Medicinal Plants for Chemoradiotherapy-Induced Oral Mucositis: A Review of Clinical Studies
AbstractOral mucositis is one of the severe complications of chemoradiotherapy in patients with cancer. Current treatments such as artificial saliva, antimicrobial agents, and local analgesics could not fully satisfy patients and thus, further investigations are essential. Medicinal plants, containing a wide variety of phytochemicals may be suitable suggestions to be investigated for the management of this complication in cancer patients. To review current literature regarding the effectiveness of herbal preparations in chemoradiotherapy-induced oral mucositis, electronic databases including PubMed, Scopus, and Cochrane library were searched using "mucositis" or "xerostomia" or "dry mouth" in the title/abstract, and "plant" or "extract" or "herb" or "phytochemical" keywords in the whole text up to August 2017. A total of 14 clinical trials were finally included. Aloe vera (aloe), Matricaria chamomilla (German chamomile), Malva sylvestris (high mallow), and Alcea digitata (hollyhock) are the most evident medicinal plants useful for the management of oral mucositis and xerpstomia. Mucilage, flavonoids, flavonolignans and terpenoids are the active ingredients which show soothing effect on the lesions of oral cavity. Herbal preparations could reduce the duration of ulceration, ulcer severity, pain and use of analgesics, as well as dysphagia and the need for total parenteral nutrition. In conclusion, medicinal plants are capable of improving chemoradiotherapy-induced oral mucositis and xerostomia in patients with cancer. Future well-designed clinical trials are required for further confirmation of the safety and efficacy of medicinal plants for the management of oral mucositis.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Davatgaran-Taghipour Y, Masoomzadeh S, Farzaei MH, Bahramsoltani R, Karimi-Soureh Z, Rahimi R, Abdollahi M. Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective. Int J Nanomedicine 2017;12:2689-2702.
Naidu MU, Ramana GV, Rani PU, Mohan IK, Suman A, Roy P. Chemotherapy-induced and/or radiation therapy-induced oral mucositis--complicating the treatment of cancer. Neoplasia 2004;6:423-431.
Rodríguez-Caballero A, Torres-Lagares D, Robles-García M, Pachón-Ibáñez J, González-Padilla D, Gutiérrez-Pérez JL. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg 2012;41:225-238.
Farzaei MH, Abdollahi M, Rahimi R. Role of dietary polyphenols in the management of peptic ulcer. World J Gastroenterol 2015; 21:6499-6517.
Hosein Farzaei M, Abbasabadi Z, Reza Shams-Ardekani M, Abdollahi M, Rahimi R. A comprehensive review of plants and their active constituents with wound healing activity in traditional Iranian medicine. Wounds 2014;26:197-206.
Budovsky A, Yarmolinsky L, Ben-Shabat S. Effect of medicinal plants on wound healing. Wound Repair Regen 2015; 23(2):171-83.
Farzaei MH, Bahramsoltani R, Rahimi R. Phytochemicals as Adjunctive with Conventional Anticancer Therapies. Curr Pharm Des 2016; 22:4201-4218.
Bahramsoltani R, Farzaei MH, Rahimi R. Medicinal plants and their natural components as future drugs for the treatment of burn wounds: an integrative review. Arch Dermatol Res 2014;306:601-617.
http://www.itis.gov.org [Accessed: August 2017].
Ali SI, Gopalakrishnan B, Venkatesalu V. Pharmacognosy, Phytochemistry and Pharmacological Properties of Achillea millefolium L.: A Review. Phytother Res 2017;31:1140-1161.
Miranzadeh S, Adib-Hajbaghery M, Soleymanpoor L, Ehsani M. Effect of adding the herb Achillea millefolium on mouthwash on chemotherapy induced oral mucositis in cancer patients: A double-blind randomized controlled trial. Eur J Oncol Nurs 2015;19:207-213.
