Pien Tze Huang (PZH) protects endothelial function in diabetic mice.

Endothelial dysfunction is the most common pathological feature of cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. It affects both macro- and micro-vasculatures, causing functional impairment of multiple organs. Pien Tze Huang (PZH) is a well-studied traditional Chinese medicine (TCM) with multiple pharmacological properties that produces therapeutic benefits against colorectal cancer, non-alcoholic steatohepatitis and neurodegenerative diseases. However, it is unknown how PZH affects vascular function under pathological conditions. Therefore, this study aimed to investigate the effect of PZH on endothelial function and the underlying mechanisms in db/db diabetic mice. The results showed that chronic treatment of PZH (250 mg/kg/day, 5 weeks) improved endothelial function by restoring endothelium-dependent relaxation through the activation of the Akt-eNOS pathway and inhibition of endothelial oxidative stress, which increased nitric oxide bioavailability. Furthermore, PZH treatment increased insulin sensitivity and suppressed inflammation in diabetic mice. These new findings suggest that PZH may have vaso-protective properties and the potential to protect against diabetic vasculopathy by preserving endothelial function.

Chromosome stability of synthetic Triticum turgidum-Aegilops umbellulata hybrids.

BACKGROUND: Unreduced gamete formation during meiosis plays a critical role in natural polyploidization. However, the unreduced gamete formation mechanisms in Triticum turgidum-Aegilops umbellulata triploid F1 hybrid crosses and the chromsome numbers and compostions in T. turgidum-Ae. umbellulata F2 still not known. RESULTS: In this study, 11 T.turgidum-Ae. umbellulata triploid F1 hybrid crosses were produced by distant hybridization. All of the triploid F1 hybrids had 21 chromosomes and two basic pathways of meiotic restitution, namely first-division restitution (FDR) and single-division meiosis (SDM). Only FDR was found in six of the 11 crosses, while both FDR and SDM occurred in the remaining five crosses. The chromosome numbers in the 127 selfed F2 seeds from the triploid F1 hybrid plants of 10 crosses (no F2 seeds for STU 16) varied from 35 to 43, and the proportions of euploid and aneuploid F2 plants were 49.61% and 50.39%, respectively. In the aneuploid F2 plants, the frequency of chromosome loss/gain varied among genomes. The chromosome loss of the U genome was the highest (26.77%) among the three genomes, followed by that of the B (22.83%) and A (11.81%) genomes, and the chromosome gain for the A, B, and U genomes was 3.94%, 3.94%, and 1.57%, respectively. Of the 21 chromosomes, 7U (16.54%), 5 A (3.94%), and 1B (9.45%) had the highest loss frequency among the U, A, and B genomes. In addition to chromosome loss, seven chromosomes, namely 1 A, 3 A, 5 A, 6 A, 1B, 1U, and 6U, were gained in the aneuploids. CONCLUSION: In the aneuploid F2 plants, the frequency of chromosome loss/gain varied among genomes, chromsomes, and crosses. In addition to variations in chromosome numbers, three types of chromosome translocations including 3UL·2AS, 6UL·1AL, and 4US·6AL were identified in the F2 plants. Furthermore, polymorphic fluorescence in situ hybridization karyotypes for all the U chromosomes were also identified in the F2 plants when compared with the Ae. umbellulata parents. These results provide useful information for our understanding the naturally occurred T. turgidum-Ae. umbellulata amphidiploids.

Phenolic profiles, antioxidant activity and inhibition of digestive enzymes of water caltrop pericarps.

