Skip to main content
SpringerLink
Log in

Jaboticaba (Myrciaria cauliflora) Fruit Extract Suppressed Aberrant Crypt Formation in 1,2-Dimetylhydrazine-Induced Rats

  • Research
  • Published:
Plant Foods for Human Nutrition Aims and scope Submit manuscript

Abstract

Early intervention can significantly improve the colorectal cancer survival rate. Foods rich in phenolic compounds, such as jaboticaba (Myrciaria cauliflora), may prevent tumorigenesis. We investigated the effectivity of jaboticaba whole fruit ethanolic extract (FEX) in suppressing aberrant crypt foci (ACF), the earliest lesion of colorectal cancer (CRC), in 1,2-dimethylhydrazine (DMH)-induced rats and the underlying mechanisms related to the gut microbiota composition and short chain fatty acid (SCFA). This study was approved by the Institutional Animal Care and Use Committee (IACUC) of Providence University (Trial Registration Number 20180419A01, registration date: 22 December 2018). The FEX contains gallic acid and an especially high ellagic acid concentration of 54.41 ± 1.80 and 209.79 ± 2.49 mg/100 g FEX. The highest total ACF number (150.00 ± 43.86) was recorded in the DMH control (D) group. After 56 days of oral FEX treatment, the total ACF number in the low FEX dosage (DL) group was significantly lower compared to the D group (p < 0.05). The large-sized ACF (> 5 foci), which has a higher probability of progressing to later stage, was significantly decreased in the high FEX dosage (DH) group. The 16s rDNA metagenomic sequencing of the cecal material revealed that the CRC biomarker Lachnoclostridium was significantly suppressed in the DH group (p < 0.05), whereas some SCFA-producing taxa and the cecal butyrate concentration were significantly elevated in the DL and DH groups (p < 0.05). This study demonstrated the potential of jaboticaba whole fruit in CRC prevention, especially in the initial stage, by shifting gut microbiota composition and improving cecal butyrate level.

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

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available upon reasonable request.

Abbreviations

ACF:

Aberrant crypt foci

ANOSIM:

Analysis of similarities

AOM:

Azoxymethane

CRC:

Colorectal cancer

DMH:

1,2-dimethylhydrazine

FEX:

Jaboticaba whole fruit extract

LEFse:

Linear discriminant analysis effect size

NMDS:

Nonmetric multidimensional scaling

PCOA:

Principal coordinates analysis

SCFA:

Short chain fatty acid

SD:

Sprague-Dawley

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72(1):7–33. https://doi.org/10.3322/caac.21708

    Article  PubMed  Google Scholar 

  3. Society AC (2022) Cancer facts & Fig. 2022. American Cancer Society. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html. Accessed 13 October 2022

  4. Bird RP (1995) Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Lett 93(1):55–71. https://doi.org/10.1016/0304-3835(95)03788-X

    Article  CAS  PubMed  Google Scholar 

  5. Takayama T, Katsuki S, Takahashi Y, Ohi M, Nojiri S, Sakamaki S, Kato J, Kogawa K, Miyake H, Niitsu Y (1998) Aberrant crypt foci of the colon as precursors of adenoma and cancer. N Engl J Med 339(18):1277–1284. https://doi.org/10.1056/NEJM199810293391803

    Article  CAS  PubMed  Google Scholar 

  6. Perše M, Cerar A (2010) Morphological and molecular alterations in 1,2-dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. J Biomed Biotechnol 2011. https://doi.org/10.1155/2011/473964

  7. Rawla P, Sunkara T, Barsouk A (2019) Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Gastroenterol Rev 14(2):89–103. https://doi.org/10.5114/pg.2018.81072

    Article  CAS  Google Scholar 

  8. Stone WL, Krishnan K, Campbell SE, Palau VE (2014) The role of antioxidants and pro-oxidants in colon cancer. World J Gastrointest Oncol 6(3):55. https://doi.org/10.4251/wjgo.v6.i3.55

    Article  PubMed  PubMed Central  Google Scholar 

  9. Salomão LC, de Siqueira DL, Aquino CF, de Lins LC (2018) Jabuticaba—Myrciaria spp. Exotic fruits. Elsevier, pp 237–244

  10. Inada KOP, Oliveira AA, Revorêdo TB, Martins ABN, Lacerda ECQ, Freire AS, Braz BF, Santelli RE, Torres AG, Perrone D (2015) Screening of the chemical composition and occurring antioxidants in jabuticaba (Myrciaria jaboticaba) and jussara (Euterpe edulis) fruits and their fractions. J Funct Foods 17:422–433. https://doi.org/10.1016/j.jff.2015.06.002

