Skip to main content
SpringerLink
Log in

The effects of the Rheum ribes plant extract on inflammation, extracellular matrix remodeling, and obesity suggest a therapeutic potential

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

The prevalence of obesity is increasing in the world, and the Type II diabetes associated with obesity led researchers to seek alternative methods to treat these two chronic diseases. In the case of obesity and diabetes, changes occur in the levels of inflammatory mediators. A study was conducted to investigate the molecular mechanism of the Rheum ribes L. plant regarding obesity and inflammation.

Methods and Results

Differentiated 3T3-L1 mouse cell lines were used as an experimental model. A dose–response relationship was established to determine at what dose and time of treatment the R. ribes L. plant extract would act effectively. To assess expression on the transcriptional level, q-PCR analyses were performed. The primers to evaluate the expression levels of genes such as Dgat1, Lpl, Fasn, ColV, Il-6, and Mcp1, which are known to be associated with obesity and insulin resistance, inflammation, and cell skeletal restructuring was designed using NCBI sequences. 18S was chosen as the housekeeping gene for normalization.

Conclusion

It was found that applying 50 µg/mL and 100 µg/mL of R. ribes root extract to 3T3-L1 adipocyte cells for 24 and 48 h resulted in anti- obesity and anti-inflammatory effects on the genes examined at the transcriptional level. It is an effective study to understand the molecular mechanisms by which R. ribes, which is known to have anti-diabetic, anti-obesity and anti- inflammatory activities, and to establish a link between these activities.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Chen HC, Farese RV Jr (2000) DGAT and triglyceride synthesis: a new target for obesity treatment? Trends Cardiovasc Med 10(5):188–192. https://doi.org/10.1016/S1050-1738(00)00066-9

    Article  CAS  PubMed  Google Scholar 

  2. Liudvytska O, Kolodziejczyk-Czepas J (2022) A review on rhubarb-derived substances as modulators of cardiovascular risk factors—a special emphasis on anti-obesity action. Nutrients 14(10):2053. https://doi.org/10.3390/nu14102053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Organization WH (2022) WHO European regional obesity report 2022. World Health Organization, Regional Office for Europe

    Google Scholar 

  4. Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Investig 121(6):2111–2117. https://doi.org/10.1172/JCI57132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee J (2013) Adipose tissue macrophages in the development of obesity-induced inflammation, insulin resistance and type 2 diabetes. Arch Pharmacal Res 36(2):208–222. https://doi.org/10.1007/s12272-013-0023-8

    Article  CAS  Google Scholar 

  6. Ranganathan G, Unal R, Pokrovskaya I, Yao-Borengasser A, Phanavanh B, Lecka-Czernik B, Rasouli N, Kern PA (2006) The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment. J Lipid Res 47(11):2444–2450. https://doi.org/10.1194/jlr.M600248-JLR200

    Article  CAS  PubMed  Google Scholar 

  7. Sharifi-Rad M, Ozcelik B, Altın G, Daşkaya-Dikmen C, Martorell M, Ramírez-Alarcón K, Alarcón-Zapata P, Morais-Braga MFB, Carneiro JN, Leal ALAB (2018) Salvia spp. plants-from farm to food applications and phytopharmacotherapy. Trends Food Sci Technol 80:242–263

    Article  CAS  Google Scholar 

  8. Salehi B, Stojanović-Radić Z, Matejić J, Sharifi-Rad M, Kumar NVA, Martins N, Sharifi-Rad J (2019) The therapeutic potential of curcumin: A review of clinical trials. Eur J Med Chem 163:527–545

    Article  CAS  PubMed  Google Scholar 

  9. Bati B, Celik I, Turan A, Eray N, Alkan EE, Zirek AK (2020) Effect of isgin (Rheum ribes L.) on biochemical parameters, antioxidant activity and DNA damage in rats with obesity induced with high-calorie diet. Arch Physiol Biochem. https://doi.org/10.1080/13813455.2020.1819338

    Article  PubMed  Google Scholar 

  10. Islam MT, Ali ES, Mubarak MS (2020) Anti-obesity effect of plant diterpenes and their derivatives: a review. Phytother Res 34(6):1216–1225

    Article  PubMed  Google Scholar 

  11. Keser S, Keser F, Karatepe M, Kaygili O, Tekin S, Turkoglu I, Demir E, Yilmaz O, Kirbag S, Sandal S (2020) Bioactive contents, In vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts. Nat Prod Res 34(23):3353–3357. https://doi.org/10.1080/14786419.2018.1560294

