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Fel Ursi is a dried product obtained from the gallbladder of Ursidae animals, such as Selenarctos thibetanus or Ursus arctos, through gallbladder surgery for bile drainage. It is one of the rare animal medicinal materials in China and is known for its therapeutic effects, including clearing heat, removing toxins, extinguishing wind, relieving spasms, clearing the liver, and improving vision. Research has also found that Fel Ursi has pharmacological effects against cardiovascular and cerebrovascular diseases, such as anti-inflammatory, anti-apoptotic, and antioxidant stress properties. Recently, numerous studies have confirmed the close relationship between cardiovascular and cerebrovascular diseases and the gut microbiota as well as gut metabolites. Fel Ursi contains bile acid components that may have bidirectional regulatory effects on the gut microbiota and gut metabolites. This aspect could represent a potential therapeutic pathway for Fel Ursi in the treatment of cardiovascular and cerebrovascular diseases. This article comprehensively summarized relevant literature in China and abroad, reviewed the research progress on the pharmacological effects of Fel Ursi against cardiovascular and cerebrovascular diseases, and explored the impact of Fel Ursi on gut microbiota and gut metabolites, thereby aiming to provide references for further in-depth research and clinical application of Fel Ursi.
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Animals , Cerebrovascular Disorders/drug therapy , Bile Acids and Salts , Lung , Liver , Ursidae , Cardiovascular Diseases/drug therapyABSTRACT
Objective To explore the effects of Hippo signaling on anti-oxidative stress of mouse marrow mesenchymal stem cells (mMSCs) in vitro. Methods mMSCs derived from C57BL/6 mice were identified using fluorescence-activated cell sorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. 2-deoxy-D-glucose (2-DG) or XMU-MP-1 was used to modulate Hippo signaling. Oxidative stress was induced by H2O2treatment and the effect of oxidative stress induced by H2O2on survival of mMSCs was evaluated using methyl thiazolyl tetrazolium (MTT) assay. The effect of oxidative stress induced by H2O2on Hippo signaling and the effect of Hippo signaling on capability of anti-oxidative stress of mMSCs were analyzed through apoptosis-regulated proteins (Bcl-2 and Bax) using Western Blot. Results Hippo signaling was activated by 2-DG in a concentration-dependent manner and the effect was most prominent by 5 mmol/L of 2-DG [compared with the blank control group, large tumor suppressor 1 (LATS1) protein (grey value): 2.33±0.25 vs. 0.98±0.03, phosphorylated Yes-associated protein (p-YAP)/YAP protein ratio (grey value): 2.30±0.35 vs. 1.01±0.05, 14-3-3 protein (grey value):2.19±0.40 vs. 0.99±0.04, all P < 0.05]; Hippo signaling was inhibited by 100 nmol/L of XMU-MP-1 [compared with the blank control group, LATS1 protein (grey value): 0.69±0.10 vs. 0.98±0.03, p-YAP/YAP protein ratio (grey value):0.65±0.06 vs. 1.01±0.05, 14-3-3 protein (grey value): 0.75±0.11 vs. 0.99±0.04, all P < 0.05]. Death of mMSCs was induced by H2O2in a concentration-dependent manner and the minimal effective concentration was 0.1 mmol/L [compared with the blank control group, survival rate of mMSCs: (81.25±11.85)% vs. (100.44±12.39)%, P < 0.05]. Inhibition of Hippo signaling was induced by H2O2in a concentration-dependent manner and the minimal effective concentration was also 0.1 mmol/L [compared with the blank control group, LATS1 protein (grey value): 0.75±0.06 vs. 1.01±0.09, p-YAP/YAP protein ratio (grey value): 0.69±0.05 vs. 0.98±0.05, both P < 0.05], those effects might associate with reduction of Bcl-2/Bax ratio (grey value: 0.48±0.18 vs. 1.06±0.09, P < 0.05). Compared with the treatment of 0.1 mmol/L of H2O2, activation of Hippo signaling by 5 mmol/L of 2-DG [ LATS1 protein (grey value):0.95±0.05 vs. 0.64±0.06, p-YAP/YAP protein ratio (grey value): 0.87±0.03 vs. 0.45±0.16, both P < 0.05] improved survival of mMSCs [(92.80±9.43)% vs. (75.47±9.43)%, P < 0.05] through an increase of Bcl-2/Bax ratio (grey value:1.14±0.16 vs. 0.77±0.12, P < 0.05); however, inhibition of Hippo signaling by 100 nmol/L of XMU-MP-1 [ LATS1 protein (grey value): 0.39±0.03 vs. 0.64±0.06, p-YAP/YAP protein ratio (grey value): 0.28±0.04 vs. 0.45±0.16, both P < 0.05] decreased survival of mMSCs [(57.54±4.59)% vs. (75.47±9.43)%, P < 0.05] through an decrease of Bcl-2/Bax ratio (grey value: 0.63±0.20 vs. 0.77±0.12, P < 0.05). Compared with normal lung tissue, acute respiratory distress syndrome (ARDS) lung tissue markedly activate Hippo signaling in mMSCs [LATS1 protein (grey value): 1.71± 0.08 vs. 1.00±0.10, p-YAP/YAP protein ratio (grey value): 2.46±0.39 vs. 1.01±0.04, 14-3-3 protein (grey value):2.27±0.52 vs. 1.01±0.08, all P < 0.05]. Conclusion Hippo signaling could affect survival and capability of anti-oxidative stress of mMSCs via modulation of Bcl-2/Bax ratio in vitro.
