The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review.

Neurological diseases place a substantial burden on public health and have a serious impact on the quality of life of patients. Despite the multifaceted pathological process involved in the occurrence and development of these neurological diseases, each disease has its own unique pathological characteristics and underlying molecular mechanisms which trigger their onset. Thus, it is unlikely to achieve effective treatment of neurological diseases by means of a single approach. To this end, we reason that it is pivotal to seek an efficient strategy that implements multitherapeutic targeting and addresses the multifaceted pathological process to overcome the complex issues related to neural dysfunction. In recent years, natural medicinal plant-derived monomers have received extensive attention as new neuroprotective agents for treatment of neurological disorders. Fisetin, a flavonoid, has emerged as a novel potential molecule that enhances neural protection and reverses cognitive abnormalities. The neuroprotective effects of fisetin are attributed to its multifaceted biological activity and multiple therapeutic mechanisms associated with different neurological disorders. In this review article, we summarize recent research progression regarding the pharmacological effects of fisetin in treating several neurological diseases and the potential mechanisms.

Antimicrobial activity and enzymatic analysis of endophytes isolated from Codonopsis pilosula.

The roots of the medicinal plant Codonopsis pilosula (Franch.) Nannf (C. pilosula) possess most medicinal supplements. In current research on C. pilosula root endophytes were isolated, identified, and evaluated for their antimicrobial activity against human pathogens such as Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Salmonella typhi, and Pseudomonas aeruginosa and the fungi Candida albicans and Aspergillus niger. Endophytes C.P-8 and C.P-20 exhibited very significant antimicrobial activity, the secondary metabolite of C.P-8 registered at retention time 24.075 by HPLC analysis. Significant minimum inhibitory concentration (MIC) of C.P-8 was exhibited at 250 µg/ml against S. aureus and 500 µg/ml against B. subtilis. Qualitative, quantitative analyses, and partial purification of enzymes and purity was analysed by molecular weight determined by SDS‒PAGE of enzymes produced by C.P-20, amylase-64 kDa, protease-64 kDa, chitinase-30 kDa, and cellulase-54 kDa. Optimum pH and temperature of the partially purified enzymes, was carried out. The partially purified enzymes from C.P-20 displayed maximum activity at pH 6-7 and temperatures of 40°C-45°C. Moreover, the above endophytes will be useful tools for producing active enzymes and active bioantimicrobial agents against human pathogens.

Hyperbaric oxygen via mediating SIRT1-induced deacetylation of HMGB1 improved cReperfusion inj/reperfusion injury.

Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro-protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF-α, IL-1ß and IL-6 related inflammatory factors. RT-qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro-inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1-induced HMGB1 deacetylation and suppressing MMP-9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1-induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.

[Effects of Exogenous Phosphorus on Rice Growth and Cadmium Accumulation and Transportation Under Cadmium Stress].

In this study, we investigated the effects of exogenous phosphorus on the accumulation and transportation of cadmium in rice plants through a hydroponic experiment. In the experiment, the rice variety was Huanghuazhan, P solution concentrations were 10.0-45.0 mg ·L-1 that was made using NaH2PO4, and Cd solution concentrations were 0.1 mg ·L-1 and 0.2 mg ·L-1. The results showed that: ① the biomass in all parts of rice plants and contents of photosynthetic pigment (chlorophyll a, chlorophyll b, and carotenoid) increased gradually with an increase in exogenous P. ② Content of Cd in rice stems, leaves, husk, and brown rice increased gradually with an increase in the amounts of exogenous P. The content of Cd in brown rice increased by 2.8%-22.8% and 40.9%-61.8% when treated with Cd concentrations of 0.1 mg ·L-1 and 0.2 mg ·L-1 in hydroponic solutions, respectively. ③ Cd accumulation in rice plants was accelerated due to the application of exogenous P. Cd accumulating amounts increased from 395.1 µg ·plant-1 to 542.6 µg ·plant-1 and 639.6 µg ·plant-1 to 1082.0 µg ·plant-1 when treated with Cd concentrations of 0.1 and 0.2 mg ·L-1 in hydroponic solutions, respectively. ④ With an increase in the applied amounts of exogenous P, the P/Cd quality ratio in rice roots increased, while those in rice stems, leaves, husks, and brown rice decreased; meanwhile, the Cd transfer coefficients from root to stem (TFroot-stem) and stem to leaf (TFstem-leaf) increased. This showed that there was a certain synergistic effect between P and Cd in the rice parts. Finally, the application of exogenous P promoted the transfer of Cd from the rice root to other rice tissues, resulting in a synergistic effect on Cd accumulation and transportation in various rice tissues and increased Cd contents in brown rice.

Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway.

BACKGROUND: PM2.5 is associated closely with an increased risk of membranous nephropathy (MN), however, whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. Triptolide, an active component in Tripterygium wilfordii Hook F, is frequently used to treat MN in China, but its effects on PM2.5-induced podocytes injury is still largely unknown. Therefore, we evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms. RESULTS: Podocytes were incubated with PM2.5 after being pre-treated with triptolide, viability, apoptosis rate and migratory capacity of podocytes were determined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) in podocytes, the cytoskeleton of podocytes, the protein expressions of nephrin, podocin, Bcl-2, Bax, nuclear factor kappa-B/p65 (NF-κB/p65) and phospho-inhibitor of NF-κB (p-IκBα) were measured. Our data showed that PM2.5 treatment significantly increased the disorganization of F-actin stress fibers, the damaged structural integrity of nucleus, the deranged and dissociated cytoskeleton in podocytes, increased the podocytes apoptosis rate, the levels of MDA and LDH, markedly up-regulated the protein expression of Bax, NF-κB/p65 and p-IκBα, down-regulated the protein expression of nephrin, podocin and Bcl-2, and significantly decreased the level of SOD, the migration rate and the viability of podocytes, compared with those of the untreated podocytes. These effects of PM2.5 on podocytes, however, were reversed by triptolide administration. CONCLUSION: These results suggest that triptolide could prevent against PM2.5-induced podocytes injury via suppressing NF-κB signaling pathway.

Detoxification and activating blood circulation decoction reduces restenosis involving the TLR4/NF-κB pathway after balloon injury.

Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-κB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. DABCD may be a potential therapeutic agent against restenosis.

TNM-PNI: a novel prognostic scoring system for patients with gastric cancer and curative D2 resection.

PURPOSE: Gastric cancer (GC) is one of the most common malignancies and has a high mortality rate. In recent years, several nutritional or inflammatory biomarkers have been shown to effectively predict the prognosis of tumors. In this study, we intended to establish a prognostic scoring system for GC patients. PATIENTS AND METHODS: Our study included a total of 501 GC patients who were diagnosed with GC stage I-III and received curative gastrectomy with D2 lymphadenectomy between January 2011 and December 2012. Survival analysis was performed using Kaplan-Meier and log-rank tests. Two Cox multivariate models, one for continuous and one for categorical variables, were established to identify independent prognostic factors. All statistical analyses were performed using SPSS 20.0. RESULTS: Univariate and multivariate analyses revealed that tumor-node-metastasis (TNM) stage, preoperative prognostic nutritional index (PNI), and adjuvant therapy were independent prognostic factors for GC patients. We established a new composite variable, TNM-PNI, which was confirmed to be a major prognostic factor for curative D2 resection, independent of whether adjuvant therapy was administered. GC patients with higher TNM-PNI scores always had worse cancer outcomes. In addition, we found that adjuvant therapy might be beneficial for the survival of GC patients with TNM-PNI =4 or 5. CONCLUSION: Preoperative PNI plays a distinctly subsidiary role to the TNM stage when predicting patient prognosis. TNM-PNI is a novel and an effective prognostic index for GC patients with curative D2 resection and a good supplement for the National Comprehensive Cancer Network Guidelines.

Screening of Serum Protein Markers for Avascular Osteonecrosis of Femoral Head Differentially Expressed after Treatment with Yuanshi Shengmai Chenggu Tablets.

