title: Investigation into the mechanism of action of essential oil of Pistacia integerrima for its antiasthmatic activity.
abstract: BACKGROUND
  Pistacia integerrima J.L. Stewart ex Brandis locally known as Karkatashringi is an important medicinal plant whose galls are valued in traditional medicine used in India for the treatment of asthma, chronic bronchitis, phthisis, diarrhea, fever, other ailments for the respiratory tract, and as antispasmodic, carminative, antiamoebic and anthelmintic. However, in vitro and in vivo investigations providing new insights into its pharmacological properties have not been thoroughly investigated yet. The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI).
  
  
  METHODS
  EOPI was tested using in vitro studies such as antioxidant activity, mast cell degranulation, angiogenesis, isolated guinea pig ileum preparation and soyabean lipoxidase enzyme activity. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry.
  
  
  RESULTS
  EOPI (5-30 µg/ml) inhibits 5-lipoxidase enzyme activity with IC50 of 19.71 µg/ml and DPPH scavenging activity up to 100 µg/ml with maximum inhibition of 44.93 ± 2.53% at 100 µg/ml. Pre-treatment with EOPI inhibited erythropoietin-induced angiogenesis. It showed dose dependent (10, 30 and 100 µg/ml) anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation to an extent 19.08 ± 0.47%. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggests that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30mg/kg i.p.) inhibited lipopolysaccharide-induced increase in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Roflumilast was used as a standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs.
  
  
  CONCLUSIONS
  The study demonstrates the effectiveness of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.
authors.affiliation: Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, India.
authors.forename: R L
authors.initials: RL
authors.lastname: Shirole
authors.affiliation: Department of Pharmaceutical Chemistry, A. R. A. College of Pharmacy, Nagaon, Dhule, India.
authors.forename: N L
authors.initials: NL
authors.lastname: Shirole
authors.affiliation: Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, India.
authors.forename: A A
authors.initials: AA
authors.lastname: Kshatriya
authors.affiliation: Department of Clinical Pharmacology T. N. Medical College and B. Y. L. Nair Charitable Hospital, Mumbai, India.
authors.forename: R
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, India. Electronic address: madhusudan.saraf@gmail.com.
authors.forename: M N
authors.initials: MN
authors.lastname: Saraf
mesh_terms: D000485:Allergens; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D002452:Cell Count; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009822:Oils, Volatile / Q000494:pharmacology* / Q000627:therapeutic use; D010047:Ovalbumin; D009195:Peroxidase / Q000378:metabolism; D027927:Pistacia; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015053:Zygote / Q000187:drug effects / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D000485:Allergens; D020533:Angiogenesis Inhibitors; D018927:Anti-Asthmatic Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D009822:Oils, Volatile; D003189:p-Methoxy-N-methylphenethylamine; D010047:Ovalbumin; D009195:Peroxidase; D001094:Arachidonate 5-Lipoxygenase
keywords: Asthma; Essential oil; Lipopolysaccharide; Lipopolysaccharide(PubChem CID:0111:B4); Pistacia integerrima J.L. Stewart ex Brandis; Spirometry