Metabolomic profiling of Sansevieria trifasciata hort ex. Prain leaves and roots by HPLC-PAD-ESI/MS and its hepatoprotective effect via activation of the NRF2/ARE signaling pathway in an experimentally induced liver fibrosis rat model

Background: Type 2 Diabetes Mellitus (T2DM) is a world-wide metabolic disease with no cure from drugs and treatment. In China, The Traditional Chinese Medicine (TCM) herbal formulations have been used to treat T2DM for centuries. Methods: In this study, we proposed a formula called ShenQi Compound (SQC), which has been used in clinical therapeutics in China for several years. We evaluated the effect of SQC in a spontaneous diabetic rat model (GK rats) by detecting a series of blood indicators and performing histological observations. Meanwhile, the gene microarray and RT-qPCR experiments were used to explore the molecular mechanism of SQC treatment. In addition, western medicine, sitagliptin was employed as a comparison. Results: The results indicated that SQC and sitagliptin could effectively improve the serum lipid (blood Total Cholesterol (TC) and blood Triglycerides (TG)), hormone levels (serum insulin (INS), Glucagon (GC) and Glucagon-Like Peptide-1 (GLP-1)), alleviated the inflammatory response (hypersensitive C-Reactive Protein (hsCRP)), blood glucose fluctuation (Mean Blood Glucose (MBG), standard deviation of blood glucose (SDBG) and Largest Amplitude of plasma Glucose Excursions (LAGE)), pancreatic tissue damage and vascular injury for T2DM. Compared with sitagliptin, SQC achieved a better effect on blood glucose fluctuation (p<0.01). Meanwhile, the gene microarray and RT-qPCR experiments indicated that SQC and sitagliptin may improve the T2DM through affecting the biological functions related to apoptosis and circadian rhythm. Moreover, SQC might be able to influence the mTOR signaling pathway by regulating Pik3r1, Ddit4 expression. Conclusion: All these results indicate that SQC is an effective therapeutic drug on T2DM. Notably, SQC presents an obvious blood glucose fluctuation-preventing ability, which might be derived from the regulation of the mTOR signaling pathway.

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Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations

International Journal of Molecular Sciences ◽

10.3390/ijms22105055 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5055

Author(s):

Catalina Atorrasagasti ◽

Flavia Piccioni ◽

Sophia Borowski ◽

Irene Tirado-González ◽

Nancy Freitag ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Liver Fibrosis ◽

Signaling Pathway ◽

Liver Damage ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Nerve Growth ◽

Fibrotic Process ◽

Ngf Signaling

Liver fibrosis results from many chronic injuries and may often progress to cirrhosis and hepatocellular carcinoma (HCC). In fact, up to 90% of HCC arise in a cirrhotic liver. Conversely, stress is implicated in liver damage, worsening disease outcome. Hence, stress could play a role in disrupting liver homeostasis, a concept that has not been fully explored. Here, in a murine model of TAA-induced liver fibrosis we identified nerve growth factor (NGF) to be a crucial regulator of the stress-induced fibrogenesis signaling pathway as it activates its receptor p75 neurotrophin receptor (p75NTR), increasing liver damage. Additionally, blocking the NGF decreased liver fibrosis whereas treatment with recombinant NGF accelerated the fibrotic process to a similar extent than stress challenge. We further show that the fibrogenesis induced by stress is characterized by specific changes in the hepatoglycocode (increased β1,6GlcNAc-branched complex N-glycans and decreased core 1 O-glycans expression) which are also observed in patients with advanced fibrosis compared to patients with a low level of fibrosis. Our study facilitates an understanding of stress-induced liver injury and identify NGF signaling pathway in early stages of the disease, which contributes to the established fibrogenesis.

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Bevacizumab regulates inflammatory cytokines and inhibits VEGFR2 signaling pathway in an ovalbumin-induced rat model of airway hypersensitivity

Inflammopharmacology ◽

10.1007/s10787-021-00798-8 ◽

2021 ◽

Author(s):

Seyed Mohammadreza Bolandi ◽

Zohreh Abdolmaleki ◽

Mohammad-Ali Assarehzadegan

Keyword(s):

Signaling Pathway ◽

Inflammatory Cytokines ◽

Rat Model ◽

Vegfr2 Signaling ◽

Airway Hypersensitivity

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The calcimimetic R-568 attenuates subarachnoid hemorrhage-induced vasospasm through PI3K/Akt/eNOS signaling pathway in the rat model

Brain Research ◽

10.1016/j.brainres.2021.147508 ◽

2021 ◽

Vol 1765 ◽

pp. 147508

Author(s):

İlker Güleç ◽

Aslıhan Şengelen ◽

Feyza Karagöz-Güzey ◽

Evren Önay-Uçar ◽

Burak Eren ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Signaling Pathway ◽

Rat Model

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5-methoxytryptophan alleviates liver fibrosis by modulating FOXO3a/miR-21/ATG5 signaling pathway mediated autophagy

Cell Cycle ◽

10.1080/15384101.2021.1897241 ◽

2021 ◽

pp. 1-13

Author(s):

Ming Tong ◽

Qing Zheng ◽

Meng Liu ◽

Liang Chen ◽

Yi-He Lin ◽

...

Keyword(s):

Liver Fibrosis ◽

Signaling Pathway

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Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

Journal of International Medical Research ◽

10.1177/0300060521997590 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052199759

Author(s):

Jiajia Tian ◽

Yanyan Zhao ◽

Lingling Wang ◽

Lin Li

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Signaling Pathway ◽

Rat Model ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Primary Response ◽

Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

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