Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Protective Effects of Grape Seed Proanthocyanidin Extract in Preventing DSS Induced Ulcerative Colitis Based on Pharmacodynamic, Pharmacokinetic and Tissue Distribution

Author(s): Xinrui Wang, Shuai Quan, Jingyang Li, Ying Liu, Huageng Sun, Jingze Zhang and Dailin Liu*

Volume 23, Issue 6, 2022

Published on: 22 July, 2022

Page: [496 - 505] Pages: 10

DOI: 10.2174/1389200223666220609151836

Price: $65

Abstract

Background: Based on pharmacodynamic, pharmacokinetic and tissue distribution studies, we explored the potential effect of grape seed proanthocyanidin extract (GSPE) on dextran sodium sulfate (DSS) -induced ulcerative colitis in mice and its underlying mechanism.

Methods: A liquid chromatography-mass spectrometry method was developed to measure the content of five components of GSPE in rat plasma and tissue. After oral administration of GSPE, correlative index levels of interleukin- 1β (IL-1β), interleukin-6 (IL-6), factor-α (TNF-α), Nitric Oxide (NO), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected in the serum and colon tissues. The protein expression levels of HO-1, Nrf2 and NF-κB in the mouse colonic mucosa were analysed using immunohistochemistry.

Results: Pharmacodynamic tests showed substantially reduced mice body weight, diarrhea, and bloody stool in the model group. The pathological damage to the colonic mucosa of mice in the GSPE groups was remarkably reduced in a dose-dependent manner. The histopathological score of the colon in the model group was significantly higher than that of the control group (P <0.05), suggesting that DSS caused severe damage to the colon. After oral administration of GSPE, the serum and colonic tissue levels of IL-1β, IL-6, TNF-α, NO, and MDA decreased, whereas SOD content increased. Moreover, the protein levels of NF-κB and Keap-1 were significantly decreased, whereas the expression levels of Nrf2 and HO-1 proteins increased (P<0.01) based on the results of the microwaveimmunohistochemical assay. The pharmacokinetic results showed that catechin, epicatechin, and procyanidins B1, B2, and B4 are widely distributed in the tissues and blood of rats and may accumulate in some tissues. Catechin and epicatechin peaked at 0.25 and 1.5 h for the first and second time, respectively. Procyanidin B1, B2, and B4 peaked at 0.5 and 1.5 h for the first and second time, respectively, owing to the effect of the hepato-enteric circulation. The active components of GSPE can reach the colon of the lesion site, and hepatoenteric circulation can increase the residence time of the active components in the body, further increasing the anti-ulcer activity.

Conclusion: Our findings suggest that GSPE has a potential protective effect against DSS-induced ulcerative colitis in mice.

Keywords: Anti-inflammatory, oligosaccharide grape seed proanthocyanins, tissue distribution, pharmacokinetics, ulcerative colitis, Crohn’s disease.

