Aß-binding with alcohol dehydrogenase drives Alzheimer's disease pathogenesis: A review.

Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aß) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aß-derived formaldehyde (FA) and FA-induced Aß aggregation in the onset course of AD. Document evidence has shown that Aß can bind with alcohol dehydrogenase (ADH) to form the complex of Aß/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived H2O2 and FA promotes Aß self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression.

Investigation on the lubrication component and mechanism for a biolubricant isolated from the agro-waste resource of Codonopsis pilosula.

Waste plant resource provides a new sustainable feedstock for the biolubricant, and purification of the effective components in biomass oil is vital to improve the performance of biolubricant. In this work, the crude extract of the aerial part of Codonopsis pilosula was divided into four different parts by petroleum ether, ethyl acetate, n-butanol and water, respectively. Their thermal stability, lubricating performances and mechanisms have been systematically investigated. In the four extracts, the petroleum ether extract displays the best thermal stability and lubricating performance over the entire test conditions, and other three extracts are confronted with lubrication failure at high loads and elevated temperatures. Triterpenoid saponin, typical for n-butanol extract exhibit the best lubricity at room temperature, followed by the fatty acid derivatives as phosphatidylcholine; flavonoid, and sugar exhibit poor lubricity. At high temperature, only the petroleum ether extract retains the good lubricity.

Jujuboside A Exhibits an Antiepileptogenic Effect in the Rat Model via Protection against Traumatic Epilepsy-Induced Oxidative Stress and Inflammatory Responses.

Traumatic brain injuries (TBI) are the greatest source of death in trauma, and post-traumatic epilepsy (PTE) is one of the common complications of TBI. Oxidative stress and inflammatory responses play an important role in the process of PTE. Many studies have shown that Jujuboside A has powerful antioxidant and anti-inflammatory properties. However, it is not known whether Jujuboside A has an anti-epileptic effect. The influences of Jujuboside A in the experimental FeCl3-induced model of PTE were tested by estimating the grade of seizures and performing behavioral tests. Following that, we detected oxidative stress indicators and inflammatory factors. Additionally, western blotting was used to test the protein levels of signaling molecules in MAPK pathways. In this study, Jujuboside A was found to have improved the recognition deficiency and epilepsy syndromes in the experimental rat model. Moreover, oxidative stress and inflammatory responses induced by FeCl3 injection were relieved by Jujuboside A. In addition, Jujuboside A was found to be capable of reducing the increased expression of p-P38 and p-ERK1/2 caused by iron ions. Collectively, our results demonstrated that Jujuboside A exhibits an antiepileptogenic effect by alleviating oxidative stress and inflammatory responses via the p38 and ERK1/2 pathways.

Effects of Tibetan medicine metacinnabar (ß-HgS) combined with imipramine or sertraline on depression-like symptoms in mice.

Depression is a common mood disorder that has exhibited an increased incidence rate worldwide, but the overall clinical efficacy of antidepressants remains unsatisfactory. In traditional Ayurveda and Tibetan medicines, ß-HgS-containing medicines have been used to treat neurological diseases for thousands of years, and our previous study found that ß-HgS ameliorated depression-like behaviors in chronic restraint stress (CRS)-treated or chronic unpredictable mild stress (CUMS)-treated mice. Hence, present study investigated the effects of ß-HgS combined with the clinical first-line antidepressants, imipramine (IMI) and sertraline (SER), on depression-like symptoms in CRS- and CUMS-co-treated mice. Our results revealed that ß-HgS promoted the antidepressant effect of SER on depression-like behavior in mice, and enhanced its effects on promoting glucocorticoid receptor (GR) expression and neuronal proliferation in key hippocampal subregions, as well as increasing interleukin 10 (IL-10) levels and decreasing malondialdehyde levels in the sera of stress-stimulated mice. As for IMI, ß-HgS enhanced its effects on preventing atrophy and severe structural damage in the hippocampus, as well as in promoting hippocampal GR levels and neuronal proliferation and serum IL-10 and superoxide dismutase (SOD) levels. Additionally, combination therapy resulted in the increased diversity of important intestinal microbiota compared to that of monotherapy, which may help sustain the health of the digestive tract and reduce inflammation to further enhance the antidepressant effects of IMI and SER in mice.

