Intravaginal Combination Therapy of Acetic and Lactic Acid in premenopausal women with recurrent vulvovaginal candidiasis: A randomized, double-blind placebo-controlled feasibility trial.

BACKGROUND: Recurrent vulvovaginal candidiasis management primarily entails azole therapy used as required or as an extended daily or weekly maintenance therapy for 6 months or more. Unfortunately, relapse within 3-6 months of ceasing maintenance therapy is experienced for more than half the patients, for whom indefinite treatment is required. OBJECTIVES: To explore the feasibility of trial design examining a prophylaxis treatment to prevent recurrent vulvovaginal candidiasis symptomatic episodes and reduce adverse effects. STUDY DESIGN: A double-blinded randomized controlled feasibility trial was conducted in Australia. Women with recurrent vulvovaginal candidiasis were enrolled. METHODS: An intravaginal prophylaxis application of lactic acid and acetic acid (Intravaginal Combination Therapy of Acetic and Lactic Acid) was compared with placebo. Primary outcomes comprised recruitment and retention, compliance to study medications and study assessments. Secondary outcomes included the reduction of symptomatic recurrence over the trial period and the acceptability, satisfaction, safety and tolerability of the intervention. The feasibility of quality-of-life measures was also explored. RESULTS: Fifteen participants were enrolled and randomized (active = 9, placebo = 6). Consent rate was 23.4%. Eight participants were lost to follow-up (active = 5, placebo = 3). Forty-seven per cent of participants (n = 7) were 100% compliant with the intervention, six of which completed the trial with good assessment compliance. The blinding process was effective. The study demonstrated a reduction in relapse in both active and placebo groups with only four participants across both groups reporting symptomatic episodes while enrolled. The intervention demonstrated good tolerability. Quality-of-life data showed minimal variance with a high quality-of-life measure. CONCLUSION: This trial assesses the feasibility of conducting a large-scale study exploring the efficacy of the Intravaginal Combination Therapy of Acetic and Lactic Acid intravaginal intervention and hints on the importance of psychological support through appropriate disease-specific communication and clinical attention. Consideration of the reported recruitment challenges, the inclusion of suitable quality-of-life measures and digital data collection is warranted for adaptation to a fully powered trial.

Interplay of the microbiome and antifungal therapy in recurrent vulvovaginal candidiasis (RVVC): A narrative review.

Recurrent vulvovaginal candidiasis (RVVC) is a microbial, immune and sexual health disorder impacting up to 10 % of the adult female population. Fluconazole is a well-established antifungal drug commonly utilized for acute and long-term RVVC treatment. This insight review provides an overview of known vaginal and gastrointestinal microbiota characteristics in RVVC, presents the potential impacts of fluconazole therapy on multi-microbiome relationships and discusses implications for future research and clinical practice. Next-generation sequencing (NGS) and molecular methods to accurately define vaginal microbiota trends in RVVC are not comprehensively available, limiting understanding of microbiota roles in RVVC. Inconsistencies and variances in Lactobacillus profiles in RVVC women suggest poorly understood disease implications on the bacterial and fungal microbiomes. Investigations of environmental conditions like vaginal pH, drug therapy's impact, especially fluconazole maintenance therapy, and the elucidation of multi-microbiome relationships in RVVC are required to further investigate disease pathogenesis and responsible antimicrobial prescribing.

Mushroom Natural Products in Neurodegenerative Disease Drug Discovery.

The variety of drugs available to treat neurodegenerative diseases is limited. Most of these drug's efficacy is restricted by individual genetics and disease stages and usually do not prevent neurodegeneration acting long after irreversible damage has already occurred. Thus, drugs targeting the molecular mechanisms underlying subsequent neurodegeneration have the potential to negate symptom manifestation and subsequent neurodegeneration. Neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, and is associated with the activation of the NLRP3 inflammasome, which in turn leads to neurodegeneration. Inflammasome activation and oligomerisation is suggested to be a major driver of disease progression occurring in microglia. With several natural products and natural product derivatives currently in clinical trials, mushrooms have been highlighted as a rich and largely untapped source of biologically active compounds in both in vitro and in vivo neurodegenerative disease models, partially supported by successful clinical trial evaluations. Additionally, novel high-throughput methods for the screening of natural product compound libraries are being developed to help accelerate the neurodegenerative disease drug discovery process, targeting neuroinflammation. However, the breadth of research relating to mushroom natural product high-throughput screening is limited, providing an exciting opportunity for further detailed investigations.

Plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis.

The endocannabinoid system (ECS) is an essential endogenous signaling system that may be involved in the pathophysiology of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS). Further research is required to understand the role of ECS in the development and maintenance of CWP and FMS. We provided the first systematic review and meta-analysis exploring the clinical relevance of ECS alterations in patients with CWP and FMS by comparing plasma and interstitial levels of endocannabinoids and N-acylethanolamines in patients and healthy controls. A systematic search was conducted to identify studies that measured plasma and/or interstitial levels of endocannabinoids and N-acylethanolamines in patients with CWP or FMS and healthy controls. A total of 8 studies were included for qualitative review, and 7 studies were included for meta-analysis. The findings identified increased plasma levels of oleoylethanolamide and stearoylethanolamide in patients with FMS compared with those in controls (P = 0.005 and P < 0.0001, respectively) and increased plasma levels of palmitoylethanolamide and interstitial levels of stearoylethanolamide in patients with CWP compared with those in controls (P = 0.05 and P = 0.001, respectively). There were no significant differences in other ECS parameters. Most studies did not account for variables that may influence ECS function, including cannabis use, concomitant medication, comorbidities, physical activity, stress levels, circadian rhythm, sleep quality, and dietary factors, suggesting that future studies should explore the correlation between these variables and endocannabinoid activity. We highlight the importance of investigating endocannabinoid activity in CWP and FMS because it will underpin future translational research in the area.

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.

Efficacy of D-cycloserine augmented brief intensive cognitive-behavioural therapy for paediatric obsessive-compulsive disorder: A randomised clinical trial.

OBJECTIVE: To examine the efficacy of weight-adjusted D-cycloserine (DCS) (35 or 70 mg) relative to placebo augmentation of intensive exposure therapy for youth with obsessive-compulsive disorder (OCD) in a double-blind, randomised controlled trial, and examine whether antidepressant medication or patient age moderated outcomes. METHODS: Youth (n = 100, 7-17 years) with OCD were randomised in a 1:1 ratio to either DCS + exposure (n = 49) or placebo + exposure (n = 51). Assessments occurred posttreatment, 1 month later, and at 3 and 6 months. Pills were ingested immediately before sessions. RESULTS: Significant improvements on all outcomes were observed at posttreatment, and to 6-month follow-up. Treatment arms did not differ across time, with no significant time-by-medication interactions on symptom severity (T1 to T2 estimate: 9.3, 95% confidence interval [CI]: -11.2 to -7.4, and estimate -10.7, 95% CI: -12.6 to -8.7), diagnostic severity (T1 to T2 estimate: -2.0, 95% CI: -2.4 to -1.5 and estimate -2.5, 95% CI: -3.0 to -2.0) or global functioning (T1 to T2 estimate: 13.8, 95% CI: 10.6 to 17.0, and estimate 16.6, 95% CI: 13.2 to 19.9). Neither antidepressants at baseline nor age moderated primary outcomes. There were significantly fewer responders/remitters at 1- and 6-month follow-up among youth in the DCS condition stabilised on SSRIs, relative to youth not taking SSRIs. CONCLUSIONS: DCS augmented intensive exposure therapy did not result in overall additional benefits relative to placebo. Intensive exposure proved effective in reducing symptoms for the overall sample.

What influences complementary medicine use for children with eosinophilic esophagitis? Findings from a cross-sectional survey.

