PHYTOTHERAPY RESEARCH
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2025
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IF 6.3
Li Li,Wenqian Cai,Hao Zhang,Jiuren Tang,Yongjie Yang,Yang Huang,Qing Xi,Rongxin Zhang
Renal fibrosis is the most common pathway for the development of end-stage renal disease (ESRD) in various kidney diseases. Currently, the treatment options for renal fibrosis are limited. Ferroptosis is iron-mediated lipid peroxidation, triggered mainly by iron deposition and ROS generation. Notably, the kidney is the most sensitive of all tissues to iron-dependent ferroptosis, and the inhibition of ferroptosis is an effective therapeutic strategy for the treatment of kidney fibrosis. Nonetheless, the pathways involved in ferroptosis in renal fibrosis are still unclear. Bergapten, a natural coumarin derivative, is mainly found in bergapten essential oil, grapefruit juice, and other commonly used plants, and it has various pharmacological effects. However, the role that ferroptosis plays in renal fibrosis and the potential therapeutic benefits of bergapten remain unclear. In this study, we investigated the therapeutic effects of bergapten on renal fibrosis and its mechanisms. We investigated the anti-fibrotic effects of bergapten in in vivo and in vitro models of renal fibrosis. Initially, network pharmacological analysis was employed to predict the potential therapeutic impact of bergapten on renal fibrosis. We then explored the potential therapeutic role of bergapten in obstructive nephropathy, which is due to unilateral ureteral obstruction (UUO). Furthermore, RNA-Seq was conducted to investigate the possible mechanism of bergapten against renal fibrosis. Additionally, Bergapten demonstrated a significant improvement in TGF-β1-induced fibrosis and RSL3-induced renal tubular epithelial cell ferroptosis; these findings are consistent with those of the in vivo studies. Our findings indicate that bergapten is a potential treatment for renal fibrosis. Treatment with bergapten significantly reduced the expression of fibronectin and α-SMA in the damaged kidneys of UUO mice, thereby improving fibrosis. Meanwhile, bergapten protected against fibrosis caused by TGF-β1 and ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibitor RSL3. Significantly, bergapten therapy alleviated renal fibrosis by modulating ferroptosis. We found that bergapten inhibited PI3K phosphorylation and indirectly restored GPX4 expression. In conclusion, we have revealed the nephroprotective effect of bergapten, whose mechanism of action is related to the inhibition of ferroptosis, and it is expected that it will be developed as a therapeutic agent for the treatment of renal fibrosis. This study aims to explore the effect of bergapten on renal fibrosis ferroptosis. Collectively, these results demonstrate that bergapten is an inhibitor of ferroptosis and provides a new treatment strategy for diseases associated with ferroptosis.
研究领域:
肾病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2025
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IF 1.3
Hao-Nan Ding,Xu-Wen Wang,Yu-Xin Qian,Ke Liu,Lei Jin
Bergapten is a natural compound with the potential to regenerate bone. However, its poor solubility and instability hinder its clinical use. We developed bergapten-loaded long-circulating liposomes (BP-LCL) to overcome these challenges. The liposomes were spherical, stable, and highly effective at delivering bergapten. We found that BP-LCL were biocompatible and enhanced the osteogenic differentiation of human dental pulp stem cells. It did this by increasing key markers like RUNX2, COL1, and OCN, and by activating the Wnt/β-catenin signaling pathway. This study suggested that BP-LCL could be a promising new approach for bone regeneration settings.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Gao Chong,Hu Zhong-He,Cui Zhen-Yu,Jiang Yu-Chen,Dou Jia-Yi,Li Zhao-Xu,Lian Li-Hua,Nan Ji-Xing,Wu Yan-Ling
Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl 4 ) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl 4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-β (TGF-β) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl 4 -induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1β, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl 4 -induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1β expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1β expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
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IF 5.6
Jia Xu,Quan Zhou,Pengjiao Hou,Yu Wang,Peiwu Geng,Zebei Lu,Yunfang Zhou,Dapeng Dai,Shuanghu Wang
Macitentan was approved by the United States Food and Drug Administration (FDA) in 2013 for the treatment of pulmonary arterial hypertension (PAH). Bergapten is a furanocoumarin that is abundant in Umbelliferae and Rutaceae plants and is widely used in many Chinese medicine prescriptions. Considering the possible combination of these two compounds, this study is aimed to investigate the effects of bergapten on the pharmacokinetics of macitentan both in vitro and in vivo . Rat liver microsomes (RLMs), human liver microsomes (HLMs), and recombinant human CYP3A4 (rCYP3A4) were used to investigate the inhibitory effects and mechanisms of bergapten on macitentan in vitro . In addition, pharmacokinetic parameters were also studied in vivo . Rats were randomly divided into two groups (six rats per group), with or without bergapten (10 mg/kg), and pretreated for 7 days. An oral dose of 20 mg/kg macitentan was administered to each group 30 min after bergapten or 0.5% CMC-Na administration on day 7. Blood was collected from the tail veins, and the plasma concentrations of macitentan and its metabolites were assessed by ultra-performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Finally, we analyzed the binding force of the enzyme and two small ligands by in silico molecular docking to verify the inhibitory effects of bergapten on macitentan. The in vitro results revealed that the IC 50 values for RLMs, HLMs, and rCYP3A4 were 3.84, 17.82 and 12.81 μM, respectively. In vivo pharmacokinetic experiments showed that the AUC (0-t) , AUC (0-∞) , and C max of macitentan in the experimental group (20,263.67 μg/L*h, 20,378.31 μg/L*h and 2,999.69 μg/L, respectively) increased significantly compared with the control group (7,873.97 μg/L*h, 7,897.83 μg/L*h and 1,339.44 μg/L, respectively), while the CL z /F (1.07 L/h/kg) of macitentan and the metabolite-parent ratio (MR) displayed a significant decrease. Bergapten competitively inhibited macitentan metabolism in vitro and altered its pharmacokinetic characteristics in vivo . Further molecular docking analysis was also consistent with the experimental results. This study provides a reference for the combined use of bergapten and macitentan in clinical practice.
研究领域:
药理学
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药剂学
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药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
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IF 2.956
Yi Zhou,Jing Wang,Weidong Yang,Xiaowen Qi,Lei Lan,Lan Luo,Zhimin Yin
Bergapten (BG) is a cumarine-derivate compound in many medicinal plants . Here, in vitro and in vivo experimental results indicated that BG possesses anti-inflammatory properties, Based on this, we further investigated the precise molecular mechanisms of BG in LPS-stimulated inflammation response . Studies revealed that BG inhibited LPS-stimulated productions of TNF-α, IL-1β, IL-6, PGE2 and NO as well as the expression of iNOS and COX-2, and at the same time, it increased LPS-induced release of IL-10 in a dose-dependent manner in RAW264.7 cells. Mechanistically, BG suppressed the activations of JAK/STAT, but not that of MAPKs and NF-κB. In addition, BG, as an antioxidant, prevented the accumulation of ROS , which further exerted its anti-inflammatory function. In vivo researches revealed that BG decreased LPS-induced mortality in mice. In conclusions, BG may be a potential candidate for inflammation therapy via inhibiting JAK/STAT activation and ROS production in RAW264.7 cells.
研究领域:
药理学
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免疫学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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