Natural compounds have garnered significant attention as potential therapeutic agents due to their inherent properties. Their notable qualities, including safety, efficacy, favorable pharmacokinetic properties, and heightened effectiveness against certain diseases, particularly inflammatory conditions, make them particularly appealing. Among these compounds, curcumin has attracted considerable interest for its unique therapeutic properties and has therefore been extensively studied as a potential therapeutic agent for treating various diseases. Curcumin exhibits diverse anti-inflammatory, antioxidant, and antimicrobial effects. Curcumin's immune system regulatory ability has made it a promising compound for treatment of various inflammatory diseases, such as psoriasis, atherosclerosis, asthma, colitis, IBD, and arthritis. Among the signaling pathways implicated in these conditions, the CD40 receptor together with its ligand, CD40L, are recognized as central players. Studies have demonstrated that the interaction between CD40 and CD40L interaction acts as the primary mediator of the immune response in inflammatory diseases. Numerous studies have explored the impact of curcumin on the CD40:CD40L pathway, highlighting its regulatory effects on this inflammatory pathway and its potential therapeutic use in related inflammatory conditions. In this review, we will consider the evidence concerning curcumin's modulatory effects in inflammatory disease and its potential therapeutic role in regulating the CD40:CD40L pathway.

Postpartum depression and anxiety are common problems in primiparous women, which can negatively affect Maternal-infant bonding and lead to sexual disorders. It's important to prevent and treat these issues, especially since medication options during breastfeeding may be limited. Our study aimed to investigate the effect of curcumin, a natural substance known for its beneficial properties, on postpartum depression and anxiety in primiparous women. A randomized controlled clinical trial was conducted on 96 primiparous women in Tabriz City. Participants were randomly assigned to either the intervention group (n = 48) or the control group (n = 48) using the random block method. The intervention group received curcumin capsules with a dose of 500 mg, while the control group received a placebo with the same dose once daily for eight weeks. Data was collected using the Edinburgh Postnatal Depression Scale (EPDS) and postpartum-specific Anxiety Scale research short-form (PSAS-RSF) questionnaires. After the intervention, the mean score of depression (mean difference: -2.5; 95% confidence interval: -3.3 to -1.7; P < 0.001) and anxiety (Mean difference: -1.4; 95% confidence interval: -2.1 to -0.7; P < 0.001) in the intervention group were significantly lower than the control group. It seems that curcumin can improve the mental health and quality of life of primiparous women postpartum due to its efficacy in reducing postpartum anxiety and depression, easy accessibility, and cost-effectiveness.

Curcumin, a compound known for its antioxidant and neuroprotective properties, faces challenges due to its low water solubility, which can limit its effectiveness. One effective method to address this issue is through amorphization. Incorporating curcumin into a polymeric matrix to form amorphous solid dispersions is a common approach. Another strategy involves co-amorphous systems, where low-molecular-weight components act as co-formers. A recent innovative approach combines these strategies. This study used tryptophan as a co-former and prepared systems using supercritical fluid technology. The amorphous nature of two systems was confirmed through X-ray powder diffraction: one with 10% curcumin and a polymer, and another with 10% curcumin, a polymer, and tryptophan. Fourier-transform infrared analysis demonstrated molecular interactions among all components in the systems. Scanning electron microscopy revealed that the amorphization process significantly modified the morphology of the powder particles. The ternary system with tryptophan notably increased curcumin solubility by over 300-fold. The amorphous form of curcumin in both systems exhibited significantly higher dissolution rates compared to its crystalline form. The system with tryptophan showed more than a threefold improvement in permeability according to the PAMPA test. The enhanced solubility led to over a sixfold increase in antioxidant activity and a 25-fold improvement in the inhibition of the enzyme butyrylcholinesterase.