    Article  CAS  PubMed  Google Scholar 

  12. Fazeli S 2016. Determination of phenolic and flavoniod compounds in rehum ribes. MS thesis. Middle East Technical University

  13. Andiç S, Tunçtürk Y, Ocak E, Köse S (2009) Some chemical characteristics of edible wild Rhubarb species (Rheum ribes L.). Res J Agric Biol Sci 5:973–977

    Google Scholar 

  14. Ekincialp A, Erdinc C, Turan S, Cakmakci O, Nadeem MA, Baloch FS, Sensoy S (2019) Genetic characterization of Rheum ribes (wild rhubarb) genotypes in Lake Van basin of turkey through ISSR and SSR markers. Int J Agric Biol 21(4):795–802

    CAS  Google Scholar 

  15. Raafat K, Aboul-Ela M, El-Lakany A (2014) Alloxan-induced diabetic thermal hyperalgesia, prophylaxis and phytotherapeutic effects of Rheum ribes L. in mouse model. Arch Pharm Res. https://doi.org/10.1007/s12272-014-0372-y

    Article  PubMed  Google Scholar 

  16. Uyar P, Coruh N, İscan M (2014) Evaluation of in vitro antioxidative, cytotoxic and apoptotic activities of Rheum ribes ethyl acetate extracts. J Plant Sci 2(6):339–346

    Article  Google Scholar 

  17. Abdulla KK, Taha EM, Rahim SM (2014) Phenolic profile, antioxidant, and antibacterial effects of ethanol and aqueous extracts of Rheum ribes L. roots. Pharm Lett 6(5):201–205

    Google Scholar 

  18. Nikbakht M-R, Esnaashari S, Heshmati Afshar F (2013) Chemical composition and general toxicity of essential oil extracted from the stalks and flowers of Rheum ribes L growing in Iran. J Rep Pharm Sci 2(2):165–170

    Google Scholar 

  19. Tartik M, Darendelioglu E, Aykutoglu G and Baydas G (2015) The various biological activities of Rheum ribes extract on different types of cell. Türk Doğa ve Fen Dergisi 4(1)

  20. Hamzeh S, Farokhi F, Heydari R, Manaffar R (2014) Renoprotective effect of hydroalcoholic extract of Rheum ribes root in diabetic female rats. Avicenna J phytomed 4(6):392

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ozbek H, Ceylan E, Kara M, Özgökçe F, Koyuncu M (2004) Hypoglycemic effect of Rheum ribes roots in alloxan induced diabetic and normal mice. Scand J Lab Animal Sci 31(2):113–115

    Google Scholar 

  22. Radhika R, Krishnakumari S, Umashankar V, Sudarsanam D (2010) Effect of enzymatic antioxidants of Rheum emodi inalloxan induced diabetic rats. Int J Biol Chem Sci 4(6):1905–1913

    Google Scholar 

  23. Kasabri V, Afifi FU, Hamdan I (2011) In vitro and in vivo acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine. J Ethnopharmacol 133(2):888–896. https://doi.org/10.1016/j.jep.2010.11.025

    Article  PubMed  Google Scholar 

  24. Fallah Huseini H, Heshmat R, Mohseni F, Jamshidi AH, Alavi S, Ahvasi M, Larijani B (2008) The efficacy of Rheum ribes L. stalk extract on lipid profile in hypercholesterolemic type II diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial. J Med Plants 7(27):92–97

    Google Scholar 

  25. Zaccardi F, Webb DR, Yates T, Davies MJ (2016) Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J 92(1084):63–69. https://doi.org/10.1136/postgradmedj-2015-133281

    Article  CAS  PubMed  Google Scholar 

  26. Ghafouri A, Jafari Karegar S, Hajiluian G, Hosseini S, Shidfar S, Kamalinejad M, Hosseini AF, Heydari I, Shidfar F (2023) The effects of aqueous and ethanolic extracts of Rheum ribes on insulin-resistance and apolipoproteins in patients with type 2 diabetes mellitus: a randomized controlled trial. BMC Complement Med Ther 23(1):1–11. https://doi.org/10.1186/s12906-023-03878-0

    Article  CAS  Google Scholar 

  27. Tokgöz HB, Altan F (2020) Hypericum perforatum L.: a medicinal plant with potential as a curative agent against obesity-associated complications. Mol Biol Rep 47(11):8679–8868. https://doi.org/10.1007/s11033-020-05912-7

