Andrographolide represses HIF-1α and VEGFA expression, thus inhibiting hypoxia-induced proliferation, oxidative stress, and inflammatory cytokine secretion in human keratinocytes

Epidermal hypoxia, hyperproliferation of keratinocytes, and inflammation in skin lesions are relevant to the pathogenesis of inflammatory skin diseases, including psoriasis. Andrographolide (Andro) is a natural labdane diterpene with diverse biofunctions. Andro has been reported to alleviate psoriasis in mice. However, the exact mechanisms need further study. Our results demonstrated that Andro inhibited hypoxia-induced proliferation of human keratinocytes. Andro also protected the keratinocytes from hypoxia-induced oxidative stress and inflammatory response. Furthermore, we found that Andro suppressed the expression of HIF-1α and VEGFA expression in hypoxia-exposed keratinocytes. Overexpression of either HIF-1α or VEGFA attenuated the inhibitory effects of Andro on hypoxia-induced proliferation, oxidative stress, and inflammatory cytokine secretion. In summary, our results demonstrated that Andro protected keratinocytes from hypoxia-induced proliferation, oxidative stress, and inflammatory cytokine secretion by suppressing HIF-1α and VEGFA expression. Our findings provide an unreported insight into the potential use of Andro as an effective agent for the treatment of inflammatory skin diseases such as psoriasis in the future.