BACKGROUND: Water caltrop (Trapa natans L.) is widely cultivated as a popular vegetable or fruit in Asian countries. In China, water caltrop pericarp is also used as a functional food to treat metabolic syndrome. However, the profiling of bioactive substances and their pharmacological activities in different water caltrop varieties remains to be investigated. In the present study, three varieties of water caltrop pericarps collected from 13 origins in China were analyzed for their phenolic substances. To investigate the pharmacological activities, samples were tested for their free radical scavenging capacity and inhibitory potency against α-glucosidase and pancreatic lipase. RESULTS: In total, 46 phenolic compounds were identified in the ethanol extract of water caltrop pericarp using a liquid chromatography-quadrupole time of flight-tandem mass spectrometry method, most of which were hydrolyzable tannins. Two cultivated varieties samples exhibited a relatively higher phenolic content and stronger antioxidant and inhibitory activities against α-glucosidase and pancreatic lipase compared to those from the wild variety. Correlation analysis between phenolic contents and biological activities suggested that phenolic compounds exhibited potential free radical scavenging capacity, α-glucosidase and pancreatic lipase inhibitory activities. CONCLUSION: It is concluded that the phenolic compounds of water caltrop pericarp are promising sources of natural antioxidants, α-glucosidase and pancreatic lipase inhibitors. © 2021 Society of Chemical Industry.

Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice.

The transcription factor NF-E2-related factor 2 (Nrf2) is a central regulator of cellular antioxidant and detoxification response. The association between Nrf2 activity and iron-related oxidative stress in neurodegenerative diseases has been studied, and Nrf2 was found to transcriptionally regulate the expression of iron transporters and ferroptosis-related factors. However, the role of Nrf2 in age-related motor dysfunction and its link to iron metabolism dysregulation in brain have not been fully elucidated. In this study, with different ages of Nrf2 knockout (KO) and wild type (WT) mice, we investigated the effects of Nrf2 deficiency on brain oxidative stress, iron metabolism and the motor coordination ability of mice. In contrast to the predicted neuroprotective role of Nrf2 in oxidative stress-related diseases, we found that Nrf2 KO remarkably improved the motor coordination of aged mice, which was associated with the reduced ROS level and decreased apoptosis of dopaminergic neurons in substantia nigra (SN) of 18-month-old Nrf2 KO mice. With high-iron and Parkinson's disease (PD) mouse models, we revealed that Nrf2 KO prevented the deposition of brain iron, particularly in SN and striatum, which may subsequently delay motor dysfunction in aged mice. The regulation of Nrf2 KO on brain iron metabolism was likely mediated by decreasing the ferroportin 1 (FPN1) level on brain microvascular endothelial cells, thus hindering the process of iron entry into the brain. Nrf2 may be a potential therapeutic target in age-related motor dysfunction diseases for its role in regulating brain iron homeostasis.

Flavonoids isolated from loquat (Eriobotrya japonica) leaves inhibit oxidative stress and inflammation induced by cigarette smoke in COPD mice: the role of TRPV1 signaling pathways.

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic respiratory conditions like COPD can easily be infected and are more prone to having severe illness and even mortality because of lung dysfunction. Loquat leaves have long been used as an important material for both pharmaceutical and functional applications in the treatment of lung disease in Asia, especially in China and Japan. Total flavonoids (TF), the main active components derived from loquat leaves, showed remarkable anti-inflammatory and antioxidant activities. However, their protective activity against CS-induced COPD airway inflammation and oxidative stress and its underlying mechanism still remain not well-understood. The present study uses a CS-induced mouse model to estimate the morphological changes in lung tissue. The results demonstrated that TF suppressed the histological changes in the lungs of CS-challenged mice, as evidenced by reduced generation of pro-inflammatory cytokines including interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) and diminished the protein expression of transient receptor potential vanilloid 1 (TRPV1). Moreover, TF also inhibited phosphorylation of IKK, IκB and NFκB and increased p-Akt. Interestingly, TF could inhibit CS-induced oxidative stress in the lungs of COPD mice. TF treatment significantly inhibited the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). In addition, TF markedly downregulated TRPV1 and cytochrome P450 2E1 (CYP2E1) and upregulated the expression of SOD-2, while the p-JNK level was observed to be inhibited in COPD mice. Taken together, our findings showed that the protective effect and putative mechanism of the action of TF resulted in the inhibition of inflammation and oxidative stress through the regulation of TRPV1 and the related signal pathway in lung tissues. It suggested that TF derived from loquat leaves could be considered to be an alternative or a new functional material and used for the treatment of CS-induced COPD.

