Therapeutic Effect of Tympanoplasty on Patients with Chronic Otitis Media with Tinnitus and Influencing Factors.

Objective: This research was conducted to investigate the therapeutic effects of tympanoplasty on patients with chronic otitis media with tinnitus and analyze the possible influencing factors for patient prognosis. Methods: This is a pre-post control group study, 86 patients with chronic otitis media were included as the subjects and enrolled into tinnitus group (n = 46) and the non-tinnitus group (n = 40). All patients underwent tympanoplasty under microscope or ear endoscopy. A tinnitus severity and efficacy assessment scale was employed for the evaluation of the severity of tinnitus among the subjects. In addition, tinnitus handicap inventory (THI) was utilized to evaluate disease alleviation. Results: Before treatment, the proportions of the patients with tinnitus at grades I, II, III, IV, and V amounted to 15.22%, 32.61%, 21.74%, 17.39%, and 13.04%, respectively, while they were 30.43%, 45.65%, 13.04%, 8.71%, and 2.17%, respectively 3 months after treatment (P < .05). THI scores for the patients in the tinnitus group before and 3 months after treatment amounted to 17.96 ± 3.66 and 16.21 ± 3.29, respectively (P < .05). After treatment, the air conduction (AC) and bone conduction (BC) thresholds and air-bone gap (ABG) of the two groups apparently declined (P < .05). No statistical significance was detected in the differences in disease classification, disease courses, and whether an electric drill was used among the patients between effective and invalid groups (P > .05). Conclusion: To some extent, tympanoplasty alleviated tinnitus among patients with chronic otitis media and promoted the restoration of hearing. Hence, it is worthy of application in clinical treatment.

[Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway].

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

Sodium chloride alleviates oxidative stress and physiological responses induced by extreme winter cold in genetically improved farmed tilapia (GIFT; Oreochromis niloticus).

A 6-week trial was designed to investigate the effects of dietary sodium chloride supplementation on physiological, metabolic, and molecular stress response parameters. The findings showed that (1) there were no significant differences between sodium chloride supplementation groups (0.05S, 0.1S, and 0.15S) and the control group (P > 0.05), except for the 0.2S diet, which showed better final body weight, weight gain rate, specific growth rate, and feed conversion ratio than the control group (P < 0.05). (2) The hypothermic stress experiment results showed that the survival rates in the 0.1S and 0.15S diets were significantly higher than the control group (P < 0.05). (3) Transcription results showed that these enriched pathways in the gill were mainly energy metabolism and apoptosis pathways, while the major enrichment pathways in the liver were mainly amino acid metabolism and carbohydrate metabolism. (4) The plasma parameter results showed, compared to the control group, the 0.15S diet significantly increased the plasma GLU, TG contents, and Na+ and K+ concentrations and decreased the plasma ALT activity (P < 0.05). In addition, the 0.1S diet increased the plasma ALB content and Cl- concentration (P < 0.05). The gill Na+/K+-ATPase activity decreased markedly when the fish were fed the 0.1S and 0.15S diets (P < 0.05). The antioxidant enzyme activity results showed that the 0.1S and 0.15S diets significantly increased the T-SOD activities (P < 0.05). Gene expression results showed that compared to the control group, the 0.1S and 0.15S diets up-regulated the expression of gys, hsp70, mlcp, mlc, myosin, tnt mRNA, and down-regulated the akt, gk, and erk mRNA expression. Based on the regression analysis, the optimum dietary sodium chloride levels range from 0.10 % to 0.13 % of the diet, which could facilitate energy regulation, improve the immune response, and ultimately strengthen the cold resistance of GIFT.

C21 steroids from the roots of Marsdenia tenacissima.

A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of the sixteen undescribed pregnane C21 steroids (1-16) and isolation of eleven known C21 steroidal analogues (17-27). Their chemical structures were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy and, high resolution-electrospray ionization mass spectrometry and their absolute configurations were determined using electronic circular dichroism or single-crystal X-ray diffraction. The in vitro anti-proliferative effects of 1-16 were evaluated against HepG2 (human hepatocellular cancer), A549 (lung cancer), and MCF-7 (human breast cancer) cell lines. Even though some of them showed moderate cytotoxic activities, marsectohexol derivative 12 exhibited significant cytotoxicity against A549 cells with an IC50 value of 5.2 µM.

