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The trafficking of the natural medicine ingredient NGR1 across the membranes of human keratinocytes is mediated by the ATP binding cassette transporter ABCG2.
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NGR1 enhances the recognition of skin sunburn injury caused by UVB irradiation.
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The WTAP/m6A/DDB2 axis was efficiently utilized by NGR1 to facilitate the repair of UVB induced DNA damage, with a specific focus on correcting CPD lesion.
AbstractUltraviolet B (UVB) radiation, a major environmental carcinogen, induces cyclobutane pyrimidine dimers (CPDs) and contributes to the development of squamous cell carcinoma. The RNA N6-methyladenosine (m6A) modification plays a critical role in regulating the DNA damage response. This study demonstrates that Notoginsenoside R1 (NGR1), a bioactive ginsenoside derived from Panax notoginseng, protects against UVB induced skin sunburn injury. ABCG2 was identified as a key epidermal transporter responsible for the uptake of NGR1 into keratinocytes, revealing a previously unrecognized function of this efflux pump, its capacity to mediate nonspecific import of this ginsenoside. Mechanistically, NGR1 significantly upregulates WTAP expression, enhances global m6A levels, and activates the m6A/DDB2 axis, resulting in a substantial reduction in CPDs. These findings elucidate a molecular pathway through which NGR1, via ABCG2 mediated transport, mitigates UVB induced DNA damage by promoting m6A dependent DNA repair, positioning it as a promising candidate for topical therapeutic intervention.
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