Radha MH, Laxmipriya NP. Evaluation of biological properties and clinical effectiveness of Aloe vera: A systematic review. J Tradit Complement Med 2014;5:21-26.
Ali S, Wahbi W. The efficacy of aloe vera in management of oral lichen planus: a systematic review and meta-analysis. Oral Dis 2017; 23:913-918.
Nair GR, Naidu GS, Jain S, Nagi R, Makkad RS, Jha A. Clinical Effectiveness of Aloe Vera in the Management of Oral Mucosal Diseases- A Systematic Review. J Clin Diagn Res 2016;10:ZE01-ZE07.
Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, Koong A, Goffinet D, Le QT. Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms. Int J Radiat Oncol Biol Phys 2004;60:171-177.
Momm F, Volegova-Neher NJ, Schulte-Mönting J, Guttenberger R. Different saliva substitutes for treatment of xerostomia following radiotherapy. A prospective crossover study. Strahlenther Onkol 2005;181:231-236.
Puataweepong P, Dhanachai M, Dangprasert S, Sithatani C, Sawangsilp T, Narkwong L, Puttikaran P, Intragumtornchai T. The efficacy of oral Aloe vera juice for radiation induced mucositis in head and neck cancer patients: a double-blind placebo-controlled study. Asian Biomed 2009;3:375-382.
Basch E, Bent S, Foppa I, Haskmi S, Kroll D, Mele M, Szapary P, Ulbricht C, Vora M, Yong S; Natural Standard Research Collaboration. Marigold (Calendula officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration. J Herb Pharmacother 2006;6:135-159.
Kodiyan J, Amber KT. A Review of the Use of Topical Calendula in the Prevention and Treatment of Radiotherapy-Induced Skin Reactions. Antioxidants (Basel) 2015;4:293-303.
Babaee N, Moslemi D, Khalilpour M, Vejdani F, Moghadamnia Y, Bijani A, Baradaran M, Kazemi MT, Khalilpour A, Pouramir M, Moghadamnia AA. Antioxidant capacity of calendula officinalis flowers extract and prevention of radiation induced oropharyngeal mucositis in patients with head and neck cancers: a randomized controlled clinical study. Daru 2013;21:18.
You WC, Hsieh CC, Huang JT. Effect of extracts from indigowood root (Isatis indigotica Fort.) on immune responses in radiation-induced mucositis. J Altern Complement Med 2009;15:771-778.
Meng LJ, Guo QL, Xu CB, Zhu CG, Liu YF, Chen MH, Lin S, Li YH, Jiang JD, Shi JG. Diglycosidic indole alkaloid derivatives from an aqueous extract of Isatis indigotica roots. J Asian Nat Prod Res 2017;19:529-540.
Zhang W, Zheng X, Cheng N, Gai W, Xue X, Wang Y, Gao Y, Shan J, Yang S, Xia X. Isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine. Int J Biol Macromol 2016;87:7-15.
Maddocks-Jennings W, Wilkinson JM, Cavanagh HM, Shillington D. Evaluating the effects of the essential oils Leptospermum scoparium (manuka) and Kunzea ericoides (kanuka) on radiotherapy induced mucositis: a randomized, placebo controlled feasibility study. Eur J Oncol Nurs 2009;13:87-93.
Porter NG, Wilkins AL. Chemical, physical and antimicrobial properties of essential oils of Leptospermum scoparium and Kunzea ericoides. Phytochemistry 1999;50:407-415.
Gasparetto JC, Martins CA, Hayashi SS, Otuky MF, Pontarolo R. Ethnobotanical and scientific aspects of Malva sylvestris L.: a millennial herbal medicine. J Pharm Pharmacol 2012;64:172-189.
Classen B, Blaschek W. High molecular weight acidic polysaccharides from Malva sylvestris and Alcea rosea. Planta Med 1998; 64:640-644.
Aghili M. Makhzan-al-Advia. Tehran University of Medical Sciences,Tehran.
