Dingkun Pill modulate ovarian function in chemotherapy-induced premature ovarian insufficiency mice by regulating PTEN/PI3K/AKT/FOXO3a signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP) is a traditional Chinese medicine that has been shown to have beneficial effects on reproductive function. However, the specific mechanism underlying its effect on POI is not well understood. AIM OF THE STUDY: To investigate the effect of different doses of Dingkun Pill on ovarian function in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) mice and to explore its molecular mechanism through PTEN/PI3K/AKT/FOXO3a signaling pathway. This study will provide valuable insights into the potential clinical application of Dingkun Pill for the treatment of POI. MATERIALS AND METHODS: Fifty female ICR mice were randomly divided into normal control (NC) group, model control (MC) group, and Dingkun Pill low, medium, high dose (DKP-L, M, H) groups. Mice were injected with CTX to construct the POI model. Mice in the DKP-L, M, and H groups were given 0.9 g/kg, 1.8 g/kg, and 3.6 g/kg of Dingkun Pill suspension for 21 days, respectively. Mice in the NC and MC groups were given the same amount of normal saline by gavage. Changes in body weight, estrous cycle and gonadal index were observed in each group of mice. Serum levels of FSH, LH, E2 and AMH were detected by ELISA. Hematoxylin-eosin (HE) staining observed the changes of ovarian pathological morphology and follicle counts at all levels. qRT-PCR was used to measure the levels of the PTEN and FOXO3a genes in ovarian tissue. The expression of PTEN/PI3K/AKT/FOXO3a signaling pathway related proteins were detected by Western-blot and immunohistochemistry (IHC). RESULTS: In POI mice, Dingkun Pill increased body weight, promoted the recovery of estrous cycle, increased ovarian index, and improved pathological morphology of the ovaries. The FSH level decreased in the medium dose group (P < 0.05), the LH level reduced significantly in the medium and high dose groups (P < 0.01), and the E2 level in the high dose group increased (P < 0.05). There was no significant difference in AMH levels across all dose groups. The number of growing follicles improved at all levels in the low and medium dose groups, but declined significantly in the high dose group. However, the number of corpus luteum increased significantly in the high dose group (P < 0.001), and the atretic follicles in the three dose groups decreased. Results from qRT-PCR, Western-blot and IHC showed that the moderate dose of Dingkun Pill suppressed the levels of the p-PI3K and p-AKT proteins by upregulating the expression of PTEN in the ovarian tissues of POI mice, thereby inhibiting the expression of the key protein p-FOXO3a. However, the inhibitory effect of the higher dose may be less than that of the lower and intermediate dose groups. CONCLUSIONS: The Dingkun Pill modulated hormonal levels, promoted follicle growth and induced ovulation in mice with CTX-induced POI, with better results in the low and moderate dose groups. Its mechanism may be related to the regulation of the PTEN/PI3K/AKT/FOXO3a signaling pathway.

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice.

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Discovery, preparation and characterization of lipid-lowering alkylphenol derivatives from Syzygium jambos fruit.

The chemical characteristics and hypolipidemic effects of alkylphenols in the fruit of Syzygium jambos were investigated in this study. Three cardanols (1-3; 1 as a new compound) and three alkylresorcinols (4-6) were isolated and identified from S. jambos fruit. Cardanols 1 and 2 (10-40 µM) suppressed lipids accumulation and reduced triglyceride content in oleic acid-overloaded HepG2 cells via the activation of AMPK/PPARα signaling pathways. Furthermore, the biological distribution of cardanols after an oral intake in mice was investigated. Compound 2 was detected in mice plasma, feces, and adipose tissues after a single oral intake (80 mg/kg body weight). In addition, an alkylphenols-enriched S. jambos fruit extract containing two bioactive compounds (95.9 and 198.6 µg/mg of compounds 1 and 2, respectively) was prepared. Findings from the current study highlight the potential usage of cardanols as well as S. jambos fruit for the management of dyslipidemia.

New phenolic glycosides from Anemone chinensis Bunge and their antioxidant activity.

