a,∗ , Ghias Uddin a , Bina S. Siddiqui b , Ajmal Khan b , Haroon Khan c , Mohammad Arfan a , Naveed Muhammad c , Abdul Wadood d a Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, KPK, Pakistan b H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan c Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan d Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan a r t i c l e i n f o Article history: Received 3 May 2014 Received in revised form 6 June 2014 Accepted 29 July 2014 Keywords: Pistacia integerrima Pistagremic acid Antinociceptive Anti-inflammatory and antipyretic effect activity Molecular docking a b s t r a c t The current study was designed to explore the antinociceptive, antiinflammatory and antipyretic activity of pistagremic acid (PA), isolated from Pistacia integerima bark in various animal paradigms. The results illustrated significant inhibition of noxious stimulation in acetic acid induced writhing test with maxi- mum effect of 68% at 10 mg/kg i.p. In tail immersion test, pretreatment with PA demonstrated marked activity during various assessment times in a dose dependent manner. The maximum pain inhibition was 59.46% at 10 mg/kg i.p. after 90 min of PA treatment. However, the injection of naloxone did not antago- nize this induced effect. PA significantly ameliorated post carrageenan induced edema dose dependently during various stages of inflammation. The effect was most dominant (60.02%) after 3 rd h of drug admin- istration when examined for 5 h. Similarly, it provoked dose dependent antipyretic effect in febrile mice with maximum of 60.04% activity at 10 mg/kg i.p. after 3rd hour of PA post treatment. Furthermore, molecular docking was carried out to understand the binding mode of PA. From the docking study it was observed that PA fits well in the active site of COX-2 enzyme due to hydrogen and hydrophobic moiety interactions to the important active site of molecule. In conclusion, PA possesses strong peripheral and central antinociceptive activity independent of opi- oidergic effect which was augmented by its anti-inflammatory and antipyretic activities. © 2014 Elsevier GmbH. All rights reserved. Introduction P. integerrima belong to family Anacardiacea, commonly known as kakar singhi or shani in Puhsto. It is found in the eastern Himalayan range from Indus to Kumaon as well as in Pakistan (Rauf et al., 2013; Uddin et al., 2011) at a height of 12,000 to 8000 ft. P. integerrima is a medium sized deciduous tree hav- ing medicinal value such as anti-inflammatory, analgesic, blood purifier, remedy for gastrointestinal disorders, expectorant, anti- asthmatic, antipyretic, antiemetic and antidiarrheal (Upadhye and Rajopadly, 2010; Uddin et al., 2012). The galls of P. integerrima are used as herbal drug for the treatment asthma, diarrhea, chronic bronchitis, disorders of respiratory tract, skin diseases, psoriasis, fever, and as appetizer, hepatitis, liver disorders, oxidative stress and counter hyperuricemia (Uddin et al., 2012; Rauf et al., 2013). ∗ Corresponding author. Tel.: +92 3469488944. E-mail addresses: Abdurraufphd@upesh.edu.pk, mashaljcs@yahoo.com, mashalics@gmail.com (A. Rauf). Triterpenoid, sterols, flavonoids, acylated oligosaccharides and phenolic constituents have been isolated from its different parts of P. integerrima (Joshi and Mishra, 2010; Ahmad et al., 2010; Arfan et al., 2011; Ullah et al., 2013). In continuation to our previous study on pistagremic acid (PA) the structure of this compound has reported on the basis of NMR and single x-rays crystal (Rauf et al., 2014a,b; Arfan et al., 2011). The current study deals with the antinociceptive and anti- inflammatory activity of pistagremic acid (PA), a triterpenic compound isolated from P. integerima in animal paradigms. Material and methods Animals BALB/c (20–25 g) mice of either sex were used in all experi- ments. Animals were purchased from the Pharmacology Section of the Department of Pharmacy, University of Peshawar, Peshawar, Pakistan. The animals were maintained in standard laboratory http://dx.doi.org/10.1016/j.phymed.2014.07.015 0944-7113/© 2014 Elsevier GmbH. All rights reserved.