Effects of intensive speech treatment on Mandarin speakers with Parkinson's Disease: A review.

BACKGROUND: Benefits of intensive speech treatment have been documented for a range of speech signs in English speakers with Parkinson's Disease (PD). However, the answer to a critical question that whether the same treatment benefits speech variables including intelligibility in Mandarin speakers is still unclear. In order to develop a targeted speech treatment for Mandarin speakers with PD, we reviewed the efficacy of intensive speech treatment to improve vocal loudness and functional communication and discuss possible explanations for efficacy on Mandarin speakers with PD. METHODS: Literatures about intensive speech treatment for Mandarin speakers with PD were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Database for Chinese Technical Periodicals (VIP) Database. Search strategy was (voice therapy OR speech therapy OR voice treatment OR speech treatment OR voice training OR speech training OR voice rehabilitation OR speech rehabilitation OR Lee Silverman voice treatment OR intensive speech treatment) and (Parkinson's disease) and (Mandarin speakers OR Chinese OR Chinese people). RESULTS: Five randomized controlled trials were selected and possible explanations for efficacy on individuals with PD are discussed. Further research directions are suggested. CONCLUSION: The existing evidence from treatment efficacy studies of intensive speech treatment provides support for improving vocal loudness, speech intelligibility, pitch and rate in Mandarin speakers with PD. Our future research will continue to work to conduct a large sample multicenter randomized controlled trial to provide high quality evidence and understand the basic mechanisms accompanying treatment-related change.

Anti-Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L.

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides (1-5) and two new sesquiterpene glycosides (6 and 7) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.

Curcumol Undermines SDF-1α/CXCR4/NF-κB Signaling Pathway to Suppress the Progression of Chronic Atrophic Gastritis (CAG) and Gastric Cancer.

CAG is the most common precancerous disease of gastric cancer, which belongs to a kind of chronic gastritis. CAG is in close association with gastric cancer, which makes itself a critical node clinically in cancer prevention and treatment. Curcumol is a main active monomer in Fuzheng Huowei decoction, which has the properties of antioxidant, antiviral, and antitumor. In this study, the expression of SDF-1α/CXCR4/NF-κB was detected by in vivo and in vitro methods. Then, we found that the expressions of NF-κB, SDF-1α, CXCR4, and p-NF-κB were decreased in the curcumol treatment group. Curcumol inhibited gastric cancer cells' viability, migration, and invasion and induced their apoptosis. After adding the lentivirus overexpressing SDF-1α to the curcumol treatment group, it was found that SDF-1α, CXCR4, NF-κB, and p-NF-κB protein expressions were all increased, and the effect of curcumol on gastric cancer cells was reversed. In the nude mouse experiment, the tumor volume in the curcumol + SDF-1α group was the largest, and the tumor volume in the Fuzheng Huowei decoction + NC group was the smallest. In conclusion, curcumol effectively protects gastric tissue and inhibits the viability of gastric cancer cells, and curcumol regulates SDF-1α/CXCR4/NF-κB to play a therapeutic role in chronic atrophic gastritis and gastric cancer.

Sesquiterpenes from Artemisia annua and Their Cytotoxic Activities.

Artemisia annua is a well-known traditional Chinese medicine. Due to its highest antimalarial efficacy, China has a long history of cultivating A. annua, and it is used for "clearing heat and detoxicating". Several, studies have shown that the A. annua extract exerts cytotoxicity. In order to clarify the basis of the cytotoxic effect of A. annua, 18 sesquiterpenes were isolated from the herb, including 2 new sesquiterpenes and 16 known analogues. The structures of new compounds were elucidated by comprehensive spectroscopic analyses, including HR-ESI-MS, NMR experiments, single-crystal X-ray, and DP4+ and electronic circular dichroism (ECD) calculations. Cytotoxic activity screening revealed three compounds that exhibited cytotoxicity in a dose-dependent manner. Additional exploration showed that compound 5 significantly inhibited the proliferation of CT26 and HCT116 cells and induced apoptosis of HCT116 cells after 24 h. These chemical constituents contributed to elucidating the mechanism of action of the cytotoxic activity of A. annua.

Dietary chlorella (Chlorella vulgaris) supplementation effectively improves body color, alleviates muscle inflammation and inhibits apoptosis in largemouth bass (Micropterus salmoides).