Development and characterization of Triticum turgidum - Aegilops comosa and T. turgidum - Ae. markgrafii amphidiploids.

Aegilops comosa and Ae. markgrafii are diploid progenitors of polyploidy species of Aegilops sharing M and C genomes, respectively. Transferring valuable genes/traits from Aegilops into wheat is an alternative strategy for wheat genetic improvement. The amphidiploids between diploid species of Aegilops and tetraploid wheat can act as bridges to overcome obstacles from direct hybridization and can be developed by the union of unreduced gametes. In this study, we developed seven Triticum turgidum - Ae. comosa and two T. turgidum - Ae. markgrafii amphidiploids. The unreduced gametes mechanisms, including first-division restitution (FDR) and single-division meiosis (SDM), were observed in triploid F1 hybrids of T. turgidum - Ae. comosa (STM) and T. turgidum - Ae. markgrafii (STC). Only FDR was observed in STC hybrids, whereas FDR or both FDR and SDM were detected in the STM hybrids. All seven pairs of M chromosomes of Ae. comosa and C chromosomes of Ae. markgrafii were distinguished by fluorescent in situ hybridization (FISH) probes pSc119.2 and pTa71 combinations with pTa-535 and (CTT)12/(ACT)7, respectively. Meanwhile, the chromosomes of tetraploid wheat and diploid Aegilops parents were distinguished by the same FISH probes. The amphidiploids possessed specific valuable traits such as multiple tillers, large seed size related traits, and stripe rust resistance that could be utilized in the genetic improvement of wheat.

Polyphenol-rich Trapa quadrispinosa pericarp extract ameliorates high-fat diet induced non-alcoholic fatty liver disease by regulating lipid metabolism and insulin resistance in mice.

In China, Trapa quadrispinosa (also called water caltrop) has long been used as a function food and folk medicine to treat diabetes mellitus for years. In the present study, the extract of T. quadrispinosa pericarp (TQPE) which mainly contains hydrolysable tannins was prepared to investigate the potential therapeutic action in non-alcoholic fatty liver disease (NAFLD) mice induced by high fat-diet (HFD). After the administration of TQPE (15, 30 mg/kg/day) for 8 weeks, the increased weight of body and liver were significantly suppressed. TQPE also ameliorated liver lipid deposition and reduced lipids parameters of blood in mice. Moreover, TQPE attenuated oxidative stress and showed a hepatoprotective effect in mice. TQPE was also found to decrease the value of homeostatic model assessment for insulin resistance. In addition, TQPE administration increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl-CoA carboxylase (ACC) and inhibited sterol regulatory element-binding protein (SREBP) in the liver tissue. Meanwhile, TQPE elevated insulin receptor substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. These results reflected that, as a nature product, TQPE is a potential agent for suppressing the process of NAFLD via regulation of the AMPK/SREBP/ACC and IRs-1/Akt pathways.

Trapa natans pericarp extract ameliorates hyperglycemia and hyperlipidemia in type 2 diabetic mice

Abstract The pericarp of Trapa natans L., an annual aquatic floating herb belonging to Lythraceae family, is used as a folk medicine in China. In this study, extracts of Trapa natans pericarp were tested both in vitro and in vivo through a high-fat diet with a single medium dosage streptozotocin injection induced type 2 diabetic mice. Different solvent extracts of Trapa natans pericarp showed α-amylase and α-glucosidase inhibitory activity. After four weeks administration, the ethyl acetate extract of Trapa natans pericarp (50 and 100 mg/kg b.w.) reduced fasting blood glucose level, ameliorated oral glucose tolerance and insulin resistance, improved serum lipids alterations in type 2 diabetic mice as well. Additionally, ethyl acetate extract significantly elevated the insulin receptor substrate 1 and Akt serine/threonine kinase phosphorylation compared to diabetic group. HPLC-MS and HPLC-DAD analysis showed that the ethyl acetate extract was rich in hydrolysable tannins. Results support the notion that Trapa natans pericarp extract has a potential hypoglycemic activity.

