Phytotherapy of Vulvovaginal Candidiasis: A Narrative Review.

Vulvovaginal candidiasis (VVC) is a real gynecological problem among women of reproductive age from 15 to 49. A recent analysis showed that 75% of women will have an occurrence at least once per year, while 5% are observed to have recurrent vaginal mycosis-these patients may become unwell four or more times a year. This pathology is caused in 85-90% of cases by fungi of the Candida albicans species. It represents an intractable medical problem for female patients due to pain and pruritus. Due to the observation of an increasing number of strains resistant to standard preparations and an increase in the recurrence of this pathology when using local or oral preferential therapy, such as fluconazole, an analysis was launched to develop alternative methods of treating VVC using herbs such as dill, turmeric, and berberine. An in-depth analysis of databases that include scientific articles from recent years made it possible to draw satisfactory conclusions supporting the validity of herbal therapy for the pathology in question. Although phytotherapy has not yet been approved by the Food and Drug Administration, it appears to be a promising therapeutic solution for strains that are resistant to existing treatments. There is research currently undergoing aimed at comparing classical pharmacotherapy and herbal therapy in the treatment of vaginal candidiasis for the purpose of increasing medical competence and knowledge for the care of the health and long-term comfort of gynecological patients.

Effect of Pulsatilla decoction on vulvovaginal candidiasis in mice. Evidences for its mechanisms of action.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common infection that affects the female reproductive tract. Pulsatilla decoction (PD), a traditional Chinese herbal medicine, is a classic and effective prescription for VVC. However, its mechanism of action remains unclear. PURPOSE: This study aimed to evaluate the efficacy and potential mechanism of action of the n-butanol extract of Pulsatilla decoction (BEPD) in VVC treatment. METHODS: High performance liquid chromatography (HPLC) was used to detect the main active ingredients in BEPD. A VVC-mouse model was constructed using an estrogen-dependent method to evaluate the efficacy of BEPD in VVC treatment. Fungal burden and morphology in the vaginal cavity were comprehensively assessed. Candida albicans-induced inflammation was examined in vivo and in vitro. The effects of BEPD on the Protein kinase Cδ (PKCδ) /NLR family CARD domain-containing protein 4 (NLRC4)/Interleukin-1 receptor antagonist (IL-1Ra) axis were analyzed using by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and reverse transcription-quantitative polymerase chain reaction (qRT-PCR). RESULTS: BEPD inhibited fungal growth in the vagina of VVC mice, preserved the integrity of the vaginal mucosa, and suppressed inflammatory responses. Most importantly, BEPD activated the "silent" PKCδ/NLRC4/IL-1Ra axis and negatively regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby exerting a therapeutic efficacy on VVC. CONCLUSIONS: BEPD effects on mice with VVC were dose-dependent. BEPD protects against VVC by inhibiting inflammatory response and NLRP3 inflammasome via the activation of the PKCδ/NLRC4/IL-1Ra axis. This study revealed the pharmacological mechanism of BEPD in VVC treatment and provided further evidence for the application of BEPD in VVC treatment.

Biological Activity and Chemical Composition of Propolis Extracts with Potential Use in Vulvovaginal Candidiasis Management.

Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural ingredients, propolis arises as an excellent alternative, being a complex substance with pharmacological properties. This work aims to explore the potential of propolis as a new pharmaceutical ingredient for the replacement of conventional vulvovaginal antifungals. Propolis extracts were obtained by Ultrasound-Assisted Extraction using different solvents (water, water/ethanol (50:50, v/v), and ethanol). Afterwards, the extracts were characterized regarding total phenolic content (TPC), antioxidant/antiradical activities, radical scavenging capacity, antifungal activity against strains of Candida species, and viability effect on two female genital cell lines. The aqueous extract achieved the best TPC result as well as the highest antioxidant/antiradical activities and ability to capture reactive oxygen species. A total of 38 phenolic compounds were identified and quantified by HPLC, among which ferulic acid, phloridzin and myricetin predominated. Regarding the anti-Candida spp. activity, the aqueous and the hydroalcoholic extracts achieved the best outcomes (with MIC values ranging between 128 and 512 µg/mL). The cell viability assays confirmed that the aqueous extract presented mild selectivity, while the hydroalcoholic and alcoholic extracts showed higher toxicities. These results attest that propolis has a deep potential for vulvovaginal candidiasis management, supporting its economic valorization.

