Formulation of Viola odorata L. Tablet and Evaluation of the Product Effect on Breast Cancer-Related Fatigue: A Randomized, Controlled Pilot Trial
-
Ghazaleh Heidarirad
,
Homa Hajimehdipoor
,
Sadegh Rajabi
,
Haniyeh Kashafroodi
,
Fatemeh Khancherli
,
Mona Malekzadeh Moghani
,
Behnaz Keramatian
,
Fatemeh Ghorbannejad
Abstract
This study was designed to formulate a Viola odorata L. tablet (VOT) and evaluate its efficacy in managing cancer-related fatigue (CRF) in breast cancer patients undergoing radiotherapy. The tablet was formulated and subjected to quality control tests. The pilot study was conducted as a randomized, double-blind trial. A total of 18 breast cancer patients were enrolled and randomly assigned to two groups. The intervention and control groups received VOT/bis in die (Bid) and placebo, respectively, for 4 weeks. All the patients completed the visual analog fatigue scale (VAFS), fatigue severity scale (FSS), and cancer fatigue scale (CFS) questionnaires before and after the intervention. The best tablet formulation contained V. odorata extract 486 mg, PVPK30 50 mg, lactose 450 mg, Avicel PH102 100 mg, SiO2 14 mg, and magnesium stearate 20 mg. Dimensions, disintegration time, hardness, friability, weight, and total phenolics as pyrogallol were 7.1×9.9×30.3 mm, 28 min, 9.5 kp, 0.37%, 1120mg, 22.8 mg/tab, respectively. More than 80% of the phenolics in the tablets were dissolved during the dissolution test in 30 min. In the pilot study, only VOT treatment significantly decreased the VAFS (p = 0.02), FSS (p = 0.08), and CFS (p=0.03) scores. The results indicated desirable VOT physicochemical characteristics and suggested it as an herbal product for managing CRF in breast cancer patients.
Scholliers A, Cornelis S, Tosi M, Opsomer T, Shaproski D, et al. Impact of fatigue on anaesthesia providers: a scoping review. Br J Anaesth 2023;130:622-635.
Lock AM, Bonetti DL, Campbell ADK. The psychological and physiological health effects of fatigue. Occup Med (Lond) 2018;68:502-511.
Finsterer J, Mahjoub SZ. Fatigue in healthy and diseased individuals. Am J Hosp Palliat Care 2014;31:562-575.
Park KH, Lee H, Park EY, Sung JH, Song MK, et al. Effects of an urban forest healing program on cancer-related fatigue in cancer survivors. Support Care Cancer 2023;32:4.
Campos MP, Hassan BJ, Riechelmann R, Del Giglio A. Cancer-related fatigue: a review. Rev Assoc Med Bras (1992) 2011;57:211-219.
Poulson MJ. Not just tired. J Clin Oncol 2001;19:4180-4181.
Bower JE. Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 2014;11:597-609.
Mirzaei H, Gharehgozlou R, Heydarirad G, Fahimi S, Ghafari S, et al. Efficacy and safety of jollab (a saffron-based beverage) on cancer-related fatigue in breast cancer patients: a double-blind randomized clinical trial. Complement Med Res 2022;29:437-445.
Bower JE, Lamkin DM. Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun 2013;30 Suppl:S48-57.
H AL, Rimawi O. Radiotherapy-induced fatigue in Palestinian breast cancer survivors. Health Psychol Behav Med 2024;12:2302569.
Bower JE, Bak K, Berger A, Breitbart W, Escalante CP, et al. Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation. J Clin Oncol 2014;32:1840-1850.
Marrelli M. Medicinal Plants. Plants 2021;10:1355.
Feyzabadi Z, Jafari F, Kamali SH, Ashayeri H, Badiee Aval S, et al. Efficacy of Viola odorata in treatment of chronic insomnia. Iran Red Crescent Med J 2014;16:e17511.
Siddiqi HS, Mehmood MH, Rehman NU, Gilani AH. Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract. Lipids Health Dis 2012;11:6.
Yadollahi H, Safaeinejad F, Hajimehdipoor H, Mousavi Z, Ara L, et al. Anti-fatigue effect of Viola odorata L. in forced swimming test in rat. Trad Integr Med 2023;8:164-169.
Fahimi S, Mortazavi SA, Abdollahi M, Hajimehdipoor H. Formulation of a traditionally used polyherbal product for burn healing and hptlc fingerprinting of its phenolic contents. Iran J Pharm Res 2016;15:95-105.
Choopani R, Hajimehdipoor H, Molaei K, Kashafroodi H, Tavakolifar F, et al. Formulation and quality evaluation of Coriander Triphala tablet. J Med Plants 2021;20:68-77.
Esmaeili S, Keramatian B, Kashafroodi H, Choopani R, Hajimehdipoor H. Capparis spinosa L. tablet: from traditional to modern dosage form. J Med Plants 2022;21:56-65.
Rowe RC, Sheskey P, Quinn M. Handbook of pharmaceutical excipients. London: Libros Digitales-Pharmaceutical Press 2009.
