Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway.

OBJECTIVE: To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro. METHODS: MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy. RESULTS: HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation. CONCLUSION: Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.

Danhong Injection Alleviates Mechanical Allodynia via Inhibiting ERK1/2 Activation and Elevates BDNF Level in Sciatic Nerve in Diabetic Rat.

Danhong injection (DHI) has been widely used in China for cardiocerebrovascular diseases treatments. And in this study, we demonstrated the therapeutic effect of DHI on experimental diabetic neuropathy for the first time. Methods. Streptozotocin- (STZ-) induced SD rats were used. In experiment 1, 4-week treatment with DHI or saline started 4 weeks after STZ injection; mechanical allodynia was measured before and every 2 weeks after STZ injection. In experiment 2, chronic intrathecal infusion of U0126 was conducted during the 8th week of diabetes. Phosphorylated and total ERK1/2 in spinal cord were analyzed by western blot. BDNF level in sciatic nerve was evaluated by ELISA. Results. DHI treatment significantly alleviated mechanical allodynia at the end of the study and downregulated the expression of phosphorylated ERK1/2 in spinal cord. In addition, DHI treatment also elevated brain-derived neurotrophic factor (BDNF) level in sciatic nerve of DPN rat. In experiment 2, inhibition of ERK1/2 activation was confirmed to result in the alleviation of mechanical allodynia. Conclusions. We demonstrated that DHI was able to alleviate mechanical allodynia in diabetic neuropathy rat through inhibiting the activation of ERK1/2. The reduction of BDNF content in sciatic nerve was also partially reversed by DHI treatment.

Phytochemical and Pharmacological Studies on the Genus Psoralea: A Mini Review.

The genus Psoralea, which belongs to the family Fabaceae, comprises ca. 130 species distributed all over the world, and some of the plants are used as folk medicine to treat various diseases. Psoralea corylifolia is a typical example, whose seeds have been widely used in many traditional Chinese medicine formulas for the treatment of various diseases such as leucoderma and other skin diseases, cardiovascular diseases, nephritis, osteoporosis, and cancer. So, the chemical and pharmacological studies on this genus were performed in the past decades. Here, we give a mini review on this genus about its phytochemical and pharmacological studies from 1910 to 2015.

[Effect of Tongmai Jiangtang Capsule on Experimental Diabetic Peripheral Neuropathy Rats].

OBJECTIVE: To observe the effect of Tongmai Jiangtang Capsule (TJC) on experimental diabetic peripheral neuropathy (DPN) rats. METHODS: Forty Wistar rats were divided into the TJC group, the mecobalamin treatment group, the model group, and the normal group according to random digit table, 10 in each group. Except rats in the normal group, DPN rat model was prepared using intraperitoneally in- jecting streptozotocin (STZ) in the rest rats. One rat in the model group died during the modeling. Different drugs were administered by gastrogavage to rats in corresponding groups from the 8th week after successful modeling. TJC (0.23 g crude drugs/mL, 10 mL/kg) was administered to rats in the TJC group by gastrogavage. Suspension of mecobalamin and normal saline (10 mL/kg, 0.05 mg/mL) was administered by gastrogavage to rats in the mecobalamin treatment group to the end of the 12th week. Meanwhile, equal volume of distilled water was administered by gastrogavage to rats in the model group and the normal group. Peripheral nerve conduction velocity was detected in each group. Gait analysis was performed. Changes of intraepidermal nerve fiber were observed by immunohistochemical assay. Pathological changes of tibial nerve tissue were observed using HE staining. RESULTS: (1) Compared with the normal group, the nerve conduction velocity was slowed down; print length (PL), intermediary toe spread (ITS), and toe spread (TS) were added in the model group, with statistical difference (P <0. 01). Compared with the mod- el group, nerve conduction velocity was speeded; PL and ITS decreased in the TJC group and the mecobal- amin treatment group, with statistical difference (P <0. 01). Besides, the nerve conduction velocity was superior in the TJC group than in the mecobalamin treatment group, with statistical difference (P <0. 05). (2) Immunohistochemical results showed, the staining of intraepidermal nerve fiber was not clear and dispersedly distributed in the model group, with no nerve fiber staining in local regions. Nerve fibers were not regular in lesser amount and shallow stained in the mecobalamin treatment group, with no nerve fiber staining in local regions. Nerve fibers were not regular in lesser amount and dispersedly distributed in the TJC group. (3) HE staining showed that tibial nerve tissue was severely swollen with swollen myelin sheath in the mod- el group. It was difficult to identity myelin sheath. Vaculole degenerated in local regions. Swollen axon could be seen. Partial axons were separated and degenerated. In the mecobalamin treatment group tibial nerve tissue was edematous with swollen myelin sheath. It was difficult to identity myelin sheath. Axons were locally separated. In the JMC group tibial nerve tissue was swollen with unclear myelin sheath and swollen axons. CONCLUSION: TJC could improve peripheral neuropathy of diabetic rats.

[Chemical constituents from the fruits of Areca catechu].

OBJECTIVE: To investigate the chemical constituents of the fruits of Areca catechu. METHODS: The chemical constituents were isolated by silica gel, RP-18 and Sephadex LH-20 column chromatographies. Their structures were determined by chemical and spectroscopic methods. RESULTS: Thirteen compounds were isolated from the 95% ethanol extract of the fruits of Areca catechu. Their structures were identified as isorhamnetin (1), quercetin (2), liquiritigenin (3), 5,7,4'-trihydroxy-3',5'-dimethoxyflavanone (4), (+)-catechin (5), resveratrol (6), ferulic acid (7), vanillic acid (8), 5,8-epidioxiergosta-6,22-dien-3beta-ol (9), stigmasta-4-en-3-one (10), beta-sitosterol (11), cycloartenol (12), and de-O-methyllasiodiplodin (13), respectively. CONCLUSION: Compounds 2-4,6,7,9,10, 12,13 are isolated from this plant for the first time.

A novel C2-domain phospholipid-binding protein, OsPBP1, is required for pollen fertility in rice.

Pollen fertility is a crucial factor for successful pollination and essential for seed formation. Recent studies have suggested that a diverse range of internal and external factors, signaling components and their related pathways are likely involved in pollen fertility. Here, we report a single C2-domain containing protein, OsPBP1, initially identified through cDNA microarray analysis. OsPBP1 is a single copy gene and preferentially expressed in pistil and pollen but down-regulated by pollination. OsPBP1 had a calcium concentration-dependent phospholipid-binding activity and was localized mainly in cytoplasm and nucleus, but translocated onto the plasma membrane in response to an intracellular Ca(2+) increase. Pollen grains of antisense OsPBP1 transgenic lines were largely nonviable, germinated poorly in vitro and of low fertility. OsPBP1 protein was localized in a region peripheral to pollen wall and vesicles of elongating pollen tube, and its repressed expression reduced substantially this association and led to alteration of microfilament polymerization during pollen germination. Taken together, these results indicate that OsPBP1 is a novel functional C2-domain phospholipids-binding protein that is required for pollen fertility likely by regulating Ca(2+) and phospholipid signaling pathways.