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Journal of Ethnopharmacology Jan 2024Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during...
ETHNOPHARMACOLOGICAL RELEVANCE
Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during the Qing dynasty. It has been used extensively to treat vulvovaginal candidiasis (VVC). However, despite its effectiveness, the mechanism of action remains unknown.
AIM OF THE STUDY
To elucidate the mechanism by which LXD relieves VVC via the Toll-like receptor/MyD88 pathway and activation of the NLRP3 inflammasome.
MATERIALS AND METHODS
Female Kunming mice (n = 96) were randomly divided into six groups: control, VVC model, LXD (10/20/40 mL/kg), and positive drug fluconazole. Mice were vaginally administered Candida albicans (C. albicans) solution (20 μL; 1 × 10 colony-forming units/mL), suspended for 5 min, and observed daily for changes in their condition. Continuous dilution was used to determine the number of colony-forming units. Gram, periodic acid-Schiff, Papanicolaou, and hematoxylin and eosin staining were used to determine the extent of infection. Enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of proinflammatory cytokines IL-1β and IL-18. TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 protein expression were determined using western blotting.
RESULTS
C. albicans infection destroyed the integrity of the vaginal mucosa, increased fungal burden and the influx of neutrophils into the vaginal cavity, and promoted the secretion of proinflammatory cytokines. C. albicans stimulated the expression of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 in vaginal tissue. Fungal burden, hyphal formation, and C. albicans adhesion were reduced in the 20 and 40 mL/kg LXD groups. Hematoxylin and eosin staining showed that inflammation was reduced and the stratum corneum had recovered in the 20 and 40 mL/kg LXD groups. LXD (20 and 40 mL/kg) significantly reduced IL-1β, IL-18 levels and the number of neutrophils in vaginal lavage and decreased TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 expression.
CONCLUSIONS
This study systematically demonstrated the therapeutic effect of LXD on protein expression and pathological conditions in VVC mice. The results showed that LXD could eliminate the invasion of vaginal hyphae in mice, reduce the recruitment of neutrophils, and reduce the expression of TLR/MyD88 pathway-related proteins and NLRP3 inflammasome. The above results clearly indicate that LXD may profoundly regulate NLRP3 inflammasome through the TLR/MyD88 pathway and play a therapeutic role in VVC.
Topics: Mice; Humans; Female; Animals; Candidiasis, Vulvovaginal; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Myeloid Differentiation Factor 88; Interleukin-18; NF-kappa B; Toll-Like Receptor 2; Toll-Like Receptor 4; Eosine Yellowish-(YS); Hematoxylin; Candida albicans; Cytokines; Caspases
PubMed: 37390876
DOI: 10.1016/j.jep.2023.116869 -
3 Biotech Nov 2023The ineffectiveness of azole drugs in treating Vulvovaginal Candidiasis (VVC) and Recurrent Vulvovaginal Candidiasis (RVVC) due to antifungal resistance of non-albicans...
The ineffectiveness of azole drugs in treating Vulvovaginal Candidiasis (VVC) and Recurrent Vulvovaginal Candidiasis (RVVC) due to antifungal resistance of non-albicans Candida has led to the investigation of inorganic nanoparticles with biological activity. Silver nanoparticles (AgNPs) are important in nanomedicine and have been used in various products and technologies. This study aimed to develop a vaginal cream and assess its in vitro antimicrobial activity against strains, specifically focusing on the synergy between AgNPs and miconazole. AgNPs were synthesized using glucose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer in varying amounts (0.50, 0.25, and 0.10 g). The AgNPs were characterized using UV-Visible (UV-Vis) and Fourier-Transform Infrared (FT-IR) spectroscopies, X-Ray Diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Energy Dispersive X-Ray Analysis (EDX). Fifty strains of were used to evaluate the synergistic activity. AgNPs synthesized with 0.5 g SDS had an average size of 77.58 nm and a zeta potential of -49.2 mV, while AgNPs with 0.25 g showed 91.22 nm and -47.2 mV, respectively. AgNPs stabilized with 0.1 g of SDS were not effective. When combined with miconazole, AgNPs exhibited significant antifungal activity, resulting in an average increase of 80% in inhibition zones. The cream developed in this study, containing half the miconazole concentration of commercially available medication, demonstrated larger inhibition zones compared to the commercial samples.
