Investigation of centrally and peripherally acting analgesic and anti inflammatory activity of biological immune response modulator (an Amazonian plant extract) in animal models of pain and inflammation

Authors

  • Mital Ravalji Department of Zoology, The M.S. University of Baroda, Vadodara, Gujarat, India
  • Edwin Cevallos-Arellano Instituto de Tumores, Quito, Ecuador
  • Suresh Balakrishnan Department of Zoology, The M.S. University of Baroda, Vadodara, Gujarat, India

Keywords:

Anti-inflammatory, Anti-nociceptive, Central analgesic, Peripheral analgesic, Biological immune response modulator

Abstract

Background: Biological immune response modulator (BIRM) - An aqueous extract of dried roots of the species Dulcamara (family Solanaceae) grown in Ecuador, considered as a natural remedy for various disease is promoted as a natural herbal medicine. Our aim of the study was to assess the central and peripheral analgesic and anti-inflammatory property of BIRM and to study its mechanism of action.

Methods: Peripheral analgesic and anti-inflammatory activity was evaluated using acetic acid induced writhing test and carrageenan paw edema test in male Swiss Albino mice (n=8 per group). Formalin test was taken up to evaluate BIRM’s centrally, as well as peripheral antinociceptive action.

Results: We observed through our studies that BIRM when administered repeatedly for 7 days (4 ml/kg, p.o.) was able to exert its anti-nociceptive and anti-inflammatory activity through central and peripheral mechanism. BIRM was able to significantly inhibit both acetic acid induced writhes and carrageenan-induced paw edema indicating it’s possible peripheral analgesic and anti-inflammatory action. BIRM was also able to inhibit both neurogenic and inflammatory pain in the formalin test indicating its action through central and peripheral nervous system.

Conclusion: Our study results show that BIRM has the potential anti-inflammatory property and is able to exert its anti-nociceptive effect through both central and peripheral mechanisms.

References

Qadrie ZL, Hawisa NT, Khan MW, Samuel M, Anandan R. Antinociceptive and anti-pyretic activity of Benincasa hispida (thunb.) cogn. in Wistar albino rats. Pak J Pharm Sci. 2009;22(3):287-90.

Smith M, Mills EJ. Select complementary/alternative therapies for prostate cancer: the benefits and risks. Cancer Pract. 2001;9(5):253-5.

Cameron M, Gagnier JJ, Little CV, Parsons TJ, Blümle A, Chrubasik S. Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part I: osteoarthritis. Phytother Res. 2009;23(11):1497-515.

Jäggi R, Würgler U, Grandjean F, Weiser M. Dual inhibition of 5-lipoxygenase/cyclooxygenase by a reconstituted homeopathic remedy; possible explanation for clinical efficacy and favourable gastrointestinal tolerability. Inflamm Res. 2004;53(4):150-7.

Bonica JJ. The need of a taxonomy. Pain. 1979;6(3):247-8.

Cevallos-Arellano E. Binational experience in the treatment of AIDS with a low molecular weight natural carbohydrate (ECA-10-142), as a stimulant of the immune system. In: 10th International Conference on AIDS; 1994; Yokohama, Japan; 1994.

Cevallos EA. In: BIRM: The future strategies of therapeutics. Abstract of World Congress of AIDS in 1996. Vancouver; 1996.

Dandekar DS, Lokeshwar VB, Cevallos-Arellano E, Soloway MS, Lokeshwar BL. An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis. Cancer Chemother Pharmacol. 2003;52(1):59 66.

Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959;18:418-20.

Henriques MG, Silva PM, Martins MA, Flores CA, Cunha FQ, Assreuy-Filho J, et al. Mouse paw edema. A new model for inflammation? Braz J Med Biol Res. 1987;20(2):243-9.

Ravichandran S, Panneerselvam P. Evaluation of anti-inflammatory activities of combined extracts of Cardiospermum halicacabum L. and Delonix elata L. leaves on experimental models. Int J Pharm. 2014;4(1):43-7.

Heughan CE, Sawynok J. The interaction between gabapentin and amitriptyline in the rat formalin test after systemic administration. Anesth Analg. 2002;94(4):975-80.

Ellis A, Benson N, Machin I, Corradini L. The rat formalin test: can it predict neuropathic pain treatments? In: Spink AJ, editor. Proceedings of Measuring Behavior; 2008.

Niazi J, Gupta V, Chakarborty P, Kumar P. Anti-inflammatory and anti-pyretic activity of Aleuritis moluccana leaves. Asian J Pharm Clin Res. 2010;3(1):35-7.

