The Prangos Ferulacea (Jashir) on the Candida Vulvovaginitis: A Study Protocol of clinical trial

The Prangos Ferulacea (Jashir) on the Candida Vulvovaginitis: A Study Protocol of clinical trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol The Prangos Ferulacea (Jashir) on the Candida Vulvovaginitis: A Study Protocol of clinical trial Leila ghiasi, Fatemeh Goudarzi, Hosein Sadeghi, Maral Gharaghani, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5729082/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Candida vulvovaginitis is one of the most common infections among women of reproductive age, ranking as the second leading cause of visits to gynecology clinics. purpose of the study is to document the effect of Prangos Ferulacea (Jashir) on the Treatment of Candida Vulvovaginitis. Methods: This study is designed as a randomized, double-blind clinical trial that will include 112 participants divided into two groups: an intervention group and a control group. The trial will be conducted at Yasuj University of Medical Sciences. Eligible participants will be married women aged 15–45 years who present with at least two clinical symptoms (cheesy vaginal discharge and itching), a Sobel score of ≥4, and a confirmed positive Candida culture. The control group will receive clotrimazole vaginal cream, instructed to apply 5 grams intravaginally using an applicator each night for one week. The intervention group will follow the same application protocol but will use a vaginal cream formulated with Prangos Ferulacea (Jashir). Discussion: This, along with the coagulation of cellular components, results in the degradation and death of fungal cells. Conclusion: . The findings are expected to offer new insights into the potential of this herbal remedy as an alternative to azole-based antifungal treatments, paving the way for more accessible and safer therapeutic options. Prangos Ferulacea Candida vulvovaginitis herbal medicine clinical trial protocol Figures Figure 1 Introduction Vaginitis is defined as a condition characterized by abnormal vaginal discharge, odor, irritation, itching, or burning sensations, often accompanied by increased vaginal discharge (leukorrhea), genital inflammation, and vaginal pain [ 1 , 2 ]. From an etiological perspective, vaginitis can be classified as either infectious (with the most common pathogens being Candida, such as Candida albicans , bacteria (bacterial vaginosis), or flagellated protozoa such as Trichomonas ) or non-infectious (when caused by non-specific processes related to irritant or allergic contact dermatitis, foreign bodies, or atrophic conditions) [ 4 ]. Vaginitis is one of the most common reasons for recurrent visits to healthcare facilities among women, with an estimated 10 million visits occurring annually. It is associated with adverse fertility and social-psychological consequences [ 2 , 3 ]. Candida vulvovaginitis is the second leading cause of referral for women of reproductive age to gynecology clinics [ 4 , 5 ]. Approximately 75% of women will experience this condition at least once during their lifetime [ 6 , 11 – 15 ], while 50% of women will experience it twice annually [ 12 , 15 ]. 8–10% of women suffer from recurrent Candida infections during their lifetime [ 7 ][ 5 ]. Common symptoms of Candida vulvovaginitis include severe itching (the most common symptom [ 5 ]), bleeding erosions, erythema and edema of the vulva, cheesy or watery vaginal discharge, dysuria, and dyspareunia [ 4 , 7 ]. These symptoms typically appear one week before the onset of the menstrual cycle [ 8 ]. Since the symptoms and signs of the disease are nonspecific, diagnosis should not rely solely on clinical manifestations, and microscopic examination and culture are required for confirmation [ 9 ]. According to a meta-analysis conducted in Iran, genital itching and burning, and cheesy vaginal discharge are the predominant clinical manifestations among Iranian women with Candida vulvovaginitis [ 10 ]. Factors that increase susceptibility to Candida vulvovaginitis include host factors such as the use of broad-spectrum antibiotics, pregnancy, oral contraceptives (especially high-dose estrogen formulations), immunosuppressants, synthetic clothing, obesity, iron deficiency anemia, uncontrolled diabetes (high serum glucose levels), psychosocial stress, sexual activity, and allergies [ 5 , 10 , 11 ]. Warm and moist environments, such as the oral cavity and vagina, are considered the most favorable places for infection development [ 12 ]. In the past two decades, a significant increase in the incidence of deep fungal infections has been observed, not only in immunocompromised patients associated with hospital infections but also in healthy individuals [ 13 ]. This infection requires treatment as it is associated with issues such as depression, stress, low self-esteem, sexual dissatisfaction in women, infertility, and, during pregnancy, an increased risk of preterm birth and low birth weight, as well as congenital skin candidiasis in the neonate [ 10 ][ 4 , 14 ]. Candida vulvovaginitis accounts for one-quarter of all vaginal infections [ 15 ], with the majority of cases (approximately 70–90%) caused by Candida albicans (the main agent) [ 16 ]. The remaining 10–30% are caused by non-albicans species, which may be less sensitive to antifungal medications [ 14 ]. Among the non-albicans species of Candida , C. glabrata is considered the second most common cause of Candida vulvovaginitis [ 12 ]. The prevalence of recurrent vulvovaginitis in Iran is estimated to be 12.3%, which is significantly higher than the estimated rates in some other countries (6–9%) [ 16 ]. The most significant risk factor for Candida vulvovaginitis in Iranian women in 2021 was the use of estrogen-based oral contraceptives (OCPs) [ 10 ]. Infection rates due to vaginitis vary across different provinces in Iran, with reports of 19.8% in Kerman, 26% in Sari, and 35% in Jiroft [ 17 , 18 ], while Yasouj city also reported 34% [ 19 ]. Overall, epidemiological studies indicate that the prevalence of Candida vulvovaginitis varies among countries and ethnic groups, and even within similar demographic groups, epidemiological characteristics can differ, with the reasons for these differences still unknown [ 20 , 21 ]. Topical and oral azoles are widely used for the treatment of vaginal candidiasis [ 14 , 15 ]. The most common of these medications are clotrimazole, followed by miconazole, ketoconazole, and fluconazole [ 5 ]. Despite the availability of clotrimazole, concerns have arisen regarding increasing resistance to this drug, particularly in recurrent Candida vulvovaginitis [ 4 ], and treatment of this condition is sometimes complicated due to contributing factors and frequent recurrences [ 22 ]. Causes of recurrence include the use of oral contraceptives, vaginal douching, the presence of non-albicans strains, and multiple courses of antibiotics [ 23 ]. Additionally, drug resistance in this condition can lead to frequent recurrences [ 15 ]. Clotrimazole vaginally may also cause some local reactions such as burning, edema, erythema, itching, and dryness of the skin [ 4 ]. In some cases, after treatment with azoles, patients may experience multiple side effects, including dizziness, chills, gastrointestinal symptoms (nausea, vomiting, stomach pain, diarrhea, constipation, bloating), headaches, neutropenia, thrombocytopenia, hepatotoxicity, neurological symptoms, and elevated liver enzymes [ 14 , 24 , 25 ]. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, reduced libido, oligospermia, sexual dysfunction, hypokalemia, hyponatremia, and rarely adrenal insufficiency [ 26 ]. On the other hand, the cost of antifungal medications is high [ 13 ]. Recent reports indicate an increase in resistance of C. albicans to azoles [ 27 ]. Given the potential negative impact on health and quality of life, high prevalence and costs, and unreliable diagnostic methods, recurrent Candida vulvovaginitis is recognized as a serious global public health challenge, with significant economic, social, and medical consequences [ 28 ]. Therefore, the use of products with antifungal effects but fewer side effects seems to be more beneficial. Herbal medicines, due to their compatibility with the natural vaginal flora, are considered suitable for treating this condition [ 15 ]. To avoid these issues, researchers have turned to alternative treatment strategies, such as using natural products, particularly essential oils (EOs) [ 13 ]. Currently, herbal medicines are being increasingly considered as substitutes for chemical drugs in the treatment of infections [ 29 ]. Prangos ferulacea is one such plant with antimicrobial properties that has been used for this purpose in traditional Iranian medicine [ 29 , 30 ]. In traditional medicine, especially complementary medicine, herbal therapy is one of the valuable legacies of Iranian medicine [ 15 ]. Natural products have historically been the primary source of compounds for therapeutic use, and most antibiotics have traditionally been derived from natural sources [ 12 ]. The history of using plants in medicine dates back a long time, with 25% of all drugs available in the United States being derived from medicinal plants [ 23 , 31 ]. In Germany, 75% of the drugs used have plant origins [ 32 ]. Iran is home to 7,500 plant species, while herbal drug consumption in Iran is between 3 to 5% [ 33 ]. Currently, 25% of the active compounds in synthetic drugs on the market are derived from plants. More than 20,000 medicinal plants have been used for medical purposes, with nearly 4,000 of these species used regularly. However, only 10% of them have commercial and practical applications. Native herbal medicines are crucial in the development of new drugs for treating diseases and also play a significant role in reducing economic costs [ 34 ]. Among various plant families, the Apiaceae family includes more medicinal and industrial plants [ 35 ]. The genus Prangos Lindl. of the Apiaceae family consists of about 30 species [ 36 ], which are primarily distributed in the plant geographic region of Iran and Turania [ 36 , 37 ]. The Prangos genus has 15 species in Iran, all of which have significant forage value. The species Prangos ferulacea (commonly known as "Jashir" in Persian) is a perennial plant, reaching a height of 80–120 cm, with thick, upright, angular stems and opposite or nearly whorled branches. Its leaves are green, lack hairs, and are rarely rough or hairy, with wide, egg-shaped, deeply divided, linear, and strap-like segments [ 35 ]. This plant produces a yellow, saffron-like gum that is extracted from its roots and stems [ 29 ]. One of the most well-known effects of these plants is their ability to alleviate various gastrointestinal symptoms [ 37 ]. Studies indicate that some biological properties, such as antioxidant, antibacterial, antispasmodic, abortifacient, analgesic, and liver-protective activities, have been reported for the aerial parts of P. ferulacea ; it has also been shown that the roots of this plant improve glucose and lipid profiles in diabetic mice [ 36 ]. Phytochemical studies of this genus have revealed that coumarins, flavonoids, and terpenoids are the main components of these plants [ 37 ]. Regarding the mechanism of action of plant essential oils (EOs) on fungi, some natural products can cause permanent damage to fungal cell membranes by increasing permeability and fluidity, leading to lipid, protein, and nucleic acid breakdown, along with coagulation of cell components, which results in fungal cell degradation and death [ 37 ]. Essential oils from some plants contain compounds that affect the phospholipid fatty acid chain in cell membranes, increasing cell permeability [ 38 , 39 ]. Another possible mechanism of action for essential oils on fungi is the inhibition of ergosterol synthesis, which delays membrane formation [ 38 , 40 , 41 ]. A study by Hekmatzadeh and colleagues showed that the main components of the Prangos ferulacea essential oil include α-pinene (18.34%), β-pinene (27.01%), δ-3-carene (24.78%), and β-caryophyllene (17.69%). α-pinene, a common compound in Prangos ferulacea , increases membrane permeability, inhibits respiration processes, and interferes with ion transport in Candida species, demonstrating that the essential oil has antifungal activity against Candida [ 38 ]. Yousefi et al. (2017) reported that the root extract of Prangos ferulacea inhibits Candida albicans growth. The methanolic extract of Prangos ferulacea also exhibited antibacterial activity against tested strains, including Pseudomonas aeruginosa , Escherichia coli , Staphylococcus aureus , and Bacillus cereus [ 42 ]. A study by Ofok Ozgen et al. in Turkey in 2009 examined the antifungal activity of methanolic and chloroform extracts from eight plant species, including Prangos ferulacea , used in Turkish traditional medicine. The study found that chloroform extracts of Prangos ferulacea had no inhibitory effect on Candida species, while the methanolic extract showed good activity against Candida [ 43 ]. Candida vaginitis, with its potential negative impact on health and quality of life, high prevalence, and unreliable diagnostic methods, has been recognized as a significant global public health challenge, with considerable economic, social, and medical consequences. Managing Candida infections faces challenges such as