Depression is a complex mental disease whose incidence increases every year; 300 million people worldwide currently suffer from it. Women are more likely to suffer from depression, twice the rate as men. It is one of the few illnesses that can lead to suicide, which makes it very dangerous - currently, 700,000 people die from suicide and it is the 4th most common cause of death in people aged 15-29. The treatment strategies for depression is a big challenge for physicians, pharmacists, scientists and classic remedies cause many side effects. Therefore, natural phytotherapy with herbs can prove to be a good solution. Phytotherapy is a popular treatment method used for centuries in Chinese medicine or Ayurveda.

The study conducted a comprehensive database search PubMed, ClinicalKey and MedNar covered the years 2015 - 2024 to provide the most up-to-date data. 13 randomized controlled trials and 1 meta - analysis were included in the systematic review.

Many plants show anti-inflammatory, antioxidant and cognitive enhancing effects, which are particularly important in depression. In the treatment of depression, plants such as Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. have proven to be effective. They show good effectiveness in human studies and alleviate the symptoms of depression. Herbal products can support classical pharmacotherapy, but this requires further research. Non-commercial clinical trials in the future should provide answers to research questions: at what stage of treatment of patients with MDD will the use of phytochemicals be most appropriate in terms of therapy efficacy and safety for the patient.

Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. in modern medicine can help improve the well-being of patients with depression. The use of herbs as an intervention was associated with a decrease in the concentration of proinflammatory cytokines and an overall improvement in the mood of patients. Further research should be undertaken into combining both therapies in order to improve patients' quality of life and reduce treatment costs.

The purpose of this study was to design nanocarriers with small-size and antioxidant properties for the effective encapsulation of curcumin. Here, procyanidins, vanillin, and amino acids were used to successfully prepare nanocarriers of a controllable size in the range of 328~953 nm and to endow antioxidant ability based on a one-step self-assembly method. The reaction involved a Mannich reaction on the phenolic hydroxyl groups of procyanidins, aldehyde groups of vanillin, and amino groups of amino acids. Subsequently, curcumin nanoparticles were prepared by loading curcumin with this nanocarrier, and the encapsulation efficiency of curcumin was 85.97%. Compared with free curcumin, the antioxidant capacity and photothermal stability of the embedded curcumin were significantly improved, and it could be slowly released into simulated digestive fluid. Moreover, using the corticosterone-induced PC12 cell injury model, the cell viability increased by 23.77% after the intervention of curcumin nanoparticles, and the cellular antioxidant capacity was also significantly improved. The nanoparticles prepared in this work can effectively improve the solubility, stability, and bioactivity of curcumin, which provides a reference for the embedding and delivery of other hydrophobic bioactive compounds.

Depression is a highly prevalent psychological disorder characterized by persistent dysphoria, psychomotor retardation, insomnia, anhedonia, suicidal ideation, and a remarkable decrease in overall well-being. Despite the prevalence of accessible antidepressant therapies, many individuals do not achieve substantial improvement. Understanding the multifactorial pathophysiology and the heterogeneous nature of the disorder could lead the way toward better outcomes. Recent findings have elucidated the substantial impact of compromised blood-brain barrier (BBB) integrity on the manifestation of depression. BBB functions as an indispensable defense mechanism, tightly overseeing the transport of molecules from the periphery to preserve the integrity of the brain parenchyma. The dysfunction of the BBB has been implicated in a multitude of neurological disorders, and its disruption and consequent brain alterations could potentially serve as important factors in the pathogenesis and progression of depression. In this review, we extensively examine the pathophysiological relevance of the BBB and delve into the specific modifications of its components that underlie the complexities of depression. A particular focus has been placed on examining the effects of peripheral inflammation on the BBB in depression and elucidating the intricate interactions between the gut, BBB, and brain. Furthermore, this review encompasses significant updates on the assessment of BBB integrity and permeability, providing a comprehensive overview of the topic. Finally, we outline the therapeutic relevance and strategies based on BBB in depression, including COVID-19-associated BBB disruption and neuropsychiatric implications. Understanding the comprehensive pathogenic cascade of depression is crucial for shaping the trajectory of future research endeavors.