Effect of the Pulsatilla decoction n-butanol extract on vulvovaginal candidiasis caused by Candida glabrata and on its virulence factors.

Vulvovaginal candidiasis (VVC) caused by Candida glabrata (C. glabrata) is more persistent and resistant to treatment than when caused by Candida albicans (C. albicans) and has been on the rise in recent years. The n-butanol extract of Pulsatilla Decoction (BEPD) has been shown to be effective in treating VVC caused by C. glabrata, but the underlying mechanism of action remains unclear. In this study, the experimenter conducted in vitro and in vivo experiments to explore the effects of BEPD on the virulence factors of C. glabrata, as well as its efficacy, with a focus on possible immunological mechanism in VVC caused by C. glabrata. The contents of Anemoside B4, Epiberberine, Berberine, Aesculin, Aesculetin, Phellodendrine and Jatrorrhizine in BEPD, detected by high-performance liquid chromatography, were 31,736.64, 13,529.66, 105,143.72, 19,406.20, 4952.67, 10,317.03, 2489.93 µg/g, respectively. In vitro experiments indicated that BEPD moderately inhibited the growth of C. glabrata, its adhesion, and biofilm formation, and affected the expression of efflux transporters in the biofilm state. In vivo experiments demonstrated that BEPD significantly reduced vaginal inflammatory manifestation and the release of proinflammatory cytokines and LDH in mice with VVC caused by C. glabrata. Moreover, it inhibited the Phosphorylation of EGFR, ERK, P38, P65, and C-Fos proteins. The results suggested that although BEPD moderately inhibits the growth and virulence factors of C. glabrata in vitro, it can significantly reduce vaginal inflammation by down-regulating the EGFR/MAPK signaling pathway in mice with VVC infected by C. glabrata.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

Extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines treats vulvovaginal candidiasis by affecting the vaginal mucosal barrier.

Aim: This study investigated the inhibition of extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines (ESCC) on Candida albicans (C. albicans) in vitro and the effect of ESCC on the vaginal mucosal barrier in vivo. Materials & methods: Susceptibility testing was performed with C. albicans SC5314. A vulvovaginal candidiasis mouse model was successfully established. The plate method, Gram staining, hematoxylin and eosin staining and ELISA were used to detect relevant inflammatory indexes: IFN-γ, IL-1 and TNF-α. Quantitative real-time PCR and western blot were used to detect mucosal immune-related factors: MUC1, MUC4, DEFB1 and DEFB2. Results: ESCC was able to inhibit the proliferative activity of C. albicans, and it affected inflammation-related factors and indicators of vaginal mucosal immunity. Conclusion: ESCC showed potential value in the treatment of vulvovaginal candidiasis.

Efficacy of a medical grade honey formulation (L-Mesitran) in comparison with fluconazole in the treatment of women with recurrent vulvovaginal candidiasis: protocol for a randomised controlled trial (HONEY STUDY).

