Two new sesquiterpenes from the stems of Tripterygium wilfordii.

Two new ß-dihydroagarofuran-type sesquiterpenes 1ß,2α,6α,8ß,15- pentaacetoxy- 9α-benzoyloxy- ß-dihydroagarofuran (1) and 1ß,2ß,6α,15-tetraacetoxy-9ß-benzoyloxy- ß-dihydroagarofuran (2), together with five known abietane diterpenoids (3-7) were isolated from ethyl acetate extract of stems of Tripterygium wilfordii. Their structures were elucidated on the basis of detailed spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against A549, HOS and MCF-7. Among them, compounds 4 and 5 exhibited manifest inhibition on A549, HOS and MCF-7 cancer cell lines.

New polyacetylenes glycoside from Eclipta prostrate with DGAT inhibitory activity.

One new polyacetylene glycoside eprostrata Ⅰ (1), together with seven known compounds (2-8), were isolated from Eclipta prostrata. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated inhibitory activity on DGAT in an in vitro assay. Compounds 1-8 were found to exhibit inhibitory activity of DGAT1 with IC50 values ranging from 74.4 ± 1.3 to 101.1 ± 1.1 µM.

Water-soluble Manganese and Iron Mesotetrakis(carboxyl)porphyrin: DNA Binding, Oxidative Cleavage, and Cytotoxic Activities.

Two new water-soluble metal carboxyl porphyrins, manganese (III) meso-tetrakis (carboxyl) porphyrin and iron (III) meso-tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they can strongly bind to ct-DNA via outside binding mode. Electrophoresis experiments revealed that both complexes can cleave pBR322 DNA efficiently in the presence of hydrogen peroxide, albeit 2-Mn exhibited a little higher efficiency. The inhibitor tests suggest the oxidative DNA cleavage by these two complexes may involve hydroxyl radical active intermediates. Notably, 2-Mn exhibited considerable photocytotoxicity against Hep G2 cell via triggering a significant generation of ROS and causing disruption of MMP after irradiation.

[The Interaction Between a New Water-Soluble Meso-Tetrakis(Carboxyl) Zinc(â ¡) Porphyrin and Human Serum Albumin].

Porphyrin is a kind of photosensitizer for photodynamic therapy of cancer. Many porphyrin derivatives have been used in clinical treatment. Human Serum Albumin (HSA) is the carrier of drug transportation. Therefore, investigation on the interaction of porphyrin with HSA is very important to understand the pharmacokinetic of the porphyrin. In this paper, a new water-soluble carboxyl porphyrins, meso-tetrakis(carboxyl) zinc(Ⅱ) porphyrin (2-Zn), was synthesized and characterized. Its interaction with human serum albumin (HSA)was investigated by UV-Vis absorption spectra, fluorescence spectra, circular dichroism (CD) spectra and molecular modeling. The results indicated that the fluorescence quenching of HSA by 2-Zn was a static process with the quenching constants are 1.96×104 L·mol-1 (298 K) and 1.37×104 L·mol-1 (310 K) and the binding constants were calculated to be 1.93×104 L·mol-1 (298 K) and 1.50×104 L·mol-1 (310 K). According to the Van't Hoff equation, the thermodynamic parameters were characterized by negative enthalpy (ΔH=-16.132 kJ·mol-1) and positive entropy (ΔS=27.905 J·mol-1·K-1), which indicated that 2-Zn binds with HSA mainly via electrostatic interaction along with the hydrogen bonding and hydrophobic interaction. Site marker competitive binding experiment confirmed that 2-Zn mainly binds at site Ⅱ. The distance between HSA and the receptor (2-Zn) and the efficiency energy transfer were obtained to be 4.01 nm and 0.163 respectively, based on the Forster theory on resonance energy transfer. Synchronous fluorescence, absorption and CD spectroscopy showed that the interaction of HSA with 2-Zn induced a conformational change of protein, and the amount of α-helical structures were decrease. Furthermore, the binding details between 2-Zn and HSA were further studied with the molecular docking, which was in good agreement with the site marker competitive binding experiments and thermodynamic parameters.