Depression is one of the most common diseases in the world, and it is also the most common mental disorder. Depressive disorders are a real threat not only to individuals, but also to the general population. This disease is a leading cause of disability and inability to work. Due to the numerous side effects of conventional drugs, attention is increasingly being paid to other solutions, including herbal medicines. Many plant species are known for their traditional uses in the treatment of anxiety, insomnia, and depression. The clinically proven effects of adaptogenic raw materials on depression symptoms are probably related to the positive impact of some secondary metabolites (terpenoids, alkaloids, glucosinolates, phenols). Currently, it is emphasized that in many cases the antioxidant and anti-inflammatory properties of plant substances play a protective role at the neurocellular level. Among the medicinal plants analyzed in clinical trials for the treatment of depression, the following seem to be particularly interesting: saffron (Crocus L.), turmeric (Curcuma L.), ginkgo (Ginkgo L.), St. John's wort (Hypericum L.), and passionflower (Passiflora L.), which have broad and strong biological activity, well-documented history of action and use, and effectiveness in preventing and/or treating anxiety and depression. These plants are still in the sphere of biochemical and phytopharmaceutical research, the results of which are very promising.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in the MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS can provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for the MS population.

Psychosocial stress may alter cortisol and/or affect the normal functioning of the immune system. Curcuminoids can promote beneficial effects in neuropsychiatric diseases. We evaluated whether curcumin supplementation for 15 consecutive days (1800 mg/day) would decrease systemic MCP-1, sCD14, and TNF alpha levels in patients with moderate anxiety (n = 81). A total number of 81 subjects were enrolled in this study, divided into the following groups according to their Hamilton scores: a control group including patients without anxiety who were not taking curcumin (Cont, n = 22) and an anxiety group including patients with moderate anxiety (Anx, n = 22). The curcumin-treated patients experienced moderate anxiety, and they take curcumin for 15 consecutive days (Anx-Cur (after), n = 15, 1800 mg/day). An evaluation of 128 patients was conducted, which allowed for their assignment to the study groups according to their scores on Hamilton scale II. The cortisol levels were quantified in salivary samples through ELISA (ng/mL), and malonaldehyde (MDA) levels were measured in plasma via the TBARS assay as an index of lipoperoxidation. Several systemic proinflammatory cytokines (pg/mL: MCP-1, TNF alpha, IL-1 beta) and mediators were quantified through ELISA (pg/mL), including systemic sCD14 levels as a marker of monocyte activation. A two-way bifactorial ANOVA was conducted to evaluate the contributions of the anxiety factor (Anx) and/or curcumin factor (Cur) in all the tested markers, including interactions between both factors. High systemic MCP-1 and elevated sCD14 levels were observed in patients with moderate anxiety, which were reduced with curcumin supplementation. In addition, curcumin prevented cortisol overexpression and decreased MDA levels as an antioxidant response in these patients. Collectively, curcumin presented anti-chemotactic effects by reducing systemic MCP-1 levels in anxiety. Curcumin decreased systemic MCP-1 as well as sCD14 levels in patients with moderate anxiety.

Curcumin is a polyphenolic natural compound that has been used to treat various ailments such as symptoms of anxiety. However, the findings of studies regarding the anti-anxiety properties of curcumin are controversial. This review aims to evaluate if there are clinical benefits of curcumin in patients with symptoms of anxiety.

PubMed, Embase, Web of Science, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) from the database inception to August 16, 2023. The random-effects model was used to estimate the standard mean difference (SMD).

A total of eight RCTs involving 567 participants were included in the analysis. A pooled analysis showed a significant effect of curcumin on anxiety symptoms (SMD: -1.56; 95% CI: -2.48, -0.64, p < 0.001; I2 = 95.6%, p-heterogeneity< 0.001).