INTRODUCTION: Recurrent vulvovaginal candidiasis (RVVC) affects up to 9% of women worldwide. This amount is expected to increase due to lifestyle changes, increased fungal resistance and biofilm formation. Treatment options are limited and in 57% of the cases, relapses occur within 12 months after starting fluconazole therapy (golden standard). The pathogenesis of RVVC is multifactorial and includes fungal biology, the vaginal microenvironment and the immune system. Fluconazole is antimicrobial and effective in inducing short-term remission but a long-term cure is hard to achieve. Medical grade honey (MGH) has antimicrobial, protective, antioxidative and immunomodulatory activity and may therefore be a good alternative treatment. This study aims to investigate the clinical cure rate and long-term efficacy of MGH compared with fluconazole in patients with RVVC. METHODS AND ANALYSIS: This study is a multicentre, randomised controlled trial (Maastricht University Medical Centre+ and Zuyderland Medical Centre). A total of 252 eligible women will be randomly assigned to the fluconazole group (control) or the MGH group (L-Mesitran, treatment). The primary objective is to investigate the mycological cure rate after 1 month assessed through a vaginal culture. Secondary objectives are the clinical cure rate regarding symptoms, the prophylactic activity after 6 months of maintenance therapy and the number of relapses within 12 months. Moreover, information about side effects, discomfort and quality of life will be collected with the use of questionnaires. ETHICS AND DISSEMINATION: Ethical approval from the Medical Ethics Review Committee of the academic hospital Maastricht/University Maastricht has been obtained (NL 73974.068.21, V.7 on 8 February 2022). Additional approval was obtained from the Ethics Committee of the Zuyderland Medical Centre Heerlen (Z2021141 on 4 March 2022). The first patient was randomised on 22 August 2022. Results will be made available to researchers and healthcare professionals via conferences, meetings and peer-reviewed international publications. TRIAL REGISTRATION NUMBER: NCT05367089.

Antibiofilm potential of Annona muricata L. ethanolic extract against multi-drug resistant Candida albicans.

ETNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Annona muricata L. (soursop) include treatment for cancer, fungal infections, and inflammatory diseases. Its phytoconstituents, mainly acetogenins and alkaloids, are associated with therapeutic activity and clinical application is currently under investigation. However, the application of phytotherapy to treat diseases caused by fungal biofilms, such as vulvovaginal candidiasis (VVC), is still limited. AIM OF THE STUDY: To investigate the activity of the ethanolic extract of A. muricata leaves (AML) against biofilms formed by multiresistant Candida albicans (ATCC® 10231) both in vitro and in a VVC experimental model. MATERIAL AND METHODS: C. albicans biofilms were grown and their adhesion, proliferation, development, and matrix composition studied by spectrophotometry, scanning electron microscopy (SEM), whole slide imaging (WSI), and biochemical assays without or with AML treatment. In parallel, in vivo experiments were conducted using a murine model of infection treated with different concentrations of the extract and nystatin. Fungal burden and histological changes were investigated. RESULTS: The proliferation and adhesion of C. albicans biofilms were significantly reduced as confirmed by SEM and WSI quantitative analyses. Furthermore, the concentration of carbohydrates, proteins and DNA was reduced in the biofilm matrix. In vivo assays demonstrated that AML was able to reduce the fungal burden and the inflammatory process. CONCLUSIONS: The findings further emphasized the therapeutic and scientific potential of AML, thus encouraging its future use in the treatment of VVC.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

Essential oil and nanocarrier-based formulations approaches for vaginal candidiasis.

An exclusive site for local drug delivery is the vagina, especially for vaginal infections. The fungus Candida albicans causes vaginal infection known as vulvovaginal candidiasis, a highly prevalent and recurrent gynaecological disease among women. Vaginal candidiasis affects over 75% of women at a certain point in their life and has a recurrence rate of 40-50%. Medicinal plants provide some very effective phytoconstituents which when delivered as nanosystems have enhanced therapeutic action and efficacy by alteration in their characteristics. Antifungal drugs are used to treat these conditions, alternative medicine is required for prophylaxis and improved prognosis. The current review focuses on the research carried out on various nanocarrier-based approaches and essential oil-based formulations for vaginal candidiasis.

The vagina is a part of a woman's body that can sometimes get sick from a fungus called Candida albicans. This sickness is called thrush, and it's very common. More than 75% of women will get it at some point, and it might come back again after it's gone. There are medicines that can help, but some plants can also be used to make powerful medicine that can heal the sickness from tiny particles called 'nanosized carriers'. Scientists are studying different ways to give the medicine to the sick area from these plants.

[Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis].

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1ß, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1ß, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1ß, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.

Comparison of tea tree oil 5%, tea tree oil 10%, and nystatin inhibition zones against vaginal Candida isolates in pregnancy.

INTRODUCTION: Vulvovaginal candidiasis (VVC) in pregnancy frequently develops into recurrent infections. Clinical study suggests that conventional topical treatments for VVC are not always enough to eradicate Candida spp. from the vaginal microenvironment. This study aimed to evaluate the antifungal activity of tea tree oil (TTO) 5% and TTO 10% against Candida species causing VVC in pregnancy. METHODOLOGY: In vitro experimental study was conducted in the Mycology Laboratory at Dermatovenereology Outpatient Clinic Dr. Soetomo General Hospital Surabaya. Eighteen isolates of Candida species were isolated from the vaginal thrush of 15 pregnant women diagnosed with VVC from March to May 2021. Antifungal susceptibility of TTO 5% and TTO 10% was evaluated by the disc diffusion method, with the inhibitory zone diameter as the main outcome. RESULTS: The mean inhibitory zone diameter of TTO 5%, TTO 10%, and nystatin against all Candida spp. was 7.26 mm, 8.64 mm, and 25.57 mm, respectively (p < 0.001). The mean inhibitory zone diameter of TTO 5%, TTO 10%, and nystatin tend to be larger in C. albicans compared to the non-albicans, but the difference is not significant. Nystatin displayed the largest mean inhibitory zone diameters compared to TTO 5% and TTO 10% (p < 0.001) in all Candida species. Increased concentration from TTO 5% to TTO 10% resulted in a slight increment in the mean inhibitory zone diameters in all-Candida species (p = 0.001). CONCLUSIONS: Tea Tree Oil displayed antifungal activity against Candida species causing VVC in pregnancy. Further studies are required to investigate optimal TTO concentrations as a VVC treatment in pregnancy.

The efficacy of complementary treatment with marshmallow (Althaea officinalis L.) on vulvovaginal candidiasis: A randomized double-blinded controlled clinical trial.

BACKGROUND: Vulvovaginal candidiasis is a common gynecologic infection, and recurring cases are yet incurable. This trial was based on Persian medicine to compare how effective marshmallow aqueous extract 4% plus clotrimazole 1% (CLOT-M) is compared to clotrimazole 1% vaginal creams on VVC. METHODS: This study randomly assigned 100 women with VVC into two groups. The target group (n = 50) was treated with CLOT-M while controls (n = 50) with clotrimazole vaginal creams for seven consecutive nights. Different VVC symptoms and signs, and yeast culture from vaginal discharge were evaluated as the outcome measures before the intervention and 7 and 30 days after. RESULTS: The efficacy of CLOT-M vaginal cream was assessed during the 1st and 2nd follow-ups, indicating a significant decrease in mean itching (P = 0.001 for both comparisons) and dyspareunia score (P = 0.001 and P = 0.04, respectively) as compared to treatment with clotrimazole vaginal cream. Moreover, after 7 days of the intervention, patients in the CLOT-M group experienced significant improvement in mean dysuria score compared to those in the control group (P = 0.001). Neither cream caused any significant adverse events. CONCLUSION: It seems that CLOT-M vaginal cream had a significant effect on the VVC symptoms improvement, without any significant side effects. However, larger sample-sized trials are needed for more evidence-based judgment.

In vitro outcomes of quercetin on Candida albicans planktonic and biofilm cells and in vivo effects on vulvovaginal candidiasis. Evidences of its mechanisms of action.