Cartwright AC. The British pharmacopoeia, 1864 to 2014: medicines, international standards and the state. Routledge 2016.
Agency EM. ICH Topic Q1A (R2) stability testing of new drug substances and products. Eur Med Agency Amsterdam, The Netherlands 2003.
Vishal A, Parveen K, Pooja S, Kannappan N, Kumar S. Diuretic, laxative and toxicity Studies of Viola odorata aerial parts. Pharmacol online 2009;1:739-748.
Dayani L, Dinani MS, Aliomrani M, Hashempour H, Varshosaz J, et al. Immunomodulatory effects of cyclotides isolated from Viola odorata in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis. Mult Scler Relat Disord 2022;64:103958.
Fallah M, Musapour A, Hajimehdipoor H, Jafari F, Rajabi S. Viola odorata alleviates airway inflammation and histopathological changes in an animal model of allergic asthma. Res J Pharmacogn 2024;11:49-57.
Saleem U, Hira S, Anwar F, Shah MA, Bashir S, et al. Pharmacological screening of Viola odorata L. for memory-enhancing effect via modulation of oxidative stress and inflammatory biomarkers. Front Pharmacol 2021;12:664832.
Karshikoff B, Sundelin T, Lasselin J. Role of inflammation in human fatigue: relevance of multidimensional assessments and potential neuronal mechanisms. Front Immunol 2017;8:21.
Schedlowski M, Engler H, Grigoleit JS. Endotoxin-induced experimental systemic inflammation in humans: a model to disentangle immune-to-brain communication. Brain Behav Immun 2014;35:1-8.
Wang XS, Woodruff JF. Cancer-related and treatment-related fatigue. Gynecol Oncol 2015;136:446-452.
Romadlon DS, Huang HC, Chen YC, Hu SH, Hasan F, et al. Fatigue following type 2 diabetes: Psychometric testing of the Indonesian version of the multidimensional fatigue Inventory-20 and unmet fatigue-related needs. PLoS One 2022;17:e0278165.
Wang W. Radiotherapy in the management of early breast cancer. J Med Radiat Sci 2013;60:40-46.
Werdani YDW, Prasetya AW. Evaluation on symptoms and self-treatment due to radiotherapy and chemotherapy based on different cancer stage. J Ilmiah Kesehatan 2020;9:129-139.
Dilalla V, Chaput G, Williams T, Sultanem K. Radiotherapy side effects: integrating a survivorship clinical lens to better serve patients. Curr Oncol 2020;27:107-112.
Barazzuol L, Coppes RP, van Luijk P. Prevention and treatment of radiotherapy-induced side effects. Mol Oncol 2020;14:1538-1554.
Hsiao CP, Daly B, Saligan LN. The Etiology and management of radiotherapy-induced fatigue. Expert Rev Qual Life Cancer Care 2016;1:323-328.
McKelvey KJ, Hudson AL, Back M, Eade T, Diakos CI. Radiation, inflammation and the immune response in cancer. Mamm Genome 2018;29:843-865.
Di Maggio FM, Minafra L, Forte GI, Cammarata FP, Lio D, et al. Portrait of inflammatory response to ionizing radiation treatment. J Inflamm (Lond) 2015;12:14.
Wang XB, Wu DJ, Chen WP, Liu J, Ju YJ. Impact of radiotherapy on immunological parameters, levels of inflammatory factors, and clinical prognosis in patients with esophageal cancer. J Radiat Res 2019;60:353-363.
Feng LR, Dickinson K, Kline N, Saligan LN. Different phenotyping approaches lead to dissimilar biologic profiles in men with chronic fatigue after radiation therapy. J Pain Symptom Manage 2016;52:832-840.
Karimi FZ, Nazari N, Lotfi F, Mazloom SR, Yousefi M, et al. Effects of Viola odorata syrup on sleep quality in menopausal women: a randomized, triple-blind, controlled trial. Sleep Breath 2024;28:1137-1144.
Feyzabadi Z, Rezaeitalab F, Badiee S, Taghipour A, Moharari F, et al. Efficacy of Violet oil, a traditional Iranian formula, in patients with chronic insomnia: A randomized, double-blind, placebo-controlled study. J Ethnopharmacol 2018;214:22-28.
Shayesteh M, Vaez-Mahdavi MR, Shams J, Kamalinejad M, Faghihzadeh S, et al. Effects of Viola odorata as an add-on therapy on insomnia in patients with obsession or depression: a pilot randomized double-blind placebo-controlled trial. J Altern Complement Med 2020;26:398-408.
Huang S, Huang Q, Zhou Z, Zhang J, Zhan Y, et al. The efficacy of V. odorata extract in the treatment of insomnia: a systematic review and meta-analysis. Front Neurol 2022;13:730311.
| Files | ||
| Issue | Vol 10, No 3, 2025 | |
| Section | Research Article(s) | |
| DOI | https://doi.org/10.18502/tim.v10i3.19759 | |
| Keywords | ||
| Viola odorata Formulation Breast cancer Cancer-related fatigue Pilot study | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