Present meta-analysis demonstrated that curcumin intake might contribute to alleviation of anxiety disorder. Due to the limited number of studies included, it is necessary to conduct more high-quality studies to confirm the clinical efficacy of curcumin.

Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly attracted the interest of the scientific research community. However, even if there is a plethora of naturally occurring bioactive compounds, most of them have low bioavailability, rendering them unable to insert into the bloodstream to exert their biological activities.

This is a comprehensive narrative review that critically summarizes and scrutinizes the new approaches to the treatment of mental disorders using curcumin, also highlighting its bioavailability properties. The most accurate were searched using effective and relevant keywords.

This narrative review reveals substantial evidence that curcumin can exert significant effects on several mental disorders. However, despite the low cost, the extensive and confirmed potency of curcumin and its involvement in signaling pathways and the scientifically confirmed data regarding its molecular mechanisms of action against mental disorders, this naturally occurring compound presents low oral bioavailability. Pharmaceutical technology has provided solutions to increase the bioavailability of curcumin. Combination with piperine, galactomannosides, liposomal formulation or nanoformulation overcomes the bioavailability and solubility disadvantages.

Although curcumin demonstrates anti-anxiety, anti-depressive and anti-stress properties, studies on humans are limited and heterogeneous. Further research is highly recommended to determine the most functional formula, dose, duration, and possible side effects of curcumin on mental disorders in humans. Based on the current knowledge, the curcumin nanoformulation and Theracurmin, a form of colloidal submicroscopic particles, seem to be the most effective bioavailable formulations, which may be examined in future clinical human studies.

Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.

Curcumin (CUR) exhibits a definite curative effect in the treatment of depression. To identify potential antidepressant targets and mechanisms of action of CUR. This study used network pharmacology to explore the signaling pathways and CUR-related targets in depression. C57BL/6 J mice (male,12-14 weeks old) were randomly divided into four groups (n = 8): saline-treated (control mice), lipopolysaccharide (LPS, 2 mg/kg/day, intraperitoneally), LPS + CUR (50 mg/kg/day, intragastrically), and LPS + CUR + LY294002 (7.5 mg/kg/day, intraperitoneally). After 1 week, behavioral tests were performed. Then, neuronal damage in the prefrontal cortex of mice was evaluated by hematoxylin-eosin (HE) staining. We uncovered the main active mechanism of CUR against depression using Western blotting and enzyme-linked immunosorbent assay (ELISA). Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the most significantly enriched pathway in CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with the PI3K-Akt signaling pathway and CUR-related targets. In addition, among the top 50 targets ranked by degree in the protein-protein interaction (PPI) network, there were 23 targets involved in the 52 intersection targets. Administration of LPS alone extended immobility time in the open field test (OFT) and tail suspension test (TST) and decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR relieved LPS-induced changes in the behavioral tests, activity of the PI3K-Akt signaling pathway, neuronal damage in the prefrontal cortex (PFC), and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 blocked the therapeutic effects of CUR. Our study indicates that CUR may be an effective antidepressant agent in an LPS-induced mouse model, partly because of its anti-inflammatory action through the PI3K-Akt signaling pathway.

Candida albicans is the main species that causes 3rd most common bloodstream infection candidiasis in hospitalization. Once it has been diagnosed and treated with antifungal medications accurately, large amounts of Candida cells are killed off rapidly known as Candida die-off or Jarisch-Herxheimer reactions. When Candida cells are killed off quickly, a large no. of toxic substances are released simultaneously. This flood of endotoxins is noxious (harmful) and causes the kidneys and liver to work overtime to try and remove them which causes worsening of symptoms in patients. As a complementary and holistic approach to addressing Candida die-off and its associated symptoms, plant-based remedies i.e., phytotherapy have been gaining increased attention. In this review paper, we have discussed major factors involved in provoking Candida die-off, their management by phytotherapy, challenges associated with the toxic effects due to die-off, and neutralization of Candida die-off through phytotherapy to manage this problem and challenges. In conclusion, this article serves as a meticulous compilation of knowledge on the intriguing subject of Candida die-off, presenting a distinct and informative perspective that has the potential to pave the way for new insights in the realm of plant-based antifungal therapeutics.