BACKGROUND AND PURPOSE: Utilization of complementary medicines (CMs) amongst children with eosinophilic esophagitis (EoE) in Australia is high. Carers' beliefs, perceptions and use of CM can influence the decision to use CM in children in their care. This study explores the factors influencing the use of CM for a child's EoE when the carer also uses CM. MATERIALS AND METHODS: Carers of children aged 0-18 years with EoE participated in a national cross-sectional online survey, conducted in Australia between September 2018 and February 2019. Data analysis included bivariate analysis, Cramer's V, backwards stepwise logistic regression and binomial logistic regression. RESULTS: Of the 181 total survey responses, 165 (91.2 %) respondents indicated they had utilized some form of CM for themselves. Children whose carer had used some form of CM for themselves were more likely to have used CM than children whose carer had not used CM (OR 4.6; p = 0.001). Of the CM self-using carers, 125 (75.8 %) had also chosen to utilize CM for their child's EoE. Use of CM in children was more likely amongst children who had used a pharmaceutical for their EoE (OR 7.51; p = 0.010), and those whose carer had consulted with "other health practitioners or health workers" for their child's EoE (OR 5.34; p < 0.001) or had consulted with a chiropractor for themselves (OR 2.70; p = 0.029). CONCLUSION: High CM self-use amongst carers is associated with their decision to also use CM for their child's EoE, a concern given the absence of evidence for CM's safety and efficacy in this population. CM use in this population warrants further attention. Effective conventional medicines for EoE are limited and utilization of CM amongst children with EoE in Australia is high. The recommendation of CM for children with EoE warrants further attention given the substantial concomitant pharmaceutical care, and the absence of evidence for CM's safety and efficacy in this population. Further research into the role of CM practitioners, products, and therapies in an integrative model between CM and conventional healthcare must be undertaken.

Evidence-based update on Australasian pharmaceutical prescribing approaches for recurrent vulvovaginal candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is a subtype of vulvovaginal candidiasis, with debilitating effects on physical and emotional well-being affecting up to 10% of Australian women. Current evidence suggests that the induction and maintenance approach for RVVC is not particularly effective with post-treatment relapse rates as high as 57%. Frequently accessed Australasian RVVC prescribing resources and guidelines were examined showing a variety of adaptations of current evidence-based induction and maintenance therapies, making it difficult to select best treatment in clinical practice. The ways to introduce more clarity and consistency into these guidelines are outlined.

Safety and Efficacy of Medicinal Cannabis in the Treatment of Fibromyalgia: A Systematic Review.

Background: Fibromyalgia (FMS) is a complex condition that is characterized by various pain syndromes and fatigue, among other symptoms experienced. Current medical treatment of FMS involves both pharmacological and nonpharmacological approaches, but often with ineffective outcomes. Medicinal cannabis has the potential to be a therapeutic option for patients with FMS due to the positive research in chronic pain management. In addition, it has been found to have fewer adverse effects compared with currently available pain medications. This literature review aims at answering whether medicinal cannabis is reported to be safe and effective for the treatment of pain and symptomology experienced by people with FMS. Methods: A systematic review was conducted on human trials utilizing cannabis in FMS. MEDLINE, Embase, CINAHL, AMED, Scopus, and Cochrane CENTRAL were used for databases search, and mesh terms were used for cannabis and FMS. The search was limited to studies conducted from 2000 to 2020. Results: From the 181 citations identified, 10 studies were included after title, abstract, and full text screening occurred. A total of 1136 of patients (intervention n = 945, control n = 108, crossover n = 83) participated in the 10 studies ranging from 9 to 383 patients (mean = 114, median = 36). Of these studies, there were three randomized controlled trials, six observational studies, and one study that compared the management of chronic pain patients with FMS patients. Cannabis was found to be safe and well tolerated in FMS. The main adverse events identified included feeling "high," dizziness/vertigo, dry mouth, cough, red eyes, and drowsiness with no serious adverse events reported. Conclusions: This literature review identified that medical cannabis may be beneficial for some people with FMS. Further studies are required to confirm its efficacy, what type of cannabis is the most effective form to use, and what assessment tools need to be utilized to understand how to quantify clinical outcomes.

Treatment Burden for Pediatric Eosinophilic Esophagitis: A Cross-Sectional Survey of Carers.