ABATRACTNine compounds, five phenolic glycosides (1, 2, 4-6), three phenylpropanoids (7-9), and a furanone glycoside (3), were isolated from aqueous soluble extract of the dried roots of Anemone chinensis Bunge. The structures of new compounds (1-4) were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A (1) demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.7 cells by reducing ROS production, enhancing antioxidant enzyme SOD activity, replenishing depleted GSH in a dose-dependent manner. Western blot analysis revealed that 1 showed antioxidant activity via activating Nrf2 signaling pathway.[Formula: see text].

Chemical characterization, antiproliferative and antifungal activities of Clinacanthus nutans.

Clinacanthus nutans Lindau (Family: Acanthaceae) is a medicinal herb widely distributed in the tropic and subtropic areas of Asia. C. nutans is traditionally consumed as vegetable or herbal tea, as well as a folk medicine for anticancer and antifungal activities. However, to date, chemical constituent responsible for observed health beneficial effects of this medicinal plant is not clear. In the current study, 32 compounds (1-32), including three new megastigmanes (1-3) were isolated from the aerial parts of C. nutans. Their structures were elucidated on the basis of comprehensive NMR, MS, and CD spectroscopic data analysis, as well as chemical hydrolysis. Among the isolates, cycloartane triterpenoids (9, 10, and 12) displayed moderate anti-proliferative effects against HepG2 cell growth with IC50 values ranging from 9.12 to 19.89 µM. Data obtained from flow cytometry analysis and western blotting assays revealed that compounds 9 and 12 induced apoptosis of HepG2 cells by modulating the expression of proteins associated to mitochondrial-mediated apoptotic pathway. Furthermore, megastigmanes 1, 2, 7, and 8 enhanced the anti-Candida albicans activity of amphotericin B (AmB), supporting the synergistic effects between megastigmanes and AmB. This is the first report of anticancer and antifungal potential of cycloartane triterpenoids and megastigmanes in C. nutans, which shed useful insights on the relationship between C. nutans's chemical constituent and its beneficial effects to health. Findings from this study support further development of this medicinal plant for potential pharmaceutical applications.

Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, In Vitro and In Vivo Investigations of Jamunones.

Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.

Chemical Characterization and Hepatoprotective Effects of a Standardized Triterpenoid-Enriched Guava Leaf Extract.

Nutraceutical/pharmaceutical agents capable of maintaining redox and inflammation homeostasis are considered as candidates for the prevention and/or treatment of liver diseases. Psidium guajava (commonly known as guava) leaf is a commercially available functional food that has been reported to possess hepatoprotective property. However, the hepatoprotective constituents in guava leaf are not known. In the current study, a standardized triterpenoid-enriched extract of guava leaves (TGL) was developed. A new ursolic acid derivative, namely 2α,3ß,6ß,23,30-pentahydroxyurs-11,13(18)-dien-28,20ß-olide (1), and 23 known triterpenoids were isolated and identified from TGL. The hepatoprotective effects of TGL were evaluated through a model using acetaminophen (APAP)-exposed C57BL/6 male mice. Pretreatment of TGL (75 and 150 mg/kg) restored the mice hepatic architecture, improved the serum ALT and AST levels, and reduced the hepatic ROS and MDA contents. Further molecular mechanistic study revealed that TGL modulated Nrf2 and MAPK signaling pathways to alleviate APAP-induced oxidative and inflammatory stress in liver. In addition, the new compound 1 from TGL showed protective effects against APAP-induced cytotoxicity via activation of the Nrf2 pathway in HepG2 cells. Overall, this is the first report on the hepatoprotective effects of a standardized triterpenoid-enriched extract of guava leaves, which supports its potential nutraceutical application in liver disease management.

[Effect of nitrogen additions on soil pH, phosphorus contents and phosphatase activities in grassland]. / æ°®æ·»åŠ å¯¹è‰åœ°ç”Ÿæ€ç³»ç»ŸåœŸå£¤pHã€ç£·å«é‡å’Œç£·é ¸é ¶æ´»æ€§çš„å½±å“.

