By modulating pAMPK/iNOS2 and MMP signalling, Immunogrit drives cellular resilience against D-galactose-induced senescence-associated stress markers in human keratinocytes.

Acharya Balkrishna, Savita Lochab, Sandeep Guin, Monali Joshi, Sudeep Verma, Jyotish Srivastava, Rishabh Dev, Anurag Varshney

Drug Discovery and Development Division, Patanjali Research Foundation, NH-58, Haridwar 249405, Uttarakhand, India; Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249405, Uttarakhand, India; Patanjali Yog Peeth (UK) Trust, 40 Lambhill Street, Kinning Park, Glasgow G41 1AU, UK.Drug Discovery and Development Division, Patanjali Research Foundation, NH-58, Haridwar 249405, Uttarakhand, India; Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249405, Uttarakhand, India; Patanjali Yog Peeth (UK) Trust, 40 Lambhill Street, Kinning Park, Glasgow G41 1AU, UK. · pubmed

Paper

Abstract

Cellular senescence is a multifactorial, progressive phenomenon that disrupts biological homeostasis by increasing stress markers, causing morphological changes, and inducing inflammation, ultimately leading to irreversible cell cycle arrest. Natural plant-based bioactive products are frequently preferred over synthetic chemicals for their safety and efficacy. This study aims to assess the therapeutic effectiveness of a botanical formulation, Immunogrit, in mitigating stress-associated senescence markers in the skin. d-Galactose (D-Gal) has been used to induce senescence-associated stress markers in HaCaT human keratinocytes. Additionally, a thorough chemical characterization employing ultra-performance liquid chromatography-mass spectrometry coupled with quadrupole time-of-flight (UPLC/MS-QToF) and high-performance thin layer chromatography (HPTLC) was performed to generate a comprehensive phytochemical profile of Immunogrit. In HaCaT cells, d-Gal-induction increased oxidative and nitrosative stress with a perturbed expression of cell cycle biomarkers. Enhanced SA-β-galactosidase activity and subsequent downregulation of nuclear protein, LMNB1, further established the suitability of d-Gal-induced HaCaT cells as the relevant skin model for investigating senescence-associated interventions at the molecular levels. Treatment of Immunogrit with d-Gal induction, prevented the upregulation of p16, p21, and p53 levels; and maintained the basal SA-β-galactosidase activity. This study also identified pAMPK and iNOS2 as the targets of d-Gal orchestrating oxidative and nitrosative stress. Immunogrit mitigated the d-Gal-modulated levels of pAMPK and iNOS2. Moreover, collagen degradation and upregulation of metalloprotease (MMP1 and MMP9) in d-Gal-induced HaCaT cells were ameliorated by Immunogrit treatment. Our findings highlight Immunogrit as a promising botanical therapy for alleviating the key cellular markers of senescence, in human keratinocytes.

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Research summary

Immunogrit treatment mitigates cellular senescence markers in human keratinocytes induced by d-galactose. The study addresses cellular senescence, a fundamental aspect of aging, by exploring a botanical formulation that may enhance cellular resilience and potentially contribute to longevity.

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