Review Article

Application of Natural Products in Radiotherapy-Induced Dermatitis: A Comprehensive Review ‎


Radiodermatitis (RD) is experienced by many cancer patients ‎receiving radiotherapy. An increasing number of these patients demand alternative natural therapies. This study aimed to review the natural products application in cancer patients who experience RD.‎ A search of studies published from 1990 to ‎‎2020 in the ‎databases including PubMed, Scopus, and Google Scholar was performed with the keywords relevant to “Radiotherapy” “Dermatitis” and “Natural Products”. Out of 73 papers obtained, 40 papers were excluded which described only protocols or were non-clinical, non-English language, or without full text. The obtained studies were ‎discussed in detail according to the outcomes and potential mechanisms of action for each natural ‎product.‎ Clinically studied natural products were found to show several outcomes from non-effective to effective in diminishing various items of RD. Outcomes on the effectiveness of Aloe vera were diverse. Some trials suggest that Silybum marianum, Boswellia, Nigella sativa, olive oil, Lianbai, and Hypericum perforatum as well as some multi-ingredient products might be effective prophylactic treatments for RD. Potential mechanisms of these natural products included topical hydrating, anti-inflammatory, antioxidant, and wound ‎healing activities. Results from this review shows that there are some promising natural product options for the prevention and treatment of RD via their multifactorial bioactivities. However, additional research is needed before any definitive conclusions. A larger sample size, optimum doses and duration of intervention as well as investigation of treatment effects in diverse populations and comorbid complications would also be essential in future studies.

Jacobson LK, Johnson MB, Dedhia RD, Niknam-Bienia S, Wong AK. Impaired wound healing after radiation therapy: A systematic review of pathogenesis and treatment. JPRAS Open 2017;13:92-105.

De Ruysscher D, Niedermann G, Burnet NG, Siva S, Lee AW et al. Radiotherapy toxicity. Nat Rev Dis Primers 2019;5:1-20.

Noble-Adams R. Radiation-induced reactions 1: an examination of the phenomenon. Br J Nurs 1999;8:1134-1140.

Merlano M, Russi E, Benasso M, Corvò R, Colantonio I et al. Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study. Ann Oncol 2011;22:712-717.

Russi EG, Merlano MC, Numico G, Corvò R, Benasso M et al. The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy. Support Care Cancer 2012;20:2141-2147.

Spałek M. Chronic radiation-induced dermatitis: challenges and solutions. Clin Cosmet Investig Dermatol 2016;9:473-482.

Harper JL, Franklin LE, Jenrette JM, Aguero EG. Skin toxicity during breast irradiation: pathophysiology and management. South Med J 2004 ;97:989-994.

Porock D. Factors influencing the severity of radiation skin and oral mucosal reactions: development of a conceptual framework. Eur J Cancer Care 2002;11:33-43.

Bray FN, Simmons BJ, Wolfson AH, Nouri K. Acute and chronic cutaneous reactions to ionizing radiation therapy. Dermatol Ther 2016;6:185-206.

Müller K, Meineke V. Radiation-induced alterations in cytokine production by skin cells. Exp Hematol 2007;35:96-104.

Wong RK, Bensadoun RJ, Boers-Doets CB, Bryce J, Chan A et al. Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC Skin Toxicity Study Group. Support Care Cancer 2013;21:2933-2948.

Russi EG, Moretto F, Rampino M, Benasso M, Bacigalupo A et al. Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus. Crit Rev Oncol Hematol 2015;96:167-182.

Togni S, Maramaldi G, Bonetta A, Giacomelli L, Di Pierro F. Clinical evaluation of safety and efficacy of Boswellia-based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma: a randomized placebo controlled trial. Eur Rev Med Pharmacol Sci 2015;19:1338-1344.

Rosenthal A, Israilevich R, Moy R. Management of acute radiation dermatitis: a review of the literature and proposal for treatment algorithm. J Am Acad Dermatol 2019;81:558-567.

Cui Z, Xin M, Yin H, Zhang J, Han F. Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients. Int J Clin Exp Med 2015;8:11000-11006.

Mansouri P, Khademi A, Pahlevan D, Memariani Z, Aliasl J et al. Review of medicinal remedies on hand eczema based on Iranian traditional medicine: A narrative review article. Iran J Public Health 2016;45:986-996.