Phosphorus is a key nutrient for all plant species and a limiting factor for grassland ecosystem function. In recent years, in response to the rapid increase of global nitrogen deposition, soil phosphorus contents and phosphatase activities changed to varying degrees in grassland ecosystems. We conducted a meta-analysis to examine the responses of soil pH, total phosphorus (TP), available phosphorus (AP), as well as activities of alkaline phosphatase (AlP) and acid phosphatase (AcP) in soils to nitrogen addition amount, nitrogen type, experimental duration, and sampling depth. The correlation between soil pH and phosphatase response ratio was investigated. The results showed that nitrogen addition significantly reduced soil pH, TP and AlP activity, while significantly increased AcP activity, but had no significant effect on AP. Soil pH and AlP activity significantly decreased under nitrogen addition >5 g·m-2·a-1, and AcP activity significantly increased under high nitrogen addition (>10 g·m-2·a-1). The contents of TP and AP significantly decreased when nitrogen addition was 5-10 g·m-2·a-1. NH4NO3 treatment significantly reduced soil TP and increased AcP activity, while urea treatment significantly reduced soil pH and AlP activity. Across all nitrogen addition amounts, when the experiment duration was 3 to 10 years, soil TP content and AlP activity were significantly reduced. Soil pH was significantly reduced after three years nitrogen addition, and AcP activitiy was significantly increased after 10 years nitrogen addition. In the 0-10 cm soil layer, the TP content and AlP activity significantly decreased, while the AP content significantly increased. In >10 cm soil layer, the AP content was significantly decreased. The significant negative correlation between soil pH and AcP activity indicated that change in soil pH caused by nitrogen addition may be an important factor for the variation of soil phosphatase activity.

Distribution Analysis of Salvianolic Acids in Myocardial Ischemic Pig Tissues by Automated Liquid Extraction Surface Analysis Coupled with Tandem Mass Spectrometry.

The distribution of active compounds of traditional Chinese medicine Salvia miltiorrhiza Bunge (Chinese name: Danshen) in vivo was determined by establishing a liquid extraction surface analysis coupled with the tandem mass spectrometry (LESA-MS/MS) method. Stability analysis and distribution analysis were designed in the present study using normal animals or a myocardial ischemia model. The model assessment was performed four weeks after surgery, and then three groups were created: a normal-dose group, a model-blank group, and a model-dose group. Meanwhile, Danshen decoction administration began in dose groups and lasted for four weeks. In stability analysis, four salvianolic acids-Danshensu (DSS), caffeic acid (CAA), rosmarinic acid (RA), and salvianolic acid A (SAA)-in kidney tissues from the normal-dose group were detected by LESA-MS/MS under four conditions, and then distribution analysis was conducted in different tissues using the same method. Ejection fraction (EF) and fractional shortening (FS) in animals from two model groups decreased significantly four weeks after surgery (P < 0.01) and were improved after four weeks of Danshen decoction administration (P < 0.01). Results of stability analysis demonstrated that this method was basically stable since there were no significant differences in signal intensities of DSS, CAA, and SAA under four conditions (P > 0.05). Distribution analysis showed the signal intensities of DSS in the liver and kidney and SAA in the heart were higher in the model-dose group than in the normal-dose group (P < 0.05 or P < 0.01). Signal intensities of RA in the liver and kidney, and SAA in the liver were lower in the model-dose group compared with the normal-dose group (P < 0.05 or P < 0.01). In conclusion, Danshen decoction has the effect of improving the ischemic condition in a chronic myocardial ischemia model, and the content of two active compounds increased in the targets. These findings contribute to an understanding of the therapeutic role of Danshen in cardiovascular disease.

Guavinoside B from Psidium guajava alleviates acetaminophen-induced liver injury via regulating the Nrf2 and JNK signaling pathways.

