Hypoglycemic activity of puerarin through modulation of oxidative stress and mitochondrial function via AMPK / 中国天然药物

Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in HepG2 cells was assayed along with the qPCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program LibDock of Discovery Studio 2018 software. The results showed that puerarin improved HepG2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.

Recent developments in natural products for white adipose tissue browning / 中国天然药物

Excess accumulation of white adipose tissue (WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke, heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige (brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue (BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products (alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes (T2DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

Therapeutic effect of low dose interleukin-2 on experimental autoimmune encephalo-myelitis in mice / 军事医学

Objective To investigate the therapeutic effect of interleukin-2(IL-2)on experimental autoimmune encephalomyelitis(EAE)mice.Methods After establishment of the EAE(experimental autoimmune encephalomyelitis) mouse models with MOG35-55 polypeptides,the mice were grouped according to the neurological function score and divided into control group,EAE group and low dose IL-2 treatment group.A double blind method was used to evaluate the neuro-logical impairment in mice.On the 29th day,pathological experiments were carried out in the mice's brain and spinal cord, hematoxylin-eosin staining was used to evaluate the scoring of inflammatory cell infiltration and luxol fast blue staining was used to evaluate the scoring of demyelinating.The proportion of regulatory T cells(Treg)and NK cells(natural killer cell, NK)was detected by flow cytometry,and the immunohistochemical method was used to detect the expressions of glial fibril -lary acidic protein(GFAP)and myelin basic protein(MBP)in the spinal cord.Results Compared with the EAE group, the neurological function score, the inflammatory cell infiltration score and the demyelinating score of the low dose IL-2 treatment group were reduced.The proportion of Treg cells in the low dose IL-2 treatment group was significantly higher than that in the EAE group,and the proportion of NK cells in the low dose IL-2 treatment group was slightly higher than that in the EAE group The expression of GFAP and MBP was detected by immunohistochemistry.The expression level of GFAP in low dose IL-2 treatment group was significantly lower than that in the EAE group,while the expression level of MBP was higher than that in the EAE group.Conclusion Low dose IL-2 has significant therapeutic effect on EAE mice.

Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism.</p><p><b>METHODS</b>Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method.</p><p><b>RESULTS</b>The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05).</p><p><b>CONCLUSION</b>Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.</p>

Effect of progesterone on MMP-3 expression in neonatal rat brain after hypoxic-ischemia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effect of progesterone on matrix metalloproteinase-3 (MMP-3) expression in neonatal rat brain after hypoxic-ischemia.</p><p><b>METHODS</b>Followed the hypoxic-ischemia of neonatal rat brain, Evans blue (EB) staining and transmission electron microscopy were used to detect the blood-brain barrier pathological changes on permeability. MMP-3 protein expression in cerebral cortex was measured with Western blot.</p><p><b>RESULTS</b>Transmission electron microscopy results showed that the blood brain barrier in hypoxic-ischemic group changed significantly compare to progesterone group. EB staining results suggested that the blood-brain barrier permeability of hypoxic-ischemic group was significantly increased compared to sham-operated group (P < 0.01). The blood-brain barrier permeability in progesterone group was also decreased in comparison to that of hypoxic-ischemic group (P < 0.05). Western blot image analysis results indicated that MMP-3 protein expression in the hypoxic-ischemic group increased significantly than that in sham-operated group (P < 0.01), and the progesterone group was decreased significantly than that in hypoxic-ischemic group (P < 0.05).</p><p><b>CONCLUSION</b>Progesterone may reduce the blood-brain barrier damage by reducing MMP-3 expression. This might be one of the protective mechanisms in the hypoxic-ischemic brain injury.</p>

Professor He Pu-ren: the founder of Santong method of acupuncture and moxibustion / 中国针灸

Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.

Effect of Progesterone on Expressions of Superoxide Dismutase and Matrix Metalloproteinase-3 in Brain Tissues of Neonatal Rats with Hypoxic-Ischemic Brain Damage / 实用儿科临床杂志

Objective To explore the expressions of superoxide dismutase(SOD)and matrix metalloproteinase-3(MMP-3) in the brain tissues of newborn rat after hypoxic-ischemic(HI) and the effects of progesterone(PROG) on SOD and MMP-3 expression.Methods Seventy-two neonatal SD rats were randomly divided into 4 groups:normal control group(normal group),sham-operated group,HI group and PROG group.The model of neonatal rat with hypoxic-ischemic brain damage(HIBD) was made.The permeability of the blood-brain barrier was observed by using transmission electron microscopy,the level of SOD in the brain was assessed by hydroxylammoniumchloride autoxidation,MMP-3 protein expression in cerebral cortex part of the brain was detected by immunohistochemical.SPSS 12.0 software was used to analyze the data.Results In normal group and sham-operated group,capillary vessel′s morphology of blood brain barrier of neonatal rats were integrity and smooth,and structure were clarity.The permeability of blood-brain barrier in HI group was obviously enhanced and had slight changes in PROG group.Compared with the sham-operated group,the level of SOD in HI group significantly decreased(P