Skip to main content
SpringerLink
Log in

In silico effect of Korean medicinal phytocompounds on gene targets of osteoarthritis

  • Research Article
  • Published:
Advances in Traditional Medicine Aims and scope Submit manuscript

Abstract

Traditional Korean medicinal plants are known for their medieval and traditional therapeutic purposes. These plants were used in different concentrations to treat challenging diseases, maximize therapeutic influence, and promote patient wellbeing. The phytochemicals of these plants possess antimicrobial, anti-inflammation, and anti-cancer properties. In comparison, traditional Chinese plant extracts and their compounds are more elaborately explored in the treatment of osteoarthritis (OA). Therefore, in this study we aimed to analyze the effects of major phytocompounds of five antioxidant Korean medicinal plants on potential gene targets of OA. This was done using an in silico gene expression database in order to evaluate the rate of expression. We selected major compounds of these plants and utilized PubChem to download the canonical SMILES, thus determining their effect on genes using the DIGEP-Pred database. The results of our analysis showed that the Korean medicinal compounds reduced the expression of SUV39H2, MIR20B, SOX4, KLF10, DNMT1, SUMO1, LGALS8, IL15, SPRY1, IL1R1, CXCL2 and APOA1, all of which are implicated in the pathogenesis of OA. They also increased the expression of COL2A1, OGG1, GCLC, HOXA11, KEAP1, FOXO1, CITED2 and BMPR1B, which are involved in the repair and maintenance of articular cartilage. Our study also demonstrated the promising activity of the Korean medicinal compounds against OA and the possession of gene targeting effects. The results of this study might be used to validate these effects in-vitro experiments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

All data and materials should be available upon request.

Code availability

Not applicable.

References

  • Abramoff B, Caldera FE (2020) Osteoarthritis: pathology, diagnosis, and treatment options. Med Clin 104:293–311

    Google Scholar 

  • Ansari MY, Ahmad N, Haqqi TM (2020) Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. Biomed Pharmacother 129:110452

    Article  CAS  Google Scholar 

  • Araki Y, Aizaki Y, Sato K, Oda H, Kurokawa R, Mimura T (2018) Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts. Clin Exp Rheumatol 36:314–316

    PubMed  Google Scholar 

  • Bokhari RA, Tantowi NACA, Lau SF, Mohamed S (2018) Java Tea (Orthosiphon stamineus) protected against osteoarthritis by mitigating inflammation and cartilage degradation: a preclinical study. Inflammopharmacology 26:939–949

    Article  CAS  Google Scholar 

  • Charlier E, Deroyer C, Ciregia F, Malaise O, Neuville S, Plener Z, Malaise M, de Seny D (2019) Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem Pharmacol 165:49–65

    Article  Google Scholar 

  • Chow YY, Chin K-Y (2020) The role of inflammation in the pathogenesis of osteoarthritis. Mediat Inflamm

  • Contartese D, Tschon M, De Mattei M, Fini M (2020) Sex specific determinants in osteoarthritis: a systematic review of preclinical studies. Int J Mol Sci 21:3696

    Article  CAS  Google Scholar 

  • de Seny D, Cobraiville G, Charlier E et al (2015) Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro-inflammatory properties. PLoS One 10:e0122904–e0122904

    Article  Google Scholar 

  • Deligiannidou G-E, Papadopoulos R-E, Kontogiorgis C, Detsi A, Bezirtzoglou E, Constantinides T (2020) Unraveling natural products’ role in osteoarthritis management—an overview. Antioxidants 9:348

    Article  CAS  Google Scholar 

  • Deng Z, Jia Y, Liu H, He M, Yang Y, Xiao W, Li Y (2019) RhoA/ROCK pathway: implication in osteoarthritis and therapeutic targets. Am J Transl Res 11:5324

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gross S, Krause Y, Wuelling M, Vortkamp A (2012) Hoxa11 and Hoxd11 regulate chondrocyte differentiation upstream of Runx2 and Shox2 in mice. PLoS One 7:e43553–e43553

    Article  CAS  Google Scholar 

  • Gu Y-T, Chen J, Meng Z-L, Ge W-Y, Bian Y-Y, Cheng S-W, Xing C-K, Yao J-L, Fu J, Peng L (2017) Research progress on osteoarthritis treatment mechanisms. Biomed Pharmacother 93:1246–1252