a limited number of antifungal drugs, toxicity, resistance to common drugs, and recurrence. Given the high prevalence, significant complications, economic losses due to recurrent infections, treatment resistance, and reduced efficacy of azoles, there is a need for better solutions and new compounds to address this issue. Therefore, this study will be conducted to design an intervention program focusing on the effects of the herbal product Jashir in the treatment of candidiasis. Methods Study Design: We will conduct a double-blind, randomized, outpatient clinical trial involving 112 women of reproductive age (15–45 years) diagnosed with candidiasis vaginitis both clinically and through laboratory confirmation. Participants will be recruited from women attending the gynecology clinic at Yasuj University of Medical Sciences. Participants: All women presenting with vaginal discharge to the clinic affiliated with Yasuj University of Medical Sciences in Yasuj, who meet the inclusion criteria, will be invited to participate in the study. Inclusion Criteria: Women of reproductive age (15–45 years). Married status. Presence of at least two symptoms, including cheesy discharge and itching [50]. A minimum Sobel score of 4. Positive culture results. Exclusion Criteria: Participants who meet any of the following conditions will not be eligible to participate in the study: unwillingness to participate, lactating women, postmenopausal women, menstruating or pregnant women, those diagnosed with diabetes, women with immunodeficiency or immunosuppressive diseases, abnormal liver function test results, presence of other vaginal infections or sexually transmitted infections, current use of oral or intravenous antifungal drugs, recurrent or persistent candidiasis vaginitis, recent treatment with systemic antibiotics or antimicrobial therapy within the last 14 days, history of hypersensitivity to Jashir or clotrimazole vaginal cream, autoimmune diseases, vaginal pH greater than 4.5, abnormal Pap smear in the past 12 months, history of uterine curettage, hysterosalpingography, uterine surgery, blood transfusion, or chemotherapy in the last two weeks. Withdrawal Criteria: Participants will be withdrawn from the study if they use other vaginal creams during the study, engage in sexual intercourse, or fail to properly use the Jashir cream. Sample Size: The objective of this study is to determine the difference in the mean symptom scores of vulvovaginal candidiasis between two groups: those receiving clotrimazole vaginal cream and those treated with Jashir vaginal cream. Based on similar studies conducted in populations comparable to the target population (receiving clotrimazole vaginal cream), the sample size was calculated using the formula for comparing the means of two populations. Using data from the study by Jafarzadeh et al. (2019), where the values were S12=3.45S_1^2 = 3.45S12=3.45, S22=3.49S_2^2 = 3.49S22=3.49, μ1=6.73\mu_1 = 6.73μ1=6.73, μ2=2.33\mu_2 = 2.33μ2=2.33, α=0.05\alpha = 0.05α=0.05, and β=0.2\beta = 0.2β=0.2, the required sample size was calculated to be 42.9 participants per group. Considering a 20% dropout rate, the final sample size will be 52 participants in each group. Randomization: All individuals involved in the study, including the researcher, participants, and statistical analyst, will be blinded to the drug allocation. Blinding will be implemented by the pharmacist. For blinding purposes, 1% clotrimazole cream produced by a pharmaceutical company will be aseptically transferred into tubes identical to those used for Jashir vaginal cream by the pharmacist. To distinguish between the two creams, the pharmacist will assign unique codes (A and B) to each cream. These codes will only be revealed by the pharmacist after the study is completed and statistical analysis is conducted. The research team will consist of an obstetrician-gynecologist, a pharmacist, and a midwife. Intervention: After selecting eligible participants, obtaining informed consent, and introducing the researcher along with the study objectives, clinical and laboratory assessments will be conducted for individuals presenting with symptoms of acute vulvovaginal candidiasis (e.g., vulvar and vaginal itching, curd-like discharge, burning, dyspareunia, and vulvar inflammation). A comprehensive medical history will be taken, and inclusion and exclusion criteria will be reviewed. For participants meeting the inclusion criteria, a demographic questionnaire will be completed, followed by a clinical examination. Initially, participants will be positioned in the lithotomy position. Before inserting the speculum, the vulvar region will be examined for edema, inflammation, erythema, and lesions. Subjective symptoms, including itching, burning, and dyspareunia, will be self-reported by participants using a 10 cm Visual Analog Scale (VAS), where 0 indicates no symptoms and 10 represents the most severe symptoms. These scores will be documented in a checklist. A moistened speculum (with normal saline, without lubricant) will be inserted into the vagina. A thorough vaginal examination will be performed, assessing inflammatory changes, ulcers, discharge, and cervical abnormalities. Vaginal acidity will be measured using a pH test strip. Objective symptoms, such as vulvovaginal inflammation (edema, erythema, and fissures), will be evaluated using Sobel’s scoring system: 0 : No inflammation, edema, erythema, or fissures. 1 : Mild inflammation, edema, erythema, or fissures. 2 : Moderate inflammation, edema, erythema, or fissures. 3 : Severe inflammation, edema, erythema, or fissures. The severity of vulvovaginal candidiasis will be determined by the total score obtained from subjective and objective symptoms using Sobel’s clinical scoring system. A total Sobel score ≥4 will be considered as probable acute vulvovaginal candidiasis, qualifying the participant for inclusion in the study. Subjective symptoms (vaginal and vulvar itching, burning, and dyspareunia) will be evaluated using the VAS tool. To confirm the diagnosis and rule out other causes such as bacterial vaginosis or cervicitis, samples of vaginal secretions will be collected from the posterior fornix, avoiding alkaline cervical discharge. Vaginal pH will also be measured: pH 4–4.5 : Indicative of candidiasis. pH >4.5 : Suggestive of mixed infections, bacterial vaginosis, or trichomoniasis (participants with these conditions will be excluded from the study). Three sterile cotton swabs will be used to collect samples from the lateral wall and posterior fornix of the vagina: The first swab will be smeared onto a glass slide, with one drop of normal saline added to prepare a wet mount for examining motile Trichomonas parasites under a microscope. The second swab will be treated with 10% potassium hydroxide (KOH) to detect fungal elements (e.g., hyphae and blastospores) under a microscope. If clue cells (indicative of bacterial vaginosis) or Trichomonas parasites are observed, the participant will be excluded and referred for treatment. A positive KOH test (presence of hyphae or blastospores) will indicate candidiasis. The third swab will be sent to the laboratory for culture on Sabouraud Dextrose Agar to confirm the diagnosis. Samples will be incubated at 30–37°C, and colonies will be examined by a mycologist after 42–72 hours. Positive culture results will confirm candidiasis, qualifying the participant for inclusion in the study. Only patients with baseline positive cultures for yeast will be included in the analysis of treatment efficacy. The probable diagnosis of candidiasis will be based on clinical symptoms and the presence of fungal elements (hyphae or blastospores) in the KOH test. Definitive diagnosis will be confirmed through culture results on Sabouraud Agar. After confirming the final diagnosis, participants will be randomly assigned to one of two groups: intervention or control. Control group : Participants in this group will receive 1% clotrimazole vaginal cream. They will be instructed to apply a 5-gram applicator of the cream vaginally each night before bedtime for one week. Intervention group : Participants in this group will receive Jashir vaginal cream. They will be instructed to apply a 5-gram applicator of the cream vaginally each night before bedtime for one week. Follow-up and Adverse Event Assessment Potential adverse drug reactions will be assessed on the second and fourth days after starting treatment using a structured questionnaire. The following symptoms will be specifically evaluated: Vaginal itching Burning sensation Redness and inflammation of the vagina Vaginal dryness Abnormal discharge Any newly emerged symptoms or worsening of existing symptoms in response to the medication will be classified as an adverse drug reaction. Outcome Assessment Seven days after completing the treatment course, participants in both groups will be evaluated for clinical improvement and laboratory results. This assessment will include: Clinical examination to assess symptoms and signs. Direct wet smear test with potassium hydroxide (KOH). Culture of vaginal discharge on Sabouraud Dextrose Agar. A negative result on both the smear and culture will indicate successful treatment. If the results are positive or symptoms persist, participants will be referred to a gynecologist for further management. Definition of Treatment Success Clinical treatment success will be defined as the resolution of baseline symptoms and signs and a reduction in the Sobel symptom severity score to ≤2. Assessment of Patient Satisfaction Seven days after completing the treatment, participant satisfaction with the medication and treatment method will be assessed using a short questionnaire with three response options: Satisfied Not satisfied Somewhat satisfied Finally, the treatment outcomes and satisfaction levels in the intervention (Jashir cream) and control (clotrimazole cream) groups will be compared and statistically analyzed. Data Collection Tools The data collection tools will include an interview form, a checklist for recording examinations and clinical observations, a drug complaint questionnaire, a medication satisfaction questionnaire, pH test paper, a Visual Analog Scale (VAS), and the semi-quantitative clinical tool Sobel. The interview form will include questions about demographic characteristics, which will consist of sections on personal information, social data, personal hygiene, and obstetric history. The checklist for recording examinations and clinical observations will include information regarding clinical symptoms and will record results from laboratory tests, including the patient’s main complaint, subjective symptoms (such as itching, burning, and pain during intercourse), and objective symptoms (including discharge, inflammation, and erythema of the vulva as identified by the examiner). It will also contain laboratory test results (such as pH test results and vaginal discharge smear results) and the code of the administered medication. Medication : The medication will be prepared by the pharmacist at Yasuj University of Medical Sciences. Drug Complaint Checklist : Potential drug side effects will be evaluated on the second and fourth days after starting treatment. The evaluation of side effects will be based on the drug complaint checklist and any newly occurred or worsened side effects (such as itching, burning, vaginal redness and inflammation, vaginal dryness, and discharge) in response to the medication will be considered as drug-related adverse effects. Medication Satisfaction Checklist : Satisfaction with the medication and treatment method will be assessed using the medication satisfaction checklist seven days after the completion of the treatment. The responses will be based on a Likert scale (Satisfied / Dissatisfied / Neutral). Method for Measuring the Validity and Reliability of Data Collection Tools : To determine the scientific validity of the questionnaire and checklist, content validity will be assessed through the opinions of faculty members from the Midwifery Department at Yasuj University of Medical Sciences. The scientific trustworthiness and reliability will be determined through a test-retest method applied to 20 patients attending the Shahid Mofatteh Clinic, with the correlation coefficient calculated using Pearson’s correlation and Cronbach's alpha. Furthermore, a wet smear test will be conducted on 10 individuals, with two separate samples labeled with different codes and sent to the laboratory for analysis. The correlation between the results of the two samples will then be evaluated. For the reliability of the pH test strip, all kits will be purchased from a reputable brand, and one kit will be tested using a standard buffer solution for every five kits. Each kit will be placed in the standard solution, and the color spectrum of the kit will be compared with the pH of the standard solution to confirm its scientific validity. Visual Analog Scale (VAS) : The Visual Analog Scale is a 100-millimeter ruler typically used to assess various health-related factors, including symptoms of disease, pain, mood, quality of life, and patient satisfaction. The patient will mark the scale according to the severity of their symptoms, and the number obtained will be described by the researcher. The scale ranges from “No Itching, No Burning” on the left to the phrase “Worst and Most Severe Symptoms