Zhinan Mei

Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE The seed of Entada phaseoloides (L.) Merr. (Entada phaseoloides) has been long used as an effective herb for the treatment of Diabetes mellitus by Dai people, one of the Chinese ethnic minorities. Saponin is an abundant type of secondary metabolic products in the seed of this plant. The aim of this study is to evaluate the potential therapeutic effects of total saponins from Entada phaseoloides (TSEP) in experimental type 2 Diabetes mellitus (T2DM) rats. MATERIALS AND METHODS T2DM rats were induced by high-fat diet and low-dose streptozotocin (STZ). Then different oral doses of TSEP (25, 50 and 100 mg/kg) were administrated to T2DM rats for 21 days. For comparison, a standard antidiabetic drug, metformin (200 mg/kg), was used as a positive control drug. Then the relative biochemical analysis and histopathological examination were made to evaluate the antidiabetic effect of TSEP. RESULTS TSEP dramatically reduced fasted blood glucose and serum insulin levels and alleviates hyperglycemia associated oxidative stress in T2DM rats. Moreover, a significantly hypolipidemic effect and an improvement in tissue steatosis could be observed after TSEP administration. Further investigations revealed a possible anti-inflammation effect of TSEP by examining serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). The effects of TSEP exhibited a dose-dependent manner and were comparable to metformin. CONCLUSION Our present study demonstrates both hypoglycemic and hypolipidemic activities of TSEP in T2DM rats, which support its antidiabetic property. This work also implies a possibility that TSEP exerts its therapeutic effect through repressing chronic inflammation responses.

Antidiabetic effect of total flavonoids from Sanguis draxonis in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated (Tang et al., 1995; Wei et al., 1998), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats. MATERIALS AND METHODS T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF. RESULTS SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). CONCLUSIONS This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF.

Chemical constituents from Eucalyptus citriodora Hook leaves and their glucose transporter 4 translocation activities.

Bioassay-guided phytochemical investigation of the EtOAc fraction from the leaves of a Chinese medicinal herb, Eucalyptus citriodora Hook, resulted in the isolation of a new compound rhodomyrtosone E (1), along with 12 known compounds (2-13). The structure of the new compound was established by 1D and 2D NMR, MS data and X-ray crystallographic analysis. Betulinic acid (2) and corosolic acid (5) increased glucose transporter 4 (GLUT-4) translocation by 2.38 and 1.78-fold, respectively.

Kurarinol induces hepatocellular carcinoma cell apoptosis through suppressing cellular signal transducer and activator of transcription 3 signaling

Kurarinol is a flavonoid isolated from roots of the medical plant Sophora flavescens. However, its cytotoxic activity against hepatocellular carcinoma (HCC) cells and toxic effects on mammalians remain largely unexplored. Here, the pro-apoptotic activities of kurarinol on HCC cells and its toxic impacts on tumor-bearing mice were evaluated. The molecular mechanisms underlying kurarinol-induced HCC cell apoptosis were also investigated. We found that kurarinol dose-dependently provoked HepG2, Huh-7 and H22 HCC cell apoptosis. In addition, kurarinol gave rise to a considerable decrease in the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) in HCC cells. Suppression of STAT3 signaling is involved in kurarinol-induced HCC cell apoptosis. In vivo studies showed that kurarinol injection substantially induced transplanted H22 cell apoptosis with low toxic impacts on tumor-bearing mice. Similarly, the transcriptional activity of STAT3 in transplanted tumor tissues was significantly suppressed after kurarinol treatment. Collectively, our current research demonstrated that kurarinol has the capacity of inducing HCC cell apoptosis both in vitro and in vivo with undetectable toxic impacts on the host. Suppressing STAT3 signaling is implicated in kurarinol-mediated HCC cell apoptosis.

Antidiabetic Effect of Methanolic Extract from Berberis julianae Schneid. via Activation of AMP-Activated Protein Kinase in Type 2 Diabetic Mice.

We have investigated the antidiabetic effect and mechanism of methanolic extract of Berberis julianae Schneid. (BJSME) in STZ induced Type 2 diabetes mellitus mice. T2DM mice were induced by high fat diet and low dose streptozotocin (STZ). BJSME was orally administrated at the doses of 60, 120, and 240 mg/kg/d, for 21 days. Metformin was used as positive control drug. Food intake, body weight, plasma glucose, oral glucose tolerance test, insulin tolerance test, insulin, and blood-lipid content were measured. The effects of BJSME on the glucose transporter 4 (GLUT4) translocation in L6 myotubes and the GLUT4 protein expression in skeletal muscle as well as phosphorylation of the AMP-activated protein kinase (AMPK) in liver and muscle were examined. In vitro and in vivo results indicate that BJSME increased GLUT4 translocation by 1.8-fold and BJSME significantly improved the oral glucose tolerance and low density lipoprotein cholesterol (LDL-C) of serum and reduced body weight, glucose, and other related blood-lipid contents. The BJSME treatment also stimulated the phosphorylation of AMPK. Thus, BJSME seems to possess promising beneficial effects for the treatment of T2DM with the possible mechanism via stimulating AMPK activity.

Analgesic effects and possible mechanisms of iridoid glycosides from Lamiophlomis rotata (Benth.) Kudo in rats with spared nerve injury

ETHNOPHARMACOLOGICAL RELEVANCE Lamiophlomis rotata (Benth.) Kudo (L. rotata) is a medical plant that has been traditionally used for centuries for the treatment of pain, such as bone and muscle pain, joint pain and dysmenorrhea. Although iridoid glycosides of L. rotata (IGLR) are the major active components of it according to reports, it still remains poorly understood about the molecular mechanisms underlying analgesic effects of IGLR. The aim of the present study was to investigate the analgesic effect of IGLR on a spared nerve injury (SNI) model of neuropathic pain. MATERIALS AND METHODS The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. Then SNI rats were treated with IGLR for 14 days, using normal saline as the negative control. The paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 9, 11, 13 and 14 after operation, respectively. After 14 days, the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10) and cyclic guanosine monophosphate (cGMP) in the spinal dorsal horn were measured by the corresponding kits, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKGI) of spinal cord were analyzed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of N-methyl-D-aspartate receptor (NMDAR) and protein kinase C (PKCγ) of the spinal dorsal horn was performed by Western blot. Before all the experiments, motor coordination performance and locomotor activity had been tested. RESULTS Our results showed that remarkable mechanical allodynia was observed on day 1 after operation in the SNI model, which was accompanied by a decrease in PMWT. Treatment with IGLR (200, 400, 800mg/kg) significantly alleviated SNI-induced mechanical allodynia, markedly decreased the levels of NO, NOS, TNF-α, IL-1β and cGMP, and increased the level of IL-10. Meanwhile, IGLR (200, 400, 800mg/kg) also inhibited the protein expression of NMDAR, PKCγ and the mRNA expression of iNOS and PKGΙ in the spinal cord. In addition, gavage with the IGLR aqueous extract (800mg/kg) did not signifiantly alter motor coordination or locomotor activity. CONCLUSIONS These results indicated IGLR could produce an anti-neuropathic pain effect that might partly be related to the inhibition of the NO/cGMP/PKG and NMDAR/PKC pathways and the level of TNF-α, IL-1β as well as to the increase of the level of IL-10 in spinal cord.

Anti-inflammatory and Anticancer Activities of Ethanol Extract of Pendulous Monkshood Root in vitro

AIM Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. MATERIALS AND METHODS The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. RESULTS The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti- inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200 μg/mL. The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. CONCLUSION Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic.

Antimicrobial Constituents from the Tubers of Bletilla ochracea

A new 2-(2-methylpropyl)butanedioic acid derivative, bletillin A ( 1), and a new bibenzyl, bletillin B ( 2), together with seventeen known compounds ( 3- 19), were isolated from the tubers of Bletilla ochracea Schltr. Their structures were established by detailed spectroscopic analyses. Phenanthrenes ( 12- 14) exhibited antibacterial activities against gram-positive bacteria Staphylococcus aureus, S. epidermidis, and Bacillus subtilis, with MIC values of 12.5-25 µg/mL.