Influence of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis.

AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mortality, pathological changes of mesenteric lymph nodes, expression levels of NF-kappa B, P-selectin, Bax, Bcl-2 and caspase-3 protein and changes in apoptotic indexes in lymph nodes were observed at 3, 6 and 12 h after operation. The blood levels of endotoxin, superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1) in blood were determined. RESULTS: SOD content, expression of Bax protein and apoptotic index were significantly higher in the treated group than in the model group at different time points (P < 0.05 or P < 0.01). Other blood-detecting indexes and histopathological scores of mesenteric lymph nodes were lower in the treated than in the model group (P < 0.05, P < 0.01 or P < 0.01). NF-kappa B protein expression was negative in all groups. Comparing P-selectin and caspase-3 expression levels among all three groups, there was no marked difference between the model and treated group. CONCLUSION: Dexamethasone can protect mesenteric lymph nodes. The mechanism may be by reducing the content of inflammatory mediators in the blood and inducing lymphocyte apoptosis.

Four new compounds isolated from Psoralea corylifolia and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

A new bakuchiol compound Δ11-12-hydroxy-12-dimethyl bakuchiol (1), a new flavanone compound 2(S)-6-methoxy-7- hydroxymethylene-4'-hydroxyl-flavanone (8), and two new isoflavanone compounds 4',7-dihydroxy-3'-(6"ß-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone (9) and 4',7-dihydroxy-3'-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone (10) together with eight known compounds (2-7, 11, 12) were isolated from the P. corylifolia. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3, 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 93.7 ±â€¯1.3 to 96.2 ±â€¯1.1 µM. Compound 1 showed inhibition activity on DGAT1 with IC50 values 73.4 ±â€¯1.3 µM and inhibition of DGAT2 with IC50 value 121.1 ±â€¯1.3 µM.

Wogonoside alleviates high glucose-induced dysfunction of retinal microvascular endothelial cells and diabetic retinopathy in rats by up-regulating SIRT1 / 南方医科大学学报

OBJECTIVE@#To investigate the effects of wogonoside on high glucose-induced dysfunction of human retinal microvascular endothelial cells (hRMECs) and streptozotocin (STZ)-induced diabetic retinopathy in rats and explore the underlying molecular mechanism.@*METHODS@#HRMECs in routine culture were treated with 25 mmol/L mannitol or exposed to high glucose (30 mmol/L glucose) and treatment with 10, 20, 30, 40 μmol/L wogonoside. CCK-8 assay and Transwell assay were used to examine cell proliferation and migration, and the changes in tube formation and monolayer cell membrane permeability were tested. ROS, NO and GSH-ST kits were used to evaluate oxidative stress levels in the cells. The expressions of IL-1β and IL-6 in the cells were examined with qRT-PCR and ELISA, and the protein expressions of VEGF, HIF-1α and SIRT1 were detected using Western blotting. We also tested the effect of wogonoside on retinal injury and expressions of HIF-1α, ROS, VEGF, TNF-α, IL-1β, IL-6 and SIRT1 proteins in rat models of STZ-induced diabetic retinopathy.@*RESULTS@#High glucose exposure caused abnormal proliferation and migration, promoted angiogenesis, increased membrane permeability (P < 0.05), and induced inflammation and oxidative stress in hRMECs (P < 0.05). Wogonoside treatment concentration-dependently inhibited high glucose-induced changes in hRMECs. High glucose exposure significantly lowered the expression of SIRT1 in hRMECs, which was partially reversed by wogonoside (30 μmol/L) treatment; interference of SIRT1 obviously attenuated the inhibitory effects of wogonoside against high glucose-induced changes in proliferation, migration, angiogenesis, membrane permeability, inflammation and oxidative stress in hRMECs. In rat models of STZ-induced diabetic retinopathy, wogonoside effectively suppressed retinal thickening (P < 0.05), alleviated STZ-induced retinal injury, and increased the expression of SIRT1 in the retinal tissues (P < 0.001).@*CONCLUSION@#Wogonoside alleviates retinal damage caused by diabetic retinopathy by up-regulating SIRT1 expression.

Four new neolignans isolated from Eleutherococcus senticosus and their protein tyrosine phosphatase 1B inhibitory activity (PTP1B).

Four new compounds, erythro-7'E-4-hydroxy-3,3'-dimethoxy-8,5'-oxyneoligna-7'-ene-7,9-diol-9'-al (1), (7S,8S)-4-hydroxy-3,1',3'-trimethoxy-4',7-epoxy-8,5'-neolign-9-ol (5), (7S,8S,7'E)-5-hydroxy-3,3'-dimethoxy-4',7-epoxy-8,5'-neolign-7'-ene-9,9'-diol (6) and (7S,8S,7'E)-5-hydroxy-3,3',9'-trimethoxy-4'-7-epoxy-8,5'-neolign-7'-ene-9-ol (7). Along with four known compounds (2-4, 8) were isolated from the EtOAc-soluble extract of Eleutherococcus senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the compounds were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, compounds 1-4 and 6-8 were found to exhibit selective inhibitory activity on PTP1B with IC50 values ranging from 17.2±1.6 to 32.7±1.2µM.

Effect of Qi Kwai Granule particles on expression of TGF-β1 and MCP-1 in kidney of diabetic nephropathy rats / 中国药理学与毒理学杂志

OBJECTIVE To observe the effect of Qi Kwai Granule particles on the expression of in-terleukin 6 (IL-6), monocyte chemotactic protein 1(MCP-1) and transforming growth factor-β1(TGF-β1) in diabetic nephropathy(DN)rats and evaluate the protective effect of Qi Kwai Granule particles against renal injury of diabetic nephropathy. METHODS This experiment adopts adopted the high-sugar-high-fat diet and intraperitoneal injection of 2％ STZ+unilateral renal ligation to establish rat model of diabet-ic nephropathy.50 model rats were then randomly divided into model group,Irbesartan group,Qi Kwai Granule particles of high, medium, low dose group, 10 rats in each group. 10 normal rats were set as the sham operation group.Intragastric administration for 8 weeks were measured in rats.Measure the value of rat blood glucose by blood glucose meter,the determination of serum interleukin 6(IL-6)con-tent by ELISA, the expression of MCP-1 and TGF-β1by immunohistochemistry method. The value of rat blood glucose were measured by blood glucose meter.Serum interleukin 6(IL-6)were determinat-ed by ELISA.Expression of MCP-1 and TGF-β1were evaluated by immunohistochemistry method.RE-SULTS The blood glucose of Qi Kwai Granule particles of high,medium groups were decreased com-pared with those of the model group(P<0.05).The content of IL-6 of Qi Kwai Granule particles of high, medium groups were reduced(P<0.01). The content of MCP-1, TGF-β1in kidney of Qi Kwai Granule particles of high, medium, low dose groups were decreased (P<0.01). CONCLUSION Qi Kwai parti-cles have protective effect on renal tissue of diabetic nephropathy rats.Its mechanism might be related to the decrease of blood glucose value and IL-6,the inhibition of the expression of MCP-1 and TGF-β1.

