Evaluation and control of Fusarium acuminatum causing leaf spot in Saposhnikovia divaricata in Northeast China.

Saposhnikovia divaricata is an authentic Chinese herbal medicine in Northeast China named Guanfangfeng, which is made from very high quality plants for sufficient efficacy. However, leaf spot causes a very large reduction in the yield and quality of S. divaricata in Shuangyashan (126°54'E, 45°81'N), Northeast China. A total of 18 isolates were isolated from the diseased leaves of S. divaricata, following Koch's postulates, and identified as Fusarium acuminatum based on morphological, molecular biological, and phylogenetic tree analyses. To the authors' knowledge, this is the first report of F. acuminatum causing S. divaricata leaf spot in China. F. acuminatum infected perilla and mung beans, but not foxtail millet, peanuts, wheat, peas, rye, red beans, or sorghum. Susceptibility assessment of F. acuminatum to fungicides using the mycelial growth rate method showed that isolates of F. acuminatum were most sensitive to prochloraz, with EC50 values of 0.0005413-0.0009523 µg·ml-1. In the two field experiments, the average control efficacy of prochloraz at 0.450 g/l on S. divaricata leaf spot caused by F. acuminatum was 75.42%. Therefore, non-host plant rotation or intercropping with suitable chemical fungicides may be used to control S. divaricata leaf spot. This study's results provide a theoretical basis for controlling S. divaricata leaf spot and will facilitate the development of effective disease management programs.

Daming capsule protects against myocardial infarction by promoting mitophagy via the SIRT1/AMPK signaling pathway.

Myocardial infarction (MI) is a myocardial injury caused by coronary thrombosis or persistent ischemia and hypoxia. Due to its high morbidity and mortality, a safer and more effective treatment strategy is urgently needed. Daming capsule (DMC), a hypolipidemic drug, reportedly exerts cardioprotective effects in clinical and basic research, although its protective mechanism remains unknown. To investigate the mechanism underlying DMC-mediated improvement of cardiac function post-MI, C57/BL6 mice subjected to coronary artery ligation were administered DMC for 4 weeks. Our data demonstrated that DMC significantly improved cardiac structure and function compared to the saline group. Moreover, DMC inhibited inflammatory response and oxidative stress and improved mitochondrial structure and function in MI mice and hypoxia-stressed cardiomyocytes. Next, our research proved that DMC increased the expression of mitophagy receptor NLRX1. Interestingly, with the administration of DMC and siNLRX1, NLRX1 expression, mitochondria and lysosome colocalization, and mitochondrial membrane potential decreased, while mitochondrial ROS accumulation increased, suggesting that DMC promoted mitophagy to improve mitochondrial function via NLRX1 regulation. Further analysis showed that DMC activated the SIRT1/AMPK signaling pathway in vivo and in vitro. Our data showed that SIRT1 knockdown downregulated NLRX1 expression, leading to structural damage and functional impairment in mitochondria, as well as increased oxidative stress, inflammatory response, and decreased cardiac function in MI mice. Collectively, our findings reveal that DMC improves cardiac function post-MI by increasing mitophagy and inhibiting oxidative stress and inflammotory response in cardiomyocytes through the SIRT1/AMPK signaling pathway.

Isolation and hypoglycemic effects of water extracts from mulberry leaves in Northeast China.

Diabetes is the main chronic disease that greatly affects human life. Up to now, many measures have been taken to cope with the disease, among which natural products with hypoglycemic effects have aroused great interest. The objective of this study was to evaluate the hypoglycemic effects of Morus abla L. cv. longsang 1 leaf-derived water extract in vitro and in vivo. These leaves were firstly subjected to water extraction, and the obtained products were further isolated for polysaccharides, flavonoids and alkaloids. The α-glucosidase activity and anti-protein glycosylation activity of the aqueous extracts were examined in vitro. Hyperglycemic mouse models were used to evaluate the hypoglycemic effects of the aqueous extract by blood biochemical parameters, intestinal microbiota, and pathological changes to the kidneys. The results showed that the main hypoglycemic components in the aqueous extracts were flavonoids and alkaloids and their inhibition rates against α-glucosidase activity were 86.12 ± 1.79% and 87.29 ± 1.32%, respectively. High-dose mulberry leaf water extracts can reduce the blood glucose of diabetic mice by 28.17% and improve glucose tolerance by 19.02%. Furthermore, mulberry leaf water extracts could reduce the serum free fatty acid (FFA), tumor necrosis factor-α (TNF-α), insulin and glycated serum protein content, while alleviating kidney damage and improving intestinal microbiota. These results indicated that the synergistic effects among the different components of mulberry leaves might explain their alleviating effects on diabetic syndrome and thus provide a simple, convenient way to obtain the hypoglycemic components from mulberry leaves.

Anthocyanidin attenuates myocardial ischemia induced injury via inhibition of ROS-JNK-Bcl-2 pathway: New mechanism of anthocyanidin action.