Farahani AM, Aryanian Z, Memariani Z, Mozaffarpur SA, Shirafkan H, A Comparison of the effect of topical preparation of sambucus ebulus L. and Hydrocortisone on hand eczema: a double-blind randomized controlled trial. J Altern Complement Med 2021;27:323-330.

Horneber M, Bueschel G, Dennert G, Less D, Ritter E et al. How many cancer patients use complementary and alternative medicine: a systematic review and metaanalysis. Integr Cancer Ther 2012;11:187-203.

Sahebnasagh A, Ghasemi A, Akbari J, Alipour A, Lashkardoost H et al. Successful treatment of acute radiation proctitis with aloe vera: a preliminary randomized controlled clinical trial. J Altern Complement Med 2017;23:858-865.

Heggie S, Bryant GP, Tripcony L, Keller J, Rose P et al. A phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue. Cancer Nurs 2002;25:442-451.

Pommier P, Gomez F, Sunyach MP, D'hombres A, Carrie C et al. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol 2004;22:1447-1453.

Yirmibesoglu E, Karahacioglu E, Kilic D, Lortlar N, Akbulut G et al. The protective effects of Ginkgo biloba extract (EGb‐761) on radiation‐induced dermatitis: an experimental study. Clin Exp Dermatol 2012;37:387-394.

Chen YJ, Dai YS, Chen BF, Chang A, Chen HC et al. The effect of tetrandrine and extracts of Centella asiatica on acute radiation dermatitis in rats. Biol Pharm Bull 1999;22:703-706.

Huang MY, Huang JJ, Chai CY, Chen SH, Kuo MP et al. The reduction effect of extracts of soybean seeds on acute radiation dermatitis. Fooyin J Health Sci. 2010;2:21-25.

Hamman B, Chinhengo A, Serafin A, Sewram V, Akudugu J. Radiomodifying effects of Centella asiatica and Withania somnifera. J Herbs Spices Med Plants 2018;24:221-228.

Iram F, Khan SA, Husain A. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review. Asian Pac J Trop Biomed 2017;7:513-523.

Bekana D, Kebede T, Assefa M, Kassa H. Comparative phytochemical analyses of resins of Boswellia species (B. papyrifera (Del.) Hochst., B. neglecta S. Moore, and B. rivae Engl.) from northwestern, southern, and southeastern Ethiopia. Int Sch Res Notices 2014;2014:374678.

Siddiqui MZ. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci 2011;73:255-261.

Mahmoud Mostafa D, Mohammed Ammar N, Hosam Abd El-Alim S, Alaa Kassem A, Ali Hussein R et al. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity. Curr Drug Deliv 2015;12:454-463.

Alluri VK, Kundimi S, Sengupta K, Golakoti T, Kilari EK. An anti-inflammatory composition of Boswellia serrata resin extracts alleviates pain and protects cartilage in monoiodoacetate-induced osteoarthritis in rats. Evid Based Complementary Altern Med 2020;2020:7381625.

Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Med 2006;72:1100-1116.

Sferra R, Vetuschi A, Catitti V, Ammanniti S, Pompili S et al. Boswellia serrata and Salvia miltiorrhiza extracts reduce DMN-induced hepatic fibrosis in mice by TGF-beta1 downregulation. Eur Rev Med Pharmacol Sci 2012;16:1484-1498.

Hamidpour R, Hamidpour S, Hamidpour M, Shahlari M. Frankincense (Boswellia species): from the selection of traditional applications to the novel phytotherapy for the prevention and treatment of serious diseases. J Tradit Complement Med 2013;3(4):221-226.

Poeckel D, Werz O. Boswellic acids: biological actions and molecular targets. Curr Med Chem 2006;13:3359-3369.

Arora D, Rani A, Sharma A. A review on phytochemistry and ethnopharmacological aspects of genus Calendula. Pharmacogn Rev 2013;7:179-187.

Silva D, Ferreira MS, Sousa-Lobo JM, Cruz MT, Almeida IF. Anti-Inflammatory Activity of Calendula officinalis L. Flower Extract. Cosmetics. 2021;8:31-37.

Preethi KC, Kuttan G, Kuttan R. Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action. Indian J Exp Biol 2009;47:113-120.

Shafeie N, Naini AT, Jahromi HK. Comparison of different concentrations of Calendula officinalis gel on cutaneous wound healing. Biomed Pharmacol J 2015;8:979-992.

Givol O, Kornhaber R, Visentin D, Cleary M, Haik J et al. A systematic review of Calendula officinalis extract for wound healing. Wound Repair Regen 2019;27:548-561.