Relaxant effect of 1-butanol fraction from Elaeagnus pungens leaf through inhibiting l-type Ca2+ channel on guinea pig tracheal smooth muscle

ETHNOPHARMACOLOGICAL RELEVANCE The leaf of Elaeagnus pungens thunb. (Family Elaeagnaceae) has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional Chinese medicine. In the past years, only a few of preliminary studies reported the chemical constituents and pharmacology effects of the herb, but their action on the tracheal relaxation has not been investigated. AIM OF THE STUDY To investigate the relaxing effect and mechanism of the extracts from Elaeagnus pungens leaves on guinea pig tracheal smooth muscle and bronchi smooth muscle cells. MATERIALS AND METHODS Four fractions of different polarities from Elaeagnus pungens leaves were tested to the tracheal strips on the resting tension or pre-contracted by histamine (20 μM) and acetylcholine (20 μM). Inhibitory effects of the 1-butanol fraction (400mg/ml) on cumulative histamine and acetylcholine (0.2-20 μM) induced contraction were measured. In order to determine the mediators on the 1-butanol fraction effect, the relaxing effect of the 1-butanol fraction was evaluated in the absence and presence of β-adrenoceptor antagonists (1 μM propranolol), K(+) channels-blockers (4-aminopyridine (2mM), tetraethylammonium chloride (5mM) or glibenclamide (10 μM)), the cyclooxygenase inhibitor (indomethacin, 10 μM), nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester, 100 μM) or L-type Ca(2+) channel inhibitor (nifedipine, 1 μM). Moreover, [Ca(2+)]i in bronchi smooth muscle cells was analyzed by measuring the fluorescence intensity with confocal system. RESULTS 1-Butanol fraction induced the highest relaxant effect among four fractions of different polarities from Elaeagnus pungens leaves, and significantly relaxed the tracheal strip in the concentration-dependent manner on the resting tension and pre-contracted by histamine phosphate and acetylcholine. It also produced an unparallel rightward shift of the cumulative concentration-response curve of histamine or acetylcholine. Furthermore, the relaxant effect of 1-butanol fraction was not affected by propranolol, glibenclamide, tetraethylammonium chloride, 4-aminopyridine, indomethacin and Nω-nitro-L-arginine methyl ester. However, 1-butanol fraction-induced relaxation decreased after adding nifedipine. It also concentration-dependently inhibited CaCl2-induced contraction in the Ca(2+)-free, 60mM K(+)-containing solution. Additionally, [Ca(2+)]i in the BSMCs significantly reduced after administration of the 1-butanol fraction. CONCLUSIONS The 1-butanol fraction from Elaeagnus pungens leaves resulted in a relaxation in the non-precontracted and pre-contracted tracheal strips. The relaxant effect was not related to K(+) channels, NO, cGMP or β-adrenoceptors, but related to the inhibition of Ca(2+) influx through L-type Ca(2+) channels.

Acridone alkaloids with cytotoxic and antimalarial activities from Zanthoxylum simullans Hance.

Background: Zanthoxylum simullans Hance is a popular natural spice belonging to the Rutaceae family and it is one of the common prescribed herbs in traditional Chinese medicine. Materials and Methods: The chemical constituents were mainly isolated and purified by silica gel column chromatography and semi-preparative High Performance Liquid Chromatography. Their structures were identified by comparing the spectral data with those reported in the literature. Cytotoxic activities for the isolated acridone alkaloids were evaluated against two prostate cancer cell lines PC-3M and Lymph Node Carcinoma of Prostate (LNCaP), and their antimalarial activities were tested against two different strains of the parasite Plasmodium falciparum 3D7, and Dd2. Results: The root bark MeOH extract of Z. simullans Hance afforded β-sitosterol, 4-methoxy benzoic acid, daucosterol, and five acridone alkaloids, normelicopidine, normelicopine, melicopine, melicopidine, and melicopicine. All five acridone alkaloids were isolated from this plant for the first time and exhibited certain cytotoxic and antimalarial activities in vitro. Conclusion: Normelicopidine was the most active against PC-3M, LNCaP and Dd2 with IC50 values of 12.5, 21.1, and 18.9 ug/mL respectively.