Ginger (Zingiber officinale) extract mediated green synthesis of silver nanoparticles and evaluation of their antioxidant activity and potential catalytic reduction activities with Direct Blue 15 or Direct Orange 26.

The green synthesis of silver nanoparticles (AgNPs) using a water extract of Ginger (Zingiber officinale) root by microwave irradiation and its antibacterial activities have been reported. However, AgNPs prepared from different parts of ginger root water or ethanol extract by ultrasound synthesis and their antioxidant activity and whether the biogenic could be used to catalyze the reduction of hazardous dye are unknown. This study concentrated on the facile green synthesis of AgNPs prepared from different parts (unpeeled ginger, peeled ginger, and ginger peel) of ginger root water or ethanol extract by the ultrasound-assisted method. We studied their antioxidant activity and catalytic degradation of hazardous dye Direct Orange 26 (DO26) and Direct Blue 15 (DB15). The surface plasmon resonance (SPR) peak of AgNPs was at 428-443 nm. The biogenic AgNPs were approximately 2 nm in size with a regular spherical shape identified from TEM analysis. The ethanol extracts of dried unpeeled ginger and peeled ginger, fresh peeled ginger and ginger peel. The Z. officinale AgNPs synthesized by dried unpeeled ginger ethanol extract showed the best antioxidant activity. Their scavenging activities were significantly better than BHT (p <0.05). The different parts of ginger extracts showed no catalytic degradation activities of DB15 and DO26. Still, the synthesized Z. officinale AgNPs exhibited good catalytic degradation activities, while their ability to catalytic degradation to DB15 was better than DO26. In the additive ratio of 3 mL DB15, 0.1 mL NaBH4 and 0.1 mL AgNPs, the degradation rates of DB15 (or DO26) at 15 min, 30 min and 60 min were only 1.8% (0.9%), 2.8% (1.4%) and 3.5% (1.6%) in the absence of AgNPs. When adding Z. officinale AgNPs prepared from dried ginger peel ethanol extract or fresh ginger peel water extract, the degradation rates of DB15 sharply increased to 97% and 93% after 30 min, respectively. In conclusion, ginger extract has good antioxidant properties. Z. officinale AgNPs biosynthesis from ginger extract exhibit excellent catalytic degradation activities, especially for the ginger peel extract. They have application value in the treatment of textile effluents and provide a new idea and method for the comprehensive development and utilization of ginger resources.

Is vitamin D deficiency a risk factor for all-cause mortality and rehospitalization in heart failure patients?: A systematic review and meta-analysis.

OBJECTIVE: The association of low 25-hydroxyvitamin D level with mortality and rehospitalization remains inconsistent in patients with heart failure. This systematic review and meta-analysis aimed to evaluate the value of blood 25-hydroxyvitamin D level in predicting all-cause mortality and hospitalization in heart failure patients. METHODS: Two reviewers independently search the articles indexed in PubMed and Embase databases until November 30, 2021. Only the prospective or retrospective cohort studies evaluating the association of blood 25-hydroxyvitamin D level with all-cause mortality and rehospitalization in heart failure patients were selected. The predictive value of 25-hydroxyvitamin D level was summarized by pooling multivariable adjusted risk estimates for the bottom versus reference top 25-hydroxyvitamin D level. RESULTS: Seven studies with a total of 5941 patients with heart failure were identified. The pooled adjusted risk ratio (RR) of all-cause mortality was 1.37 (95% confidence interval [CI] 1.13-1.66), with significant heterogeneity (I2 = 70.5%; P = 0.002). However, there was no clear association between low 25-hydroxyvitamin D level and all-cause rehospitalization risk (RR 1.38; 95% CI 0.87-2.19). CONCLUSIONS: Low blood level of 25-hydroxyvitamin D may be an independent risk factor for all-cause mortality in patients with heart failure. Serum 25-hydroxyvitamin D level may provide prognostic information in heart failure patients. Additional randomized controlled trials are required to explore whether treatment of 25-hydroxyvitamin D deficiency by supplementation of vitamin D can improve survival in heart failure patients.

