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Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids during bovine sub-clinical mastitis

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Abstract

The current work is focused on establishing therapeutic protocol using unconventional drugs of herbal origin and studying their mechanism of action at molecular level in the treatment of bovine sub-clinical mastitis. It explores the potential of different cytokines which can be used for diagnosis, prognosis and monitoring of bovine sub-clinical mastitis. Prosopis juliflora alkaloids was administered intramammarily in 24 sub-clinically affected quarters once a day for 5 consecutive days at the rate of 10 ml of 1% formulation. In 18 disease control quarters, sterile normal saline was infused. The bacterial cultural examination, somatic cell count (SCC) and cytokines (IL-1β, IL-6, IL-8, IL-12, GM-CSF, IFN-γ, TNF-α) expression by real-time PCR were evaluated on day 7, 14, 21 and 28 post-last treatment from milk samples. Around 75.0% of treatment group quarters showed significant (p < 0.05) reduction in SCC on day 28 post-last treatment, whereas 94.4% control group quarters did not show any significant decline in SCC. 58.3% of treated quarters showed both bacteriological cure as well as significant (p < 0.05) reduction in SCC on day 28 post-last treatment. While, among control group quarters, 83.3% quarters not only remained bacteriological positive, they also did not show any significant decline in SCC. The in vitro antimicrobial activity of alkaloids of P. juliflora was evaluated. Lower concentrations of alkaloids (0.25% and 0.50%) dissolved in normal saline showed zone of inhibition against 12 out of 15 isolates, however higher concentration (1, 1.5, 2, 2.5 and 5%) showed zone of inhibition against all 15 bacterial isolates. The gene expression level of IL-1β, IL-8 and IFN-γ cytokines exhibited significant difference between healthy and sub-clinically affected quarters highlighting the potential of these cytokines in the diagnosis of bovine sub-clinical mastitis. Down-regulation of IL-1, IL-6, IL-8 and IFN-γ cytokines in treated quarters can be explored for making the prognosis and monitoring post-treatment disease progression of bovine sub-clinical mastitis. The P. juliflora alkaloid demonstrated strong in vitro and in vivo antibacterial activity, along with causing immunomodulation by enhancing post-treatment gene expression of IL-1, IL-6 and IL-8 cytokines. Therefore, P. juliflora alkaloids hold a strong claim as an effective alternative herbal therapy in bovine sub-clinical mastitis.

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References

  • Ahmad VU, Basha A, Haque W (1978) New alkaloids from Prosopis juliflora. Z Naturforsch 33:347–348

    Article  Google Scholar 

  • Ahmad A, Khan KA, Ahmad VU, Qazi S (1986) Antibacterial Activity of juliflorine isolated from Prosopis juliflora. Planta Med 4:285–288

    Article  Google Scholar 

  • Ahmad A, Khursheed AK, Sabiha Q, Viqaruddin A (1989a) Antifungal activity of some hydrosoluble Prosopis juliflora alkaloids. Fitoterapia 60:86–89

    CAS  Google Scholar 

  • Ahmad VU, Sultana A, Qazi S (1989b) Alkaloids from the leaves of Prosopis juliflora. J Nat Prod 5:497–501

    Article  Google Scholar 

  • Ahmad A, Khan KA, Ahmad V (1992) Immunomodulating effect of juliflorine on the antibody response to Listeria hemolysin. J Islam Acad Sci 5:189–193

    Google Scholar 

  • Alluwaimi AM (2004) The cytokines of bovine mammary gland: prospects for diagnosis and therapy. Res Vet Sci 77:211–222

    Article  CAS  Google Scholar 

  • Alluwaimi AM, Cullor JS (2002) Cytokines gene expression patterns of bovine milk during mid and late stages of lactation. J Vet Med B 49:105–110

    Article  CAS  Google Scholar 

  • Aqeel A, Khursheed AK, Viqaruddin A, Sabiha Q (1989) Antimicrobial activity of julifloricine isolated from Prosopis juliflora, Arzneim. Forsch Drug Res 39:652–655

    CAS  Google Scholar 

  • Aziz MA, Khan AH, Adnan M, Ullah H (2018) Traditional uses of medicinal plants used by indigenous communities for veterinary practices at Bajaur Agency, Pakistan. J Ethnobio Ethnomed 14:11

    Article  Google Scholar 

  • Bansal BK, Gupta DK (2009) Economic analysis of bovine mastitis in India and Punjab—a review. Indian J Dairy Sci 62:337–345

    Google Scholar 

  • Bansal BK, Bajwa NS, Randhawa SS, Ranjan R, Dhaliwal PS (2011) Elimination of erythromycin in milk after intra-mammary administration in cows with specific mastitis: relation to dose, milking frequency and udder health. Trop Anim Health Prod 43:323–329