Imaginable” at the far right. The severity of itching can be measured using unidimensional scales, such as the Visual Analog Scale (VAS), Numerical Rating Scale (NRS), Verbal Rating Scale (VRS), and various multidimensional questionnaires, including the Itch Severity Scale (ISS). Several studies have investigated the correlation between VRS and VAS, as well as the validity and reliability of the unidimensional itch severity scales. The image below illustrates a sample of the VAS for measuring itching. Sobel Scale : The Sobel scoring system is a semi-quantitative clinical rating scale that determines the severity of vulvovaginal symptoms. It will assign scores to both the objective and subjective symptoms of candidal vaginitis, and the initial classification of candidal vaginitis will be based on the symptom scores. In this system, scores for symptoms such as itching, erythema of the vulva and vagina, edema, cuts/small fissures are as follows: absent (0), mild (1), moderate (2), and severe (3). The total symptom score is the cumulative score of all symptoms, with a score of less than 4 indicating mild vaginitis, a score of 4 or higher indicating moderate vaginitis, and a score of 7 or higher classifying it as severe. Patients with a total score greater than 4 and a history of vaginitis in the past 12 months will be considered as having candidal vaginitis. Statistical Analysis : Data analysis will be performed using SPSS software (Inc, Chicago, IL, USA), version 25. Descriptive statistics, including mean, standard deviation, absolute frequency, and relative frequency percentage, will be presented. To compare quantitative variables such as age, independent t-tests will be used. For comparing categorical variables such as education level and the main variables before and after intervention between the two groups, the chi-square test will be used. To control for potential confounding factors, Fisher’s exact test will be conducted between the two groups. Ethical Approval and Informed Consent : This trial has been approved by the Medical Ethics Committee of Yasuj University of Medical Sciences, Yasuj, Iran (IR.YUMS.REC.1402.030). This study will be conducted in accordance with the Declaration of Helsinki in terms of ethical considerations. Written informed consent will be obtained from all participants before their inclusion in the study. This randomized double-blind clinical trial is registered with the Iranian Registry of Clinical Trials (IRCT) under registration number IRCT20230521058245N1, dated June 27, 2023. The trial is accessible at http://en.irct.ir/trial/70331. Consent for publication is not applicable. Results In this protocol, a two-phase clinical intervention is designed to evaluate the effect of the Jashir plant product on the improvement of symptoms of candidal vaginitis in symptomatic women. In the first phase, based on a researcher-created checklist, the conditions of the participants are reviewed, and sample selection is carried out. Then, for patients presenting with complaints of acute candidal vulvovaginitis with symptoms (itching of the vulva and vagina, cheesy discharge, burning, pain during intercourse, and inflammatory symptoms of the vulva), a medical history will be taken, and the inclusion and exclusion criteria will be assessed. Participants who meet the inclusion criteria will complete a demographic questionnaire, followed by a clinical examination, and the vulvovaginal symptom form will be completed. Subjective symptoms of the vulva and vagina, such as itching, burning, and dyspareunia, will be assessed by the participants using a 10 cm Visual Analog Scale (VAS), ranging from 0 (no itching/burning/dyspareunia) to 10 (most severe itching/burning/dyspareunia). These scores will be recorded in the checklist. Then, a speculum moistened with normal saline, without lubricant, will be inserted into the vagina, and a detailed vaginal examination will be conducted to assess for inflammatory changes, wounds, discharge, inflammation, and cervical changes. After examining the vagina and cervix for symptoms such as lesions, inflammation, and discharge, the vaginal pH will be measured using a pH test strip. Objective Symptoms Objective symptoms include inflammatory vulvovaginal signs (edema, inflammation, erythema of the vagina and vulva, and fissures) based on the examiner’s observations and the Sobel scoring system. The scoring for these symptoms is as follows: no inflammation, edema, erythema, or fissures (0), mild inflammation, edema, erythema, and fissures (1), moderate inflammation, edema, erythema, and fissures (2), severe inflammation, edema, erythema, and fissures (3). The total score will classify the symptoms accordingly. To confirm the diagnosis and exclude other causes of vaginitis and cervicitis, vaginal discharge will be collected from the posterior fornix to avoid contamination with alkaline cervical discharge. Vaginal pH will be measured using a pH strip. A pH between 4.0 and 4.5 will indicate candidiasis, while participants with a pH higher than 4.5 (which suggests mixed vaginal infections, such as Gardnerella vaginitis) will be excluded from the study. Next, three sterile cotton swabs will be used to collect discharge samples from the vaginal wall and posterior fornix. One swab will be spread on a glass slide, a drop of normal saline will be added, and a wet mount will be prepared. This will be examined under the microscope for the presence of Trichomonas (flagellated parasite). The second swab will be analyzed for fungal elements, and 10% potassium hydroxide will be added. Both swabs will be examined under a microscope at 40x magnification, and if Trichomonas or key cells (for bacterial vaginosis) are observed on the first slide, the participant will be excluded from the study and referred for treatment. If Candida (hyphae and blastospores) is seen on the second slide, the sample will be considered positive for candidiasis, and the third swab will be sent for final confirmation by Sabouraud Dextrose Agar culture. Phase Two The samples will be incubated at 30-37°C for 42-72 hours. After colony formation, a mycologist will examine the cultures, and if positive for yeast, the sample will be included as a confirmed case. Only patients with a positive baseline culture for yeast will be included in the efficacy analysis. Phase Three Once candidiasis is confirmed, the participants will be randomly assigned into two groups: one receiving vaginal cream containing Jashir and the other receiving vaginal clotrimazole cream. Participants in the control group will be instructed to use a 5-gram applicator of clotrimazole vaginal cream nightly for one week, while those in the intervention group will use a 5-ml applicator of Jashir vaginal cream in the same manner. The researcher will complete the checklists and forms, and follow-up will be conducted through telephone calls to ensure participant adherence. Adverse Effects Adverse drug reactions will be evaluated on the second and fourth days after the start of treatment. The assessment will rely on a drug complaint questionnaire and include possible adverse effects such as itching, burning, vaginal redness, inflammation, dryness, or changes in discharge that have either newly occurred or worsened in response to the medication. These will be recorded as potential side effects of the treatment. Discussion Vaginitis is defined as a condition characterized by abnormal vaginal discharge, odor, irritation, itching, or burning, and is commonly associated with increased vaginal discharge (leukorrhea), genital inflammation, and vaginal pain% of women suffer from recurrent candidal infections during their lifetime. Common symptomndidiasis include intense itching (the most frequent symptom), bleeding erosions, erythema and he vulva, white, cheesy or watery vaginal discharge, dysuria, and dyspareunia. This infection requires treatment as it can lead to complications such as depression, stress, low self-esteem, sexual dissatisfaction in women, infertility, and during pregnancy, it is associated with an increased risk of preterm birth and low birth weight, as well as congenital cutaneous candidiasis. Medicinal plants, known for their compal flora, are considered appropriate for the treatment of this condition. Several studies have investigated the effect of herbal medicines on vaginitis; however, the effect on candidal vaginitis specifically has not been studied extensively in clinical settings. The Prangos species, used both as a spice and in traditional medicine in Asia, particularly in Iran, Turkey, and Iraq, holds significant importance. Phytochemical investigations of this genus have shown that coumarins, fand terpenoids are the major components of these plants. Analysis of the essential oil of the aerial parts of P. ferulacea revealed the ion of 27 compounds, mainly β-pinene (43.1%), α-pinene (22.1%), and δ-3-carene (16.9%). Regarding the mechanism of action of essential oils on fungi, certain natural products can fungal cell membrane by increasing permeability and fluidity, leading to the breakdown of lipids, proteins, and nucleic acids. This, along with the coagulation of cellular components, results in the degradation and death of fungal cells. A study by Hakimzadeh et al. demonstrated that the main components of P. ferulacea essential oil inene (18.34%), β-pinene (27.01%), δ-3-carene (24.78%), and β-caryophyllene (17.69%). α-pinene, a common and principal compound in P. ferulacea , has been shown to increase membrane permeability, inhibit respiration processes, and affect ion transport in Candida species. This study concluded that P. ferulacea essential oil exhibits inhibitory activity against Candida , and both P. ferulacea and P. uloptera oils could be utilized as novel antifungal agents. Yousefi and colleagues (2017) reported that the root extract of Prangos ferulacea showed inhibitory activit Candida albicans*. Furthermore, methanolic extracts of P. ferulacea exhibited antibacterial activity against tested strains, including Pseudomonas aeruginosa , Escherichia coli , Staphylococcus aureus , and Bacillus cereus . Several studies have confirmed that Prangos species possess antifungal activity. The safety and non-toxicity of using Prangos (Jashir) in various dosages have been extensively studied in animal, in vitro, and clinical studies, all of which generally show that this plant is free of side effects. A key strength of this study lies in the use of culture media to identify Candida samples and conducting the research in women with symptoms of candidal vaginitis. Given the resistance that Candida species exhibit against chemical drugs, it is hoped that this research will provide valuable data for designing an intervention program using products containing Jashir extract for treating candidal vaginitis. The application of this product in treatment could contribute to improving women's health. The strategies outlined in this intervention program could be both significant and cost-effective, making this approach promising. Therefore, we hope the success of such an intervention will be a step forward in advancing women's health. Declarations Ethics approval and consent to participate: This randomized, double-blind clinical trial was approved by the Medical The ethics committee that approved the study of Yasuj University of Medical Sciences, Yasuj, Iran (IR.YUMS.REC.1401.004). Written informed consent will be obtained from all participants prior to enrollment. This study was registered on June 27, 2023, in the Iranian Registry of Clinical Trials (IRCT20230521058245N1). Consent for publication: Consent for publication is not applicable. Availability of data and materials: Availability of data and materials: The datasets used and/or analyzed during the current study will be available from the corresponding author upon reasonable request. Competing interests: The authors declare that they have no competing interests Funding : This research protocol was funded by Yasuj University of Medical Sciences (Grant No. 4010152), Yasuj, Iran. The funder played no role in the study design and will not be involved in the study implementation, data analysis and interpretation, or decisions regarding the submission of results This research was funded by Yasuj University of Medical Sciences,Yasuj.Iran. Authors' contributions: This article is part of a master's thesis in midwifery and was approved and funded by the Research Vice Chancellor of Yasuj University of Medical Sciences, Yasuj, Iran No. 4010152. The authors would like to thank the participants in this study . FG, AR, DR, and MT designed the study. FG and AR conducted the literature search. DR and FG determined the dosage of Prangos Ferulacea product based on the studies. DR prepared the Prangos Ferulacea and placebo product. AR will perform the sampling. S. D.Y will administer the drug and placebo to the participant and monitor the results of the product administration and its side effects. FG will conduct the data analysis. FG wrote the manuscript. All authors read and approved the final version. Acknowledgements : This article is based on a research project. The authors thank Yasuj University of Medical Sciences for supporting this study. Study Status This study is currently recruiting participants. References Paladine, H.L. and U.A. Desai, Vaginitis: diagnosis and treatment. American family physician, 2018. 