Božo Radić

Background: We recently demonstrated in a randomized controlled trial (RCT) that a Standardized Propolis Extract (SPE), produced via a patented non‐alcoholic PEG 400/lecithin process, achieves significant clinical anti‐wrinkle efficacy (34% wrinkle depth reduction). The present study investigates the underlying molecular mechanisms, specifically its potential senomorphic activity—the ability to modulate the Senescence‐Associated Secretory Phenotype (SASP) without inducing cell death. Objective: To evaluate the senomorphic activity of this chemically defined SPE (standardized to 1318.43 μg/g total phenolic markers) in an in vitro model of oxidative stress‐induced senescence, providing molecular insights into its clinically observed anti‐aging effects. Methods: Human Dermal Fibroblasts (HDFs) were pre‐treated with SPE (0.01%, 0.05%) or Rapamycin (3 μM, reference senomorphic control). Senescence was induced via a validated stress‐induced premature senescence (SIPS) protocol (200 μM H ₂ O ₂ , 2 h). Gene expression for senescence markers (CDKN2A/p16, CDKN1A/p21), SASP cytokines (IL‐6, IL‐8), and cell cycle regulators (CDK4, CDK2, CCNE1) was quantified by qPCR. An exploratory study on Mesenchymal Stem Cells (MSCs) assessed SA‐β‐galactosidase activity qualitatively. Results: The 0.05% SPE demonstrated potent senomorphic activity, significantly suppressing the key SASP marker IL‐6 (FC: −7.78, p = 0.003)—comparable to the Rapamycin control (FC: −8.1, p = 0.003). Uniquely, SPE induced transcriptional upregulation of CDK4 (FC: +6.71, p = 0.002) and CDKN1A/p21 (FC: +2.33, p = 0.005), effects not observed with Rapamycin. In exploratory MSC experiments, SPE qualitatively reduced SA‐β‐gal staining. Conclusion: This first‐in‐class standardized propolis extract demonstrates distinct senomorphic activity, suppressing the inflammatory SASP (IL‐6) while inducing transcriptional modulation of pro‐regenerative pathways (CDK4). These molecular findings provide mechanistic insights consistent with the extract's clinically proven anti‐wrinkle efficacy, supporting its positioning as an evidence‐based active ingredient for dermo‐cosmetic formulations targeting inflammaging.

Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share symptoms such as abdominal pain, bloating, and altered bowel habits. Both are linked to dysbiosis and gut–brain axis dysfunction. IBS is a multifactorial disorder characterized by abnormal motility, visceral hypersensitivity, low-grade inflammation, and alterations in the microbiota. In contrast, SIBO is defined by excessive bacterial colonization of the small intestine that can mimic or worsen IBS symptoms. Gut microbes and their metabolites influence motility, immune activation, barrier integrity, and gas production; methanogen overgrowth is associated with constipation-predominant presentations, while hydrogen- and hydrogen sulfide-related pathways may contribute to diarrhea and bloating. Because recurrent or empiric antibiotic use is common—particularly in suspected SIBO—yet carries risks of resistance, microbiome disruption, and relapse, there is a strong rationale to prioritize effective non-antibiotic strategies. Accordingly, this review synthesizes current evidence on IBS/SIBO pathophysiology and microbiota interactions. It evaluates non-pharmacological interventions including dietary approaches, probiotics/prebiotics, herbal therapies, and mind–body treatments (e.g., cognitive behavioral therapy and gut-directed hypnotherapy). We emphasize an integrative framework that supports symptom control and quality of life while helping reduce unnecessary antibiotic exposure.

Background We recently demonstrated in a randomized controlled trial (RCT) that a Standardized Propolis Extract (SPE), produced via a patented non-alcoholic PEG 400/lecithin process, achieves significant clinical anti-wrinkle efficacy (34% wrinkle depth reduction). The present study investigates the underlying molecular mechanisms, specifically its potential senomorphic activity—the ability to modulate the Senescence-Associated Secretory Phenotype (SASP) without inducing cell death. Objective To evaluate the senomorphic activity of this chemically defined SPE (standardized to 1318.43 µg/g total phenolic markers) in an in vitro model of oxidative stress-induced senescence, providing molecular insights into its clinically observed anti-aging effects. Methods Human Dermal Fibroblasts (HDFs) were pre-treated with SPE (0.01%, 0.05%) or Rapamycin (3µM, reference senomorphic control). Senescence was induced via a validated stress-induced premature senescence (SIPS) protocol (200µM H₂O₂, 2 hours). Gene expression for senescence markers (CDKN2A/p16, CDKN1A/p21), SASP cytokines (IL-6, IL-8), and cell cycle regulators (CDK4, CDK2, CCNE1) was quantified by qPCR. An exploratory study on Mesenchymal Stem Cells (MSCs) assessed SA-β-galactosidase activity qualitatively. Results The 0.05% SPE demonstrated potent senomorphic activity, significantly suppressing the key SASP marker IL-6 (FC: -7.78, p = 0.003)—comparable to the Rapamycin control (FC: -8.1, p = 0.003). Uniquely, SPE induced transcriptional upregulation of CDK4 (FC: +6.71, p = 0.002) and CDKN1A/p21 (FC: +2.33, p = 0.005), effects not observed with Rapamycin. In exploratory MSC experiments, SPE qualitatively reduced SA-β-gal staining. Conclusion This first-in-class standardized propolis extract demonstrates distinct senomorphic activity, suppressing the inflammatory SASP (IL-6) while inducing transcriptional modulation of pro-regenerative pathways (CDK4). These molecular findings provide mechanistic insights consistent with the extract's clinically proven anti-wrinkle efficacy, supporting its positioning as an evidence-based active ingredient for dermo-cosmetic formulations targeting inflammaging.

Propolis is a natural mixture of honeybee-released and plant-derived compounds produced by honeybees. Poplar propolis is rich in bioactive polyphenolic compounds, and due to its many health benefits, it is commonly used as a food supplement or functional food ingredient. However, it is the only honeybee product whose proteome hasn’t been analyzed. Here, we report a first proteome analysis of poplar-type propolis, a challenging glue-type resinous sample for protein characterization. Raw propolis mixture was precipitated with cold acetone to obtain the protein fraction. Proteins were digested with trypsin, and generated peptides were analyzed on nano-ESI-qTOF SYNAPT G2-Si mass spectrometer (MS) by data-independent acquisition (DIA) and data-dependent acquisition (DDA). Identified peptides and inferred proteins suggest the presence of new bioactive molecules as components of propolis. The poplar-type propolis proteome is composed of a mixture of proteins from the Apis and Populus genera. This is the first-ever report of the proteome of any type of propolis.