    Article  Google Scholar 

  • Bustin SA (2000) Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol 25:169–193

    Article  CAS  Google Scholar 

  • Chhabra SC, Shao JF, Mshiu EN (1992) Antifungal activity among traditionally used herbs in Tanzania. Dar-es-Salam Med J 9:68–73

    Google Scholar 

  • Chomczynski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15:532–537

    CAS  PubMed  Google Scholar 

  • Cowan ST, Steel JK (1970) Manual for the identification of the medical bacteria, 3rd edn. Cambridge University Press, Cambridge

    Google Scholar 

  • Daetwyler P, Ott-Longoni R, Schöpp E, Hesse M (1981) Juliprosine, a further alkaloid from Prosopis juliflora A. DC. Helv Chim Acta 64:1959–1963

    Article  CAS  Google Scholar 

  • Dallman MJ, Montgomery RA, Larsen CP, Wanders A, Wells AF (1991) Cytokine gene expression: analysis using northern blotting, polymerase chain reaction and in situ hybridization. Immunol Rev 119:163–179

    Article  CAS  Google Scholar 

  • De UK, Mukherjee R (2013) Dynamics of milk leukocytes in response to a biological response modifier during bovine subclinical mastitis. Res Vet Sci 95:352–357

    Article  CAS  Google Scholar 

  • Eisenblätter M, Buchal A, Gayum H, Jasny E, Renner Viveros P, Ulrichs T, Schneider T, Schumann RR, Zweigner J, Ignatius R (2012) Nocardia farcinica activates human dendritic cells and induces secretion of interleukin-23 (IL-23) rather than IL-12p70. Infect Immun 80:4195–4202

    Article  Google Scholar 

  • Feyera T, Mekonnen E, Wakayo BU, Assefa S (2017) Botanical ethnoveterinary therapies used by agro-pastoralists of Fafan Zone, Eastern Ethiopia. BMC Vet Res 13:232

    Article  Google Scholar 

  • Gonzalez DD, Rimondi A, Perez Aguirreburualde MS, Mozgovoj M, Bellido D, Wigdorovitz A, Dus Santos MJ (2013) Quantitation of cytokine gene expression by real-time PCR in bovine milk and colostrum cells from cows immunized with a bovine rotavirus VP6 experimental vaccine. Res Vet Sci 95:703–708

    Article  CAS  Google Scholar 

  • Gonzalo C, Martinez JR, Carriedo JA, Primitivo FS (2003) Fossomatic cell-counting on ewe milk: comparison with direct microscopy and study of variation factors. J Dairy Sci 86:138–145

    Article  CAS  Google Scholar 

  • Hagiwara K, Satoshi K, Yamanaka H, Kirisawa R, Iwai H (2000) Detection of cytokines in bovine colostrum. Vet Immunol Immunopathol 76:183–190

    Article  CAS  Google Scholar 

  • Higuchi R, Fockler C, Dollinger G, Watson R (1993) Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnology 11:1026–1030

    CAS  PubMed  Google Scholar 

  • International Dairy Federation (1987) Bovine mastitis. Definition and guidelines for diagnosis. Brussels, Belgium. IDF Bull 211:24

    Google Scholar 

  • Kabilan L, Andersson G, Lolli F, Ekre HP, Olsson T, Troye-Blomberg M (1990) Detection of intracellular expression and secretion of interferon-gamma at the single-cell level after activation of human T cells with tetanus toxoid in vitro. Eur J Immunol 20:1085–1089

    Article  CAS  Google Scholar 

  • Leutenegger CM, Alluwaimi AM, Smith WL, Perani L, Cullor JS (2000) Quantitation of bovine cytokine mRNA in milk cells of healthy cattle by real-time Taq Man polymerase chain reaction. Vet Immunol Immunopathol 77:275–287

    Article  CAS  Google Scholar 

  • McClenahan D, Krueger R, Lee HY, Thomas C, Kehrli ME Jr, Czuprynski C (2006) Interleukin-8 expression by mammary gland endothelial and epithelial cells following experimental mastitis infection with E. coli. Comp Immunol Microbiol Infect Dis 29:127–137

    Article  Google Scholar 

  • Mukherjee R, Ram GC, Dash PK, Goswami T (2004) The activity of milk leukocytes in response to a water-soluble fraction of Mycobacterium phlei in bovine sub-clinical mastitis. Vet Res Commun 28:47–54

    Article  CAS  Google Scholar 

  • Mukherjee R, De UK, Ram GC (2010) Evaluation of mammary gland immunity and therapeutic potential of Tinospora cordifolia against bovine subclinical mastitis. Trop Anim Health Prod 42:645–651

