Xerostomia,Medicine, Persian traditional,Hollyhocks,Common mallow,Cancer," /> Xerostomia,Medicine, Persian traditional,Hollyhocks,Common mallow,Cancer,"/> Efficacy of a traditional Persian medicine preparation for radiation-induced xerostomia: A randomized, open-label, active-controlled trial
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Journal of Integrative Medicine ›› 2017, Vol. 15 ›› Issue (3): 201-208.doi: 10.1016/S2095-4964(17)60333-9

• Research Article • Previous Articles     Next Articles

Efficacy of a traditional Persian medicine preparation for radiation-induced xerostomia: A randomized, open-label, active-controlled trial

Ghazaleh Heydarirada, Hossein Rezaeizadehb, Rasool Choopania, Seyed Hamdollah Mosavatc,d, Ahmad Amerie   

  1. a Department of Traditional Medicine, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran 15167-45811, Iran;
    b Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Science,Tehran 16687-53961, Iran;
    c Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz 71356-44144, Iran;
    d Essence of Parsiyan Wisdom Institute, Traditional Medicine and Medicinal Plant Incubator, Shiraz University of Medical Sciences, Shiraz 71356-44144, Iran;
    e Department of Radiation Oncology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran 19946-15611, Iran
  • Received:2016-10-22 Accepted:2017-02-06 Online:2017-05-15 Published:2017-05-15
  • Contact: Seyed Hamdollah Mosavat, Assistant Professor, MD, PhD; E-mail: hamdi_88114@yahoo.com


Xerostomia is one of the most common side effects of radiation therapy among patients with head and neck cancers (HNC). However, conventional medicine lacks an effective treatment for radiation-induced xerostomia.


Synthesizing the traditional use of Alcea digitata and Malva sylvestris with their known beneficial effects from recent studies, we evaluated the efficacy of the herbs in the quality of life (QOL) of HNC patients with radiation-induced xerostomia.

Design, Setting, Participants and Interventions

This study is a randomized, double-arm, open-label active-controlled clinical trial. We evaluated the effect of A. digitata and M. sylvestris on QOL of HNC patients with radiation-induced xerostomia compared with Hypozalix (artificial saliva). Patients were enrolled from the Imam Hossein Hospital's oncology clinic in Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Main Outcome Measures

Primary outcome measures in this trial were changes in patients' QOL assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Module (EORTC QLQ-H&N 35).


Between-group analysis showed that the intervention group patients obtained significantly lower (better) total EORTC QLQ-H&N 35 scores as compared to the control group at the end of the intervention period (P = 0.007). Mean scores of dry mouth of EORTC QLQ-H&N 35 was also significantly lower (better) in the intervention group as compared to the control group (P = 0.017).


Traditional Persian medicine preparation of hollyhocks and common mallow should be considered as a suitable treatment for xerostomia and improving QOL in HNC patients with radiation-induced xerostomia.

Trial registration

The trial was registered in ClinicalTrials.gov with Identifier: NCT02854358.

Key words: Xerostomia, Medicine, Persian traditional, Hollyhocks, Common mallow, Cancer