Benzophenone glycosides are a major type of polyphenols present in guava. To date, there is still poor understanding of the relationship between benzophenone glycosides and the hepatoprotective effects attributed to this edible fruit. Herein, the protective effects of guavinoside B (GUB), a main benzophenone glycoside present in guava fruit, against acetaminophen (APAP)-induced liver injury were investigated in vitro and in vivo. Fluorescence measurement demonstrated that GUB (at a concentration of 30 µM) significantly reduced the intracellular ROS levels in APAP-treated HepG2 cells. In addition, GUB (100 mg kg-1 d-1) pretreatment markedly alleviated APAP-induced hepatocyte infiltration and necrosis in C57BL/6 mice, and improved serum and hepatic biochemical parameters, such as ALT, AST, SOD, GSH, ROS, MDA, and TNF-α levels. RT-PCR and western blot experiments revealed that GUB up-regulated Nrf2, GCLC and NQO1, while reducing p-JNK gene expression in the liver. The fermentation experiment further revealed that the displayed beneficial effects of GUB in vivo might be related to the gut microbial metabolite gallic acid. These promising data suggested that GUB showed potent hepatoprotective effects through regulating the Nrf2 and JNK signaling pathways. Further investigation of the absorption and metabolism of benzophenones would be warranted to promote the utilization of these phenolics as functional food ingredients against oxidative stress-induced chronic diseases.

New anti-inflammatory withanolides from Physalis pubescens fruit.

Physalis pubescens L. is a medicinal plant widely cultivated in northeast of China. Investigation on the extract of P. pubescens fruit led to the isolation and identification of four new withanolides, namely, physapubescins J-M (1, 2, 4 and 5), together with four known analogues (3, 6-8) and fifteen other compounds. Their structures were elucidated on the basis of comprehensive NMR, MS, and ECD spectroscopic data analysis. Among isolates, physapubescin J (1) contained an unusual sulphide linkage, and four withanolides (3, 5, 7 and 8) showed anti-inflammatory potential in LPS-induced RAW264.7 cells. This study supports P. pubescens fruit could be a valuable source of withanolides. Further studies to investigate anti-inflammatory activities of isolated withanolides using in vivo models are warranted.

Barringtogenol C-type Triterpenoid Saponins from the Stem Bark of Norway Maple (Acer Platanoides).

Four new barringtogenol C-type triterpenoid saponins, namely acerplatanosides A - D (1: -4: ), along with 22 known compounds (5: -26: ), were isolated from the stem bark of Norway maple (Acer platanoides). Their structures were elucidated on the basis of comprehensive spectroscopic analyses and chemical hydrolysis. This is the first report of triterpenoid saponins isolated from Norway maple. Compounds 1, 3: , and 4: showed cytotoxicity against 4 human cancer cell lines with IC50 values ranging from 9.4 to 39.5 µM.

Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats.

This study aimed to investigate the therapeutic effect of traditional Chinese medicine-Buxin Yishen decoction (BXYS) on type 2 cardiorenal syndrome (CRS) caused by myocardial infarction and explore the possible mechanism BXYS works. A chronic heart failure (CHF) rat model induced by left anterior descending coronary artery ligation was used and five groups were created that included a sham group, a CHF model group, a fosinopril group, a BXYS (0.4 g/kg) group and a BXYS (0.8 g/kg) group. Heart function, renal hemodynamics, neuroendocrine factors, serum, and urine concentration of soluble form connective tissue growth factor (sCTGF), expression of CTGF mRNA, CTGF, α-smooth muscle actin (α-SMA), and low-density lipoprotein receptor-related protein (LRP) in renal tissues were evaluated after 28 days and 60 days of drug administration. Histological analysis of kidney tissues was also performed. In vitro experiments were designed to verify the results of in vivo experiments by detecting factors including CTGF, α-SMA, in NRK-52E cells. Rats with CHF showed obvious pathophysiological changes including: altered renal hemodynamic parameters; dysregulated heart function; changes to serum concentrations of angiotensin II (AngII), cyclic guanosine monophosphate (cGMP), serum creatinine (Scr), blood urea nitrogen (BUN), C-reactive protein (CRP), brain natriuretic peptide (BNP); high serum and urine sCTGF concentration; high CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues; increased extracellular matrix (ECM) deposition and fibrosis in renal tissues. Treatment of BXYS was correlated with a restoration of heart function and improvement of renal hemodynamics, lower serum and urine sCTGF, lower CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues and lower ECM deposition. In addition, in vitro experiments showed that treatment with BXYS reduced the α-SMA and LRP concentration in NRK-52E cells, which were similar in vivo experiments. In conclusion, the current study provided evidences that BXYS played a role in improving heart function and delaying the progress of renal fibrosis. Meanwhile, the CTGF-LRP pathway might be one of the therapeutic targets for myocardial infarction caused type 2 CRS which showed a positive change after BXYS treatment and is worthy of further exploration.

