Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catalpol and puerarin are two monomers of Rehmannia glutinosa and Lobed Kudzuvine Root, which are two herbs commonly used together in ancient prescriptions of traditional Chinese medicine for cerebral ischemia. Our previous study shows that the lyophilized powder of the two monomers improved the outcome of cerebral ischemia excellently in rodents. However, if it protects vessels from ischemia is unknown. The present research studied the protection of lyophilized powder of catalpol and puerarin (CP) on endothelial cells and the relative mechanism in vivo and in vitro. Middle cerebral artery occlusion (MCAO) rats were used to study the improvement of CP on neurological deficiency, regional cerebral blood flow (rCBF), and infarct volume. The morphology of vessels and the apoptosis of brain vascular endothelial cells (BVECs) were observed and detected by immunohistochemistry approaches. To study how CP protected primary BVECs (pBVECs) from ischemic penumbra, oxygen glucose deprivation (OGD)-damaged pBVECs were cultured in the condition of insufficient nutrition and low oxygen which recapitulate the low perfusion of ischemic penumbra. Using the cell model, the mechanism by which CP protected pBVECs was studied by shRNA and pathway inhibitors. CP at the dose of 65.4 mg/kg increased regional cerebral blood flow (rCBF), reduced infarct volume, protected vessel integrity and inhibited endothelial cell apoptosis in vivo. But it only improved rCBF, vessel integrity and BVECs apoptosis at the dose of 32.7 mg/kg. In vitro, the protection of CP on pBVECs was proved to be ERK/HIF-1a- and PI3K/AKT/mTOR/HIF-1a-dependent. This study indicates a possibility of CP being a new drug for cerebral ischemia. Besides, this research provides an alternative cell model for penumbra ECs study.
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PMID:Lyophilized Powder of Catalpol and Puerarin Protected Cerebral Vessels from Ischemia by Its Anti-apoptosis on Endothelial Cells. 2836 97

Aim: This study aimed to investigate the effects of catalpol on sciatic nerve crush injury (SNCI) and further explore the role of Akt/mTOR pathway in its pharmacological efficacy. Methods: Mice with SNCI in the right were treated with catalpol. Rapamycin was used to block mTOR signal activation. After sciatic motor nerve function was observed, the gastrocnemius muscles, injury sciatic nerve and spinal cord L4-L6 were isolated. TUNEL staining was done to assess the neuronal apoptosis; Transmission electron microscopy (TEM) was performed to observe the microstructure of regenerated myelinated nerve fibers. The expression of proteins in Akt/mTOR pathway, those related to axon regeneration and cell apoptosis was detected by Western blotting. Brain derived neurotrophic factor (BDNF), phosphatase and tensin homolog deleted on chromosome ten (PTEN), growth associated protein-43 (GAP-43), pro- and anti-apoptosis protein including Bax and BCL-2. Results: Catalpol significantly improved the function of injured sciatic motor nerve and facilitated the sciatic motor and sensory nerve fiber growth and the reinnervation of gastrocnemius muscles. TEM showed catalpol increased the density and thickness of regenerated myelinated nerve fibers, which exhibited a regular arrangement. Catalpol significantly reduced the number of apoptotic cells and increased the Bcl-2/Bax ratio in the L4-L6 spinal cord anterior horn. Importantly, catalpol significantly increased the expression of p-Akt, p-mTOR, p-p70S6K, GAP-43 and BDNF, but decreased PTEN expression. Blockade of mTOR activation was partially abrogated by catalpol. Conclusion: Catalpol may improve SCNI by enhancing the axonal growth via activating the Akt/mTOR pathway and modulating BDNF and PTEN expression.
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PMID:Catalpol improves axonal outgrowth and reinnervation of injured sciatic nerve by activating Akt/mTOR pathway and regulating BDNF and PTEN expression. 3097 64

Catalpol, an iridoid glycoside extracted from Rehmannia glutinosa, has been found to ameliorate diabetic nephropathy (DN), but the mechanism has not been clarified. Podocyte injury play a key role in the pathogenesis of DN. This study mainly investigated the protective effect and potential mechanism of catalpol on podocyte injury of DN in vivo and in vitro. The results indicated that the pathological features of DN in mice were markedly ameliorated after treatment with catalpol. Moreover, podocyte foot process effacement, and down-regulation of nephrin and synaptopodin expression in DN mice were also significantly improved after treatment with catalpol. In vitro, catalpol rescued disrupted cytoskeleton and increased migration ratio in podocytes induced by high glucose, the effect might be attributable to the inhibition of RhoA and Cdc42 activities but not Rac1. Furthermore, the impaired podocyte autophagy in DN mice was significantly enhanced after catalpol treatment. And catalpol also enhanced autophagy and lysosome biogenesis in cultured podocytes under high glucose condition. In addition, we found that catalpol could inhibit mTOR activity and promote TFEB nuclear translocation in vivo and in vitro experiments. Our study demonstrated that catalpol could ameliorate podocyte injury in DN, and the protective effect of catalpol might be attributed to the stabilization of podocyte cytoskeleton and the improvement of impaired podocyte autophagy.
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PMID:Catalpol Ameliorates Podocyte Injury by Stabilizing Cytoskeleton and Enhancing Autophagy in Diabetic Nephropathy. 3192 Jun 63

Disrupted follicular development may result in increased follicular atresia, which is a crucial mechanism of various ovarian pathologies. It has been demonstrated that oxidative stress is associated with disrupted follicular development. Catalpol is a natural compound that has been found to possess antioxidative stress. However, the effects of catalpol on oxidative stress-induced disrupted follicular development remain unclear. In the present study, we evaluated the protective effect of catalpol on hydrogen peroxide (H2O2)-induced oxidative damage in granulosa cells (GCs), which play crucial roles in the follicular development. Our results showed that catalpol significantly improved cell viability, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) production, and elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in H2O2-induced GCs. Catalpol treatment caused significant increase in bcl-2 expression, and decreases in bax and caspase-9 expressions. Compared with the H2O2-induced GCs, caspase-3 activity in catalpol-treated cells was markedly decreased. Furthermore, catalpol caused significant activation of PI3K/Akt/mTOR pathway in GCs in response to H2O2 stimulation. Additionally, inhibition of this pathway reversed the inhibitory effects of catalpol on H2O2-induced oxidative injury and apoptosis in GCs. In conclusion, these findings suggested that catalpol protected GCs from H2O2-induced oxidative injury and apoptosis via activating PI3K/Akt/mTOR signaling pathway. Thus, catalpol might serve as a therapeutic approach for regulating disrupted follicular development.
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PMID:Catalpol protects rat ovarian granulosa cells against oxidative stress and apoptosis through modulating the PI3K/Akt/mTOR signaling pathway. 3222 25