« Previous
Graphical Abstract

[1]
Li-Jun, S.; Wen-chang, Z.; Hong-zhu, D. Inhibition of aloperine on dextran sulphate sodium-induced chronic colitis in C57BL/6 mice. Chin. Herb. Med., 2012, 4(3), 218-223.
[2]
Vande Casteele, N.; Khanna, R. Therapeutic drug monitoring of golimumab in the treatment of ulcerative colitis. Pharm. Res., 2017, 34(8), 1556-1563.
[http://dx.doi.org/10.1007/s11095-017-2150-2] [PMID: 28374338]
[3]
Burisch, J.; Munkholm, P. The epidemiology of inflammatory bowel disease. Scand. J. Gastroenterol., 2015, 50(8), 942-951.
[http://dx.doi.org/10.3109/00365521.2015.1014407] [PMID: 25687629]
[4]
Novak, G.; Hindryckx, P.; Khanna, R.; Jairath, V.; Feagan, B.G. The safety of vedolizumab for the treatment of ulcerative colitis. Expert Opin. Drug Saf., 2017, 16(4), 501-507.
[http://dx.doi.org/10.1080/14740338.2017.1300251] [PMID: 28276855]
[5]
Zhang, Z.; Li, S.; Cao, H.; Shen, P.; Liu, J.; Fu, Y.; Cao, Y.; Zhang, N. The protective role of phloretin against dextran sulfate sodium-induced ulcerative colitis in mice. Food Funct., 2019, 10(1), 422-431.
[http://dx.doi.org/10.1039/C8FO01699B] [PMID: 30604787]
[6]
Akaberi, M.; Sahebkar, A.; Emami, S.A. Turmeric and curcumin: From traditional to modern medicine. Adv. Exp. Med. Biol., 2021, 1291, 15-39.
[http://dx.doi.org/10.1007/978-3-030-56153-6_2] [PMID: 34331682]
[7]
Sul, O.J.; Kim, J.H.; Lee, T.; Seo, K.W.; Cha, H.J.; Kwon, B.; Ahn, J.J.; Cho, Y.S.; Oh, Y.M.; Jegal, Y.; Ra, S.W. GSPE protects against bleomycin-induced pulmonary fibrosis in mice via ameliorating epithelial apoptosis through inhibition of oxidative stress. Oxid. Med. Cell. Longev., 2022, 2022, 8200189.
[http://dx.doi.org/10.1155/2022/8200189] [PMID: 35355866]
[8]
Gerges Geagea, A.; Rizzo, M.; Eid, A.; Hajj Hussein, I.; Zgheib, Z.; Zeenny, M.N.; Jurjus, R.; Uzzo, M.L.; Spatola, G.F.; Bonaventura, G.; Leone, A.; Massaad-Massade, L.; Jurjus, A. Tea catechins induce crosstalk between signaling pathways and stabilize mast cells in ulcerative colitis. J. Biol. Regul. Homeost. Agents, 2017, 31(4), 865-877.
[PMID: 29254289]
[9]
Kwak, S.C.; Cheon, Y.H.; Lee, C.H.; Jun, H.Y.; Yoon, K.H.; Lee, M.S.; Kim, J.Y. grape seed proanthocyanidin extract prevents bone loss via regulation of osteoclast differentiation, apoptosis, and proliferation. Nutrients, 2020, 12(10), 12.
[http://dx.doi.org/10.3390/nu12103164] [PMID: 33081167]
[10]
Jiang, X.; Jiang, Y.; Sun, D.; Rong, L. Protective effect of magnesium lithospermate B against dextran sodiumsulfate induced ulcerative colitis in mice. Environ. Toxicol. Pharmacol., 2013, 36(1), 97-102.
[http://dx.doi.org/10.1016/j.etap.2013.03.010] [PMID: 23603461]
[11]
Hu, Y.; Wei, M.; Niu, Q.; Ma, R.; Li, Y.; Wang, X.; Feng, G.; Li, S.; Pang, L. Grape seed proanthocyanidin extract alleviates arsenic-induced lung damage through NF-κB signaling. Exp. Biol. Med. (Maywood), 2019, 244(3), 213-226.
[http://dx.doi.org/10.1177/1535370219829881] [PMID: 30869553]
[12]
Zhang, H.; Deng, A.; Zhang, Z.; Yu, Z.; Liu, Y.; Peng, S.; Wu, L.; Qin, H.; Wang, W. The protective effect of epicatechin on experimental ulcerative colitis in mice is mediated by increasing antioxidation and by the inhibition of NF-κB pathway. Pharmacol. Rep., 2016, 68(3), 514-520.