PubMed: 37810191
DOI: 10.1007/s13205-023-03776-9 -
Archives of Microbiology Jun 2024Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to... (Review)
Review
Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants.
Topics: Fungal Vaccines; Humans; Adjuvants, Immunologic; Mycoses; Animals; Fungi
PubMed: 38850421
DOI: 10.1007/s00203-024-04010-7 -
Current Issues in Molecular Biology Mar 2024In the present work, we evaluated the antifungal activities of two novel ebselen analogs, -allyl-benzisoselenazol-3(2H)-one (-allyl-bs) and...
In the present work, we evaluated the antifungal activities of two novel ebselen analogs, -allyl-benzisoselenazol-3(2H)-one (-allyl-bs) and -3-methylbutylbenzisoselenazol-3(2H)-one (-3mb-bs). Colorimetric and turbidity assays were performed to determine the minimum inhibitory concentration (MIC) of these compounds in S1 (fluconazole-sensitive) and S2 (fluconazole-resistant) strains of . -3mb-bs was more active than the -allyl-bs compound. It is noteworthy that the concentration of -3mb-bs observed to inhibit fungal growth by 50% (18.2 µM) was similar to the concentration observed to inhibit the activity of the yeast plasma membrane H-ATPase (Pma1p) by 50% (19.6 µM). We next implemented a mouse model of vulvovaginal candidiasis (VVC) using the S1 strain and examined the mouse and yeast proteins present in the vaginal lavage fluid using proteomics. The yeast proteins detected were predominately glycolytic enzymes or virulence factors associated with while the mouse proteins present in the lavage fluid included eosinophil peroxidase, desmocollin-1, and gasdermin-A. We then utilized the -3mb-bs compound (12.5 mg/kg) in the mouse VVC model and observed that it significantly reduced the vaginal fungal burden, histopathological changes in vagina tissue, and expression of myeloperoxidase (MPO). All in all, the present work has identified a potentially promising drug candidate for VVC treatment.
PubMed: 38534773
DOI: 10.3390/cimb46030157 -
Tropical Medicine and Infectious Disease May 2024Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives.... (Review)
Review
Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all spp., remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal-fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.
PubMed: 38787047
DOI: 10.3390/tropicalmed9050114 -
Patient Education and Counseling Jan 2024This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising... (Review)
Review
OBJECTIVE
This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising published findings.
METHODS
Five databases were searched for studies on patient and healthcare professional experiences managing recurrent thrush. Two reviewers independently screened and quality assessed qualitative, quantitative, and mixed-methods studies. Findings from eligible studies were thematically synthesised.
RESULTS
720 papers were identified, and 29 were included. Four descriptive themes were developed to depict the repeated management of recurrent thrush. These themes were: (re)experiencing impacts, (re)identifying recurrent thrush, (re)considering consultations, and (re)trying treatments. An analytic high-order frame of 'interwoven and reoccurring uncertainties' was used to understand these themes.
CONCLUSIONS
Patients and healthcare providers face uncertainties when managing recurrent thrush. The inconsistencies raised across papers suggests an unaddressed gap in knowledge about patient experiences and their informational and support needs; this includes insights about this condition's diagnosis, management, treatment, impacts, and meaning.
PRACTICE IMPLICATIONS
This review has implications for patient education, health promotion, and communication between patients and providers. Our interpretations suggest the need for more research and resources to help support patients and clinicians in managing this condition to promote more understanding, communication, and collaborative care.
Topics: Humans; Health Personnel; Communication; Delivery of Health Care; Qualitative Research
PubMed: 37826917
DOI: 10.1016/j.pec.2023.108004 -
Nanomedicine (London, England) Aug 2023Vulvovaginal candidiasis is primarily caused by (). Here, a novel organoselenium compound (G20) was synthesized and evaluated for anti- activity. Growth-inhibition...