Avascular necrosis of the femoral head (ANFH) is an a frequently occurring orthopaedic disease with high morbidity. Traditional Chinese Medicine (TCM) Yuanshi Shengmai Chenggu Tablet is a valid prescription for treating steroid-induced femoral head necrosis. However, there are rare investigations about the serum protein marker expression after the acting of drugs on hormone and TCM. In the present study, we aimed to systematically discover and validate the serum biomarkers expression difference in patients with steroid-induced avascular necrosis of femoral head (SANFH) after taking Yuanshi Shengmai Chenggu Tablets (SANFH-TCM), so as to reveal the action mechanism of TCM from the molecular level by using isobaric tags for relative and absolute quantification (iTRAQ) with multiple reaction monitoring quantification. Significant differences in fibrinogen alpha, fibrinogen beta, fibrinogen gamma, fibronectin, C-reactive protein, apolipoprotein A, apolipoprotein D, and apolipoprotein E were found among SANFH, SANFH-TCM, and healthy controls. Therefore, our study proposes potential biomarkers for SANFH diagnosis and for the prognosis of femoral head necrosis after Traditional Chinese Medicine treatment.

Increased serum protein levels by Yuanshi Shengmai Chenggu Tablet in treatment of avascular osteonecrosis of the femoral head.

The traditional Chinese medicine (TCM) Yuanshi Shengmai Chenggu Tablet is used for treating the common orthopedic disease, hormone­induced avascular necrosis of the femoral head (ANFH) in China. However, its underlying mechanism and the changes induced in the treatment of ANFH remain to be fully elucidated. In the present study, through the use of isobaric Tag for Relative and Absolute Quantitation and multiple reaction monitoring quantifications, corticosteroid­induced femoral head necrosis and the effects of treatment with Yuanshi Shengmai Chenggu Tablet were examined. The aim was to identify serum proteins, which may be potential serum markers for the early clinical diagnosis of ANFH, and maybe used to develop more rapid and convenient detection strategies. A total of five proteins were identified, comprising Ig mu chain C region, keratin, type I cytoskeletal 9, properdin, apolipoprotein A­IV, and IQ and AAA domain­containing protein 1. The expression levels of all five proteins were lower in ANFH and were higher following TCM treatment. These findings were confirmed using ELISA and western blot analysis.

[Clinical Observation of Heat-sensitive Moxibustion Combined with Kegel Exercise Therapy for Female Stress Urinary Incontinence].

OBJECTIVE: To compare the clinical effects of heat-sensitive moxibustion combined with kegel exercise therapy and simple kegel exercise therapy on female stress urinary incontinence. METHODS: Forty-five female patients with stress urinary incontinence were randomly divided into a treatment group (n=23) and a control group (n=22). Kegel exercise therapy was applied in the two groups. Heat-sensitive moxibustion was used at Zhongji (CV 3), Qihai (CV 6), Ciliao (BL 32) and Shen-shu (BL 23) in the treatment group, once a day for the first 10 times, and once every other day until 5 sessions were given, 10 times as one session. 1-hour pad test, International Incontinence Advisory Board questionnaire (ICIQ-SF) and the number of urine leakage were observed before and after treatment. And the clinical effect was evaluated. RESULTS: The curative rate of 43.48%(10/23) and the total effective rate of 95.65%(22/23) in the treatment group were respectively better than those of 18.18% (4/22) and 63.64%(14/22) in the control group (both P<0.05). After treatment, 1-hour pad test and ICIQ-SF score were lower than those before treatment in the two groups, and the number of urine leakage decreased (all P<0.01). The above three indexes of the treatment group were better than those of the control group (all P<0.01). CONCLUSIONS: Heat-sensitive moxibustion combined with kegel exercise therapy achieves better effect than simple kegel exercise therapy on female stress urinary incontinence.

Treatment with EGCG in NSCLC leads to decreasing interstitial fluid pressure and hypoxia to improve chemotherapy efficacy through rebalance of Ang-1 and Ang-2.