BACKGROUND AND PURPOSE: Candida albicans is a fungus that produces common fungal infection in humans, including vulvovaginal candidiasis (VVC). While quercetin (QC) has potential antifungal activities against C. albicans, studies on the in vivo anti-VVC activity of QC are limited. This study evaluated the antifungal capacity of QC against cultured C. albicans strain SC5314 or in C. albicans-infected mice. METHODS: Microdilution and XTT reduction assay were used to determine the minimum inhibitory concentration (MIC) and biofilm formation of QC on C. albicans, respectively. Immunofluorescence was performed to detect the anti-invasive capacity of QC upon co-culturing C. albicans with VK2/E6E7 cells. The potential anti-VVC effects of QC were assessed in C. albicans-infected mice with VVC. Further, inflammatory cytokine levels were determined using ELISA. PAS and Papanicolaou staining were used to detect C. albicans cells and polymorphonuclear leukocytes (PMNs) in vaginal tissues. Western blotting and immunohistochemistry were performed to measure the expression of MAPK, ERK, JUN, and P38. RESULTS: MIC and minimal fungicidal concentration (MFC) of QC for C. albicans were 128 µM and > 512 µM, respectively. QC concentration lower than 128 µM (32-128 µM) could not inhibit C. albicans. QC (16 µM) notably inhibited C. albicans biofilm formation and suppressed the adhesion and invasion of C. albicans to VK2/E6E7 cells. In addition, the pharmacokinetic parameters of orally administered QC in mice showed rapid absorption (approximately 1 h) and slow elimination (approximately 6 h). Oral QC showed an effective protective function against C. albicans infection with no toxic effects a in mouse VVC model. QC significantly reduced IL-1α, TNF-α, IL-22 and IL-23 levels in vaginal lavage solution, inhibited invasive C. albicans and PMN infiltration in vaginal tissue, and effectively protected the integrity of vaginal mucosa. CONCLUSIONS: The present study showed that QC has rapid oral absorption, slow elimination, good viral distribution, and a lack of toxicity. QC not only inhibited biofilm formation, adhesion, and invasion of C. albicans in vitro, but also ameliorated C. albicans-induced inflammation and protected the integrity of the vaginal mucosa in vivo, suggesting that QC has the potential for the treatment of candidiasis.

Improved treatment of vulvovaginal candidiasis with Clotrimazole plus probiotic Lacidophilin Vaginal Capsules: A prospective, real-world study.

BACKGROUND: Clotrimazole has long been used to treat vulvovaginal candidiasis (VVC), yet the antibiotic resistance, adverse effects and recurrences still bring about a great challenge for the clinicians. To explore the effect of probiotic Lacidophilin Vaginal Capsules plus Clotrimazole Vaginal Tablets (500mg) in the treatment of uncomplicated VVC, a self-controlled real-world study was conducted. METHODS: Twenty-seven women with a normal vaginal flora and 15 women with uncomplicated VVC were recruited. The patients were treated with the single dose of Clotrimazole Vaginal Tablets (500mg) supplemented with 2 Lacidophilin Vaginal Capsules for the following 7 days. The patients were prospectively examined 4 times and the time points were at m0 (the first visit), m1 (8-10 days after the first visit), m2 (30 days after the second visit) and m3 (30 days after the third visit). However, women in the healthy normal control group were examined just once at the first visit. The obtained vaginal secretions were examined by high-throughput sequencing. RESULTS: The mean age in healthy control group and case group was 28.63 ± 5.40y and 27.67 ± 3.33y, respectively. Finally, 46.67% (7/15) of patients were cured at the second visit, 61.54% (8/13) were cured at the third visit and eventually 72.73% (8/11) were cured. A total of 81 samples were sequenced, generating 1668 operation taxonomy units among all the samples. The bacterial composition of women in the healthy control group was exceedingly abundant and dominated by Lactobacillus, especially by Lactobacillus. crispatus, and followed by Lactobacillus. iners, Lactobacillus. jensenii and Gardneralla. On the contrary, the bacterial composition of women with VVC was relatively few and dominated by Lactobacillus. iners. During the process of treatment, the bacterial abundance of VVC patients was increased gradually. At the final visit, the abundance of vaginal flora was augmented further with the dominant bacteria being Lactobacillus. crispatus, followed by Lactobacillus. iners. CONCLUSION: Clotrimazole Vaginal Tablets plus probiotic Lacidophilin Vaginal Capsules could improve the effect in treating uncomplicated VVC. This improved effect was achieved perhaps through improving the composition of vaginal flora and restoring vaginal microecology.