Exploring the mechanisms of action of Cordyceps sinensis for the treatment of depression using network pharmacology and molecular docking.

Background: Depression is the most common type of psychological disorder, with continuous, prolonged, and persistent bad moods as the main clinical feature. Cordyceps sinensis is a complex consisting of the ascospores and bodies of insect larvae from the Hepialidae family that have been parasitized by Cordyceps sinensis militaris. Previous studies have reported that this herb has antidepressant activity. The present study used network pharmacology and molecular docking techniques to investigate the potential antidepressant mechanisms of Cordyceps sinensis. Methods: The active ingredients of Cordyceps sinensis were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the potential targets were predicted using the PharmMapper platform. The GeneCards database was then used to obtain sub-targets for depression. Common targets were screened and enrichment analyses were performed using the Metascape platform. Finally, the relationship between the active ingredients and the core targets were verified by molecular docking. Results: Through network pharmacological analysis, 7 active ingredients in Cordyceps sinensis and 41 common targets of drugs and diseases were identified. The active ingredients of Cordyceps sinensis may exert antidepressant effects by acting on important targets such as catalase (CAT), CREB binding protein (CREBBP), epidermal growth factor (EGF), and E1A binding protein P300 (EP300), and by modulating the signaling pathways in which these targets are involved. Subsequently, the core targets were docked to the active ingredients and good binding was observed. Conclusions: The active ingredients of Cordyceps sinensis may exert antidepressant effects by regulating the CREB binding protein and anti-oxidative stress effects. The foxo signaling pathway (hsa04068), hypoxia-inducible factor 1 (HIF-1) signaling pathway (hsa04066), and Huntington's disease (hsa05016) may be involved in the underlying mechanisms of Cordyceps sinensis. The joint application of network pharmacology and molecular docking provides a new approach to study the mechanisms of action of traditional Chinese medicine. Cordyceps sinensis may play an important role in the future treatment of patients with depression.

Optimization of the extraction conditions and dermal toxicity of oil body fused with acidic fibroblast growth factor (OLAF).

INTRODUCTION: Oil body (OB), a subcellular organelle that stores oil in plant seeds, is considered a new transdermal drug delivery system. With the increasing understanding of the OB and its main protein (oleosin), numerous studies have been conducted on OB as "carrier" for the expression of exogenous proteins. In our previous study, oil body fused with aFGF (OLAF) was obtained using a plant oil body expression system that had been preliminarily proven to be effective in accelerating the healing of skin wounds. However, no dermal toxicological information on OLAF is available. OBJECTIVE: To ensure the dermal safety of OLAF, a series of tests (the acute dermal toxicity test, 21-day repeat dermal toxicity test, dermal irritation test and skin sensitisation test) were conducted after optimising the extraction protocol of OLAF. MATERIALS AND METHODS: To improve the extraction rate of OLAF, response surface methodology (RSM) was first employed to optimise the extraction conditions. Then, Wistar rats were exposed to OLAF (400 mg·kg-1 body weight) in two different ways (6 hours/time for 24 hours and 1 time/day for 21 days) to evaluate the acute dermal toxicity and 21-day repeated dermal toxicity of OLAF. In the acute dermal toxicity test, clinical observations were conducted to evaluate the toxicity, behaviour, and health of the animals for 14 consecutive days. Similarly, the clinical signs, body weight, haematological and biochemical parameters, histopathological changes and other indicators were also detected during the 21 days administration. For the dermal irritation test, single and multiple doses of OLAF (125 mg·kg-1 body weight) were administered to albino rabbits for 14 days (1 time/day). The irritation reaction on the skin of each albino rabbit was recorded and scored. Meanwhile, skin sensitisation to OLAF was conducted using guinea pigs for a period of 28 days. RESULTS: Suitable extraction conditions for OLAF (PBS concentration 0.01, pH of PBS 8.6, solid-liquid ratio 1:385 g·mL-1) were obtained using RSM. Under these conditions, the extraction rate and particle size of OLAF were 7.29% and 1290 nm, respectively. In the tests of acute dermal toxicity and 21-day repeated dermal toxicity, no mortality or significant differences were observed in terms of clinical signs, body weight, haematological parameters, biochemical parameters and anatomopathological analysis. With respect to the dermal irritation test and skin sensitisation test, no differences in erythema, oedema or other abnormalities were observed between treatment and control groups on gross and histopathological examinations. CONCLUSIONS: The results of this study suggest that OLAF does not cause obvious toxicity, skin sensitisation or irritation in animals.

Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression.

Indoleamine 2, 3-dioxygenase 1 (IDO1) has been implicated in the pathogenesis of depression, though its molecular mechanism is still poorly understood. We investigated the molecular mechanism of IDO1 in depression by using the chronic unpredictable mild stress (CUMS) model in Ido1-/- mice and WT mice. The brain blood oxygen level dependent (BOLD) signals in mice were collected by functional magnetic resonance imaging (fMRI) technology. IDO1 inhibitor INCB024360 was intervened in dorsal raphe nucleus (DRN) through stereotactic injection. We found an elevation of serum IDO1 activity and decreased 5-HT in CUMS mice, and the serum IDO1 activity was negatively correlated with 5-HT level. Consistently, IDO1 was increased in hippocampus and DRN regions, accompanied by a reduction of hippocampal BDNF levels in mice with CUMS. Specifically, pharmacological inhibition of IDO1 activity in the DRN alleviated depressive-like behaviour with improving hippocampal BDNF expression and neurogenesis in CUMS mice. Furthermore, ablation of Ido1 exerted stress resistance and decreased the sensitivity of depression in CUMS mice with the stable BOLD signals, BDNF expression and neurogenesis in hippocampus. Thus, IDO1 hyperactivity played crucial roles in modulating 5-HT metabolism and BDNF function thereby impacting outcomes of hippocampal neurogenesis and BOLD signals in depressive disorder.

Ma-Nuo-Xi decoction has an immunostimulating effect in cyclophosphamide-immunosuppressed mice.

BACKGROUND: Ma-Nuo-Xi decoction (MNXD), as well as its hundreds of derivative preparations, has been used in Tibetan medicine since the 14th century. MNXD is in accordance with the theory of treatment determination based on syndrome differentiation. This study aimed to compare the effect of the auxiliary MNXD prescription (MNXD-AD) with that of the basic MNXD prescription (MNXD-BD) on the immunostimulating activity of MNXD. METHODS: The immunopotentiation of MNXD, MNXD-BD, and MNXD-AD was evaluated using a cyclophosphamide (CTX)-immunosuppressed mouse model. Their influences on non-specific and specific immunity were evaluated using immune organ indexes, peripheral white blood cell (WBC) count, red blood cell (RBC) count, platelet count, phagocytosis, macrophage-secreted nitric oxide (NO) and cytokines, natural killer (NK) cytotoxic activity, lymphocyte proliferation, serum cytokines, splenic T-lymphocyte subpopulations, and quantitative hemolysis of sheep red blood cell (QHS SRBC) assays. RESULTS: MNXD, MNXD-BD, and MNXD-AD increased the spleen and thymus indexes, as well as the peripheral WBC, RBC, and platelet counts. They also promoted phagocytosis, NO and cytokine secretion from macrophages, NK cytotoxic activity, and lymphocyte proliferation, and also raised the CD4+ /CD8+ T-cell ratio, serum cytokine concentrations, and haemolysin formation in CTX-treated immunosuppressed mice. Compared with MNXD-BD and MNXD-AD, MNXD was superior in restoring the phagocytic index, concanavalin A (ConA)-induced T-lymphocyte proliferation, NO secretion from macrophages, and haemolysin formation, as well as the levels of interleukin 1 beta (IL-1ß), and serum interleukin-2 (IL-2) and interferon gamma (INF-γ). CONCLUSIONS: MNXD, MNXD-BD, and MNXD-AD have excellent immunostimulating and myelosuppression-restoring activities on CTX-immunosuppressed mice. Among them, MNXD-AD might be an immunomodulator, which may happen to be in line with the clinical experience of Tibetan medicine physicians of using it to promote the efficacy of MNXD-BD.