Sakat SS, Mani K, Demidchenko YO, Gorbunov EA, Tarasov SA, Mathur A, et al. Release-active dilutions of diclofenac enhance anti-inflammatory effect of diclofenac in carrageenan-induced rat paw edema model. Inflammation. 2014;37(1):1-9.

Yoon MH, Yaksh TL. Evaluation of interaction between gabapentin and ibuprofen on the formalin test in rats. Anesthesiology. 1999;91(4):1006-13.

Deraedt R, Jouquey S, Delevallée F, Flahaut M. Release of prostaglandins E and F in an algogenic reaction and its inhibition. Eur J Pharmacol. 1980;61:17-24.

Bentley GA, Newton SH, Starr J. Studies on the antinociceptive action of alpha-agonist drugs and their interactions with opioid mechanisms. Br J Pharmacol. 1983;79(1):125-34.

Dirig DM, Isakson PC, Yaksh TL. Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan-evoked thermal hyperalgesia in rats. J Pharmacol Exp Ther. 1998;285(3):1031-8.

Rajalakshmi M, Sudha Madhuri A, Ramabhimaiah S. Evaluation of analgesic activity of aqueous extract of Mangifera indica leaves in albino rats. Int J Basic Clin Pharmacol. 2015;4:107-10.

Bley KR, Hunter JC, Eglen RM, Smith JA. The role of IP prostanoid receptors in inflammatory pain. Trends Pharmacol Sci. 1998;19(4):141-7.

Necas J, Bartosikova L. Carrageenan: a review. Vet Med. 2013;58(4):187-205.

Zhou H, Wong YF, Cai X, Liu ZQ, Jiang ZH, Bian ZX, et al. Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory and nociceptive models in rodents. Biol Pharm Bull. 2006;29(2):253-60.

Thakare VN, Suralkar AA, Deshpande AD, Naik SR. Stem bark extraction of Ficus bengalensis Linn for anti-inflammatory and analgesic activity in animal models. Indian J Exp Biol. 2010;48(1):39-45.

Posadas I, Bucci M, Roviezzo F, Rossi A, Parente L, Sautebin L, et al. Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression. Br J Pharmacol. 2004;142(2):331-8.

do Amaral JF, Silva MI, Neto MR, Neto PF, Moura BA, de Melo CT, et al. Antinociceptive effect of the monoterpene R-(+)-limonene in mice. Biol Pharm Bull. 2007;30(7):1217 20.

Dalal A, Tata M, Allègre G, Gekiere F, Bons N, Albe-Fessard D. Spontaneous activity of rat dorsal horn cells in spinal segments of sciatic projection following transection of sciatic nerve or of corresponding dorsal roots. Neuroscience. 1999;94(1):217-28.

Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain. 1992;51(1):5-17.

Lariviere WR, Sattar MA, Melzack R. Inflammation-susceptible Lewis rats show less sensitivity than resistant Fischer rats in the formalin inflammatory pain test and with repeated thermal testing. J Neurophysiol. 2006;95(5):2889 97.

Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998;38:97-120.

Yamamoto T, Nozaki-Taguchi N. Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor. Brain Res. 1996;739(1-2):104-10.

Malmberg AB, Yaksh TL. Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther. 1992;263(1):136-46.

Yamamoto T, Sakashita Y. COX-2 inhibitor prevents the development of hyperalgesia induced by intrathecal NMDA or AMPA. Neuroreport. 1998;9(17):3869-73.

Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT, et al. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol. 1996;118(4):829-38.

Guay J, Bateman K, Gordon R, Mancini J, Riendeau D. Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1. J Biol Chem. 2004;279(23):24866-72.

Ichitani Y, Shi T, Haeggstrom JZ, Samuelsson B, Hökfelt T. Increased levels of cyclooxygenase-2 mRNA in the rat spinal cord after peripheral inflammation: an in situ hybridization study. Neuroreport. 1997;8(13):2949-52.

Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci U S A. 1994;91(25):12013-7.

Ibuki T, Matsumura K, Yamazaki Y, Nozaki T, Tanaka Y, Kobayashi S. Cyclooxygenase-2 is induced in the endothelial cells throughout the central nervous system during carrageenan-induced hind paw inflammation; its possible role in hyperalgesia. J Neurochem. 2003;86(2):318 28.

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Published

2017-01-21

How to Cite

Ravalji, M., Cevallos-Arellano, E., & Balakrishnan, S. (2017). Investigation of centrally and peripherally acting analgesic and anti inflammatory activity of biological immune response modulator (an Amazonian plant extract) in animal models of pain and inflammation. International Journal of Basic & Clinical Pharmacology, 4(2), 342–348. Retrieved from https://www.ijbcp.com/index.php/ijbcp/article/view/924

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