Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (1): 84-90.doi: 10.3736/jcim20110114

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Dusuqing Granule on toll-like receptor 4 signaling in multiple organ injury induced by bacterial pneumonia in aged rats

Shou-fu Wang1, Hui-jian Zhang2, Jian-sheng Li2(), Jin-li Qin2, Su-yun Li2, Hai-bin Yu2, Feng Wang3, Ya Li2, Si-hua Liu2   

  1. 1. Henan Academy of Traditional Chinese Medicine, Zhengzhou 450004, Henan Province, China
    2. Institute of Geriatrics, Henan College of Traditional Chinese Medicine, Zhengzhou 450008, Henan Province, China
    3. Department of Encephalopathy, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou 450002, Henan Province, China
  • Received:2010-09-05 Accepted:2010-09-16 Online:2011-01-20 Published:2011-01-15
  • Contact: Li Jian-sheng E-mail:li_js8@163.com

Objective: To study the protective mechanism of Dusuqing Granule, a compound Chinese herbal medicine, on the senile multiple organ injury caused by bacterial pneumonia by observing the expression changes of molecules related to toll-like receptor 4 (TLR4) signaling.
Methods: A total of 55 male Sprague-Dawley aged rats were divided into control group, untreated group, Dusuqing group and lomefloxacin group. There were 25 rats in the untreated group and 10 rats in each of the other three groups. Multiple organ injury in a rat model of pneumonia was induced by injection of Klebsiella pneumoniae through tracheal intubation. By means of immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), examinations were made on mRNA expressions of lipopolysaccharide-binding protein (LBP), CD14, TLR4 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in the tissues of the lung, heart and small intestine, and also on the protein expressions of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6) and nuclear factor-κB (NF-κB) .
Results: Expressions of LBP, CD14, TLR4 and IRAK-1 mRNAs in the tissues of the lung, heart and small intestine in the untreated group were stronger than those in the control group (P<0.01 or P<0.05). The protein expressions of TLR4, TRAF6 and NF-κB were increased dramatically in the untreated group as compared with the control group (P<0.01 or P<0.05). Compared with the untreated group, the expressions of LBP, CD14, TLR4 and IRAK-1 mRNAs in the tissues of the lung, heart and small intestine in the Dusuqing group were weakened significantly (P<0.01 or P<0.05). Meanwhile, the protein expressions of TLR4, TRAF6 and NF-κB were decreased markedly in the Dusuqing group (P<0.01 or P<0.05).
Conclusion: Dusuqing Granule is effective in suppressing toll-like receptor signal transduction activation and reducing the secretion of cytokines and inflammatory mediators, which can further reduce the organ tissue injury. Dusuqing Granule can decrease the levels of TLR signal transduction activation including the targets LBP, CD-14, TLR4, IRAK-1, TRAF6 and NF-κB, which is different from the special inhibitor that acts only on some segments.

Key words: drugs,Chinese herbal, multiple organ failure, toll-like receptor, signal transduction, rats