Ameri A, Heydarirad G, Rezaeizadeh H, Choopani R, Ghobadi A, Gachkar L. Evaluation of Efficacy of an Herbal Compound on Dry Mouth in Patients With Head and Neck Cancers: A Randomized Clinical Trial. J Evid Based Complementary Altern Med 2016;21:30-33.
Heydarirad G, Rezaeizadeh H, Choopani R, Mosavat SH, Ameri A. Efficacy of a traditional Persian medicine preparation for radiation-induced xerostomia: a randomized, open-label, active-controlled trial. J Integr Med 2017;15:201-208.
Singh O, Khanam Z, Misra N, Srivastava MK. Chamomile (Matricaria chamomilla L.): An overview. Pharmacogn Rev 2011;5:82-95.
Braga FT, Santos AC, Bueno PC, Silveira RC, Santos CB, Bastos JK, Carvalho EC. Use of Chamomilla recutita in the Prevention and Treatment of Oral Mucositis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Randomized, Controlled, Phase II Clinical Trial. Cancer Nurs 2015;38:322-329.
Tavakoli Ardakani M, Ghassemi S, Mehdizadeh M, Mojab F, Salamzadeh J, Ghassemi S, Hajifathali A. Evaluating the effect of Matricaria recutita and Mentha piperita herbal mouthwash on management of oral mucositis in patients undergoing hematopoietic stem cell transplantation: A randomized, double blind, placebo controlled clinical trial. Complement Ther Med 2016;29:29-34.
Al-Alawi RA, Al-Mashiqri JH, Al-Nadabi JS, Al-Shihi BI, Baqi Y. Date Palm Tree (Phoenix dactylifera L.): Natural Products and Therapeutic Options. Front Plant Sci 2017;8:845.
Tahvilzadeh M, Hajimahmoodi M, Rahimi R. The Role of Date Palm (Phoenix dactylifera L) Pollen in Fertility: A Comprehensive Review of Current Evidence. J Evid Based Complementary Altern Med 2016;21:320-324.
Elkerm Y, Tawashi R. Date palm pollen as a preventative intervention in radiation- and chemotherapy-induced oral mucositis: a pilot study. Integr Cancer Ther 2014;13:468-472.
Qi YJ, Cui S, Lu DX, Yang YZ, Luo Y, Ma L, Ma Y, Wuren T, Chang R, Qi L, Ben BJ, Han J, Ge RL. Effects of the aqueous extract of a Tibetan herb, Rhodiola algida var. tangutica on proliferation and HIF-1α, HIF-2α expression in MCF-7 cells under hypoxic condition in vitro. Cancer Cell Int 2015;15:81.
Cui S, Hu X, Chen X, Hu Z. Determination of p-tyrosol and salidroside in three samples of Rhodiola crenulata and one of Rhodiola kirilowii by capillary zone electrophoresis. Anal Bioanal Chem 2003;377:370-374.
Loo WT, Jin LJ, Chow LW, Cheung MN, Wang M. Rhodiola algida improves chemotherapy-induced oral mucositis in breast cancer patients. Expert Opin Investig Drugs 2010;19:S91-100.
Tamayo C, Diamond S. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Integr Cancer Ther 2007;6:146-157.
Elyasi S, Hosseini S, Niazi Moghadam MR, Aledavood SA, Karimi G. Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother Res 2016;30:1879-1885.
Bahramsoltani R, Farzaei MH, Abdolghaffari AH, Rahimi R, Samadi N, Heidari M, Esfandyari M, Baeeri M, Hassanzadeh G, Abdollahi M, Soltani S, Pourvaziri A, Amin G. Evaluation of phytochemicals, antioxidant and burn wound healing activities of Cucurbita moschata Duchesne fruit peel. Iran J Basic Med Sci 2017;20:798-805.
Morton JF. Mucilaginous plants and their uses in medicine. J Ethnopharmacol 1990;29:245-266.