New Acylated Phenolic Glycosides with ROS-Scavenging Activity from Psidium guajava Leaves.

Reactive oxygen species and subsequent oxidative stress are reported to play important roles in chronic metabolic diseases. Plant-derived polyphenols, especially food-derived phenolics, have attracted a lot of attention due to their potential usage against oxidative stress-related diseases. The leaf of Psidium guajava (known as guava) is regarded as a good resource of polyphenols and its products are commercially available in Japan as functional foods against multiple chronic metabolism disorders. In the course of finding novel polyphenols with antioxidative activities from guava leaf, 11 acylated phenolic glycosides (1-11), including 5 new oleuropeic acid-conjugated phenolic glycosides, named guajanosides A-E (1, 2, and 5-7), along with 17 known meroterpenoides (12-28), were isolated and identified. Their structures were determined by spectroscopic data analysis, chemical degradation, and acid hydrolysis. Compounds 1, 2, and 5-11 displayed potent reactive oxygen species-scavenging activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Western blot revealed that compound 6 markedly increased the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and the glutamate-cysteine ligase catalytic subunit. The current study revealed the presence of oleuropeic acid-derived phenolic glycosides in guava leaf and highlighted the potential usage of this type of phenolics against oxidative stress-related metabolic diseases via activation of the Nrf2 signaling pathway.

Jamun (Eugenia jambolana Lam.) Fruit Extract Prevents Obesity by Modulating the Gut Microbiome in High-Fat-Diet-Fed Mice.

SCOPE: Published data support that gut microbiota play an important role in the pathological process of obesity and related metabolic disorders. In the current study, it is investigated whether a standardized extract from Jamun (Eugenia jambolana), a widely consumed tropical fruit, could alleviate obesity and alter gut microbial community in high-fat diet (HFD)-fed mice. METHODS AND RESULTS: C57BL/6 mice are fed either a standard diet (SD) or HFD with or without Jamun fruit extract (JFE; 100 mg kg-1 day-1 ) by oral gavage for 8 weeks. JFE supplementation significantly alleviated diet-induced obesity, insulin resistance, and liver steatosis. JFE supplementation also improved HFD-induced gut dysbiosis by restoring the ratio of Firmicutes to Bacteroidetes as revealed by 16S rDNA analyses. The relative abundance of certain genera, as well as levels and proportion of intestinal-derived short-chain fatty acids are improved in JFE-treated mice in comparison to the HFD-fed control group. CONCLUSION: These promising data show the potential association between gut microbiota modulation and metabolism improvement of the JFE administration, and support the utilization and further investigation of Jamun fruit as a dietary intervention strategy for the prevention of obesity and related metabolic disorders.

Phenolics from Eugenia jambolana seeds with advanced glycation endproduct formation and alpha-glucosidase inhibitory activities.

Published data suggest that dietary-derived phenolics exert beneficial effects against hyperglycemia-mediated diseases, such as diabetes, through inhibiting the formation of advanced glycation endproducts (AGEs) and carbohydrate hydrolyzing enzyme activities. In the course of our investigation on the edible berry, Eugenia jambolana (known as Jamun), 21 phenolics (1-21) were isolated and identified from its seeds. Among these, one compound (1) is new and eleven compounds (3, 6, 9-13, 17, and 19-21) are being reported from E. jambolana for the first time. The anti-AGE activities of thirteen pure isolates (2-7, 9-12, 14, 15, and 20) were either comparable or superior to the synthetic anti-glycation agent, aminoguanidine, at three test concentrations (20, 50, and 100 µM) in the BSA-fructose assay. Most of these phenolics with anti-AGE activity exhibited potent free radical scavenging activity in the DPPH assay, and attenuated intracellular levels of LPS-induced reactive oxygen species in RAW264.7 macrophage. In addition, compounds 2-6, and 14 showed superior α-glucosidase inhibitory activity (IC50 = 5.0-21.2 µM) compared to the clinical α-glucosidase inhibitor, acarbose (IC50 = 289.9 µM). This is the first report of the anti-AGE effects of compounds 2-6 and 9-12, and α-glucosidase inhibitory activities of compounds 3-6, 9, 11 and 14. The current study supports the role of phenolics in the antidiabetic properties attributed to this edible berry, and warrants further animal studies to evaluate their potential as dietary agents for the prevention and/or therapy of hyperglycemia-mediated diseases.

