Skip to main content
Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: A study protocol

  • Romina Fili,

    Roles Conceptualization, Investigation, Methodology, Software, Visualization, Writing – original draft, Writing – review & editing

    Affiliation Babol University of Medical Sciences, Babol, I.R. Iran

  • Fereshteh Behmanesh ,

    Roles Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing

    f.behmanesh2015@gmail.com

    Affiliation Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, I.R. Iran

  • Sana Nazmi,

    Roles Conceptualization, Writing – review & editing

    Affiliation Babol University of Medical Sciences, Babol, I.R. Iran

  • Maryam Nikpour,

    Roles Conceptualization, Formal analysis, Methodology, Writing – review & editing

    Affiliation Non-Communicable Pediatric Diseases Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, I.R. Iran

  • Zahra Memariani

    Roles Conceptualization, Methodology, Software, Writing – review & editing

    Affiliation Pharmaceutical Sciences Research Center, Babol University of Medical Sciences, Babol, I.R. Iran

Abstract

Background

Episiotomy is associated with side effects, such as pain and wound infection. Additionally, discomfort after episiotomy affects the quality of life of both the mother and the baby. Medicinal herbs are one alternative method for the treatment of episiotomy wounds. This study will investigate the effectiveness of the combination of olive and black seed oil on pain intensity and the healing of episiotomy wounds in primiparous women.

Methods

This randomized clinical trial will be conducted on primiparous women who have had a normal delivery with an episiotomy. There are 3 groups in this study: one group will receive a combination of olive oil and black seed oil, another group will receive olive oil alone, and the use of oils will start 24 hours after delivery. Ten drops will be applied topically 3 times a day for 10 days. The third group (control) will receive only routine care. Data will be collected through a demographic characteristics questionnaire, REEDA (Redness, Edema, Ecchymosis, Discharge, and Approximation) Scale, and Visual Analog Scale. To determine and compare the effects of pharmaceutical interventions on pain intensity and episiotomy wound healing in the groups, an analysis of variance (ANOVA) test with repeated measurements will be used with SPSS version 22.

Discussion

The results of this study will show the effects of a combination of olive and black seed oil, as well as olive oil alone, on pain intensity and episiotomy wound healing in primiparous women. The positive effects observed in this trial with these oils could be valuable for women who have undergone an episiotomy.

Introduction

Episiotomy is an incision in the area between the perineum and the anus, performed to enlarge the perineum and facilitate the process of natural childbirth, especially in primiparous women [13]. The prevalence of episiotomy varies in different countries and races [4]. For example, in Asian countries, due to the anatomical features of the perineum, episiotomy is used as a method to facilitate natural delivery. But there is no inferable statistics of the prevalence of episiotomy in Iran [5]. However, the rate of using episiotomy in a study in Iran was 41.5% [6]. This intervention is associated with side effects such as pain [3, 7, 8]. Studies have shown that approximately 30% of women experience pain in the first two weeks, and 7% experience it up to 3 months after natural delivery [9]. Due to the lack of direct observation of the mother and the proximity of the wound area to the anus, there is a possibility of wound infection [5, 10, 11]. Discomfort after episiotomy affects the quality of life of both the mother and the baby [3, 12, 13]. Considering that the baby requires the mother’s presence and support for growth and development, especially in the early days after birth, it is crucial to pay attention and provide support to mothers who have undergone an episiotomy [10, 14].

Since Iran’s current policy is to increase the birth rate and population, more attention should be paid to prenatal and post-pregnancy care, especially for vaginal childbirth. An unpleasant experience during childbirth can affect a mother’s future pregnancies and may lead to her deciding not to have more children, ultimately reducing population growth [9]. On the other hand, if episiotomy is not used, there is a risk of perineal tears that may cause problems for the mother, such as a reduced quality of sexual life [7, 15] and difficulties with breastfeeding [2, 16]. In Iran, episiotomy is still common, with a prevalence of over 41% among primiparous women [17].

