Efficacy of Black Mulberry Mouthwash for Prevention of Chemotherapy-Induced Oral Mucositis: A Double-Blind Randomized Clinical Trial
The Efficacy of Black Mulberry on Oral Mucositis
-
Anahita Ghorbani
,
Zahra Ghasemzadeh
,
Seyed Mohammad Mehdi Ghaffari Hamedani
,
Jafar Akbari
,
Mahmood Moosazadeh
,
Fatemeh Mirzaee
,
Maryam Zamanzadeh
,
Somayeh Shahani
Abstract
Objectives: Oral mucositis is a common side effect of cancer chemotherapy. Traditionally, black mulberry or Morus nigra L. (M. nigra) fruit is used for treatment of oral inflammatory conditions. The aim of the present study was to evaluate the efficacy of black mulberry mouthwash for prevention of oral mucositis caused by 5-fluorouracil.
Materials and Methods: This double-blind clinical trial was performed on 62 patients with colon adenocarcinoma undergoing chemotherapy with 5-fluorouracil. The patients were randomly divided into two groups (n=31) to receive 10mL of 1% black mulberry juice (BMJ) or the placebo mouthwash, 3 times a day for 2 weeks. The patients were followed up for 7 and 14 days after the treatment onset to record the degree of mucositis according to the World Health Organization (WHO) criteria. Spectrophotometric assays were conducted for quantitative analysis of the bioactive compounds in the composition of BMJ. Data were analyzed with the Chi-square and Fisher’s exact tests (alpha=0.05).
Results: The severity of oral mucositis was slightly, but not significantly, lower in the follow-up sessions in the BMJ mouthwash group (P>0.05). The total anthocyanin content of the BMJ was calculated to be 506.5±3.51 and 476.2±7.99mg cyanidin 3-glucoside equivalent per 100g of dried juice, before and after the sterilization process, respectively.
Conclusion: The present results showed that the BMJ mouthwash can be effective as an adjunct treatment to reduce the incidence and severity of mucositis in patients undergoing chemotherapy. Anthocyanins appear to be mainly involved in the observed effect.
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18. Khandpur P, Gogate PR. Evaluation of ultrasound based sterilization approaches in terms of shelf life and quality parameters of fruit and vegetable juices. Ultrason Sonochem. 2016 Mar;29:337-53.
19. Tiwari B, O'donnell C, Cullen P. Effect of non thermal processing technologies on the anthocyanin content of fruit juices. Trends Food Sci Technol. 2009 Apr; 20(3-4):137-45.
20. Lee J, Durst RW, Wrolstad RE. Determination of total monomeric anthocyanin pigment content of fruit juices, beverages, natural colorants, and wines by the pH differential method: collaborative study. J AOAC Int. 2005 Sep;88(5):1269-78.
21. Makkar HPS, Blummel M, Borowy NK, Becker K. Gravimetric determination of tannins and their correlations with chemical and protein precipitation methods. J Sci Food Agric. 1993;61(2):161-5.
22. Sembiring EN, Elya B, Sauriasari R. Phytochemical screening, total flavonoid and total phenolic content and antioxidant activity of different parts of Caesalpinia bonduc (L.) Roxb. Pharmacogn. 2018;10(1): 123-7.
23. Chimhete PN, Machona O, Mangoyi R. Preparation of an antibacterial herbal mouthwash Containing extract of Erythrina Abyssinica. Global J Res Dent Sci. 2021 Nov;1(3):67-72.
24. Ashktorab T, Yazdani Z, Mojab F, Majd HA, Madani H. Preventive effects of an oral rinse peppermint essence on chemotherapy-induced oral mucositis. Koomesh. 2010 Sep;12(1):8-13.
25. Kong M, Hwang DS, Yoon SW, Kim J. The effect of clove-based herbal mouthwash on radiation-induced oral mucositis in patients with head and neck cancer: a single-blind randomized preliminary study. Onco Targets and therapy. 2016 Jul;9:4533-8.
