Antidepressive mechanisms of rhynchophylline in mice with chronic unpredictable stress-induced depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.

Allantoin ameliorates amyloid ß-peptide-induced memory impairment by regulating the PI3K/Akt/GSK-3ß signaling pathway in rats.

Alzheimer's disease (AD) is a brain disease that causes problems in memory, thinking, and behavior. Allantoin has been shown to have antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we aimed to investigate the effect and mechanism of action of allantoin on AD-related memory impairment. We investigated the effect of allantoin on an amyloid ß1-42 peptide (Aß1-42)-induced AD model in rats and evaluated its memory-enhancing effect using the Morris water maze test. Pathological changes in the hippocampus and cortex were examined by hematoxylin-eosin staining. The expression of the phosphorylated Tau protein and PI3K/Akt/GSK-3ß signaling pathway was analyzed by western blotting. The results of the water maze test showed that after treatment with allantoin, the rats could reduce their swimming time and travel distances to find the platform. Allantoin treatment also increased the time spent in the quadrant in which the platform was located. Histological assessment showed that Aß1-42 could cause morphological alterations in nerve cells in the hippocampal CA1 region, and that allantoin could repair the damage to these cells. Western blotting revealed that allantoin treatment increased the expression of p-PI3K, p-Akt, and p-GSK-3ß and decreased p-Tau in the hippocampus and cortex of rats. These effects were inhibited by LY294002. These findings showed that allantoin could improve cognitive impairment in Aß1-42-induced rats by activating the PI3K/Akt/GSK-3ß signaling pathway to reduce abnormal hyperphosphorylation of Tau. Thus, allantoin may be a potential therapeutic agent for neurodegenerative diseases.

Comparison of area under the curve in various models of diabetic rats receiving chronic medication.

Introduction: The oral glucose tolerance test (OGTT) is widely used as a diagnostic tool for impaired glucose tolerance (IGT) in clinical settings and animal experiments. The area under the curve (AUC) is then developed to quantify the total increase in blood glucose during the OGTT. Similarly, attenuation of the increased AUC indicates the improvement of IGT in animals. Variations in fasting plasma glucose between individuals stimulate the development of incremental area under the curve (iAUC). However, the iAUC determined from subtracting the baseline value of fasting plasma glucose (similar to ΔAUC) has been challenged as problematic without evidence. Material and methods: We developed four different diabetic animal models. In each model, rats were treated with metformin, dapagliflozin, and insulin respectively for 1 week. OGTTs were performed after 7 days of the drug treatment. The acute blood glucose changes induced by one-time treatment of drugs were also compared. Results: After a daily application of each drug at an effective dose for 7 days, results indicated potency in the following order: insulin > dapagliflozin > metformin. This was determined by calculation using the AUC in all diabetic models. However, the order changed when using the calculation with iAUC. Additionally, signals were changed before the OGTT in each model that received repeated treatment of each drug. Notably, drug potency was shown to be the same in OGTT calculated from iAUC and AUC in diabetic rats receiving acute treatment. Conclusions: iAUC seems unsuitable for application in cases where subjects are receiving chronic medication(s).

Anxiolytic effect of an extract of Salvia miltiorrhiza Bunge (Danshen) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has demonstrated in modern studies for its pharmacological activities in treatments of CNS disorders like insomnia, dysphoria. However, its application on anxiolytic effect from the ethanol extract of Salvia miltiorrhiza Bunge (SMEtOH) has not yet been reported. MATERIALS AND METHODS: This study investigated the anxiolytic effect of the SMEtOH using the elevated plus-maze test (EPM) and the hole-board test (HBT) with diazepam and buspirone as positive controls. Also, the spontaneous locomotor activity of mice had been investigated in the open field. Further, we have illustrated the anxiolytic mechanisms of SMEtOH with its influencing upon GABAergic and/or serotonergic nervous systems via a method that SMEtOH was co-administered with flumazenil, a benzodiazepine (BZD) antagonist, or a drug (WAY-100635), a selective 5HT1A receptor antagonist. RESULTS: In hole-board test, results presented that SMEtOH increased head-dip counts and duration time. On the other hand, a decrease in spontaneous locomotor activity was observed. In the EPM test, SMEtOH increased the percentage of open-arm entries and the percentage of time spent in open arms. However, when SMEtOH co-administered with flumazenil or WAY-100635, the anxiolytic effect of SMEtOH was significantly counteracted. CONCLUSION: From these results, we can conclude that the anxiolytic mechanism of SMEtOH is exerted through an activation of the BZD and 5HT1A receptors.

