Natural products in non-alcoholic fatty liver disease (NAFLD): Novel lead discovery for drug development.

With changing lifestyles, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. A substantial increase in the incidence, mortality, and associated burden of NAFLD-related advanced liver disease is expected. Currently, the initial diagnosis of NAFLD is still based on ultrasound and there is no approved treatment method. Lipid-lowering drugs, vitamin supplementation, and lifestyle improvement treatments are commonly used in clinical practice. However, most lipid-lowering drugs can produce poor patient compliance and specific adverse effects. Therefore, the exploration of bio-diagnostic markers and active lead compounds for the development of innovative drugs is urgently needed. More and more studies have reported the anti-NAFLD effects and mechanisms of natural products (NPs), which have become an important source for new drug development to treat NAFLD due to their high activity and low side effects. At present, berberine and silymarin have been approved by the US FDA to enter clinical phase IV studies, demonstrating the potential of NPs against NAFLD. Studies have found that the regulation of lipid metabolism, insulin resistance, oxidative stress, and inflammation-related pathways may play important roles in the process. With the continuous updating of technical means and scientific theories, in-depth research on the targets and mechanisms of NPs against NAFLD can provide new possibilities to find bio-diagnostic markers and innovative drugs. As we know, FXR agonists, PPARα agonists, and dual CCR2/5 inhibitors are gradually coming on stage for the treatment of NAFLD. Whether NPs can exert anti-NAFLD effects by regulating these targets or some unknown targets remains to be further studied. Therefore, the study reviewed the potential anti-NAFLD NPs and their targets. Some works on the discovery of new targets and the docking of active lead compounds were also discussed. It is hoped that this review can provide some reference values for the development of non-invasive diagnostic markers and new drugs against NAFLD in the clinic.

Naringin protects against inflammation and apoptosis induced by intestinal ischemia-reperfusion injury through deactivation of cGAS-STING signaling pathway.

Effective amelioration of ischemia/reperfusion (I/R)-induced intestinal injury and revealing its mechanisms remain the challenges in both preclinic and clinic. Potential mechanisms of naringin in ameliorating I/R-induced intestinal injury remain unknown. Based on pre-experiments, I/R-injured rat intestine in vivo and hypoxia-reoxygenation (H/R)-injured IEC-6 cells in vitro were used to verify that naringin-alleviated I/R-induced intestinal injury was mediated via deactivating cGAS-STING signaling pathway. Naringin improved intestinal damage using hematoxylin and eosin staining and decreased alanine aminotransferase and aspartate aminotransferase contents in plasma. Naringin decreased inflammation characterized by reducing IL-6, IL-1ß, TNF-α, and IFN-ß contents in both plasma and IEC-6 cells. Naringin mitigated oxidative stress via recovering superoxide dismutase, glutathione, and malondialdehyde levels in the I/R-injured intestine. Naringin reduced the expression of apoptotic proteins, including Bax, caspase-3, and Bcl-2, and reduced terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells both in vivo and in vitro, and decreased Hoechst 33342 signals in vitro. cGAS, STING, p-TBK1, p-IRF3, and NF-κB expressions were up-regulated both in vivo and in vitro respectively and the up-regulated indexes were reversed by naringin. Transfection of cGAS-siRNA and cGAS-cDNA significantly down-regulated and up-regulated cGAS-STING signaling-related protein expressions, respectively, and partially weakened naringin-induced amelioration on these indexes, suggesting that deactivation of cGAS-STING signaling is the crucial target for naringin-induced amelioration on I/R-injured intestine.

Protection of pancreatic ß-cell by phosphocreatine through mitochondrial improvement via the regulation of dual AKT/IRS-1/GSK-3ß and STAT3/Cyp-D signaling pathways.