97(5): p. 321-329. Edalatpanah, Y., et al., Evaluation of Antifungal Effects of Prangos ferulace and Plantago major L Plants Against Fluconazole-resistant Candida albicans Species in Extracorporeal Conditions. Navid No, 2020. 23(74): p. 44-52. Brown, H. and M. Drexler, Improving the diagnosis of vulvovaginitis: perspectives to align practice, guidelines, and awareness. Population health management, 2020. 23(S1): p. S-3-S-12. Zakeri, S., et al., The effect of Achillea millefolium L. on vulvovaginal candidiasis compared with clotrimazole: A randomized controlled trial. Complementary Therapies in Medicine, 2020. 52: p. 102483. 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Sasani, E., et al., Vulvovaginal candidiasis in Iran: A systematic review and meta-analysis on the epidemiology, clinical manifestations, demographic characteristics, risk factors, etiologic agents and laboratory diagnosis. Microbial pathogenesis, 2021. 154: p. 104802. Farr, A., et al., Guideline: vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses, 2021. 64(6): p. 583-602. Bonifacio, B.V., et al., Antifungal activity of a hydroethanolic extract from Astronium urundeuva leaves against Candida albicans and Candida glabrata. Frontiers in microbiology, 2019. 10: p. 2642. Mandras, N., et al., Liquid and vapour-phase antifungal activities of essential oils against Candida albicans and non-albicans Candida. BMC complementary and alternative medicine, 2016. 16(1): p. 1-7. Saghafi, N., et al., The effect of a vaginal suppository formulation of dill (Anethum graveolens) in comparison to clotrimazole vaginal tablet on the treatment of vulvovaginal candidiasis. 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Bayani, M., et al., Association of clinical symptoms and laboratory results in diagnoses of Candida vaginitis. Journal of Babol University of Medical Sciences, 2014. 16(1): p. 50-55. ESMAEILZADEH, S., O.S. MAHDAVI, and Z. Rahmani, Frequency and etiology of vulvovaginal candidiasis in women referred to a gynecological center in Babol, Iran. 2009. Deriu, A., et al., In vitro activity of essential oil of Myrtus communis L. against Helicobacter pylori. International Journal of Antimicrobial Agents, 2007. 30(6): p. 562-563. Azadbakht, M., et al., Effect of Methanolic essence and extract of Myrtus Communis on Trichomonas Vaginalis. 2004. Salem, M.E.A., et al., Vaginitis among married women attending primary healthcare in Tanta District, El-Gharbia governorate, Egypt. Menoufia Medical Journal, 2017. 30(1): p. 87. Mollazadeh-Narestan, Z., et al., Comparing the Effect of Probiotic and Fluconazole on Treatment and Recurrence of Vulvovaginal Candidiasis: a Triple-Blinded Randomized Controlled Trial. Probiotics and Antimicrobial Proteins, 2022: p. 1-11. Benitez, L.L. and P.L. Carver, Adverse effects associated with long-term administration of azole antifungal agents. Drugs, 2019. 79(8): p. 833-853. Thamkhantho, M. and C. Chayachinda, Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study. Archives of Gynecology and Obstetrics, 2021. 303(1): p. 151-160. Murina, F., et al., The role of female intimate hygiene practices in the management of vulvovaginal candidiasis: A randomized, controlled open-label trial. Health Care for Women International, 2022: p. 1-12. Azadpour Motlagh, A., et al., Comparative examination of the therapeutic deficiency of oral metronidazole plus prangos ferulacea vaginal cream versus oral metronidazole plus placebo vaginal cream in accelerating trichomonas vaginalis infection recovery: A triple-blind clinical trial. International Journal of Women’s Health and Reproduction Sciences, 2020. Kafash-Farkhad, N., M. Asadi-Samani, and M. Rafieian-Kopaei, A review on phytochemistry and pharmacological effects of Prangos ferulacea (L.) Lindl. Life Science Journal, 2013. 10(SUPPL): p. 360-367. Ali, B., et al., Comparision of the effect of myrtus communis extract and clotrimazole on candida albicans isolated from patients with candida vaginitis. Journal of Kerman University of Medical Sciences, 1997. 5(2): p. 78-83. Gündüz, G.T., Ş.A. Gönül, and M. Karapinar, Efficacy of myrtle oil against Salmonella Typhimurium on fresh produce. International journal of food microbiology, 2009. 130(2): p. 147-150. Yadegarinia, D., et al., Biochemical activities of Iranian Mentha piperita L. and Myrtus communis L. essential oils. Phytochemistry, 2006. 67(12): p. 1249-1255. Mahmoudvand, H., et al., Antimicrobial Activities of Satureja khuzestanica Jamzad; A Review. Ecophytochemical Quarterly of Medicinal Plants, 2020. 31(8). Mirzaei Mosivand, A. Phytochemical study of the essential oil of the plant Lindl ferulacea Prangos in different habitats of Delfan city. Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders), 2021. 21(2): p. 161-167. Delnavazi, M.-R., et al., Isolation of phenolic derivatives and essential oil analysis of Prangos ferulacea (L.) Lindl. aerial parts. Iranian Journal of Pharmaceutical Research: IJPR, 2017. 16(Suppl): p. 207. Mottaghipisheh, J., et al., The Prangos genus: A comprehensive review on traditional use, phytochemistry, and pharmacological activities. Phytochemistry Reviews, 2020. 19(6): p. 1449-1470. Zadeh, S.F.H., et al., Chemical composition of Prangos ferulacea (L.) Lindl., and Prangos uloptera DC. essential oils and their antifungal activities. Journal of Herbmed Pharmacology, 2022. 11(4). Carson, C.F., K.A. Hammer, and T.V. Riley, Melaleuca alternifolia (tea tree) oil: a review of antimicrobial and other medicinal properties. Clinical microbiology reviews, 2006. 19(1): p. 50-62. Inouye, S., et al., Inhibitory effect of essential oils on apical growth of Aspergillus fumigatus by vapour contact. Mycoses, 2000. 43(1-2): p. 17-23. Inouyea, S., T. Takizawab, and H. Yamaguchia, Antibacterial activity of essential oils and their major constituents against respiratory tract pathogens by gaseous contact. J Antimicrob Chemother, 2001. 47: p. 565-73. Yousefi, K., et al., An in vitro ethnopharmacological study on Prangos ferulacea: a wound healing agent. BioImpacts: BI, 2017. 7(2): p. 75. Yiğit, D., N. Yiğit, and U. Özgen, An investigation on the anticandidal activity of some traditional medicinal plants in Turkey. Mycoses, 2009. 52(2): p. 135-140. Additional Declarations No competing interests reported. Supplementary Files 2.png Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5729082","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":398379994,"identity":"3ca00c77-869a-4cc5-bfa5-640560deaefc","order_by":0,"name":"Leila ghiasi","email":"","orcid":"","institution":"Yasuj University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Leila","middleName":"","lastName":"ghiasi","suffix":""},{"id":398379995,"identity":"776aa09e-723a-4717-81ca-ba60bbb80af2","order_by":1,"name":"Fatemeh Goudarzi","email":"","orcid":"","institution":"Yasuj University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Goudarzi","suffix":""},{"id":398379996,"identity":"3cf0ebd9-9840-4bde-a7ef-0d4b600d0194","order_by":2,"name":"Hosein Sadeghi","email":"","orcid":"","institution":"Yasuj University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hosein","middleName":"","lastName":"Sadeghi","suffix":""},{"id":398379997,"identity":"f2ccd953-8f23-4bf7-afaf-bdcfcb18b067","order_by":3,"name":"Maral Gharaghani","email":"","orcid":"","institution":"Yasuj University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Maral","middleName":"","lastName":"Gharaghani","suffix":""},{"id":398379998,"identity":"b4a3548b-a20e-4fc6-8ce7-8e73a53a9664","order_by":4,"name":"Seyedeh Fatemeh Hekmatzadeh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYDAC5gNsDAwHIGwJxgYbIElIC1sCRAsPREsa6VoOE9Yi38bA9uDDmW3y9vyHH974uON8Yv/s5oMPGGpsonFpMTjGwG4448Ztwx6GY8aWM8/cTpxx51iyAcOxtNwGXFrkG9ikeT7cZuxhbDCT5m27ndhwI8cM5EKcWkAOk/7z4bZ9DzP7N+m/becS5xPSwnAMqIXhxu3EHjYeM2nGtgOJGwhpMTjG2CbZc+Z2cs8ZnmLL3rZk44030pINEvD4Rb6N+ZjEj2O3bdv7j2+88bPNTnbejeSDDz7U2OB2GAMjqpQjmJuAUzkWYE+K4lEwCkbBKBgZAABo92Gx0UWTxwAAAABJRU5ErkJggg==","orcid":"","institution":"Yasuj University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Seyedeh","middleName":"Fatemeh","lastName":"Hekmatzadeh","suffix":""}],"badges":[],"createdAt":"2024-12-29 08:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5729082/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5729082/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73269965,"identity":"e06fbfba-54f4-40d7-a720-ac2f8e363484","added_by":"auto","created_at":"2025-01-08 10:47:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":286859,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the Methods section.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5729082/v1/3c07773731dd8f935ac0cdb2.png"},{"id":73272825,"identity":"02419e1f-583c-4ffc-93bc-6c08271fb44f","added_by":"auto","created_at":"2025-01-08 11:11:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":862041,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5729082/v1/c2c281cf-ad90-4d76-bc07-4b0ea9d3a517.pdf"},{"id":73269979,"identity":"77d40c6d-c804-40fc-9e93-30b6f072e1c0","added_by":"auto","created_at":"2025-01-08 10:47:21","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":88951,"visible":true,"origin":"","legend":"","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5729082/v1/aac2cdfb0d8fc44987e8196c.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Prangos Ferulacea (Jashir) on the Candida Vulvovaginitis: A Study Protocol of clinical trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVaginitis is defined as a condition characterized by abnormal vaginal discharge, odor, irritation, itching, or burning sensations, often accompanied by increased vaginal discharge (leukorrhea), genital inflammation, and vaginal pain [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. From an etiological perspective, vaginitis can be classified as either infectious (with the most common pathogens being Candida, such as \u003cem\u003eCandida albicans\u003c/em\u003e, bacteria (bacterial vaginosis), or flagellated protozoa such as \u003cem\u003eTrichomonas\u003c/em\u003e) or non-infectious (when caused by non-specific processes related to irritant or allergic contact dermatitis, foreign bodies, or atrophic conditions) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Vaginitis is one of the most common reasons for recurrent visits to healthcare facilities among women, with an estimated 10\u0026nbsp;million visits occurring annually. It is associated with adverse fertility and social-psychological consequences [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCandida vulvovaginitis is the second leading cause of referral for women of reproductive age to gynecology clinics [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Approximately 75% of women will experience this condition at least once during their lifetime [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], while 50% of women will experience it twice annually [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e8\u0026ndash;10% of women suffer from recurrent Candida infections during their lifetime [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Common symptoms of Candida vulvovaginitis include severe itching (the most common symptom [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]), bleeding erosions, erythema and edema of the vulva, cheesy or watery vaginal discharge, dysuria, and dyspareunia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These symptoms typically appear one week before the onset of the menstrual cycle [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Since the symptoms and signs of the disease are nonspecific, diagnosis should not rely solely on clinical manifestations, and microscopic examination and culture are required for confirmation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. According to a meta-analysis conducted in Iran, genital itching and burning, and cheesy vaginal discharge are the predominant clinical manifestations among Iranian women with Candida vulvovaginitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFactors that increase susceptibility to Candida vulvovaginitis include host factors such as the use of broad-spectrum antibiotics, pregnancy, oral contraceptives (especially high-dose estrogen formulations), immunosuppressants, synthetic clothing, obesity, iron deficiency anemia, uncontrolled diabetes (high serum glucose levels), psychosocial stress, sexual activity, and allergies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Warm and moist environments, such as the oral cavity and vagina, are considered the most favorable places for infection development [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the past two decades, a significant increase in the incidence of deep fungal infections has been observed, not only in immunocompromised patients associated with hospital infections but also in healthy individuals [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This infection requires treatment as it is associated with issues such as depression, stress, low self-esteem, sexual dissatisfaction in women, infertility, and, during pregnancy, an increased risk of preterm birth and low birth weight, as well as congenital skin candidiasis in the neonate [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCandida vulvovaginitis accounts for one-quarter of all vaginal infections [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], with the majority