Antiasthmatic activity of 2-piperidone by selective animal models

Abstract

2-piperidone is a six membered heterocyclic compound existing naturally in piperaceae and portulaceae families. The synthetic derivatives of piperidone are promising bioactive molecules. They are antioxidant and antiinflammatory agents. Antihistaminic and anticholinergic studies are used as a part of antiasthmatic study. In the current study antihistaminic and anticholinergic studies were carried out using guinea pig bronchi and ilei in naturally isolated compound 2-piperidone from the plant Talinum portulacifolium. The results indicate that the compound (2 mg/kg 10.81 ± 1.29*** at p<0.001) showed profound antihistaminic activity significantly in histamine induced bronchospasm model than standard drug chlorpheniramine (2 mg/kg 8.77±0.43** at ** p<0.01). The compound can be further studied for antiasthmatic activity by various other ways to establish its mechanism of action as well as drug development studies to render it a novel antiasthmatic drug.

Keywords

• Antiasthmatic
• bronchospasm
• antihistaminic
• 2-piperidone

References

1. [1] Broide D H. Molecular and cellular mechanisms of allergic disease. J Allergy Clin Immunol. 2001; 108(2): S65–S71. [CrossRef]
2. [2] Ward C E, Baptist A P. Characteristics of Complementary and Alternative Medicine (CAM) use among older adults with asthma. J Asthma. 2016; 53(5): 546–552. [CrossRef]
3. [3] Taniguchi T and Ogasawara K. A diastereocontrolled synthesis of (+)-febrifugine: A potent antimalarial piperidine alkaloid. Org Lett. 2000. 2(20): 3193–3195. [CrossRef]
4. [4] Maedeh Mohammadi, Ghasem D. Najafpour, Maryam Nikzad. Piperine-The Bioactive Compound of Black Pepper: From Isolation to Medicinal Formulations. Compr Rev Food Sci F. 2017; 16: 124-140. [CrossRef]
5. [5] Darshan S, Doreswamy R. Patented anti-inflammatory plant drug development from traditional medicine. Phytother Res. 2004; 18: 343-357. [CrossRef]
6. [6] Meghwal M, Goswami T. Piper nigrum and piperine: An update. Phytother Res. 2013; 27: 1121–1130. [CrossRef]
7. [7] Pachauri M, Gupta ED, Ghosh PC. Piperine loaded PEG‐PLGA nanoparticles: preparation, characterization, and targeted delivery for adjuvant breast cancer chemotherapy. J Drug Delivery Sci Technol. 2015; 29: 269–282. [CrossRef]
8. [8] Takeuchi Y, Azuma K, Takakura K, Abe H, and Harayama T. Asymmetric synthesis of febrifugine and isofebrifugine using yeast reduction. ChemComm. 2001; 17: 1643–1644. [CrossRef]

9. [9] El-Subbagh H I, Abu-Zaid S M, Mahran M A, Badria F A, Al-Obaid A M. Synthesis and biological evaluation of certain α,β-unsaturated ketones and their corresponding fused pyridines as antiviral and cytotoxic agents. J Med Chem. 2000; 43(15): 2915–2921. [CrossRef]
10. [10] Venkatesa Perumal R, Adiraj M, and Shanmuga Pandiyan P. Synthesis, analgesic and anti inflammatory evaluation of substituted 4-piperidones. Indian Drugs. 2001; 38(3): 156–159.
11. [11] Koh PF, Wang P, Huang JM, Loh TP. Biomass derived furfural-based facile synthesis of protected (2S)-phenyl-3- piperidone, a common intermediate for many drugs. ChemComm. 2014; 50 (61): 8324-8327. [CrossRef]
12. [12] Vani M, Abdul Rahaman Sk, Prameela Rani A. In vitro, in vivo Anti-Asthmatic Studies of Talinum portulacifolium F Asian J Pharm. 2017; 11(2): S289-S301.
13. [13] Vani M, Abdul Rahaman Sk, Prameela Rani A. Hepatoprotective studies of 2-piperidone isolated from leaf extracts of Talinum portulacifolium (Forssk.) Asch. ex Schweinf in CCl4 induced hepatotoxicity. J Pharm Pharmacogn Res. 2019; 7(4): 234-245.
14. [14] Sagar R, Sahoo HB, Kar B, Mishra NK, Mohapatra R, Sarangi SP. Pharmacological evaluation of Calendula officinalis L. on bronchial asthma in various experimental animals. Int J Nutr Pharmacol Neurol Dis. 2014; 4(2): 95-103. [CrossRef]
15. [15] Goyal RK, Practical in Pharmacology, third ed., B.S. Shah Prakashan, India, 2003. [16] Kubo N, Minami T, Hori Y, Yamashita T, Kumazawa T. Enhanced parasympathetic nerve activities in experimentally induced nasal hyper sensitivity. Acta Otolaryngol Suppl. 1989; 463: 14-20. [CrossRef]
16. [17] Stephen OO, Gerald IE, Ifeanyi HA, Ogochukwu LI, Dickson OU, Viona O. Evaluation of the anti-asthma activity of aqueous root bark extract of Ficus exasperata Vahl (Moraceae). Int J Health Res. 2012; 5: 5–12
17. [18] Sagar R, Sahoo H B. Evaluation of the antiasthmatic activity of ethanolic extract of Elephantopus scaber L. leaves. Indian J Pharmacol. 2012; 44: 398–401. [CrossRef]
18. [19] Mc Clements J, Decker EA. Lipid oxidation in oil-in-water emulsions: Impact of molecular environment on chemical reactions in heterogeneous food systems. J Food Sci. 2000; 65: 1270. [CrossRef]
19. [20] De Meglio PG, Corradi F, Ravenna F, Gentili P, Tempra-Gabbiati G, Cristina T, Riva M. Pyrrolidone and piperidone derivatives with antihistaminic and antianaphylactic activities, Synthesis and pharmacological study. Chem Inform. 1987; 42(5): 359-82. [CrossRef]
20. [21] Li L, Chen M, Jiang FC. Design, synthesis, and evaluation of 2-piperidone derivatives for the inhibition of β-amyloid aggregation and inflammation mediated neurotoxicity. Bio org Med Chem. 2016; 24(8): 1853-1865. [CrossRef]
21. [22] Ortiz de Urbina AV, Martin ML, Montero MJ, Carron R, Sevilla MA, San Roman L. Antihistaminic activity of pulegone on the guinea-pig ileum. J Pharm Pharmacol. 1990; 42(4): 295-296. [CrossRef]
22. [23] OECD guidelines for the testing of chemicals-425. Acute oral toxicity-up and down procedure (UDP) 2008. http://www.oecd.org (accessed on 25 December 2019). [CrossRef]
23. [24] Chandrakant Nimgulkar C, Dattatray Patil S, Dinesh Kumar B. Anti-asthmatic and anti-anaphylactic activities of Blatta orientalis mother tincture. Homeopathy. 2011; 100: 138–143.
24. [25] Erhirhie EO, Ekene NE, Ajaghaku DL. Guidelines on dosage calculation and stock solution preparation in experimental animal studies. J Nat Sci Res. 2014; 4(18): 100-106.
25. [26] OECD GD 24 Guidance document on Acute Oral Toxicity. Environmental Health and Safety Monograph Series on Testing and Assessment. 2000. http://www.oecd.org (accessed on 25 December 2019). [CrossRef]