1 Curado MP, Hashibe M.Recent changes in the epidemiology of head and neck cancer.Curr Opin Oncol. 2009; 21(3): 194-200.
2 Khademi B, Taraghi A, Mohammadianpanah M.Anatomical and histopathological profile of head and neck neoplasms in Persian pediatric and adolescent population.Int J Pediatr Otorhinolaryngol. 2009; 73(9): 1249-1253.
3 Yang WF, Liao GQ, Hakim SG, Ouyang DQ, Ringash J, Su YX.Is ilocarpine effective in preventing radiation-induced xerostomia? A systematic review and meta-analysis.Int J Radiat Oncol Biol Phys. 2016; 94(3): 503-511.
4 Omidvari S, Saboori H, Mohammadianpanah M, Mosalaei A, Ahmadloo N, Mosleh-Shirazi MA, Jowkar F, Namaz S.Topical betamethasone for prevention of radiation dermatitis.Indian J Dermatol Venereol Leprol. 2007; 73(3): 209.
5 Villa A, Wolff A, Aframian D, Vissink A, Ekström J, Proctor G, McGowan R, Narayana N, Aliko A, Sia YW, Joshi RK, Jensen SB, Kerr AR, Dawes C, Pedersen AM. World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment.Clin Oral Investig. 2015; 19(7): 1563-1580.
6 Mohammadianpanah M, Razmjou-Ghalaei S, Shafizad A, Ashouri-Taziani Y, Khademi B, Ahmadloo N, Ansari M, Omidvari S, Mosalaei A, Mosleh-Shirazi MA.Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II- III clinical trial.J Cancer Res Ther. 2011; 7(4): 442-447.
7 Kakoei S, Haghdoost AA, Rad M, Mohammadalizadeh S, Pourdamghan N, Nakhaei M, Bahador M.Xerostomia after radiotherapy and its effect on quality of life in head and neck cancer patients.Arch Iran Med. 2012; 15(4): 214-218.
8 Perno Goldie M.Xerostomia and quality of life.Int J Dent Hyg. 2007; 5(1): 60-61.
9 Sahba S, Talaeepour AR, Hadad P.The efficacy of Iranian made saliva substitutevs. VA-OraLube in improvement of oral-health-related quality of life in radiotherapy-induced xerostomia. J Dent Sch. 2009; 27(3): 136-145.
10 Cho JH, Chung WK, Kang W, Choi SM, Cho CK, Son CG.Manual acupuncture improved quality of life in cancer patients with radiation-induced xerostomia.J Altern Complement Med. 2008; 14(5): 523-526.
11 Wu AJ.Optimizing dry mouth treatment for individuals with Sjögren’s syndrome.Rheum Dis Clin North Am. 2008; 34(4): 1001-1010.
12 Fani MM, Azar MR, Ramzi M, Azad A, Hajizadeh E, Nasrabadi NI, Mogharrabi S.The effect of the low-level laser on prevention of chemotherapy-induced oral mucositis in patients with acute leukemia.J Dent Lasers. 2013; 7(1): 22-26.
13 Fox PC, Cummins MJ, Cummins JM.A third study on the use of orally administered anhydrous crystalline maltose for relief of dry mouth in primary Sjogren’s syndrome.J Altern Complement Med. 2002; 8(5): 651-659.
14 Plemons JM, Al-Hashimi I, Marek CL, American Dental Association Council on Scientific Affairs. Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs.J Am Dent Assoc. 2014; 145(8): 867-873.
15 Fox PC, Cummins MJ, Cummins JM.Use of orally administered anhydrous crystalline maltose for relief of dry mouth.J Altern Complement Med. 2001; 7(1): 33-43.
16 Braga FP, Lemos Junior CA, Alves FA, Migliari DA.Acupuncture for the prevention of radiation-induced xerostomia in patients with head and neck cancer.Braz Oral Res. 2011; 25(2): 180-185.
17 Hendershot KA, Dixon M, Kono SA, Shin DM, Pentz RD.Patients’ perceptions of complementary and alternative medicine in head and neck cancer: a qualitative, pilot study with clinical implications.Complement Ther Clin Pract. 2014; 20(4): 213-218.
18 Ling CQ, Yue XQ, Ling C.Three advantages of using traditional Chinese medicine to prevent and treat tumor.J Integr Med. 2014; 12(4): 331-335.
19 Rezaeizadeh H, Alizadeh M, Naseri M, Shams Ardakani MR.The traditional Iranian medicine point of view on health and disease.Iran J Public Health. 2009; 38(Suppl 1): 169-172.
20 Shoara R, Hashempur MH, Ashraf A, Salehi A, Dehshahri S, Habibagahi Z.Efficacy and safety of topicalMatricaria chamomilla L.(chamomile) oil for knee osteoarthritis: a randomized controlled clinical trial. Complement Ther Clin Pract. 2015; 21(3): 181-187.
21 Zohalinezhad ME, Imanieh MH, Samani SM, Mohagheghzadeh A, Dehghani SM, Haghighat M, Salehi A, Faridi P, Akbarzadeh AR.Effects of quince syrup on clinical symptoms of children with symptomatic gastroesophageal reflux disease: a double-blind randomized controlled clinical trial.Complement Ther Clin Pract. 2015; 21(4): 268-276.
22 Heyadri M, Hashempur MH, Ayati MH, Quintern D, Nimrouzi M, Heyadri M.The use of Chinese herbal drugs in Islamic medicine.J Integr Med. 2015; 13(6): 363-367.
23 Hashempur MH, Heydari M, Mosavat SH, Heydari ST, Shams M.Complementary and alternative medicine use in Iranian patients with diabetes mellitus.J Integr Med. 2015; 13(5): 319-325.
