Anti-inflammatory and anti-angiogenesis effect of bee pollen methanolic extract using air pouch model of inflammation

Tahereh Eteraf-Oskouei , Ayda Shafiee-Khamneh, Fariba Heshmati-Afshar, Abbas Delazar

Abstract


Background and purpose: Research on new drugs with a natural source and low side effects is                         a priority in pharmacology studies. The present study was conducted to investigate the anti-inflammatory  and anti-angiogenesis effects of bee pollen extract in the air pouch model of inflammation.

Experimental approach: To achieve this goal, male rats were moderately anesthetized and then 20              and 10 mL of sterile air were subcutaneously injected into the intrascapular area of the back of the rat on first and third days, respectively. On day 6, inflammation was induced by intrapouch injection of carrageenan. Normal saline in the control group and bee pollen methanolic extract (50, 100, and 200 mg/pouch)                    were administered at day 6, simultaneously with carrageenan, and then for 2 consecutive days only normal saline and the extracts were injected. Following sacrificing the rats the pouch was opened and the exudate volume, leukocyte accumulation, granulation tissue weight, vascular endothelial growth factor (VEGF), interleukin 1beta, and tumor necrosis factor alpha (TNF-α) concentrations were determined 3 days                     after induction of inflammation. In order to investigate the angiogenesis, the granulation tissue was removed, homogenized in the Drabkin's reagent, and then centrifuged. The supernatant was filtered and the hemoglobin concentration was determined using a spectrophotometer.

Results: Bee pollen extract significantly decreased the exudate volume, leukocyte accumulation, granulation tissue weight, angiogenesis, VEGF, and TNF-α concentration.

Conclusion and implications: The findings of the current study revealed that bee pollen methanolic extract has an anti-inflammatory and anti-angiogenesis effect, which could be attributed to the inhibition of VEGF and TNF-α production in the inflammatory exudates.


Keywords


Air pouch; Angiogenesis; Bee pollen; Inflammation; TNF-α; VEGF.

Full Text:

PDF

References


Mattei RA, Dalmarco EM, Fröde TS. Etanercept administration prevents the inflammatory response induced by carrageenan in the murine air pouch model. Naunyn Schmiedebergs Arch Pharmacol. 2015;388(12):1247-57.

Negm AA, Furst DE. Nonsteroidal Anti-Inflammatory Drugs, Disease-Modifying Antirheumatic Drugs, Nonopioid Analgesics, & Drugs Used in Gout. In: Katzung BG. Basic & Clinical Pharmacology,. 14th ed. New York: McGraw-Hill Education; 2018. pp. 643.

Yıldız O, Can Z, Saral Ö, Yuluğ E, Öztürk F, Aliyazıcıoğlu R, et al. Hepatoprotective potential of chestnut bee pollen on carbon tetrachloride-induced hepatic damages in rats. Evid Based Complement Alternat Med. 2013:2013;2013:461478,1-9.

Larki A, Hemmati AA, Arzi A, Borujerdnia MG, Esmaeilzadeh S, Zad Karami MR. Regulatory effect of caffeic acid phenethyl ester on type I collagen and interferon-gamma in bleomycin-induced pulmonary fibrosis in rat. Res Pharm Sci. 2013;8(4):243-252.

Feás X, Vázquez-Tato MP, Estevinho L, Seijas JA, Iglesias A. Organic bee pollen: botanical origin, nutritional value, bioactive compounds, antioxidant activity and microbiological quality. Molecules. 2012;17(7):8359-8377.

Maruyama H, Sakamoto T, Araki Y, Hara H. Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema. BMC Complement Altern Med. 2010;10(1):30-40.

Duarte DB, Vasko MR, Fehrenbacher JC. Models of inflammation: carrageenan air pouch. Curr Protoc Pharmacol. 2016;5:1-12.

MacDonald IJ, Liu S, Su C, Wang Y, Tsai C, Tang C., Implications of angiogenesis involvement in arthritis. Int J Mol Sci, 2018;19(7):1-18.

Dana SHj, L Rafiee, N. Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line. Res Pharm Sci. 2015;10(2):117-124.

Ashraf S, Mapp PI, Walsh DA. Angiogenesis and the persistence of inflammation in a rat model of proliferative synovitis. Arthritis Rheum. 2010;62(7):1890-1898.

Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med. 2018;13:26-45.

Delazar A, Shoeb M, Kumarasamy Y, Byres M, Nahar L, Modarresi M, et al. Two bioactive ferulic acid derivatives from Eremostachys glabra. DARU J Pharm Sci. 2004;12(2):49-53.

