Department and Institute of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biomed Pharmacother. 2024 Feb;171:116101. doi: 10.1016/j.biopha.2023.116101. Epub 2024 Jan 15.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood.
A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms.
In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-β/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-β.
In general, ALP may exert therapeutic effects on pulmonary fibrosis by modulating the differentiation, proliferation, and apoptosis of fibroblasts. Although its safety has been demonstrated in mice, further studies are required to investigate the efficacy of ALP in treatment of patients with IPF.
特发性肺纤维化（IPF）是一种进行性和不可逆转的间质性肺疾病，预后不良。山奈素（ALP）来源于益智，已显示出作为各种疾病治疗措施的潜力。然而，ALP 用于治疗肺纤维化及其潜在机制仍不完全清楚。
本研究采用博来霉素（BLM）诱导的肺纤维化小鼠模型。研究了 ALP 对组织病理学表现和纤维化标志物表达水平的抗纤维化作用。随后，研究了 ALP 对成纤维细胞分化、增殖、凋亡和相关信号通路的影响，以阐明其潜在机制。
本研究观察到 ALP 可有效减轻 BLM 诱导的小鼠肺纤维化，表现在组织病理学表现和纤维化标志物的表达水平上。此外，体外实验表明，ALP 处理可减弱成纤维细胞向肌成纤维细胞分化的能力。在机制上，我们的研究结果表明，ALP 通过抑制 TGF-β/ALK5/Smad 信号通路抑制成纤维细胞向肌成纤维细胞的分化。ALP 被发现具有抑制 TGF-β诱导的成纤维细胞增殖和促进其凋亡的能力。
总的来说，ALP 通过调节成纤维细胞的分化、增殖和凋亡，可能对肺纤维化发挥治疗作用。尽管其在小鼠中的安全性已得到证实，但仍需要进一步研究 ALP 治疗 IPF 患者的疗效。