To alleviate the pain intensity of episiotomy and facilitate its faster healing, various treatment methods, including oral, rectal, and sitz baths, are used [14, 18]. Given the increasing prevalence of herbal medicine in recent decades [19] and the adverse effects associated with chemical drugs, such as high costs [7] and mild drowsiness to cardiotoxicity [20], it is advisable to consider herbal medicine, following the recommendations of the World Health Organization [21]. It appears that plant oils, such as olive oil and black seed oil, may be effective in promoting the healing and repair of perineal wounds [21, 22]. According to studies, many medicinal plants, especially olive oil, can accelerate wound healing and reduce pain and complications caused by episiotomy [16, 23]. In a previous study by the author, the use of olive oil sitz baths was found to be effective in reducing pain intensity and promoting episiotomy wound healing in primiparous women [14]. Olive oil is rich in substances that provide it with antimicrobial, antifungal, and anti-inflammatory properties [24, 25]. These include phenolic compounds that promote cell repair, antioxidants that help reduce inflammation, and oleocanthal that can alleviate pain [14, 23, 26]. Moreover, various studies have shown the beneficial effects of olive oil [27], its unsaturated fatty acids, including oleic acid [28], and its phenolic compounds [29] on wound healing. Olive oil has been found effective in treating skin diseases, suppressing the growth of viruses and bacteria, and promoting wound healing [14, 30]. Black seed contains 30% to 40% oil and is particularly rich in a type of antioxidant called thymoquinone [31, 32], as well as phenols, linoleic acid, and oleic acid, which have been the subject of various studies demonstrating their positive effects on wound healing [33]. Additionally, black seed exhibits anti-inflammatory and analgesic properties, along with antiviral and antifungal effects [34, 35]. These effects can be attributed to thymoquinone, which is one of the main constituents of black seed [36]. Thymoquinone is a monoterpene diketone with a molecular weight of 164.204 g/mol and is considered a lipophilic compound [37]. In fact, most of the plant’s properties are attributed to thymoquinone [38]. Studies have shown that black seed is suitable for promoting wound healing in the human body and can help prevent infections [35, 39]. Furthermore, adding black seed oil to olive oil enhances its antioxidant properties [40]. Given the limited number of human clinical studies on black seed oil and the scarcity of research regarding the local effectiveness of the combination of olive oil and black seed oil in alleviating pain and promoting episiotomy wound healing, the present study aims to evaluate the effectiveness of the combination of olive and black seed oil in reducing pain intensity and facilitating episiotomy wound healing in primiparous women. This study will be implemented in Shahid Yahya Nejad Hospital, Babol city. In this hospital, low risk mothers are admitted for delivery. Routine care after episiotomy in these mothers includes sitting in a basin of warm water, and the mothers do not use any oil to repair episiotomy. Recently, some gynecologists prescribe Nivasha spray for faster healing of episiotomy wounds, but these mothers will not be included in the study due to interference with the results of our study. This study adopts a parallel design to compare the side effects caused by drug use, such as burning, itching, episiotomy wound opening, and the need for repair, among 3 groups.

Materials and methods

Study design

This randomized clinical trial will be conducted as a parallel-group, non-inferiority study on postpartum women who have undergone episiotomy in the hospitals of Babol city. The schedule of enrolment, interventions, and assessments was shown in Fig 1. The research design is based on the interpretive standards of trial reports (Fig 2). This study was approved by the Ethics Committee of Babol University of Medical Sciences (code: IR.MUBABOL.REC.1401.145). Additionally, the study protocol was registered in the Iranian Registry of Clinical Trials (code: IRCT20180218038783N2) (S1 File). All methods will be performed in accordance with the relevant guidelines and regulations, including the Declaration of Helsinki, and written informed consent will be obtained from all participants. The trial results will be communicated to participants, health care professionals, the public, and other relevant groups, as well as researchers and sponsors, through the publication of results and reporting in results databases. The SPIRIT Checklist has been shown in S1 Checklist.

thumbnail
Fig 1. The schedule of enrolment, interventions, and assessments.

https://doi.org/10.1371/journal.pone.0302161.g001

thumbnail
Fig 2. CONSORT (Consolidated Standards of Reporting Trials) flow diagram.<

/Figure_Caption>

https://doi.org/10.1371/journal.pone.0302161.g002

Eligibility criteria

Women interested in participating in the study will be invited. After explaining the research objectives and obtaining written informed consent, the researcher will proceed with convenient sampling. Then, based on the inclusion criteria, the samples will be randomly divided into two intervention groups and one routine care group.

Inclusion criteria are primiparous women, natural vaginal delivery with episiotomy, literacy, and BMI < 30. Exclusion criteria are unwillingness of participants to continue participating in the study, fourth-degree tear, history of dermatitis, history of allergy and eczema diagnosed related to plants, and history of gestational diabetes and overt diabetes.