of cases (approximately 70\u0026ndash;90%) caused by \u003cem\u003eCandida albicans\u003c/em\u003e (the main agent) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The remaining 10\u0026ndash;30% are caused by non-albicans species, which may be less sensitive to antifungal medications [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Among the non-albicans species of \u003cem\u003eCandida\u003c/em\u003e, \u003cem\u003eC. glabrata\u003c/em\u003e is considered the second most common cause of Candida vulvovaginitis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The prevalence of recurrent vulvovaginitis in Iran is estimated to be 12.3%, which is significantly higher than the estimated rates in some other countries (6\u0026ndash;9%) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The most significant risk factor for Candida vulvovaginitis in Iranian women in 2021 was the use of estrogen-based oral contraceptives (OCPs) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Infection rates due to vaginitis vary across different provinces in Iran, with reports of 19.8% in Kerman, 26% in Sari, and 35% in Jiroft [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], while Yasouj city also reported 34% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Overall, epidemiological studies indicate that the prevalence of Candida vulvovaginitis varies among countries and ethnic groups, and even within similar demographic groups, epidemiological characteristics can differ, with the reasons for these differences still unknown [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTopical and oral azoles are widely used for the treatment of vaginal candidiasis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The most common of these medications are clotrimazole, followed by miconazole, ketoconazole, and fluconazole [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite the availability of clotrimazole, concerns have arisen regarding increasing resistance to this drug, particularly in recurrent Candida vulvovaginitis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and treatment of this condition is sometimes complicated due to contributing factors and frequent recurrences [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Causes of recurrence include the use of oral contraceptives, vaginal douching, the presence of non-albicans strains, and multiple courses of antibiotics [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Additionally, drug resistance in this condition can lead to frequent recurrences [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Clotrimazole vaginally may also cause some local reactions such as burning, edema, erythema, itching, and dryness of the skin [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In some cases, after treatment with azoles, patients may experience multiple side effects, including dizziness, chills, gastrointestinal symptoms (nausea, vomiting, stomach pain, diarrhea, constipation, bloating), headaches, neutropenia, thrombocytopenia, hepatotoxicity, neurological symptoms, and elevated liver enzymes [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, reduced libido, oligospermia, sexual dysfunction, hypokalemia, hyponatremia, and rarely adrenal insufficiency [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. On the other hand, the cost of antifungal medications is high [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Recent reports indicate an increase in resistance of \u003cem\u003eC. albicans\u003c/em\u003e to azoles [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Given the potential negative impact on health and quality of life, high prevalence and costs, and unreliable diagnostic methods, recurrent Candida vulvovaginitis is recognized as a serious global public health challenge, with significant economic, social, and medical consequences [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherefore, the use of products with antifungal effects but fewer side effects seems to be more beneficial. Herbal medicines, due to their compatibility with the natural vaginal flora, are considered suitable for treating this condition [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. To avoid these issues, researchers have turned to alternative treatment strategies, such as using natural products, particularly essential oils (EOs) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Currently, herbal medicines are being increasingly considered as substitutes for chemical drugs in the treatment of infections [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. \u003cem\u003ePrangos ferulacea\u003c/em\u003e is one such plant with antimicrobial properties that has been used for this purpose in traditional Iranian medicine [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn traditional medicine, especially complementary medicine, herbal therapy is one of the valuable legacies of Iranian medicine [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Natural products have historically been the primary source of compounds for therapeutic use, and most antibiotics have traditionally been derived from natural sources [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The history of using plants in medicine dates back a long time, with 25% of all drugs available in the United States being derived from medicinal plants [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In Germany, 75% of the drugs used have plant origins [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Iran is home to 7,500 plant species, while herbal drug consumption in Iran is between 3 to 5% [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Currently, 25% of the active compounds in synthetic drugs on the market are derived from plants. More than 20,000 medicinal plants have been used for medical purposes, with nearly 4,000 of these species used regularly. However, only 10% of them have commercial and practical applications. Native herbal medicines are crucial in the development of new drugs for treating diseases and also play a significant role in reducing economic costs [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong various plant families, the Apiaceae family includes more medicinal and industrial plants [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The genus \u003cem\u003ePrangos Lindl.\u003c/em\u003e of the Apiaceae family consists of about 30 species [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], which are primarily distributed in the plant geographic region of Iran and Turania [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The \u003cem\u003ePrangos\u003c/em\u003e genus has 15 species in Iran, all of which have significant forage value. The species \u003cem\u003ePrangos ferulacea\u003c/em\u003e (commonly known as \"Jashir\" in Persian) is a perennial plant, reaching a height of 80\u0026ndash;120 cm, with thick, upright, angular stems and opposite or nearly whorled branches. Its leaves are green, lack hairs, and are rarely rough or hairy, with wide, egg-shaped, deeply divided, linear, and strap-like segments [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This plant produces a yellow, saffron-like gum that is extracted from its roots and stems [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. One of the most well-known effects of these plants is their ability to alleviate various gastrointestinal symptoms [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies indicate that some biological properties, such as antioxidant, antibacterial, antispasmodic, abortifacient, analgesic, and liver-protective activities, have been reported for the aerial parts of \u003cem\u003eP. ferulacea\u003c/em\u003e; it has also been shown that the roots of this plant improve glucose and lipid profiles in diabetic mice [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Phytochemical studies of this genus have revealed that coumarins, flavonoids, and terpenoids are the main components of these plants [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding the mechanism of action of plant essential oils (EOs) on fungi, some natural products can cause permanent damage to fungal cell membranes by increasing permeability and fluidity, leading to lipid, protein, and nucleic acid breakdown, along with coagulation of cell components, which results in fungal cell degradation and death [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Essential oils from some plants contain compounds that affect the phospholipid fatty acid chain in cell membranes, increasing cell permeability [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Another possible mechanism of action for essential oils on fungi is the inhibition of ergosterol synthesis, which delays membrane formation [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. A study by Hekmatzadeh and colleagues showed that the main components of the \u003cem\u003ePrangos ferulacea\u003c/em\u003e essential oil include α-pinene (18.34%), β-pinene (27.01%), δ-3-carene (24.78%), and β-caryophyllene (17.69%). α-pinene, a common compound in \u003cem\u003ePrangos ferulacea\u003c/em\u003e, increases membrane permeability, inhibits respiration processes, and interferes with ion transport in \u003cem\u003eCandida\u003c/em\u003e species, demonstrating that the essential oil has antifungal activity against \u003cem\u003eCandida\u003c/em\u003e [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eYousefi et al. (2017) reported that the root extract of \u003cem\u003ePrangos ferulacea\u003c/em\u003e inhibits \u003cem\u003eCandida albicans\u003c/em\u003e growth. The methanolic extract of \u003cem\u003ePrangos ferulacea\u003c/em\u003e also exhibited antibacterial activity against tested strains, including \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, \u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, and \u003cem\u003eBacillus cereus\u003c/em\u003e [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. A study by Ofok Ozgen et al. in Turkey in 2009 examined the antifungal activity of methanolic and chloroform extracts from eight plant species, including \u003cem\u003ePrangos ferulacea\u003c/em\u003e, used in Turkish traditional medicine. The study found that chloroform extracts of \u003cem\u003ePrangos ferulacea\u003c/em\u003e had no inhibitory effect on \u003cem\u003eCandida\u003c/em\u003e species, while the methanolic extract showed good activity against \u003cem\u003eCandida\u003c/em\u003e [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCandida vaginitis, with its potential negative impact on health and quality of life, high prevalence, and unreliable diagnostic methods, has been recognized as a significant global public health challenge, with considerable economic, social, and medical consequences. Managing \u003cem\u003eCandida\u003c/em\u003e infections faces challenges such as a limited number of antifungal drugs, toxicity, resistance to common drugs, and recurrence. Given the high prevalence, significant complications, economic losses due to recurrent infections, treatment resistance, and reduced efficacy of azoles, there is a need for better solutions and new compounds to address this issue. Therefore, this study will be conducted to design an intervention program focusing on the effects of the herbal product \u003cem\u003eJashir\u003c/em\u003e in the treatment of candidiasis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe will conduct a double-blind, randomized, outpatient clinical trial involving 112 women of reproductive age (15\u0026ndash;45 years) diagnosed with candidiasis vaginitis both clinically and through laboratory confirmation. Participants will be recruited from women attending the gynecology clinic at Yasuj University of Medical Sciences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;All women presenting with vaginal discharge to the clinic affiliated with Yasuj University of Medical Sciences in Yasuj, who meet the inclusion criteria, will be invited to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eWomen of reproductive age (15\u0026ndash;45 years).\u003c/li\u003e\n \u003cli\u003eMarried status.\u003c/li\u003e\n \u003cli\u003ePresence of at least two symptoms, including cheesy discharge and itching [50].\u003c/li\u003e\n \u003cli\u003eA minimum \u003cem\u003eSobel score\u003c/em\u003e of 4.\u003c/li\u003e\n \u003cli\u003ePositive culture results.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants who meet any of the following conditions will not be eligible to participate in the study: unwillingness to participate, lactating women, postmenopausal women, menstruating or pregnant women, those diagnosed with diabetes, women with immunodeficiency or immunosuppressive diseases, abnormal liver function test results, presence of other vaginal infections or sexually transmitted infections, current use of oral or intravenous antifungal drugs, recurrent or persistent candidiasis vaginitis, recent treatment with systemic antibiotics or antimicrobial therapy within the last 14 days, history of hypersensitivity to Jashir or clotrimazole vaginal cream, autoimmune diseases, vaginal pH greater than 4.5, abnormal Pap smear in the past 12 months, history of uterine curettage, hysterosalpingography, uterine surgery, blood transfusion, or chemotherapy in the last two weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWithdrawal Criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be withdrawn from the study if they use other vaginal creams during the study, engage in sexual intercourse, or fail to properly use the Jashir cream.