26. Kamiloglu S, Serali O, Unal N, Capanoglu E. Antioxidant activity and polyphenol composition of black mulberry (Morus nigra L.) products. J Berry Res. 2013 Jan;3(1):41-51.
27. Harman M, Ovayolu N, Ovayolu O. The effect of three different solutions on preventing oral mucositis in cancer patients undergoing stem cell transplantation: a non-randomized controlled trial: A Turkish study-non-randomized trial. J Pak Med Assoc. 2019;69(6):811-6.
28. Doğan MD, Can G, Meral R. Effectiveness of black mulberry molasses in prevention of radiotherapy-induced oral mucositis: a randomized controlled study in head and neck cancer patients. J Altern Complement Med. 2017 Dec;23(12):971-9.
29. Yiğitaslan S, Özkaraman A, Açıkgöz A, Alparslan GB, Toprak Ç, Göger F, et al. Therapeutic potential of Morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats. Osmangazi Tıp Dergisi. 2020 Mar;24(4):363-72.
30. Chen H, Yu W, Chen G, Meng S, Xiang Z, He N. Antinociceptive and antibacterial properties of anthocyanins and flavonols from fruits of black and non-black mulberries. Molecules. 2017 Dec;23(1):4.
31. Naibaho EN, Dharmajaya R, Harahap IA. Effectiveness of oral care using normal saline and baking soda towards pain and comfort in mucositis patients undergoing chemotherapy. Indian J Public Health Res Dev. 2020 Oct;11(10):222-8.
32. Hashemi A, Bahrololoumi Z, Khaksar Y, Saffarzadeh N, Neamatzade H, Foroughi E. Mouth-rinses for the prevention of chemotherapy induced oral mucositis in children: a systematic review. Iran J Ped Hematol Oncol. 2015;5(2):106-12.
33. Weber F, Larsen LR. Influence of fruit juice processing on anthocyanin stability. Int Food Res J. 2017 Oct;100:354-65.
34. Tomas M, Toydemir G, Boyacioglu D, Hall R, Beekwilder J, Capanoglu E. The effects of juice processing on black mulberry antioxidants. Food chem. 2015 Nov;186:277-84.
35. Hassimotto N, Genovese M, Lajolo F. Identification and characterisation of anthocyanins from wild mulberry (Morus nigra L.) growing in Brazil. Food Sci Technol Int. 2007 Feb;13(1):17-25.
36. Pergola C, Rossi A, Dugo P, Cuzzocrea S, Sautebin L. Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. Nitric oxide. 2006 Aug;15(1):30-9.
37. Morais CA, de Rosso VV, Estadella D, Pisani LP. Anthocyanins as inflammatory modulators and the role of the gut microbiota. J Nutr Biochem. 2016 Jul; 33:1-7.
2. Naidu MUR, Ramana GV, Rani PU, Suman A, Roy P. Chemotherapy-induced and/or radiation therapy-induced oral mucositis-complicating the treatment of cancer. Neoplasia. 2004 Sep;6(5):423-31.
3. Rajesh V Lalla STS, Duoglas E petersone. Management of oral mucositis in patients with cancer. Dent Clin North Am. 2008 Jan;52(1):61-8.
4. D'Hondt Lionel LC, Marc A, Jean-Luc C. Oral mucositis induced by anticancer treatments: physiopathology and treatments. Ther Clin Risk Manage. 2006;2(2):159-68.
5. Nagi R, Patil DJ, Rakesh N, Jain S, Sahu S. Natural agents in the management of oral mucositis in cancer patients-systematic review. J Oral Biol Craniofac Res. 2018 Sep;8(3):245-54.
6. Okatan V, Polat M, Askin MA. Some physico-chemical characteristics of Black mulberry (Morus nigra L.) in Bitlis. Sci Papers Ser B Hortic. 2016;60:27-30.