The Efficacy of Kundur (Boswellia serrata Roxb. Ex Colebr.) in Vulvovaginal Candidiasis: A Randomized Control Trial.

Context: Kundur, Boswellia serrata Roxb. ex Colebr., is prescribed by Unani (Greco-Arab) scholars clinically under conditions similar to vulvovaginal candidiasis (VVC) and has been supported by recent pharmacological studies, but scientific evidence is scarce. Objectives: The study intended to investigate the drug's scientific parameters and to compare its efficacy and safety to that of Miconazole nitrate (2% w/w) in treatment of VVC. Design: The research team designed a randomized controlled trial (RCT). Setting: The RCT was performed in the Department of Ilmul Qabalat wa Amraze Niswan at Luqman Unani Medical College Hospital and Research Center in Vijaypura, India, between November 2018 and March 2020. Participants: Participants were 40 married women, aged 18 to 45 years, who had been clinically examined and diagnosed with VVC. Interventions: Participants were randomly allocated to the Boswellia serrata (Kundur) group, the intervention group (n = 20), or to the miconazole group, the control group (n = 20). The Kundur group took a one-gram tablet of Kundur as a vaginal insert every day at bedtime for 21 days, while the control group used vaginal suppositories with 100 mg of miconazole (2% w/w) every day at bedtime for seven days. Outcome Measures: The primary outcome measures were changes: (1) in vulval itching (pruritus), (2) in vaginal discharge, (3) in painful urination (dysuria), (4) in recurrent genital pain (dyspareunia), and (5) in quality of life (QoL). The secondary outcome measures were mycological clearing on a potassium hydroxide (KOH) test and a per-speculum pelvic examination for the presence or absence of curdy discharge, vulval erythema, and vulval swelling. Results: The response to the intervention was greater than that of the control in reducing pruritus vulvae and vaginal discharge. However, both drugs were equally effective in improving the rest of the parameters, including QoL. Conclusion: The VVC symptoms were equally and significantly improved in both the intervention and the control groups, and Boswellia serrata Roxb. ex Colebr. was shown to be efficacious in the management of VVC. Further studies with a rigorous design and larger sample size are needed to reinforce scientific evidence.

Effects of n-butanol extract of Pulsatilla decoction on the NLRP3 inflammasome in macrophages infected with Candida albicans.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction is a traditional Chinese medicine from Shang Han Lun that has been reported to have therapeutic efficacy in vulvovaginal candidiasis (VVC), and is a growth inhibitor of Candida albicans (C. albicans) in vitro, the causative agent of VVC. AIM OF THE STUDY: In previous studies, Pulsatilla decoction has shown therapeutic benefits for VVC. With further chemical extraction of the decoction, the n-butanol extract (of Pulsatilla decoction; BEPD) was most effective against C. albicans and therapeutic for VVC. The mechanism, however, has not been elucidated. The regulation of NOD-like receptor protein 3 (NLRP3) inflammasome has recently been demonstrated as a critical component of the inflammasome complex that initiates the vaginal inflammatory response. Therefore, the effect of BEPD on NLRP3 associated with VVC was investigated. MATERIALS AND METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for detecting the principal compounds of BEPD (Anemoside B4, Esculin, esculetin, Epiberberine, Berberine, Jatrorrhizine and Phellodendrine). BEPD-containing serum is prepared by intragastric administration of BEPD (4.6875 g/kg for seven days) in rats. PMA-induced THP-1 cells were challenged with C. albicans. The expression of CD68 to identify macrophages was examined by flow cytometry, the viability of THP-1 cells were assessed by CCK8 assay, the release of lactate dehydrogenase (LDH) was detected by LDH kit, and the secretion levels of IL-1ß and IL-18 were evaluated through enzyme-linked immunosorbent assay (ELISA), the levels of NLRP3 were quantified by immunofluorescence, the levels of reactive oxygen species (ROS) were measured by ROS kit, and the expression of Dectin-1, Syk, TLR2, TLR4, MyD88, NF-κB, NLRP3, Caspase-1, and ASC proteins were detected by Western blot. RESULTS: After administration of BEPD-containing serum, the levels of IL-1ß, IL-18 and LDH released from macrophages were reduced in the BEPD-containing serum group compared to the model group. In addition, BEPD-containing serum inhibited the expression of ROS in macrophages, suppressed the expression of NLRP3 and inhibited the expression of TLRs/MyD88 and Dectin-1/Syk signaling pathway-related proteins. CONCLUSIONS: BEPD suppressed the NLRP3 inflammasome and related signaling pathways in macrophages infected with C. albicans in vitro, thereby providing insight into the mechanism of BEPD action on VVC.

Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis / 中国中药杂志

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.

Lived experience of medical management in recurrent vulvovaginal candidiasis: a qualitative study of an uncertain journey.

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is experienced by up to 10% of pre-menopausal women globally, yet there is limited research exploring the perspective of women living with this challenging condition. METHODS: Semi-structured interviews with Australian women experiencing RVVC were conducted between April-July 2021. Interviews were transcribed verbatim, and qualitative interpretative phenomenological analysis (IPA) was conducted. RESULTS: Ten RVVC patients were interviewed. IPA revealed an uncertain journey living with RVVC for all participants ranging from initial symptoms and difficulties in obtaining a diagnosis, the trial and error of symptom management, to the overall debilitating impact of living with a personal and intimate health condition. Four key themes were identified: Theme 1 outlined challenges and delays in diagnosis and clinically appropriate management. Theme 2 found that health care professional (HCP) knowledge limitations impacted RVVC management. Theme 3 illustrated the consequences of a lack of HCP support leading to self-referral and self-education. Theme 4 details the significant emotional and psycho-social repercussions of RVVC. CONCLUSIONS: This debilitating, life-long disease has a prolonged effect on women both physically and psychologically. Living with RVVC seems an uncertain journey that, to a large degree, women feel they must navigate alone. While resilience and self-empowerment were noted, better support through evidence-based treatment options, educated and evidence-informed HCPs and a sympathetic social support network is needed to decrease the disease burden. Future clinical management guidelines and patient support need to consider the findings of this study.

Effectiveness of redcore lotion in patients with vulvovaginal candidiasis: a systematic review and Meta-analysis.

OBJECTIVE: To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of randomized controlled trials. METHODS: A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019. Randomized controlled trials in the treatment for VVC were included; only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included. Relative risk (RR) and 95% confidence intervals (CI) were used in the Meta-analysis. RESULTS: Seven studies involving 768 patients suffering from VVC were identified; 468 of the patients were pregnant women (60.9%). Combination group (Redcore lotion plus miconazole) was more effective in reduCIng symptomatic episodes of VVC than miconazole alone, with respect to cure rate (RR, 1.31; 95% CI, 1.09-1.57; P = 0.01), fungal culture negative rate (RR, 1.21; 95% CI, 1.04-1.41; P = 0.01), and effective rate (RR, 1.18; 95% CI, 1.05-1.35; P = 0.01). Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate (RR, 1.48; 95% CI, 1.16-1.88, P < 0.01), fungal culture negative rate (RR, 1.26; 95% CI; 1.09-1.47; P < 0.01), and effective rate (RR, 1.25; 95% CI, 1.10-1.42; P < 0.01). Additionally, the observed risk of adverse events was lower in the combination medication group (RR, 0.30; 95% CI, 0.14-0.65; P < 0.01). CONCLUSIONS: Though overall quality of individual studies was low, Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.