Treatment of Early Diabetic Retinopathy by Liuwei Dihuang Pill Combined Ginkao Leaf Tablet / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the prevention and clinical efficacy of combination of Liuwei Dihuang Pill (LDP) and Ginkgo Leaf Tablet (GLT) for early diabetic retinopathy (DR).</p><p><b>METHODS</b>Using randomized, double-blind, double simulation, parallel controlled clinical trial, 140 type 2 diabetes mellitus (T2DM) outpatients were recruited and assigned to the treatment group and the control group, 70 in each group. All patients received basic Western medicine treatment (such as blood glucose and pressure control). Patients in the treatment group took LDP (8 pills each time, 3 times per day) and GLT (19.2 mg each time, 3 times per day), while those in the control group took LDP placebos and GLT placebos. All treatment lasted for 24 consecutive months. All subjects were followed-up every month. The general clinical data as sex, age, and metabolic data such as blood glucose, blood pressure, blood lipid, and DR prevalence rate were collected and statistically analyzed.</p><p><b>RESULTS</b>There was no significant difference in levels of blood glucose, blood pressure, or blood lipid between the two groups (P > 0.05). After treatment the DR incidence rate was significantly lower in the treatment group than in the control group [3.1% (2/64) vs 18.6% (11/59), P < 0.05)]. Meanwhile, the DR prevalence rate of the treatment group was also significantly lower than that of the control group [6.3% (4/64) vs 20.0% (13/59), P < 0.05].</p><p><b>CONCLUSION</b>Combination of LDP and GLT could effectively prevent and treat the development of DR in T2DM patients.</p>

Autoimmune polyendocrinopathy syndrome type 2 with Guillain-Barre syndrome and scleroderma: a case report / 南方医科大学学报

Autoimmune polyendocrinopathy syndrome is a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. We present a case of autoimmune polyendocrinopathy syndrome type 2 in a 42-year-old woman with Guillain-Barre syndrome and scleroderma. This combination of syndromes has not been reported and warrants further investigation.

Central administration of Orphanin FQ inhibits GnRH secretion by ORL1 receptor in the median eminence of freely moving ovariectomized rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>This study aimed to investigate the possible role of Orphanin FQ (OFQ) in the regulation of hypo-thalamic gonadotropin-releasing hormone (GnRH) secretion.</p><p><b>METHODS</b>The method of push-pull perfusion and radioimmuno-assay (RIA) were adopted to examine the secretory profile of GnRH in the median eminence (ME) in freely moving ovari-ectomized (OVX) rats after intracerebroventricular (icv) injection of OFQ and/or [Nphe(1)]NC(1-13)NH(2) (NC13), a competitive antagonists of the opioid receptor-like 1 receptor (ORL1 receptor).</p><p><b>RESULTS</b>GnRH release from ME significantly decreased from 40 min to 80 min after the administration of 20 and 200 nmol OFQ in OVX rats (P < 0.05). This inhibitory effect of 20 nmol OFQ could be abolished by pretreatment with equal dose of NC13. More interestingly, GnRH secretion from ME was increased markedly 60 min after icv injection of 100 and 200 nmol NC13 (P < 0.05).</p><p><b>CONCLUSION</b>Our results suggested central administration of OFQ could inhibit the release of GnRH in the ME of hypothalamus through ORL1 receptor, providing further in vivo evidence supporting the role of OFQ in the control of GnRH secretion.</p>

Effect of Liuwei Dihuang soft capsule and Ginkgo leaf tablet on serum regulated upon activation, normal T cell expressed and secreted in patients with diabetes mellitus type 2 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Liuwei Dihuang Soft Capsule(LDSC) and Ginkgo Leaf Tablet (GLT) on serum regulated upon activation, normal T cell expressed and secreted (RANTES) in the patients with diabetes mellitus type 2 (DM2).</p><p><b>METHODS</b>Forty patients with early stage DM2 were randomly assigned to two groups, 20 in each group. Based on the conventional treatment with hypoglycemic agents, patients in the treated group were treated with LDSC plus GLT additionally, and those in the placebo group with placebo for 6 months, respectively. The levels of serum RANTES, blood glucose, blood lipids and glycosylated hemoglobin, as well as micro-content of albumin in urine were measured before and after treatment.</p><p><b>RESULTS</b>In the treated group, the serum level of RANTES decreased significantly after treatment, and it was significantly lower as compared with that in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>LDSC and GLT can decrease serum RANTES level in patients with DM2. They play a preventive and therapeutic role on diabetic complications by their anti-inflammatory effect.</p>