Mangiferin attenuates UV-B-induced premature senescence through suppression of mitochondrial ROS and restoration of mitochondrial dynamics in human dermal fibroblasts and BALB/c mice.

Human skin is continuously exposed to harmful Ultraviolet Radiations from the Sun leading to various morphological (pigmentation, sun burn, loss of elasticity and wrinkling) and physiological (ROS generation, oxidative stress, inflammation, DNA damage and cell death) alterations. All these changes make skin more susceptible to skin aging out of which cellular senescence plays a major role in UV-B driven skin aging. Senescence is the phenomenon of cell cycle arrest associated with changes at morphological and cellular levels i.e. compromised nuclear integrity, dysfunctional mitochondria producing excessive ROS, release of certain proinflammatory cytokines (SASP) which establish paracrine senescence in the neighboring cells. SASP is associated with the release of extracellular matrix metalloproteinases which break down the collagen fibres driving skin towards premature aging. In this study, we have unravelled the role of Mangiferin, a xanthonoid, in preventing UV-B induced premature senescence in HDF cells and BALB/c mice. Xanthonoids are a group of polyphenolic compounds known to possess cytoprotective, anti-inflammatory and antioxidant activities. Many xanthonoids including Mangiferin (MGN) are known to alleviate mitochondrial ROS production. As mitochondrial ROS is a key driver of cellular senescence in UV-B irradiated HDF cells, we have studied the role of Mangiferin in preventing/ attenuating the premature senescence in UV-B exposed HDF cells by inhibiting mitochondrial ROS production. Mangiferin significantly inhibited premature senescence in skin by quenching mitochondrial ROS production. And topical application of Mangiferin on BALB/c mice showed reduced signs of Photodamage and senescence, implying that it has potential to be developed as therapeutic agent for UV-B driven premature senescence induced photoaging in skin dermal cells.