Immunostimulating effect of polysaccharides isolated from Ma-Nuo-Xi decoction in cyclophosphamide-immunosuppressed mice.

Ma-Nuo-Xi Decoction (MNXD) is well-known in Tibetan medicine to be in line with the theory of treatment determination based on syndrome differentiation. However, the components responsible for its immunomodulating effect are unknown. In this study, three polysaccharide components-MNXD-P, MNXD-BD-P, and MNXD-AD-P-were isolated from MNXD and its basic and auxiliary prescription decoctions, of which MNXD-BD-P is composed of ß-(1,4)-d-glucan and RG-I pectin, MNXD-AD-P contains mainly α-(1,4)-d-glucan and some amount of arabinogalactan and/or arabinorhamnogalactan, and MNXD-P contains components of both MNXD-BD-P and MNXD-AD-P. And treatment with these polysaccharides could significantly improve the host's specific and non-specific immunity, including cellular and humoral immunities, as well as promote recovery from myelosuppression in cyclophosphamide (CTX)-immunosuppressed mice. To our knowledge, this is the first report on chemical and immunoactivity study on polysaccharides from traditional Tibetan medicine compounds, which may provide a new idea for development of carbohydrate drugs from them.

Modified Xiaoyaosan reverses aberrant brain regional homogeneity to exert antidepressive effects in mice.

The aim of this study is to explore the macroscale neural mechanisms of the antidepressant effects of Xiaoyaosan, a traditional Chinese herbal formula. We analyzed blood oxygen level-dependent (BOLD) functional magnetic resonance imaging signals. To further minimize the hemodynamic variations of BOLD signals and analyze the intra-region neural activity or temporal coherence, we employed the newly developed regional homogeneity (ReHo) approach to determine aberrant functional connectivity using the chronic unpredictable mild stress (CUMS) mouse model of depression and to also explore the brain-region rescue effect of modified Xiaoyaosan (MXYS) in such mice. We found the aberrant ReHo in CUMS mice replicated previous discoveries in patients with depression. Intriguingly, MXYS only normalized several limbic regions, which suggests the essential roles of these regions in mediating the antidepressant effects of MXYS. Our results provide a reliable framework for the use of ReHo analysis with animal models of depression and further suggest a new perspective to elucidate the antidepressant effects of MXYS.

Corrigendum: Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent FMRI Signals and Improving Hippocampal Neurogenesis in Mice.

[This corrects the article DOI: 10.3389/fphar.2018.01098.].

Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent fMRI Signals and Improving Hippocampal Neurogenesis in Mice.

As the traditional Chinese herbal formula, Xiaoyaosan and its modified formula have been described in many previous studies with definite anti-depressive effects, but its underlying mechanism remains mystery. Previous work in our lab has demonstrated that depression induced by chronic stress could generate brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals disorder, accompanied by the impairment of hippocampal neuronal plasticity, decrease of brain-derived neurotrophic factor, and reduction of the number and complexity of adult neurons in the dentate gyrus. We hypothesized that herbal formula based on Xiaoyaosan could exert anti-depressive effects through restoring these neurobiological dysfunctions and rectifying BOLD-fMRI signals. To test this hypothesis, we examined the effect of modified Xiaoyaosan (MXYS) on depressive-like behaviors, as well as hippocampal neurogenesis and BOLD signals in a mice model of chronic unpredictable mild stress (CUMS)-induced depression. MXYS exerted anti-depressant effects on CUMS-induced depression that were similar to the effects of classical antidepressants drug (fluoxetine hydrochloride), with a significant alleviation of depressive-like behaviors, an improvement of hippocampal neurogenesis, and a reversal of activation of BOLD in the limbic system, particularly in the hippocampus. These results suggested that MXYS attenuated CUMS-induced depressive behaviors by rectifying the BOLD signals in the mice hippocampus. These novel results demonstrated that MXYS had anti-depressive effects accompanied by improving BOLD signals and hippocampal neurogenesis, which suggested that BOLD-fMRI signals in brain regions could be a key component for the evaluation of novel antidepressant drugs.

