SUBSCRIBE
Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (11): 1060-1069.doi: 10.3736/jcim20101110

• Original Expreimental Research • Previous Articles     Next Articles

Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions and activities of matrix metalloproteinases in human skin fibroblasts and human leukemia cell line THP-1

Ya-hui Lianga,b,Ping Lia, Jing-xia Zhaoa, Xin Liua, Qi-fu Huangc   

  1. a Beijing Institute of Chinese Medicine, Beijing Hospital of Chinese Medicine, Capital Medical University, Beijing 100010, China
    b Beijing Rehabilitation Center, Beijing 100144, China
    c School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2010-04-05 Accepted:2010-07-07 Online:2010-11-20 Published:2010-11-15
  • Contact: Ping Li E-mail:liping411@yahoo.com.cn

RichHTML

1

PDF (PC)

59

Like

Objective

In order to reveal the treatment mechanism of Chinese medicine with the effect of activating blood and resolving putridity, we selected acetyl-11-keto-beta-boswellic acid (AKBA) and arsenic trioxide (ATO), the main monomeric components of frankincense and arsenolite which are two most commonly used Chinese medicine with effect of activating blood and resolving putridity. We combined AKBA and ATO as a compound, and explored its regulatory role in productions and activities of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 in human skin fibroblasts (HSFbs) and human acute monocytic leukemia cell line THP-1 in inflammatory state.

Methods

In order to simulate the inflammatory micro-environment of chronic wounds, we established 3 cell models: HSFb model activated by tumor necrosis factor-alpha (TNF-α), THP-1 cell model activated by phorbol-12-myristate-13-acetate (PMA) and HSFb-THP-1 cell coculture system. AKBA and ATO were cocultured with these cell models. Enzyme-linked immunosorbent assay (ELISA), gelatin zymography assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to test the secretions, activities and mRNA expressions of MMP-1, MMP-2 and MMP-9. In the study of the regulatory mechanism of AKBA and ATO on MMPs, AKBA and ATO were cocultured with the cell models. ELISA was used to test the secretions of TNF-α and interleukin-1beta (IL-β) and Western blot was used to test the phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated proteinkinase (p38MAPK).

Results

Compound of AKBA and ATO inhibited MMP-1, MMP-2 and MMP-9 mRNA expressions, secretions and activities respectively in HSFbs and THP-1 cells in inflammatory state (P<0.05, P<0.01). Also compound of AKBA and ATO inhibited secretions of TNF-α and IL-1β in THP-1 cells and cell coculture system (P<0.01). It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFbs and THP-1 cells (P<0.05, P<0.01).

Conclusion

The combined use of AKBA and ATO which in line with the rule of activating blood and resolving putridity inhibits fibroblasts and inflammatory cells in producing MMPs in inflammatory state through inhibiting the release of inflammatory factors and MAPK cascade pathway.

Key words: Acetyl-ll-keto-beta-boswellic acid, Arsenic trioxide, Fibroblasts, Monocytes, THP-1, Matrix metalloproteinases

Figure 1

Identification of fibroblasts by immunocytochemical method (Light microscopy, ×200) A: Expression of vimentin in fibroblasts; B: Negative control (anti-vimentin antibody was replaced by PBS)."

Table 1

Cytotoxicity of AKBA to HSFb and THP-1 cells"

Table 2

Cytotoxicity of ATO to HSFb and THP-1 cells"

Table 3

Cytotoxicity of AKBA and ATO combination to HSFb and THP-1 cells"

Table 4

Effects of AKBA and ATO on secretion of MMP-1, MMP-2 and MMP-9 by HSFb and THP-1 cells"

Figure 2

Effects of AKBA and ATO combination on expression of MMP-1 mRNA in HSFb 1: Control group; 2: TNF-α group; 3: TNF-α+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. △P<0.05, △△P<0.01, vs TNF-α group"

Figure 3

Effects of AKBA and ATO combination on expression of MMP-2 mRNA in HSFb1: Control group; 2: TNF-α group; 3: TNF-α+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. △P<0.05, △△P<0.01, vs TNF-α group."

Figure 4

Effects of AKBA and ATO combination on expression of MMP-9 mRNA in THP-1 cells1: Control group; 2: PMA group; 3: PMA+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. ▲▲P<0.01, vs PMA group."