Lim TK. Calendula officinalis. In: Edible Medicinal And Non-Medicinal Plants. Springer, Dordrecht, 2014; pp 213-244.

Dinda M, Dasgupta U, Singh N, Bhattacharyya D, Karmakar P. PI3K‐mediated proliferation of fibroblasts by Calendula officinalis tincture: implication in wound healing. Phytother Res 2015;29:607-616.

Hu JJ, Cui T, Rodriguez-Gil JL, Allen GO, Li J et al. Complementary and alternative medicine in reducing radiation-induced skin toxicity. Radiat Environ Biophys 2014;53:621-626.

Sharp L, Finnilä K, Johansson H, Abrahamsson M, Hatschek T et al. No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions–results from a randomised blinded trial. Eur J Oncol Nurs 2013;17:429-435.

Kodiyan J, Amber KT. A review of the use of topical calendula in the prevention and treatment of radiotherapy-induced skin reactions. Antioxidants. 2015;4:293-303.

Hekmatpou D, Mehrabi F, Rahzani K, Aminiyan A. The effect of Aloe vera clinical trials on prevention and healing of skin wound: a systematic review. Iran J Med Sci 2019;44:1-10.

Surjushe A, Vasani R, Saple DG. Aloe vera: a short review. Indian J Dermatol 2008;53:163-166.

Salehi B, Albayrak S, Antolak H, Kręgiel D, Pawlikowska E et al. Aloe genus plants: from farm to food applications and phytopharmacotherapy. Int J Mol Sci 2018;19:2843-2891.

Fox LT, Mazumder A, Dwivedi A, Gerber M, Du Plessis J et al. In vitro wound healing and cytotoxic activity of the gel and whole-leaf materials from selected aloe species. J Ethnopharmacol 2017;200:1-7.

Fox LT, Du Plessis J, Gerber M, Van Zyl S, Boneschans B et al. In vivo skin hydration and anti-erythema effects of Aloe vera, Aloe ferox and Aloe marlothii gel materials after single and multiple applications. Pharmacogn Mag 2014;10:S392-S403.

Hamman JH. Composition and applications of Aloe vera leaf gel. Molecules. 2008;13:1599-1616.

Williams MS, Burk M, Loprinzi CL, Hill M, Schomberg PJ et al. Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys 1996;36:345-349.

Haddad P, Amouzgar–Hashemi F, Samsami S, Chinichian S, Oghabian MA. Aloe vera for prevention of radiation-induced dermatitis: a self-controlled clinical trial. Curr Oncol 2013;20:345-348.

Farrugia CJ, Burke ES, Haley ME, Bedi KT, Gandhi MA. The use of Aloe vera in cancer radiation: An updated comprehensive review. Complement Ther Clin Pract 2019;35:126-30.

Paul S, Modak D, Chattaraj S, Nandi D, Sarkar A et al. Aloe vera gel homogenate shows anti-inflammatory activity through lysosomal membrane stabilization and downregulation of TNF-α and Cox-2 gene expressions in inflammatory arthritic animals. Future J Pharm Sci 2021;7:1-8.

Heggers JP, Elzaim H, Garfield R, Goodheart R, Listengarten D et al. Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model. J Altern Complement Med 1997;3:149-153.

Rao S, Hegde SK, Baliga-Rao MP, Palatty PL, George T et al. An Aloe vera-based cosmeceutical cream delays and mitigates ionizing radiation-induced dermatitis in head and neck cancer patients undergoing curative radiotherapy: a clinical study. Medicines. 2017;4:44.

Nyström J, Svensk AC, Lindholm-Sethson B, Geladi P, Larson J et al. Comparison of three instrumental methods for the objective evaluation of radiotherapy induced erythema in breast cancer patients and a study of the effect of skin lotions. Acta Oncol 2007;46:893-899.

Olsen DL, Raub W, Bradley C, Johnson M, Macias JL et al. The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncol Nurs Forum 2001;28:543-547.

Fisher J, Scott C, Stevens R, Marconi B, Champion L et al. Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13. Int J Radiat Oncol Biol Phys 2000;48:1307-1310.

Ahlawat KS, Khatkar BS. Processing, food applications and safety of aloe vera products: a review. J Food Sci Technol 2011;48:525-533.