    Article  CAS  Google Scholar 

  • Han N-R, Sim W-M, Sul M-C et al (2013) Genuine traditional Korean medicine, BaekJeol-Tang for the treatment of rheumatoid arthritis. Tang. https://doi.org/10.5667/tang.2013.0010

    Article  Google Scholar 

  • Haq I, Murphy E, Dacre J (2003) Osteoarthritis. Postgrad Med J 79:377–383

    Article  CAS  Google Scholar 

  • He Z, Leong DJ, Xu L et al (2019) CITED2 mediates the cross-talk between mechanical loading and IL-4 to promote chondroprotection. Ann N Y Acad Sci 1442:128–137

    Article  CAS  Google Scholar 

  • He Y, Li Z, Alexander PG, Ocasio-Nieves BD, Yocum L, Lin H, Tuan RS (2020) Pathogenesis of osteoarthritis: risk factors, regulatory pathways in chondrocytes, and experimental models. Biology (Basel) 9:194

    CAS  Google Scholar 

  • Hiligsmann M, Cooper C, Arden N et al (2013) Health economics in the field of osteoarthritis: an expert’s consensus paper from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO). Semin Arthritis Rheum 43:303–313

    Article  Google Scholar 

  • Hou S-M, Chen P-C, Lin C-M, Fang M-L, Chi M-C, Liu J-F (2020) CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway. Arthritis Res Ther 22:251

    Article  CAS  Google Scholar 

  • Jamshidi-Kia F, Lorigooini Z, Amini-Khoei H (2018) Medicinal plants: past history and future perspective. J Herbmed Pharmacol 7

  • Kang HJ, Hong SH, Kang K-H, Park C, Choi YH (2015) Anti-inflammatory effects of Hwang-Heuk-San, a traditional Korean herbal formulation, on lipopolysaccharide-stimulated murine macrophages. BMC Complement Altern Med 15:447

    Article  Google Scholar 

  • Khan NM, Haseeb A, Ansari MY, Devarapalli P, Haynie S, Haqqi TM (2017) Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes. Free Radic Biol Med 106:288–301

    Article  CAS  Google Scholar 

  • Kurakazu I, Akasaki Y, Hayashida M et al (2019) FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor β1 signaling. J Biol Chem 294:17555–17569

    Article  Google Scholar 

  • Lagunin A, Ivanov S, Rudik A, Filimonov D, Poroikov V (2013) DIGEP-Pred: web service for in silico prediction of drug-induced gene expression profiles based on structural formula. Bioinformatics 29:2062–2063

    Article  CAS  Google Scholar 

  • Lee S-E, Seong N-S, Bang J-K, Park C-G, Sung J-S, Song J (2003) Antioxidative activities of Korean medicinal plants. Korean J Med Crop Sci 11:127–134

    Google Scholar 

  • Lee H-H, Chang C-C, Shieh M-J, Wang J-P, Chen Y-T, Young T-H, Hung S-C (2013) Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect. Sci Rep 3:2683

    Article  Google Scholar 

  • Lian C, Wang X, Qiu X et al (2019) Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1 – SMAD1 interaction. Bone Res 7:8

    Article  Google Scholar 

  • Ma S, Zhang A, Li X, Zhang S, Liu S, Zhao H, Wu S, Chen L, Ma C, Zhao H (2020) MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1. Arthritis Res Ther 22:99

    Article  CAS  Google Scholar 

  • Mang T, Kleinschmidt-Doerr K, Ploeger F, Schoenemann A, Lindemann S, Gigout A (2020) BMPR1A is necessary for chondrogenesis and osteogenesis, whereas BMPR1B prevents hypertrophic differentiation. J Cell Sci 133:jcs246934

  • Moreau A, Taheri M, Pellicelli M, Picard C, Lavoie J-F, Lavigne P, Gorman KF, Franco A (2017) Role of SUMOylation in primary osteoarthritis pathogenesis. Osteoarthr Cartil 25:S19–S20

    Article  Google Scholar 

  • Nakano K, Boyle DL, Firestein GS (2013) Regulation of DNA methylation in rheumatoid arthritis synoviocytes. J Immunol 190:1297–1303

    Article  CAS  Google Scholar 

  • O’Neill TW, McCabe PS, McBeth J (2018) Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Pract Res Clin Rheumatol 32:312–326

    Article  Google Scholar 

  • Pelttari K, Barbero A, Martin I (2015) A potential role of homeobox transcription factors in osteoarthritis. Ann Transl Med 3:254