Afshar FH, Delazar A, Nazemiyeh H, Esnaashari S, Moghadam SB. Comparison of the total phenol, flavonoid contents and antioxidant activity of methanolic extracts of Artemisia spicigera and A. splendens growing in Iran. Pharm Sci. 2012;18(3):165-170.

Eteraf-Oskouei T, Akbarzadeh‐Atashkhosrow A, Maghsudi M, Najafi M. Effects of salbutamol on the inflammatory parameters and angiogenesis in the rat air pouch model of inflammation. Res Pharm Sci. 2017;12(5):364-372 .

Abbas A, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 8th ed. Philadelphia: Elsevier; 2014. pp. 82-85.

Eteraf-Oskouei T, Allahyari S, Akbarzadeh-Atashkhosrow A, Delazar A, Pashaii M, Gan SH, et al. Methanolic extract of Ficus carica Linn. leaves exerts antiangiogenesis effects based on the rat air pouch model of inflammation. Evid Based Complement Alternat Med. 2015;2015:1-9.

Pascoal A, Rodrigues S, Teixeira A, Feás X, Estevinho LM. Biological activities of commercial bee pollens: antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food Chem Toxicol. 2014;63:233-239.

Delves PJ, Martin SJ, Burton DR, Roitt IM. Roitt's Essential Immunology. 1st ed. London: John Wiley & Sons; 2017. pp. 11-29.

Owczarek K, Lewandowska U. The impact of dietary polyphenols on COX-2 expression in colorectal cancer. Nutr Cancer. 2017;69(8):1105-1118.

Ahmed MA, ELosaily GM. Role of oxytocin in deceleration of early atherosclerotic inflammatory processes in adult male rats. Int J Clin Exp Med. 2011;4(3):169-178.

Sato K, Komatsu N, Higashi N, Imai Y, Irimura T. Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1. Clin Immunol. 2005;115(1):47-50.

Colville-Nash P, Lawrence T. Air-pouch models of inflammation and modifications for the study of granuloma-mediated cartilage degradation. Methods Mol Biol. 2003;225:181-189.

Kimura H, Esumi H. Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis. Acta Biochim Pol. 2003;50(1):49-59.

Muniz-Junqueira MI, de Paula-Coelho VN. Meglumine antimonate directly increases phagocytosis, superoxide anion and TNF-alpha production, but only via TNF-alpha it indirectly increases nitric oxide production by phagocytes of healthy individuals, in vitro. Int Immunopharmacol. 2008;8(12):1633-1638.

Balogh E, Biniecka M, Fearon U, Veale DJ, Szekanecz Z. Angiogenesis in inflammatory arthritis. Isr Med Assoc J. 2019;5(21):345-352.

Buijs N, Oosterink JE, Jessup M, Schierbeek H, Stolz DB, Houdijk AP, et al. A new key player in VEGF-dependent angiogenesis in human hepatocellular carcinoma: dimethylarginine dimethylaminohydrolase 1. Angiogenesis. 2017;20(4):557-565.

Izuta H, Shimazawa M, Tsuruma K, Araki Y, Mishima S, Hara H. Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells. BMC Complement Altern Med. 2009;9:45-54.

Croll SD, Ransohoff RM, Cai N, Zhang Q, Martin FJ, Wei T, et al. VEGF-mediated inflammation precedes angiogenesis in adult brain. Exp Neurol. 2004;187(2):388-402.

Kim TK, Park CS, Na HJ, Lee K, Yoon A, Chung J, et al. Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFalpha-induced angiogenesis. Exp Mol Med. 2017;49(2):1-11.

Lee JH. Intracellular antioxidant activity and inhibition of bee pollens on the production of inflammatory mediators (P06-081-19). Curr Devel Nut. 2019;3(Suppl 1):296.

Eteraf-Oskouei T, Najafi M, Gharehbagheri A. Natural honey: a new and potent anti-angiogenic agent in the air-pouch model of inflammation. Drug Res (Stuttg). 2014;64(10):530-536.

Kaczmarek MM, Blitek A, Kaminska K, Bodek G, Zygmunt M, Schams D, et al. Assessment of VEGF-receptor system expression in the porcine endometrial stromal cells in response to insulin-like growth factor-I, relaxin, oxytocin and prostaglandin E 2. Mol Cell Endocrinol. 2008;291(1-2):33-41.

Chakrabarti S, Rizvi M, Morin K, Garg R, Freedman JE. The role of CD40L and VEGF in the modulation of angiogenesis and inflammation. Vascular pharmacology. 2010;53(3-4):130-137.

Bridi R, Atala E, Pizarro PN, Montenegro G. Honeybee pollen load: phenolic composition and antimicrobial activity and antioxidant capacity. J Nat Prod. 2019;82(3):559-565.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.