Hoopfer D, Holloway C, Gabos Z, Alidrisi M, Chafe S et al. Three-arm randomized phase III trial: quality aloe and placebo cream versus powder as skin treatment during breast cancer radiation therapy. Clin Breast Cancer 2015;15:181-190.

Ahmadloo N, Kadkhodaei B, Omidvari S, Mosalaei A, Ansari M et al. Lack of prophylactic effects of Aloe vera gel on radiation induced dermatitis in breast cancer patients. Asian Pac J Cancer Prev 2017;18:1139.

Adeyemi MM, Habila JD, Enemakwu TA, Okeniyi SO, Salihu L. Aloe vera Prevents Radiation-Induced Dermatitis among the Black Population.Trop J Nat Prod Res 2018;2:433-437.

Richardson J, Smith JE, McIntyre M, Thomas R, Pilkington K. Aloe vera for preventing radiation-induced skin reactions: a systematic literature review. Clin Oncol 2005;17:478-484.

Igile G, Essiet G, Uboh F, Edet E. Rapid method for the identification and quantification of allantoin in body creams and lotions for regulatory activities. Int J Curr Microbiol App Sci 2014;3:552-557.

Freedman GM. Topical agents for radiation dermatitis in breast cancer: 50 shades of red or same old, same old?. Int J Radiat Oncol Biol Phys 2014;90:736-738.

Chan RJ, Mann J, Tripcony L, Keller J, Cheuk R et al. Natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer: a phase 3, double-blind, randomized, controlled trial. Int J Radiat Oncol Biol Phys 2014;90:756-764.

Chan RJ, Keller J, Cheuk R, Blades R, Tripcony L et al. A double-blind randomised controlled trial of a natural oil-based emulsion (Moogoo Udder Cream®) containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer. Radiat Oncol 2012;7:1-7.

Chou HL, Shueng PW, Liao LJ, Hsu CX, Kuo DY et al.Prophylactic NS-21 maintains the skin moisture but does not reduce the severity of radiation dermatitis in patients with head and neck cancer: a randomized control trial. Radiat Oncol 2019;14:1-9.

Dos Santos DS, Barreto RD, Serafini MR, Gouveia DN, Marques RS et al. Phytomedicines containing Matricaria species for the treatment of skin diseases: A biotechnological approach. Fitoterapia 2019;138:104267.

Ferreira EB, Ciol MA, Vasques CI, Bontempo PD, Vieira NN et al. Gel of chamomile vs. urea cream to prevent acute radiation dermatitis in patients with head and neck cancer: a randomized controlled trial. J Adv Nurs 2016;72:1926-1934.

Wu YN, Xu Y, Yao L. Anti-inflammatory and anti-allergic effects of German chamomile (Matricaria chamomilla L.). J Essent Oil-Bear Plants 2012;15:75-83.

Maiche AG, Grohn P, Maki-Hokkonen H. Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncol 1991;30:395-396.

Ferreira EB, Ciol MA, De Meneses AG, Bontempo PD, Hoffman JM et al. Chamomile gel versus urea cream to prevent acute radiation dermatitis in head and neck cancer patients: Results from a preliminary clinical trial. Integr Cancer Ther 2020;19:1-12.

Zholobenko A, Modriansky M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia 2014;97:122-132.

Gharagozloo M, Velardi E, Bruscoli S, Agostini M, Di Sante M et al. Silymarin suppress CD4+ T cell activation and proliferation: effects on NF-κB activity and IL-2 production. Pharmacol Res 2010;61:405-409.

Fehér P, Vecsernyés M, Fenyvesi F, Váradi J, Kiss T et al. Topical application of Silybum marianum extract. Arad Med J 2011;14:5-8.

Becker-Schiebe M, Mengs U, Schaefer M, Bulitta M, Hoffmann W. Topical use of a silymarin-based preparation to prevent radiodermatitis. Strahlenther Onkol 2011;187:485.

Karbasforooshan H, Hosseini S, Elyasi S, Fani Pakdel A, Karimi G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double‐blind, placebo‐controlled clinical trial. Phytother Res 2019;33:379-386.

Dehmlow C, Murawski N, de Groot H. Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells. Life Sci 1996;58:1591-1600.

Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. J Complement Med Res 2007;14:70-80.

Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci 2011;14:308-317.

Křen V, Walterová D. Silybin and silymarin-new effects and applications. Biomed Pap 2005;149:29-41.