A homogalacturonan from Hippophae rhamnoides L. Berries enhance immunomodulatory activity through TLR4/MyD88 pathway mediated activation of macrophages.

Our previous study isolated a natural high-methoxyl homogalacturonan (HRWP-A) from Hippophae rhamnoides and showed antitumor activity in vivo. In this study, the immunomodulatory activity and mechanisms of action of HRWP-A were further investigated. Results showed that HRWP-A could recover the body condition and activated macrophage in Cyclophosphamide (CTX)-induced immunosuppressed mice. Further, we investigated the possible mechanism underlying the effects of HRWP-A on mouse peritoneal macrophages. qPCR and western blot revealed that HRWP-A upregulated the expression of TLR4 mRNA in vitro. This process was accompanied by a clear increase in MyD88 expression and p-IκB-α, but these effects were largely abrogated by pretreatment with anti-TLR4 antibodies. The effects of HRWP-A on macrophage NO, IL-1ß and IL-6 production were also inhibited by anti-TLR4 antibodies and were greatly influenced by the NF-κB inhibitor PDTC. Moreover, HRWP-A failed to induce the production of NO, IL-1ß and IL-6 in peritoneal macrophages prepared from C3H/HeJ mice, which have a point mutation in the Tlr4 gene, suggesting the involvement of the TLR4 molecule in HRWP-A-mediated macrophage activation. These results may have important implications for our understanding of the structure-activity relationship of immunopotentiating polysaccharides from medicinal herbs.

Effects of Xiao Yao San on interferon-α-induced depression in mice.

BACKGROUND AND OBJECTIVE: Xiao Yao San (XYS) is a traditional Chinese medicine used to treat depression; however, the mechanism underlying its antidepressant properties remains unclear. The objective of the present study was to investigate the effects and action mechanisms of XYS on interferon-α-induced depression in mice. METHOD: Mice were divided into six groups: control; model; low-, medium-, and high-dose XYS; and escitalopram-treated group. Except for the control mice, all groups of mice were injected with interferon (IFN)-α to establish the depression model. XYS and escitalopram were then administered to the respective mice daily for 21 days. Sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used to measure behavioral indices. High-performance liquid chromatography (HPLC) was used to measure serotonin (5-HT) concentrations, while western blots were used to examine indoleamine-2,3-dioxygenase 1 (IDO1) expression in the dorsal raphe nucleus (DRN). The number of microglia in the DRN was observed using immunofluorescence. RESULTS: Compared with that of the control group, the model group showed a significant decrease in sucrose consumption (P < 0.05) and significant increase in the duration of immobility in the FST and TST (P  < 0.05). These parameters improved significantly after XYS or escitalopram treatment. There was also a significantly higher and lower expression of IDO1 protein and 5-HT in the mouse DRN, respectively, which were reversed by administering XYS and escitalopram (P < 0.05). Moreover, the number of microglia in the mouse DRN increased significantly and was reduced by XYS and escitalopram (P < 0.05). CONCLUSION: XYS reduced the number of microglia and expression of IDO1, which increased the levels of 5-HT in the mouse DRN and, thereby, improved the depressive behavior of mice. This may explain, at least in part, the antidepressant properties of XYS in patients.

Characterization and cardioprotective activity of anthocyanins from Nitraria tangutorum Bobr. by-products.