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe objective of this study is to determine the difference in the mean symptom scores of vulvovaginal candidiasis between two groups: those receiving clotrimazole vaginal cream and those treated with \u003cem\u003eJashir\u003c/em\u003e vaginal cream. Based on similar studies conducted in populations comparable to the target population (receiving clotrimazole vaginal cream), the sample size was calculated using the formula for comparing the means of two populations.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" height=\"110\" width=\"362\"\u003e\u003c/p\u003e\n\u003cp\u003eUsing data from the study by Jafarzadeh et al. (2019), where the values were S12=3.45S_1^2 = 3.45S12=3.45, S22=3.49S_2^2 = 3.49S22=3.49, \u0026mu;1=6.73\\mu_1 = 6.73\u0026mu;1=6.73, \u0026mu;2=2.33\\mu_2 = 2.33\u0026mu;2=2.33, \u0026alpha;=0.05\\alpha = 0.05\u0026alpha;=0.05, and \u0026beta;=0.2\\beta = 0.2\u0026beta;=0.2, the required sample size was calculated to be 42.9 participants per group. Considering a 20% dropout rate, the final sample size will be 52 participants in each group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll individuals involved in the study, including the researcher, participants, and statistical analyst, will be blinded to the drug allocation. Blinding will be implemented by the pharmacist. For blinding purposes, 1% clotrimazole cream produced by a pharmaceutical company will be aseptically transferred into tubes identical to those used for Jashir vaginal cream by the pharmacist. To distinguish between the two creams, the pharmacist will assign unique codes (A and B) to each cream. These codes will only be revealed by the pharmacist after the study is completed and statistical analysis is conducted.\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eThe research team will consist of an obstetrician-gynecologist, a pharmacist, and a midwife.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter selecting eligible participants, obtaining informed consent, and introducing the researcher along with the study objectives, clinical and laboratory assessments will be conducted for individuals presenting with symptoms of acute vulvovaginal candidiasis (e.g., vulvar and vaginal itching, curd-like discharge, burning, dyspareunia, and vulvar inflammation).\u003c/p\u003e\n\u003cp\u003eA comprehensive medical history will be taken, and inclusion and exclusion criteria will be reviewed. For participants meeting the inclusion criteria, a demographic questionnaire will be completed, followed by a clinical examination.\u003c/p\u003e\n\u003cp\u003eInitially, participants will be positioned in the lithotomy position. Before inserting the speculum, the vulvar region will be examined for edema, inflammation, erythema, and lesions. Subjective symptoms, including itching, burning, and dyspareunia, will be self-reported by participants using a 10 cm Visual Analog Scale (VAS), where 0 indicates no symptoms and 10 represents the most severe symptoms. These scores will be documented in a checklist.\u003c/p\u003e\n\u003cp\u003eA moistened speculum (with normal saline, without lubricant) will be inserted into the vagina. A thorough vaginal examination will be performed, assessing inflammatory changes, ulcers, discharge, and cervical abnormalities. Vaginal acidity will be measured using a pH test strip.\u003c/p\u003e\n\u003cp\u003eObjective symptoms, such as vulvovaginal inflammation (edema, erythema, and fissures), will be evaluated using Sobel\u0026rsquo;s scoring system:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003e0\u003c/strong\u003e: No inflammation, edema, erythema, or fissures.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e1\u003c/strong\u003e: Mild inflammation, edema, erythema, or fissures.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e2\u003c/strong\u003e: Moderate inflammation, edema, erythema, or fissures.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e3\u003c/strong\u003e: Severe inflammation, edema, erythema, or fissures.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe severity of vulvovaginal candidiasis will be determined by the total score obtained from subjective and objective symptoms using Sobel\u0026rsquo;s clinical scoring system. A total Sobel score \u0026ge;4 will be considered as probable acute vulvovaginal candidiasis, qualifying the participant for inclusion in the study.\u003c/p\u003e\n\u003cp\u003eSubjective symptoms (vaginal and vulvar itching, burning, and dyspareunia) will be evaluated using the VAS tool. To confirm the diagnosis and rule out other causes such as bacterial vaginosis or cervicitis, samples of vaginal secretions will be collected from the posterior fornix, avoiding alkaline cervical discharge. Vaginal pH will also be measured:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003epH 4\u0026ndash;4.5\u003c/strong\u003e: Indicative of candidiasis.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003epH \u0026gt;4.5\u003c/strong\u003e: Suggestive of mixed infections, bacterial vaginosis, or trichomoniasis (participants with these conditions will be excluded from the study).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThree sterile cotton swabs will be used to collect samples from the lateral wall and posterior fornix of the vagina:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eThe first swab will be smeared onto a glass slide, with one drop of normal saline added to prepare a wet mount for examining motile \u003cem\u003eTrichomonas\u003c/em\u003e parasites under a microscope.\u003c/li\u003e\n \u003cli\u003eThe second swab will be treated with 10% potassium hydroxide (KOH) to detect fungal elements (e.g., hyphae and blastospores) under a microscope. If clue cells (indicative of bacterial vaginosis) or \u003cem\u003eTrichomonas\u003c/em\u003e parasites are observed, the participant will be excluded and referred for treatment. A positive KOH test (presence of hyphae or blastospores) will indicate candidiasis.\u003c/li\u003e\n \u003cli\u003eThe third swab will be sent to the laboratory for culture on Sabouraud Dextrose Agar to confirm the diagnosis. Samples will be incubated at 30\u0026ndash;37\u0026deg;C, and colonies will be examined by a mycologist after 42\u0026ndash;72 hours. Positive culture results will confirm candidiasis, qualifying the participant for inclusion in the study.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eOnly patients with baseline positive cultures for yeast will be included in the analysis of treatment efficacy. The probable diagnosis of candidiasis will be based on clinical symptoms and the presence of fungal elements (hyphae or blastospores) in the KOH test. Definitive diagnosis will be confirmed through culture results on Sabouraud Agar.\u003c/p\u003e\n\u003cp\u003eAfter confirming the final diagnosis, participants will be randomly assigned to one of two groups: intervention or control.\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eControl group\u003c/strong\u003e: Participants in this group will receive 1% clotrimazole vaginal cream. They will be instructed to apply a 5-gram applicator of the cream vaginally each night before bedtime for one week.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIntervention group\u003c/strong\u003e: Participants in this group will receive Jashir vaginal cream. They will be instructed to apply a 5-gram applicator of the cream vaginally each night before bedtime for one week.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up and Adverse Event Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePotential adverse drug reactions will be assessed on the second and fourth days after starting treatment using a structured questionnaire. The following symptoms will be specifically evaluated:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eVaginal itching\u003c/li\u003e\n \u003cli\u003eBurning sensation\u003c/li\u003e\n \u003cli\u003eRedness and inflammation of the vagina\u003c/li\u003e\n \u003cli\u003eVaginal dryness\u003c/li\u003e\n \u003cli\u003eAbnormal discharge\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAny newly emerged symptoms or worsening of existing symptoms in response to the medication will be classified as an adverse drug reaction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeven days after completing the treatment course, participants in both groups will be evaluated for clinical improvement and laboratory results. This assessment will include:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003e\u003cstrong\u003eClinical examination\u003c/strong\u003e to assess symptoms and signs.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDirect wet smear test\u003c/strong\u003e with potassium hydroxide (KOH).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCulture of vaginal discharge\u003c/strong\u003e on Sabouraud Dextrose Agar.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eA negative result on both the smear and culture will indicate successful treatment. If the results are positive or symptoms persist, participants will be referred to a gynecologist for further management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of Treatment Success\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical treatment success will be defined as the resolution of baseline symptoms and signs and a reduction in the Sobel symptom severity score to \u0026le;2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of Patient Satisfaction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeven days after completing the treatment, participant satisfaction with the medication and treatment method will be assessed using a short questionnaire with three response options:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eSatisfied\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNot satisfied\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSomewhat satisfied\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eFinally, the treatment outcomes and satisfaction levels in the intervention (Jashir cream) and control (clotrimazole cream) groups will be compared and statistically analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection Tools\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data collection tools will include an interview form, a checklist for recording examinations and clinical observations, a drug complaint questionnaire, a medication satisfaction questionnaire, pH test paper, a Visual Analog Scale (VAS), and the semi-quantitative clinical tool Sobel.\u003c/p\u003e\n\u003cp\u003eThe interview form will include questions about demographic characteristics, which will consist of sections on personal information, social data, personal hygiene, and obstetric history. The checklist for recording examinations and clinical observations will include information regarding clinical symptoms and will record results from laboratory tests, including the patient\u0026rsquo;s main complaint, subjective symptoms (such as itching, burning, and pain during intercourse), and objective symptoms (including discharge, inflammation, and erythema of the vulva as identified by the examiner). It will also contain laboratory test results (such as pH test results and vaginal discharge smear results) and the code of the administered medication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedication\u003c/strong\u003e:\u003cbr\u003e\u0026nbsp;The medication will be prepared by the pharmacist at Yasuj University of Medical Sciences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrug Complaint Checklist\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePotential drug side effects will be evaluated on the second and fourth days after starting treatment. The evaluation of side effects will be based on the drug complaint checklist and any newly occurred or worsened side effects (such as itching, burning, vaginal redness and inflammation, vaginal dryness, and discharge) in response to the medication will be considered as drug-related adverse effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedication Satisfaction Checklist\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSatisfaction with the medication and treatment method will be assessed using the medication satisfaction checklist seven days after the completion of the treatment. The responses will be based on a Likert scale (Satisfied / Dissatisfied / Neutral).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod for Measuring the Validity and Reliability of Data Collection Tools\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo determine the scientific validity of the questionnaire and checklist, content validity will be assessed through the opinions of faculty members from the Midwifery Department at Yasuj University of Medical Sciences. The scientific trustworthiness and reliability will be determined through a test-retest method applied to 20 patients attending the Shahid Mofatteh Clinic, with the correlation coefficient calculated using Pearson\u0026rsquo;s correlation and Cronbach\u0026apos;s alpha.