Muscle quality, antioxidant status, and inflammatory and apoptotic molecule expression were investigated in juvenile largemouth bass fed five levels of Chlorella for 60 days. The results showed that muscle quality can be improved by increasing the muscle crude protein content, muscle and skin brightness value (L*), redness value (a*) and yellowness value (b*) in Chlorella-supplemented diets without affecting the growth and muscle fiber development of fish. Chlorella supplementation did not cause oxidative stress in muscle, but optimal Chlorella administration alleviated the muscle inflammatory response by downregulating the nuclear factor κB (NF-κB)-mediated proinflammatory factors such as interleukin 1ß (IL-1ß) and interleukin 8 (IL-8). Moreover, anti-apoptotic effects were induced by upregulation of anti-apoptotic genes, such as b cell lymphoma-2 (bcl-2) and myeloid cell leukemia-1 (mcl-1), and downregulation of pro-apoptotic genes, including bcl2-associated x (bax) and caspase3. In conclusion, Chlorella improved muscle quality, alleviated muscle inflammation and resisted muscle apoptosis.

Pharmacokinetics and anti-liver fibrosis characteristics of amygdalin: Key role of the deglycosylated metabolite prunasin.

BACKGROUND: Amygdalin (Amy) is a cyanoside and is one of the chief active ingredients in Persicae Semen, Armeniacae Semen Amarum, and Pruni Semen. Amy has extensive and remarkable pharmacological activities, including against anti-hepatic fibrosis. However, the pharmacokinetic and anti-liver fibrosis effects of Amy and its enzyme metabolite prunasin (Pru) in vivo have not been studied and compared, and studies on Pru are limited. PURPOSE: To investigate the pharmacokinetic characteristics and anti-liver fibrosis effect of Amy and its metabolite Pru in vivo and in vitro, and elucidate whether the metabolism of Amy in vivo for Pru is activated. METHODS: Pru was prepared from Amy via the enzymatic hydrolysis of ß-glucosidase, and isolated by silica gel column chromatography. An efficient and sensitive ultrahigh-performance liquid chromatography-Q exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry was developed and validated to determine simultaneously Amy and Pru in rat plasma after dosing intravenously and orally for pharmacokinetic studies. The affinities of Amy and Pru for ß-glucosidase were compared by enzyme kinetic experiments to explain the possible reasons for the differences in pharmacokinetic behavior. In vitro, the inhibitory effects of Amy and Pru on hepatic stellate cell activation and macrophage inflammation on JS1 and RAW 264.7 cells were determined. In vivo, the ameliorative effects of Amy and Pru on liver fibrosis effects were comprehensively evaluated by CCl4-induced liver fibrosis model in mice. RESULTS: The standard curves of Amy and Pru in rat plasma showed good linearity within the concentration range of 1.31-5000.00 ng/ml, with acceptable selectivity, carry-over, detection limit and quantification limits, intra- and inter-day precision, accuracy, matrix effect, and stability. The Cmax and AUC(0-∞) of Pru (Cmax = 1835.12 ± 268.09 ng/ml, AUC(0-∞) = 103,913.17 ± 14,202.48 ng•min/ml) were nearly 79.51- and 66.22-fold higher than those of Amy (Cmax = 23.08 ± 5.08 ng/ml, AUC(0-∞) = 1569.22 ± 650.62 ng•min/ml) after the oral administration of Amy. The oral bioavailability of Pru (64.91%) was higher than that of Amy (0.19%). The results of enzyme hydrolysis kinetics assay showed that the Vmax and Km of Pru were lower than those of Amy in commercial ß-glucosidase and intestinal bacteria. In vitro cellular assays showed that Amy and Pru were comparable in inhibiting the NO production in the RAW264.7 cell supernatant and the mRNA expression of α-SMA and Col1A1 in JS1 cells. Amy and Pru were also showed comparable activity in ameliorating CCl4-induced liver fibrosis in mice. CONCLUSION: The pharmacokinetic characteristics of Amy and Pru in rat plasma were significantly different. After the separate gavage of Amy and Pru, Amy was absorbed predominantly as it's metabolite Pru, whereas Pru was absorbed predominantly as a prototype. The anti-liver fibrosis effects of Amy and its deglycosylated metabolite Pru were comparable in vivo and in vitro. The deglycosylated activated metabolite Pru of Amy plays an important role in anti-liver fibrosis. These findings will facilitate the further exploitation of Amy and Pru.

