Thematic Special Issue: Modern Drug Discovery – Current Challenges & Future Perspectives 2022 | 22 ANTI-INFLAMMATORY POTENTIAL OF ALOE VERA IN ORAL MUCOSITIS THERAPY: SYSTEMATIC REVIEW Review Article VERRELY CHRISTIAN CHANDRA 1 , NANAN NUR’AENY 2 , INDAH SUASANI WAHYUNI 2* 1 Bachelor Program in Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Indonesia, 2 Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Indonesia Email: indah.wahyuni@fkg.unpad.ac.id Received: 17 Apr 2021, Revised and Accepted: 31 May 2022 ABSTRACT This review aims to analyse the potency of Aloe vera for Oral Mucositis (OM) therapy. Articles searched using the keywords “Oral Mucositis” AND “Aloe vera”, conducted through PubMed, ScienceDirect, and Cochrane Library databases, and adapted to the PICO (Population, Intervention, Comparison, Outcome) framework. The inclusion criteria for articles were: Randomized Controlled Trial (RCT) study design; in English; full paper available; published in the range between 2011-2021 and with low risk of bias. RoB-tools JADAD Oxford Quality Scoring System was used. This paper writing refers to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. A total of 5 (five) articles met the criteria for a qualitative review and all showed a high range of quality articles. It was found that both Aloe vera solution 70% and Aloe vera gel 10% showed a reduction of radiotherapy or chemotherapy-induced oral mucositis grade. Aloe vera mouthwash has an equal anti-inflammation effect compare to benzydamine on the patient with radiotherapy-induced oral mucositis, whereas the use of other formula containing Aloe vera with other herbal materials did not show an anti-inflammatory effect. Drug formulation containing Aloe vera can be used as an alternative therapy in the management of Oral Mucositis (OM) with anti-inflammatory potency that can reduce pain and the severity of oral mucositis. Keywords: Aloe vera, Anti-inflammation, Oral mucositis © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2022.v14ti.21 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Oral Mucositis (OM) is a toxic side effect of chemotherapy and/or radiotherapy treatment for malignancy/cancer [1]. The clinical feature of OM in the form of erosion and ulceration lesions on the oral mucosa that are usually widespread and painful, thus causing problems related to basic psychological needs such as chewing and swallowing food and can directly or indirectly affect a person quality of life [1]. OM involves a variety of complex biological interactions, such as: changes in tissue structure, infiltration of inflammatory cells, and oral microbiome [2]. It is estimated that 40-70% of patients who are undergoing chemotherapy and/or radiotherapy will experience OM with varying levels accompanied by clinical features that also varies [3, 4]. OM can also cause complications such as dysphagia, changes in taste, weight loss, and the appearance of secondary infections [5]. These complications can disrupt the schedule of cancer treatment so inadequate and complicate or extend the treatment time for malignancy conditions/cancer suffered [5]. Based on these problems, the therapy recommended according to the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) for OM is currently in the form of basic oral care. Therapies that use growth factors and cytokines, cryotherapy, photobiomodulation, anti-inflammatory drugs, anti-microbial drugs, coating agents, anesthetics, analgesics, and various natural ingredients are some of the basic oral care [6]. Steroids are also one of the drugs used as therapies for OM, but their use has several side effects [7]. This causes the scientist to look for steroid replacement alternatives with other drugs with equivalent but more potential, few or no side effects [7]. Currently, herbal products are being widely researched and used with therapeutic purposes because they are considered more economical, relatively safe, and generally have low toxicity [8]; however, the effectiveness and safety of these herbal medicines still need to be scientifically proven before they can be used to prevent or treat disease [9, 10]. Among these herbal products is Aloe vera (Aloe barbadensis miller) which is a shrub-like plant, can survive for years, xerophyte, succulent, and green in colour. Aloe vera belongs to the family Asphodelaceae (Liliaceae) [11]. All types of Aloe vera (AV) contain gels that have more than 70 biological compounds with various properties such as anti-inflammatory, antimicrobial, antioxidant, antidiabetic, wound healing, immune system enhancer [12], antiviral, and anticancer [13]. This plant includes types of plants that are easy to grow and do not require special care. AV can grow in areas at altitudes of 0-1500 meters above sea level, air temperatures range from 16 °C–33 °C, and rainfall of 1000-3000 mm per year [14]. Until now, there have been several clinical trials on the use of Aloe vera as an OM therapy [15–20], as well as the writing of systematic review published in 2016, on the clinical effectiveness of Aloe vera in the management of oral mucosal disease [21] and systematic review published in 2021 on the effectiveness and safety of herbal plants for oral mucositis therapy [22], but the two did not discuss specifics regarding Aloe vera therapy for OM. Based on this, the writing of this review is intended to specifically discuss the potential and therapeutic response of using Aloe vera as an OM therapy so that it can be the basis of treatment (evidenced-based) for OM therapy scientifically. MATERIALS AND METHODS This article is a systematic review compiled following the guidelines of Preferred Reporting Items for Systematic Review and Meta- analysis (PRISMA) [23]. Research questions are determined according to the purpose of writing, guided by the PICO (Population, Intervention, Comparison, and Outcome) [24] framework as follows: (1) Population: patients with Oral Mucositis (OM) diagnosis; (2) Intervention: Aloe vera; (3) Comparison: placebo and conventional therapy; (4) Outcome: (a) Subjective parameters of assessing pain; (b) Objective assessment parameters using the World Health Organization-Oral Mucositis (WHO-OM) grading system; (c) Complication parameters: dysphagia, nasogastric tube placement, intravenous hydration, need of supportive drugs, weight loss, and interruption of radiotherapy; (d) Side effects. The search method for research questions was conducted using the keywords "Oral Mucositis" AND "Aloe vera" Filters: Full text, Randomized Controlled Trial, in the last 10 y, Humans, English. The digital data bases used are: PubMed, Science Direct, and Cochrane Library. Additional article searches are also done manually by checking the list of article references that have been obtained, will be used if relevant to the research topic and have good article quality. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Thematic Special Issue 2022