Hung CF, Lin YK, Huang ZR, Fang JY. Delivery of resveratrol, a red wine polyphenol, from solutions and hydrogels via the skin. Biol Pharm Bull 2008;31:955-962.

Chen HJ, Chung CP, Chiang W, Lin YL. Anti-inflammatory effects and chemical study of a flavonoid-enriched fraction from adlay bran. Food Chem 2011;126:1741-1748.

Son ES, Kim SH, Kim YO, Lee YE, Kyung SY et al. Coix lacryma-jobi var. ma-yuen Stapf sprout extract induces cell cycle arrest and apoptosis in human cervical carcinoma cells. BMC Complement Altern Med 2019;19:1-9.

Chung CP, Hsu HY, Huang DW, Hsu HH, Lin JT et al. Ethyl acetate fraction of adlay bran ethanolic extract inhibits oncogene expression and suppresses DMH-induced preneoplastic lesions of the colon in F344 rats through an anti-inflammatory pathway. J Agric Food Chem 2010;58:7616-7623.

Huang DW, Wu CH, Shih CK, Liu CY, Shih PH et al. Application of the solvent extraction technique to investigation of the anti-inflammatory activity of adlay bran. Food chem 2014;145:445-453.

Chung CP, Hsia SM, Lee MY, Chen HJ, Cheng F et al. Gastroprotective activities of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) on the growth of the stomach cancer AGS cell line and indomethacin-induced gastric ulcers. J Agric Food Chem 2011;59:6025-6033.

Yao HT, Lin JH, Chiang MT, Chiang W, Luo MN et al. Suppressive effect of the ethanolic extract of adlay bran on cytochrome P-450 enzymes in rat liver and lungs. J Agric Food Chem 2011;59:4306-4314.

Zhao M, Zhu D, Sun-Waterhouse D, Su G, Lin L et al. In vitro and in vivo studies on adlay-derived seed extracts: phenolic profiles, antioxidant activities, serum uric acid suppression, and xanthine oxidase inhibitory effects. J Agric Food Chem 2014;62:7771-7778.

Chung CP, Hsu CY, Lin JH, Kuo YH, Chiang W et al. Antiproliferative lactams and spiroenone from adlay bran in human breast cancer cell lines. J Agric Food Chem 2011;59:1185-1194.

Lee MY, Lin HY, Cheng F, Chiang W, Kuo YH. Isolation and characterization of new lactam compounds that inhibit lung and colon cancer cells from adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) bran. Food Chem Toxicol 2008;46:1933-1939.

Huang CJ, Hou MF, Kan JY, Juan CH, Yuan SS et al. Prophylactic treatment with adlay bran extract reduces the risk of severe acute radiation dermatitis: A prospective, randomized, double-blind study. Evid Based Complement Alternat Med 2015;2015.

Huang BW, Chiang MT, Yao HT, Chiang W. The effect of adlay oil on plasma lipids, insulin and leptin in rat. Phytomedicine 2005;12:433-439.

Cirak C, Radusiene J, Jakstas V, Ivanauskas L, Seyis F et al. Secondary metabolites of seven Hypericum species growing in Turkey. Pharm Biol 2016;54:2244-2253.

Silva AR, Taofiq O, Ferreira IC, Barros L. Hypericum genus cosmeceutical application–A decade comprehensive review on its multifunctional biological properties. Ind Crops Prod 2021;159:113053.

Süntar IP, Akkol EK, Yılmazer D, Baykal T, Kırmızıbekmez H et al. Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol 2010;127:468-477.

Sosa S, Pace R, Bornanciny A, Morazzoni P, Riva A et al. Topical anti-inflammatory activity of extracts and compounds from Hypericum perforatum L. J Pharm Pharmacol 2007;59:703-709.

Haag SF, Tscherch K, Arndt S, Kleemann A, Gersonde I et al. Enhancement of skin radical scavenging activity and stratum corneum lipids after the application of a hyperforin-rich cream. Eur J Pharm Biopharm 2014;86:227-233.

Huang N, Rizshsky L, Hauck C, Nikolau BJ, Murphy PA et al. Identification of anti-inflammatory constituents in Hypericum perforatum and Hypericum gentianoides extracts using RAW 264.7 mouse macrophages. Phytochemistry 2011;72:2015-2023.

Tedeschi E, Menegazzi M, Margotto D, Suzuki H, Förstermann U, Kleinert H. Anti-inflammatory actions of St. John's wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1α (STAT-1α) activation. J Pharmacol Exp Ther 2003;307:254-261.