\u003c/p\u003e\n\u003cp\u003eFurthermore, a wet smear test will be conducted on 10 individuals, with two separate samples labeled with different codes and sent to the laboratory for analysis. The correlation between the results of the two samples will then be evaluated.\u003c/p\u003e\n\u003cp\u003eFor the reliability of the pH test strip, all kits will be purchased from a reputable brand, and one kit will be tested using a standard buffer solution for every five kits. Each kit will be placed in the standard solution, and the color spectrum of the kit will be compared with the pH of the standard solution to confirm its scientific validity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisual Analog Scale (VAS)\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Visual Analog Scale is a 100-millimeter ruler typically used to assess various health-related factors, including symptoms of disease, pain, mood, quality of life, and patient satisfaction. The patient will mark the scale according to the severity of their symptoms, and the number obtained will be described by the researcher. The scale ranges from \u0026ldquo;No Itching, No Burning\u0026rdquo; on the left to the phrase \u0026ldquo;Worst and Most Severe Symptoms Imaginable\u0026rdquo; at the far right.\u003c/p\u003e\n\u003cp\u003eThe severity of itching can be measured using unidimensional scales, such as the Visual Analog Scale (VAS), Numerical Rating Scale (NRS), Verbal Rating Scale (VRS), and various multidimensional questionnaires, including the Itch Severity Scale (ISS). Several studies have investigated the correlation between VRS and VAS, as well as the validity and reliability of the unidimensional itch severity scales.\u003c/p\u003e\n\u003cp\u003eThe image below illustrates a sample of the VAS for measuring itching.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSobel Scale\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Sobel scoring system is a semi-quantitative clinical rating scale that determines the severity of vulvovaginal symptoms. It will assign scores to both the objective and subjective symptoms of candidal vaginitis, and the initial classification of candidal vaginitis will be based on the symptom scores. In this system, scores for symptoms such as itching, erythema of the vulva and vagina, edema, cuts/small fissures are as follows: absent (0), mild (1), moderate (2), and severe (3). The total symptom score is the cumulative score of all symptoms, with a score of less than 4 indicating mild vaginitis, a score of 4 or higher indicating moderate vaginitis, and a score of 7 or higher classifying it as severe. Patients with a total score greater than 4 and a history of vaginitis in the past 12 months will be considered as having candidal vaginitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData analysis will be performed using SPSS software (Inc, Chicago, IL, USA), version 25. Descriptive statistics, including mean, standard deviation, absolute frequency, and relative frequency percentage, will be presented. To compare quantitative variables such as age, independent t-tests will be used. For comparing categorical variables such as education level and the main variables before and after intervention between the two groups, the chi-square test will be used. To control for potential confounding factors, Fisher\u0026rsquo;s exact test will be conducted between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and Informed Consent\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis trial has been approved by the Medical Ethics Committee of Yasuj University of Medical Sciences, Yasuj, Iran (IR.YUMS.REC.1402.030). This study will be conducted in accordance with the Declaration of Helsinki in terms of ethical considerations.\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eWritten informed consent will be obtained from all participants before their inclusion in the study. This randomized double-blind clinical trial is registered with the Iranian Registry of Clinical Trials (IRCT) under registration number IRCT20230521058245N1, dated June 27, 2023. The trial is accessible at http://en.irct.ir/trial/70331. Consent for publication is not applicable.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn this protocol, a two-phase clinical intervention is designed to evaluate the effect of the Jashir plant product on the improvement of symptoms of candidal vaginitis in symptomatic women.\u003c/p\u003e\n\u003cp\u003eIn the first phase, based on a researcher-created checklist, the conditions of the participants are reviewed, and sample selection is carried out. Then, for patients presenting with complaints of acute candidal vulvovaginitis with symptoms (itching of the vulva and vagina, cheesy discharge, burning, pain during intercourse, and inflammatory symptoms of the vulva), a medical history will be taken, and the inclusion and exclusion criteria will be assessed. Participants who meet the inclusion criteria will complete a demographic questionnaire, followed by a clinical examination, and the vulvovaginal symptom form will be completed.\u003c/p\u003e\n\u003cp\u003eSubjective symptoms of the vulva and vagina, such as itching, burning, and dyspareunia, will be assessed by the participants using a 10 cm Visual Analog Scale (VAS), ranging from 0 (no itching/burning/dyspareunia) to 10 (most severe itching/burning/dyspareunia). These scores will be recorded in the checklist. Then, a speculum moistened with normal saline, without lubricant, will be inserted into the vagina, and a detailed vaginal examination will be conducted to assess for inflammatory changes, wounds, discharge, inflammation, and cervical changes. After examining the vagina and cervix for symptoms such as lesions, inflammation, and discharge, the vaginal pH will be measured using a pH test strip.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective Symptoms\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Objective symptoms include inflammatory vulvovaginal signs (edema, inflammation, erythema of the vagina and vulva, and fissures) based on the examiner\u0026rsquo;s observations and the Sobel scoring system. The scoring for these symptoms is as follows: no inflammation, edema, erythema, or fissures (0), mild inflammation, edema, erythema, and fissures (1), moderate inflammation, edema, erythema, and fissures (2), severe inflammation, edema, erythema, and fissures (3). The total score will classify the symptoms accordingly.\u003c/p\u003e\n\u003cp\u003eTo confirm the diagnosis and exclude other causes of vaginitis and cervicitis, vaginal discharge will be collected from the posterior fornix to avoid contamination with alkaline cervical discharge. Vaginal pH will be measured using a pH strip. A pH between 4.0 and 4.5 will indicate candidiasis, while participants with a pH higher than 4.5 (which suggests mixed vaginal infections, such as Gardnerella vaginitis) will be excluded from the study.\u003c/p\u003e\n\u003cp\u003eNext, three sterile cotton swabs will be used to collect discharge samples from the vaginal wall and posterior fornix. One swab will be spread on a glass slide, a drop of normal saline will be added, and a wet mount will be prepared. This will be examined under the microscope for the presence of \u003cem\u003eTrichomonas\u003c/em\u003e (flagellated parasite). The second swab will be analyzed for fungal elements, and 10% potassium hydroxide will be added. Both swabs will be examined under a microscope at 40x magnification, and if \u003cem\u003eTrichomonas\u003c/em\u003e or key cells (for bacterial vaginosis) are observed on the first slide, the participant will be excluded from the study and referred for treatment. If \u003cem\u003eCandida\u003c/em\u003e (hyphae and blastospores) is seen on the second slide, the sample will be considered positive for candidiasis, and the third swab will be sent for final confirmation by Sabouraud Dextrose Agar culture.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePhase Two\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe samples will be incubated at 30-37\u0026deg;C for 42-72 hours. After colony formation, a mycologist will examine the cultures, and if positive for yeast, the sample will be included as a confirmed case. Only patients with a positive baseline culture for yeast will be included in the efficacy analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePhase Three\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOnce candidiasis is confirmed, the participants will be randomly assigned into two groups: one receiving vaginal cream containing \u003cem\u003eJashir\u003c/em\u003e and the other receiving vaginal clotrimazole cream. Participants in the control group will be instructed to use a 5-gram applicator of clotrimazole vaginal cream nightly for one week, while those in the intervention group will use a 5-ml applicator of \u003cem\u003eJashir\u003c/em\u003e vaginal cream in the same manner.\u003c/p\u003e\n\u003cp\u003eThe researcher will complete the checklists and forms, and follow-up will be conducted through telephone calls to ensure participant adherence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse Effects\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdverse drug reactions will be evaluated on the second and fourth days after the start of treatment. The assessment will rely on a drug complaint questionnaire and include possible adverse effects such as itching, burning, vaginal redness, inflammation, dryness, or changes in discharge that have either newly occurred or worsened in response to the medication. These will be recorded as potential side effects of the treatment.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eVaginitis is defined as a condition characterized by abnormal vaginal discharge, odor, irritation, itching, or burning, and is commonly associated with increased vaginal discharge (leukorrhea), genital inflammation, and vaginal pain% of women suffer from recurrent candidal infections during their lifetime. Common symptomndidiasis include intense itching (the most frequent symptom), bleeding erosions, erythema and he vulva, white, cheesy or watery vaginal discharge, dysuria, and dyspareunia. This infection requires treatment as it can lead to complications such as depression, stress, low self-esteem, sexual dissatisfaction in women, infertility, and during pregnancy, it is associated with an increased risk of preterm birth and low birth weight, as well as congenital cutaneous candidiasis.\u003c/p\u003e\n\u003cp\u003eMedicinal plants, known for their compal flora, are considered appropriate for the treatment of this condition. Several studies have investigated the effect of herbal medicines on vaginitis; however, the effect on candidal vaginitis specifically has not been studied extensively in clinical settings.\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003ePrangos\u003c/em\u003e species, used both as a spice and in traditional medicine in Asia, particularly in Iran, Turkey, and Iraq, holds significant importance. Phytochemical investigations of this genus have shown that coumarins, fand terpenoids are the major components of these plants. Analysis of the essential oil of the aerial parts of \u003cem\u003eP. ferulacea\u003c/em\u003e revealed the ion of 27 compounds, mainly \u0026beta;-pinene (43.1%), \u0026alpha;-pinene (22.1%), and \u0026delta;-3-carene (16.9%). Regarding the mechanism of action of essential oils on fungi, certain natural products can fungal cell membrane by increasing permeability and fluidity, leading to the breakdown of lipids, proteins, and nucleic acids. This, along with the coagulation of cellular components, results in the degradation and death of fungal cells.\u003c/p\u003e\n\u003cp\u003eA study by Hakimzadeh et al. demonstrated that the main components of \u003cem\u003eP. ferulacea\u003c/em\u003e essential oil inene (18.34%), \u0026beta;-pinene (27.01%), \u0026delta;-3-carene (24.78%), and \u0026beta;-caryophyllene (17.69%). \u0026alpha;-pinene, a common and principal compound in \u003cem\u003eP. ferulacea\u003c/em\u003e, has been shown to increase membrane permeability, inhibit respiration processes, and affect ion transport in \u003cem\u003eCandida\u003c/em\u003e species. This study concluded that \u003cem\u003eP. ferulacea\u003c/em\u003e essential oil exhibits inhibitory activity against \u003cem\u003eCandida\u003c/em\u003e, and both \u003cem\u003eP. ferulacea\u003c/em\u003e and \u003cem\u003eP. uloptera\u003c/em\u003e oils could be utilized as novel antifungal agents.\u003c/p\u003e\n\u003cp\u003eYousefi and colleagues (2017) reported that the root extract of \u003cem\u003ePrangos ferulacea\u003c/em\u003e showed inhibitory activit Candida albicans*. Furthermore, methanolic extracts of \u003cem\u003eP. ferulacea\u003c/em\u003e exhibited antibacterial activity against tested strains, including \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, \u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, and \u003cem\u003eBacillus cereus\u003c/em\u003e. Several studies have confirmed that \u003cem\u003ePrangos\u003c/em\u003e species possess antifungal activity.\u003c/p\u003e\n\u003cp\u003eThe safety and non-toxicity of using \u003cem\u003ePrangos\u003c/em\u003e (Jashir) in various dosages have been extensively studied in animal, in vitro, and clinical studies, all of which generally show that this plant is free of side effects.\u003c/p\u003e\n\u003cp\u003eA key strength of this study lies in the use of culture media to identify Candida samples and conducting the research in women with symptoms of candidal vaginitis. Given the resistance that \u003cem\u003eCandida\u003c/em\u003e species exhibit against chemical drugs, it is hoped that this research will provide valuable data for designing an intervention program using products containing \u003cem\u003eJashir\u003c/em\u003e extract for treating candidal vaginitis. The application of this product in treatment could contribute to improving women\u0026apos;s health. The strategies outlined in this intervention program could be both significant and cost-effective, making this approach promising. Therefore, we hope the success of such an intervention will be a step forward in advancing women\u0026apos;s health.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis randomized, double-blind clinical trial was approved by the Medical The ethics committee that approved the study of Yasuj University of Medical Sciences, Yasuj, Iran (IR.YUMS.REC.1401.004).\u0026nbsp;Written informed consent will be obtained from all participants prior to enrollment. This study was registered on June 27, 2023, in the Iranian Registry of Clinical Trials (IRCT20230521058245N1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication: \u003c/strong\u003eConsent for publication is not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials: \u003c/strong\u003eAvailability of data and materials: The datasets used and/or analyzed during the current study will be available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This research protocol was funded by Yasuj University of Medical Sciences (Grant No. 4010152), Yasuj, Iran. The funder played no role in the study design and will not be involved in the study implementation, data analysis and interpretation, or decisions regarding the submission of results\u003c/p\u003e\n\u003cp\u003eThis research was funded by Yasuj University of Medical Sciences,Yasuj.Iran. \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article is part of a master\u0026apos;s thesis in midwifery and was approved and funded by the Research Vice Chancellor of Yasuj University of Medical Sciences, Yasuj, Iran No. 4010152. The authors would like to thank the participants in this study .\u003c/p\u003e\n\u003cp\u003eFG, AR, DR, and MT designed the study. FG and AR conducted the literature search. DR and FG determined the dosage of Prangos Ferulacea\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eproduct based on the studies. DR prepared the Prangos Ferulacea\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eand placebo product. AR will perform the sampling. S. D.Y will administer the drug and placebo to the participant and monitor the results of the product administration and its side effects. FG will conduct the data analysis. FG wrote the manuscript. All authors read and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cspan dir=\"RTL\"\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/span\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis article is based on a research project. The authors thank Yasuj University of Medical Sciences for supporting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is currently recruiting participants.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePaladine, H.L. and U.A. Desai, Vaginitis: diagnosis and treatment. American family physician, 2018. 97(5): p. 321-329.\u003c/li\u003e\n\u003cli\u003eEdalatpanah, Y., et al., Evaluation of Antifungal Effects of Prangos ferulace and Plantago major L Plants Against Fluconazole-resistant Candida albicans Species in Extracorporeal Conditions. Navid No, 2020. 23(74): p. 44-52.\u003c/li\u003e\n\u003cli\u003eBrown, H. and M. Drexler, Improving the diagnosis of vulvovaginitis: perspectives to align practice, guidelines, and awareness. Population health management, 2020. 23(S1): p. S-3-S-12.\u003c/li\u003e\n\u003cli\u003eZakeri, S., et al., The effect of Achillea millefolium L. on vulvovaginal candidiasis compared with clotrimazole: A randomized controlled trial. Complementary Therapies in Medicine, 2020. 52: p. 102483.\u003c/li\u003e\n\u003cli\u003eMohammadi, S., et al., Comparing the effectiveness of Arnebia euchroma with clotrimazolevaginal cream for the treatment of vulvovaginal candidiasis: A randomized controlled triple-blind trial. Iranian Journal of Nursing and Midwifery Research, 2022. 27(2): p. 112.\u003c/li\u003e\n\u003cli\u003eMohankumar, B., et al., Vaginosis: Advances in new therapeutic development and microbiome restoration. Microbial Pathogenesis, 2022: p. 105606.\u003c/li\u003e\n\u003cli\u003eYano, J., et al., Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes. BMC women\u0026apos;s health, 2019. 19: p. 1-9.\u003c/li\u003e\n\u003cli\u003eJs, B., Berek \u0026amp; Novak\u0026rsquo;s gynecology. Translate to Persian by: Ghazijahani B, Zonuzi A, Bahrami N. Tehran: Golban pub, 2007: p. 471-501.\u003c/li\u003e\n\u003cli\u003eEbrahimy, F., et al., Comparison of the therapeutic effects of Garcin\u0026reg; and fluconazole on Candida vaginitis. Singapore medical journal, 2015. 56(10): p. 567.\u003c/li\u003e\n\u003cli\u003eSasani, E., et al., Vulvovaginal candidiasis in Iran: A systematic review and meta-analysis on the epidemiology, clinical manifestations, demographic characteristics, risk factors, etiologic agents and laboratory diagnosis. Microbial pathogenesis, 2021. 154: p. 104802.\u003c/li\u003e\n\u003cli\u003eFarr, A., et al., Guideline: vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses, 2021. 64(6): p. 583-602.\u003c/li\u003e\n\u003cli\u003eBonifacio, B.V., et al., Antifungal activity of a hydroethanolic extract from Astronium urundeuva leaves against Candida albicans and Candida glabrata. Frontiers in microbiology, 2019. 10: p. 2642.\u003c/li\u003e\n\u003cli\u003eMandras, N., et al., Liquid and vapour-phase antifungal activities of essential oils against Candida albicans and non-albicans Candida. BMC complementary and alternative medicine, 2016. 16(1): p. 1-7.\u003c/li\u003e\n\u003cli\u003eSaghafi, N., et al., The effect of a vaginal suppository formulation of dill (Anethum graveolens) in comparison to clotrimazole vaginal tablet on the treatment of vulvovaginal candidiasis. Journal of Obstetrics and Gynaecology, 2018. 38(7): p. 985-988.\u003c/li\u003e\n\u003cli\u003eSheidaei, S., et al., Herbal medicine and vaginal candidiasis in Iran: a review. Evidence Based Care, 2017. 7(2): p. 71-77.\u003c/li\u003e\n\u003cli\u003eEsfahani, A., et al., Molecular epidemiology, antifungal susceptibility, and ERG11 gene mutation of candida species isolated from vulvovaginal candidiasis: Comparison between recurrent and non-recurrent infections. Microbial Pathogenesis, 2022: p. 105696.\u003c/li\u003e\n\u003cli\u003eSheidaei, S., et al., Comparison of vaginal cream of coconut oil and clotrimazole on candidal infection of vagina. Journal of Babol University of Medical Sciences, 2019. 21(1): p. 93-98.\u003c/li\u003e\n\u003cli\u003eKhanjani, N., et al., The prevalence of Candida albicans infection and related factors in women referring to health centers of Jiroft in 2010: a short report. Journal of Rafsanjan University of Medical Sciences, 2014. 13(6): p. 569-576.\u003c/li\u003e\n\u003cli\u003eAslam, B., et al., Antibiotic resistance: a rundown of a global crisis. Infection and drug resistance, 2018. 11: p. 1645.\u003c/li\u003e\n\u003cli\u003eBayani, M., et al., Association of clinical symptoms and laboratory results in diagnoses of Candida vaginitis. Journal of Babol University of Medical Sciences, 2014. 16(1): p. 50-55.\u003c/li\u003e\n\u003cli\u003eESMAEILZADEH, S., O.S. MAHDAVI, and Z. Rahmani, Frequency and etiology of vulvovaginal candidiasis in women referred to a gynecological center in Babol, Iran. 2009.\u003c/li\u003e\n\u003cli\u003eDeriu, A., et al., In vitro activity of essential oil of Myrtus communis L. against Helicobacter pylori. International Journal of Antimicrobial Agents, 2007. 30(6): p. 562-563.\u003c/li\u003e\n\u003cli\u003eAzadbakht, M., et al., Effect of Methanolic essence and extract of Myrtus Communis on Trichomonas Vaginalis. 2004.\u003c/li\u003e\n\u003cli\u003eSalem, M.E.A., et al., Vaginitis among married women attending primary healthcare in Tanta District, El-Gharbia governorate, Egypt. Menoufia Medical Journal, 2017. 30(1): p. 87.\u003c/li\u003e\n\u003cli\u003eMollazadeh-Narestan, Z., et al., Comparing the Effect of Probiotic and Fluconazole on Treatment and Recurrence of Vulvovaginal Candidiasis: a Triple-Blinded Randomized Controlled Trial. Probiotics and Antimicrobial Proteins, 2022: p. 1-11.\u003c/li\u003e\n\u003cli\u003eBenitez, L.L. and P.L. Carver, Adverse effects associated with long-term administration of azole antifungal agents. Drugs, 2019. 79(8): p. 833-853.\u003c/li\u003e\n\u003cli\u003eThamkhantho, M. and C. Chayachinda, Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study. Archives of Gynecology and Obstetrics, 2021. 303(1): p. 151-160.\u003c/li\u003e\n\u003cli\u003eMurina, F., et al., The role of female intimate hygiene practices in the management of vulvovaginal candidiasis: A randomized, controlled open-label trial. Health Care for Women International, 2022: p. 1-12.\u003c/li\u003e\n\u003cli\u003eAzadpour Motlagh, A., et al., Comparative examination of the therapeutic deficiency of oral metronidazole plus prangos ferulacea vaginal cream versus oral metronidazole plus placebo vaginal cream in accelerating trichomonas vaginalis infection recovery: A triple-blind clinical trial. International Journal of Women\u0026rsquo;s Health and Reproduction Sciences, 2020.\u003c/li\u003e\n\u003cli\u003eKafash-Farkhad, N., M. Asadi-Samani, and M. Rafieian-Kopaei, A review on phytochemistry and pharmacological effects of Prangos ferulacea (L.) Lindl. Life Science Journal, 2013. 10(SUPPL): p. 360-367.\u003c/li\u003e\n\u003cli\u003eAli, B., et al., Comparision of the effect of myrtus communis extract and clotrimazole on candida albicans isolated from patients with candida vaginitis. 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Clinical microbiology reviews, 2006. 19(1): p. 50-62.\u003c/li\u003e\n\u003cli\u003eInouye, S., et al., Inhibitory effect of essential oils on apical growth of Aspergillus fumigatus by vapour contact. Mycoses, 2000. 43(1-2): p. 17-23.\u003c/li\u003e\n\u003cli\u003eInouyea, S., T. Takizawab, and H. Yamaguchia, Antibacterial activity of essential oils and their major constituents against respiratory tract pathogens by gaseous contact. J Antimicrob Chemother, 2001. 47: p. 565-73.\u003c/li\u003e\n\u003cli\u003eYousefi, K., et al., An in vitro ethnopharmacological study on Prangos ferulacea: a wound healing agent. BioImpacts: BI, 2017. 7(2): p. 75.\u003c/li\u003e\n\u003cli\u003eYiğit, D., N. Yiğit, and U. \u0026Ouml;zgen, An investigation on the anticandidal activity of some traditional medicinal plants in Turkey. Mycoses, 2009. 52(2): p. 135-140.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Prangos Ferulacea, Candida vulvovaginitis, herbal medicine, clinical trial protocol","lastPublishedDoi":"10.21203/rs.3.rs-5729082/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5729082/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Candida vulvovaginitis is one of the most common infections among women of reproductive age, ranking as the second leading cause of visits to gynecology clinics. purpose of the study is to document the effect \u0026nbsp;of Prangos Ferulacea (Jashir) on the Treatment of Candida Vulvovaginitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This study is designed as a randomized, double-blind clinical trial that will include 112 participants divided into two groups: an intervention group and a control group. The trial will be conducted at Yasuj University of Medical Sciences. Eligible participants will be married women aged 15–45 years who present with at least two clinical symptoms (cheesy vaginal discharge and itching), a Sobel score of ≥4, and a confirmed positive Candida culture. The control group will receive clotrimazole vaginal cream, instructed to apply 5 grams intravaginally using an applicator each night for one week. The intervention group will follow the same application protocol but will use a vaginal cream formulated with Prangos Ferulacea\u003cstrong\u003e \u003c/strong\u003e(Jashir).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eThis, along with the coagulation of cellular components, results in the degradation and death of fungal cells.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e. The findings are expected to offer new insights into the potential of this herbal remedy as an alternative to azole-based antifungal treatments, paving the way for more accessible and safer therapeutic options.\u003c/p\u003e","manuscriptTitle":"The Prangos Ferulacea (Jashir) on the Candida Vulvovaginitis: A Study Protocol of clinical trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-08 10:47:15","doi":"10.21203/rs.3.rs-5729082/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1184f77c-5f8c-40b1-87ba-34b1b1517fdf","owner":[],"postedDate":"January 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-16T14:08:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-08 10:47:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5729082","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5729082","identity":"rs-5729082","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}