OBJECTIVE: To investigate treatment burden and impact on health-related quality of life (HRQoL) for children with eosinophilic esophagitis (EoE) and their carers. METHODS: An Australian cross-sectional online survey of carers of children aged 18 years and under with EoE between September 2018 to February 2019. RESULTS: Of 181 complete responses, more than half of carers experienced reduced HRQoL since their child's diagnosis. Reported mean out-of-pocket expenditure for healthcare utilization (practitioner visits and treatment) was AUD$3064.3 annually. Backwards stepwise linear regression models showed that reduced ability to manage on income and missing more than one workday in the previous 30 days were significant predictors of lower carer HRQoL. Ability to manage on the current income described as "difficult some of the time," "difficult all of the time," and "impossible" were associated with lower child HRQoL. When compared with EoE diagnosis between 13 and 23 months of age, diagnosis between 2 and 4 years was a significant predictor of lowered child HRQoL. CONCLUSIONS: Pediatric EoE in Australia leads to high treatment burden for carers. Changes in carer employment and income manageability can negatively impact carer psychosocial wellbeing. Carers of children with EoE need to be informed about available financial and social support to reduce treatment-related burden and improve the quality of life of both the carer and child.

Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data.

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists. SCOPE AND APPROACH: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review. KEY FINDINGS AND CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

Ethnobotany and Antimicrobial Peptides From Plants of the Solanaceae Family: An Update and Future Prospects.

The Solanaceae is an important plant family that has been playing an essential role in traditional medicine and human nutrition. Members of the Solanaceae are rich in bioactive metabolites and have been used by different tribes around the world for ages. Antimicrobial peptides (AMPs) from plants have drawn great interest in recent years and raised new hope for developing new antimicrobial agents for meeting the challenges of antibiotic resistance. This review aims to summarize the reported AMPs from plants of the Solanaceae with possible molecular mechanisms of action as well as to correlate their traditional uses with reported antimicrobial actions of the peptides. A systematic literature study was conducted using different databases until August 2019 based on the inclusion and exclusion criteria. According to literature, a variety of AMPs including defensins, protease inhibitor, lectins, thionin-like peptides, vicilin-like peptides, and snaking were isolated from plants of the Solanaceae and were involved in their defense mechanism. These peptides exhibited significant antibacterial, antifungal and antiviral activity against organisms for both plant and human host. Brugmansia, Capsicum, Datura, Nicotiana, Salpichora, Solanum, Petunia, and Withania are the most commonly studied genera for AMPs. Among these genera, Capsicum and the Solanum ranked top according to the total number of studies (35%-38% studies) for different AMPs. The mechanisms of action of the reported AMPs from Solanaceae was not any new rather similar to other reported AMPs including alteration of membrane potential and permeability, membrane pore formation, and cell aggregation. Whereas, induction of cell membrane permiabilization, inhibition of germination and alteration of hyphal growth were reported as mechanisms of antifungal activity. Plants of the Solanaceae have been used traditionally as antimicrobial, insecticidal, and antiinfectious agents, and as poisons. The reported AMPs from the Solanaceae are the products of chemical shields to protect plants from microorganisms and pests which unfold an obvious link with their traditional medicinal use. In summary, it is evident that AMPs from this family possess considerable antimicrobial activity against a wide range of bacterial and fungal pathogens and can be regarded as a potential source for lead molecules to develop new antimicrobial agents.

Health Service Use and Treatment Choices for Pediatric Eosinophilic Esophagitis: Findings From a Cross-Sectional Survey of Australian Carers.

