Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Protective effects of Huang-Qi-Ge-Gen decoction against diabetic liver injury through regulating PI3K/AKT/Nrf2 pathway and metabolic profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. AIM OF THE STUDY: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. MATERIALS AND METHODS: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg-1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg-1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. RESULTS: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. CONCLUSIONS: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.

[Transurethral plasma resection of the prostate for acute urinary retention in patients with advanced prostate cancer].

OBJECTIVE: To compare the safety of transurethral plasma resection of the prostate (TuPkRP) in the treatment of advanced PCa (APC)-related acute urinary retention (AUR) with that in the treatment of BPH-related AUR and investigate the oncologic characteristics of the PCa patient after TuPkRP. METHODS: In this retrospective study, we first compared the baseline data between the patients with APC-related AUR (group A, n = 32) and those with BPH-related AUR (group B, n = 45) as well as their surgical parameters, such as the operation time, pre- and post-operative hemoglobin levels, IPSS at 3 months after TuPkRP and length of postoperative hospital stay. Then, we observed possible TuPkRP-induced tumor progression by comparing the oncologic parameters, such as the PSA level and ECT-manifested bone metastasis, between the APC-AUR patients treated by androgen-deprivation therapy (ADT) + TuPkRP and those treated by ADT only (group C, n = 24). RESULTS: There were no statistically significant differences in the baseline data between the APC-AUR and BPH-AUR patients (P > 0.05). The operation time and postoperative hospital stay were significantly longer in the APC-AUR than in the BPH-AUR group (P < 0.05), but the decreases in the hemoglobin level and IPSS at 3 months after operation showed no significant differences between the two groups of patients (P > 0.05). Besides, no statistically significant differences were observed in the oncologic parameters between the APC-AUR patients treated by ADT + TuPkRP and those by ADT only (P > 0.05). CONCLUSION: The safety of TuPkRP was not significantly lower and the rates of postoperative complications and adverse events were not significantly higher in the patients with APC-related AUR than in those with BPH-related AUR. And this surgical strategy did not significantly improve the progression of APC.

Combination of UHPLC-Q Exactive-Orbitrap MS, Bioinformatics and Molecular Docking to Reveal the Mechanism of Huan-Lian-Jie-Du Decoction in the Treatment of Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients' quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC-Q Exactive-Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb-Compound-Target network was constructed and enrichment analysis was used. In addition, a protein-protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb-Compound-Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.

[Medication rules of traditional Chinese medicine compounds for pain].

The present study collected data on traditional Chinese medicine(TCM) compounds effective in relieving pain from the patent database of the State Intellectual Property Office(SIPO), sorted out the TCM compounds against pain in patents, and analyzed the medication rules to provide references for the research and development of new TCM drugs against pain. The data were subjected to frequency statistics, association rules, cluster analysis, and complex network analysis by IBM SPSS Modeler 18.3 and SPSS Statistical 26.0. The results showed that among the 101 oral prescriptions included in the statistics, the top 5 drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma, and among the 49 external prescriptions included in the statistics, the top 5 drugs were Myrrha, Olibanum, Angelicae Dahuricae Radix, Borneolum Syntheticum, and Chuanxiong Rhizoma. Whether oral or external prescriptions, the drugs were mainly warm in nature, and bitter, pungent, and sweet in flavor. According to TCM complex network analysis, the core drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, and Chuanxiong Rhizoma in oral prescriptions, and Olibanum, Myrrha, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Angelicae Sinensis Radix in external prescriptions. Overall, the therapeutic principles of oral prescriptions were mainly replenishing Qi, nourishing blood, and promoting Qi and blood circulation, while those of external prescriptions were activating blood, resolving stasis, promoting Qi flow, and relieving pain on the basis of the oral prescriptions. In the future research and development of TCM compounds against pain, the prescriptions should be modified with mind-tranquilizing and depression-relieving drugs. With the modernization of TCM, the development of new pain-relieving TCM compound patents based on ancient methods and clinical experience adhering to the guidance of TCM treatment based on syndrome differentiation can meet the new demand for pain treatment in the current society and give full play to the advantages of TCM in pain treatment.

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of ß-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

The relationship between mindfulness and mental health among Chinese college students during the closed-loop management of the COVID-19 pandemic: A moderated mediation model.

To prevent the spread of the COVID-19 epidemic on campus, universities in outbreak areas in China can implement closed-loop management. OBJECTS: This study aimed to explore the relationship between mindfulness and mental health of college students under closed-loop management. MEASURES: 11,939 college students from a university in Changsha, China participated in the online survey during the closed-loop management period. The Chinese version of Perceived Stress Scale, the Emotion Regulation Questionnaire-Cognitive Reappraisal, the Mindful Attention Awareness Scale, the 7-item General Anxiety Disorder questionnaire, and the 9-item Patient Health Questionnaire were administered to the college students. RESULTS: We found that mindfulness was negative association with mental health during the closed-loop management period. Perceived stress mediated the relationship between mindfulness and mental health. Cognitive reappraisal moderated the relationship between mindfulness and perceived stress. Specifically, when the level of mindfulness is the same, individuals with more cognitive reappraisal tend to experience a less perceived stress. CONCLUSION: The results of this study are of great significance to improve the mental health of college students during closed-loop management period.

Medication rules of traditional Chinese medicine compounds for pain / 中国中药杂志

The present study collected data on traditional Chinese medicine(TCM) compounds effective in relieving pain from the patent database of the State Intellectual Property Office(SIPO), sorted out the TCM compounds against pain in patents, and analyzed the medication rules to provide references for the research and development of new TCM drugs against pain. The data were subjected to frequency statistics, association rules, cluster analysis, and complex network analysis by IBM SPSS Modeler 18.3 and SPSS Statistical 26.0. The results showed that among the 101 oral prescriptions included in the statistics, the top 5 drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma, and among the 49 external prescriptions included in the statistics, the top 5 drugs were Myrrha, Olibanum, Angelicae Dahuricae Radix, Borneolum Syntheticum, and Chuanxiong Rhizoma. Whether oral or external prescriptions, the drugs were mainly warm in nature, and bitter, pungent, and sweet in flavor. According to TCM complex network analysis, the core drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, and Chuanxiong Rhizoma in oral prescriptions, and Olibanum, Myrrha, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Angelicae Sinensis Radix in external prescriptions. Overall, the therapeutic principles of oral prescriptions were mainly replenishing Qi, nourishing blood, and promoting Qi and blood circulation, while those of external prescriptions were activating blood, resolving stasis, promoting Qi flow, and relieving pain on the basis of the oral prescriptions. In the future research and development of TCM compounds against pain, the prescriptions should be modified with mind-tranquilizing and depression-relieving drugs. With the modernization of TCM, the development of new pain-relieving TCM compound patents based on ancient methods and clinical experience adhering to the guidance of TCM treatment based on syndrome differentiation can meet the new demand for pain treatment in the current society and give full play to the advantages of TCM in pain treatment.

Traditional Chinese medicine for prevention and treatment of hepatocellular carcinoma: A focus on epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Epithelial-mesenchymal transition (EMT), which endows epithelial cells with mesenchymal properties, plays an important role in the early stages of metastasis. Conventional cancer therapies have promising effects, but issues remain, such as high rates of metastasis and drug resistance. Thus, exploring and evaluating new therapies is an urgent need. Traditional Chinese medicines (TCMs) have been acknowledged for their multi-target and coordinated intervention effects against HCC. Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC. However, studies on the effects of TCM on EMT in HCC are scarce. In this review, we summarized recent developments in anti-EMT TCMs and formulae, focusing on their underlying pharmacological mechanisms, to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC.

Effects of soy isoflavone supplementation on patients with diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials.

Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.

Sustained release of arsenic trioxide benefits interventional therapy on rabbit VX2 liver tumor.

The benefit of chemotherapy as a constituent of transcatheter arterial chemoembolization (TACE) is still in debate. Recently we have developed arsenic trioxide nanoparticle prodrug (ATONP) as a new anticancer drug, but its systemic toxicity is a big issue. In this preclinical TACE study, ATONP emulsified in lipiodol behaved as drug-eluting bead manner. Sustained release of arsenic from ATONP within occluded tumor caused very low arsenic level in plasma, avoiding the "rushing out" effect as ATO did. Correspondingly, intratumoral arsenic accumulation and inorganic phosphate deprivation were simultaneously observed, and arsenic concentration was much higher as ATONP was transarterially administered than ATO, or intravenously injected. Tumor necrosis and apoptosis were remarkably more severe in ATONP group than ATO, but no significant hepatic and renal toxicity was perceived. In brief, ATONP alleviated arsenic toxicity and boosted the therapeutic effect of TACE via Pi-activated drug sustainable release.

Interaction between Traditional Chinese Medicine and Anticoagulant/Antiplatelet Drugs.

BACKGROUND: Traditional Chinese medicine (TCM) has been used for medical purposes since the ancient time and has gradually gained recognition worldwide. Nowadays, patients with thrombus presiding to anticoagulant/ antiplatelet drugs prefer taking TCM. However, an increasing number of studies on herb-drug interactions have been shown. Nevertheless, findings are frequently conflicting and vague. In this review, we discuss the herb-drug interactions between TCM and anticoagulant/antiplatelet drugs to provide guidance on concomitant ingestion with anticoagulant/antiplatelet drugs. METHODS: We undertook a structured search of medicine and drug databases for peer-reviewed literature using focused review questions. RESULTS: Danshen, Ginkgo, Ginger, H. Perforatum, SMY and Puerarin injection had directional regulation effects on the efficacy of anticoagulant drugs by altering the CYPs, pharmacokinetic indexs and hemorheological parameters. H. Perforatum inhibited the efficacy of Clopidogrel by enhancing the CYP3A4 activity and Ginkgo increased the efficacy of Ticlopidine. Additionally, Renshen, the formulae except SMY and injections except Puerarin injection could increase or decrease the efficacy of anticoagulant/antiplatelet drugs via regulating the CYPs, platelet aggregation, hemorheological parameters and others. CONCLUSION: Some cases have reported that TCMs may increase the bleeding risk or has no effect on coagulation when anticoagulant/antiplatelet drugs are concurrently used. However, pharmacokinetic studies have presented either consistent or slightly varying results. So it is difficult to ascertain whether the concurrent use of TCM may increase or reduce the pharmacologic effects of anticoagulant/antiplatelet drugs with adverse reactions. Therefore, herb-drug interactions of TCM and anticoagulant/antiplatelet drugs should be further explored and defined.

[Study on commodity specification and grade standard and quality evaluation of Galla Chinensis].

This paper is aimed to study the commodity specification and grade standard of Galla Chinensis,for standardizing market order and guide the market circulation,and provide a basis for standardization of Galla Chinensis. With 33 samples of Galla Chinensis from market as the object of the research,the herbal textual research and market research were carried out. Then the grading indicator were selected by the descriptive statistics,principal component analysis and cluster analysis,combining with production practice,the commodity specification and grade standard of Galla Chinensis were set out. The data of moisture,ash,gallic acid as the internal index were used to analyze the relationship between the quality difference between grades and the appearance characters and the intrinsic composition. Herbal textual research and market research found that the high quality of Galla Chinensis characterized with large,complete,wall thick,grayish brown characteristics,and Galla Chinensis could be divided into gallnuts and horned gall. Through principal component analysis and cluster analysis,combining actual production and herbal record,screening,the length,diameter,single weight,the number of 500 g were determined as 4 grading indicators,the commodity specification was divided into two: gallnuts and horned gall,the grades was divided into two: selected goods and mixed goods. The result of correlation analysis showed there was no significant correlation between the internal index and the appearance characters of Galla Chinensis. The result of multiple comparison showed that the ash content of the selected goods was smaller than that of the mixed goods,but it did not reach significant. The content of gallic acid of the selected goods and the mixed goods of gallnuts were higher than selected goods of horned gall,and higher than mixed goods of horned galls. Using the length,diameter,single weight,the number of 500 g as the appearance characters index. Combining with the herbal textual research and market research,we have divided two specifications and two grades for the commodity specification and grade standard of Galla Chinensis,which can provide a basis for industry standards and national standards.

Hydrogen peroxide alleviates P starvation in rice by facilitating P remobilization from the root cell wall.

Phosphorus (P) deficiency limits rice production. Increasing the remobilization of P stored in the root cell wall is an efficient way to alleviate P starvation in rice. In the current study, we found that the addition of 50 µM H2O2 significantly increased soluble P content in rice. H2O2 stimulated pectin biosynthesis and increased pectin methylesterase (PME) activity, thus stimulating the release of P from the cell wall in roots. H2O2 also regulates internal P homeostasis by increasing the expression of P transporter genes OsPT2, OsPT6, and OsPT8 at different treatment times. In addition, the H2O2 treatment increased the expression of nitrate reductase (NR) genes OsNIA1 and OsNIA2 and the activity of NR, then increased the accumulation of nitric oxide (NO) in the rice root. The application of the NO donor sodium nitroprusside (SNP) and the H2O2 scavenger 4-hydroxy-TEMPO significantly increased soluble P content by increasing pectin levels and PME activity to enhance the remobilization of P from the cell wall. However, the addition of NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) with and without H2O2 had the opposite effect, suggesting that NO functions downstream of H2O2 to increase the remobilization of cell wall P in rice.

Extraction and Separation of Eight Ginsenosides from Flower Buds of Panax Ginseng Using Aqueous Ionic Liquid-Based Ultrasonic-Assisted Extraction Coupled with an Aqueous Biphasic System.

Ionic liquids (ILs) are recognized as a possible replacement of traditional organic solvents, and ILs have been widely applied to extract various compounds. The present work aims to extract ginsenosides from Panax ginseng flower buds using aqueous ionic liquid based ultrasonic assisted extraction (IL-UAE). The extraction yields of 1-alkyl-3-methylimidazolium ionic liquids with different anions and alkyl chains were evaluated. The extraction parameters of eight ginsenosides were optimized by utilizing response surface methodology (RSM). The model demonstrated that a high yield of total ginsenosides could be obtained using IL-UAE, and the optimum extraction parameters were 0.23 M [C4mim][BF4], ultrasonic time of 23 min, temperature of extraction set to 30 °C, and liquid-solid ratio of 31:1. After that, an aqueous biphasic system (ABS) was used to separate ginsenosides further. The nature and concentration of salt, as well as the value of pH in ionic liquid were evaluated, and the optimal conditions (6.0 mL IL extract, 3 g NaH2PO4, and pH 5.0) were obtained. The preconcentration factor was 2.58, and extraction efficiency reached 64.53%. The results indicate that as a simple and efficient method, an IL-UAE-ABS can be considered as a promising method for extracting and separating the natural active compounds from medicinal herbs.

Ammonium mitigates Cd toxicity in rice (Oryza sativa) via putrescine-dependent alterations of cell wall composition.

In plants, different forms of nitrogen (NO3- or NH4+) affect nutrient uptake and environmental stress responses. In the present study, we tested whether NO3- and NH4+ affect the ability of rice (Oryza sativa) to tolerate the toxic heavy metal cadmium (Cd). Compared with NO3-, NH4+ treatment significantly increased chlorophyll contents and reduced Cd2+ levels in rice cultivars Nipponbare (japonica) and Kasalath (indica) grown in 0.2 mM Cd2+. NH4+ significantly reduced the pectin and hemicellulose contents and inhibited the pectin methylesterase (PME) activity in rice roots, thereby reducing the negative charges in the cell wall and decreasing the accumulation of Cd2+ in roots. In addition, NH4+ reduced the absorption and root-to-shoot translocation of Cd2+ by decreasing the expression of OsHMA2 and OsNramp5 in the root. Levels of the signaling molecule putrescine were significantly higher in the roots of both rice cultivars provided with NH4+ compared with NO3-. The addition of putrescine reduced Cd2+ contents in both rice cultivars and increased the chlorophyll content in shoots by reducing root cell wall pectin and hemicellulose contents, inhibiting PME activity and suppressing the expression of OsHMA2 and OsNramp5 in the root. Taken together, these results indicate that NH4+ treatment alleviated Cd toxicity, enabling rice to withstand the noxious effects of Cd by modifying the cell wall Cd-binding capacity due to alterations of pectin and hemicellulose contents and Cd transport, processes induced by increasing putrescine levels. Our findings suggest methods to decrease Cd accumulation in rice by applying NH4+ fertilizers.

Anti-Inflammatory Effects of p-Coumaric Acid, a Natural Compound of Oldenlandia diffusa, on Arthritis Model Rats.

OBJECTIVES: In China, Oldenlandia diffusa (OD) is a natural herb that is widely used and has been proven to be effective in the treatment of rheumatoid arthritis (RA). This study aimed to preliminarily reveal the mechanism by which OD exerts its beneficial effect. METHODS: Ultra-performance liquid chromatography photodiode array was applied to identify the absorbable compounds in the plasma of collagen-induced arthritis (CIA) model rats. After 2 weeks, an OD decoction or the identified absorbable compound was administered to CIA rats. Morphology, X-ray images of the joints, pathological images, arthritis index, and cytokine (TNF-α and IL-6) levels were evaluated. RESULTS: p-Coumaric acid (p-CA) was identified as the absorbed compound in plasma. After administration of p-CA solution or the OD decoction, symptoms in the treated rats were alleviated as compared to the untreated model rats, and inflammatory cell infiltration was suppressed. The arthritis index and serum levels of TNF-α and IL-6 were decreased as compared to the control group. CONCLUSIONS: OD may exert its anti-inflammatory effect on RA via its active ingredient, p-CA. This information sheds light on the mechanism by which OD exerts its anti-inflammatory effort in RA and forms the basis for further development of therapeutic agents for RA.

Mineral and metabolic profiles in tea leaves and flowers during flower development.

Tea [Camellia sinensis (L.) O. Kuntze] is one of the most popular non-alcoholic beverage crops in the world, and the physiological processes and gene regulations involved in development in tea plants have been well characterized. However, relatively little is known about the metabolic changes combined with mineral distributions that occur during flower development. Here we detected the contents of 11 elements in tea leaves and flowers and found that, some of them, especially phosphorus, sulfur and copper, showed significant changes during tea flowering. We also detected 122 metabolites in tea leaves and flowers and found that, 72 of them showed significant differences between flowers and leaves, of which sugars, organic acids, and flavonoids dominated. The sugars, such as trehalose and galactose, all accumulated in tea flowers, and the organic acids, such as malic acid, citric acid and fumaric acid involved in TCA cycle. The flavonoids, like epicatechin, catechin gallate and epigallocatechin, were more abundant in leaves. Furthermore, we found that the contents of 33 metabolites changed during the development of flowers. Especially, citric acid, phenylalanine and most flavonoids decreased while fructose and galactose increased during flowering stages in flowers. We also analyzed the correlations between the ions and metabolites and found that, some mineral nutrients including phosphorus, sulfur, manganese and zinc had close relations to organic acids, flavonoids, sugars and several amino acids during flowering. We mapped the metabolic pathway according to the KEGG database. This work will serve as the foundation for a systems biology approach to the understanding of mineral metabolism.

Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats.

BACKGROUND: Asymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied. METHODS: Dyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern. RESULTS: At baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups. CONCLUSION: In rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.

Antibacterial activity and kinetics of Litsea cubeba oil on Escherichia coli.

Litsea cubeba oil is extracted from the fresh fruits of Litsea cubeba by distillation. In this study, its chemical constituents, antibacterial activity, kinetics and effects against Escherichia coli were studied. Its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were both 0.125% (v/v) by toxic food method. Moreover, the antibacterial kinetic curves indicated 0.0625% (v/v) of litsea cubeba oil was able to prolong the growth lag phase of E. coli cells to approximate 12 hours while 0.125% (v/v) of litsea cubeba oil was able to kill the cells completely. Furthermore, transmission electron microscope (TEM) observation showed most E. coli cells treated with 0.125% (v/v) of litsea cubeba oil were killed or destroyed severely within 2 hours. The litsea cubeba oil might penetrate and destroy the outer and inner membrane of E. coli cells. Thus many holes and gaps were observed on the damaged cells, which led to their death eventually. The antibacterial effects of litsea cubeba oil mainly attributed to the presence of aldehydes, which accounted for approximately 70% in its whole components analyzed by GC/MS. Based on the antimicrobial properties, litsea cubeba oil would have a broad application in the antimicrobial industry.