Reveals of New Candidate Active Components in Hemerocallis Radix and Its Anti-Depression Action of Mechanism Based on Network Pharmacology Approach.

The global depression population is showing a significant increase. Hemerocallis fulva L. is a common Traditional Chinese Medicine (TCM). Its flower buds are known to have ability to clear away heat and dampness, detoxify, and relieve depression. Ancient TCM literature shows that its roots have a beneficial effect in calming the spirit and even the temper in order to reduce the feeling of melancholy. Therefore, it is inferred that the root of Hemerocallis fulva L. can be used as a therapeutic medicine for depression. This study aims to uncover the pharmacological mechanism of the antidepressant effect of Hemerocallis Radix (HR) through network pharmacology method. During the analysis, 11 active components were obtained and screened using ADME-absorption, distribution, metabolism, and excretion- method. Furthermore, 267 HR targets and 740 depressive disorder (DD) targets were gathered from various databases. Then protein-protein interaction (PPI) network of HR and DD targets were constructed and cluster analysis was applied to further explore the connection between the targets. In addition, gene ontology (GO) enrichment and pathway analysis was applied to further verify that the biological process related to the target protein is associated with the occurrence of depression disorder. In conclusion, the most important bioactive components-anthraquinone, kaempferol, and vanillic acid-can alleviate depression symptoms by regulating MAOA, MAOB, and ESR1. The proposed network pharmacology strategy provides an integrating method to explore the therapeutic mechanism of multi-component drugs on a systematic level.

Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet-and Streptozotocin-Induced NAFLD and Diabetes through Improvement of ß-oxidation and Ketogenesis.

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of ß-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.

Hepatoprotective Mechanisms of Taxifolin on Carbon Tetrachloride-Induced Acute Liver Injury in Mice.

OBJECTIVE: To investigate the hepatoprotective mechanisms of taxifolin in mice with acute liver injury induced by CCl4. METHODS: ICR (Institute of Cancer research) mice were orally pretreated using taxifolin for 7 consecutive days and were then given single intraperitoneal (i.p.) injections of 0.2% CCl4 (10 mL/kg body weight, i.p.). Liver injury was then determined using assays of serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST). Further, to investigate the hepatoprotective mechanisms of taxifolin, we determined malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) activities. RESULTS: CCl4-induced liver injury led to significant increases in sALT and sAST activities, and these increases were limited by taxifolin and silymarin (Sily) pretreatments. Histological analyses also indicated that taxifolin and Sily decreased the range of liver lesions in CCl4-treated mice and vacuole formation, neutrophil infiltration, and necrosis were visibly reduced. In addition, SOD, GPx, and GRd activities were increased and MDA levels were decreased after taxifolin and Sily treatments. CONCLUSION: The hepatoprotective mechanisms of taxifolin and Sily are related to decreases in MDA levels presumably due to increased antioxidant enzyme activities. These outcomes suggest that taxifolin mitigates acute liver injury resulted from CCl4 in mice, demonstrating the hepatoprotective effects of taxifolin.

Comparing the Protection Imparted by Different Fraction Extracts of Garlic (Allium sativum L.) against Der p-Induced Allergic Airway Inflammation in Mice.