    Article  Google Scholar 

  • Nagao S, Masayuki N, Hiroshi K, Katsuro Y, Shoichi K, Tetsuo S, Atsushi T, Shozo K, Nakano H, Nakajima E, Hiradate H, Fujii Y, Yamada K, Shigemori H, Hasegawa A (1990) Macrophages are stimulated by muramyl dipeptide to induce polymorphonuclear leukocyte accumulation in the peritoneal cavities of guinea pigs. Infect Immun 58:536–542

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nakano H, Nakajima E, Hiradate H, Fujii Y, Yamada K, Shigemori H, Hasegawa A (2004) Growth inhibitory alkaloids from mesquite (Prosopis julispora (Sw.) DC.) leaves. Phytochemistry 65:587–591

    Article  CAS  Google Scholar 

  • Paape M, Mehrzad J, Zhao X, Detilleux J, Burvenich C (2002) Defense of the bovine mammary gland by polymorphonuclear neutrophil leukocytes. J Mammary Gland Biol Neoplasia 7:109–121

    Article  Google Scholar 

  • Person Waller K, Colditz IG, Lun S, Ostensson K (2003) Cytokines in mammary lymph and milk during endotoxin-induced bovine mastitis. Res Vet Sci 74:31–36

    Article  Google Scholar 

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:E45

    Article  CAS  Google Scholar 

  • Pfaffl MW, Wittmann SL, Meyer HH, Bruckmaier RM (2003) Gene expression of immunologically important factors in blood cells, milk cells, and mammary tissue of cows. J Dairy Sci 86:538–545

    Article  CAS  Google Scholar 

  • Salinas-Carmona MC, Torres-Lopez E, Ramos AI, Licon-Trillo A, Gonzalez-Spencer D (1999) Immune response to Nocardia brasiliensis antigens in an experimental model of actinomycetoma in BALB/c mice. Infect Immun 67:2428–2432

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sinha MK, Thombare NN, Mondal B (2014) Subclinical mastitis in dairy animals: incidence, economics, and predisposing factors Sci World J 2014:523984

    Google Scholar 

  • Stevens MG, De Spiegeleer B, Peelman L, Boulougouris XJ, Capuco AV, Burvenich C (2012) Compromised neutrophil function and bovine E. coli mastitis: is C5a the missing link? Vet Immunol Immunopathol 149:151–156

    Article  CAS  Google Scholar 

  • Trebichavsky I, Barot-Ciorbaru R, Charley B, Splíchal I (1993) Induction of inflammatory cytokines by Nocardia fractions. Folia Biol 39:243–249

    CAS  Google Scholar 

  • Verdi RJ, Barbano DM (1991) Properties of proteases from milk somatic cells and blood leucocytes. J Dairy Sci 74:2077–2081

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are thankful to Government of India’s Rashtriya Krishi Vikas Yojana (RKVY) Stream-I Project (B.H. 18442) for providing financial support. KS is appreciative of Dr. Vaibhav Bhatt, Dr. Pradeep Kumar Sharma, Dr. Maulik Upadhyay and Dr. Kamlesh Sadaria for the invaluable interactions. KS expresses his gratitude towards the milkers of Livestock Research Station of Anand Agricultural University for extending their support during the entire study.

Funding

This study was funded by Rashtriya Krishi Vikas Yojana (RKVY) (Stream-I), Government of India. Money earmarked for RKVY projects is given to Government of Gujarat, which is allocated to different universities by former. The funds were allocated by Anand Agricultural University under the Budget Head (B.H.) 18442.

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Authors and Affiliations

  1. Department of Veterinary Medicine, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, 388001, India

    Kunal N. Shah, Piyush Valand & Dev S. Nauriyal

  2. Department of Animal Biotechnology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, 388001, India

    C. G. Joshi

Authors
  1. Kunal N. Shah
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  2. Piyush Valand
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  3. Dev S. Nauriyal
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  4. C. G. Joshi
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Corresponding author

Correspondence to Kunal N. Shah.

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Ethical approval

Based on the results of the acute dermal and oral toxicity test carried out on male Wistar rats (as per OECD New Draft Guideline 434) the use of P. juliflora alkaloids was approved by the Institution Animal Ethics Committee (IAEC 2007/VPT/26). All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Conflict of interest

Prof. Dr. Dev S. Nauriyal has received research grant from Rashtriya Krishi Vikas Yojana (RKVY) (Stream-I), Government of India, as Principal Investigator for project entitled “Use of Recent Molecular Techniques to Reduce Economic Losses Incurred due to Bovine Mastitis by Evolving Diagnostic, Therapeutic and Preventive Measures” under the B.H. 18442. Prof. Dr. C. G. Joshi is Co-PI in this project. The authors declare that they have no conflict of interest.

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Shah, K.N., Valand, P., Nauriyal, D.S. et al. Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids during bovine sub-clinical mastitis. 3 Biotech 8, 409 (2018). https://doi.org/10.1007/s13205-018-1438-1

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