Apple phenolic extracts ameliorate lead-induced cognitive impairment and depression- and anxiety-like behavior in mice by abating oxidative stress, inflammation and apoptosis via the miR-22-3p/SIRT1 axis.

Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.

Quercetin, the Ingredient of Xihuang Pills, Inhibits Hepatocellular Carcinoma by Regulating Autophagy and Macrophage Polarization.

BACKGROUND: The key active component(s) in an anti-tumor preparation used in traditional Chinese medicine, Xihuang Pills, remains unclear. METHODS: We used a network pharmacology analysis to construct a component-disease-target network diagram and used this to determine quercetin as a critical active ingredient in Xihuang Pills. Subsequently, human hepatocellular carcinoma (HCC) cell lines, H22 and HepG2 cells, were treated with quercetin, and BALB/c mice were injected with H22 cells and treated with different concentrations of quercetin. Tumor volume and weight were determined in these mice with and without quercetin administration. Immune and pro-inflammatory factors were measured using Enzyme Linked Immunosorbent Assay (ELISA). Macrophage polarization was assessed by western blot and flow cytometry. Finally, PD-L1, autophagy-related proteins, and the NF-κB pathway were also analyzed. RESULTS: Quercetin could significantly inhibit the proliferation, migration, and invasion characteristics of HCC cells and promote apoptosis in a concentration-dependent manner in vitro. After quercetin treatment, tumor volume and weight significantly decreased in vivo. Granulocyte-macrophage and granulocyte colony-stimulating factor (GM-CSF and G-CSF, respectively) levels were blunted in response to quercetin, as well as the PD-L1 level. CD86+ cell ratio was increased, while the CD206+ cell ratio was decreased, suggesting that macrophages tend to undergo M1 polarization in response to quercetin. The expression of LC3 II/I was increased, while the expression of p62 was down-regulated. The pro-inflammatory factors TNF-α, IL-6, and IL-17A, as well as NF-κB signaling were suppressed in a quercetin concentration-dependent manner. CONCLUSIONS: Quercetin is a key ingredient of anti-HCC activity in Xihuang Pills by regulating macrophage polarization and promoting autophagy via the NF-κB pathway.

Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway.

Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. We used a mouse model of SCI, and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, pyroptosis, and AMPK-related signaling pathways were also examined. Our results showed that BA significantly improved functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS level and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induced mitophagy to eliminate the accumulation of ROS and inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Those results showed that BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS.

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

Acylated iridoid glucosides from Pseudocaryopteris paniculata (C.B.Clarke) P.D.Cantino.

Phytochemical investigation of the ethyl acetate fraction of Pseudocaryopteris paniculata C.B.Clarke P.D.Cantino resulted in the identification of 26 undescribed iridoid glucosides (paniculosides A-Z), along with 7 known iridoid glucosides. Their structures were elucidated via two-dimensional nuclear-magnetic-resonance (2D-NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and chemical-hydrolysis methods. All isolated substances were analyzed for their cytoprotective effects against t-BHP-induced toxicity in HepG2 cells. Among the tested compounds, paniculoside A, paniculoside I, paniculoside T, and paniculoside U exhibited moderate cytoprotective activities with IC50 values in the range of 11.72-34.22 µM against t-BHP-induced toxicity.

The mediating effect of perceived social support on the relationship between mindfulness and burnout in special education teachers.

This study aimed to explore the mediating effect of perceived social support on the relationship between mindfulness and burnout in Chinese special education teachers. Three hundred and seven teachers completed the Five-Facet Mindfulness Questionnaire, Multi-dimensional Scale of Perceived Social Support Scale, and Teacher Burnout Inventory. The results showed that burnout was negatively correlated with mindfulness and perceived social support, while perceived social support was positively correlated with mindfulness. Moreover, perceived social support partially mediated the effect of mindfulness on special education teachers' burnout. These results suggest that the use of mindfulness combined with perceived social support may be beneficial for preventing and mitigating burnout among special education teachers.

Perspectives on the recent developments with green tea polyphenols in drug discovery.