Figure 5

Effects of AKBA and ATO combination on MMP-2 activity in culture supernatants of HSFb1: Control group; 2: TNF-α group; 3: TNF-α+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. △P<0.05, △△P<0.01, vs TNF-α group."

Figure 6

Effects of AKBA and ATO combination on MMP-9 activity in culture supernatants of THP-1 cells1: Control group; 2: PMA group; 3: PMA+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. ▲▲P<0.01, vs PMA group."

Figure 7

Effects of AKBA and ATO on MMP-2 and MMP-9 activities in supernatants of cell coculture system1: Control group; 2: PMA group; 3: PMA+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. □P<0.05, □□P<0.01, vs PMA group."

Table 5

Effects of AKBA and ATO combination on secretions of TNF-α and IL-1β by THP-1 cells and cell coculture system"

Figure 8

Effects of AKBA and ATO combination on phosphorylation of ERK1/2 and p38MAPK in HSFbs1: Control group; 2: TNF-α group; 3: TNF-α+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. △P<0.05, △△P<0.01, vs TNF-α group."

Figure 9

Effects of AKBA and ATO combination on phosphorylation of ERK1/2 and p38MAPK in THP-1 cells1: Control group; 2: PMA group; 3: PMA+AKBA+ATO group. Data were represented as $\overline{x}$±s, n=3. ▲P<0.05, ▲▲P<0.01, vs PMA group."