Despite treatment options available to date, myocardial ischemia (MI) remains the leading cause of death worldwide. Studies are focused on finding effective therapeutic strategies against MI injury. Growing interest has been developed in natural compounds possessing medicinal properties with scarcer side effects. Here, we have evaluated the cardioprotective potential of anthocyanidin against MI injury and explored its underlying protective mechanism. Left anterior descending coronary artery was ligated to induce MI in mice. Neonatal mice cardiomyocytes were treated with H2 O2 to induce oxidative stress (a major contributor to MI injury) in vitro. Anthocyanidin pretreatment significantly reduced the infarct size, preserved the cell viability, and protected against ischemia-induced cardiac injury in treatment groups compared with the H2 O2 -treated group in vitro. Measurement of reactive oxygen species (ROS) validated the strong antioxidant potential of anthocyanidin, as significant reduction in oxidative stress was observed in anthocyanidin-pretreated groups. Mechanistically, pretreatment with anthocyanidin significantly subdued the activation of JNK (to p-JNK) and elevated Bcl-2 levels. Both in vivo and in vitro findings suggest that anthocyanidin can induce a state of myocardial resistance against ischemic insult. We have provided the experimental evidence for inhibition of ROS/p-JNK/Bcl-2 pathway being the underlying mechanism of action of anthocyanidin. Our results support the use of anthocyanidin as therapeutic strategy against MI injury.

Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma.

BACKGROUND: The anti-carcinogenic effects of anthocyanin are well documented. Oral squamous cell carcinoma is one of the most common and lethal cancer types due to its high degree of malignancy and poor prognosis. The main purpose of the current study was to investigate the potential inhibitory effects of anthocyanin on oral squamous cell carcinoma and identify effective targets for therapy. METHODS: Cell viability was measured using cell counting kit-8 (CCK8). Cell migration and invasion abilities were determined using scratch-wound and Transwell invasion assays, respectively. mRNA and protein expression patterns of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), caspase-1 and IL-1ß were detected using qRT-PCR, immunofluorescence and western blot. The gasdermin D (GSDMD) level was determined via confocal microscopy and western blot. RESULTS: Anthocyanin reduced the viability of oral squamous cell carcinoma cells and inhibited migration and invasion abilities. Simultaneously, activation of pyroptosis was associated with enhanced expression of NLRP3, caspase-1, and IL-1ß. Upon administration of caspase-1 inhibitors, anthocyanin-activated pyroptosis was suppressed and cell viability, migration, and invasion rates concomitantly enhanced. CONCLUSION: Anthocyanin promotes the death of oral squamous cell carcinoma cells through activation of pyroptosis and inhibits tumor progression.

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle.

Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti-diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti-diabetic and anti-insulin-resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti-insulin-resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti-diabetic and anti-insulin-resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections.

[Effect of sophocarpine on HERG K+ channels].

Human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important effect on both proarrhythmia and antiarrhythmia. To investigate the effect of sophocarpine (SC) on HERG channel stably expressing in human embryonic kidney-293 (HEK293) cells, whole-cell patch-clamp technique was used to record HERG current and kinetic curves. As the result, it was found that SC inhibited HERG current in a concentration-dependent manner (10, 30, 100, and 300 micromol x L(-1)). At 0 mV, 10, 30, 100, and 300 micromol x L(-1) SC respectively inhibited IHERG by Istep ( 10.7 +/- 2.8)% , (11.3 +/- 5.5)% , (47.0 +/- 2.3)% and (53.7 +/- 2.5)% , and Itail (1.1 +/- 3.0)%, (17.1 +/- 3.3)%, (32.7 +/- 1.9)% (P < 0.05, n = 12) and (56.0 +/- 2.4)% (P < 0.05, n = 13). The time constants of inactivation, recovery from inactivation and onset of inactivation were accelerated. SC did not change other channel kinetics (activation and deactivation). It is concluded that SC inhibited the transfected HERG channels by influencing the inactivation state, which is the probable anti-arrhythmic mechanism.

Flavonoids from Chinese Viscum coloratum produce cytoprotective effects against ischemic myocardial injuries: inhibitory effect of flavonoids on PAF-induced Ca2+ overload.

Viscum coloratum has been used in the indigenous system of medicine for the treatment of various diseases such as myocardial ischemia and arrhythmia. Platelet-activating factor (PAF) is an important player in cardiovascular diseases. The aim of this study was to investigate the protective effects of Viscum coloratum flavonoids (VCF) against ischemic myocardial injuries in vivo and to further investigate its regulatory effect on PAF. Studies were performed in a rat model of myocardial infarction and in isolated myocytes. It was found that VCF relieved myocardial injuries during ischemia. PAF (10(-11) m) significantly increased the intracellular free Ca2+ concentration ([Ca2+]i) and VCF inhibited the changes induced by PAF in single cardiac myocytes. The results suggest that VCF can improve cardiac function and that VCF reduces ischemic myocardial injuries via blocking the signaling pathway of PAF. Therefore, PAF blockers may be candidate drugs for preventing cardiac injuries during ischemia/reperfusion, and subsequently improving cardiac function.

The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2.

MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3'-untranslated regions of target mRNAs. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and oncogenesis. Of more than 300 miRNAs that have been identified, miR-1 and miR-133 are considered to be muscle specific. Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. miR-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing KCNJ2 (which encodes the K(+) channel subunit Kir2.1) and GJA1 (which encodes connexin 43), and this likely accounts at least in part for its arrhythmogenic potential. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.