Complementary Therapies in Clinical Practice 22 (2016) 93e98 Contents lists available at ScienceDirect Complementary Therapies in Clinical Practice journal homepage: www.elsevier.com/locate/ctcp Evaluation of the efficacy of a polyherbal mouthwash containing Zingiber officinale, Rosmarinus officinalis and Calendula officinalis extracts in patients with gingivitis: A randomized double-blind placebo-controlled trial Saman Mahyari a, Behnam Mahyari b, Seyed Ahmad Emami c, d, Bizhan Malaekeh-Nikouei e, Seyedeh Pardis Jahanbakhsh a, Amirhossein Sahebkar f, g, * Amir Hooshang Mohammadpour a, a Pharmaceutical Research Center, Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran b Mahyari Dentistry Clinic, Iran Square, Neyshabour, Iran c Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran d Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran e Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran f Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran g Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia article info abstract Article history: Background: Gingivitis is a highly prevalent periodontal disease resulting from microbial infection and Received 12 November 2015 subsequent inflammation. The efficacy of herbal preparations in subjects with gingivitis has been re- Accepted 3 December 2015 ported in some previous studies. Objective: To investigate the efficacy of a polyherbal mouthwash containing hydroalcoholic extracts of Keywords: Zingiber officinale, Rosmarinus officinalis and Calendula officinalis (5% v/w) compared with chlorhexidine Randomized controlled trial and placebo mouthwashes in subjects with gingivitis. Gingivitis Methods: Sixty patients participated in this randomized double-blind placebo-controlled trial and were Ginger ¼ ¼ Rosemary randomly assigned to the polyherbal mouthwash (n 20), chlorhexidine mouthwash (n 20) or placebo ¼ Marigold mouthwash (n 20). Participants were instructed to use the mouthwash twice a day (after breakfast and dinner) for 30 s for a period of two weeks. Gingival and plaque indices were assessed using MGI, GBI and MQH scales at baseline, day 7 and day 14 of the trial. Results: There were significant improvements in all assessed efficacy measures i.e. MGI, GBI and MQH scores from baseline to the end of trial in both polyherbal and chlorhexidine mouthwash groups; however, the scores remained statistically unchanged in the placebo group. MGI, BGI and MQH scores in the treatment groups were significantly lower compared with those of the control group at both day 7 and day 14 of the trial. However, there was no significant difference between the polyherbal and chlorhexidine groups, neither at day 7 nor day 14 of the trial. Polyherbal mouthwash was safe and there was neither report of adverse reactions, nor any drop-out during the course of study. Conclusion: Polyherbal mouthwash containing hydroalcoholic extracts of Z. officinale, R. officinalis and C. officinalis (5%) was effective in the treatment of gingivitis and its efficacy was comparable to that of chlorhexidine mouthwash. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Periodontal diseases have a destructive effect on the supporting tooth tissues. The mildest form of these diseases is gingivitis [1] * Corresponding author. which is characterized by bleeding, plaque formation and gum E-mail address: [email protected] (A.H. Mohammadpour). http://dx.doi.org/10.1016/j.ctcp.2015.12.001 1744-3881/© 2015 Elsevier Ltd. All rights reserved. 94 S. Mahyari et al. / Complementary Therapies in Clinical Practice 22 (2016) 93e98 inflammation. Gingivitis has a high prevalence in the general also prepared as placebo. For the preparation of 280 mL of the population, that reflects lack of adequate oral hygiene especially in formulation, 14g of the dried hydroalcoholic extract of each plant certain areas of the mouth and teeth. Bacteria are one of the most was added to 197.2 mL of water. Active and placebo mouthwash important factors responsible for periodontal inflammation [2]. preparations were prepared by the Pharmaceutical Department at Several lines of evidence have shown that elimination of microbial the School of Pharmacy (Mashhad, Iran), and were filled in identical dental plaque biofilm prevents gingivitis and dental cavities [3,4]. label-free bottles. Although the use of mechanical plaque control techniques such as twice daily teeth brushing and daily flossing helps controlling bacterial accumulation and plaque formation, still over 50% of 2.2. Inclusion and exclusion criteria adults have gingivitis in at least 3 to 4 teeth [5]. Furthermore, flossing and teeth brushing