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Objective To investigate the changes of content or activity of Nrf2 and anti-oxidative stress-related factors in rat models of traumatic brain injury,and explore the mechanisms of protective effect of curcumin on brain damage and oxidative stress in rats. Methods Twenty healthy SPF male SD rats were divided into 4 groups: the control group, brain injury model group(TBI group),brain injury and solvent-treated group(TBI+S group),brain injury and curcumin-treated group(TBI+C group),5 rats ineach group. The control group received only saline and anesthesia. The TBI,TBI+S and TBI+C groups were given free falling body brain injury modeling device to establish the models and then received curcumin(5 mg/kg), an equal amount of DMSO solvent(0.05%)and an equal amount of physiological saline, respectively. The rats were sacrificed at the next day and the RNA and proteins of brain tissues were extracted. qRT-PCR and Western blot were used to detect the mRNA and protein expression of Nrf2. Chemocolorimetry was used to detect the content or activity of MDA, GSH, CAT and SOD in the brain tissues of rats. ELISA was used to detect the contents of iNOS and HO-1. Results Compared with the control group,the mRNA and protein expressions of Nrf2, the content of MDA,the activity of HO-1 and iNOS were significantly increased,the content of GSH, the activity of SOD and CAT were significantly decreased in the TBI group and TBI+S group,with a significant difference(P< 0.05). Compared with the TBI and TBI+S groups,the mRNA and protein expressions of Nrf2,the content of MDA,the activities of HO-1 and iNOS were significantly decreased,the content of GSH,the activity of SOD and CAT were significantly increased in the TBI+C group,showing a sigfnificant difference(P< 0.05),but there were no significant differences between the TBI group and TBI+S group(P< 0.05). Conclusions Curcumin has an anti-oxidative stress effect on rats with brain injury. It can reduce the expression of Nrf2,change the anti-oxidant stress-related indicators,therefore to protect the TBI-impaired brain tissues.
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<p><b>OBJECTIVE</b>To investigate the protective effect of monoside against triptolide-induced liver injury and explore its molecular mechanism.</p><p><b>METHODS</b>BALB/C mice treated with gastric lavage with triptolide and monoside, either alone or in combination, were examined for changes of hepatic biochemical parameters using the serological method. The growth inhibition rate of HepG2 cells treated with triptolide or monoside or both was assessed with MTT assay, and the cell morphological changes were observed using laser confocal microscopy; the expressions of the target proteins in the antioxidative stress pathway were detected using flow cytometry and Western blotting.</p><p><b>RESULTS</b>In BALB/C mice, gastric lavage of triptolide induced obvious hepatic damage. In HepG2 cells, treatment with triptolide significantly inhibited the cell growth, resulting in a cell viability as low as 72.83% at 24 h; triptolide also induced obvious cell apoptosis and cell nucleus deformation, causing an apoptosis rate of 43.1% in the cells at 24 h. Triptolide significantly reduced the expressions of Nrf2 and HO-1 proteins related with the oxidative stress pathway. Combined treatment with morroniside obviously reversed these changes, resulting in significantly decreased hepatic biochemical parameters and the liver index in BALB/C mice and in significantly lowered cell apoptosis rate, improved cell morphology, and increased Nrf2 and HO-1 protein expressions in HepG2 cells.</p><p><b>CONCLUSIONS</b>Monoside protects against triptolide-induced liver injury possibly by relieving oxidative stress.</p>
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Diabetic peripheral neuropathy (DPN) seriously affects the quality of life in patients with type 2 diabetes mellitus. This paper reviews the role of Chinese medicine in the main treatment goal of DPN, including protecting pancreatic β-cells, in the use of antioxidation therapy to delay disease progression, and in the endpoint of neural repair and regeneration. We propose that protecting the body from injury caused by high glucose and oxidative stress, and promoting repair and regeneration of nerves should be the research direction for the prevention and treatment of DPN.
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As an inhibitory amino acid similar to gama-aminobutyric acid,taurine can activate the corticostriatal pathway as an endogenous ligand for glycine receptors,establishing equilibrium between the excitatory and inhibitory processes in the brain.In mammalian brains,taurine concentrations increase during the developmental period of the brain until weaning,and subsequently decline reaching stable concentrations in adulthood.With abilities of anti-oxidative stress,anti-inflammatory and anti-apoptosis,taurine can improve the hypoxic-ischemic brain injury,promote the proliferation and differentiation of neurons and affect brain development,It needs more investigations to prove when and how taurine supplementation during gestation,baby,children or adult can assist the development of the brain and prevent the damage of the brain from hypoxic and ischemic damage.