Franco P, Potenza I, Moretto F, Segantin M, Grosso M et al. Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study. Radiat Oncol 2014;9:1-7.

Koeberle A, Rossi A, Bauer J, Dehm F, Verotta L et al. Hyperforin, an anti-inflammatory constituent from St. John's wort, inhibits microsomal prostaglandin E2 synthase-1 and suppresses prostaglandin E2 formation in vivo. Front Pharmacol 2011;2:7.

Franco P, Rampino M, Ostellino O, Schena M, Pecorari G et al. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients. Med Oncol 2017;34:30.

Lee CJ, Chen LG, Liang WL, Wang CC. Anti-inflammatory effects of Punica granatum Linne in vitro and in vivo. Food chem. 2010;118:315-322.

Bhandary SK, Sharmila KP, Suchetha KN, Bhat VS, Sanjeev G. Ameliorative activity of Punica granatum extracts and ellagic acid against radiation induced biochemical changes in swiss albino mice. Res J pharm biol chem sci 2014;5:1097-1107.

Thotambailu AM, Bhandary BS, Sharmila KP. Protective effect of punica granatum extract in head and neck cancer patients undergoing radiotherapy. Indian J Otolaryngol Head Neck Surg 2019;71:318-320.

Guha G, Rajkumar V, Kumar RA, Mathew L. Antioxidant activity of Lawsonia inermis extracts inhibits chromium (VI)-induced cellular and DNA toxicity. Evid Based Complement Alternat Med 2011;2011.

Nayak BS, Isitor G, Davis EM, Pillai GK. The evidence based wound healing activity of Lawsonia inermis Linn. Phytother Res 2007;21:827-831.

Philip JP, Madhumitha G, Mary SA. Free radical scavenging and reducing power of Lawsonia inermis L. seeds. Asian Pac J Trop 2011;4:457-461.

Hosseini SV, Tanideh N, Kohanteb J, Ghodrati Z, Mehrabani D et al. Comparison between Alpha and silver sulfadiazine ointments in treatment of Pseudomonas infections in 3rd degree burns. Int J Surg 2007;5:23-26.

Hadisi Z, Nourmohammadi J, Nassiri SM. The antibacterial and anti-inflammatory investigation of Lawsonia Inermis-gelatin-starch nano-fibrous dressing in burn wound. Int J Biol Macromol 2018;107:2008-2019.

Semwal RB, Semwal DK, Combrinck S, Cartwright-Jones C, Viljoen A. Lawsonia inermis L.(henna): Ethnobotanical, phytochemical and pharmacological aspects. J Ethnopharmacol 2014;155:80-103.

Chaibi R, Drine SA, Ferchichi A. Chemical study and biological activities of various extracts from Lawsonia inermis (Henna) seeds. Acta Med Mediterr 2017;33:981-986.

Lozza L, Moura-Alves P, Domaszewska T, Crespo CL, Streata I et al. The Henna pigment Lawsone activates the Aryl Hydrocarbon Receptor and impacts skin homeostasis. Sci Rep 2019;9:1-21.

Daemi A, Farahpour MR, Oryan A, Karimzadeh S, Tajer E. Topical administration of hydroethanolic extract of Lawsonia inermis (henna) accelerates excisional wound healing process by reducing tissue inflammation and amplifying glucose uptake. Kaohsiung J Med Sci 2019;35:24-32.

Ansari M, Dehsara F, Mosalaei A, Omidvari S, Ahmadloo N et al. Efficacy of topical alpha ointment (containing natural henna) compared to topical hydrocortisone (1%) in the healing of radiation-induced dermatitis in patients with breast cancer: a randomized controlled clinical trial. Iran J Med Sci 2013;38:293-300.

Chitapanarux I, Tovanabutra N, Chiewchanvit S, Sripan P, Chumachote A et al. Emulsion of olive oil and calcium hydroxide for the prevention of radiation dermatitis in hypofractionation post-mastectomy radiotherapy: a randomized controlled trial. Breast care 2019;14:394-400.

Cárdeno A, Sánchez-Hidalgo M, Alarcón-De-La-Lastra C. An up-date of olive oil phenols in inflammation and cancer: molecular mechanisms and clinical implications. Curr Med Chem 2013;20:4758-4776.

Lin TK, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol 2018;19:70.