    Article  CAS  PubMed  Google Scholar 

  28. Çınar Ayan İ, Çetinkaya S, Dursun HG, Süntar İ (2021) Bioactive compounds of Rheum ribes L. and its Anticancerogenic effect via Induction of Apoptosis and miR-200 family expression in human colorectal cancer cells. Nutr Cancer. https://doi.org/10.1080/01635581.2020.1792947

    Article  PubMed  Google Scholar 

  29. Huang DM, Hung Y, Ko BS, Hsu SC, Chen WH, Chien CL, Tsai CP, Kuo CT, Kang JC, Yang CS (2005) Highly efficient cellular labeling of mesoporous nanoparticles in human mesenchymal stem cells: implication for stem cell tracking. FASEB J 19(14):2014–2016. https://doi.org/10.1096/fj.05-4288fje

    Article  CAS  PubMed  Google Scholar 

  30. Uytan G, Tokgöz HB, Ünal R, Altan F (2021) Transcriptional analyses of the effects of Catharanthus roseus L. medicinal plant extracts on some markers related to obesity and inflammation in 3T3-L1 mouse cell lines. Biologia 76(1):297–306. https://doi.org/10.2478/s11756-020-00567-y

    Article  CAS  Google Scholar 

  31. Sahib NG, Hamid AA, Kitts D, Purnama M, Saari N, Abas F (2011) The effects of Morinda citrifolia, Momordica charantia and Centella asiatica extracts on lipoprotein lipase and 3t3-l1 preadipocytes. J Food Biochem 35(4):1186–1205. https://doi.org/10.1111/j.1745-4514.2010.00444.x

    Article  CAS  Google Scholar 

  32. Berndt J, Kovacs P, Ruschke K, Klöting N, Fasshauer M, Schön M, Körner A, Stumvoll M, Blüher M (2007) Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes. Diabetologia 50(7):1472–1480. https://doi.org/10.1007/s00125-007-0689-x

    Article  CAS  PubMed  Google Scholar 

  33. Liu X, Xu Q, Liu W, Yao G, Zhao Y, Xu F, Hayashi T, Fujisaki H, Hattori S, Tashiro S-i (2018) Enhanced migration of murine fibroblast-like 3T3-L1 preadipocytes on type I collagen-coated dish is reversed by silibinin treatment. Mol Cell Biochem 441(1):35–62. https://doi.org/10.1007/s11010-017-3173-z

    Article  CAS  PubMed  Google Scholar 

  34. Hsieh C-C, Chou M-J, Wang C-H (2017) Lunasin attenuates obesity-related inflammation in RAW264 7. cells and 3T3-L1 adipocytes by inhibiting inflammatory cytokine production. PLoS ONE 12(2):e0171969. https://doi.org/10.1371/journal.pone.0171969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zagotta I, Dimova EY, Debatin K-M, Wabitsch M, Kietzmann T, Fischer-Posovszky P (2015) Obesity and inflammation: reduced cytokine expression due to resveratrol in a human in vitro model of inflamed adipose tissue. Front Pharmacol 6:79. https://doi.org/10.3389/fphar.2015.00079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chooi YC, Ding C, Magkos F (2019) The epidemiology of obesity. Metabolism 92:6–10. https://doi.org/10.1016/j.metabol.2018.09.005

    Article  CAS  PubMed  Google Scholar 

  37. Spencer M, Unal R, Zhu B, Rasouli N, McGehee RE Jr, Peterson CA, Kern PA (2011) Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. J Clin Endocrinol Metab 96(12):E1990–E1998. https://doi.org/10.1210/jc.2011-1567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Naqishbandi AM, Josefsen K, Pedersen ME, Jäger AK (2009) Hypoglycemic activity of Iraqi Rheum ribes root extract. Pharm Biol 47(5):380–383. https://doi.org/10.1080/13880200902748478

    Article  CAS  Google Scholar 

  39. Rizzatti V, Boschi F, Pedrotti M, Zoico E, Sbarbati A, Zamboni M (2013) Lipid droplets characterization in adipocyte differentiated 3T3-L1 cells: size and optical density distribution. Eur J Histochem 57(3):24. https://doi.org/10.4081/ejh.2013.e24

    Article  CAS  Google Scholar 

  40. Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, Iida K, Okimura Y, Kaji H, Kitazawa S (2008) Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Lett 582(5):573–578. https://doi.org/10.1016/j.febslet.2008.01.023

