Halmurat Upur

In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice

AIM OF THE STUDY This study aimed to evaluate in vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. (AEAA), which has been used for the treatment of liver disorders in Traditional Uighur Medicine. MATERIALS AND METHODS Qualitative and quantitative phytochemical analysis of the AEAA was performed by means of thin layer chromatography and spectrophometric assays. Aqueous extract (50, 100 or 200 mg/kg body weight/day) was administered orally to experimental mice. Liver injury was induced chemically, by a single CCl(4) administration (0.1% in olive oil, 10 ml/kg, i.v.), or immunologically, by injection of endotoxin (LPS, 10 microg, i.v.) in BCG-primed mice. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in mouse sera, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA) in mouse liver tissues were measured. The biochemical observations were supplemented by histopathological examination. RESULTS Obtained results demonstrated that the pretreatment with AEAA significantly (P<0.001) and dose-dependently prevented chemically or immunologically induced increase in serum levels of hepatic enzymes. Furthermore, AEAA significantly (P<0.05) reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes SOD and GPx towards normal levels. In the BCG/LPS model, increase of the levels of important pro-inflammatory mediators TNF-alpha and IL-1 was significantly (P<0.01) suppressed by AEAA pretreatment. Histopathology of the liver tissue showed that AEAA attenuated the hepatocellular necrosis and led to reduction of inflammatory cells infiltration. Phytochemical analyses revealed the presence of sesquiterpene lactones, flavonoids, phenolic acids and tannins in the AEAA. CONCLUSIONS The results of this study strongly indicate the protective effect of AEAA against acute liver injury which may be attributed to its antioxidative and/or immunomodulatory activity, and thereby scientifically support its traditional use.

Protective effect of Cichorium glandulosum root extract on carbon tetrachloride-induced and galactosamine-induced hepatotoxicity in mice.

Cichorium glandulosum Boiss. et Huet is a native plant used in Traditional Uighur Medicine, especially for treating a variety of liver disorders. In the present study, in vivo hepatoprotective effect of C. glandulosum root extract (CGRE) was evaluated using two experimental models, carbon tetrachloride (CCl4)- and galactosamine (GalN)-induced acute hepatotoxicity in mice. Pretreatment with CGRE (800 mg/kg/day, p.o.) for seven days significantly reduced the impact of CCl4 toxicity (10 mL/kg, i.p.) on the serum markers of liver damage, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Protective effect was reconfirmed against GalN-induced injury (800 mg/kg b.w., i.p.) and elevated serum enzymatic levels were significantly (p<0.05)and dose dependently restored towards normalization by the extracts. Furthermore, considering the well-known implication of free radicals in tissue injury, in vitro antioxidant properties of the extract were determined with a view to suggest the possible mechanism of activity. The extract showed noticeable antioxidant activity, comparable with standard antioxidants, through its ability to scavenge several free radicals (DPPH, O(2)(-), NO()) and efficiency against lipid peroxidation. Therefore, presented results suggest that CGRE is potent hepatoprotective agent that could protect liver against the acute injury and this ability might be attributed to its antioxidant potential.

Structure of the Leanyer orthobunyavirus nucleoprotein–RNA complex reveals unique architecture for RNA encapsidation

Negative-stranded RNA viruses cover their genome with nucleoprotein (N) to protect it from the human innate immune system. Abrogation of the function of N offers a unique opportunity to combat the spread of the viruses. Here, we describe a unique fold of N from Leanyer virus (LEAV, Orthobunyavirus genus, Bunyaviridae family) in complex with single-stranded RNA refined to 2.78 Å resolution as well as a 2.68 Å resolution structure of LEAV N–ssDNA complex. LEAV N is made up of an N- and a C-terminal lobe, with the RNA binding site located at the junction of these lobes. The LEAV N tetramer binds a 44-nucleotide-long single-stranded RNA chain. Hence, oligomerization of N is essential for encapsidation of the entire genome and is accomplished by using extensions at the N and C terminus. Molecular details of the oligomerization of N are illustrated in the structure where a circular ring-like tertiary assembly of a tetramer of LEAV N is observed tethering the RNA in a positively charged cavity running along the inner edge. Hydrogen bonds between N and the C2 hydroxyl group of ribose sugar explain the specificity of LEAV N for RNA over DNA. In addition, base-specific hydrogen bonds suggest that some regions of RNA bind N more tightly than others. Hinge movements around F20 and V125 assist in the reversal of capsidation during transcription and replication of the virus. Electron microscopic images of the ribonucleoprotein complexes of LEAV N reveal a filamentous assembly similar to those found in phleboviruses.

