title: N-Methyl-6, 7-dimethoxyisoquinolone in Annona squamosa twigs is the major immune modifier to elicit polarized Th1 immune response in BALB/c mice.
abstract: Annona squamosa (AS) has traditionally been used as ethnomedicine. We have earlier extracted and fractionated the twigs of AS based upon its bioactivity and observed its immune potentiating activity that was localized in its three fractions. Present communication deals with the phytochemical analysis and pharmacological investigation of the most active chloroform fraction that led to isolation and identification of a number of compounds whose structures were elucidated using 1D and 2D NMR spectroscopic analysis. Amongst the twelve pure compounds isolated, five compounds Lanuginosine (1), (+)-O-methylarmepavine (2), (+)-anomuricine (3), Isocorydine (4), and N-methyl-6, 7-dimethoxyisoquinolone (5) were evaluated in vivo for their immune modifier activities in BALB/c mice after oral administration at three log doses of 0.3, 1.0 and 3.0mg/kg for 14 consecutive days. Of these, three compounds (1, 2 and 5) showed dose dependent immune stimulating activity. However, the uppermost activity was noted in the compound N-methyl-6, 7-dimethoxyisoquinolone at the 3.0mg/kg oral dose. The activity was assessed in the form of increased splenic T and B cellular proliferation, up-regulated CD4+, CD8+ and CD19+ cell population and accentuation in the peritoneal macrophage function. The compound possibly acted modifying the expression of Th1- and Th2- cytokines via stimulation of pro-inflammatory Th1 cytokines IL-2 and IFN-γ. These results warrant the use of the above compounds as an efficient immune-stimulant or immune-adjuvant against diseases with immune suppression. The analogs of the compound may further be chemically synthesized to achieve desired immune modifying activity.
authors: Division of Parasitology, Central Drug Research Institute, M.G. Marg, Lucknow (U.P.), India.
authors: Vishal Kumar
authors: VK
authors: Soni
authors: Dinesh Kumar
authors: DK
authors: Yadav
authors: Nasreen
authors: N
authors: Bano
authors: Preety
authors: P
authors: Dixit
authors: Manisha
authors: M
authors: Pathak
authors: Rakesh
authors: R
authors: Maurya
authors: Mahendra
authors: M
authors: Sahai
authors: Swatantra Kumar
authors: SK
authors: Jain
authors: Shailja
authors: S
authors: Misra-Bhattacharya
mesh_terms: D000818:Animals; D031041:Annona / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: C571376:N-methyl-6, 7-dimethoxyisoquinolone; D015363:Quinolones; D017382:Reactive Oxygen Species