Diabetes mellitus (DM) is a group of metabolic disorders in which high blood sugar levels occur over a prolonged period. Approximately 4% of the global population is affected by DM. Western medical treatment methods for diabetes including injection or oral hypoglycemic drugs have some toxic or side effects, economic pressures, and so on. Many researchers turn to discover new drugs from natural products or Traditional Chinese Medicine (TCM). Flavonoids are widely distributed in plants, and many studies have shown that flavonoids possess antidiabetic properties, exhibiting not only well-recognized antidiabetic and hypoglycemic activities but also activity in the treatment of diabetic complications. In this review, we systematically summarized anti-diabetic flavonoid compounds based on structure classification by examining the PubMed, Springer Link, Web of Science, and CNKI databases. There are 13 flavonoid compounds listed which have been studied extensively and have antidiabetic features respectively. Apigenin, baicalein, and catechin mainly reduces blood glucose via anti-oxidation; hesperidin is good for diabetic neuropathy; glycyrrhiza flavonoids have a significant effect on gestational DM; quercetin takes advantage of crossing the blood-brain barrier and improving renal function. Some compounds have protective and preventive effects on diabetic complications, such as kaempferol and puerarin which are beneficial to cardiomyopathy; myricetin has therapeutic potential in the treatment of DN; dihydromyricetin might improve CI. It is a pity or might be a pointcut that most studies remain in the animal experimental stage, and further investigation should be carried out.

https://www.worldscientific.com/doi/pdf/10.1142/S0192415X19500496

Antidiabetic Potential of Flavonoids from Traditional Chinese Medicine: A Review.

Diabetes mellitus (DM) is a gradually rising metabolic disease which is currently affecting millions of people worldwide. Diabetes is associated with various complications like nephropathy, neuropathy, retinopathy, diabetic foot, cognitive impairment, and many more. Evidence suggests that cognitive dysfunction is a rising complication of diabetes which adversely affects the brain of patients suffering from diabetes. Age-related memory impairment is a complication having its major effect on people suffering from diabetes and Alzheimer's. Patients suffering from diabetes are at two times higher risk of developing cognitive dysfunction as compared with normal individuals. Multiple factors which are involved in diabetes related complications are found to play a role in the development of neurodegeneration in Alzheimer's. The problem of insulin deficiency and insulin resistance is well reported in diabetes but there are many studies which suggest dysregulation of insulin levels as a reason behind the development of Alzheimer's. As the link between diabetes and Alzheimer disease (AD) is deepening, there is a need to understand the plausible tie-ins between the two. Emerging role of major factors like insulin imbalance, advanced glycation end products and micro-RNA's involved in diabetes and Alzheimer's have been discussed here. This review helps in understanding the plausible mechanism underlying the pathophysiology of amyloid beta (Aβ) plaque formation and tau hyperphosphorylation as well provides information about studies carried out in this area of research. The final thought is to enhance the scientific knowledge on this correlation and develop future therapeutics to treat the same.

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease.

Chemistry, metabolism and pharmacology of carcinogenic alkaloids present in areca nut and factors affecting their concentration.

Cholestatic liver disease is caused by the obstruction of bile synthesis, transport, and excretion in or outside the liver by a variety of reasons. Long-term persistent cholestasis in the liver can trigger inflammation, necrosis, or apoptosis of hepatocytes. Bile acid nuclear receptors have received the most attention for the treatment of cholestasis, while the drug development for bile acid nuclear receptors has made considerable progress. However, the targets regulated by bile acid receptor drugs are limited. Thus, as anticipated, intervention in the expression of bile acid nuclear receptors alone will not yield satisfactory clinical results. Therefore, this review comprehensively summarized the literature related to cholestasis, analyzed the molecular mechanism that bile acid damages cells, and status of drug development. It is hoped that this review will provide some reference for the research and development of drugs for cholestasis treatment in the future.

/pdf/mechanism-of-hydrophobic-bile-acid-induced-hepatocyte-injury-ein9hky2s9.pdf

Mechanism of Hydrophobic Bile Acid-Induced Hepatocyte Injury and Drug Discovery.

https://hal.umontpellier.fr/hal-01837194/document

Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way.