    PubMed  PubMed Central  Google Scholar 

  • Qian K, Zhang L, Shi K (2019) Triptolide prevents osteoarthritis via inhibiting hsa-miR-20b. Inflammopharmacology 27:109–119

    Article  Google Scholar 

  • Shen J, Abu-Amer Y, O’Keefe RJ, McAlinden A (2017) Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res 58:49–63

    Article  CAS  Google Scholar 

  • Sun K, Luo J, Guo J, Yao X, Jing X, Guo F (2020) The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review. Osteoarthr Cartil 28:400–409

    Article  CAS  Google Scholar 

  • Takahata Y, Nakamura E, Hata K, Wakabayashi M, Murakami T, Wakamori K, Yoshikawa H, Matsuda A, Fukui N, Nishimura R (2019) Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5. FASEB J 33:619–630

    Article  CAS  Google Scholar 

  • Vincent TL (2019) IL-1 in osteoarthritis: time for a critical review of the literature. F1000Research 8:F1000 Faculty Rev-934

  • Wang M, Liu L, Zhang CS, Liao Z, Jing X, Fishers M, Zhao L, Xu X, Li B (2020a) Mechanism of traditional Chinese medicine in treating knee osteoarthritis. J Pain Res 13:1421

    Article  Google Scholar 

  • Wang C, Shen J, Ying J, Xiao D, O’Keefe RJ (2020) FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis. Proc Natl Acad Sci 117:30488–30497

    Article  CAS  Google Scholar 

  • Warner SC, Nair A, Marpadga R, Chubinskaya S, Doherty M, Valdes AM, Scanzello CR (2020) IL-15 and IL15RA in osteoarthritis: association with symptoms and protease production, but not structural severity. Front Immunol 11:1385

    Article  CAS  Google Scholar 

  • Weinmann D, Kenn M, Schmidt S, Schmidt K, Walzer SM, Kubista B, Windhager R, Schreiner W, Toegel S, Gabius H-J (2018) Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and – 3. Cell Mol Life Sci 75:4187–4205

    Article  CAS  Google Scholar 

  • Xue X-H, Xue J-X, Hu W, Shi F-L, Yang Y (2020) Nomilin targets the Keap1-Nrf2 signalling and ameliorates the development of osteoarthritis. J Cell Mol Med 24:8579–8588

    Article  CAS  Google Scholar 

  • Yao B, Lu B, Gao H, Zhang M, Leng X, Zhao D (2018) Guzhi Zengsheng Zhitongwan, a traditional Chinese medicinal formulation, stimulates chondrocyte proliferation through control of multiple genes involved in chondrocyte proliferation and differentiation. Evidence-based complement. Altern Med

  • Yudoh K, Karasawa R, Yui N, Yoshioka H (2014) DNA oxidative damage and its repair enzyme (Ogg1) in osteoarthritic chondrocytes. Osteoarthr Cartil 22:S166–S167

    Article  Google Scholar 

  • Zheng L, Lu H, Li H, Xu X, Wang D (2020) KLF10 is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by upregulating Acvr1 and suppressing inhbb expression. Acta Histochem 122:151528

    Article  CAS  Google Scholar 

  • Zhu Z, Xie J, Manandhar U, Yao X, Bian Y, Zhang B (2021) RNA binding protein GNL3 up-regulates IL24 and PTN to promote the development of osteoarthritis. Life Sci 267:118926

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Research Foundation of Korea (NRF) funded by the Korean Government (MEST) (2020R1I1A3069699).

Author information

Authors and Affiliations

  1. Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, 32588, Republic of Korea

    Fahad Hassan Shah & Song Ja Kim

Authors
  1. Fahad Hassan Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Song Ja Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally to this study.

Corresponding author

Correspondence to Song Ja Kim.

Ethics declarations

Ethical statement

This article does not contain any studies involving animals performed by any of the authors. This article does not contain any studies involving human participants performed by any of the authors.

Conflict of interest

Fahad Hassan Shah has no conflict of interest. Song Ja Kim has no conflict of interest

Consent for publication

All authors hereby approve this manuscript for publication.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, F.H., Kim, S.J. In silico effect of Korean medicinal phytocompounds on gene targets of osteoarthritis. ADV TRADIT MED (ADTM) 22, 99–106 (2022). https://doi.org/10.1007/s13596-021-00616-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13596-021-00616-0

Keywords

Search

Navigation