Hepatoprotective Effect of Seed Coat ofEuryale ferox Extract in Non-alcoholic Fatty Liver Disease Induced by High-fat Diet in Mice by Increasing IRs-1 and Inhibiting CYP2E1.

Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease characterized by hepatic steatosis, affects 30-40% of the population in the world. The seed of Euryale ferox salisb. possesses several pharmacological actions, including metabolic syndrome. However, the seed coat of E. ferox was usually discarded as waste, which contains comparatively abundant polyphenols, and its biological activity has been rarely investigated. In this work, we evaluate the hepatoprotective effect of E. ferox seed coat extract (EFSCE), in NAFLD mice induced by high-fat diet (HFD). The HPLC-MS analysis indicated that the main components of EFSCE were polyphenols. And then, mice were treated with HFD for 4 weeks to induce NAFLD. The result showed that the body weight, weight of adipose tissue, the ratio of liver to body weight in NAFLD mice increased compared with control group. In addition, blood lipids parameters including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) also increased in NAFLD mouse model. It was showed that, after treated with EFSCE (15 and 30 mg/kg/day) for 4 weeks, the body weight, lipids deposition in the liver and blood lipids in HFD-induced NAFLD mice markedly reduced. Compared with NAFLD mice, EFSCE administration could also prevent malondialdehyde (MDA) overproduction and strengthen Superoxide Dismutase (SOD) activity to counteract oxidative stress. Moreover, EFSCE was also found effective in reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in HFD-induced NAFLD model, which indicated liver injury in NAFLD. Therefore, EFSCE (rich in polyphenols) is indicated as bioactive nature product for HFD-induced NAFLD treatment, by eliminating lipid accumulation and oxidative stress via regulation of IRs-1 and CYP2E1.

Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway.

As a promising new target, miR-233 may regulate oxidative stress by targeting keap1-Nrf2 system to affect the pathological process of liver injury in T2DM. Ellagic acid (EA) is versatile for protecting oxidative stress damage and metabolic disorders. In the present study, we investigated the effect of EA on oxidative stress and insulin resistance in high glucose-induced T2DM HepG2 cells and examined the role of miR-223/keap1-Nrf2 pathway in system. HepG2 cells were incubated in 30 mM of glucose, with or without EA (15 and 30 µM) or metformin (Met, 150 µM) for 12 h. Glucose consumption, phosphorylation of IRS1, Akt and ERK under insulin stimulation, ROS and O2- production, MDA level, SOD activity and miR-223 expression, as well as protein levels of keap1, Nrf2, HO-1, SOD1 and SOD2 were analyzed. Furthermore, dual luciferase reporter assay, miR-223 mimic and inhibitor were implemented in cellular studies to explore the possible mechanism. EA upregulated glucose consumption, IRS1, Akt and ERK phosphorylation under insulin stimulation, reduced ROS and O2- production and MDA level, and increased SOD activity in high glucose-exposed HepG2 cells. In addition, EA elevated miR-223 expression level, downregulated mRNA and protein levels of keap1, and upregulated Nrf2, HO-1, SOD1 and SOD2 protein levels in this cell model. What's more, dual luciferase reporter assay, miR-223 mimic and inhibitor transfection confirmed that EA activated keap1-Nrf2 system via elevating miR-223. The miR-223, a negative regulator of keap1, represents an attractive therapeutic target in hepatic injury in T2DM. EA ameliorates oxidative stress and insulin resistance via miR-223-mediated keap1-Nrf2 activation in high glucose-induced T2DM HepG2 cells.