AIM: Microvasculature and microenvironment play important roles in proliferation, invasion, metastasis and prognosis in non-small cell lung cancer (NSCLC), which might be altered by many anti-angiogenic drugs. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors, such as endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and angiopoietins (ANGs). Hypothesizing that EGCG might regulate microvasculature and microenvironment in NSCLC, the effects of EGCG on microvessel density (MVD), expression of Ang-1 and Ang-2, interstitial fluid pressure (IFP), tumor hypoxia, and chemotherapy sensitivity were examined. METHODS AND RESULTS: EGCG treatment of A549 cells in mice bearing xenografts in vivo led to a significant decrease of MVD detected by CD31, and of Ang-2 expression detected by quantum dots double-label immunofluorescence assessment, while Ang-1 decreased with no significance. Decreased IFP was measured by the Wink-in-needle method, while hypoxia was assessed by polarographic electrode and pimonidazole (PIMO) immunohistochemistry. Assuming that these changes would increase response to chemotherapy, tumor growth studies were p[erformed in nude mice with xenografts, which were then treated with EGCG and the chemotherapeutic agent cisplatin. EGCG therapy combined with cisplatin led to synergistic inhibition of tumor growth, compared with administration of each treatment separately (P < 0.001). According to linear regression analysis, IFP was positively correlated with PIMO staining (R(2) = 0.618, P = 0.002), Ang-2 was correlated with MVD (R(2) = 0.423, P = 0.022), IFP (R(2) = 0.663, P = 0.01) and PIMO staining (R(2) = 0.694, P = 0.01). CONCLUSION: IFP and delivery of oxygen might be improved by rebalance of Ang-1/Ang-2 under the treatment of EGCG in NSCLC, which also acts as a sensitizer of chemotherapy. These studies established a new mechanism for using EGCG as an adjuvant chemotherapy agent through modifying microvasculature and microenvironment.

Janus-type AT nucleosides: synthesis, solid and solution state structures.

Novel Janus-type nucleoside analogues (1a-d) were synthesized. Their pyrimido[4,5-d]pyrimidine base moiety has one face with a bidentate Watson-Crick donor-acceptor (DA) H-bond array of adenine and the other face with an acceptor-donor (AD) H-bond array of thymine. These nucleosides may self-associate through the self-complementary base pair. Indeed, in the solid state, compound 6d displayed a honeycomb-like supramolecular structure with tetrameric membered cavities formed through the combination of reverse Watson-Crick base pairs and aromatic stacking, in which the solvent molecules were accommodated. The result of temperature-dependent CD studies showed that the free nucleosides can form higher order chiral structures in aqueous solution.

[Studies on the chemical constituents from Cissus assamica].

OBJECTIVE: To study the chemical constituents from Cissus assamica and obtain a more comprehensive understanding of its effective components. METHODS: Compounds were isolated by various column chromatographies with silica gel. Their structures were elucidated by spectral analysis (IR, MS, 1H-NMR, 13C-NMR) and chemical evidence. RESULTS: Eight compounds were isolated and elucidated as ursolic acid (I), lupeol (II), n-hexacosinc acid (III), isolariciresinol-9-O-beta-D-glucopyranoside (IV), dauco sterin (V), 3,3'-dimethyl ellagic acid (VI), beta-Sitosterol (VII), bergenin (VIII). CONCLUSION: Among these compounds, I-V are isolated from this plant for the first time.

Characteristics of Se-enriched mycelia by Stropharia rugoso-annulata and its antioxidant activities in vivo.

Selenium (Se) is an essential trace element for humans and animals. Stropharia rugoso-annulata is a nutritional and functional mushroom containing many kinds of bioactive ingredients. The aims of this study were to investigate the Se-enrichment characteristics of S. rugoso-annulata in submerged culture and evaluate the antioxidant activities of Se-enriched mycelia in vivo in terms of the values of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA). The optimum parameters of Se-enrichment under the optimal Se concentration (150 microg/mL) in media were as follows: biomass 8.11 +/- 0.25 g/L, Se content in mycelia 4,727.68 +/- 13 microg/g, Se-accumulated rate 24.68 +/- 1.67%, and percentage of organic Se 96.27 +/- 3.26%. The mainly subsistent forms of selenium in Se-enriched mycelia were selenoprotein and selenium-polysaccharide. The contents of total amino acids (TAA) and essential amino acids (EAA) in Se-enriched mycelia were increased by 13.5 +/- 1.09% and 12.8 +/- 0.89%, respectively. It was efficient for Se-enriched mycelia to elevate GSH-Px and SOD activities and decrease MDA content. These results indicated that Se-enriched mycelia of S. rugoso-annulata represent a novel dietary source of bioavailable supplemental selenium.