    Article  CAS  Google Scholar 

  11. Reynertson KA, Wallace AM, Adachi S, Gil RR, Yang H, Basile MJ, D’Armiento J, Weinstein IB, Kennelly EJ (2006) Bioactive depsides and anthocyanins from jaboticaba (Myrciaria cauliflora). J Nat Prod 69(8):1228–1230. https://doi.org/10.1021/np0600999

    Article  CAS  PubMed  Google Scholar 

  12. Plaza M, Batista ÂG, Cazarin CBB, Sandahl M, Turner C, Östman E, Júnior MRM (2016) Characterization of antioxidant polyphenols from Myrciaria jaboticaba peel and their effects on glucose metabolism and antioxidant status: a pilot clinical study. Food Chem 211:185–197. https://doi.org/10.1016/j.foodchem.2016.04.142

    Article  CAS  PubMed  Google Scholar 

  13. Alam MN, Almoyad M, Huq F (2018) Polyphenols in colorectal cancer: current state of knowledge including clinical trials and molecular mechanism of action. Biomed Res Int 2018. https://doi.org/10.1155/2018/4154185

  14. do Carmo MAV, Fidelis M, de Oliveira PF, Feitoza LQ, Marques MJ, Ferreira EB, Oh WY, Shahidi F, Hellström J, Almeida LA (2021) Ellagitannins from jabuticaba (Myrciaria jaboticaba) seeds attenuated inflammation, oxidative stress, aberrant crypt foci, and modulated gut microbiota in rats with 1,2-dimethyl hydrazine-induced colon carcinogenesis. Food Chem Toxicol 154:112287. https://doi.org/10.1016/j.fct.2021.112287

    Article  CAS  PubMed  Google Scholar 

  15. Kasprzak-Drozd K, Oniszczuk T, Stasiak M, Oniszczuk A (2021) Beneficial effects of phenolic compounds on gut microbiota and metabolic syndrome. Int J Mol Sci 22(7):3715. https://doi.org/10.3390/ijms22073715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. De Santis S, Liso M, Vacca M, Verna G, Cavalcanti E, Coletta S, Calabrese FM, Eri R, Lippolis A, Armentano R (2021) Dysbiosis triggers ACF development in genetically predisposed subjects. Cancers 13(2):283. https://doi.org/10.3390/cancers13020283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Selma MV, Espin JC, Tomas-Barberan FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57(15):6485–6501. https://doi.org/10.1021/jf902107d

    Article  CAS  PubMed  Google Scholar 

  18. Anderson JC, Swede H, Rustagi T, Protiva P, Pleau D, Brenner BM, Rajan TV, Heinen CD, Levine JB, Rosenberg DW (2012) Aberrant crypt foci as predictors of colorectal neoplasia on repeat colonoscopy. Cancer Causes Control 23(2):355–361. https://doi.org/10.1007/s10552-011-9884-7

    Article  PubMed  Google Scholar 

  19. Thomas F, Hehemann J-H, Rebuffet E, Czjzek M, Michel G (2011) Environmental and gut Bacteroidetes: the food connection. Front Microbiol 2:93. https://doi.org/10.3389/fmicb.2011.00093

    Article  PubMed  PubMed Central  Google Scholar 

  20. Liang JQ, Li T, Nakatsu G, Chen YX, Yau TO, Chu E, Wong S, Szeto CH, Ng SC, Chan FK (2020) A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer. Gut 69(7):1248–1257. https://doi.org/10.1136/gutjnl-2019-318532

    Article  CAS  PubMed  Google Scholar 

  21. Goncalves P, Martel F (2016) Regulation of colonic epithelial butyrate transport: focus on colorectal cancer. Porto Biomed J 1(3):83–91. https://doi.org/10.1016/j.pbj.2016.04.004

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mirzaei R, Afaghi A, Babakhani S, Sohrabi MR, Hosseini-Fard SR, Babolhavaeji K, Akbari SKA, Yousefimashouf R, Karampoor S (2021) Role of microbiota-derived short-chain fatty acids in cancer development and prevention. Biomed Pharmacother 139:111619. https://doi.org/10.1016/j.biopha.2021.111619

    Article  CAS  PubMed  Google Scholar 

  23. Perrin P, Pierre F, Patry Y, Champ M, Berreur M, Pradal G, Bornet F, Meflah K, Menanteau J (2001) Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Gut 48(1):53–61. https://doi.org/10.1136/gut.48.1.53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nogal A, Louca P, Zhang X, Wells PM, Steves CJ, Spector TD, Falchi M, Valdes AM, Menni C (2021) Circulating levels of the short-chain fatty acid acetate mediate the effect of the gut microbiome on visceral fat. Front Microbiol:1943. https://doi.org/10.3389/fmicb.2021.711359