The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect.

The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted.

The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration.

TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.

Diverse chemical messengers are responsible for maintaining homeostasis in the human body, for example, hormones and neurotransmitters. Various Hawaiian plant species produce compounds that exert effects on these messengers and the systems of which they are a part. The main purpose of this review article is to evaluate the potential effects of Hawaiian plants on reducing pain and anxiety and improving sleep and mood. A comprehensive literature search was conducted in SciFinder, PubMed, Science Direct, Scopus, Google Scholar, and Scientific Information Database between 2019 and 2023 to identify related articles. Results indicate that several Hawaiian plant species, such as M. citrifolia and P. methysticum, have medicinal properties associated with these effects. These plants have been used in traditional Hawaiian cultural practices for centuries, suggesting their potential to benefit human health and well-being. This review presents a comprehensive analysis of the available evidence concerning the potential impacts of Hawaiian plants on sleep, anxiety, mood, and pain.

The increase in proinflammatory cytokine expression causes behavioral changes consistent with sickness behavior, and this led to the suggestion that depression might be a psychoneuroimmunological phenomenon. Here, we evaluated the effects of the pretreatment with fluoxetine (10 mg/kg, i.p.) and curcumin (0.5 mg/kg, i.p.) on the immune response elicited by the inoculation of an Aeromonas hydrophila bacterin in zebrafish. Non-pretreated but A. hydrophila-inoculated and sham-inoculated groups of fish served as controls. The social preference, locomotor, exploratory activities, and cerebral expression of il1b, il6, tnfa, and bdnf mRNA were compared among the groups. Behavioral changes characteristic of sickness behavior and a significant increase in the expression of il1b and il6 cytokines were found in fish from the immunostimulated group. The behavioral alterations caused by the inflammatory process were different between males and females, which was coincident with the increased expression of cerebral BDNF. Fluoxetine and curcumin prevented the sickness behavior induced by A. hydrophila and the increased expression of proinflammatory cytokines. Our results point to the potential of zebrafish as a translational model in studies related to neuroinflammation and demonstrate for the first time the effects of fluoxetine and curcumin on zebrafish sickness behavior.

Curcumin, from the rhizome of turmeric (Curcuma longa L.), has a wide variety of biological activities. Unfortunately, its poor water-solubility greatly limits its bioavailability. The purpose of this study was to evaluate CUMINUP60®, a novel preparation utilizing a solvent-free, co-grinding method designed to improve curcumin's bioavailability. We performed a single-center crossover experiment to compare the new product with standard 95% curcumin in the blood plasma of twelve healthy adults (10 males, 2 females). Total bioavailability of curcumin and its sulfate and glucuronide conjugates from the test product, measured by their areas under the curve over 12 h (AUC_0-T), showed a combined increase of 178-fold over standard curcumin and its conjugates from the reference product. The new product represents a significant improvement for providing greater bioavailability of curcumin, as compared with several other branded preparations. It therefore has broad applications for preparing curcumin as a more effective health ingredient in functional foods, beverages, and nutraceuticals.