[1] Xue JG . The medication features of categorized formula of Shengji Powder[J]. Zhong Yi Wai Zhi Za Zhi, 1995,4(6):34-35
薛建国 . 生肌散类方用药特点探讨[J]. 中医外治杂志, 1995,4(6):34-35
[2] Ravanti L, Kähäri VM . Matrix metalloproteinases in wound repair(review)[J]. Int J Mol Med, 2000,6(4):391-407
doi: 10.3892/ijmm.6.4.391 pmid: 10998429
[3] Xue M, Le NT, Jackson CJ . Targeting matrix metalloproteases to improve cutaneous wound healing[J]. Expert Opin Ther Targets, 2006,10(1):143-155
doi: 10.1517/14728222.10.1.143 pmid: 16441234
[4] Trengove NJ, Stacey MC , MacAuley S. Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors[J]. Wound Repair Regen, 1999,7(6):442-452
doi: 10.1046/j.1524-475X.1999.00442.x
[5] Xue QS. Principles and techniques of culture in vitro[M]. Beijing: Science Press, 2001: 442-445
薛庆善 . 体外培养的原理与技术[M]. 北京: 科学出版社, 2001: 442-445
[6] Kanangat S, Postlethwaite A, Hasty K, Kang A, Smeltzer M, Appling W, Schaberg D . Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts by Staphylococcus aureus: implications in the pathogenesis of septic arthritis and other soft tissue infections[J]. Arthritis Res Ther, 2006,8(6):R176
doi: 10.1186/ar2086
[7] Ge H, Zhang JF, Guo BS, He B, Wang BR, Wang CQ . Resveratrol inhibits expression of EMMPRIN from macrophages[J]. Yao Xue Xue Bao, 2006,41(7):625-630
doi: 10.3321/j.issn:0513-4870.2006.07.009
葛恒, 张俊峰, 郭炳诗, 何奔, 王彬尧, 王长谦 . 白藜芦醇抑制巨噬细胞细胞外基质金属蛋白酶诱导物的表达[J]. 药学学报, 2006,41(7):625-630
doi: 10.3321/j.issn:0513-4870.2006.07.009
[8] Medina A, Scott PG, Ghahary A, Tredget EE . Pathophysiology of chronic nonhealing wounds[J]. J Burn Care Rehabil, 2005,26(4):306-319
doi: 10.1097/01.BCR.0000169887.04973.3A pmid: 16006837
[9] Bennett NT, Schultz GS . Growth factors and wound healing: Part Ⅱ. Role in normal and chronic wound healing[J]. Am J Surg, 1993,116(1):74-81
doi: 10.1016/S0002-9610(05)80589-6 pmid: 8392302
[10] Nwomeh BC, Yager DR, Cohen IK . Physiology of the chronic wound[J]. Clin Plast Surg, 1998,25(3):341-356
doi: 10.1016/S0278-2391(99)90091-5 pmid: 9696897
[11] Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H . Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and nondiabetic patients[J]. Diabetologia, 2002,45(7):1011-1016
doi: 10.1007/s00125-002-0868-8
[12] Yager DR, Zhang LY, Liang HX, Diegelmann RF, Cohen IK . Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids[J]. J Invest Dermatol, 1996,107(5):743-748
doi: 10.1111/1523-1747.ep12365637
[13] Wysocki AB, Staiano-Coico L, Grinnell F . Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9[J]. J Invest Dermatol, 1993,101(1):64-68
doi: 10.1111/1523-1747.ep12359590
[14] Barone EJ, Yager DR, Pozez AL, Olutoye OO, Crossland MC, Diegelmann RF . Interleukin-1α and collagenase activity elevated in chronic wounds[J]. Plast Reconstr Surg, 1998,102(4):1023-1027
doi: 10.1097/00006534-199809020-00016 pmid: 9734419
[15] Weckroth M, Vaheri A, Lauharanta J, Sorsa T, Konttinen YT . Matrix metalloproteinases, gelatinase and collagenase, in chronic leg ulcers[J]. J Invest Dermatol, 1996,106(5):1119-1124
doi: 10.1111/1523-1747.ep12340167 pmid: 8618050
[16] Drinkwater SL, Smith A, Burnand KG . What can wound fluids tell us about the venous ulcer microenvironment[J]. Int J Low Extrem Wounds, 2002,1(3):184-190
doi: 10.1177/153473460200100307 pmid: 15871971
[17] Mwaura B, Mahendran B, Hynes N, Defreitas D, Avalos G, Adegbola T . The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2, and PDGF-AA on the chronicity of venous leg ulcers[J]. Eur J Vasc Endovasc Surg, 2006,31(3):306-310
doi: 10.1016/j.ejvs.2005.08.007
[18] Parks WC . Matrix metalloproteinases in repair[J]. Wound Repair Regen, 1999,7(6):423-432
doi: 10.1046/j.1524-475X.1999.00423.x pmid: 10633001
[19] Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF . Impaired wound healing[J]. Clin Dermatol, 2007,25(1):19-25
doi: 10.1016/j.clindermatol.2006.12.005
[20] Subramaniam K, Pech CM, Stacey MC, Wallace HJ . Induction of MMP-1, MMP-3 and TIMP-1 in normal dermal fibroblasts by chronic venous leg ulcer wound fluid[J]. Int Wound J, 2008,5(1):79-86
doi: 10.1111/j.1742-481X.2007.00336.x
[21] Ammon HP . Boswellic acids(components of frankincense) as the active principle in treatment of chronic inflammatory diseases[J]. Wien Med Wochenschr, 2002,152(15-16):373-378
doi: 10.1046/j.1563-258X.2002.02056.x
[22] Zhou LF, Yin KS, Yang Y, Huang M, Zhang XL, Wang T, Zhu ZL, Feng ZQ . Effect of arsenic trioxide on IκB-alpha expression and nuclear factor κB activation by arsenic trioxide[J]. Zhongguo Lin Chuang Kang Fu, 2004,8(24):5017-5020