Hypoglycemic and hypolipidemic effects of triterpenoid-enriched Jamun (Eugenia jambolana Lam.) fruit extract in streptozotocin-induced type 1 diabetic mice.

The edible berries of Eugenia jambolana Lam. (known as Jamun) are consumed in various parts of the world. Our previous studies revealed that a triterpenoid-enriched Jamun fruit extract (TJFE) showed beneficial effects on glucose homeostasis in non-diabetic mice. Herein, the anti-diabetic effects of TJFE (100 mg kg-1 by oral gavage for ten days) were evaluated in streptozotocin (STZ)-induced type 1 diabetic mice. TJFE significantly attenuated STZ-induced hyperglycemia and glucose intolerance, suppressed the abnormal elevation of hepatic gluconeogenesis, and improved dyslipidemia in the mice. Histopathology and mechanism-based studies revealed that TJFE preserved the architecture and function of pancreatic islets, attenuated insulin secretion deficiency, enhanced insulin/Akt signaling transduction, reduced lipogenic gene expression, and prevented the abnormal activation of Erk MAPK in the liver tissues of the STZ-induced diabetic mice. The current study adds to previously published data supporting the potential beneficial effects of this edible fruit on diabetes management.

New Sesquiterpenoids from Eugenia jambolana Seeds and Their Anti-microbial Activities.

Twenty four sesquiterpenoids, 1-24, including 11 new sesquiterpenoids, jambolanins A-K, and two new norsesquiterpenoids, jambolanes A and B, along with six known triterpenoids, were isolated from the seeds of Eugenia jambolana fruit. Their structures were elucidated on the basis of NMR and MS spectrometry data analysis. Among the isolates, compound 13 possessed a rare 6,7-seco-guaiene skeleton, and compounds 14 and 15 were norsesquiterpenoids containing a spiro[4.4]nonane skeleton. Antimicrobial assay evaluation revealed that sesquiterpenoids, 4, 5/6, 17, 19, 21, 23, and 24 inhibited the growth of the Gram-positive bacterium, Staphylococcus aureus. The current study advances scientific knowledge of E. jambolana phytochemicals and suggests that its sesquiterpenoids may contribute, in part, to the anti-infective effects attributed to the edible fruit of this plant.

Anti-Inflammatory Effects, SAR, and Action Mechanism of Monoterpenoids from Radix Paeoniae Alba on LPS-Stimulated RAW 264.7 Cells.

Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous phytochemistry investigations. Their anti-inflammatory effects were determined in the present study. The expression and production of pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells were measured using an Elisa assay and nitric oxide (NO) release was determined using the Griess method. The results demonstrated that the most of the monoterpenoids suppressed the LPS-induced production of NO, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The anti-inflammatory activities of these monoterpenoids were closely related to their structural characteristics. Paeoniflorins and paeonidanins presented stronger anti-inflammatory activities than those of albiflorin derivatives. Furthermore, the action mechanisms of MBPF, having a strong anti-inflammatory effect, were investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods. The results indicated that MBPF could down-regulate the mRNA and protein expression level of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells. The mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor κB (NF-κB) signaling pathways are involved in mediating the role of MBPF in suppressing the expression and production of pro-inflammatory cytokines in RAW 264.7 cells.

SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion.

We have found that Fas/FasL-mediated "extrinsic" pathway promoted cell apoptosis induced by renal ischemic injury. This study is to elucidate the upstream mechanism regulating FasL-induced extrinsic pathway during renal ischemia/reperfusion. Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression and activation of caspase8 and caspase3, triggering cell apoptosis during renal ischemia/reperfusion. The administration of SIRT2 inhibitor AGK2 prior to renal ischemia decreased significantly the number of apoptotic renal tubular cells and alleviated ultrastructure injury. These results indicate that inhibition of FOXO3a deacetylation might be a promising therapeutic approach for renal ischemia /reperfusion injury.