Garlic (Allium sativum L.) has been used extensively as a food ingredient and medicinally, but the effect on asthmatic airway inflammation has not been studied in detail. We accordingly explored the protective effects exerted by various garlic fraction extracts against airway inflammation with Dermatophagoides pteronyssinus (Der p)-induced allergic asthma in vivo and in vitro. Garlic extraction was realized using n-hexane, dichloromethane, ethylacetate, n-butanol, and water in sequence to obtain different fraction extracts. Mice were orally administered different fractions (80 mg/kg) daily for four weeks. The histological results showed that the water fraction could ameliorate lung-based goblet cell hyperplasia, inflammatory cell infiltration, and mucus hypersecretion. The water fraction extracts decreased IgE and IgG1, and they decreased inflammatory cells as quantified in bronchoalveolar lavage fluid (BALF); however, they increased IgG2a in serum. Moreover, the water fraction extracts increased IFN-γ and IL-12 (both constituting Th1 cytokines) in BALF, but they reduced IL-13, -4, and -5 (all constituting Th2 cytokines), and also inhibited the expression of IL-1ß, IL-6, and TNF-α. The water fraction also inhibited the PI3K/Akt/NF-κB signal pathways in A549 cells. These findings suggest that water fraction extracts of garlic have a clear anti-inflammatory effect on Der p-induced allergic asthma.

The Protective Role of Garlic on Allergen-Induced Airway Inflammation in Mice.

Asthma is the most prevalent chronic respiratory disease worldwide. Garlic extracts have long been used as a food source and in traditional medicine. Crude extracts of garlic are used as an anti-inflammatory agent and have been reported to exhibit antiasthmatic properties. However, molecular mechanisms of garlic extracts in the context of antiasthmatic airway inflammation are still unclear. In this study, the antiasthmatic effect of garlic extracts on Th1, Th2, and Th3 cytokine profiles and immunoregulatory mechanism were explored using an animal model of allergic asthma. Garlic extracts significantly reduced total inflammatory cell counts and eosinophil infiltration and decreased the production of Dermatophagoides pteronyssinus IgE in serum and Th1/Th2/Th3 cytokine in bronchoalveolar fluid. Enzyme-linked immunosorbent assay analysis demonstrated that garlic extracts downregulated the levels of cytokines and chemokines, namely Th2-related IL-4, IL-5, and IL-13; but they simultaneously upregulated Th1-related IFN-γ, IL-12, and Th3-related IL-10 and TGF-ß expression in BALF. The mechanism may be ascribed to the modulation of Th1-, Th2-, and Th3-related cytokine imbalance.

Effects of processing adjuvants on traditional Chinese herbs.

Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs). Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs.

Hepatoprotective effect of the ethanol extract of Polygonum orientale on carbon tetrachloride-induced acute liver injury in mice.

Polygonum orientale L. (Polygonaceae) fruits have various medicinal uses, but their hepatoprotective effects have not yet been studied. This study investigated the hepatoprotective activity of the ethanolic extract of P. orientale (POE) fruits against carbon tetrachloride (CCl4)-induced acute liver injury (ALI). Mice were pretreated with POE (0.1, 0.5, and 1.0 g/kg) or silymarin (0.2 g/kg) for 5 consecutive days and administered a dose of 0.175% CCl4 (ip) on the 5th day to induce ALI. Blood and liver samples were collected to measure antioxidative activity and cytokines. The bioactive components of POE were identified through high-performance liquid chromatography (HPLC). Acute toxicity testing indicated that the LD50 of POE exceeded 10 g/kg in mice. Mice pretreated with POE (0.5, 1.0 g/kg) experienced a significant reduction in their serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels and reduction in the extent of liver lesions. POE reduced the malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels, and increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in liver. HPLC revealed peaks at 11.28, 19.55, and 39.40 min for protocatechuic acid, taxifolin, and quercetin, respectively. In summary, the hepatoprotective effect of POE against CCl4-induced ALI was seemingly associated with its antioxidant and anti-proinflammatory activities.

Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice.

Major depression is a common mental disorder that has been established to be associated with a decrease in serotonin and/or serotonin transporters in the brain. Peroxisome proliferator-activated receptor δ (PPARδ) has been introduced as a potential target for depression treatment. Telmisartan was recently shown to activate PPARδ expression; therefore, the effectiveness of telmisartan in treating depression was investigated. In unpredictable chronic mild stress (UCMS) model, treatment with telmisartan for five weeks notably decrease in the time spent in the central and the reduced frequency of grooming and rearing in open filed test (OFT) and the decreased sucrose consumption in sucrose preference test (SPT) compared with the paradigms. Telmisartan also reversed the decrease in PPARδ and 5-HTT levels in the hippocampus of depression-like mice. Administration of PPARδ antagonist GSK0660 and direct infusion of sh-PPARδ into the brain blocked the effects of telmisartan on the improvement of depression-like behavior in these mice. Moreover, telmisartan enhanced the expression of PPARδ and 5HTT in H19-7 cells. In conclusion, the obtained results suggest that telmisartan improves symptoms of stress-induced depression in animals under chronic stress through activation of PPARδ. Therefore, telmisartan may be developed as a potential anti-depressant in the future.

Association of Activation of Induced COX-2, iNOS and Cytokines with NF-kappa B Depression by Taiwan Wild Grape Ethanolic Extract in Mice.

Taiwan wild grape (Vitis thunbergii var. taiwaniana; VTT) is an important traditional herbal medicine used to treat muscle injuries and acute and chronic pain of the ligaments. Information on its bioactivity and the underlying mechanisms, which have not been elucidated thus far, is needed to demonstrate its value for pharmacological and clinical use. This study presents evidence to clarify the antinociceptive and anti-inflammatory activities of an ethanolic extract of VTT stem (VTTEtOH) and the possible molecular mechanisms involved in such biactivities. In the mice, VTTEtOH significantly reduced the acetic acid-induced writhing response (P < 0.01), formalin-induced licking time (P < 0.01), and edema paw volume at 4 and 5 h after λ-carrageenan injection. VTTEtOH obviously decreased the levels of tumor necrosis factor alpha (P < 0.01), interleukin (IL)-1ß (P < 0.05), interleukin (IL)-6 (P < 0.001), nuclear factor-kappa B (P < 0.001), iNOS (P < 0.001), cyclooxygenase-2 (P < 0.001) and Nitric oxide (P < 0.001) in edema-paw tissue. The molecular mechanisms underlying these effects might involve significant inhibition of the activity of cyclooxygenase-2 through suppression of nuclear factor-kappa B and inducible nitric oxide synthase expression and reduction of the levels of various inflammatory mediators, including tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6, and nitric oxide. Our findings provided pharmacological and histopathological evidences that VTTEtOH alleviates inflammatory pain-related diseases.

Heme oxygenase-1 mediates anti-adipogenesis effect of raspberry ketone in 3T3-L1 cells.

BACKGROUND: Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Raspberry ketone (RK), a major aromatic compound in red raspberry, was recently reported to possess anti-obesity effects. However, its mechanisms are unclear. AIM: Adipogenesis plays a critical role in obesity and, therefore, this study aimed to investigate the effect and mechanisms of action of RK on adipogenesis in 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3T3-L1 preadipocytes were differentiated in medium containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Adipocyte lipid contents were determined using oil-red O staining while adipogenic transcription factor and lipogenic protein expressions were determined using western blotting. RESULTS: RK (300-400µM) strongly inhibited lipid accumulation during 3T3-L1 preadipocyte differentiation into adipocytes. RK reduced the CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferation-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4) expressions and increased heme oxygenase-1 (HO-1), Wnt10b, and ß-catenin expressions in 3T3-L1 adipocytes. Additionally, RK inhibited lipid accumulation, and adipogenic transcription factor and lipogenic protein expressions were all decreased by inhibiting HO-1 or ß-catenin using tin protoporphyrin (SnPP) or ß-catenin short-interfering RNA (siRNA), respectively. Furthermore, Wnt10b and ß-catenin expressions were negatively regulation by SnPP. CONCLUSION: RK may exert anti-adipogenic effects through modulation of the HO-1/Wnt/beta-catenin signaling pathway.

Changes in PPARδ expression in a rat model of stress-induced depression.

Depression is a common mental disorder that has been linked to a decrease in the expression of serotonin and/or the serotonin transporter in the brain. Antidepressants that target the monoaminergic system are widely used in the clinical setting. Peroxisome proliferator-activated receptor δ (PPAR δ) overexpression or activation is thought to improve depression-like behaviours in rodents. The present study was designed to characterize the changes in PPARδ expression in the hippocampus in rats with stress-induced depression. We used an unpredictable chronic mild stress (CMS) model in rats to study the role of PPARδ in the hippocampus. Behaviour was evaluated via a forced swim test (FST), a tail suspension test (TST), and a sucrose preference test (SPT). Then, the changes in PPARδ expression and other signals were determined using Western blots. We found that PPARδ expression in the hippocampus was markedly reduced in rats with depression. Moreover, the expression of the serotonin transporter was also significantly decreased. Treatment with a PPARδ agonist enhanced the expression of PPARδ and the serotonin transporter in the hippocampus of rats with stress-induced depression. Additionally, treatment with a PPARδ agonist increased the expression of the serotonin transporter in cultured hippocampal (H19-7) cells, and this action was ablated in the absence of PPARδ, which was attenuated with shRNA. Taken together, we found that PPARδ plays an important role in the regulation of serotonin transporter expression and that chronic stress may lower PPARδ expression in the brain via apoptosis and may attenuate serotonin transporter expression, thus inducing depression in rats.

Hepatoprotective effect of Coreopsis tinctoria flowers against carbon tetrachloride-induced liver damage in mice.

BACKGROUND: Coreopsis tinctoria is a traditional remedy for the management of various diseases including hepatitis. The hepatoprotective role of the plant is not scientifically explored till now. This study was designed to investigate the hepatoprotective potentials of the ethanol extract from C. tinctoria (CTEtOH) using an animal model of carbon tetrachloride (CCl4)-induced acute liver injury. METHODS: CTEtOH (0.5 and 1.0 g/kg) and silymarin (200 mg/kg) were administered to the experimental mice for 7 days followed by 0.2% CCl4 (10 mL/kg of body weight (bw), ip), then all mice were sacrificed after 24 h. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Histological analysis of liver was performed. The tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), nitric oxide (NO), malondialdehyde (MDA), and antioxidant enzymatic activities were also measured.. RESULTS: The results revealed that the serum ALT and AST levels significantly decreased after treatment with CTEtOH. Moreover, histological analyses indicated that CTEtOH (0.5 and 1.0 g/kg) and silymarin reduced the extent of CCl4-induced liver lesions. CTEtOH (0.5 and 1.0 g/kg) reduced the levels of malondialdehyde, nitric oxide, and proinflammatory cytokines (TNF-α and IL-1ß). Furthermore, CTEtOH (1.0 g/kg) reduced the level of IL-6. The activities of antioxidant enzymes, namely superoxide dismutase and glutathione reductase, significantly increased after treatment with CTEtOH (0.5 and 1.0 g/kg) and that of glutathione peroxidase increased after treatment with 1.0 g/kg of CTEtOH. CONCLUSIONS: These results demonstrate the hepatoprotective effect of CTEtOH against CCl4-induced acute liver injury in mice, and the underlying hepatoprotective mechanisms are associated with antioxidant and antiproinflammatory activities.

Improving the Concentrations of the Active Components in the Herbal Tea Ingredient, Uraria crinita: The Effect of Post-harvest Oven-drying Processing.

