Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. AIM OF THE STUDY: To explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. MATERIAL AND METHODS: 75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. RESULTS: TJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. CONCLUSION: According to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.

Ginsenoside ompound K reduces neuronal damage and improves neuronal synaptic dysfunction by targeting Aß.

Background: Alzheimer's disease (AD) is the most common neurodegenerative condition worldwide, with amyloid ß (Aß) fibrils presenting as its main pathological feature. This study investigated whether Ginsenoside Compound K (CK) has activity against Aß and its mechanism in reducing synaptic damage and cognitive impairment. Methods: The binding capacity of CK to Aß42 and Nrf2/Keap1 was determined using molecular docking. Transmission electron microscopy was used to monitor CK-mediated degradation of Aß fibrils. The effect of CK on the survival of Aß42-damaged HT22 cells was determined using a CCK-8 assay. The therapeutic efficacy of CK in a scopoletin hydrobromide (SCOP) induced cognitive dysfunction mouse model was measured using a step-down passive avoidance test. GO enrichment analysis of mouse brain tissue was peformed using Genechip. Hydroxyl radical scavenging and reactive oxygen species assays were performed to verify the antioxidant activity of CK. The effects of CK on the expression of Aß42, the Nrf2/Keap1 signaling pathway, and other proteins were determined by western blotting, immunofluorescence, and immunohistochemistry. Results: Molecular docking results showed that CK interacts with Lys16 and Glu3 of Aß42. CK reduced the aggregation of Aß42 as observed using transmission electron microscopy. CK increased the level of insulin-degrading enzyme and decreased the levels ß-secretase and γ-secretase; therefore, it can potentially inhibit the accumulation of Aß in neuronal extracellular space in vivo. CK improved cognitive impairment and increased postsynaptic density protein 95 and synaptophysin expression levels in mice with SCOP-induced cognitive dysfunction. Further, CK inhibited the expression of cytochrome C, Caspase-3, and cleaved Caspase-3. Based on Genechip data, CK was found to regulate molecular functions such as oxygen binding, peroxidase activity, hemoglobin binding, and oxidoreductase activity, thus affecting the production of oxidative free radicals in neurons. Further, CK regulated the expression of the Nrf2/Keap1 signaling pathway through its interaction with the Nrf2/Keap1 complex. Conclusion: Our findings show that CK regulates the balance between Aß monomers production and clearance, CK binds to Aß monomer to inhibits the accumulation of Aß, increases the level of Nrf2 in neuronal nuclei, reduces oxidative damage of neurons, improves synaptic function, thus ultimately protecting neurons.

Biomechanical study of the male lower urinary tract: Simulation of internal and external sphincters dyssynergia.

Urethral sphincter dysfunction is an important cause of stress urinary incontinence (SUI). The most effective treatment is the insertion of an artificial urethral sphincter (AUS), which relies to a large extent on the surgeon's experience. However, there is no quantitative standard for cuff tightness, resulting in frequent postoperative complications. This study aimed to investigate the effect of internal and external sphincter dyssynergia on urodynamic parameters in the lower urinary tract. A geometric model of male lower urinary tract tissue was constructed from collodion slices, accounting for the active behavior of the internal and external sphincters. Normal and dyssynergic internal and external sphincters (active sphincter behavior was individually injured by 25%, 50%, 75%, or 100%) were simulated with fluid-structure interactions and changes in urethral stress, displacement, and urine flow rate were detected. We found that when the internal sphincter was injured by 25%, 50%, 75%, and 100%, urethral stress near the internal sphincter decreased by 8.3%, 15.6%, 24.3%, and 35.7%, respectively. Additionally, when the external sphincter was injured by 25%, 50%, 75%, and 100%, urethral stress near the external sphincter was reduced by 13.3%, 24.3%, 38.6%, and 46.6%, respectively. Internal sphincter injury primarily affects positions near the internal sphincter and prostate, while external sphincter injury affects the area between the prostate and urethral outlet. These data could facilitate the standardized evaluation of internal and external sphincter dysfunction and lead to novel methods of preoperative assessment for AUS surgery.

