Yinchen gongying decoction mitigates CCl4-induced chronic liver injury and fibrosis in mice implicated in inhibition of the FoxO1/TGF-ß1/ Smad2/3 and YAP signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to assess the impact of YGD on a carbon tetrachloride (CCl4) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis. MATERIALS AND METHODS: LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl4-induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation. RESULTS: YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl4-induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-ß1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. CONCLUSION: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-ß1/Smad2/3 and YAP signal pathways.

Pseudoginsenoside-F11 ameliorates okadiac acid-induced learning and memory impairment in rats via modulating protein phosphatase 2A.

We have reported that pseudoginsenoside-F11 (PF11) can significantly improve the cognitive impairments in several Alzheimer's disease (AD) models, but the mechanism has not been fully elucidated. In the present study, the effects of PF11 on AD, in particular the underlying mechanisms related with protein phosphatase 2A (PP2A), were investigated in a rat model induced by okadaic acid (OA), a selective inhibitor of PP2A. The results showed that PF11 treatment dose-dependently improved the learning and memory impairments in OA-induced AD rats. PF11 could significantly inhibit OA-induced tau hyperphosphorylation, suppress the activation of glial cells, alleviate neuroinflammation, thus rescue the neuronal and synaptic damage. Further investigation revealed that PF11 could regulate the protein expression of methyl modifying enzymes (leucine carboxyl methyltransferase-1 and protein phosphatase methylesterase-1) in the brain, thus increase methyl-PP2A protein expression and indirectly increase the activity of PP2A. Molecular docking analysis, structural alignment and in vitro results showed that PF11 was similar in the shape and electrostatic field feature to a known activator of PP2A, and could directly bind and activate PP2A. In conclusion, the present data indicate that PF11 can ameliorate OA-induced learning and memory impairment in rats via modulating PP2A.

Buckwheat Rutin Inhibits AngII-induced Cardiomyocyte Hypertrophy via Blockade of CaN-dependent Signal Pathway.

Buckwheat rutin has been found to be able to inhibit angiotensin II (AngII) - induced hypertrophy in cultured neonatal rat cardiomyocytes, but the mechanism remains uncertain. In this study, myocardial hypertrophy model was made by adding AngII to the medium of cardiac myocytes of neonatal rats; meanwhile, different concentrations of buckwheat rutin were applied to observe their effects. Intracellular Ca(2+) level was detected by Hitachi - 850 fluorospectrophotometer, calcineurin (CaN) activity was measured by colorimetric method, the expression of CaN protein was observed with immunocytochemistry, and the proto - oncogene c - fos mRNA expression was assessed with reverse transcription polymerase chain reaction (RT - PCR). Compared with control group, AngII could greatly stimulate the increase of intracellular Ca(2+) level, the activities and protein expression of cardiomyocytes CaN, and the expression of proto - oncogene c - fos mRNA in cultured neonatal rat cardiomyocytes, which could be effectively decreased by buckwheat rutin. Our results demonstrated that buckwheat rutin exhibited inhibitory effect on AngII - induced hypertrophy in cultured neonatal rat cardiomyocytes via Ca(2+) antagonism action thus block the CaN - dependent signal pathway.

The Effects of Total Flavonoids from Buckwheat Flowers and Leaves on Renal Damage and PTP1B Expression in Type 2 Diabetic Rats.

Clinical data showed consumption of buckwheat played a very positive role in the relief of diabetes and its complications. The purpose of this study was to explore the effects and mechanisms of the overall flavonoids from buckwheat flowers and leaves (TFBFL) on renal damage in type 2 diabetes mellitus (T2DM) rats. Seventy male Wistar rats were selected. Ten rats were randomly allocated into a normal group and the other sixty were intragastrically injected with a lipid emulsion and small doses of alloxan to induce the T2DM model. T2DM inducement was judged by the fasting blood glucose (FBG) and oral glucose tolerance test (OGTT). Those whose FBG was ≥ 16.7 mmol/L and less tolerant to glucose were considered as being T2DM rats. These rats were then randomly divided into a groups termed: model (purified water, 5 mL.kg(-1) . d(-1)), BNPL (positive control) (Benazepril, 4 mg.kg(-1) . d(-1)), L-TFBFL (TFBFL 100 mg.kg(-1) . d(-1)), M-TFBFL (TBFL 200 mg.kg(-1) . d(-1)) and H-TFBFL (TFBFL 400 mg.kg(-1) . d(-1)). Each group then received medication for a period of 4 weeks. The normal rats were treated with purified water in a synchronous manner. Subsequently, FBG, plasma insulin (INS), OGTT, 24 h urinary protein output, blood and urinary creatinine content were assayed. Then the insulin sensitive index (ISI), bilateral kidney index, and creatinine clearance rate (Ccr) were calculated. Renal morphological changes and expression of protein tyrosine phosphatase 1B (PTP1B) in the kidneys were observed. TFBFL lowered FBG, improved insulin resistance, caused Ccr, and renal morphological changes, down-regulated the expression of PTP1B in T2DM rats and showed dose-dependence. TFBFL had a significant protective effect on renal damage in T2DM rats. This effect may be due to lowering blood glucose and diminishing renal damage by inhibiting PTP1B expression.

[Effects of flavones of buckwheat flower and leaf on insulin resistance and liver PTP1B in type 2 diabetic rats].

OBJECTIVE: To explore the effect and mechanism of flavones of buckwheat flower and leaf (FBFL) on lowering blood glucose and improving insulin resistance in type 2 diabetic rats. METHOD: Seventy healthy male Wistar rats were used in this trial. Ten of them were selected randomly as normal group; the others were given fat milk by intragastric administration daily, from the 14th day on, low dose tetraoxypyrimidine was added by intraperitoneal injection every other day for three times. Rats with fasting (72 hours after the last injection) blood sugar > or = 16.7 mmol x L(-1) and K(IPT) < 60% of normal group were selected as type 2 diabetic model with insulin resistance, which were randomly divided into 5 groups: model group. LGLT group; low, moderate and high dosage FBFL groups (L-FBFL; M-FBFL; H-FBFL). Every rat was treated accordingly for 4 weeks; then FBG, FFA, INS were detected and ISI was calculated to evaluate the degree of insulin resistance. Liver PTP1B expression was determined by immunohistochemistry method. staining were observed by light microscopy. RESULT: FBFL could dose-dependently inhibit the rising of FBG, FFA, INS, improve the state of insulin resistance and reduce the expression level of liver PTP1B. CONCLUSION: FBFL could effectively improve insulin resistance in type 2 diabetic rats induced by tetraoxypyrimidine and fat milk and showed dose-dependence relationship.