Vulvovaginal candidiasis is primarily caused by (). Here, a novel organoselenium compound (G20) was synthesized and evaluated for anti- activity. Growth-inhibition studies and medium acidification assays to assess the inhibition of the yeast plasma membrane H-ATPase (Pma1p) were carried out using G20. A self-nanoemulsifying formulation (SNEP) of G20 was prepared and evaluated for antimycotic activity in a mouse model. G20 inhibited the growth of through a mechanism that, at least in part, involves the inhibition of Pma1p. The G20-SNEP formulation significantly reduced vaginal colonization and vaginal inflammation relative to yeast-infected but untreated control mice. G20-SNEP exhibits potent antimycotic activity in a mouse model of vulvovaginal candidiasis.
Topics: Female; Humans; Mice; Animals; Candidiasis, Vulvovaginal; Isoindoles; Azoles; Candida albicans; Antifungal Agents
PubMed: 37724540
DOI: 10.2217/nnm-2022-0323 -
Fitoterapia Mar 2024Vulvovaginal candidiasis (VVC) caused by Candida glabrata (C. glabrata) is more persistent and resistant to treatment than when caused by Candida albicans (C. albicans)...
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.
Topics: Female; Humans; Animals; Mice; Candidiasis, Vulvovaginal; Candida glabrata; 1-Butanol; Pulsatilla; Virulence Factors; Butanols; Vagina; Molecular Structure; Candida albicans; Plant Extracts; ErbB Receptors; Antifungal Agents
PubMed: 38219843
DOI: 10.1016/j.fitote.2024.105825 -
Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3.Gynecologic Oncology Nov 2023To evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus (HPV)-associated Vulvar...
OBJECTIVE
To evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus (HPV)-associated Vulvar intraepithelial neoplasia (VIN) 2/3.
METHODS
Participants were enrolled on a prospective, IRB-approved, dose-escalation phase I trial testing either 1, 2 or 3 treatment cycles (5 days), every other week, as applicable. Clinical assessments were completed prior to each dose cycle and included exam and review of adverse event (AE) diary cards. HPV testing and colposcopy was completed at 15 and 28 weeks. AEs were assessed according to CTCAE 4.0 criteria. Complete responders (CR) underwent biopsy of the treated site at the 28-weeks while partial (PR) and non (NR)-responders underwent surgical resection or biopsy and ablation.
RESULTS
Fifteen patients consented to and began treatment. Per-protocol assessments were completed in 100% at 15- and 80% at 28-weeks. All patients completed prescribed cycles with no grade 3 or 4 AEs. Vulvovaginal burning/ was the most common AE occurring in 93.3%. AEs were grade 2 in 23.7% and included vulvovaginal pruritus (n = 3), swelling (n = 3) and candidiasis (n = 2). The highest ORR was in the 3-cycle group (88.9% with 55.6% CR). HPV-16 was detected either alone (46.7%) or with other subtypes (33.3%) in 80% of lesions and 5 of 8 (62.5%) with CR had complete viral clearance.
CONCLUSIONS
Topical artesunate for treatment of high-grade VIN shows high tolerability, low toxicity and evidence for clinical response in this initial small series. The safety and observed responses support further study in a Phase II trial.
Topics: Female; Humans; Artesunate; Papillomavirus Infections; Prospective Studies; Biopsy; Neoplasms; Vulvar Neoplasms; Carcinoma in Situ
PubMed: 37839312
DOI: 10.1016/j.ygyno.2023.10.003 -
ACS Nano Jul 2023Phototherapy is an effective strategy to control () infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of...
Phototherapy is an effective strategy to control () infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for 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 at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on . 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- efficacy under near-infrared irradiation. In an intravaginal -infected murine model, treatment with the nanoplatform leads to a significantly decreased burden, particularly when leveraging candidalysin for further elevated phototherapy and inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical isolates. Overall, this biomimetic nanoplatform can target and bind with and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving infection with the power of enhancing phototherapy for improved anti- efficacy.
Topics: Humans; Animals; Mice; Cells, Cultured; Candida albicans; Candidiasis, Vulvovaginal; Phototherapy; Epithelial Cells; Photosensitizing Agents
PubMed: 37200053
DOI: 10.1021/acsnano.2c12644