Gastric cancer, a common malignant disease, seriously endangers human health and life. The high mortality rate due to gastric cancer can be attributed to a lack of effective therapeutic drugs. Cancer cells utilize the glycolytic pathway to produce energy even under aerobic conditions, commonly referred to as the Warburg effect, which is a characteristic of gastric cancer. The identification of new targets based on the glycolytic pathway for the treatment of gastric cancer is a viable option, and accumulating evidence has shown that phytochemicals have extensive anti-glycolytic properties. We reviewed the effects and mechanisms of action of phytochemicals on aerobic glycolysis in gastric cancer cells. Phytochemicals can effectively inhibit aerobic glycolysis in gastric cancer cells, suppress cell proliferation and migration, and promote apoptosis, via the PI3K/Akt, c-Myc, p53, and other signaling pathways. These pathways affect the expressions of HIF-1α, HK2, LDH, and other glycolysis-related proteins. This review further assesses the potential of using plant-derived compounds for the treatment of gastric cancer and sheds insight into the development of new drugs.

Post-SSRI sexual dysfunction (PSSD) is a set of heterogeneous sexual problems, which may arise during the administration of selective serotonin reuptake inhibitors (SSRIs) and persist after their discontinuation. PSSD is a rare clinical entity, and it is commonly associated with non-sexual concerns, including emotional and cognitive problems and poor quality of life. To date, however, no effective treatment is available. The aim of this study was to retrospectively evaluate the potential efficacy of the different treatments used in clinical practice in improving male PSSD. Of the 30 patients referred to our neurobehavioral outpatient clinic from January 2020 to December 2021, 13 Caucasian male patients (mean age 29.53 ± 4.57 years), previously treated with SSRIs, were included in the study. Patients with major depressive disorder and/or psychotic symptoms were excluded a priori to avoid overlapping symptomatology, and potentially reduce the misdiagnosis rate. To treat PSSD, we decided to use drugs positively affecting the brain dopamine/serotonin ratio, such as bupropion and vortioxetine, as well as other compounds. This latter drug is known not to cause or reverse iatrogenic SD. Most patients, after treatment with vortioxetine and/or nutraceuticals, reported a significant improvement in all International Index of Erectile Function-(IIEF-5) domains (p < 0.05) from baseline (T0) to 12-month follow-up (T1). Moreover, the only patient treated with pelvic muscle vibration reached very positive results. Although our data come from a retrospective open-label study with a small sample size, drugs positively modulating the central nervous system serotonin/dopamine ratio, such as vortioxetine, could be used to potentially improve PSSD. Large-sample prospective cohort studies and randomized clinical trials are needed to investigate the real prevalence of this clinical entity and confirm such a promising approach to a potentially debilitating illness.

The Mediterranean diet (MED), a dietary pattern rich in fruits and vegetables, whole grains, legumes, nuts, fish, and olive oil, has anti-oxidative and anti-inflammatory effects. Although some data suggest that MED adherence is associated with decreased manifestation of depressive symptoms, it remains necessary to further analyze this apparent non-linear association as well as the influence of different factors on the relationship between MED and depression. Here, we investigated associations between the alternate MED (aMED) score and depressive symptom via multivariate logistic regression, weighted generalized additive (GAM) and two-step linear regression models, analyzing data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). The most important factor relevant to aMED score that contributed to the prevalence of depressive symptom was assessed using random forest. Furthermore, we examined whether the relationship between aMED score and depressive symptom differs by age, race, sex, socioeconomic variables, lifestyle- and health-related variables, and chronic medical conditions, via subgroup analyses. A total of 19,477 participants (20-80 years of age) were included in this cross-sectional study. In crude and adjusted (1-5) multivariate logistic regression models, increased aMED score was noted to associate with non-depressive status, as defined using the Patient Health Questionnaire-9 (P < 0.05). Data analyses via GAM and two-piecewise linear regression revealed a non-linear association between aMED and depressive symptom, which had an inflection point of 3. Random forest results revealed that vegetable score contributes greatest to the relationship between aMED and depressive symptom. Subgroup analyses revealed that aMED score is significantly negatively related with depressive symptom in most different populations (P < 0.05) with the exception of high annual income, diabetes, borderline blood glucose level and Parkinson's disease (PD) (P > 0.05). In conclusion, we observed a non-linear association between aMED score and depressive symptom. Further studies are needed to validate our results.