2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38732UV light has been well documented as a complete carcinogen responsible for initiation and promotion of both basal and squamous cell carcinomas. Long-term exposure of the skin to UV radiation results in degenerative processes involved in photoaging and photocarcinogenesis. To study photoaging process, an animal model was developed by applying repeated low-dose UVB irradiation to the skin of hairless mice, and since then, many studies have been carried out using this model. As it is ethically unacceptable to continue experimental UV irradiation of human skin for long enough to induce the photoaging and skin cancer, an animal model that shows skin changes characteristic of photoaged skin as closer to human skin as possible is urgently needed. Histologically, guinea pig skin is more resemble to human skin. This prompts us to develop hairless guinea pig model to mimic UV effect on human skin based on the hairless mice model. Glycyrrhizic acid (GL) has been reported to have many biological and pharmacological activities including anti-inflammation, antiviral, and chemoprotective activity against tumors. Taking the advantage that we have already built up the basic underlying mechanisms of inhibitory effects of GL both on UV-induced viral gene expression, viral replication and neuroprotective effect against glutamate-induced neuronal cell apoptosis via the inhibition of NF-kB, we are further extending these findings to investigate the molecular basis of protective effect of GL on UV-induced skin aging and skin cancer. To improve the GL protective efficacy, we have modified the parental compound and synthesized 15 GL derivatives. To test the protective effects of these new compounds against UV-induced skin damage and study its underlying mechanisms, we design a three-year project based on the above rationale and our previous findings and experiences with GL. Our overall objectives are: 1) to develop hairless guinea pig model to mimic human skin for studying photodamage, 2) to use this animal model for new drug design and discovery based on the parental compound GL as a lead, which we have previously demonstrated to exhibit antiviral activity, neuroprotective effect, and anti-apoptotic effect against UV-induced cell death.文獻已有完備記載指出，皮膚長期暴露於紫外輻射易導致退化，包括光老化和光致癌。 為研究光老化的過程， Kligman 在1989 年建立一種動物模型，就是重覆的用低量UVB 照射無毛的老鼠皮膚。從那以後, 許多研究便使用這個模型。以人類的皮膚直接來研究 紫外線對皮膚引起老化及皮膚癌的實驗是不被醫學倫理所接受的，所以一個能顯示跟人 類皮膚老化造成的特徵改變的動物模型是迫切需要的。從組織學的角度上，天竺鼠皮膚 是極類似人類的皮膚。基於上述事實，我們發展出無毛天竺鼠模型去模擬紫外線對人類 皮膚的影響。 從過去的研究報導知道，甘草酸具有許多生物學和藥物學方面的作用，包括抗腫瘤、抗 發炎、抗病毒、和化學保護作用。本實驗室近五年來對甘草酸的一系列研究，我們已經 掌握了甘草酸在紫外線引起的病毒基因表達以及病毒複製的抑制作用的根本機制，另外 也掌握了，透過NF-kB 的抑制，甘草酸能對麩氨酸引起的神經細胞凋零有保護作用。 利用我們對甘草酸的根本機制所;瞭解的優勢, 我們擴大這些研究的發現，進一步探討甘 草酸在保護紫外線引起的皮膚老化和皮膚癌之防護作用的分子機制。為了增進甘草酸防 護效力，我們設計合成了15 種衍生物。為測試這些新化合物對紫外線引起的皮膚損害 所做的防護，以及研究其中的基本機制, 我們根據上述緣由和早先在甘草酸研究結果和 經驗，設計了三年的研究計畫。 我們的整體目標是： 1) 開發無毛天竺鼠模型模擬人的皮膚，以研究紫外線引起的皮膚損害。 2) 利用這個動物模型，依據甘草酸的基本化學結構為先導，去設計和研發新藥Project