Objectives: The incidence and the prevalence of eosinophilic esophagitis (EoE) are increasing, and healthcare utilization among children with EoE is high. This study provides novel insights into the health services and the treatments, including complementary medicines (CMs), used by carers to manage their children's EoE as well as the carers' beliefs and attitudes toward these treatments. Methods: A national cross-sectional online survey was conducted in Australia between September 2018 and February 2019. The survey included questions about health service and treatment utilization, health insurance and government support, health-related quality of life of children with EoE and their carers, views and attitudes toward CM use, and perceived efficacy of treatment. Results: The survey was completed by 181 carers (96.6% of whom were mothers) of EoE children. Most children (91.2%, n = 165) had seen a medical doctor for their EoE, and almost half had consulted with a CM practitioner (40.3%, n = 73). Pharmaceuticals (n = 156, 86.2%) were the most commonly used treatment option, followed by dietary changes (n = 142, 78.5%), CM products (n = 109, 60.2%), and CM therapies (n = 42, 23.2%). Most children received care from numerous practitioners on multiple occasions, indicating a substantial financial and treatment-related burden. Conclusions: A variety of practitioners are involved in the care of children with EoE, and a high rate of CM use warrants further attention to ensure that appropriate treatment is provided. Carer involvement and guidance, combined with individual practitioner expertise, referrals, and collaboration between providers, is essential to successfully navigate this complex disease and provide adequate care for these patients.

D-cycloserine-augmented one-session treatment of specific phobias in children and adolescents.

BACKGROUND: D-Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo-controlled double-blind pilot trial of DCS-augmented one-session treatment (OST) for youth (7-14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within-session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7-10 years) would have greater benefits than adolescents (11-14 years), and that DCS effects would be stronger for participants with the greater within-session fear reduction during the OST. METHODS: Thirty-five children and adolescents were randomized to either OST combined with DCS (n = 17), or OST combined with placebo (PBO; n = 18) and assessed at 1 week, 1 month, and 3 month following treatment. RESULTS: There were no significant pre- to post-treatment or follow-up benefits of DCS relative to placebo. Secondary analyses of age indicated that relative to PBO, DCS was associated with greater improvements for children (but not adolescents) on measures of severity at 1-month follow-up. Children in the DCS condition also showed significantly greater improvement to 1 month on global functioning relative to other groups. Conversely, adolescents had significant post-treatment benefits in the PBO condition on symptom severity measures relative to DCS, and adolescents in the DCS condition had significantly poorer functioning at 3 months relative to all other groups. Finally, there was a trend for within-session fear reduction to be associated with moderating effects of DCS, whereby greater reduction in fear was associated with greater functioning at one-month follow-up for children who received DCS, relative to PBO. LIMITATIONS: The study sample was small and therefore conclusions are tentative and require replication. CONCLUSIONS: Age and within-session fear reduction may be important moderators of DCS-augmented one-session exposure therapy, which requires testing in a fully powered randomized controlled trial.

Biophysical characterization and structural determination of the potent cytotoxic Psathyrella asperospora lectin.

A lectin with strong cytotoxic effect on human colon cancer HT29 and monkey kidney VERO cells was recently identified from the Australian indigenous mushroom Psathyrella asperospora and named PAL. We herein present its biochemical and structural analysis using a multidisciplinary approach. Glycan arrays revealed binding preference towards N-acetylglucosamine (GlcNAc) and, to a lesser extent, towards sialic acid (Neu5Ac). Submicromolar and millimolar affinity was measured by surface plasmon resonance for GlcNAc and NeuAc, respectively. The structure of PAL was resolved by X-ray crystallography, elucidating both the protein's amino acid sequence as well as the molecular basis rationalizing its binding specificity. Proteins 2017; 85:969-975. © 2016 Wiley Periodicals, Inc.

Brief intensive CBT for pediatric OCD with E-therapy maintenance.

Cognitive behaviour therapy (CBT), incorporating exposure and response prevention (ERP), has received strong empirical support for the treatment of paediatric OCD, and moreover, is considered the first line treatment of choice (Geller & March, 2012). However, despite the availability of effective treatments for this chronic and debilitating disorder, only a small proportion of youth receive these evidence-based approaches. The present study aimed to examine the effectiveness of an intensive ERP-based treatment for youth OCD, using a multiple baseline controlled design. Children and youth (N=10; aged 11-16 years) with a primary diagnosis of OCD were randomly assigned to a 1- or 2-week baseline monitoring condition followed by the intervention. The efficacy of the intensive treatment, involving 1 session psychoeducation, 2-sessions ERP plus e-therapy maintenance was examined across parent- child- and clinician-rated measures at post-treatment and 6-month follow-up. Overall, there were significant reductions across time on almost all measures (except self-report anxiety), and moreover, the majority of the sample (80%) were considered reliably improved, and meeting clinically significant change. At post-treatment, 60% were in remission of symptoms, and at 6-month follow-up this increased to 70%. These findings provide strong support for intensive, time-limited approaches to ERP-based CBT for children and youth with OCD.

Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial.

Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry's physical and mental health benefits.

A new cytotoxic diterpenoid glycoside from the leaves of Blumea lacera and its effects on apoptosis and cell cycle.

A new diterpenoid glycoside, 6E,10E,14Z-(3S)-17-hydroxygeranyllinalool-17-O-ß-d-glucopyranosyl-(1 → 2)-[α-l-rhamnopyranosyl-(1 → 6)]-ß-d-glucopyranoside (1) together with the known diterpenoid glycoside (2) and two known flavonoid glycosides (3, 4) were isolated from the methanol extract of Blumea lacera leaves. The structures were determined by the interpretation of their spectroscopic data and comparison with the literature. All compounds were isolated for the first time from B. lacera and evaluated for their cytotoxic activity. Only the new compound (1) showed strong cytotoxic activity with the lowest IC50 value (8.3 µM) being displayed against MCF-7 breast cancer cells. In apoptosis and cell cycle analysis, 1 revealed strong apoptotic activity against MCF-7 cells (45.5% AV+/PI-) after 24 h, but showed no arresting of any of the cell cycle phases in MCF-7.

A New Cytotoxic Steroidal Glycoalkaloid from the Methanol Extract of Blumea lacera Leaves.

PURPOSE: Blumea lacera (B. lacera) (Asteraceae) is a well-known Bangladeshi medicinal plant. This study aimed to identify and characterize constituents associated with the significant cytotoxic activity of this plant that we reported previously. Here, we describe the isolation and characterization of a new steroidal glycoalkaloid (SGA) 1, the evaluation of its cytotoxic activity, apoptotic potential, and effect on cell cycle in comparison to analogous steroidal glycoalkaloids (SGAs). METHODS: SGA 1 was isolated using C18 SPE and HPLC, and subsequently structurally characterized using 1D and 2D NMR, MS and other spectroscopic methods, along with a comparative inspection of the literature. Cytotoxic activity of 1 and seven SGA analogues and steroidal alkaloids (SAs), (ß-solamarine, α-solanine, ß-solamargine, α-solasonine, khasianine, solasodine, tomatidine HCl) were evaluated for their cytotoxicity against two healthy (NIH3T3 and VERO) and four human cancer (AGS, HT-29, MCF-7 and MDA-MB-231) cell lines using the MTT assay. Cytotoxic SGAs were further evaluated for apoptosis-inducing potential and cell cycle arresting ability against breast cancer cells (MCF-7) using the FITC Annexin V and propidium iodide (PI) assay. RESULTS: Bioactivity guided fractionation of the methanol extract of B. lacera led to isolation of compound 1: (25R)-3ß-{O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-rhamnopyranosyl-(1 → 4)-[O-α-L-rhamnopyranosyl-(1 → 2)]-α-L-rhamnopyranosyl}-22αN-spirosol-5-ene. SGA 1 was the most cytotoxic compound against a number of human cancer cell lines with an IC50 of 2.62 µM against MCF-7 cells. It displayed the highest apoptotic potential (32% AV+/PI-) on MCF-7 cells compared to other cytotoxic SGA analogues and a slight, but significant cell cycle arresting effect. CONCLUSIONS: A new SGA 1 was isolated from B. lacera and its cytotoxic activity, as well as that of other SAGs, was evaluated. SAR investigations on SGA 1, in relation to SGA analogues, show that the number and nature of sugar moieties along with the linkages of the sugar to the aglycone are crucial for cytotoxic and apoptotic activity. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Mushroom lectins: specificity, structure and bioactivity relevant to human disease.

Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell-cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity.