S-equol (AUS-131) / Ausio Pharma - LARVOL DELTA

S-Equol Alleviates Palmitic Acid-Induced Muscle Atrophy by Modulating the ERβ-AMPK-Autophagy Axis in L6 Cells. (PubMed, J Nutr Metab) - "Our findings demonstrate that Eq alleviates PA-induced myotube atrophy by promoting autophagy, potentially through modulation of the ERβ-AMPK signaling axis. These results highlight Eq as a potential nutritional therapy for the prevention and treatment of diabetic sarcopenia."

Journal • Diabetes • Metabolic Disorders • Muscular Atrophy • Sarcopenia • AMPK • ER

Microbial conversion of daidzein to S-equol enhances protection against menopause-associated metabolic dysfunction by suppressing pancreatic inflammation, inhibiting DPP-4/PTP1B, activating AMPK/Akt, and enhancing energy catabolism. (PubMed, Tissue Cell) - "Moreover, Eq and Dzn improved insulin signaling by inhibiting DPP-4 and PTP1B and activating AMPK and Akt/PKB pathways, and stimulated carbohydrate and lipid catabolism via increased activities of Krebs cycle enzymes (IDH, SDH, and MDH). Collectively, these findings showed that microbial Eq as a potent phytoestrogen that mitigates menopausal metabolic and pancreatic alterations."

Journal • Diabetes • Dyslipidemia • Inflammation • Metabolic Disorders • ELANE • MPO • PTPN1

How Gut Microbes Transform Dietary Phytonutrients: Enzymatic Pathways and Human Metabolite Exposure. (PubMed, Molecules) - "This critical narrative review examines pathways resolved beyond taxonomic association: daidzein-to-S-equol conversion; cooperative urolithin and enterolignan formation; flavone reduction and C-ring cleavage; stereoselective catechin metabolism; glucosinolate activation; and transformations of resveratrol and hydroxycinnamate-derived metabolites...We conclude that microbiota-dependent exposure should be claimed only when reaction-level evidence is connected to precursor-specific human metabolites. This framework separates established conversion from unresolved spontaneous and host processing and specifies the evidence needed to explain individual responses."

Journal • Review

Metabolic Outputs of the Gut Microbiome: Implications for Epilepsy. (PubMed, Cells) - "Some microbial-derived metabolites may serve as promising biomarkers and mechanistic mediators of epilepsy; however, further investigation is needed to define the molecular and cellular pathways through which these metabolites influence seizure susceptibility and epileptogenesis."

Journal • Review • CNS Disorders • Epilepsy

Microbial Metabolites and Neural Epigenetic Circuitry in Emotional Homeostasis and Depression. (PubMed, Nutr Rev) - "The current evidence indicates that the gut microbial metabolism converts dietary polyphenols into bioactive metabolites, including urolithins, S-equol, phenyl-γ-valerolactones, and short-chain fatty acids, with greater bioavailability and neurobiological activity than their parent compounds...This review highlights the gut microbiota as a key mediator linking dietary polyphenols with brain function through microbial metabolism and epigenetic regulation. Understanding these interactions provides a mechanistic basis for precision nutrition and supports the development of microbiota-targeted dietary strategies for preventing and managing mood disorders."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry

S-equol shifts afatinib-altered mucosal immune-epithelial defense indices toward baseline and attenuates increases in DEFA5 and SOX9 promoter methylation indices. (PubMed, Immunol Lett) - "Across complementary epithelial and animal models, S-equol shifted selected afatinib-associated mucosal immune-epithelial and promoter methylation readouts toward their corresponding control values. These findings identify molecular responses that warrant further investigation using direct intestinal functional measurements and models that evaluate compatibility with afatinib-mediated tumor control."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • CFTR • DEFA5 • SOX9 • WNT3

Effectiveness of a Natural S-Equol Supplement for Premenstrual Symptoms: A Randomized Controlled Trial. (PubMed, Tohoku J Exp Med) - No abstract available

Journal

The Vascular Contribution to Dementia. World Stroke Organisation Scientific Statement. (PubMed, Int J Stroke) - "We highlight the potential for vascular interventions to treat not only vascular dementia, but also the vascular component of neurodegenerative dementia. We review recent clinical trials targeting multiple pathways, including nitric oxide signalling, high blood pressure, the GABAergic system, angiogenic activity, microglial inhibition, PDE3 and PDE5 inhibition, as well as dietary supplementation with omega-3-fatty acid, s-equol and vitamin E. Finally, we consider upcoming opportunities and challenges relevant to vascular disease in dementia."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Fibrosis • Hypertension • Immunology • Ischemic stroke • COL4A1 • HTRA1 • IL6 • MMP9 • TRIM47

Quantitative Analysis of Placebo Response Models to Optimize Clinical Trials in Premenstrual Disorders: A Model-Based Meta-analysis. (PubMed, Biopsychosoc Sci Med) - "The placebo response models of common evaluation indicators in clinical trials of drugs for premenstrual disorders have been established, providing an important basis for the optimized design and decision-making of subsequent clinical trials."

Clinical • Journal • Retrospective data • CNS Disorders • Depression • Gynecology • Mood Disorders • Psychiatry

Reconstitution of gut microbiota by medicinal plant isoflavones ameliorates heart failure with preserved ejection fraction. (PubMed, Pharmacol Res) - "Here, we demonstrated that the isoflavone extract of Pueraria lobata (Iso-Pl), puerarin, or its microbial metabolite S-equol, improved left ventricular diastolic dysfunctions, reduced hypertension, and ameliorated metabolic disorders in an HFD and L-NAME-induced HFpEF mouse model...These activities collectively contributed to the alleviation of HFpEF by Iso-Pl. Collectively, our findings demonstrate that the cardioprotective effects of Iso-Pl are closely linked with the gut microbiota-dependent metabolic reprogramming and highlight P. lobata isoflavones as promising therapeutic agents for HFpEF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Metabolic Disorders • Transplantation • ER • NOS3

S-equol Modulates T3-Induced Transcription and Neurite Outgrowth in Neuronal Cells. (PubMed, Int J Mol Sci) - "Collectively, these findings indicate that S-equol functions as a dual-acting modulator that may modulate T3 signaling involving TR-ER interaction. Although S-equol may exert beneficial effects on neurodevelopment, it may also act as an endogenous endocrine modulator that alters the fine regulation of TH action during development, warranting careful evaluation from physiological and toxicological perspectives."

Journal • Brain Cancer • Glioma • Neuroblastoma • Oncology • Solid Tumor • DLG4

Gut Microbiota-Skin Axis in Melasma: Microbial Metabolites and Hormonal Crosstalk. (PubMed, FEMS Microbiol Lett) - "Microbial metabolites-including short-chain fatty acids, exopolysaccharides, β-glucuronidase, and S-equol-modulate key processes such as inflammation, estrogen metabolism, and cellular senescence...This mini-review highlights microbial drivers of gut-skin crosstalk in melasma and underscores the microbiota as a source of potential biomarkers and therapeutic targets. We propose that gut dysbiosis contributes to melasma pathogenesis through microbiota-derived metabolites that modulate estrogen signalling and cellular senescence pathways, establishing a mechanistic framework linking immunometabolic dysregulation to persistent hyperpigmentation."

Journal • Dermatology • Dermatopathology • Inflammation • Metabolic Disorders

S-equol promotes ferroptosis in triple negative breast cancer by coordinating NCOA4-mediated ferritinophagy and PPARγ-mediated lipid metabolism. (PubMed, Mol Cell Biochem) - "The results of NCOA4 knockdown or PPARγ overexpression further verified the previous mechanism of S-equol. In conclusion, these findings revealed that S-equol promotes ferroptosis in TNBC by suppressing PPARγ-mediated lipid metabolism and promoting NCOA4-mediated ferritinophagy, which was largely dependent on the regulation of the PI3K/AKT/mTOR signaling pathways."

Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • GPX4 • NCOA4 • PPARG • STAT3

Can the Posterior Segment Findings of the Eye and Serum Microbiota Metabolites Be a Biomarker in Schizophrenia? (PubMed, Medicina (Kaunas)) - "The aim of this study was to examine the possible relationship between the retina, choroid, and nerve fibre layer thicknesses measured on optic coherence tomography (OCT) and the serum microbiota metabolite levels of trimethyl amine-N-oxide (TMAO), S-equol, Indoxyl sulphate (IS), and Maresin 1 (MaR1)... The study results showed that fundus changes are associated with serum microbiota metabolite levels in schizophrenia patients. Therefore, these parameters may be considered potential exploratory biomarkers; however, their clinical applicability requires validation in larger longitudinal studies."

Biomarker • Journal • CNS Disorders • Psychiatry • Schizophrenia

S-equol producing bacteria: isolation and identification from Albino Wistar rat gut microbiota. (PubMed, Appl Microbiol Biotechnol) - "• Soybean fermentation enables efficient conversion of daidzin to bioactive S-equol. • Novel S-equol-producing microbes were isolated and identified."

Journal • Preclinical • Cardiovascular • Oncology

Exploratory multi-omics analysis of gut microbiota and fecal metabolites in relation to serum S-equol levels in older adults with osteoporosis from a tropical community: a pilot study. (PubMed, Front Nutr) - "Network and heatmap analyses illustrated differences in microbial-metabolite association patterns between groups. In conclusion, low levels of serum S-equol in older adults with osteoporosis were associated with distinct changes in gut microbiota composition and fecal metabolic profiles in this pilot study."

Journal • Inflammation • Metabolic Disorders • Osteoporosis • Rheumatology • IL1B

S-Equol: a novel therapeutic for HIV-1-associated gastrointestinal dysbiosis. (PubMed, NeuroImmune Pharm Ther) - "Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes. SE may provide a novel adjuvant treatment in addition to cART for HIV-1-associated dysbiosis and associated neurocognitive dysfunction."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease

Exercise and Carnosine Modulate Microbiota-Derived Metabolites, Myokines, and Cardiometabolic Profiles in Rats: A Randomized Controlled Trial. (PubMed, Biomedicines) - "The trimethylamine N-oxide (TMAO) was lowest and S-equol highest in HICTCA, whereas indoxyl sulfate (IS) peaked in HICT and was lowest in the C group. Principal component analysis revealed strong positive associations between HICTCA and cardiometabolic biomarkers. High-intensity training combined with carnosine may reduce weight gain, improve lipid and glycemic profiles, and enhance myokines and microbiota-derived metabolites."

Journal • Preclinical

S-Equol as a Gut-Derived Phytoestrogen Targeting Estrogen Receptor β: A Promising Bioactive Nutrient for Bone Health in Aging Women and Men: A Narrative Review. (PubMed, Nutrients) - " S-equol represents a promising model for "precision nutrition," where microbiome, hormonal, and host factors converge with potential to prevent age-related bone fragility. Rigorous trials that integrate microbiome phenotyping and advanced imaging are needed to validate this approach, translate mechanistic promise into clinical benefit, and better define safety."

Journal • Review • Osteoporosis • Rheumatology • ER

Lack of effects of S-equol-containing supplement on the pharmacokinetics of oral hormone therapy drugs for breast cancer. (PubMed, Cancer Chemother Pharmacol) - "S-equol-containing supplement has no clinically significant effects on the exposure of oral hormone therapy drugs for breast cancer. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: jRCTs031200084, August 13th, 2020."

Journal • PK/PD data • Breast Cancer • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Pain • Solid Tumor

Mechanisms Underlying S-Equol–Mediated Suppression of Neuronal Hyperexcitability (AES 2025) - "These findings suggest that S-equol's suppressive effects on neuronal hyperexcitability are not mediated through ESRβ or BK channels in this model but instead involve GPR30/GPER1 signaling. Our results highlight a previously unrecognized mechanism of S-equol's neuroprotective action in TMEV-induced seizures and underscore the complexity of its molecular targets, warranting further investigation."

CNS Disorders • Epilepsy • Infectious Disease • GPER1

S-Equol: A Novel Therapeutic For HIV-1-Associated Gastrointestinal Dysbiosis. (PubMed, bioRxiv) - "Prevotella_UCG_001 was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease

S-equol status modulates skin response to soy isoflavones in postmenopausal women: results from a randomized placebo-controlled pilot trial. (PubMed, Front Nutr) - P=N/A | "Findings suggest region-specific, time-sensitive effects dependent on S-equol levels. https://clinicaltrials.gov/study/NCT06047145, NCT06047145."

Journal

In Vivo and In Vitro Mechanisms of Equol Synthesis and Key Influencing Factors: A Critical Review. (PubMed, Nutrients) - "Background: Equol exists in two enantiomers of S-equol and R-equol... This review suggests that breakthroughs based on synthetic biology and gene editing technology will support the efficient in vitro synthesis of equol. This review serves as a valuable reference for future research."

Journal • Preclinical • Review • Cardiovascular

Maresin-1 and S-Equol as Emerging Metabolic Biomarkers in Gestational Diabetes-Associated Inflammation. (PubMed, Diagnostics (Basel)) - " The observed reductions in MaR-1 and S-Equol levels among GDM patients suggest a potential role for these anti-inflammatory mediators in the inflammatory processes associated with GDM. That is, these findings imply that the advantages of using these MaR-1 and S-Equol could be predictive for GDM."

Biomarker • Journal • Diabetes • Gestational Diabetes • Inflammation • Metabolic Disorders • CRP