Study sample and sampling

The required sample size was estimated to be 36 based on a previous study on pain intensity of episiotomy using G Power software. The effect size (mean difference) was determined to be 1.4 (pain intensity of episiotomy between the intervention and control groups), with an α of 0.05 and a β of 5% [20].

The researcher will select the samples according to the inclusion criteria and randomly allocate them into 3 groups of 36 individuals using a random-numbers table. The block size will be 6, and the table will be managed by a researcher who is not involved in the sampling process. The person responsible for sampling (a midwifery student) will receive the intervention code from the managing researcher after selecting the sample based on the inclusion criteria. To blind the random allocation list, a unique code will be assigned to each of the intervention groups, known only to the herbal pharmacist associate. The supervisor, researcher, and statistical analyst will be blinded to ensure proper management. To ensure the reliability of this research, the person who examines the episiotomy wound on the first and tenth days will be the same for all mothers. A skilled and trained midwifery student will collect the data by examining the mothers.

Data collection and management

This research will be conducted after obtaining permission from the Ethics Committee of Babol University of Medical Sciences, registering with the Iranian Registry of Clinical Trials, and obtaining the necessary sampling permits. After contacting the midwifery department of the hospitals affiliated with Babol University of Medical Sciences, the researcher invites eligible women to participate in the study. The researcher will first explain the study’s purpose and the nature of the intervention to the women. The researcher ensures the confidentiality of their information, clarifies her responsibility for any treatment complications, and assures them that the treatment interventions will not change if they choose not to participate. Participants are then requested to provide written consent. Additionally, participants are assured that they can withdraw from the study at any stage. Subsequently, the researcher (a midwifery student) informs the supervisor about the sample’s inclusion in the study, and the supervisor shares the intervention code with the researcher.

All study subjects will be educated on following post-delivery health tips and caring for episiotomy wounds. The intervention groups (one group receiving olive oil plus black seed oil and the other receiving olive oil alone) will also receive instructions on how to use the containers containing the oils. Women in the intervention groups will use the oils 24 hours after delivery, applying 10 drops topically 3 times a day for 10 days. Given that each milliliter contains 15 drops, and mothers are required to use the oils 3 times a day, approximately 30 mL of each type of oil will be provided to mothers for the duration of 10 days.

The participants will be instructed to wash and dry their perineum before applying the oils. They should then wear gloves and slowly apply 10 drops of oil to the perineum, massaging it in with their hands. The control group will receive only routine care. All mothers will be provided with painkillers as needed. The type and number of painkillers used by each group will be recorded using a checklist completed by the mother over 10 days. This data will be evaluated and considered as an auxiliary variable in the final analysis. All mothers will be examined again on the 10th day after delivery to determine the severity of pain and healing of the episiotomy wound.

In this research, 3 questionnaires will be administered within the first 24 hours and 10 days after delivery.

  1. Demographic Characteristics Questionnaire: This questionnaire comprises 22 questions that gather information such as age, education level, place of residence, employment status, height, weight, number of pregnancies and abortions, duration of hospitalization during labor, receipt of antibiotics during labor and post-delivery, and hospitalization of the baby in the intensive care unit. The questionnaire was designed based on the research objectives to identify potential confounding variables.
  2. Visual Analog Scale for Measuring Episiotomy Pain Intensity: The Visual Analog Scale, also known as the McGill Pain Ruler, is a linear scale used for pain assessment. It consists of a 10-cm ruler, with 0 indicating no pain and 10 indicating the most severe pain possible. Between these 2 endpoints, the scale is divided into 3 levels: mild pain (1–3), moderate pain (4–7), and severe pain (8–10) [41]. Perineal pain intensity refers to the pain experienced by mothers in their perineal area and is self-reported before and after the intervention.
  3. The Redness, Edema, Ecchymosis, Discharge, and Approximation Scale: The REEDA (Redness, Edema, Ecchymosis, Discharge, and Approximation) Scale is a standardized tool for assessing episiotomy wound healing, including variables such as swelling, bruising, discharge, redness, and the distance between the 2 edges of the episiotomy wound. Each of these variables is scored on a scale from 0 to 3. The researcher records the scores for each variable separately after observing and examining the patient both before and after the examination. The overall score on the scale ranges from 0 to 15, with higher scores indicating less favorable wound healing and lower scores indicating better wound healing. In a reliability analysis conducted by Alvarenga et al. (2015), the kappa coefficient was reported for this scale. The results indicated good agreement for the variable of redness (0.46 < Kappa ≥ 0.66), marginal to good agreement in the first 3 assessments of edema (0.16 < Kappa ≥ 0.46), marginal agreement in the evaluation of ecchymosis (0.25 < Kappa ≥ 0.42), and good agreement in the assessment of the discharge item (0.75 < Kappa ≥ 0.88) [42].

The primary outcomes of this study include the assessment of pain intensity in the episiotomy area and the evaluation of episiotomy wound healing. Secondary outcomes include the monitoring of symptoms such as burning and itching, as well as the occurrence of episiotomy opening and the need for painkillers. These secondary outcomes will be assessed through a combination of examinations conducted by the researcher and self-reports provided by the mothers. Additionally, any side effects reported by each participant will be carefully reviewed, and the total number of side effects within each group will be documented.

The product used in the study is a combination of cold-pressed black seed oil and standard extra-virgin olive oil, both of which adhere to national standards. The standard extra-virgin olive oil is manufactured by a pharmaceutical-grade company called Pishgaman Chemi, while the cold-pressed black seed oil is obtained from the pharmaceutical company Barij Essance. These two oils are mixed in equal proportions [43]. Importantly, both products meet approved specifications in terms of microbial and pollution control, as well as chemical and physical standards. The process of mixing and packaging these two oils is conducted under hygienic conditions within the traditional pharmacy laboratory of the Faculty of Traditional Medicine.

Data analysis

The analysis method used in this study is intention-to-treat analysis, ensuring the maintenance of the random allocation process.

All analyses will be conducted using SPSS version 22, including both descriptive and analytical analyses. A comprehensive outline of the analysis procedures will be documented in the statistical analysis plan.

Descriptive information will be presented using means and SDs or as numbers and percentages. To assess the correlation between quantitative variables, Pearson’s correlation test will be used, while the chi-square test will be used to examine the correlation between 2 qualitative variables.

For comparing pain intensity and episiotomy wound healing after the intervention in the 3 groups, the analysis of covariance (ANCOVA) test will be used, taking into account the measurements taken prior to the intervention. Multilevel linear regression will be conducted to adjust for confounding variables, including demographic, midwifery, and delivery-related factors.

Additionally, the effect size will be demonstrated through mean differences and 95% CIs. A significance level of P < 0.05 will be considered as the threshold for statistical significance.

Report

Researchers will enhance their interaction with individuals to ensure comprehensive data collection. To achieve this, we will establish more robust communication channels with the participants via social media and phone to provide medication reminders.

In this process, one of the researchers (RF) will assume responsibility for data collection, while another individual (SN) will be tasked with entering the data into the SPSS software. A data manager (MN) will review all the data without knowledge of the treatment allocations. These procedures will be conducted under the supervision of FB.

Discussion

This study aims to investigate the effectiveness of a combination of olive and black seed oil on pain intensity and episiotomy wound healing in primiparous women. Olive oil is known for its rich content of substances that impart antimicrobial, antifungal, and anti-inflammatory properties [24, 25], including peniphenol that promotes cell repair, antioxidants that help reduce inflammation, and oleocanthal that suppresses pain [14, 23, 26]. Black seed oil, on the other hand, contains 30% to 40% oil and is particularly rich in thymoquinone, a type of antioxidant [31, 32], along with phenols, linoleic acid, and oleic acid, which various studies have shown to be effective in wound healing [33]. Studies have shown that black seed oil is suitable for wound healing in the human body and can prevent infection [35, 39]. Moreover, combining black seed oil with olive oil enhances its antioxidant properties [40].

Skin wound healing is a critical physiological process that involves the collaboration of various cell types and their products. The repair process begins early in the inflammatory phase, leading to the replacement of specialized structures through collagen deposition and regeneration, which involves cell proliferation and subsequent differentiation from existing tissue cells [44].

While the individual effects of black seed oil [21] and olive oil [9, 14] on episiotomy have been evaluated in previous studies, this research conducted by the study team is the first to examine the combined impact of these 2 oils on episiotomy. Clinical research on whether topical application of this oil combination can effectively promote episiotomy repair and alleviate perineal pain severity is limited. If the results of this study show that the combination of these 2 substances is indeed effective in reducing episiotomy pain intensity and enhancing healing, it could be proposed as a cost-effective treatment option. One of the major limitations of the current study is that some mothers may not return on the 10th day due to the recovery or because of hospitalization of the baby and another limitation is that sterile tape won’t be used and visual inspection will be used in the assessing of wound healing.

Conclusion

The results of this study will show the effects of the combination of olive oil and black seed and olive oil alone on pain intensity and episiotomy wound healing in primiparous women. The potential positive outcomes from testing these oils may propose a viable solution for the use of low-risk methods after childbirth.

Acknowledgments

The authors would like to thank the Deputy of Research and Technology of Babol University of Medical Sciences and mothers who will participate in this study.

References

  1. 1. Tara F, Golmakani N, Motlagh ER, Assili J, Shakeri M. P284 The effects of turmeric (Curcuma longa L) ointment on healing of episiotomy site in primiparous women. Int J Gynaecol Obstet. 2009; 107:S493–S4. https://doi.org/10.1016/S0020-7292(09)61774-4
  2. 2. Vakilian K, Atarha M, Bekhradi R, Chaman R. Healing advantages of lavender essential oil during episiotomy recovery: a clinical trial. Complement Ther Clin Pract. 2011; 17:50–3. pmid:21168115
  3. 3. Moradi M, Niazi A, Mazloomi E, Mousavi SF, Lopez V. Effect of lavender on episiotomy wound healing and pain relief: a systematic review. Evid. Based Care J. 2020;10: 61–9. pmid:33066851
  4. 4. Abedian S, Abedi P, Jahanfar S, Iravani M, Zahedian M. The effect of Lavender on pain and healing of episiotomy: A systematic review. Complementary Therapies in Medicine. 2020; 53:102510. pmid:33066851
  5. 5. Torkashvand S, Jafarzadeh-Kenarsari F, Donyaei-Mobarrez Y, Chaboki BG. Effectiveness of Olea Herbal Ointment on Episiotomy Wound Healing Among Primiparous Women: A Randomized Clinical Trial. Jundishapur Journal of Natural Pharmaceutical Products. 2021; 16: 348–354. https://doi.org/10.5812/jjnpp.104570
  6. 6. Rasouli M, Keramat A, Khosravi A, Mohabatpour Z. Prevalence and factors associated with episiotomy in Shahroud City, northeast of Iran. Int J Womens Health Reprod Sci. 2016; 4:125–129 https://doi.org/10.15296/ijwhr.2016.29
  7. 7. Sabzaligol M, Safari N, Baghcjeghi N, Latifi M, Bekhradi R, Taghizadeh M, et al. The effect of Aloevera gel on prineal pain & wound healing after episiotomy. Complementary Medicine Journal. 2014; 4:766–775.
  8. 8. Shayan A, Sourinezhad H, Barzegar F, Ahmadinia H, Masoumi Z, Moradkhani S, et al. The effect of olive oil and honey combination on episiotomy wound healing and pain relief: A randomized clinical trial. Curr Womens Health Rev. 2020; 16:145–151. https://doi.org/10.2174/1573404816666200123111718
  9. 9. Hables RM. Effect of Olive Oil, Lavender Oil and Placebo on Pain Intensity and Healing of Episiotomy in Women. Tnta Sci. Nurs. J. 2021; 20:47–63. https://doi.org/10.21608/tsnj.2021.168849
  10. 10. Mardani F, Hadizadeh-Talasaz F, Bahri N. Effect of medicinal plants on episiotomy wound healing in Iran: a systematic review study. Iran. J. Obstet. Gynecol. Infertil. 2020; 23:79–94. https://doi.org/10.22038/IJOGI.2020.16618
  11. 11. Nikpour M, Delavar MA, Khafri S, Ghanbarpour A, Moghadamnia AA, Esmaeilzadeh S, et al. The use of honey and curcumin for episiotomy pain relief and wound healing: A three-group double-blind randomized clinical trial. Nurs. Midwifery Stud. 2019; 8:64–69. https://doi.org/10.4103/nms.nms_74_17
  12. 12. Sheikhan F, Jahdi F, Khoei EM, Shamsalizadeh N, Sheikhan M, Haghani H. Episiotomy pain relief: Use of Lavender oil essence in primiparous Iranian women. Complement. Ther. Clin. Pract. 2012; 18:66–70. pmid:22196577
  13. 13. Golozar S, Namjouian F, Latifi SM, Mirahi A. Evaluating the effect of oral bromelain (pineapple) on episiotomy wound healing in primiparus women. KAUMS. J. (FEYZ). 2011; 15:84–90. (In Persian). https://www.researchgate.net/publication/321161941
  14. 14. Behmanesh F, Aghamohammadi A, Zeinalzadeh M, Khafri S. Effects of olive oil sitz bath on improvement of perineal injury after delivery. Koomesh. 2013; 14: 309–315. (In Persian) http://koomeshjournal.semums.ac.ir/article-1-1694-en.html
  15. 15. Hartmann K, Viswanathan M, Palmieri R, Gartlehner G, Thorp J, Lohr KN. Outcomes of routine episiotomy: a systematic review. Jama. 2005; 293:2141–2148. pmid:15870418
  16. 16. Kaviani M, Sepasi S, Azima S, Emamghoreishi M, Asadi N, Haghpanah S. The effects of olive leaf extract ointment on pain intensity and early maternal complications in primiparous women. Int J Pharm Pharm Sci. 2017; 9:31–34. https://doi.org/10.22159/ijpps.2017v9i7.15387
  17. 17. Radnia N, Khansari S, Jiriaei N, Hosseini SA, Salemi L, Hamoon M. The relationship between perineal size and episiotomy during delivery. JML. 2022; 15: 1379–1383. pmid:36567847
  18. 18. Mohamed H, El-Nagger NS. Effect of self perineal care instructions on episiotomy pain and wound healing of postpartum women. J Am Sci. 2012; 8:640–650.
  19. 19. Ahad B, Shahri W, Rasool H, Reshi Z, Rasool S, Hussain T. Medicinal plants and herbal drugs: An overview. Medicinal and Aromatic Plants: Healthcare and Industrial Applications. 2021:1–40.
  20. 20. Huang L-C, Wu X, Chen JY. Predicting adverse side effects of drugs. BMC genomics. 2011; 12:1–10. pmid:22369493
  21. 21. Barati N, Kordi M. The effect of black seed cream on episiotomy pain in primiparous women: a clinical trial study. The third international conference on new findings in obstetrics, gynecology, childbirth and infertility 2020. (In Persian). https://civilica.com/doc/1167637/ pmid:28299294
  22. 22. Amani R, Kariman N, Mojab F, Alavi H, Majidi S. Comparison of the effects of cold compress with gel packs and topical‎ olive oil on episiotomy wound healing. J. Babol Univ. Med. Sci. 2015; 17:7–12. https://doi.org/10.22088/jbums.17.11.7
  23. 23. Abooei Mehrizi M, Eidi A, Mortazavi P. Study of effect of olive oil on re-epithelialization of epithelial tissue in excision wound healing model in rats. J. Comp. Pathol. 2016; 13:1875–1883. (In Persian)
  24. 24. Preedy VR, Watson RR. Olives and olive oil in health and disease prevention: Academic press; 2020. ISBN: 9780128195284. eBook ISBN: 9780128199893
  25. 25. Donato-Trancoso A, Monte-Alto-Costa A, Romana-Souza B. Olive oil-induced reduction of oxidative damage and inflammation promotes wound healing of pressure ulcers in mice. J. Dermatol. Sci. 2016; 83:60–69. pmid:27091748
  26. 26. Raisi A, Farjanikish G, Salahi P. Comparing Healing Effects of olive leaf extract ointment and dermaheal ointment on cutaneous wound in diabetic rats. J. Maz. Univ. Med. 2019; 29:11–21. http://jmums.mazums.ac.ir/article-1-12665-en.html
  27. 27. Taheri M, Amiri-Farahani L. Anti-Inflammatory and Restorative Effects of Olives in Topical Application. Dermatol Res Pract. 2021. pmid:34257643
  28. 28. Sales-Campos H, Reis de Souza P, Crema Peghini B, Santana da Silva J, Ribeiro Cardoso C. An overview of the modulatory effects of oleic acid in health and disease. Mini Rev Med Chem. 2013; 13:201–210. https://doi.org/10.2174/138955713804805193 pmid:23278117
  29. 29. Carrara M, Kelly MT, Roso F, Larroque M, Margout D. Potential of olive oil mill wastewater as a source of polyphenols for the treatment of skin disorders: a review. J. Agric. Food Chem. 2021; 69:7268–7284. pmid:34180235
  30. 30. Bayir Y, Un H, Ugan RA, Akpinar E, Cadirci E, Calik I, et al. The effects of Beeswax, Olive oil and Butter impregnated bandage on burn wound healing. Burns. 2019; 45:1410–1417. pmid:31126777
  31. 31. Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed)—a review. Am. J. Chinese Med. 2011; 39:1075–1091. pmid:22083982
  32. 32. Vedaei S, Aarabi A. An investigation on the effect of cold press and soxhlet methods of extracting Iranian black seed oil on physicochemical and antioxidant properties. J. Food Process. Preserv. 2021; 13:89–101. https://doi.org/10.22069/EJFPP.2021.16355.1535
  33. 33. Sallehuddin N, Nordin A, Bt Hj Idrus R, Fauzi MB. Nigella sativa and its active compound, thymoquinone, accelerate wound healing in an in vivo animal model: A comprehensive review. IJERPH. 2020; 17:1–17. pmid:32545210
  34. 34. Noorbar E, Mirazi N. Study of Nigella sativa L. Effect of hydroethanolic extract of Nigella sativa L. on skin wound healing process in diabetic male rats. INT J PREV MED. 2019; 1–7. pmid:30820305
  35. 35. Gumus ZP, Guler E, Demir B, Barlas FB, Yavuz M, Colpankan D, et al. Herbal infusions of black seed and wheat germ oil: Their chemical profiles, in vitro bio-investigations and effective formulations as phyto-nanoemulsions. Colloids Surf. B. 2015; 133:73–80. pmid:26087391
  36. 36. Shaterzadeh-Yazdi H, Noorbakhsh M-F, Samarghandian S, Farkhondeh T. An overview on renoprotective effects of thymoquinone. Kidney Dis. 2018; 4:74–82. pmid:29998122
  37. 37. Pottoo FH, Ibrahim AM, Alammar A, Alsinan R, Aleid M, Alshehhi A, et al. Thymoquinone: Review of its potential in the treatment of neurological diseases. Pharmaceuticals. 2022; 15:408. pmid:35455405
  38. 38. Tavakkoli A, Mahdian V, Razavi BM, Hosseinzadeh H. Review on clinical trials of black seed (Nigella sativa) and its active constituent, thymoquinone. JoP. 2017; 20:: 179–193. pmid:30087794
  39. 39. Zaid MHM, Hanafi MF, Haris MS. A review of black seed extract as an agent in the wound healing process. J. Pharm. 2021; 1:87–96. https://doi.org/10.31436/jop.v1i2.67
  40. 40. Shaheen M, Dolganova N, Shinkar EV, Sukhenko LT, Astafieva OV. Study of biotecnology raise antioxidanr propertiesof olive oil and black seed oil. Carpathian J. Food Sci. Technol. 2020; 12:146–151. https://doi.org/10.34302/crpjfst/2020.12.2.15
  41. 41. Hekmatzadeh S, Mirmolaei S, Hoseini N. The effect of boiled dill (Anethum graveolens) seeds on the long active phase and labor pain intensity. Armaghane danesh. 2012; 17:50–59. (In Persian)
  42. 42. Alvarenga MB, Francisco AA, Oliveira SMJVd, Silva FMBd, Shimoda GT, Damiani LP. Evaluación de la curación de episiotomía: confiabilidad de la escala de Enrojecimiento, Edema, Equimosis, Drenaje, Aproximación (REEDA). Rev Lat Am Enfermagem. 2015; 23:162–168. https://doi.org/10.1590/0104-1169.3633.2538
  43. 43. Yaman I, Durmus A, Ceribasi S, Yaman M. Effects of Nigella sativa and silver sulfadiazine on burn wound healing in rats. Vet Med (Praha). 2010; 55:619–624. https://doi.org/10.17221/2948-VETMED
  44. 44. Gonzalez ACdO, Costa TF, Andrade ZdA, Medrado ARAP. Wound healing-A literature review. Bras Dermatol. 2016; 91:614–620. pmid:27828635