The Nitraria tangutorum Bobr. fruit is an indigenous berry of the shrub belonging to the Zygophyllaceae family which grows at an altitude of over 3000 m in the Tibetan Plateau, and has been used as a native medicinal food for treating weakness of the spleen, stomach syndrome, dyspepsia, neurasthenia, dizziness, etc. for thousands of years. Nowadays, N. tangutorum industrial juice by-products generated from health food production can be a potential low cost source of some unique bioactive ingredients. In a prior study, we established a simultaneous microwave/ultrasonic assisted enzymatic extraction method for extracting antioxidant ingredients from the industrial by-products of N. tangutorum juice. In this study, these ingredients were selectively fractionated by cation-exchange resin chromatography to obtain an anthocyanin fraction namely NJBAE. NJBAE was found to be composed of 16 anthocyanins derived from six anthocyanidins by HPLC-ESI-MS, and has an appreciable cardioprotective effect on doxorubicin-induced injured H9c2 cardiomyocytes. The cardioprotective mechanism research showed that NJBAE could directly scavenge ROS, restrict further generation of ROS, promote the activity of key antioxidase, enhance glutathione redox cycling, then affect the apoptotic signaling changes in a positive way, and finally mediate caspase-dependent cell death pathways. Therefore, NJBAE has great potential to be used for preventing and treating cardiovascular disease in the food, pharmaceutical and other emerging industries.

Enterolactone has stronger effects than enterodiol on ovarian cancer.

BACKGROUND: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. METHODS: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. RESULTS: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. CONCLUSION: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.

Anticancer and immunostimulating activities of a novel homogalacturonan from Hippophae rhamnoides L. berry.

Our previous study isolated an anti-fatigue polysaccharide (HRWP) from the Hippophae rhamnoides berry. In this study, using ion-exchange chromatography and gel filtration chromatography in turn, a water-soluble homogenous polysaccharide HRWP-A was isolated from HRWP. Structural analysis determined that HRWP-A was a polysaccharide with repeating units of (1→4)-ß-d-galactopyranosyluronic residues, of which 85.16% were esterified with methyl groups. An antitumor activity assay showed that HRWP-A could significantly inhibit the Lewis lung carcinoma (LLC) growth in tumor-bearing mice. Further experiments suggested that the antitumor effect of HRWP-A might be mediated through immunostimulating activity, as it enhances the lymphocyte proliferation, augments the macrophage activities, as well as promoting NK cell activity and CTL cytotoxicity in tumor-bearing mice. To our knowledge, this is the first report on a natural antitumor high-methoxyl homogalacturonan pectin from the H. rhamnoides berry-a compound that acts as a potential immunostimulant and anticancer adjuvant.

Boronyl as a terminal ligand in boron oxide clusters: hexagonal ring C(2v) B6O4 and ethylene-like D(2h) B6O4(-/2-).

Considerable recent research effort has been devoted to the development of boronyl (BO) chemistry. Here we predict three perfectly planar boron boronyl clusters: C2v B6O4 (1, (1)A1), D2h B6O4(−) (2, (2)B3u), and D2h B6O4(2−) (3, (1)Ag). These are established as the global-minimum structures on the basis of the coalescence kick and basin hopping structural searches and electronic structure calculations at the B3LYP/aug-cc-pVTZ level, with complementary CCSD/6-311+G* and single-point CCSD(T)/6-311+G*//B3LYP/aug-cc-pVTZ calculations for 2. The C2v B6O4 neutral cluster features a hexagonal B4O2 ring with two terminal BO groups. The D2h B6O4(−/2−) clusters have ethylene-like structures and are readily formulated as B2(BO)4(−/2−), in which a B2 core with double bond character is bonded to four terminal BO groups. Chemical bonding analyses show that B6O4 (1) possesses an aromatic π bonding system with three delocalized, six-centered π bonds over the hexagonal ring, rendering it an inorganic analogue of benzene, whereas the B6O4(−/2−) (2 and 3) species closely resemble ethylene in terms of structures and bonding. This work provides new examples for the analogy between boron oxides and hydrocarbons.