    Article  CAS  PubMed  Google Scholar 

  41. Stienstra R, Kersten S (2011) Fight fat with DGAT 1. J Lipid Res 52(4):591–592. https://doi.org/10.1194/jlr.E014381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang H, Eckel RH (2009) Lipoprotein lipase: from gene to obesity. Am J Physiol-Endocrinol Metab 297(2):E271–E288. https://doi.org/10.1152/ajpendo.90920.2008

    Article  CAS  PubMed  Google Scholar 

  43. Senanayake GV, Maruyama M, Sakono M, Fukuda N, Morishita T, Yukizaki C, Kawano M, Ohta H (2004) The effects of bitter melon (Momordica charantia) extracts on serum and liver lipid parameters in hamsters fed cholesterol-free and cholesterol-enriched diets. J Nutr Sci Vitaminol 50(4):253–257. https://doi.org/10.3177/jnsv.50.253

    Article  CAS  PubMed  Google Scholar 

  44. Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Brönneke HS (2014) Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol 15(5):423–430. https://doi.org/10.1038/ni.2865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lee S-L, Chin T-Y, Tu S-C, Wang Y-J, Hsu Y-T, Kao M-C, Wu Y-C (2015) Purple sweet potato leaf extract induces apoptosis and reduces inflammatory adipokine expression in 3T3-L1 differentiated adipocytes. Evidence-Based Complement Altern Med. https://doi.org/10.1155/2015/126302

    Article  Google Scholar 

  46. Kowalska K, Olejnik A, Zielińska-Wasielica J, Olkowicz M (2019) Raspberry (Rubus idaeus L.) fruit extract decreases oxidation markers, improves lipid metabolism and reduces adipose tissue inflammation in hypertrophied 3T3-L1 adipocytes. J Funct Foods 62:103568. https://doi.org/10.1016/j.jff.2019.103568

    Article  CAS  Google Scholar 

  47. Gögebakan Ö, Osterhoff MA, Schüler R, Pivovarova O, Kruse M, Seltmann A-C, Mosig AS, Rudovich N, Nauck M, Pfeiffer AF (2015) GIP increases adipose tissue expression and blood levels of MCP-1 in humans and links high energy diets to inflammation: a randomised trial. Diabetologia 58(8):1759–1768. https://doi.org/10.1007/s00125-015-3618-4

    Article  CAS  PubMed  Google Scholar 

  48. Kang J-H, Kim C-S, Han I-S, Kawada T, Yu R (2007) Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett 581(23):4389–4396. https://doi.org/10.1016/j.febslet.2007.07.082

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Zekiye Buket YILMAZ for critical reading and language editing; Dr. Hasan YILDIRIM for identifying the plant material, and to Dr. Mehmet VAROL for his expertise and assistance in technical editing. This study was a master thesis of Hasret KAYA and was supported by the Scientific and Technological Research Council of Turkey (TUBITAK), 2210-C National Priority Fields Master’s Scholarship Program

Funding

This study was a master thesis of Hasret KAYA and was supported by the Scientific and Technological Research Council of Turkey (TUBITAK), 2210-C National Priority Fields Master's Scholarship Program. Türkiye Bilimsel ve Teknolojik Araştırma Kurumu,2210-C,Hasret KAYA

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science, Muğla Sıtkı Koçman University, 48000, Muğla, Kötekli, Turkey

    Hasret Kaya, Hilal Büşra Tokgöz, Resat Unal & Filiz Altan

  2. Denizli Vocational School of Health Services, Medical Services and Techniques Department, Pamukkale University, 20160, Denizli, Kınıklı, Turkey

    Hilal Büşra Tokgöz

Authors
  1. Hasret Kaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hilal Büşra Tokgöz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Resat Unal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filiz Altan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

FA principal investigator, provided funding, designed the study, and supervised the experiments, HK and HBT carried out laboratory studies and HK performed the statistical analysis and helped to draft the manuscript. RÜ helped to draft the manuscript and valuable scientific support and critical reading. All these authors have substantial contributions to the final manuscript and approved this submission.

Corresponding author

Correspondence to Filiz Altan.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

None.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Research involving human and animal participants

This article does not contain any studies with human or animal subjects.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaya, H., Tokgöz, H.B., Unal, R. et al. The effects of the Rheum ribes plant extract on inflammation, extracellular matrix remodeling, and obesity suggest a therapeutic potential. Mol Biol Rep 50, 5223–5232 (2023). https://doi.org/10.1007/s11033-023-08478-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08478-2

Keywords

Search

Navigation