Diabetes mellitus (DM) is a metabolic syndrome, caused by insufficient insulin secretion or insulin resistance (IR). DM enhances oxidative stress and induces mitochondrial function in different kinds of cell types, including pancreatic ß-cells. Our previous study has showed phosphocreatine (PCr) can advance the mitochondrial function through enhancing the oxidative phosphorylation and electron transport ability in mitochondria damaged by methylglyoxal (MG). Our aim was to explore the potential role of PCr as a molecule to protect mitochondria from diabetes-induced pancreatic ß-cell injury with insulin secretion deficiency or IR through dual AKT/IRS-1/GSK-3ß and STAT3/Cyclophilin D (Cyp-D) signaling pathways. MG-induced INS-1 cell viability, apoptosis, mitochondrial division and fusion, the morphology, and function of mitochondria were suppressed. Flow cytometry was used to detect the production of intracellular reactive oxygen species (ROS) and the changes of intracellular calcium, and the respiratory function was measured by oxygraph-2k. The expressions of AKT, IRS-1, GSK-3ß, STAT3, and Cyp-D were detected using Western blot. The result showed that the oxidative stress-related kinases were significantly restored to the normal level after the pretreatment with PCr. Moreover, PCr pretreatment significantly inhibited cell apoptosis, decreased intracellular calcium, and ROS production, and inhibited mitochondrial division and fusion, and increased ATP synthesis damaged by MG in INS-1 cells. In addition, pretreatment with PCr suppressed Cytochrome C, p-STAT3, and Cyp-D expressions, while increased p-AKT, p-IRS-1, p-GSK-3ß, caspase-3, and caspase-9 expressions. In conclusion, PCr has protective effect on INS-1 cells in vitro and in vivo, relying on AKT mediated STAT3/ Cyp-D pathway to inhibit oxidative stress and restore mitochondrial function, signifying that PCr might become an emerging candidate for the cure of diabetic pancreatic cancer ß-cell damage.

Neuroprotective Effect of Dioscin against Parkinson's Disease via Adjusting Dual-Specificity Phosphatase 6 (DUSP6)-Mediated Oxidative Stress.

Exploration of lead compounds against Parkinson's disease (PD), a neurodegenerative disease, is of great important. Dioscin, a bioactive natural product, shows various pharmacological effects. However, the activities and mechanisms of dioscin against PD have not been well investigated. In this study, the tests on 6-hydroxydopamine (6-OHDA)-induced PC12 cells and rats were carried out. The results showed that dioscin dramatically improved cell viability, decreased reactive oxygen species (ROS) levels, improved motor behavior and tyrosine hydroxylase(TH) levels and restored the levels of glutathione (GSH) and malondialdehyde (MDA) in rats. Mechanism investigation showed that dioscin not only markedly increased the expression level of dual- specificity phosphatase 6 (DUSP6) by 1.87-fold in cells and 2.56-fold in rats, and decreased phospho-extracellular regulated protein kinases (p-ERK) level by 2.12-fold in cells and 2.34-fold in rats, but also increased the levels of nuclear factor erythroid2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), superoxide dismutase (SOD) and decreased the levels of kelch-1ike ECH-associated protein l (Keap1) in vitro and in vivo. Furthermore, DUSP6 siRNA transfection experiment in PC12 cells validated the protective effects of dioscin against PD via regulating DUSP6 to adjust the Keap1/Nrf2 pathway. Our data supported that dioscin has protection against PD in regulating oxidative stress via DUSP6 signal, which should be considered as an efficient candidate for the treatment of PD in the future.

Rosmarinic acid exerts an antagonistic effect on nonalcoholic fatty liver disease by regulating the YAP1/TAZ-PPARγ/PGC-1α signaling pathway.

Rosmarinic acid (RA) is a water-soluble phenolic compound extracted from Boraginaceae and Lamiaceae. This study was designed to investigate the role and mechanism of action of RA in improving nonalcoholic fatty liver disease (NAFLD). Male SD rats maintained on a high fat diet and L02 cells stimulated with oleic acid were treated with RA. Our results showed that RA significantly reduced total cholesterol, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels and increased high-density lipoprotein cholesterol, superoxide dismutase and adenosine triphosphate levels both in vivo and in vitro. Hematoxylin and eosin staining and oil red O staining showed that RA had a good lipid-lowering effect and substantial protective effects on liver injury. Transmission electron microscopy and JC-1 fluorescence results showed that RA could improve mitochondrial damage in hepatocytes. Additionally, flow cytometry results indicated that RA inhibited ROS generation and apoptosis in L02 cells. The impaired hepatocytes were restored by using RA in NAFLD models characterized by down-regulating YAP1 and TAZ, meanwhile up-regulating PPARγ and PGC-1α. When YAP1 was over-expressed, RA reduced the expression of YAP1; however, the action of RA was significantly blocked by silencing YAP1. The experimental results indicated that RA markedly alleviated NAFLD by repairing mitochondrial damage and regulating the YAP1/TAZ-PPARγ/PGC-1α signaling pathway.