[http://dx.doi.org/10.1016/j.pharep.2015.12.011] [PMID: 26878122]
[13]
Amin, F.; Bano, B. Spectroscopic studies on free radical coalescing antioxidants and brain protein cystatin. J. Biomol. Struct. Dyn., 2019, 37(11), 2949-2959.
[http://dx.doi.org/10.1080/07391102.2018.1500946] [PMID: 30044189]
[14]
Bao, L.; Li, J.; Zha, D.; Zhang, L.; Gao, P.; Yao, T.; Wu, X. Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-ĸB pathways. Int. Immunopharmacol., 2018, 54, 245-253.
[http://dx.doi.org/10.1016/j.intimp.2017.11.021] [PMID: 29161661]
[15]
Jaramillo, M.C.; Zhang, D.D. The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev., 2013, 27(20), 2179-2191.
[http://dx.doi.org/10.1101/gad.225680.113] [PMID: 24142871]
[16]
Liu, D-y.; Gao, L.; Zhang, J.; Huo, X.; Ni, H.; Cao, L. Anti-inflammatory and Anti-oxidant Effects of Licorice Flavonoids on Ulcerative Colitis in Mouse Model. Chin. Herb. Med., 2017, 9(4), 358-368.
[http://dx.doi.org/10.1016/S1674-6384(17)60116-3]
[17]
Baba, S.; Osakabe, N.; Natsume, M.; Terao, J. Absorption and urinary excretion of procyanidin B2 [epicatechin-(4beta-8)-epicatechin] in rats. Free Radic. Biol. Med., 2002, 33(1), 142-148.
[http://dx.doi.org/10.1016/S0891-5849(02)00871-7] [PMID: 12086692]
[18]
Borges, G.; Ottaviani, J.I.; van der Hooft, J.J.J.; Schroeter, H.; Crozier, A. Absorption, metabolism, distribution and excretion of (-)-epicatechin: A review of recent findings. Mol. Aspects Med., 2018, 61, 18-30.
[http://dx.doi.org/10.1016/j.mam.2017.11.002] [PMID: 29126853]
[19]
Abrahamse, S.L.; Kloots, W.J.; Amelsvoort, J.M.M. Absorption, distribution, and secretion of epicatechin and quercetin in the rat. Nutr. Res., 2005, 25, 305-317.
[20]
Zhang, S.Q.; Zhang, S.Z. Oral absorption, distribution, metabolism, and excretion of icaritin in rats by Q-TOF and UHPLC-MS/MS. Drug Test. Anal., 2017, 9(10), 1604-1610.
[http://dx.doi.org/10.1002/dta.2188] [PMID: 28303675]
[21]
Kahle, K.; Kraus, M.; Scheppach, W.; Richling, E. Colonic availability of apple polyphenols-a study in ileostomy subjects. Mol. Nutr. Food Res., 2005, 49(12), 1143-1150.
[http://dx.doi.org/10.1002/mnfr.200500132] [PMID: 16252309]
[22]
Choy, Y.Y.; Jaggers, G.K.; Oteiza, P.I.; Waterhouse, A.L. Bioavailability of intact proanthocyanidins in the rat colon after ingestion of grape seed extract. J. Agric. Food Chem., 2013, 61(1), 121-127.
[http://dx.doi.org/10.1021/jf301939e] [PMID: 23244439]
[23]
Ding, Y.; Li, H.; Li, Y.; Liu, D.; Zhang, L.; Wang, T.; Liu, T.; Ma, L.; De la Puerta, R. Protective effects of grape seed proanthocyanidins on the kidneys of diabetic rats through the Nrf2 signalling pathway. Evid. Based Complement. Alternat. Med., 2020, 2020, 5205903.
[http://dx.doi.org/10.1155/2020/5205903] [PMID: 33062013]
[24]
Bashir, N.; Manoharan, V.; Miltonprabu, S. Grape seed proanthocyanidins protects against cadmium induced oxidative pancreatitis in rats by attenuating oxidative stress, inflammation and apoptosis via Nrf-2/HO-1 signaling. J. Nutr. Biochem., 2016, 32, 128-141.
[http://dx.doi.org/10.1016/j.jnutbio.2016.03.001] [PMID: 27142746]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy