Unraveling cellular longevity pathways in poultry under heat stress: functional and computational characterization of...

Heat stress significantly disrupts physiological and molecular balance in poultry, leading to oxidative damage, inflammatory responses, and metabolic dysregulation. Among emerging solutions, phytogenic adaptogens have shown promise as natural agents that enhance resilience against these environmental challenges. This exploratory study examined the transcriptomic effects of Phytocee™, a proprietary phytogenic formulation, in heat-stressed broilers, alongside in silico predictions of its phytochemical interactions with longevity-associated pathways. Phytocee™ consists of a formulation of adaptogenic medicinal plants. The primary bioactive components contributing to these adaptogenic properties include hydrolyzable tannins, withanolides, and triterpenoids. Comprehensive identification, quantification, and confirmation of these phytochemicals were conducted using liquid chromatography-mass spectrometry (LC-MS), and the formulation's integrity was validated through high-performance liquid chromatography coupled with photodiode-array detection for routine quality assurance. The transcriptomic analysis demonstrated that heat stress led to the upregulation of several vital DNA repair and cell cycle regulatory genes, including FANCF, BRCA1, and EXO1. The supplementation of Phytocee™ resulted in further increases in these genes, reaching a log2 fold change of 1.32 with a significance level of p < 0.013. Additionally, resilience markers against oxidative stress such as SOD2, CAT, HSP25, HSPA2, and SOD3 along with metabolic adaptation indicators like IDH3A, ATP6V0D2, RRM2, ME1, FADS2, ALDH1L2, and DHCR7 showed significant enhancement post-treatment. There was also a restoration of several downregulated protective genes, including NFKBIA and BIRC5. DIGEP-Pred 2.0 and pathway enrichment were used in the in-silico analyses, which predicted that the key Phytocee™ phytochemicals interact with FOXO, AMPK, SIRT1, and mTOR network components. Transcriptomic patterns, such as upregulated DNA repair, oxidative resilience, and metabolic genes correlatively overlapped with this prediction. Again, no model validation or functional activation was performed. This exploratory study contributes to a hypothesis-producing framework for these associations to be tested in heat-stressed broilers but has several limitations related to the correlative nature of findings, absence of confirmation at the protein level, or functional assays, such as autophagy or pathway inhibition or direct measures of thermotolerance or production. Thus, confirmatory studies are warranted to test these implied mechanistic associations.

The online version contains supplementary material available at 10.1007/s40203-026-00589-5.