Evaluation of chiral separation based on bovine serum albumin-conjugated carbon nanotubes as stationary phase in capillary electrochromatography.

In this work, we utilized adsorbed BSA and multiwalled carbon nanoparticles (BSA/MWCNTs) as a stationary phase in open tubular (OT) capillary for separation of chiral drugs. (3-Aminopropyl)triethoxysilane was used to assist fabrication of BSA/MWCNTs-coated OT column by covalent bonding. Incorporation of MWCNTs nanomaterials into a polymer matrix could increase the phase ratio and take advantage of the easy preparation of an open tubular CEC column. SEM was carried out to characterize the BSA/MWCNTs OT columns. The electrochromatographic performance of the OT columns was evaluated by separation of ketoprofen, ibuprofen, uniconazole, and hesperidin. The effects of MWCNTs concentration, background solution pH and concentration, and applied voltage on separation were investigated. Chiral separations of ketoprofen, ibuprofen, uniconazole, and hesperidin were achieved using the BSA/MWCNTs-coated OT column with resolutions of 24.20, 12.81, 1.50, and 1.85, respectively. Their optimas were found in the 30 mM phosphate buffers at pH 5.0, 6.5, 7.0, and 6.5, respectively. In addition, the columns demonstrated good repeatability and stability with the run-to-run, day-to-day, and batch-to-batch RSDs of migration times less than 3.5%.

Correction: Zhao, X.W., et al. Dioscin Induces the Apoptosis of Human Cervical Carcinoma HeLa and SiHa Cells Through ROS-mediated DNA Damage, Cell Cycle Arrest and Mitochondrial Signaling Pathways. Molecules 2016, 21, 730.

During the course of a review of our publications, an error in the title paper [...].

Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo-FOXO3A and PI3K/AKT signaling pathways.

Atherosclerosis (AS), a progressive disorder, is one of the tough challenges in the clinic. Scutellarin, an extract from Herba Erigerontis, is found to have oxygen-free radicals scavenging effects and antioxidant effects. In this study, we aimed to investigate the anti-AS effects of scutellarin is related to controlling the Hippo-FOXO3A and PI3K/AKT signal pathway. To establish an AS model, the rats in the scutellarin and model groups were intraperitoneally injected with vitamin D 3 and then fed a high-fat diet for 12 weeks. In addition, in vitro angiotensin II-induced apoptosis of human aortic endothelial cells (HAECs) were used to establish models. Scutellarin significantly reduced blood lipid levels and increased antioxidase levels in both models. Additionally, scutellarin inhibited reactive oxygen species generation and apoptosis in HAECs. The impaired vascular barrier function was restored by using scutellarin in AS rats and in HAECs cells characterized by inhibiting mammalian sterile-20-like kinases 1 (Mst1) phosphorylation, Yes-associated protein (YAP) phosphorylation, forkhead box O3A (FOXO3A) phosphorylation at serine 207, nuclear translocation of FOXO3A, and upregulating protein expression of AKT and FOXO3A phosphorylation at serine 253. Scutellarin significantly reduced Bcl-2 interacting mediator of cell death (Bim), caspase-3, APO-1, CD95 (Fas), and Bax: Bcl-2-associated X (Bax) levels and activated Bcl-2: B-cell lymphoma-2 (Bcl-2). Scutellarin also significantly inhibited the expression of Mst1, YAP, FOXO3A at the messenger RNA level. When Mst1 was overexpressed or phosphoinositide 3-kinases suppressed, the effects of scutellarin were significantly blocked. In conclusion, the results of the present study suggest that scutellarin exerts protective effects against AS by inhibiting endothelial cell injury and apoptosis by regulating the Hippo-FOXO3A and PI3K/AKT signal pathways.

Combination of dihydromyricetin and ondansetron strengthens antiproliferative efficiency of adriamycin in K562/ADR through downregulation of SORCIN: A new strategy of inhibiting P-glycoprotein.