Aparicio‐Soto M, Redhu D, Sánchez‐Hidalgo M, Fernández‐Bolaños JG, Alarcón‐de‐la‐Lastra C et al. Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway. Mol Nutr Food Res 2019;63:1-10.

Koukourakis G, Pissakas G, Ganos CG, Sivolapenko G, Kardamakis D. Effectiveness and Tolerability of Natural Herbal Formulations in the Prevention of Radiation-Induced Skin Toxicity in Patients Undergoing Radiotherapy. Int J Low Extrem Wounds 2020:1-12.

Baliga MS, Venkatesh S, Mrinal S, Bala N, Palatty PL. Turmeric (Curcuma longa L.) the Indian Golden Curry Spice as a Skin Care Agent: Validation of the Traditional Uses. In: Bioactive Dietary Factors and Plant Extracts in Dermatology. Humana Press, Totowa, NJ, 2013; pp 93-102.

Gopinath D, Ahmed MR, Gomathi K, Chitra K, Sehgal PK et al. Dermal wound healing processes with curcumin incorporated collagen films. Biomaterials 2004;25:1911-1917.

López-Jornet P, Camacho-Alonso F, Jiménez-Torres MJ, Orduña-Domingo A, Gómez-García F. Topical curcumin for the healing of carbon dioxide laser skin wounds in mice. Photomed Laser Surg 2011;29:809-814.

Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M et al. The effects of topical treatment with curcumin on burn wound healing in rats. J Mol Histol 2013;44:83-90.

Aggarwal BB, Surh YJ, Shishodia S. The molecular targets and therapeutic uses of curcumin in health and disease. Springer Science & Business Media 2007; pp 1-75.

Bhagavathula N, Warner RL, DaSilva M, McClintock SD, Barron A et al. A combination of curcumin and ginger extract improves abrasion wound healing in corticosteroid‐impaired hairless rat skin. Wound Repair Regen 2009;17:360-366.

Jagetia GC, Rajanikant GK. Role of curcumin, a naturally occurring phenolic compound of turmeric in accelerating the repair of excision wound, in mice whole-body exposed to various doses of γ-radiation. J Surg Res 2004;120:127-138.

Phan TA, Halliday GM, Barnetson RS, Damian DL. Melanin differentially protects from the initiation and progression of threshold UV‐induced erythema depending on UV waveband. Photodermatol Photoimmunol Photomed 2006;22:174-180.

Kim J, Park S, Jeon BS, Jang WS, Lee SJ et al. Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model. J Vet Sci 2016;17:435-444.

Ryan JL, Heckler CE, Ling M, Katz A, Williams JP et al. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 2013;180:34-43.

Wolf JR, Heckler CE, Guido JJ, Peoples AR, Gewandter JS et al. Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients. Support Care Cancer 2018;26:1543-1552.

Wolf JR, Gewandter JS, Bautista J, Heckler CE, Strasser J et al. Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial. Support Care Cancer 2020;28:3303-3311.

Palatty PL, Azmidah A, Rao S, Jayachander D, Thilakchand KR et al. Topical application of a sandal wood oil and turmeric based cream prevents radiodermatitis in head and neck cancer patients undergoing external beam radiotherapy: a pilot study. Br J Radiol Suppl 2014;87:20130490.

Santha S, Dwivedi C. α‐Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis. Photochem Photobiol 2013;89:919-926.

Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol 2016;190:372-386.

Amin B, Hosseinzadeh H. Black cumin (Nigella sativa) and its active constituent, thymoquinone: an overview on the analgesic and anti-inflammatory effects. Planta Med 2016;82:8-16.

Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int Immunopharmacol 2015;28:295-304.

Schneider-Stock R, Fakhoury IH, Zaki AM, El-Baba CO, Gali-Muhtasib HU. Thymoquinone: fifty years of success in the battle against cancer models. Drug Discov Today 2014;19:18-30.

Rafati M, Ghasemi A, Saeedi M, Habibi E, Salehifar E et al. Nigella sativa L. for prevention of acute radiation dermatitis in breast cancer: A randomized, double-blind, placebo-controlled, clinical trial. Complement Ther Med 2019;47:102205.

El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta Gen Subj 2007;1770:556-564.

Sayed AA, Morcos M. Thymoquinone decreases AGE‐induced NF‐κB activation in proximal tubular epithelial cells. Phytother Res 2007;21:898-899.

Ma H, Zhang X, Bai M, Wang X. Clinical effects of lianbai liquid in prevention and treatment of dermal injury caused by radiotherapy. J Tradit Chin Med 2007;27:193-196.

