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CC BY-NC-ND 4.0 · Eur J Dent 2019; 13(02): 229-234
DOI: 10.1055/s-0039-1694314
Original Article
Dental Investigation Society

Morus alba Stem Extract Suppresses Matrix Metalloproteinases (MMP)-1, MMP-9, and Tissue Inhibitors of Metalloproteinase (TIMP)-1 Expression via Inhibition of IκBα Degradation Induced by Porphyromonas gingivalis LPS Signal in THP-1 Cells

Ichaya Yiemwattana
1   Department of Preventive Dentistry, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand
,
Ruchadaporn Kaomongkolgit
2   Department of Oral Diagnosis, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand
,
Sodsi Wirojchanasak
1   Department of Preventive Dentistry, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand
,
Niratcha Chaisomboon
3   Research Laboratory, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand
› Author Affiliations Funding This study received a grant from Naresuan University (R2561B012).
Further Information

Publication History

Publication Date:
30 September 2019 (online)

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Abstract

Objectives The aim of this study is to evaluate the inhibitory effects of M. alba stem extract (MSE) on the expression of matrix metalloproteinases (MMP)-1, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1 in Porphyromonas gingivalis lipopolysaccharide (LPS)-activated-acute monocytic leukemia cell line (THP-1).

Materials and Methods THP-1 cells were treated with noncytotoxic concentrations of MSE combined with 1 µg/mL of P. gingivalis LPS. The mRNA levels of MMP-1, MMP-9, and TIMP-1 were evaluated via quantitative real-time polymerase chain reaction. The secreted proteins in the culture media were detected by enzyme-linked immunosorbent assay. The degradation of inhibitor of kappa B-alpha (IκBα) protein was tracked by Western blotting.

Statistical Analysis Comparisons in experiments were analyzed with analysis of variance followed by Tukey honestly significant difference comparison test.

ResultsTwenty and 40 µg/mL of MSE significantly downregulated MMP-1 and MMP-9 genes and protein expression but upregulated the gene expression of TIMP-1 (p < 0.05). P. gingivalis LPS induced degradation of IκBα, while addition of MSE (20 and 40 µg/mL) increased IκBα cytosolic levels. MSE was able to suppress the P. gingivalis LPS-induced MMPs expression and also increased the gene expression of TIMP-1 via the inhibition of the cytoplasmic IκBα degradation in THP-1 cells.

Conclusions The present observations suggest that MSE exerted a positive effect on the regulatory mechanism between MMPs and TIMP, which is an important implication for the therapeutic potential of MSE in periodontitis.

Keywords

matrix metalloproteinases - lipopolysaccharide - monocytes - M. alba stem extract
 

  • References

  • 1 Franco C, Patricia HR, Timo S, Claudia B, Marcela H. Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci 2017; 18 (02) 440
    CrossrefPubMedGoogle Scholar
  • 2 Cifcibasi E, Kantarci A, Badur S, Issever H, Cintan S. Impact of metronidazole and amoxicillin combination on matrix metalloproteinases-1 and tissue inhibitors of matrix metalloproteinases balance in generalized aggressive periodontitis. Eur J Dent 2015; 9 (01) 53-59
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Khurshid Z, Mali M, Naseem M, Najeeb S, Zafar MS. Human gingival crevicular fluids (GCF) proteomics: an overview. Dent J (Basel) 2017; 5 (01) 12
    CrossrefPubMedGoogle Scholar
  • 4 Tüter G, Kurtiş B, Serdar M. Effects of phase I periodontal treatment on gingival crevicular fluid levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1. J Periodontol 2002; 73 (05) 487-493
    CrossrefPubMedGoogle Scholar
  • 5 Rai B, Kaur J, Jain R, Anand SC. Levels of gingival crevicular metalloproteinases-8 and -9 in periodontitis. Saudi Dent J 2010; 22 (03) 129-131
    CrossrefPubMedGoogle Scholar
  • 6 Marcaccini AM, Meschiari CA, Zuardi LR. et al. Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy. J Clin Periodontol 2010; 37 (02) 180-190
    CrossrefPubMedGoogle Scholar
  • 7 Gölz L, Memmert S, Rath-Deschner B. et al. Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-κB activation in PDL cells and periodontal diseases. Mediators Inflamm 2015; 2015: 438085
    PubMedGoogle Scholar
  • 8 Jacobs MD, Harrison SC. Structure of an IkappaBalpha/NF-kappaB complex. Cell 1998; 95 (06) 749-758
    CrossrefPubMedGoogle Scholar
  • 9 Chan EWC, Lye PY, Wong SK. Phytochemistry, pharmacology, and clinical trials of Morus alba. Chin J Nat Med 2016; 14 (01) 17-30
    PubMedGoogle Scholar
  • 10 Soonthornsit N, Pitaksutheepong C, Hemstapat W, Utaisincharoen P, Pitaksuteepong T. In vitro anti-inflammatory activity of. Morus alba . L. stem extract in LPS-stimulated RAW 264.7 cells. Evid Based Complement Alternat Med 2017; 2017: 3928956
    PubMedGoogle Scholar
  • 11 Chung KO, Kim BY, Lee MH. et al. In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol 2003; 55 (12) 1695-1700
    CrossrefPubMedGoogle Scholar
  • 12 Yiemwattana I, Chaisomboon N, Jamdee K. Antibacterial and anti-inflammatory potential of Morus alba stem extract. Open Dent J 2018; 12: 265-274
    CrossrefPubMedGoogle Scholar
  • 13 Gupta P. Natural products as inhibitors of matrix metalloproteinases. Nat Prod Chem Res 2016; 4: 1
    Google Scholar
  • 14 Weiss T, Shalit I, Blau H. et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines. Antimicrob Agents Chemother 2004; 48 (06) 1974-1982
    CrossrefPubMedGoogle Scholar
  • 15 Kou Y, Inaba H, Kato T. et al. Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols. J Periodontol 2008; 79 (01) 174-180
    CrossrefPubMedGoogle Scholar
  • 16 Vilela Pd, de Oliveira JR, de Barros PP, Leão MV, de Oliveira LD, Jorge AO. In vitro effect of caffeic acid phenethyl ester on matrix metalloproteinases (MMP-1 and MMP-9) and their inhibitor (TIMP-1) in lipopolysaccharide-activated human monocytes. Arch Oral Biol 2015; 60 (09) 1196-1202
    CrossrefPubMedGoogle Scholar
  • 17 Lee JH, Chung JH, Cho KH. The effects of epigallocatechin-3-gallate on extracellular matrix metabolism. J Dermatol Sci 2005; 40 (03) 195-204
    CrossrefPubMedGoogle Scholar
  • 18 Howard EW, Bullen EC, Banda MJ. Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem 1991; 266 (20) 13064-13069
    CrossrefPubMedGoogle Scholar
  • 19 Jin UH, Chung TW, Kang SK. et al. Caffeic acid phenyl ester in propolis is a strong inhibitor of matrix metalloproteinase-9 and invasion inhibitor: isolation and identification. Clin Chim Acta 2005; 362 (01) (02) 57-64
    CrossrefPubMedGoogle Scholar
  • 20 Ambili R, Janam P. A critique on nuclear factor-kappa B and signal transducer and activator of transcription 3: the key transcription factors in periodontal pathogenesis. J Indian Soc Periodontol 2017; 21 (05) 350-356
    PubMedGoogle Scholar