Antitussive and expectorant properties of growing and fallen leaves of loquat (Eriobotrya japonica)

ABSTRACT Folium Eriobotryae, the dried leaves of loquat (Eriobotrya japonica, (Thunb.) Lindl., Rosaceae), is a traditional Chinese medicine used to treat cough with phlegm in China. Fallen and growing loquat leaves were tested for their effect on coughing and expectoration in mice. HPLC-ELSD and HPLC-MS analyses of aqueous and ethanol extracts of fallen or growing leaves were used to identify the chemical components responsible for this effect. Both the aqueous and ethanol extracts of growing and fallen leaves of loquat contained antitussive and expectorant activities. Moreover, an aqueous extract of growing loquat leaves with a higher flavonoid content displayed a stronger expectorant activity while the ethanol extract of fallen loquat leaves that contained a higher content of triterpenoid acids induced a stronger antitussive activity.

A novel sesquiterpene glycoside from Loquat leaf alleviates oleic acid-induced steatosis and oxidative stress in HepG2 cells.

Loquat (Eriobotrya japonica) leaf has displayed beneficial effect on metabolic syndrome. In our previously study, total sesquiterpene glycosides (TSG) isolated from Loquat leaf exhibited therapeutic effect on Non-alcoholic fatty liver disease (NAFLD) in vivo, but the accurate active compound remains unknown. Sesquiterpene glycoside 1 (SG1) is a novel compound, which is exclusively isolated from Loquat leaf, but its biological activity has been rarely reported. The present study was designed to evaluate the pharmacological effect of SG1, the main component of TSG, in oleic acid (OA)-induced HepG2 cell model of NAFLD with its related mechanisms of action. In this study, both SG1 and TSG were found to significantly reduce the lipid deposition in the cell model. They could also decrease total cholesterol (TC), triglyceride (TG) and intracellular free fatty acid (FFA) contents. Compared with OA-treated cells, the superoxide dismutase (SOD) level increased, and the malondialdehyde (MDA) and 4-hydroxynonenal levels respectively decreased after the administration of SG1 or TSG. The high dose of SG1 (140 µg/mL) displayed a similar therapeutic effect as TSG at 200 µg/mL. Both SG1 and TSG were found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) and its downstream target c-Jun in OA-treated cell. These results demonstrate again that TSG are probably the main responsible chemical profiles of Loquat leaf for the treatment of NAFLD, for which it can effectively improve OA-induced steatosis and reduce oxidative stress, probably by downregulating of CYP2E1 expression and JNK/c-Jun phosphorylation, while SG1 may be the principle compound.

Recombination between G2 and G6 strains of rabbit hemorrhagic disease virus (RHDV) in China.

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the lagovirus rabbit hemorrhagic disease virus (RHDV), which was first reported in 1984 in China. Genetic characterization of RHDV has demonstrated that two different genogroups (G2 and G6) are present in China. To gain a better understanding of the molecular evolution of RHDV, we searched for recombination events by analyzing all full-length RHDV capsid VP60 sequences of Chinese isolates belonging to the genogroups 2 and 6. Our results revealed a recombinant origin for the NanBu/China/2011 isolate. This recombination event occurred between G2 and G6 strains with two breakpoints located at nucleotide positions 393 and 1079 of the VP60 sequence. Phylogenetically, the NanBu/China/2011 strain clustered with genogroup G6 in the entire capsid gene sequence except in the fragment between nucleotides 394 and 1078, where it clustered with genogroup G2. As the consequences of the presence of a G2/G6 recombinant strain in China are unpredictable, the circulation of RHDV in the populations should be carefully monitored.

Biology of ageing and role of dietary antioxidants.