7. Chen H, Pu J, Liu D, Yu W, Shao Y, Yang G, et al. Anti-inflammatory and antinociceptive properties of flavonoids from the fruits of black mulberry (Morus nigra L.). PloS one. 2016 Apr;11(4):e0153080.
8. Darias-Martín J, Lobo-Rodrigo G, Hernández-Cordero J, Díaz-Díaz E, Díaz-Romero C. Alcoholic beverages obtained from black mulberry. Food Sci Biotechnol. 2003 Jun;41(2):173-6.
9. Hussain F, Rana Z, Shafique H, Malik A, Hussain Z. Phytopharmacological potential of different species of Morus alba and their bioactive phytochemicals: A review. Asian Pac J Trop Biomed. 2017 Oct;7(10):950-6.
10. Rodrigues EL, Marcelino G, Silva GT, Figueiredo PS, Garcez WS, Corsino J, et al. Nutraceutical and medicinal potential of the Morus species in metabolic dysfunctions. Int J Mol Sci. 2019 Jan;20(2):301.
11. Zhang Q-Y, Wang F-X, Jia K-K, Kong L-D. Natural product interventions for chemotherapy and radiotherapy-induced side effects. Front Pharmacol. 2018 Nov;9:1253.
12. Mandal A. Nutraceutical and Medicinal Property of Mulberry Fruits: A Review on Its Pharmacological Potential. Preprints. 2020; 2020040105.
13. Huang HP, Ou TT, Wang CJ. Mulberry (桑葚子 Sang Shèn Zǐ) and its bioactive compounds, the chemoprevention effects and molecular mechanisms in vitro and in vivo. J Tradit Complement. 2013 Jan;3(1):7-15.
14. Eslami Farouji A, Khodayari H. Ethnomedicinal plants of Farouj district, North Khorasan province, Iran. J Herb Med. 2016;7(1):21-36.
15. Kim I, Lee J. Variations in anthocyanin profiles and antioxidant activity of 12 genotypes of mulberry (Morus spp.) fruits and their changes during processing. Antioxidants. 2020 Mar;9(3):242.
16. Zhou R, Li D, Kou Q, Jiao Z, Ning Z. Evaluation of anti-inflammatory, antimicrobial and wound healing activity of Morus nigra. S Afr J Bot. 2019 Aug;124:540-5.
17. Akkol EK, Süntar I, Keleş H, Sezik E, Gürler G. Bioassay-guided isolation and characterization of wound healer compounds from Morus nigra L.(Moraceae). Rec Nat Prod. 2015 Oct;9(4):123-7.
18. Khandpur P, Gogate PR. Evaluation of ultrasound based sterilization approaches in terms of shelf life and quality parameters of fruit and vegetable juices. Ultrason Sonochem. 2016 Mar;29:337-53.
19. Tiwari B, O'donnell C, Cullen P. Effect of non thermal processing technologies on the anthocyanin content of fruit juices. Trends Food Sci Technol. 2009 Apr; 20(3-4):137-45.
20. Lee J, Durst RW, Wrolstad RE. Determination of total monomeric anthocyanin pigment content of fruit juices, beverages, natural colorants, and wines by the pH differential method: collaborative study. J AOAC Int. 2005 Sep;88(5):1269-78.
21. Makkar HPS, Blummel M, Borowy NK, Becker K. Gravimetric determination of tannins and their correlations with chemical and protein precipitation methods. J Sci Food Agric. 1993;61(2):161-5.
22. Sembiring EN, Elya B, Sauriasari R. Phytochemical screening, total flavonoid and total phenolic content and antioxidant activity of different parts of Caesalpinia bonduc (L.) Roxb. Pharmacogn. 2018;10(1): 123-7.
23. Chimhete PN, Machona O, Mangoyi R. Preparation of an antibacterial herbal mouthwash Containing extract of Erythrina Abyssinica. Global J Res Dent Sci. 2021 Nov;1(3):67-72.