[1] Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S . Cutting edge: Toll-like receptor 4(TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product[J]. J Immunol, 1999,162(7):3749-3752
[2] Tsujimoto H, Ono S, Efron PA, Scumpia PO, Moldawer LL, Mochizuki H . Role of toll-like receptors in the development of sepsis[J]. Shock, 2008,29(3):315-321
[3] Li JS, Li JG, Ren ZX, Sun HG, Miao MS . Protective effect of Dusuqing on organ pathological damage induced by endotoxin in aged mice[J]. Zhongguo Lao Nian Xue Za Zhi, 1999,19(2):167-169
李建生, 李建国, 任周新, 孙红光, 苗明三 . 毒素清对内毒素所致衰老模型小鼠脏器病理损伤保护作用的研究[J]. 中国老年学杂志, 1999,19(2):167-169
[4] Li JS, Wang SF, Qin JL, Zhang HJ, Li SY, Yu HB, Wang F, Liu SH, Li Y . A model of multiple organ injury induced by Klebsiella pneumoniae pneumonia in aged rats[J]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2009,21(4):226-229
李建生, 王守富, 秦金利, 张慧俭, 李素云, 余海滨, 王峰, 刘四化, 李亚 . 克雷伯杆菌肺炎老龄大鼠多器官损伤模型的建立[J]. 中国危重病急救医学, 2009,21(4):226-229
[5] Hu S, Sheng ZY. Multiple organ dysfunction syndromes[M]. Beijing: Science Press, 1999: 186-204
胡森, 盛志勇 . 多器官功能障碍综合征[M]. 北京: 科学出版社, 1999: 186-204
[6] Qian XS, Han YL, Hou YT, Xue Q, Liu XH, Liu JL . Clinical features of multiple organ failure in the elderly: a report of 1 605 cases[J]. Zhonghua Lao Nian Duo Qi Guan Ji Bing Za Zhi, 2002,1(1):7-10
钱小顺, 韩亚玲, 侯允天, 薛桥, 刘雪红, 刘建立 . 1 605例老年多器官功能衰竭的临床分析[J]. 中华老年多器官疾病杂志, 2002,1(1):7-10
[7] Qi HY, Yin CH . Research progress of multiple organ dysfunction syndrome in the elderly[J]. Zhonghua Lao Nian Duo Qi Guan Ji Bing Za Zhi, 2007,6(4):281-284
齐海宇, 阴赪宏 . 老年多器官功能障碍综合征的研究进展[J]. 中华老年多器官疾病杂志, 2007,6(4):281-284
[8] Akira S . Mammalian Toll-like receptors[J]. Curr Opin Immuno1, 2003,15(2):5-11
doi: 10.1016/S0952-7915(02)00013-4
[9] Verstak B, Hertzog P, Mansell A . Toll-like receptor signalling and the clinical benefits that lie within[J]. Inflamm Res, 2007,56(1):1-10
doi: 10.1007/s00011-007-6093-7
[10] Olson JK, Miller SD . Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs[J]. J Immunol, 2004,173(6):3916-3924
doi: 10.4049/jimmunol.173.6.3916
[11] Bochkov VN, Kadl A, Huber J, Gruber F, Binder BR, Leitinger N . Protective role of phospholipid oxidation products in endotoxin-induced tissue damage[J]. Nature, 2002,419(6902):77-81
doi: 10.1038/nature01023
[12] Akira S, Uematsu S, Takeuehi O . Pathogen recognition and innate immunity[J]. Cell, 2006,124(4):783-801
doi: 10.1016/j.cell.2006.02.015
[13] Ma HY, Yin GQ . Role of Toll-like receptors during septic shock[J]. Dong Nan Da Xue Xue Bao Yi Xue Ban, 2004,23(6):422-426
马海鹰, 殷国庆 . Toll样受体在感染性休克中的作用[J]. 东南大学学报(医[14]Knuefermann P, Nemoto S, Baumgarten G, Misra A, Sivasubramanian N, Carabello BA, Vallejo JG.Cardiac inflammation and innate immunity in septic shock: is there a role for Toll-like receptors[J].Chest, 2002,121(4):1329-1336
[15] Huang YS, Misior A, Li LW . Novel role and regulation of the interleukin-1 receptor-associated kinase(IRAK) family proteins[J]. Cell Mol Immunol, 2005,2(1):36-39
[16] Zapata JM, Lefebvre S, Reed JC . Targeting TRAFs for therapeutic intervention[J]. Adv Exp Med Biol, 2007,597:188-201
doi: 10.1007/978-0-387-70630-6
[17] Hayden MS, Ghosh S . Shared principles in NF-κB signaling[J]. Cell, 2008,132(3):344-362
doi: 10.1016/j.cell.2008.01.020
[18] Böhrer H, Qiu F, Zimmermann T, Zhang Y, Jllmer T , Mönnel D, Böttiger BW, Stern DM, Waldherr R, Saeger HD, Ziegler R, Bierhaus A, Martin E, Nawroth PP.Role of NF-κB in the mortality of sepsis[J]. J Clin Invest, 1997,100(5):972-985
doi: 10.1172/JCI119648
[1] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[2] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[3] Yu-fan Shen, Xue Zhang, Ying Wang, Fan-fan Cao, Georges Uzan, Bin Peng, Deng-hai Zhang. Celastrol targets IRAKs to block Toll-like receptor 4-mediated nuclear factor-κB activation. Journal of Integrative Medicine, 2016, 14(3): 203-208.
[4] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[5] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[6] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[7] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[8] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[9] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[10] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[11] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[12] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
[13] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
[14] Amir Rashidian​, Saeed Mehrzadi, Ali Reza Ghannadi, Parvin Mahzooni, Samira Sadr, Mohsen Minaiyan​. Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: A light microscopic evaluation. Journal of Integrative Medicine, 2014, 12(2): 115-120.
[15] Dilpesh Jain​, Manish Kumar Bansal, Rahul Dalvi​, Aman Upganlawar​, Rahul Somani​. Protective effect of diosmin against diabetic neuropathy in experimental rats. Journal of Integrative Medicine, 2014, 12(1): 35-41.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[2] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[3] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[6] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[7] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[8] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022
[9] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[10] Bing Hu , Hong-mei An , Ke-ping Shen , Qin Du. Senescence-inducing effects of Chinese herbal medicine Tenglong Buzhong Decoction on human colon carcinoma LS-174-T cells and the mechanism. Journal of Chinese Integrative Medicine, 2010, 8(11): 1048-1052