    Article  Google Scholar 

  25. Daniel EM, Krupnick AS, Heur Y-H, Blinzler JA, Nims RW, Stoner GD (1989) Extraction, stability, and quantitation of ellagic acid in various fruits and nuts. J Food Compos Anal 2(4):338–349. https://doi.org/10.1016/0889-1575(89)90005-7

    Article  CAS  Google Scholar 

  26. Kumar KN, Raja SB, Vidhya N, Devaraj SN (2012) Ellagic acid modulates antioxidant status, ornithine decarboxylase expression, and aberrant crypt foci progression in 1,2-dimethylhydrazine-instigated colon preneoplastic lesions in rats. J Agric Food Chem 60(14):3665–3672. https://doi.org/10.1021/jf204128z

    Article  CAS  PubMed  Google Scholar 

  27. Giftson JS, Jayanthi S, Nalini N (2010) Chemopreventive efficacy of gallic acid, an antioxidant and anticarcinogenic polyphenol, against 1,2-dimethylhydrazine induced rat colon carcinogenesis. Investig New Drugs 28(3):251–259. https://doi.org/10.1007/s10637-009-9241-9

    Article  CAS  Google Scholar 

  28. Núñez-Gómez V, Periago MJ, Navarro-González I, Campos-Cava MP, Baenas N, González-Barrio R (2021) Influence of raspberry and its dietary fractions on the in vitro activity of the Colonic Microbiota from normal and overweight subjects. Plant Foods Hum Nutr 76(4):494–500. https://doi.org/10.1007/s11130-021-00923-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rodríguez-Daza MC, Pulido-Mateos EC, Lupien-Meilleur J, Guyonnet D, Desjardins Y, Roy D (2021) Polyphenol-mediated gut microbiota modulation: toward prebiotics and further. Front Nutr 8:689456. https://doi.org/10.3389/fnut.2021.689456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim YS, Milner JA (2007) Dietary modulation of colon cancer risk. J Nutr 137(11):2576S–2579. https://doi.org/10.1093/jn/137.11.2576S. S

    Article  PubMed  Google Scholar 

  31. Fidelis M, Santos JS, Escher GB, Rocha RS, Cruz AG, Cruz TM, Marques MB, Nunes JB, do, Carmo MAV, de Almeida LA (2021) Polyphenols of jabuticaba [Myrciaria jaboticaba (Vell.) O. Berg] seeds incorporated in a yogurt model exert antioxidant activity and modulate gut microbiota of 1,2-dimethylhydrazine-induced colon cancer in rats. Food Chem 334:127565. https://doi.org/10.1016/j.foodchem.2020.127565

Download references

Acknowledgements

This research was supported by the Ministry of Science and Technology, R.O.C. Taiwan (MOST 110-2320-B-126-003-MY3). Its financial support is greatly appreciated.

Funding

This study was supported by Ministry of Science and Technology, R.O.C. Taiwan (MOST 110-2320-B-126-003-MY3).

Author information

Authors and Affiliations

  1. Department of Food and Nutrition, Providence University, No. 200, Section 7, Taiwan Blvd, Shalu District, Taichung City, 43301, Republic of China (Taiwan)

    Katharina Ardanareswari, Webiana Lowisia & Yun-Chin Chung

  2. Department of Food Technology, Soegijapranata Catholic University, Semarang, Indonesia

    Katharina Ardanareswari, Webiana Lowisia & Bernadeta Soedarini

  3. Graduate Institute of Veterinary Pathobiology, National Chung-Hsing University, Taichung City, Republic of China (Taiwan)

    Jiunn-Wang Liao

Authors
  1. Katharina Ardanareswari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Webiana Lowisia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernadeta Soedarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiunn-Wang Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun-Chin Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.A. and W.L. conducted animal study, data collections, and almost all the assays. K.A. did the data analysis. B.S. and Y.C. designed the study and supervised the research. J.L. supervised animal study. K.A. and Y.C. prepared the manuscript which then reviewed by all authors.

Corresponding author

Correspondence to Yun-Chin Chung.

Ethics declarations

Ethical Approval

This study was approved by Institutional Animal Care and Use Committee (IACUC) of Providence University (Trial Registration Number 20180419A01, registration date 22 December 2018).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare that there is no conflict of interests.

Additional information

Publisher’s Note

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

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

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

Ardanareswari, K., Lowisia, W., Soedarini, B. et al. Jaboticaba (Myrciaria cauliflora) Fruit Extract Suppressed Aberrant Crypt Formation in 1,2-Dimetylhydrazine-Induced Rats. Plant Foods Hum Nutr 78, 286–291 (2023). https://doi.org/10.1007/s11130-023-01051-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-023-01051-z

Keywords

Search

Navigation