Though the advancement of chemotherapy drugs alleviates the progress of cancer, long-term therapy with anticancer agents gradually leads to acquired multidrug resistance (MDR), which limits the survival outcomes in patients. It was shown that dihydromyricetin (DMY) could partly reverse MDR by suppressing P-glycoprotein (P-gp) and soluble resistance-related calcium-binding protein (SORCIN) independently. To reverse MDR more effectively, a new strategy was raised, that is, circumventing MDR by the coadministration of DMY and ondansetron (OND), a common antiemetic drug, during cancer chemotherapy. Meanwhile, the interior relation between P-gp and SORCIN was also revealed. The combination of DMY and OND strongly enhanced antiproliferative efficiency of adriamycin (ADR) because of the increasing accumulation of ADR in K562/ADR-resistant cell line. DMY could downregulate the expression of SORCIN and P-gp via the ERK/Akt pathways, whereas OND could not. In addition, it was proved that SORCIN suppressed ERK and Akt to inhibit P-gp by the silence of SORCIN, however, not vice versa. Finally, the combination of DMY, OND, and ADR led to G2/M cell cycle arrest and apoptosis via resuming P53 function and restraining relevant proteins expression. These fundamental findings provided a promising approach for further treatment of MDR.

MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1.

As one classic anticancer drug, clinical application of Doxorubicin (Dox) is limited due to its side effects. In our previous work, we have investigated the drug targets to treat Dox-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. In this paper, the mechanisms and new drug-target associated with Dox-induced hepatotoxicity were explored. The results showed that Dox markedly inhibited cell viability and cellular respiration, induced cell morphologic change and increased ROS level. Moreover, Dox increased ALT and AST levels, caused pathological damage, increased MDA level and decreased SOD level in mice. Mechanism investigation showed that Dox markedly up-regulated the expression level of miR-128-3p, down-regulated Sirt1 expression level and affected the protein levels of Nrf2, Keap1, Sirt3, NQO1 and HO-1 to cause oxidative stress in liver. Furthermore, double-luciferase reporter assay, and co-transfection test showed that miR-128-3p directly targeted Sirt1. In addition, miR-128-3p mimics in AML-12 cells enhanced Dox-induced oxidative damage via inhibiting cellular respiration, increasing ROS level and mitochondrial superoxide formation. The protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1 in miR-128-3p mimic + Dox group were decreased compared with Dox group. Transfection of miR-128-3p inhibitor weakened Dox-induced oxidative damage via increasing cellular respiration, suppressing cellular ROS level and mitochondrial superoxide formation. The protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1 in miR-128-3p inhibitor + Dox group were increased compared with Dox group. In mice, Dox-induced liver damage was deteriorated by miR-128-3p agomir via increasing the levels of ALT, AST, MDA, and down-regulating the protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1. While, miR-128-3p antagomir alleviated liver injury via decreasing the levels of ALT, AST, MDA, and up-regulating the protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1. Our data showed that miRNA-128-3p aggravated Dox-induced liver injury by promoting oxidative stress via targeting Sirt1, which should be considered as one new drug target to treat Dox-induced liver injury.

Dioscin ameliorates intestinal ischemia/reperfusion injury via adjusting miR-351-5p/MAPK13-mediated inflammation and apoptosis.

Inflammatory reaction and cell apoptosis are two important processes in intestinal ischemia/reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating inflammation and apoptosis is critical important. In this paper, the results indicated that dioscin significantly increased cell viability, and inhibited inflammation and apoptosis caused by hypoxia-reoxygenation (H/R) injury in IEC-6 cells. in vivo II/R injury, dioscin markedly suppressed inflamma- tion and apoptosis, improved pathological changes, and depressed chiu' score in rats. Mechanistic studies indicated that dioscin notably up-regulated the expression level of MAPK13 through decreasing miR-351-5p level, and thereby decreased the expression levels of p-PKD1, NF-κB, Apaf-1, cleaved Caspase-3 and cleaved Caspase-9. Furthermore, miR-351-5p mimic and inhibitor experiments in IEC-6 cells further proved that dioscin up-regulated MAPK13 expression by decreasing miR-351-5p level to inhibit inflammation and apoptosis. Therefore, dioscin showed protective effect against II/R injury via adjusting miR-351-5/MAPK13-mediated inflammation and apoptosis. Dioscin should be considered as one potent candidate and miR-351-5/ MAPK13 should be one effective drug target for the treatment of II/R injury.

Correction to: Protective effects of dioscin against alcohol­induced liver injury.

During the course of writing and revision of this paper, the band of GAPDH.

