Chrysophanol localizes in mitochondria to promote cell death through upregulation of mitochondrial cyclophilin D in HepG2 cells / 中草药·英文版

Objective: Chrysophanol (Chry) displays potent anticancer activity in human cancer cells and animal models, but the cellular targets of Chry have not been fully defined. Herein, we speculated whether mitochondria were a target involved in Chry-induced cytotoxicity. Methods: Human liver cancer cell line HepG2 was incubated. The cytotoxicity was evaluated by MTT assay. Mitochondria localization was evaluated by a confocal microscopy. Mitochondrial membrane potential ΔΨm was detected by TMRE staining and determined by the flow cytometer. The levels of ATP, mitochondrial superoxide anions, and GSH/GSSG were determined according to the assay kits. The apoptosis were evaluated through Hoechst33342/PI and Annexin V/PI staining, respectively. The expression of cyclophilin D (CyPD) was determined by immunoblot method, and the interaction between CyPD and Chry was analyzed by molecule docking procedure. Results: Chry itself mainly localized in mitochondria to cause mitochondrial dysfunction and cell death in HepG2 cells. As regard to the mechanism, cyclosporin A as the inhibitor for the formation of mitochondrial permeability transition pore (mPTP) moderately suppressed cell death, indicating mPTP involved in the process of cell death. Further, Chry enhanced the protein expression of Cyclophilin D (CyPD) which is a molecular componentry and a modulator of mPTP, while antioxidant N-acetyl-L-cysteine inhibited the expression of CyPD. Molecule docking procedure disclosed two hydrogen-bonds existed in CyPD-Chry complex with −11.94 kal/mol of the binding affinity value. Besides, the mtDNA-deficient HepG

Roles and mechanism of microRNAs in the regulation of skeletal muscle insulin resistance / 生理学报

Insulin resistance is a common pathophysiological mechanism of obesity and type 2 diabetes mellitus. Skeletal muscle is one of the major target organs of insulin-mediated glucose uptake, metabolism and utilization, and it is the earliest and most important site of insulin resistance. Studies have shown that the impairments of glucose uptake, insulin signaling pathway and mitochondrial biosynthesis are closely related to skeletal muscle insulin resistance. When insulin resistance develops in skeletal muscle, multiple microRNAs (miRNAs) are up-regulated (miR-106b, miR-23a, miR-761, miR-135a, Let-7 and miR-29a) or down-regulated (miR-133a, miR-149 and miR-1). They participate in the regulation of skeletal muscle glucose uptake, insulin signaling pathway and mitochondrial biogenesis, and thus play important roles in the occurrence and development of skeletal muscle insulin resistance. Therefore, these miRNAs may serve as potential targets for the treatment of skeletal muscle insulin resistance or diabetes.

Signaling pathways controlling skeletal muscle mass / 生理学报

The skeletal muscle mass accounts for more than 40% of the body weight of healthy adults. The skeletal muscle not only plays an important role in physical activities but also affects the function of other organs as a secretory organ secreting multiple muscle factors. Therefore, it is important to maintain the normal quantity and function of skeletal muscle. Skeletal muscle mass is the basis of skeletal muscle function and is often affected by many factors such as exercise and disease. Resistance exercise training induces increased protein synthesis in skeletal muscle cells, while limb disuse, chronic obstructive pulmonary disease, heart failure, chronic kidney disease, cachexia, Duchenne muscular dystrophy and many other pathological conditions lead to decreased protein synthesis or enhanced protein degradation of skeletal muscle cells. The process of skeletal muscle hypertrophy involves changes in multiple signaling pathways, such as IGF-1/PI3K/Akt, myostatin and G protein. On the other hand, activations of the ubiquitin-proteasome system, IGF-1/Akt/FoxO, autophagy-lysosomal pathway, NF-κB, and the glucocorticoid-mediated signaling pathways play important roles in regulating muscle atrophy. These signaling pathways regulate skeletal muscle mass and are modulated by some different conditions. This review briefly summarizes the signaling pathways of skeletal muscle mass control.

Effect on clinical symptoms and mechanism of chloasma in premenopausal women with liver stagnation treated with acupoint catgut embedding / 中国针灸

OBJECTIVE@#To explore the therapeutic effect and mechanism of acupoint catgut embedding for chloasma in premenopausal women with liver stagnation.@*METHODS@#A total of 92 patients of chloasma in premenopausal women with liver stagnation were randomized into an observation group and a control group, 46 cases in each one.In the observation group, acupoint catgut embedding was applied at Ganshu (BL 18), Pishu (BL 20), Sanyinjiao (SP 6), also the surrounding acupuncture was performed at facial part, once a week. In the control group, vitamin C (200 mg per time, 3 times a day) and vitamin E (100 mg per time, once a day) were prescribed for oral administration. Both of the two groups were given treatment for 12 weeks. The score of chloasma area and severity index (MASI), the serum levels of follicular stimulating hormone (FSH), leuteinizing hormone (LH) and estradiol (E) before and after treatment were observed in the two groups, and the clinical effect of the two groups were compared after 3 months of treatment.@*RESULTS@#Finally, 44 cases in the observation group and 43 cases in the control group completed the study. The effective rate in the observation group was 88.6% (39/44), which was higher than 55.8% (24/43) in the control group (0.05). There was no significant difference between before treatment and in follow-up in the levels of FSH, LH and E in the control group (>0.05). In follow-up, the levels of FSH and LH in the observation group were lower than the control group (0.05).@*CONCLUSION@#Acupoint catgut embedding can improve the clinical symptoms of chloasma in premenopausal women with liver stagnation, the mechanism may be related to regulate the serum level of sex hormone to reduce high sensitivity of melanocytes to estrogen.

Fat deposition in skeletal muscle and its regulation / 生理学报

Under normal condition, there are a few lipid droplets in skeletal muscle. But in skeletal muscle acute injury, muscular dystrophy, muscle atrophy, obesity, diabetes and other pathological conditions, the fat deposition in skeletal muscle increases, which implicate that the fat deposition may play an important role in the pathogenesis of these diseases. However, the mechanisms of development and regulation of fat deposition in skeletal muscle are not clear. Clarifying the key signaling pathways and regulatory factors that affect fat deposition in skeletal muscle, and exploring new ways to improve the fat deposition in skeletal muscle will not only help to deepen our understanding of the pathogenesis of these diseases, but also provide new ideas for the treatment of these diseases. This paper reviews the research progresses and main mechanisms of fat deposition in skeletal muscle.

Antioxidant activities of cold-nature Tibetan herbs are signifcantly greater than hot-nature ones and are associated with their levels of total phenolic components / 中国天然药物

Tibetan medicinal plants have been used for more than 2 000 years. In order to find their differences in antioxidant activity, total phenolics and total flavonoids between "hot-nature" and "cold-nature" herbs, we investigated the antioxidant activities of 40 Tibetan herbs from Qinghai plateau, with 20 herbs in cold-nature and 20 herbs in hot-nature. Antioxidant capacities were evaluated by the following methods: scavenging ABTS•(+) (2, 2'azinobis-(3-ethylbenz-thiazoline-6-sulfonic acid), scavenging O2•(-), and Ferric-reducing antioxidant power (FRAP). The effects on inhibition of mitochondrion lipid peroxidation were determined by measuring the formation of TBARS (Thiobarbituric acid reactive substrates). Total phenolics and flavonoids were estimated by Folin-Ciocalteu and NaNO2-Al(NO3)3-NaOH colorimetric methods. Interestingly, the cold-nature herbs displayed higher antioxidant activities than the hot-nature ones, corresponding to nearly three-fold higher total phenolic contents in the cold-nature herbs. Moreover, the antioxidant activities correlated linearly with the levels of total phenolics for both cold-nature and hot-nature herbs, but only with the levels of total flavonoids for the hot-nature herbs. The results suggested that the phenolic compounds, but not the flavonoids, play the major role in antioxidant capacities of the cold-nature herbs. These findings could shed new lights on the study the theory of Tibetan medicine.

Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A bioactive compound from Paecilomyces tenuipes (BCPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress (CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.</p><p><b>METHODS</b>The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21. Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone (CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.</p><p><b>RESULTS</b>Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.</p><p><b>CONCLUSIONS</b>BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.</p>