Huangqi Shengmai Yin Ameliorates Myocardial Fibrosis by Activating Sirtuin3 and Inhibiting TGF-ß/Smad Pathway.

Myocardial fibrosis (MF) is an important pathological process in which a variety of cardiovascular diseases transform into heart failure. The main manifestation of MF is the excessive deposition of collagen in the myocardium. Here, we explored whether Huangqi Shengmai Yin (HSY) can inhibit isoprenaline (ISO)-induced myocardial collagen deposition in rats, thereby reducing the cardiac dysfunction caused by MF. The results of echocardiography showed that HSY upregulated fractional shortening and ejection fraction, and reduced the left ventricular systolic dysfunction in the rats with MF. Pathological results showed that HSY protected myocardium, inhibited apoptosis, and effectively reduced collagen deposition. HSY also inhibited the expression of collagen I and III and α-smooth muscle actin (α-SMA) in the heart tissue. HSY increased the expression of Sirtuin 3 (Sirt3) and inhibited the protein levels of the components in the transforming growth factor-ß (TGF-ß)/Smad pathway. At the same time, it also regulated the expression of related proteins in the matrix metalloproteinases family. In summary, HSY played a therapeutic role in rats with ISO-induced MF by protecting myocardium and inhibiting collagen deposition. Therefore, HSY is a potential therapeutic agent for ameliorating MF.

Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism.

Diabetic cardiomyopathy (DCM) is one of the many complications of diabetes. DCM leads to cardiac insufficiency and myocardial remodeling and is the main cause of death in diabetic patients. Abnormal lipid metabolism plays an important role in the occurrence and development of DCM. Huangqi Shengmai Yin (HSY) has previously been shown to alleviate signs of heart disease. Here, we investigated whether HSY could improve cardiomyopathy caused by type 1 diabetes mellitus (T1DM) and improve abnormal lipid metabolism in the diabetic heart. Streptozotocin (STZ) was used to establish the T1DM mouse model, and T1DM mice were subsequently treated with HSY for eight weeks. The changes in the cardiac conduction system, histopathology, blood myocardial injury indices, and lipid content and expression of proteins related to lipid metabolism were evaluated. Our results showed that HSY could improve electrocardiogram; decrease the serum levels of CK-MB, LDH, and BNP; alleviate histopathological changes in cardiac tissue; and decrease myocardial lipid content in T1DM mice. These results indicate that HSY has a protective effect against T1DM-induced myocardial injury in mice and that this effect may be related to the improvement in myocardial lipid metabolism.

Ginsenoside compound K ameliorates Alzheimer's disease in HT22 cells by adjusting energy metabolism.

Energy metabolism disorders have been shown to exert detrimental effects on the pathology of Alzheimer's disease (AD). The ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has an ameliorating effect against AD, but the relevant molecular mechanism remains unclear. We hypothesized that the improvement of AD by CK is mediated by the energy metabolism signaling pathway induced by amyloid ß peptide (Aß) and tested this hypothesis in HT22 cells. HT22 cells were incubated with CK and exposed to Aß. Cell viability was analyzed using the MTT assay. Cell growth curves were derived from real-time cell analysis. Apoptosis was determined by flow cytometry, Aß localization and expression by immunofluorescence, and ATP content by a specific assay kit. The expression of proteins related to the energy metabolism signaling pathway was analyzed using Western blotting. CK treatment improved cell viability, cell growth, and apoptosis induced by Aß, and the cellular localization and expression of Aß. Moreover, CK increased ATP content by promoting the activity of glucose transporters (GLUTs). Therefore, the neuroprotective effect of CK against Aß injury was mainly realized through the activation of the energy metabolism signaling pathway. CK treatment inhibits neuronal damage caused by Aß through the activation of the energy metabolism signaling pathway, revealing that CK might be one of the key bioactive ingredients of ginseng in the treatment of Alzheimer's disease and may serve as a preventive or therapeutic agent for Alzheimer's disease.