Sudip Ghosh

Scalp itch and beard irritation are multifactorial neurocutaneous disorders associated with microbial dysbiosis, impaired skin barrier function, inflammation, and activation of the transient receptor potential vanilloid 1 (TRPV1) ion channel, a key mediator of itch signalling and neurogenic inflammation. Although conventional therapies such as ketoconazole, zinc pyrithione, and hydrocortisone provide symptomatic relief, their long-term use is limited by adverse effects, irritation, and regulatory concerns, highlighting the need for safer steroid-free alternatives. In the present study, the molecular mechanism underlying the antipruritic potential of FERMENZA, a natural postbiotic formulation, was investigated using an integrated computational approach. LC-MS metabolite profiling identified major phytochemicals, which were subjected to molecular docking against the TRPV1 vanilloid-binding pocket, followed by 40 ns molecular dynamics simulations in a POPC lipid bilayer under physiological conditions. Among the identified metabolites, rutin exhibited the highest binding affinity (-12.76 kcal mol^-1), followed by ellagic acid (-11.83 kcal mol^-1), outperforming the reference antagonist capsazepine (-8.96 kcal mol^-1) as well as hydrocortisone (-8.06 kcal mol^-1), ketoconazole (-6.56 kcal mol^-1), and zinc pyrithione (-6.06 kcal mol^-1). Both phytochemicals formed stable hydrogen bonds and hydrophobic interactions with key residues in the TRPV1 binding pocket. Molecular dynamics simulations confirmed stable protein-ligand complexes without ligand dissociation throughout the simulation. Rutin showed the highest structural stability, reflected by the lowest backbone RMSD (3.72 ± 0.37 Å), stable radius of gyration, minimal solvent-accessible surface area fluctuations, and negligible perturbation of the surrounding POPC membrane. Overall, the findings identify rutin, followed by ellagic acid, as promising natural TRPV1 modulators and provide a molecular basis for the antipruritic activity of FERMENZA, supporting its potential as a safe, drug-free and steroid-free natural formulation for managing scalp itch and beard hypersensitivity.

This study investigates the comparative impact of fermentation versus conventional extraction methods on the bioactive potency of “FERMENZA”, a patented, affordable, natural fermented cider-based topical formulation. Through comprehensive in vitro analysis, the fermented extract demonstrated superior antioxidant efficacy, with an IC₅₀ value of 0.77 ± 0.03 mg/mL, significantly outperforming solvent and steam-distilled extracts, which showed IC₅₀ values of 2.49 ± 0.01 mg/mL and 4.11 ± 0.03 mg/mL, respectively. Notably, the nitric oxide scavenging activity of the fermented extracts was markedly higher than that of conventional extracts, with IC₅₀ values ranging from 1.12 ± 0.03 to 2.29 ± 0.03 mg/mL. Fermentation also enhanced total phenolic content (TPC), with mixed fruit extracts (pomegranate-beetroot, banana-papaya) reaching TPC levels of 2.43 ± 0.03 mg gallic acid equivalent/g, surpassing individual and conventionally processed samples. The study employed a Quality by Design approach to optimize fermentation conditions, achieving peak yields of gallic acid and TPC at 35 °C and 72 h, which further validates the process affordability. Under these conditions, the fermented extracts from pomegranate and beetroot demonstrated exceptional antimicrobial properties against E. coli, S. aureus, P. aeruginosa, P. acne, and M. furfur, with minimum inhibitory concentration values ranging from 0.25 mg/mL to 0.60 mg/mL, superior to those observed in conventionally extracted samples from pomegranate and beetroot. These findings highlight the efficacy of fermentation in enhancing bioactive compound availability, positioning FERMENZA as a potent fermented formulation for probable skin and hair-related cosmeceutical applications.

Background: Dandruff and related scalp disorders, often caused by Malassezia furfur, pose significant dermatological challenges. This study evaluates FERMENZA®, a novel, patented formulation derived from pomegranate and beetroot fermented extracts, as a natural alternative to synthetic agents like ketoconazole and zinc pyrithione. Methodology and Results: In this study, mixed substrate fermentation was utilized for synergistic effect on bioactivity of natural fruits and vegetable extracts. The pomegranate-beetroot fermented extract demonstrated impressive antifungal efficacy against Malassezia furfur MTCC 1374, with percent inhibition of 96% and 86.7% compared to active pharmaceutical ingredients ketoconazole and zinc pyrithione, respectively. The investigational formulation FERMENZA® derived from pomegranate and beetroot fermented extract exhibited the highest zone of inhibition (ZOI) of 28 ± 0.12 mm, outperforming marketed products A and B lotions by achieving 93 ± 0.04% and 60 ± 0.09% inhibition, respectively. Minimum inhibitory concentration (MIC) studies revealed potent activity of the formulation at 8mg/ml. The MIC90 value was observed at 20µg/mL achieving 92 ± 0.01% inhibition compared to ketoconazole. A time-kill assay highlighted the superior antifungal potency of FERMENZA® against M. furfur, significantly reducing fungal growth intensity within 48 hours, starting from 6 hours of incubation. The mechanism of fungicidal action is attributed to gallic acid, a key active component of pomegranate and beetroot fermented extract which disrupts fungal cell structures.Conclusion: Efficacy and sensory evaluation confirmed FERMENZA®’s ability to alleviate dandruff, itching, flaking, and scaling within 10 days, with moderate benefits in reducing hairfall. These results underscore FERMENZA®'s potential as a comprehensive, natural solution for managing dandruff and scalp disorders, providing a safer alternative to synthetic antifungal agents.

Acne vulgaris and Malassezia folliculitis are common dermatological conditions that require effective treatments to avoid antimicrobial resistance development. Natural postbiotic extracts, offers a potential alternative therapy due to its antimicrobial, anti-inflammatory, and skin-renewing properties. This study aims to evaluate the antimicrobial efficacy, chemical composition, and efficacy assessment of FERMENZA postbiotic gel for the treatment of acne vulgaris and malassezia folliculitis, in comparison to traditional antimicrobial treatments. Metabolite profiling of the postbiotic extract through LC-MS analysis revealed presence of compounds such as gallic acid and ellagic acid, which exhibit synergistic antimicrobial and anti-inflammatory properties. The postbiotic extract and FERMENZA gel showed significant antimicrobial activity, with inhibition rates of 85% and 81%, respectively, against P. acnes (MTCC 1951) compared to clindamycin 2% active ingredient. The MIC50 for FERMENZA postbiotic gel against P. acnes was 0.25 mg/ml. The MIC potency against M. furfur (MTCC 1374) was found to be 8 mg/ml in our previous study which was comparable to ketoconazole 2% active ingredient. Time-kill assays confirmed that FERMENZA gel reduced bacterial counts within 24 hours, with efficacy comparable to clindamycin 2% marketed gel. Nucleotide efflux assays indicated that postbiotic components compromised bacterial membrane integrity, causing leakage of intracellular contents. Stability studies showed that FERMENZA gel remained stable and within acceptable limits for all tested parameters over six months. Consumer trials indicated that FERMENZA gel provided superior pain relief and fading of acne spots compared to clindamycin, with a gentle, non-irritating formulation. This study positions FERMENZA postbiotic gel as a promising alternative for the treatment of Acne vulgaris and Malassezia folliculitis. The formulation's dual-action mechanism, driven by natural phenolic acids and polyphenols, provides an effective, sustainable solution without the risks of resistance development.