Neuroprotective Effect of Dioscin on the Aging Brain.

Our previous works have shown that dioscin, a natural product, has various pharmacological activities, however, its role in brain aging has not been reported. In the present study, in vitro H2O2-treated PC12 cells and in vivo d-galactose-induced aging rat models were used to evaluate the neuroprotective effect of dioscin on brain aging. The results showed that dioscin increased cell viability and protected PC12 cells against oxidative stress through decreasing reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels. In vivo, dioscin markedly improved the spatial learning ability and memory of aging rats, reduced the protein carbonyl content and aging cell numbers, restored the levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and nitric oxide synthase (NOS) in brain tissue, and reversed the histopathological structure changes of nerve cells. Mechanism studies showed that dioscin markedly adjusted the MAPK and Nrf2/ARE signalling pathways to decrease oxidative stress. Additionally, dioscin also significantly decreased inflammation by inhibiting the mRNA or protein levels of TNF-α, IL-1ß, IL-6, CYP2E1 and HMGB1. Taken together, these results indicate that dioscin showed neuroprotective effect against brain aging via decreasing oxidative stress and inflammation, which should be developed as an efficient candidate in clinical to treat brain aging in the future.

Correction: Zhao, L.S., et al. Protective Effect of the Total Flavonoids from Rosa laevigata Michx Fruit on Renal Ischemia-Reperfusion Injury through Suppression of Oxidative Stress and Inflammation. Molecules 2016, 21, 952.

During the course of a review of our publications, an error in the title paper [...].

Correction: Liu, M., et al. Potent Effects of Flavonoid-Rich Extract from Rosa laevigata Michx Fruit against Hydrogen Peroxide-Induced Damage in PC12 Cells via Attenuation of Oxidative Stress, Inflammation and Apoptosis. Molecules 2014, 19, 11816-11832.

During the course of a review of our publication, an error in the title paper [...].

Targeting P-glycoprotein and SORCIN: Dihydromyricetin strengthens anti-proliferative efficiency of adriamycin via MAPK/ERK and Ca2+ -mediated apoptosis pathways in MCF-7/ADR and K562/ADR.

Recently, a new target Ca2+ -binding protein SORCIN was reported to participate in multidrug resistance (MDR) in cancer. Here we aim to investigate whether dihydromyricetin (DMY), a dihydroflavonol compound with anti-inflamatory, anti-oxidant, anti-bacterial and anti-tumor actions, reverses MDR in MCF-7/ADR and K562/ADR and to elucidate its potential molecular mechanism. DMY enhanced cytotoxicity of adriamycin (ADR) by downregulating MDR1 mRNA and P-gp expression through MAPK/ERK pathway and also inhibiting the function of P-gp significantly. Meanwhile, DMY decreased mRNA and protein expression of SORCIN, which resulted in elevating intracellular free Ca2+ . Finally, we investigated co-administration ADR with DMY remarkably increased ADR-induced apoptosis. Further study showed DMY elevated ROS levels and caspase-12 protein expression, which signal apoptosis in endoplasmic reticulum. At the same time, proteins related to mitochondrial apoptosis were also changed such as Bcl-2, Bax, caspase-3, caspase-9, and PARP. Finally, nude mice model also demonstrated that DMY strengthened anti-tumor activity of ADR in vivo. In conclusion, DMY reverses MDR by downregulating P-gp, SORCIN expression and increasing free Ca2+ , as well as, inducing apoptosis in MCF-7/ADR and K562/ADR. These fundamental findings provide evidence for further clinical research in application of DMY as an assistant agent in the treatment of cancer.

Anticancer effect of SZC015 on pancreatic cancer via mitochondria-dependent apoptosis and the constitutive suppression of activated nuclear factor κB and STAT3 in vitro and in vivo.

Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Advances in therapeutic strategies such as chemotherapy have improved the clinical outcomes for pancreatic cancer patients. However, developing new therapeutic compounds against pancreatic cancer is still urgent due to the poor prognosis. Here, we show that SZC015, an oleanolic acid derivative, exhibits potent inhibitory effect on both pancreatic cancer cells in vitro and the corresponding xenograft tumors in vivo. Mechanistically, the activation of intrinsic apoptosis and G1 phase arrest resulting from mitochondria damage caused by SZC015 contribute significantly to the anticancer effects of SZC015. SZC015 also has remarkably inhibitory effects on the transcription factors that are extensively activated in pancreatic cancer tissues. As a constitutively activated transcription factor in pancreatic cancer, the nuclear factor κB is highly suppressed after SZC015 treatment in vitro or administration in vivo. Based on the bioinformatics analysis of microarray data, we validate that JAK2/STAT3 signaling is indeed activated in the human pancreatic cancer tissues and SZC015 also shows inhibitory effect on this signaling both in vitro and in vivo. These data suggest the potent effects of SZC015 on pancreatic cancer and also provided novel insights into the mechanisms of SZC015 as a new potent candidate for treating pancreatic cancer.

Phosphocreatine attenuates endoplasmic reticulum stress-mediated hepatocellular apoptosis ameliorates insulin resistance in diabetes model.

Diabetes mellitus (DM) associated liver damage is a major health burden. Hepatocellular-damage in DM characterized with elevated endoplasmic reticulum stress (ER) and may enhanced insulin-resistance. Phosphocreatine (PCr) a rapidly high-energy-reserve molecule of phosphates naturally occurs in liver, brain and skeletal muscle. This study aimed to investigate the protective effect of PCr on the liver-injury-associated with DM and to report the mechanism involved. Wistar rat's diabetes model was induced using streptozotocin (STZ), and the animals were treated with 20 mg/kg, or 50 mg/kg PCr injection. Blood glucose level, and body wt were recorded. Liver tissues homogenate were analyzed for liver damage markers alanine transaminase (ALT), aspartate transaminase (AST). Liver tissues proteins further evaluated for apoptosis, endoplasmic reticulum stress (ER), and insulin resistance biomarkers using western blotting. Our results revealed that PCr reduced blood glucose level, improved body wt, ameliorates liver function enzymes. Furthermore, PCr upregulates anti-apoptotic Bcl2 proteins expression, and down-regulates significantly pro-apoptotic casp3 and Bax proteins expression in vivo and invitro. Moreover, ER stress CHOP, GRP78 and ATF4 biomarkers level were significantly attenuated in PCr treated animals comparing to STZ diabetes associated liver-damage model with significant improving in insulin-resistance Akt and IRS-1. Our results revealed that treating with PCr in diabetes-associated liver injury models decreased blood glucose level and possess protective effect in-vitro and in-vivo, which could be suggested as potential therapeutic strategy for diabetes associated liver injury patients.

Dioscin: A diverse acting natural compound with therapeutic potential in metabolic diseases, cancer, inflammation and infections.

Currently, the numbers of patients with cancer, fibrosis, diabetes, chronic kidney disease, stroke and osteoporosis are increasing fast and fast. It's critical necessary to discovery lead compounds for new drug development. Dioscin, one active compound in some medicinal plants, has anti-inflammation, immunoregulation, hypolipidemic, anti-viral, anti-fungal and anti-allergic effects. In recent years, dioscin has reached more and more attention with its potent effects to treat liver, kidney, brain, stomach and intestine damages, and metabolic diseases including diabetes, osteoporosis, obesity, hyperuricemia as well as its anti-cancer activities through adjusting multiple targets and multiple signals. Therefore, dioscin is a promising multi-target candidate to treat various diseases. This review paper summarized the progress on pharmacological activities and mechanisms of dioscin, which may provide useful data for development and exploration of this natural product in the further.

Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms.

Epidemiological studies have implied that diabetes mellitus (DM) will become an epidemic accompany with metabolic and endocrine disorders worldwide. Most of DM patients are affected by type 2 diabetes mellitus (T2DM) with insulin resistance and insulin secretion defect. Generally, the strategies to treat T2DM are diet control, moderate exercise, hypoglycemic and lipid-lowing agents. Despite the therapeutic benefits for the treatment of T2DM, most of the drugs can produce some undesirable side effects. Considering the pathogenesis of T2DM, natural products (NPs) have become the important resources of bioactive agents for anti-T2DM drug discovery. Recently, more and more natural components have been elucidated to possess anti-T2DM properties, and many efforts have been carried out to elucidate the possible mechanisms. The aim of this paper was to overview the activities and underlying mechanisms of NPs against T2DM. Developments of anti-T2DM agents will be greatly promoted with the increasing comprehensions of NPs for their multiple regulating effects on various targets and signal pathways.