[Effects of Selaginella doederleinii on human nasopharyngeal carcinoma TW03 cells in vitro and its mechanism].

OBJECTIVE: To study the inhibition and mechanism of Selaginella doederleinii (SLG) on the growth of nasopharyngeal carcinoma (NPC) TW03 cells in vitro. METHODS: Cell suppression rates were measured by MTT assay, cell cycles were measured by flow cytometry (FCM) and expressions of Bc1-2 and Bax protein were detected by immunohistochemistry. RESULTS: Inhibition on the growth of NPC cell was intensed by SLG in a dose and time dependent manner in vitro (P < 0.05). The ratio of S phase cells increased and the ratios of G0/G1 and G2/M phase cells decreased, with the addition of SLG. Meanwhile, the expression of Bcl-2 protein was down-regulated and Bax protein was up-regulated. CONCLUSION: SLG could inhibit the growth of human NPC TW03 cells by directing cell cycle arrested at S phase, down-regulating Bcl-2 protein expression and up-regulating Bax protein expression.

[Identification on three kinds of Diphylleia sinensis (I)].

OBJECTIVE: In order to provide reference for the development of quality standards and distinction of authenticity, some sources of Diphylleia sinensis Li. in the market were identified by sampling. METHODS: To identify the traits and microscopic features of six batches of Diphylleia sinensis Li. in the market. RESULTS: They were the dried rhizome of Diphylleia sinensis Li., Dysosma versipellis (Hance) M. Cheng and D. pleiantha (Hance) Woods. CONCLUSION: The differences in traits and microscopic features of them are obvious.

[Identification on three kinds of Diphylleia sinensis (II)].

OBJECTIVE: In order to provide reference for the development of quality standards and distinction of authenticity, some sources of Diphylleia sinensis Li. in the maket were identified by sampling. METHODS: The TLC of six batches of Diphylleia sinensis Li. in the market were identified. RESULTS: They were the dried rhizome of Diphylleia sinensis Li., Dysosma versipellis (Hance.) M. Cheng and D. pleiantha (Hance) Woods. According to the pharmaceutical characteristics, retrieval tables of identification on plants, traits, microscopic and TLC were established. CONCLUSION: It is simple and reliable to use TLC and retrieval table to identify three sources of Diphylleia sinensis Li.

[Effect of Liangge San on lipopolysaccharide-induced nuclear factor kappa B activation in cultured mouse macrophages].

OBJECTIVE: To investigate the effect of Liangge San, a recipe of traditional Chinese herbal medicine, on lipopolysaccharide (LPS)-induced nuclear factor kB (NF-kB) activation in mouse macrophages cultured in vitro and explore the signal transduction mechanism of the detoxifying effect of Liangge San. METHODS: The mice were given oral administration of concentrated decoction of Liangge San to obtain the drug-containing serum. Macrophages from mouse abdominal cavity were collected, incubated and subsequently re-incubated with LPS and the prepared serum at different doses. Immunofluorescence method was adopted to examine the expression of NF-kB subunit p65 in the nuclei of the macrophages, and the fluorescence intensity of p65 expression was measured by laser scanning confocal microscope (LSCM). RESULTS: The fluorescence intensity of p65 expression in the nuclei of macrophages incubated with LPS for 1 h was significantly increased compared with that in the cells without LPS stimulation and Liangge San serum-treated cells. The fluorescence intensities were significantly decreased in cells treated with the inhibitor TLCK and different doses of Liangge San serum in comparison with those in LPS-stimulated cells. The fluorescence intensities were the lowest in cells treated with TLCK and high-dose Liangge San serum, and the cells treated with moderate and low doses of the serum both showed lower intensity compared with that of LPS-stimulated cells. p65 expression was similar between the macrophages incubated with LPS and those treated with serum that contained no Liangge San. CONCLUSIONS: Mouse serum containing Liangge San can inhibit LPS-induced p65 expression in mouse macrophages in a dose-dependent manner, which may be one of the signal transduction mechanisms of the detoxifying effect of Liangge San.