Browse > Article
http://dx.doi.org/10.3831/KPI.2016.19.003

IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms  

Firashathulla, Syed (Department of Pharmacology, Al-Ameen College of Pharmacy)
Inamdar, Mohammed Naseeruddin (Department of Pharmacology, Al-Ameen College of Pharmacy)
Rafiq, Mohamed (R&D Center, The Himalaya Drug Company)
Viswanatha, Gollapalle Lakshminarayanashastry (R&D Center, The Himalaya Drug Company)
Kumar, Lakkavalli Mohan Sharath (R&D Center, The Himalaya Drug Company)
Babu, Uddagiri Venkanna (R&D Center, The Himalaya Drug Company)
Ramakrishnan, Shyam (R&D Center, The Himalaya Drug Company)
Paramesh, Rangesh (R&D Center, The Himalaya Drug Company)
Publication Information
Journal of Pharmacopuncture / v.19, no.1, 2016 , pp. 21-27 More about this Journal
Abstract
Objectives: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. Methods: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM-133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. Results: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM-133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, ${\beta}$-sitosterol, nonaeicosanol, ${\beta}$-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. Conclusion: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.
Keywords
carbon clearance test; Escherichia coli-induced sepsis; immunomodulator; IM-133N; LC-MS/MS;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Rao CS, Raju C, Gopumadhavan S, Chauhan BL, Kulkarni RD, Mitra SK. Immunotherapeutic modification by an ayurvedic formulation septilin. Indian J Exp Biol. 1994;32(8):553-8.
2 Daswani BR, Yegnanarayan R. Immunomodulatory activity of septilin, a polyherbal preparation. Phytother Res. 2002;16(2):162-5.   DOI
3 Mehrzad J, Shajari M, Saleh-Moghaddam M, Sarmad-Nabavi M. Stressed (acute) mice display neuroimmunodysregulation and defective innate immune response against coliform infection. Int Immunopharmacol. 2015;28(1):168-74.   DOI
4 Bermudez RC, Fontaine R, Garcia N, laurado G, Marcos J, Morris HJ. Immunomodulating effects of hot-water extract from Plurotus ostereatus mycelium on cyclophosphamide treated mice. Micol Aplicada Int. 2003;15(1):7-13.
5 Das UN. Current advances in sepsis and septic shock with particular emphasis on the role of insulin. Med Sci Monit. 2003;9(8):181-92.
6 Varma RS, Guruprasad KP, Satyamoorthy K, Kumar LM, Babu UV, Patki SP. IM-133N modulates cytokine secretion by RAW264.7 and THP-1 cells. J Immunotoxicol. 2016;13(2):217-25.   DOI
7 Tiwari U, Rastogi B, Singh P, Saraf DK, Vyas SP. Immunomodulatory effect of aqueous extract of Tridax procumbens in experimental animals. J Ethanopharmacol. 2004;92(1):113-9.   DOI
8 Gokhlale AB, Damre AS, Saraf MN. Investigation in the immuno-modulatory activity of Argyreia speciosa. J Ethanopharmacol. 2003;84(1):109-14.   DOI
9 Raphael TJ, Kuttan G. Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system. Phytomedicine. 2003;10(6-7):483-9.   DOI
10 Belapurkar P, Goyal P, Tiwari-Barua P. Immunomodulatory effects of Triphala and its individual constituents: a review. Indian J Pharm Sci. 2014;76(6):467-75.
11 Yun Y, Han S, Park E, Yim D, Lee S, Lee CK, et al. Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages. Arch Pharm Res. 2003;26(12):1087-95.   DOI
12 Fraile L, Crisci E, Cordoba L, Navarro MA, Osada J, Montoya M. Immunomodulatory properties of beta-sitosterol in pig immune responses. Int Immunopharmacol. 2012;13(3):316-21.   DOI
13 Gulati K, Ray A, Debnath PK, Bhattacharya SK. Immunomodulatory indian medicinal plants. J Nat Remedies. 2002;2(2):121-31.
14 Valentova K, Sima P, Rybkova Z, Krizan J, Malachova K, Kren V. (Anti)mutagenic and immunomodulatory properties of quercetin glycosides. J Sci Food Agric. 2015. DOI: 10.1002/jsfa.7251.   DOI
15 Sameksha K, Rattan LK. Immunomodulatory activity of phytoconstituent of Melissa officinalis. Der Pharmacia Lettre. 2013;5(1):141-5.
16 Aranha I, Clement F, Venkatesh YP. Immunostimulatory properties of the major protein from the stem of the Ayurvedic medicinal herb, guduchi (Tinospora cordifolia). J Ethnopharmacol. 2012;139(2):366-72.   DOI
17 Chahar MK, Sanjaya Kumar DS, Lokesh T, Manohara KP. In-vivo antioxidant and immunomodulatory activity of mesuol isolated from Mesua ferrea L. seed oil. Int Immunopharmacol. 2012;3(4):386-91.
18 Kumar D, Arya V, Kaur R, Bhat ZA, Gupta VK, Kumar V. A review of immunomodulators in the Indian traditional health care system. J Microbiol Immunol Infect. 2012;45(3):165-84.   DOI
19 Sagrawat H, Khan MY. Immunomodulatory plants: a phytopharmacological review. Pharmacog Rev. 2007;1:248-60.
20 Wichers H. Immunomodulation by food: promising concept for mitigating allergic disease?. Anal Bioanal Chem. 2009;395(1):37-45.   DOI
21 Wang J, Xiang M. Targeting potassium channels Kv1.3 and KC a 3.1: routes to selective immunomodulators in autoimmune disorder treatment?. Pharmacotherapy. 2013;33(5):515-28.   DOI
22 Tzianabos AO. Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev. 2000;13(4):523-33.   DOI
23 Makare N, Bodhankar S, Rangari V. Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice. J Ethanopharmacol. 2001;78(2-3):133-7.   DOI
24 Mitra SK, Gupta M, Suryanarayana T, Sarma DN. Immunoprotective effect of IM 133. Int J Immunopharmacol. 1999;21(2):115-20.   DOI
25 Miyamoto M, Sakagami H, Minagawa K, Kikuchi H, Nishikawa H, Satoh K, et al. Tumor-specificity and radical scavenging activity of poly-herbal formula. Anticancer Res. 2002;22(2):1217-23.
26 Aschaffenburg R. The nutritive value of colostrums for the calf. British J Nutrition. 1949;3(2-3): 200-4.   DOI
27 McEwan AD, Fisher EW, Selman IE, Penhale WJ. Turbidity test for the estimation of immune globulin levels in neonatal calf serum. Clin Chim Acta. 1970;27(1):155-63.   DOI