Objective To observe the effects of dihydromyricetin(DHM) on cognitive dysfunction and expression of brain derived neurotrophic factor(BDNF) protein in hippocampus of type 2 diabetic mice(T2DM). Methods Forty C57BL/6J mice were randomly divided into two groups, normal control group (n=8):normal diet feeding; T2DM model group (n=32):high-glucose and high-fat combined with 100 mg/kg streptozocin(STZ) treatment (five mice died during modeling and three failed). Twenty-four diabetic mice were modeled successfully and divided into three groups (T2DM group, T2DM+L-DHM group and T2DM+H-DHM group). Three groups mice were fed with high-glucose and high-fat diet, and treated with equal volume of normal saline, 125 mg/(kg·d) DHM or 250 mg/(kg·d) DHM for 16 weeks respectively. The control mice were fed with normal diet and treated with equal volume of saline (once a day, gavage) for 16 weeks. After 16 weeks, the body weight and fasting blood glucose were measured, intraperitoneal glucose tolerance test and related behavioral experiment were performed. Finally, the expression of BDNF protein in hippocampus of mice was detected by Western blot. Results The model of type 2 diabetes mellitus was established successfully with high-glucose and high-fat combined with 100 mg/kg STZ. After 16 weeks, the body weight of T2DM group was significantly decreased, the fasting blood glucose was significantly increased and the glucose tolerance was significantly abnormal compared with the normal control group. Compared with T2DM group, the body weight of T2DM+DHM groups mice was increased, while the levels of fasting blood glucose were decreased. And H-DHM could significantly improve the abnormal glucose tolerance of T2DM mice. Behavior test results showed that the ability of learning and memory of T2DM mice was significant decreased compared with control group, but these phenomena were improved in T2DM+DHM groups mice, and T2DM+H-DHM group was more obvious. Western blot analysis showed that the expression of BDNF protein in hippocampus of T2DM group was significantly lower than that of control group, while T2DM+DHM group was significant increased compared with T2DM mice. Conclusions Dihydromyricetin can improve the cognitive dysfunction in type 2 diabetic mice. The mechanism may be through hypoglycemic effect and activation of BDNF protein expression in hippocampus.

The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice

OBJECTIVE To explore the effects of arecoline on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism. METHODS Forty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model. rats were randomly divided into 5 groups (n = 8): control group, model group and model group were treated with different dose (0, 0.5, 1, 5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot. RESULTS 1.5 mg/kg arecoline could significantly decrease the level of fasting blood glucose, blood lipid, blood insulin level and liver G6Pase, PEPCK, IL-6, TNF-alpha mRNA level in type 2 diabetes rats. 1.5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression. CONCLUSION Arecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the creased glucose metabolism and inflammation related genes expression.

The role of arecoline on hepatic insulin resistance in type 2 diabetes rats

Objective To observe the effects of arecoline on proliferation and apoptosis of MCF-7 human breast cancer cells and to ex-plore its possible mechanism. Methods Human breast cancer MCF-7 cells were treated with arecoline at the concentrations of 0,10,30,50, 100,300,500μmol/L, the cell proliferation were detected by MTT assay, cell apoptosis were analyzed by Hoechst 33342 staining and flow cy-tometry, the protein expression of Bax,Bcl-2 and P53 were detected by Western blot. Results Low concentration(0,10,30, 50 μmol/L) arecoline had no effect on the proliferation and apoptosis of MCF-7. However, high concentration(100,300,500μmol/L) arecoline inhibited proliferation and induced apoptosis of MCF-7 cells in a concentration-dependent manner, arecoline also significantly increased P53 and Bax protein expression and decreased Bcl-2 protein expression. Conclusions High concentration arecoline inhibited the proliferation and induced the apoptosis of MCF-7 cells, the mechanism was probably corrected with increasing P53 and Bax protein expression and decreasing Bcl-2 pro-tein expression.

[Effect of arecoline on proliferation and apoptosis of MCF-7 human breast cancer cells].

Objective To observe the effects of arecoline on lipid metabolism in 3T3-L1 adipocytes and explore its possible mechanisms. Methods 3T3-L1 pre-adipocytes were induced into adipocytes with the classic "cocktail" method, subsequently, adipocytes were treated with arecoline at the concentrations of 0, 25, 50 and 100 μmol/L for 72 hours. After 72 hours, cell vability was measured with MTT method, lipid droplet accumulation in the cytoplasm was observed with oil red O staining, the protein expression of fatty acid synthase (FAS), adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were detected by Western blot assay. Results There were a large number of lipid droplets in the cytoplasm in the differentiated 3T3-L1 adipocytes. MTT results showed that 0~100 μmol/L arecoline had no significant effect on cell vability; oil red O staining found arecoline reduced lipid amount in 3T3-L1 adipocytes; Western blot results showed that compared with 0 μmol/L arecoline group (the control group), arecoline significantly reduced the protein level of FAS and increased the protein levels of ATGL and HSL, and 50 μmol/L arecoline group was the most significant. Conclusions Arecoline significantly increased lipolysis of 3T3-L1 adipocyte, which might be associated with decreased the FAS expression of key enzyme of lipid synthesis and increased the ATGL and HSL expression of key enzyme of adipolysis.

Kai-Fang Zhang

Papers

The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice

The role of arecoline on hepatic insulin resistance in type 2 diabetes rats

[Effect of arecoline on proliferation and apoptosis of MCF-7 human breast cancer cells].

[The effects of arecoline on the lipid metabolism of 3T3-L1 adipocytes].