are often difficult and ineffective for Inclusion criteria were: (1) age between 18 and 65 yrs (2) most of the people, because these methods are unable to diagnosis of gingivitis, (3) having at least 18 natural teeth, (4) a fi completely remove plaque on all tooth surfaces [6,7]. In addition to Modi ed Gingival Index (MGI) score between 1.3 and 2.75, and (5) a fi mechanical oral hygiene approaches, there is a need for additional Modi ed Quigley-Hein (MQH) plaque score of at least 1.5. Exclusion measures to control bacterial plaque formation by using antimi- criteria were: (1) requirement to antibiotic therapy for the treat- crobial dentifrices or anti-plaque mouthwashes [8]. Currently, the ment of gingivitis, (2) antibiotic therapy during the preceding 14 fl most frequently used oral antiplaque and antiseptic mouthwash is days before the start of trial, (3) using anti-in ammatory, antico- chlorhexidine gluconate [9]. However, long-term use of chlorhex- agulant and immunosuppressive drugs during the study, (4) idine gluconate and other synthetic drugs (e.g. metronidazole and advanced periodontal or orthodontic diseases, (5) pregnancy and cetylpyridinium) is associated with adverse effects [10,11]. Hence, lactation, and (6) Sjogren's Syndrome. finding newer antiplaque and antimicrobial agents with a natural origin is important to increase treatment compliance and reduce 2.3. Study design adverse effects upon long-term application [4]. In previous clinical trials, some herbal dentifrices were shown to prevent gingivitis This study was designed as a randomized double-blind placebo- when used concomitantly with brushing [4,12]. Also, some studies controlled trial, and was conducted at the Mahyari Dental Clinic have shown that plant extracts can inhibit the growth of bacteria (Neyshabour, Iran) and Pharmaceutical Research Center (Mashhad, and fungi in subgingival plaques, thereby reducing gingivitis Iran) between May 2015 and September 2015. Patients fulfilling the e symptoms [13 16]. inclusion criteria were randomly (in a 1:1:1 order) assigned to the Pathologic changes in gingivitis are related to the existence of polyherbal mouthwash; (n ¼ 20), placebo mouthwash; (n ¼ 20) and collagenase-producing oral microorganisms attached to the 0.2% (w/v) chlorhexidine gluconate mouthwash (positive control; gingival and tooth tissues [17]. These microorganisms can activate n ¼ 20). All patients and investigators were unaware of the contents fl monocytes/macrophages to produce pro-in ammatory vasoactive of each bottle. The patients were given instructions to use the mediators such as prostaglandin E2 (PGE2) and interleukin-1 (IL-1) mouthwash for a period of 14 days. Dental examinations were [18,19]. In addition, plaque accumulation causes morphologic and performed at baseline, day 7 and day 14 of the trial. functional changes in gingiva [20]. Verbal and written information were given to all patients about Recent pharmacological studies have shown that rosemary the study and all patients gave written informed consent prior to fi (Rosmarinus Of cinalis L.) extract has antibacterial [21] and anti- the participation. The study protocol was approved by the Ethics oxidant properties [22], and can improve the healing of mouth Committee of the Mashhad University of Medical sciences (Mash- fi ulcers and bleeding gums [23,24]. Ginger (Zingiber of cinale)is had, Iran). All procedures in this study were in accordance with the another medicinal plant that can reduce prostaglandin biosynthesis ethical principles specified by the Declaration of Helsinki. The study [25], and exert inhibitory effects against periodontal bacterial protocol has been registered in the Iranian Registry of Clinical Trials growth [26]. Several previous studies have demonstrated the anti- (IRCT.ir) under the identification code IRCT2015070523078N1. inflammatory properties of marigold (Calendula officinalis) [27,28]. The efficacy of a polyherbal mouthwash containing calendula in preventing gingival bleeding has also been shown in a previous 2.4. Efficacy measures clinical trial [29]. Owing to the positive antibacterial, anti-inflammatory and The severity of gingivitis was assessed at baseline, day 7 and day wound-healing properties of the above-mentioned plant species, 14 of the trial using MGI on the lingual and buccal marginal the present randomized double-blind placebo-controlled trial gingivae and interdental papillae of all scorable teeth (Table 1). MGI aimed to evaluate the therapeutic efficacy of a polyherbal mouth- is a non-invasive tool for the evaluation of initial visual changes in wash formulation containing rosemary,