Khalighi et al. Clinical Phytoscience (2021) 7:73 https://doi.org/10.1186/s40816-021-00306-z ORIGINAL CONTRIBUTION Open Access Impact of Althaea Officinalis extract in patients with atopic eczema: a double- blind randomized controlled trial Negar Khalighi1, Farahzad Jabbari-Azad1, Maral Barzegar-Amini1, Jalil Tavakkol-Afshari2, Pouran Layegh3 and Roshanak Salari4* Abstract Background: Althaea Officinalis introduced as an emerging anti-inflammatory agent with immunomodulatory effects that may suppress the symptoms of atopic eczema. In this study, we aimed to investigate the impact of liposomal formulation of Althaea Officinalis flower extract compared with steroids for atopic eczema treatment. Methods: In this randomized, double-blind controlled trial phase II, forty patients with moderate to severe allergic atopic eczema confirmed by skin prick test were enrolled in the study from October 2018 to January 2019. Steroids on the lesions of the left side of the body and topical Althaea Officinalis extract (intervention) or eucerin as a topical placebo on the lesions of the right side of the body were tested. SCORAD (SCORing Atopic Dermatitis) was assessed at the baseline, and two, and four weeks after completing the trial. Data were analyzed by SPSS version 22. Results: In the active treatment group, after two weeks, the SCORAD was significantly lower in the left side (recovery with steroid treatment) (p < 0.001), and after 4 weeks the SCORAD was lower on both sides, and there were no significant differences between two sides (similarity between Althaea Officinalis and steroid effects). In the control group, the SCORAD score was significantly lower on the left side (steroid) after two and four weeks (p < 0.001). There was no side effect and reaction to drugs. Conclusions: Considering the potential side effects of steroids, and the similar efficacy of Althaea Officinalis flower extract, using this component may be accompanied by higher benefits in patients with atopic eczema. Trial registration: IRCT2016102323235N5. Keywords: Althaea Officinalis extract, Atopic eczema, SCORing Atopic Dermatitis Introduction antidepressants and topical therapies and topical treat- Atopic eczema is one of the most prevalent diseases ments such as topical corticosteroids, antibiotics, and dif- worldwide with a wide age distribution that is a debilitat- ferent eucerin in the treatment of atopic eczema with ing medical condition affecting psychological and somatic various severity indices [3]. Recently, alternative medicine functions [1, 2]. Current data support the use of systemic using traditional herbal medicines has gained great inter- therapies such as novel monoclonal antibodies and Janus est, especially in refractory and severe cases in different kinase inhibitors beside systemic corticosteroids and age groups with or without the supervision of clinicians [4, 5]. Components such as honey, beeswax, olive oil, and * Correspondence: [email protected] marshmallow (Althaea Officinalis) showed promising re- 4Department of Pharmaceutical Sciences in Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical sults on dermatologic disorders with autoimmune and/or Sciences, Mashhad, Iran inflammatory basis [6–8]. Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Khalighi et al. Clinical Phytoscience (2021) 7:73 Page 2 of 6 Althaea officinalis, (common name: Marshmallow), Methods which showed in Fig. 1, is a perennial species indigenous This was a randomized, double-blind controlled trial to Europe, Western Asia, and North Africa, which is phase II in forty patients with atopic eczema. The trial used in alternative medicine and as an ornamental plant was conducted from October 2018 to January 2019, at [9]. Its active compounds modulate the immune system Qaem Educational Hospital; the largest tertiary referral through stimulation of monocytes leading to secretion of hospital in Mashhad, Iran. This study is a pilot which interleukin-6 and tumor necrosis factor (TNF) [10, 11]. considering of the other similar articles, 20 people in Althaea Officinalis introduced as an emerging anti- each group were selected and each patient had both inflammatory agent [12] with immunomodulatory effects intervention and control (two Body side selected) to pre- that may suppress the symptoms of atopic eczema. vent sensory effects (severity of itching that depends on Therefore, it might suppress the symptoms of atopic the individual). eczema. The active treatment group included 20 patients with The prevalence of atopic dermatitis is increasing with moderate to severe allergic atopic eczema confirmed by the industrialization of communities. Regarding the ef- skin prick test were received steroids (Hydrocortisone fects of severe pruritus in patients, which is especially acetate ointment (1 %) or Triamcinolone, depending on children, its mental health problems on the patients and the age of the patient) on the lesions of the left side of parents, the side effects of topical steroids in high con- the body and topical Althaea officinalis extract (inter- sumption and increasing the systemic absorption, the re- vention) of the right side of their body. sistance and fear of parents in using topical steroids, and In the control group, 20 patients with moderate to se- vice versa overuse and its side effects, we decided to find vere allergic atopic eczema confirmed by skin prick test a suitable and low-risk solution to control the disease were received steroids on the lesions of the left side of and itching. Due to the anti-inflammatory and itching the body, and eucerin as a topical placebo on lesions of effects of marshmallows, we aimed to investigate the ef- the right side of their body. To make all patients uni- ficacy and safety of topical liposomal formulation of form and occurs no mistakes in completing the ques- Althaea officinalis flower extract for treating atopic tionnaire, the left side was chosen for steroids (constant eczema. side). Patients with simultaneous dermatologic disorders in- cluding bacterial infection, the patient using systemic immunosuppressive drugs, and patients who missed follow-up sessions showing poor compliance of them, were excluded. Also, before the randomization, all pa- tients were tested for hyper-reactive responses and were excluded if they had them. The online random generator was used to generate random choices (https://www. random.org/). The Intervention group received topical formulation of Althaea officinalis 10 %. In the summer of 2018, we bought the herb from the validated centers of medicinal herbs in Mashhad. The herbal extract was encapsulated in liposomes to improve its penetration through the skin. The active control group received topical steroids with a similar prescription pattern. For the effect of these compounds and their compari- son with steroids, it is necessary to remove confounding factors such as lesion severity, patient tolerance, skin thickness, and nutrition, etc. therefore, to achieve this goal, the effects of both drugs (marshmallow and hydro- cortisone) were examined in each person. This means that both groups were prescribed topical steroids. Patients or parents were asked to use the new formu- lation in half of the body (right) and steroids ointment in the second half (left). The duration of treatment was one month. Comparison of the Althaea Officinalis Fig. 1 Althaea Officinalis plant [13] flower extracts liposomal formulation with steroids Khalighi et al. Clinical Phytoscience (2021) 7:73 Page 3 of 6 Table 1 Demographic data between two groups of case and control Variable Active treatment group Active control group P-value Subjects enrolled 20 20 - Sex Male 18 (45 %) 16 (40 %) 0.651 Female 22 (55 %) 24 (60 %) Age (months) 34.00 (15.75-90.00) 31.00 (16.50–72.00) 0.787 ointment in the relieving symptoms (itching, redness, redness, bulge, scaling, and fissure. The objective bumps, scaling, and fissures) were done every 2 weeks SCORAD is a scoring system based on the assessment of (twice) after treatment by the therapist with patient his- extent and intensity in a standardized manner. The ex- tory and the SCORAD questionnaire. tent of lesions is scored by applying the rule of nine after drawing the lesions on an evaluation form. The intensity Herbal medicine formulation is determined by grading the 6 items on a scale from 0 In the summer of 2018, we bought the herb from the to 3 (erythema, edema/population, oozing/crusts, excori- validated centers of medicinal herbs in Mashhad. To ation, lichenification, and dryness). produce topical liposomal formulation of Althaea Offici- Data were analyzed by SPSS 25