24. Ashktorab T, Yazdani Z, Mojab F, Majd HA, Madani H. Preventive effects of an oral rinse peppermint essence on chemotherapy-induced oral mucositis. Koomesh. 2010 Sep;12(1):8-13.
25. Kong M, Hwang DS, Yoon SW, Kim J. The effect of clove-based herbal mouthwash on radiation-induced oral mucositis in patients with head and neck cancer: a single-blind randomized preliminary study. Onco Targets and therapy. 2016 Jul;9:4533-8.
26. Kamiloglu S, Serali O, Unal N, Capanoglu E. Antioxidant activity and polyphenol composition of black mulberry (Morus nigra L.) products. J Berry Res. 2013 Jan;3(1):41-51.
27. Harman M, Ovayolu N, Ovayolu O. The effect of three different solutions on preventing oral mucositis in cancer patients undergoing stem cell transplantation: a non-randomized controlled trial: A Turkish study-non-randomized trial. J Pak Med Assoc. 2019;69(6):811-6.
28. Doğan MD, Can G, Meral R. Effectiveness of black mulberry molasses in prevention of radiotherapy-induced oral mucositis: a randomized controlled study in head and neck cancer patients. J Altern Complement Med. 2017 Dec;23(12):971-9.
29. Yiğitaslan S, Özkaraman A, Açıkgöz A, Alparslan GB, Toprak Ç, Göger F, et al. Therapeutic potential of Morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats. Osmangazi Tıp Dergisi. 2020 Mar;24(4):363-72.
30. Chen H, Yu W, Chen G, Meng S, Xiang Z, He N. Antinociceptive and antibacterial properties of anthocyanins and flavonols from fruits of black and non-black mulberries. Molecules. 2017 Dec;23(1):4.
31. Naibaho EN, Dharmajaya R, Harahap IA. Effectiveness of oral care using normal saline and baking soda towards pain and comfort in mucositis patients undergoing chemotherapy. Indian J Public Health Res Dev. 2020 Oct;11(10):222-8.
32. Hashemi A, Bahrololoumi Z, Khaksar Y, Saffarzadeh N, Neamatzade H, Foroughi E. Mouth-rinses for the prevention of chemotherapy induced oral mucositis in children: a systematic review. Iran J Ped Hematol Oncol. 2015;5(2):106-12.
33. Weber F, Larsen LR. Influence of fruit juice processing on anthocyanin stability. Int Food Res J. 2017 Oct;100:354-65.
34. Tomas M, Toydemir G, Boyacioglu D, Hall R, Beekwilder J, Capanoglu E. The effects of juice processing on black mulberry antioxidants. Food chem. 2015 Nov;186:277-84.
35. Hassimotto N, Genovese M, Lajolo F. Identification and characterisation of anthocyanins from wild mulberry (Morus nigra L.) growing in Brazil. Food Sci Technol Int. 2007 Feb;13(1):17-25.
36. Pergola C, Rossi A, Dugo P, Cuzzocrea S, Sautebin L. Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. Nitric oxide. 2006 Aug;15(1):30-9.
37. Morais CA, de Rosso VV, Estadella D, Pisani LP. Anthocyanins as inflammatory modulators and the role of the gut microbiota. J Nutr Biochem. 2016 Jul; 33:1-7.
| Issue | Vol 22 (Continuously Published Article-Based) | |
| Section | Original Article | |
| Keywords | ||
| Morus Mouthwashes Mucositis Adenocarcinoma Fluorouracil | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Ghorbani A, Ghasemzadeh Z, Ghaffari Hamedani SMM, Akbari J, Moosazadeh M, Mirzaee F, Zamanzadeh M, Shahani S. Efficacy of Black Mulberry Mouthwash for Prevention of Chemotherapy-Induced Oral Mucositis: A Double-Blind Randomized Clinical Trial. Front Dent. 2025;22.
