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RhoA/ROCK通路
FITOTERAPIA · 2025 · IF 2.6

Integrating LC-MS and molecular docking technology to investigate the effect of Spatholobi caulis flavonoids in alleviating primary dysmenorrhea via regulating the RhoA/ROCK pathway

Xuan Zhang,Jie Weng,Yi Luo,Hongcun Liu,Jing Yan,Zhiqiang Gong,Chaonan Kong,Xue Li,Lifang Yang,Mingguo Jiang

To elucidate the efficacy and potential molecular mechanisms underlying the therapeutic effects of Spatholobi Caulis flavonoids (SCF) in the treatment of primary dysmenorrhea (PD). The present study established oxytocin-induced uterine contractions in vitro and a model of PD in rats evoked by estradiol benzoate and oxytocin. The uterine contraction experiments demonstrated that SCF significantly inhibited uterine smooth muscle tone by 62.07 %. SCF effectively attenuated the torsional response in PD rats, normalised the PGF2α/PGE2 ratio, and reduced NO and Ca 2+ levels. The constituents of SCF were evaluated by using a Liquid Chromatograph Mass Spectrometer(LC-MS) method, and 11 flavonoid components were preliminarily deduced. Network pharmacology and molecular docking (MD) techniques were used to predict therapeutic targets, with the former suggesting key targets such as RhoA, VEGFA, and PIK3CA, while the latter indicated that 10 compounds had a strong binding affinity for RhoA. The expression of CALM, RhoA, ROCK1, PIK3CA, and AKT was down-regulated at both the protein and mRNA levels. Additionally, the expression levels of genes associated with VEGFA, IP3R, MLCK and NOS3 were found to be regulated. The collective evidence from this study suggests that SCF may attenuate uterine spasm by inhibiting the RhoA/ROCK signaling pathway, decreasing the levels of PGF2α, NO and Ca 2+ , and increasing the content of PGE2. This study provides a theoretical basis for the application of SCF in the treatment of PD.

研究领域: 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Deoxynivalenol Induces Intestinal Epithelial Barrier Damage through RhoA/ROCK Pathway-Mediated Apoptosis and F-Actin-Associated Tight Junction Disruption

Chenjiao Miao,Zuoyao Wu,Yafei Sun,Zheng Cao

Deoxynivalenol (DON) poses a serious global food safety risk due to its high toxicity and contamination rate. It disrupts the intestinal epithelial barrier, allowing exogenous toxins to enter the circulation and resulting in sepsis and systemic toxicity. In this research, 32 male Kunming mice and Porcine Small Intestinal Epithelial (IPEC-J2) cells were treated with DON at 0–4.8 mg/kg (7 d) and 0–12 μM (24 h), respectively. Histopathological results revealed that DON disrupted the intestinal epithelial barrier, causing apoptosis and tight junction (TJ) injury. Immunofluorescence and protein expression results showed that DON-induced p53-dependent mitochondrial pathway apoptosis and fibrillar actin (F-actin)-associated TJ injury and that the RhoA/ROCK pathway were activated in mice jejunal tissue and IPEC-J2 cells. Pretreatment with RhoA or ROCK inhibitors (Rosin or Y-27632) maintained DON-induced apoptosis and F-actin-associated TJ injury in IPEC-J2 cells. Thus, DON induces damage to the intestinal epithelial barrier through the RhoA/ROCK pathway-mediated apoptosis and F-actin-associated TJ disruption.

CAS / MDL:
研究领域: 毒理学 · 细胞生物学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Oral Acid-Activated Hydrogen-Producing Nanoparticles Reduce Aortic Dissection Progression via RhoA/ROCK Inhibition in Mice

Longwu Xu,Lin Ma,Xiufeng Xu,Yifan Wang,Qiuhong Jiao,Shulan Pang,Yuying Wang,Weiwei Yang,Shuai Mao,Yudan Zhao,Jie Hao,Tao Huang,Peikang Dong,Yingshuai Wang,Tao Wang

Aortic dissection (AD) is a life-threatening condition with a high mortality rate. Oxidative stress and endothelial and vascular smooth muscle cell migration contribute to AD pathogenesis. Herein, we investigated the therapeutic potential of hydrogen (H2), delivered via magnesium diboride nanosheets (MBNs), in a murine model of β-aminopropionitrile-induced AD. This treatment significantly improved survival rate and reduced AD progression, as evidenced by improved aortic wall structure and reduced false lumen formation. Transcriptomic analysis indicated modulation of the RhoA/ROCK pathway, confirmed using Western blotting, immunohistochemistry, and immunofluorescence, which showed significant downregulation of RhoA and ROCK2 after 28 days of treatment (P < 0.05). These findings suggest that hydrogen released from MBNs attenuates AD progression through reactive oxygen species scavenging and RhoA/ROCK pathway inhibition.

CAS / MDL: 2079-89-2
研究领域: 医学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Biomaterials Science & Engineering · 2024 · IF 5.4

Aligned Nanofibers Promote Myoblast Polarization and Myogenesis through Activating Rac-Related Signaling Pathways

Xiangyu Dong,Shan Su,Qian Sun,Peng Wang,Qian Hu,Qiang Wei

The extracellular matrix (ECM) plays a crucial role in regulating cellular behaviors and functions. However, the impact of ECM topography on muscle cell adhesion and differentiation remains poorly understood from a mechanosensing perspective. In this study, we fabricated aligned and random electrospun polycaprolactone (PCL) nanofibers to mimic the structural characteristics of ECM. Mechanism investigations revealed that the orientation of nanofibers promoted C2C12 polarization and myogenesis through Rac-related signaling pathways. Conversely, cells cultured on random fibers exhibited spreading behavior mediated by RhoA/ROCK pathways, resulting in enhanced stress fiber formation but reduced capacity for myogenic differentiation. Our findings highlight the critical role of an ECM structure in muscle regeneration and damage repair, providing novel insights into mechanosensing mechanisms underlying muscle injury diseases.

研究领域: 生物医学工程 · 细胞生物学 · 组织工程 · 再生医学
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