周林福, 殷凯生, 杨玉, 黄茂, 张希龙, 王彤, 朱自路, 冯振卿 . 三氧化二砷对哮喘小鼠肺组织IκB表达和核因子κB激活的作用[J]. 中国临床康复, 2004,8(24):5017-5020
[1] Stefania Lamponi, Anna Maria Aloisi, Claudia Bonechi, Marco Consumi, Alessandro Donati, Gemma Leone, Claudio Rossi, Gabriella Tamasi, Luana Ghiandai, Ersilia Ferrini, Paolo Fiorenzani, Ilaria Ceccarelli, Agnese Magnani. Evaluation of in vitro cell and blood compatibility and in vivo analgesic activity of plant-derived dietary supplements. Journal of Integrative Medicine, 2019, 17(3): 213-220.
[2] Takanobu Takata, Yoshiharu Motoo, Naohisa Tomosugi. Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts. Journal of Integrative Medicine, 2014, 12(6): 495-503.
[3] Zhou Xian-mei, Zhao Yang, He Cui-cui, Li Jian-xin. Preventive effects of Citrus reticulata essential oil on bleomycin-induced pulmonary fibrosis in rats and the mechanism. Journal of Chinese Integrative Medicine, 2012, 10(2): 200-209.
[4] Anisur Rahman Khuda-Bukhsh, Antara Banerjee, Surjyo Jyoti Biswas, Susanta Roy Karmakar, Pathikrit Banerjee, Surajit Pathak, Bibhas Guha, Saiful Haque, Debarsi Das, Arnab De, Durba Das, Naoual Boujedaini. An initial report on the efficacy of a millesimal potency Arsenicum Album LM 0/3 in ameliorating arsenic toxicity in humans living in a high-risk arsenic village. Journal of Chinese Integrative Medicine, 2011, 9(6): 596-604.
[5] Jin-xin Xu, Yu Zhang, Xue-zeng Zhang, Ying-ying Ma. Anti-angiogenic effects of genistein on synovium in a rat model of type Ⅱ collagen-induced arthritis. Journal of Chinese Integrative Medicine, 2011, 9(2): 186-193.
[6] Wen Sun, Jian Yu, Yu-min Shi, Hao Zhang, Ying Wang, Bing-bing Wu. Effects of Cordyceps extract on cytokines and transcription factors in peripheral blood mononuclear cells of asthmatic children during remission stage. Journal of Chinese Integrative Medicine, 2010, 8(4): 341-346.
[7] Ling-ying Liu, Xiao-dong Chen, Bo-yu Wu, Qiong Jiang. Influence of Aloe polysaccharide on proliferation and hyaluronic acid and hydroxyproline secretion of human fibroblasts in vitro. Journal of Chinese Integrative Medicine, 2010, 8(3): 256-262.
[8] Shuang-nian Xu , Jie-ping Chen, Jian-ping Liu, Yun Xia . Efficacy of arsenic trioxide for acute promyelocytic leukemia: A systematic review and meta-analysis. Journal of Chinese Integrative Medicine, 2009, 7(9): 801-808.
[9] Dong-mei Zhang , Ying Qin , Xi-ying Lu , Ai-ming Wu , Ling-qun Zhu , Shuo-ren Wang , Liang-duo Jiang . Effects of tetramethylpyrazine on angiotensin Ⅱ-induced proliferation and type Ⅰ collagen synthesis of rat cardiac fibroblasts. Journal of Chinese Integrative Medicine, 2009, 7(3): 232-236.
[10] Ya-hui Liang, Ping Li , Qi-fu Huang , Jing-xia Zhao , Xin Liu , Miao-ke Dai. Salvianolic acid B in vitro inhibited matrix metalloproteinases-1, -2, and -9 activities. Journal of Chinese Integrative Medicine, 2009, 7(2): 145-150.
[11] Shuang-nian Xu, Jie-ping Chen, Jian-ping Liu, Yun Xia. Arsenic trioxide in combination with all-trans retinoic acid for acute promyelocytic leukemia: A systematic review and meta-analysis. Journal of Chinese Integrative Medicine, 2009, 7(11): 1023-1034.
[12] Shan Mou, Zhao-hui Ni, Qing-yi Zhang. Expression of c-met in human kidney fibroblasts induced by high glucose in vitro and the regulation of Radix Astragali. Journal of Chinese Integrative Medicine, 2008, 6(5): 482-487.
[13] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44.
[14] Meng-chang Wang​, Shan-xi Liu​, Peng-bo Liu​. Changes of gene expression profile of multiple myeloma cell line RPMI 8226 treated by arsenic trioxide. Journal of Chinese Integrative Medicine, 2006, 4(2): 160-165.
[15] Bo-hua Yang, Jian-hui Qin, Ling-qun Zhu, Lei Chen, Hong Lu, Feng-tong Liu, You-shan Li. Treatment of lower limb ischemia with combination of traditional Chinese medicine and transplantation of autologous bone marrow mononuclear cells: A report of 23 cases. Journal of Chinese Integrative Medicine, 2005, 3(1): 28-30.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] 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
[7] 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
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228
Journal of Integrative Medicine, ISSN: 2095-4964 CN 31-2083/R
Copyright © Journal of Integrative Medicine
Powered by Beijing Magtech Co. Ltd
沪公网安备31010602003416号      沪ICP备18017633号-3