Uraria crinita is widely used as a popular folk drink; however, little is known about how the post-harvest operations affect the chemical composition and bioactivity of UC. We assessed three drying methods (Oven-drying, Air-drying, Sun-drying), as well as the Oven-drying temperature using metabolomics approaches and bioactivity assays. The samples processed at 40 degree show a greater effect on the levels of estrogen receptor-alpha activity and nuclear factor erythroid 2-related factor 2 activity, anti-oxidative activity, and cyclooxygenase-2 inhibition compared with the other samples. A multivariate analysis showed a clear separation between the 40 degree Oven-dried samples and the other samples, which is consistent with the results of bioactivity assay. These results are ascribed to at least two-fold increase in the concentrations of flavonoids, spatholosineside A and triterpenoids in the oven-dried samples compared with the other groups. The proposed Oven-drying method at 40 degree results in an improved quality of UC.

Hepatoprotective Effect of Cuscuta campestris Yunck. Whole Plant on Carbon Tetrachloride Induced Chronic Liver Injury in Mice.

Cuscuta seeds and whole plant have been used to nourish the liver and kidney. This study was aimed to investigate the hepatoprotective activity of the ethanol extract of Cuscuta campestris Yunck. whole plant (CCEtOH). The hepatoprotective effect of CCEtOH (20, 100 and 500 mg/kg) was evaluated on carbon tetrachloride (CCl4)-induced chronic liver injury. Serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol were measured and the fibrosis was histologically examined. CCEtOH exhibited a significant inhibition of the increase of serum alanine aminotransferase, aspartate aminotransferase, triglyceride and cholesterol. Histological analyses showed that fibrosis of liver induced by CCl4 were significantly reduced by CCEtOH. In addition, 20, 100 and 500 mg/kg of the extract decreased the level of malondialdehyde (MDA) and enhanced the activities of anti-oxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. We demonstrate that the hepatoprotective mechanisms of CCEtOH were likely to be associated to the decrease in MDA level by increasing the activities of antioxidant enzymes such as SOD, GPx and GRd. In addition, our findings provide evidence that C. campestris Yunck. whole plant possesses a hepatoprotective activity to ameliorate chronic liver injury.

Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid ß-oxidation.

Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid ß-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX.

The use of Chinese herbal medicines associated with reduced mortality in chronic hepatitis B patients receiving lamivudine treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamivudine associated mutation and resistance reduces the effect of anti-hepatitis B virus. Pharmacological studies in cell and animal model suggest that Chinese herbal medicines (CHMs) have anti-hepatitis B virus effect. Observational studies offer mixed results. The aim of this study was to evaluate the relation between the use of CHMs and outcome in patients with chronic hepatitis B receiving lamivudine treatment and further estimate the association of Jia-Wei-Xiao-Yao-Sang (JWXYS) use with mortality of those patients. MATERIALS AND METHODS: We conducted a cohort study among patients age 20-90 years within a National Health Insurance Healthcare system. Information on the use of CHMs and covariates were obtained from Taiwan National Health Insurance Research Database. We used Cox proportional hazards models to estimate the hazard ratio and 95% confidence intervals (95% CI) for all-cause mortality among CHMs users compared to nonusers. RESULTS: Among 1037 patients studied from 2004 to 2011, median follow-up time 5.3 years and 88 deaths were identified. During the study period, 49% of patients used CHMs and the median duration of use was 2.4 years. We found that significant difference on all-cause mortality among CHMs users (aHR=0.45, 95% CI: 0.27-0.76) compared to CHMs nonusers. All-cause mortality also differed by JWXYS use (aHR=0.26, 95% CI: 0.08-0.83). CONCLUSIONS: This study reveals that the use of CHMs may lower the risk of death in patients with chronic hepatitis B receiving lamivudine treatment. Further randomized-controlled trials are required to validate these findings.