24 Mosavat SH, Ghahramani L, Sobhani Z, Haghighi ER, Heydari M.TopicalAllium ampeloprasum subsp Iranicum (Leek) extract cream in patients with symptomatic hemorrhoids: a pilot randomized and controlled clinical trial. J Evid Based Complementary Altern Med. 2015; 20(2): 132-136.
25 Heydarirad G, Choopani R.“Dry mouth” from the perspective of traditional Persian medicine and comparison with current management.J Evid Based Complementary Altern Med. 2015; 20(2): 137-142.
26 Razavi SM, Zarrini G, Molavi G, Ghasemi G.Bioactivity ofMalva sylvestris L., a medicinal plant from Iran. Iran J Basic Med Sci. 2011; 14(6): 574-579.
27 Mojab F, Kamalinejad M, Ghaderi N, Vahidipour HR.Phytochemical screening of some species of Iranian plants.Iran J Pharm Res. 2003; 2(2): 77-82.
28 IbneSina H. Al-Qanoon fi al-Tibb (The canon of medicine). Beirut: Dare Ehia Attorath Al Arabi. 2005. Arabic.
29 Ameri A, Heydarirad G, Mahdavi Jafari J, Ghobadi A, Rezaeizadeh H, Choopani R.Medicinal plants contain mucilage used in traditional Persian medicine (TPM).Pharm Biol. 2015; 53(4): 615-623.
30 Gasparetto JC, Martins CAF, Hayashi SS, Otuky MF, Pontarolo R.Ethnobotanical and scientific aspects ofMalva sylvestris L.: a millennial herbal medicine. J Pharm Pharmacol. 2012; 64(2): 172-189.
31 Mosavat SH, Ghahramani L, Rahmanian Haghighi E, Rostami Chaijan M, Hashempur MH, Heydari M.Anorectal diseases in avicennas “Canon of Medicine”.Acta Med Hist Adriat. 2015; 13(Suppl 2): 103-114.
32 Fleming T.PDR for herbal medicine. 2nd ed. Montval New Jersy: Medical Economics Company. 2000: 829-830.
33 Al-Snafi AE.The pharmaceutical importance ofAlthaea officinalis and Althaea rosea: a review. Int J Pharm Tech Res. 2013; 5(3): 1387-1385.
34 Kardošová A, Machová E.Antioxidant activity of medicinal plant polysaccharides.Fitoterapia. 2006; 77(5): 367-373.
35 Prudente AS, Loddi AM, Duarte MR, Santos AR, Pochapski MT, Pizzolatti MG, Hayashi SS, Campos FR, Pontarolo R, Santos FA, Cabrini DA, Otuki MF.Pre-clinical antiinflammatory aspects of a cuisine and medicinal millennial herb:Malva sylvestris L. Food Chem Toxicol. 2013; 58: 324-331.
36 Savaese DM. Common terminology criteria for adverse events (CTCAE). Version 4.0. (2009) [2017-01-19]. https:// www.uptodate.com/contents/common-terminology-criteriafor- adverse-events.
37 Kim J, Shin W.How to do random allocation (randomization).Clin Orthop Surg. 2014; 6(1): 103-109.
38 Mosavat SH, Ghahramani L, Sobhani Z, Haghighi ER, Chaijan MR, Heydari M.The effect of leek (Allium iranicum (Wendelbo)) leaves extract cream on hemorrhoid patients: a double blind randomized controlled clinical trial. Eur J Integr Med. 2015; 7(6): 669-673.
39 Han G, Ko SJ, Kim J, Oh JY, Park JW, Kim J.A randomized, double-blind, placebo-controlled trial of a traditional herbal formula, Yukmijihwang-tang in elderly subjects with xerostomia.J Ethnopharmacol. 2016; 182: 160-169.
40 Park JW, Lee BJ, Bu YM, Yeo IK, Kim JS, Ryu BH.Effects of Korean red ginseng on dry mouth: a randomized, doubleblind, placebo-controlled trial.J Ginseng Res. 2010; 34(3): 183-191.
41 Wang Q, Liu H, Qiao N. Effects of traditional Chinese medicine on salivary glands in the patients with head and neck cancer during radiotherapy. Zhongguo Zhong Xi Yi Jie He Za Zhi.1998; 18(11): 662-664. Chinese with abstract in English.
42 Murakami M, Wei MX, Ding W, Zhang QD.Effects of Chinese herbs on salivary fluid secretion by isolated and perfused rat submandibular glands.World J Gastroenterol. 2009; 15(31): 3908-3915.
43 Jiang ZX, Qian Y, Jiang YL. Effects of Chinese herbs on salivary glands of patients with head and neck cancer during radiotherapy. Jiangxi Yi Xue Yuan Xue Bao.2006; 46(2): 68-69, 72. Chinese with abstract in English.
44 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(1): 30-33.
45 Kaplan I, Zuk-Paz L, Wolff A.Association between salivary flow rates, oral symptoms, and oral mucosal status.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 106(2): 235-241.
46 Lee JY, Jun SA, Hong SS, Ahn YC, Lee DS, Son CG.Systematic review of adverse effects from herbal drugs reported in randomized controlled trials.Phytother Res. 2016; 30(9): 1412-1419.
47 Emami M, Nazarinia MA, Rezaeizadeh H, Zarshenas MM.Standpoints of traditional Persian physicians on geriatric nutrition.J Evid Based Complementary Altern Med. 2014; 19(4): 287-291.
48 Sharifi AR, Homayounfar A, Mosavat SH, Heydari M, Naseri M.Premature ejaculation and its remedies in medieval Persia.Urology. 2016; 90: 225-228.
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