Interest in relationship between diet and ageing is growing. Research has shown that dietary calorie restriction and some antioxidants extend lifespan in various ageing models. On the one hand, oxygen is essential to aerobic organisms because it is a final electron acceptor in mitochondria. On the other hand, oxygen is harmful because it can continuously generate reactive oxygen species (ROS), which are believed to be the factors causing ageing of an organism. To remove these ROS in cells, aerobic organisms possess an antioxidant defense system which consists of a series of enzymes, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). In addition, dietary antioxidants including ascorbic acid, vitamin A, vitamin C, α-tocopherol, and plant flavonoids are also able to scavenge ROS in cells and therefore theoretically can extend the lifespan of organisms. In this connection, various antioxidants including tea catechins, theaflavins, apple polyphenols, black rice anthocyanins, and blueberry polyphenols have been shown to be capable of extending the lifespan of fruit flies. The purpose of this review is to brief the literature on modern biological theories of ageing and role of dietary antioxidants in ageing as well as underlying mechanisms by which antioxidants can prolong the lifespan with focus on fruit flies as an model.

Molecular epidemiological analysis of Newcastle disease virus isolated in China in 2005.

Eighty-three strains of Newcastle disease virus (NDV) were obtained from outbreaks in chickens, pigeons, geese, and ducks in China in 2005 and characterized genotypically. The main functional region of the F gene (535 nucleotides) was amplified and sequenced. A phylogenetic tree based on nucleotides 47-435 of the F gene was created using sequences from 83 isolates and representative NDV sequences obtained from GenBank. Phylogenetic analysis showed that all newly characterized strains belonged to six genetic groups: I, II, III, VIb, VIIc, and VIId. All the isolates belonging to groups I and II (14 total) were lentogenic according to the amino acid sequences of the fusion protein cleavage site, and either V4 or LaSota-type, depending on the vaccines that were used. Most isolates (64 total) were classified in group VIId, a predominant genotype responsible for most Newcastle disease outbreaks since the end of the last century. One strain, NDV05-055, was in group VIIc, three pigeon strains were in group VIb, and one isolate, NDV05-041, was in group III, and characterized as a velogenic strain. This study revealed that genotype VIId was the major NDV strain responsible for the 2005 ND epizoonosis that occurred in China.

[Physiological responses of 2-year-old Acer davidii seedings to short-term enhanced UV-B radiation].

At the Maoxian Ecological Experimental Station of Chinese Academy of Sciences in northwest Sichuan Province, 2-year-old native maple(Acer davidii) seedlings were potted outdoors with enhanced UV-B radiation(280 - 320 nm) of 0.27 W x m(-2) (7.7 kJ x m(-2) x d(-1)), which was approximated to the predicted enhanced UV-B reaching the earth surface when stratosphere ozone was depleted by 15% in the local area, with the control plant received ambient UV-B. The gas exchange index and chlorophyll fluorescence, and the contents of chlorophyll and UV-absorbing compounds were examined after 50 days of the radiation. The results showed that enhanced UV-B radiation significantly lowered the maximal net photosynthetic rate (CK = 6.214, TR = 4.452), raised the dark respiration rate(CK = 0.413, TR = 1.295) and light compensation point (CK = 21.629, TR = 59.861), but had little effect on quantum yield (CK = 0.021, TR = 0.032). Under enhanced UV-B radiation, the diurnal changes in net photosynthetic rate, water use efficiency, quantum efficiency of photosystem II centers (Fv/Fm), and quantum yield of photosystem II photochemistry (phi(pspi)) were reduced, chlorophyll a, total chlorophylls, and chlorophyll a/b (CK= 16.23, 5.39, TR = 13.17, 4.93) were also markedly reduced, but chlorophyll b remained nearly unchanged. Contrary to the previous studies, enhanced UV-B radiation decreased the content of UV-absorbing compounds (CK = 0.87, TR = 0.79) in 2-year-old Acer davidii seedling leaves, indicating that the measurement of leaf UV-B absorbing compounds didn't necessarily provide a good indicator of plant tolerance to UV-B. It could be concluded that enhanced UV-B radiation had some inhibitory effects on the photosynthesis of Acer davidii seedlings. Long-term researches are necessary to confirm this conclusion.