Meng FC, Wu ZF, Yin ZQ, Lin LG, Wang R et al. Coptidis rhizoma and its main bioactive components: recent advances in chemical investigation, quality evaluation and pharmacological activity. Chin Med 2018;13:1-8.

Sun H, Wang H, Zhang A, Yan G, Han Y et al. Chemical discrimination of cortex Phellodendri amurensis and cortex Phellodendri chinensis by multivariate analysis approach. Pharmacogn Mag 2016;12:41-49.

Choi YY, Kim MH, Han JM, Hong J, Lee TH et al. The anti-inflammatory potential of Cortex Phellodendron in vivo and in vitro: down-regulation of NO and iNOS through suppression of NF-κB and MAPK activation. Int Immunopharmacol 2014;19:214-220.

Zou K, Li Z, Zhang Y, Zhang HY, Li B et al. Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacol Sin 2017;38:157-167.

Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H et al. Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomed Pharmacother 2018;97:233-239.

Takahara M, Takaki A, Hiraoka S, Adachi T, Shimomura Y et al. Berberine improved experimental chronic colitis by regulating interferon-γ-and IL-17A-producing lamina propria CD4+ T cells through AMPK activation. Sci Rep 2019;9:1-3.

Kalmarzi RN, Naleini SN, Ashtary-Larky D, Peluso I, Jouybari L et al. Anti-inflammatory and immunomodulatory effects of barberry (Berberis vulgaris) and its main compounds. Oxid Med Cell Longev 2019;2019.

Sharma V, Sharma L, Sandhu KS. Cucumber (Cucumis sativus L.). In: Antioxidants in Vegetables and Nuts-Properties and Health Benefits. Springer, Singapore, 2020; pp 333-340.

Uthpala TG, Marapana RA, Lakmini K, Wettimuny DC. Nutritional bioactive compounds and health benefits of fresh and processed cucumber (Cucumis Sativus L.). Sumerianz J Biotechnol 2020;3:75-82.

Heidari H, Kamalinejad M, Noubarani M, Rahmati M, Jafarian I et al. Protective mechanisms of Cucumis sativus in diabetes-related modelsof oxidative stress and carbonyl stress. BioImpacts 2016;6:33.

Agatemor UM, Nwodo OF, Ozah IR. Inhibition of phospholipase A2 and prostaglandin synthase activities as possible mechanisms for the anti-inflammatory effect of Cucumis sativus fruit homogenate. Acta Sci Pharm Sci 2019;3:68-73.

Trejo-Moreno C, Méndez-Martínez M, Zamilpa A, Jiménez-Ferrer E, Perez-Garcia MD et al. Cucumis sativus aqueous fraction inhibits angiotensin II-induced inflammation and oxidative stress in vitro. Nutrients. 2018;10:276-289.

Thanthong S, Nanthong R, Kongwattanakul S, Laebua K, Trirussapanich P et al. Prophylaxis of radiation-induced dermatitis in patients with breast cancer using herbal creams: a prospective randomized controlled trial. Integr Cancer Ther 2020;19:1-9.

Matceyevsky D, Hahoshen NY, Asna N, Khafif A, Ben-Yosef R. Assessing the effectiveness of Dead Sea products as prophylactic agents for acute radiochemotherapy-induced skin and mucosal toxicity in patients with head and neck cancers: a phase 2 study. Chemotherapy 2007;9:439-442.

Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res 2012;49:35-43.

Bower JE, Ganz PA, Irwin MR, Kwan L, Breen EC et al. Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism?. J Clin Oncol 2011;29:3517-3522.

Ong ZY, Gibson RJ, Bowen JM, Stringer AM, Darby JM et al. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis. Radiat Oncol 2010;5:1-8.

Korinko A, Yurick A. Maintaining skin integrity during radiation therapy. Am J Nurs 1997;97:40-44.

Jamwal R. Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers. J Integr Med 2018;16:367-374.

IssueVol 6, No 3, 2021 QRcode
SectionReview Article(s)
Herbal medicine Phytochemical Radiodermatitis Radiotherapy Radioprotective Skin ‎disorders

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Rezghi M, Moradi Farahani A, Asadi F, Mitra S, Dash R, Mozaffarpour SA, Memariani Z. Application of Natural Products in Radiotherapy-Induced Dermatitis: A Comprehensive Review ‎. Trad Integr Med. 2021;6(3):259-287.