INTRODUCTION: Increasing evidence has expanded the role of green tea from a traditional beverage to a source of pharmacologically active molecules with diverse health benefits. However, conclusive clinical results are needed to better elucidate the cancer-preventive and therapeutic effects of green tea polyphenols (GTPs). Areas covered: The authors describe GTPs' chemical compositions and metabolic biotransformations, and their recent developments in drug discovery, focusing on their cancer chemopreventive and therapeutic effects. They then review the recent development of GTP-loaded nanoparticles and GTP prodrugs. Expert opinion: GTPs possess potent anticarcinogenic activities through interfering with the initiation, development and progression phases of cancer. There are several challenges (e.g. poor bioavailability) in developing GTPs as therapeutic agents. Use of nanoparticle-based delivery systems has provided unique advantages over purified GTPs. However, there is still a need to determine the actual magnitude and pharmacological mechanisms of GTPs encapsulated in nanoparticles, in order to address newly emerging safety issues associated with the potential 'local overdose' effect. The use of Pro- epigallocatechin gallate (Pro-EGCG) as a prodrug appears to offer improved in vitro stability as well as better in vivo bioavailability and efficacies in a number of animal studies, suggesting its potential as a therapeutic agent for further study and development.

Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND METHODS: The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues. RESULTS: The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (P<0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with scopolamine-treated group. CONCLUSIONS: EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.

Detection of Adulterated Vegetable Oils Containing Waste Cooking Oils Based on the Contents and Ratios of Cholesterol, ß-Sitosterol, and Campesterol by Gas Chromatography/Mass Spectrometry.

A simple and accurate authentication method for the detection of adulterated vegetable oils that contain waste cooking oil (WCO) was developed. This method is based on the determination of cholesterol, ß-sitosterol, and campesterol in vegetable oils and WCO by GC/MS without any derivatization. A total of 148 samples involving 12 types of vegetable oil and WCO were analyzed. According to the results, the contents and ratios of cholesterol, ß-sitosterol, and campesterol were found to be criteria for detecting vegetable oils adulterated with WCO. This method could accurately detect adulterated vegetable oils containing 5% refined WCO. The developed method has been successfully applied to multilaboratory analysis of 81 oil samples. Seventy-five samples were analyzed correctly, and only six adulterated samples could not be detected. This method could not yet be used for detection of vegetable oils adulterated with WCO that are used for frying non-animal foods. It provides a quick method for detecting adulterated edible vegetable oils containing WCO.

Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L.

BACKGROUND: The aerial parts of Peganum harmala L. (APP) is a well-known and effective herbal medicine in China, and has been commonly used for treating various ailments, including cough and asthma. OBJECTIVES: To evaluate the antitussive, expectorant, and bronchodilating effects of the quinazoline alkaloids (±)-vasicine (VAS), deoxyvasicine (DVAS) (both isolated from the alkaloid fraction of APP) and (±)-vasicinone (VAO) (synthesized from VAS). METHODS: The three quinazoline alkaloids were tested as antitussive on cough models in mice and guinea pigs. VAO was synthesized from VAS via the oxidation of hydrogen peroxide. VAS, VAO, and DVAS were orally administered at dosages of 5, 15, and 45 mg/kg. Cough in these models was induced by ammonia, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity of the alkaloids. Bronchodilating effects were evaluated by using a bronchoconstrictive induced by acetylcholine chloride and histamine in guinea pigs. RESULTS: In antitussive tests, VAS, VAO, and DVAS significantly inhibited coughing frequency and prolonged the cough latency period in animals. At the highest doses tested (45 mg/kg), they showed antitussive activities similar to codeine phosphate (30 mg/kg) in mice and guinea pigs. Expectorant evaluation showed that VAS, VAO, and DVAS could significantly increase phenol red secretion in mice by 0.54-, 0.79- and 0.97-fold, by 0.60-, 0.99-, and 1.06-fold, and by 0.46-, 0.73-, and 0.96-fold, respectively, at dosages of 5, 15, and 45 mg/kg compared with the control (0.5% CMC-Na, 20 ml/kg). Ammonium chloride at 1500 mg/kg increased phenol red secretion in mice by 0.97-fold compared with the control. Bronchodilation tests showed that VAS, VAO, and DVAS prolonged the pre-convulsive time for 28.59%, 57.21%, and 29.66%, respectively, at a dose of 45 mg/kg in guinea pigs, whereas aminophylline prolonged the pre-convulsive time by 46.98% compared with pretreatment. CONCLUSIONS: Quinazoline alkaloids VAS, VAO, and DVAS have significant antitussive, expectorant, and bronchodilating activities. VAS, VAO, and DVAS are the active ingredients in APP, which can be used to treat respiratory disease.