Buy Psoralea Corylifolia Extract

Click Here >>> https://fancli.com/2tkjvZ

Estrogenic activities of ethanol extract and its active components from Psoralea corylifolia L. were studied using various in vitro assays. The main components from ethanol extract were analyzed to be bakuchiol, psoralen, isobavachalcone, isobavachromene, and bavachinin. In a fractionation procedure, hexane and chloroform fractions showed estrogenic activity in yeast transactivation assay and E-screen assay. In yeast transactivation assay, ethanol extract, hexane, and chloroform fractions showed significantly higher activities at a concentration of 1.0 ng/ml, and bakuchiol at the concentration of 10(-6) M was showed the highest activity, especially, which was higher than genistein at the same concentration. In E-screen assay, cell proliferation of bakuchiol (10(-6) M) showed similar estrogenic activity with genistein (10(-6) M). In ER binding assay, bakuchiol displayed the strongest ER-binding affinity (IC(50) for ERα=1.0110(-6) M, IC(50) for ERβ=1.2010(-6) M) and bakuchiol showed five times higher affinity for ERα than for ERβ.

PCS extract has generated much interest due to its various biological activities, including anti-inflammation, anti-apoptosis, and anti-hyperglycemic effects [20,22,23], suggesting further study on its effect on diabetic complications such as nephropathy. Therefore, we investigated anti-diabetic nephropathy effects of PCS extract in STZ-induced diabetic mice, which develop renal injury with similarities to human diabetic nephropathy [24].

The increase in urinary albumin excretion, one of the marked renal pathological features in diabetic nephropathy, is caused by mesangial expansion due to accumulation of extracellular matrix components [25]. Our STZ-induced diabetic mice showed an increase in urinary albumin concentration and a corresponding increase in the mesangial matrix index relative to non-diabetic control mice. In addition, the level of creatinine clearance, the most widely used clinical marker of kidney function [26], was higher in diabetic mice than control mice, indicating the presence of diabetic nephropathy with renal hyperfiltration in our STZ-induced diabetic mice. Eight-weeks of PCS extract treatment attenuated the increased albuminuria, creatinine clearance, and mesangial expansion in the glomeruli of STZ-induced diabetic mice. These results demonstrated that PCS extract has potent effects by counteracting mesangial expansion and hyperfiltration in diabetic mice, possibly leading to the amelioration or delay in the development of advanced diabetic renal injury.

We observed that hyperfiltration induced by STZ injection led to a decrease in serum urea nitrogen levels, but administration of PCS extract did not recover this to normal levels. These results show lack of correlation with creatinine clearance and serum urea nitrogen, and this is consistent with another study in STZ-induced diabetic rats fed a high fat diet [27].

Previously, we reported that PCS extract treatment showed anti-hyperglycemic effects via reduced lipid accumulation and reduced inflammation in the liver of mice fed a high fat diet [20]. In the present study, treatment of diabetic mice with PCS extract ameliorated creatinine clearance and mesangial matrix accumulation, but had no impact on glucose homeostasis (Figure S1). These conflicting results might be the result of the different mechanisms used to induce different diabetic mouse models [28]: such as type 1 diabetes (present study) versus type 2 diabetes (previous study). Moreover, effect of PCS extract regarding improvement of renal injury was similar to the losartan-treated group, suggesting that PCS extract might directly improve kidney function by glucose-independent mechanisms.

Several studies have demonstrated that increased TGF-β expression in mesangial cells promotes extracellular matrix accumulation and hypertrophy during progression of diabetic nephropathy [29,30]. Moreover, as increased TGF-β is known to be a potent inducer of Col4a2, fibronectin, and PAI-1 expression [31], we investigated whether PCS extract reduced the expression of these molecules. Treatment with PCS extract inhibited the expression level of fibrosis markers both in the kidney tissue of diabetic mice and in high glucose-treated MES-13 mesangial cells, and also increased cell viability. These results show that the anti-fibrotic effects of PCS extract provided effective protection from high glucose-mediated kidney damage.

Apoptosis plays a pathological role leading to the death of mesangial cells, which is associated with progressive glomerulosclerosis [32,33]. Khera et al. reported that high glucose-mediated TGF-β activation decreases nuclear factor-kB activation and in turn, alters the expression ratio of Bcl-2:Bcl-2-associated X protein favoring caspase-3 activation and increased apoptosis [8]. We also found that expression level of apoptotic makers was increased under diabetic nephropathy conditions, and PCS extract treatment attenuated cleaved PARP and increased Bcl-2 expression and phosphorylation of Bad (Ser-112). Although we did not evaluate the correlation between fibrosis and apoptosis pathways in glucose-treated mesangial cells, these results suggest that inhibition of apoptosis under conditions of high glucose toxicity is an important mechanism of PCS extract in reducing glomerulosclerosis in diabetic nephropathy.

We found that treatment with major compounds of PCS extract (bakuchiol, psoralen, and isopsoralen) inhibited mesangial cell death, but the anti-apoptotic and anti-fibrotic responses varied. Two coumarins, psoralen and isopsoralen, increased cell viability and decreased apoptotic protein expression, and bakuchiol showed anti-apoptotic effects at much lower concentration compared with psoralen or isopsoralen. Similarly, previous studies found that psoralen or isopsoralen inhibits apoptotic cell death in H2O2-treated INS-1 cells [18] or palmitate-treated PC12 cells [34]. Psoralen or isopsoralen decreased mRNA expression level of fibronectin and PAI-1, suggesting that the effects of PCS extract in diabetic nephropathy was mediated primarily by these compounds. However, total PCS extract treatment significantly increased the expression of PAI-1. PCS extract contains other chemical compounds such as coryfolin, corylin, and 3-hydroxybakuchiol [13], which might have resulted in the increase of PAI-1 expression in apoptotic mesangial cells seen after PCS treatment.

Pancreatic beta-cell death is known to be the cause of deficient insulin production in diabetes mellitus. Oxidative stress is one of the major causes of beta-cell death. In this study, we investigated the effects of Psoralea corylifolia L. seed (PCS) extract on beta-cell death. Oral administration of PCS extract resulted in a significant improvement of hyperglycemia in streptozotocin-induced diabetic mice. PCS extract treatment improved glucose tolerance and increased serum insulin levels. To study the mechanisms involved, we investigated the effects of PCS extract on H2O2-induced apoptosis in INS-1 cells. Treatment with PCS extract inhibited cell death. PCS extract treatment decreased reactive oxygen species level and activated antioxidative enzymes. Among the major components of PCS extract, psoralen and isopsoralen (coumarins), but not bakuchiol, showed preventive effects against H2O2-induced beta-cell death. These findings indicate that PCS extract may be a potential pharmacological agent to protect against pancreatic beta-cell damage caused by oxidative stress associated with diabetes.

To investigate whether PCS extract has protective effect on oxidative stress-induced beta-cell apoptosis, we examined the effects of PCS extract on cell death in H2O2-treated INS-1 cells. Western blot analysis of cleaved PARP and cleaved caspase-3, apoptosis-related proteins, showed that H2O2 treatment increased the expression of these proteins, and PCS extract pretreatment inhibited this increase in a dose-dependent manner. Mitogen-activated protein kinases (MAPK) are key molecules in the apoptotic signaling pathways, and ROS are known to induce MAPK signaling pathway activation [2]. Thus, we also checked phosphorylated p38 MAPK and p-JNK and found that the expression of these proteins was similarly inhibited by PCS extract pretreatment (Figure 3(a)).

Bakuchiol, psoralen, and isopsoralen are known to be active components of PCS extract. To determine whether any of these compounds might be responsible for the antiapoptotic effect of PCS extract in H2O2-induced beta-cell death, we examined the antiapoptotic effects of purified bakuchiol, psoralen, and isopsoralen on INS-1 cells. As shown in Figure 4, INS-1 cells treated with H2O2 showed reduced cell viability by approximately 60% relative to control cells. When the cells were pretreated with PCS extract, the cell survival rate increased dose dependently (Figure 4(a)). The H2O2-induced cytotoxic effect was not affected by cotreatment with bakuchiol (Figure 4(b)) but was significantly attenuated by cotreatment with psoralen (Figure 4(c)) or isopsoralen (Figure 4(d)).

In both type 1 and type 2 diabetes, oxidative stress is thought to mediate beta-cell death, by inflammatory processes in the case of type 1 diabetes and by chronic hyperglycemia in the case of type 2 diabetes [5, 7, 27]. Diabetes increases the production of tissue-damaging ROS by glucose autoxidation and nonenzymatic protein glycosylation. Thus, protecting beta-cells against damage induced by oxidative stress is an important strategy for the treatment of diabetes. PCS have been used traditionally as a medicine in Asia and are known to have antioxidant activity [23, 26]. In this study, we investigated the protective effects of PCS extracts against beta-cells apoptosis induced by oxidative stress using STZ-induced diabetic mice as an animal model. Although this animal model does not mimic either the autoimmune destruction of beta-cells found in type 1 diabetes or the insulin resistance found in type 2 diabetes, STZ does substantially increase the ROS level in the pancreas and cause selective pancreatic beta-cell death [28, 29], thus providing a model in which the possible protective effect of PCS can be studied. 59ce067264

https://www.goodvibesyogafitness.com/group/mysite-200-group/discussion/4620f5b3-cbdc-4e74-837a-2dc4d101ddb1