Department of Emergency, Yan'an Hospital of Kunming City, Panlong District, 245 Renmin East Road, Kunming, 650051, China.
Department of Emergency, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wu Hua District, Kunming, 650032, China.
BMC Complement Med Ther. 2020 Mar 17;20(1):88. doi: 10.1186/s12906-020-2873-1.
Sedum sarmentosum is traditionally used to treat various inflammatory diseases in China. It has protective effects against acute liver injury, but the exact mechanism of such effects remains unclear. This study investigated the protective effects of S. sarmentosum extract on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury in mice and the mechanism of such effects.
Mice were randomly divided into control, treatment, model, and model treatment groups. Acute liver injury was induced in model mice via intraperitoneal injection of LPS and D-GalN with doses of 10 μg/kg of LPS and 500 mg/kg, respectively. The mRNA expression levels of miR-124, Hedgehog, Patched (Ptch), Smoothened (Smo), and glioma-associated oncogene homolog (Gli) in liver tissues were determined through RT-PCR, and the protein levels of Hedgehog, Ptch, Smo, Gli, P13k, Akt, HMGB1, TLR4, IkB-α, p-IkB-α, and NF-kB65 were evaluated via Western blot analysis. The serum levels of IL-6, TNF-α, CRP, IL-12, and ICAM-1 were determined via ELISA. TLR4 and NF-κBp65 activity and the levels of DNA-bound NF-KB65 and TLR4 in LPS/D-GalN-induced liver tissues were also determined. We recorded the time of death, plotted the survival curve, and calculated the liver index. We then observed the pathological changes in liver tissue and detected the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) in the serum and myeloperoxidase (MPO) and plasma inflammatory factors in the liver homogenate. Afterward, we evaluated the protective effects of S. sarmentosum extracts on acute liver injury in mice.
Results showed that after S. sarmentosum extract was administered, the expression level of miR-124 increased in liver tissues. However, the protein expression levels of Hedgehog, Ptch, Smo, Gli, P13k, p-Akt, HMGB1, TLR4, p-IκB-α, and NF-κB65 and the mRNA expression levels of Hedgehog, Ptch, Smo, and Gli decreased. The MPO level in the liver, the IL-6, TNF-α, CRP, IL-12, and MMP-9 levels in the plasma, and the serum ALT and AST levels also decreased, thereby reducing LPS/D-GalN-induced liver injury and improving the survival rate of liver-damaged animals within 24 h.
S. sarmentosum extract can alleviate LPS/D-GalN-induced acute liver injury in mice and improve the survival rate of mice. The mechanism may be related to the increase in miR-124 expression, decrease in Hedgehog and HMGB1 signaling pathway activities, and reduction in inflammatory responses in the liver. Hedgehog is a regulatory target for miR-124.
景天三七常用于中国治疗各种炎症性疾病。它对急性肝损伤有保护作用，但确切的作用机制尚不清楚。本研究探讨了景天三七提取物对脂多糖（LPS）/D-半乳糖胺（D-GalN）诱导的小鼠急性肝损伤的保护作用及其作用机制。
将小鼠随机分为对照组、治疗组、模型组和模型治疗组。通过腹腔注射 LPS 和 D-GalN 诱导模型小鼠急性肝损伤，剂量分别为 10μg/kg LPS 和 500mg/kg D-GalN。通过 RT-PCR 测定肝组织中 miR-124、Hedgehog、Patched（Ptch）、Smoothened（Smo）和 Glioma-associated oncogene homolog（Gli）的 mRNA 表达水平，通过 Western blot 分析测定 Hedgehog、Ptch、Smo、Gli、P13k、Akt、HMGB1、TLR4、IkB-α、p-IkB-α和 NF-κB65 的蛋白水平。通过 ELISA 测定血清中 IL-6、TNF-α、CRP、IL-12 和 ICAM-1 的水平。还测定了 LPS/D-GalN 诱导的肝组织中 TLR4 和 NF-κBp65 活性以及 DNA 结合的 NF-KB65 和 TLR4 的水平。我们记录了死亡时间，绘制了生存曲线，并计算了肝指数。然后观察肝组织的病理变化，检测血清中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）和肝匀浆中髓过氧化物酶（MPO）和血浆炎症因子的水平。然后，我们评估了景天三七提取物对小鼠急性肝损伤的保护作用。
结果表明，给予景天三七提取物后，肝组织中 miR-124 的表达水平增加。然而，Hedgehog、Ptch、Smo、Gli、P13k、p-Akt、HMGB1、TLR4、p-IκB-α和 NF-κB65 的蛋白表达水平以及 Hedgehog、Ptch、Smo 和 Gli 的 mRNA 表达水平均降低。肝组织中 MPO 水平、血浆中 IL-6、TNF-α、CRP、IL-12 和 MMP-9 水平以及血清 ALT 和 AST 水平均降低，从而减轻 LPS/D-GalN 诱导的肝损伤，提高 24 小时内肝损伤动物的存活率。
景天三七提取物可减轻 LPS/D-GalN 诱导的小鼠急性肝损伤，提高小鼠存活率。其机制可能与 miR-124 表达增加、Hedgehog 和 HMGB1 信号通路活性降低以及肝脏炎症反应减轻有关。Hedgehog 是 miR-124 的调节靶点。