Serum metabolic profiling of abnormal savda by liquid chromatography/ mass spectrometry

Abnormal savda is a special symptom in Uigur medicine. The understanding of its metabolic origins is of great importance for the subsequent treatment. Here, a metabonomic study of this symptom was carried out using LC-MS based human serum metabolic profiling. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) was used for the classification and prediction of abnormal savda. Potential biomarkers from metabonomics were also identified for a metabolic understanding of abnormal savda. As a result, our OSC-PLS-DA model had a satisfactory ability for separation and prediction of abnormal savda. The potential biomarkers including bilirubin, bile acids, tryptophan, phenylalanine and lyso-phosphatidylcholines indicated that abnormal savda could be related to some abnormal metabolisms within the body, including energy metabolism, absorption of nutrition, metabolism of lecithin on cell membrane, etc. To the best of our knowledge, this is the first study of abnormal savda based on serum metabolic profiling. The LC/MS-based metabonomic platform could be a powerful tool for the classification of symptoms and for the development of this traditional medicine into an evidence-based one.

Inhibition of Cell Growth and Cellular Protein, DNA and RNA Synthesis in Human Hepatoma (HepG2) Cells by Ethanol Extract of Abnormal Savda Munziq of Traditional Uighur Medicine

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation, commonly used for the treatment and prevention of cancer. We tested the effects of ethanol extract of ASMq on cultured human hepatoma cells (HepG2) to explore the mechanism of its putative anticancer properties, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide, neutral red and lactate dehydrogenase (LDH) leakage assays, testing the incorporation of 3[H]-leucine and 3[H]-nucleosides into protein, DNA and RNA, and quantifying the formation of malondialdehyde-thiobarbituric acid (MDA) adducts. ASMq ethanol extract significantly inhibited the growth of HepG2 and cell viability, increased the leakage of LDH after 48 hours or 72 hours treatment, in a concentration- and time-dependent manner (P < .05). Cellular protein, DNA and RNA synthesis were inhibited in a concentration- and time-dependent manner (P < .05). No significant MDA release in culture medium and no lipid peroxidation in cells were observed. The results suggest that the cytotoxic effects of ASMq ethanol extract might be related to inhibition of cancer cell growth, alteration of cell membrane integrity and inhibition of cellular protein, DNA and RNA synthesis.

Cytotoxicity of abnormal Savda Munziq aqueous extract in human hepatoma (HepG2) cells.

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation commonly used to treat diseases such as diabetes, cardiovascular diseases, chronic asthma and especially digestive cancer. Earlier studies have shown that ASMq is a free radical scavenger and could prevent mitochondrial and DNA oxidative damage. In this study, we tested the effects of aqueous extract of ASMq on human hepatoma cells (HepG2) to explore the possible mechanism of its putative anticancer properties. Aqueous extract of ASMq was tested on HepG2 proliferation (MTT assay) at 72 h, cell viability at 48 h (neutral red assay), lactate dehydrogenase release over 48 or 72 h as a measure of cytoplasmic leakage, lipid peroxidation (malondialdehyde–thiobarbituric acid adducts) at 48 h, and incorporation of [3H]‐leucine, [3H]‐thymidine and [3H]‐uridine into cellular protein, DNA and RNA, respectively, at 24 or 48 h to assess the inhibition effects to cellular macromolecule synthesis. Our results showed a significant (P < 0.05) time‐ and concentration‐dependent inhibition of HepG2 proliferation and viability, with increased cytoplasmic leakage, and time‐ and concentration‐dependent inhibition of protein, DNA and RNA synthesis. No lipid peroxidation was found at these concentrations. The results of the present study suggest that the putative anticancer mechanisms of ASMq may at least involve cytotoxicity.

Epidemiological Survey on the Prevalence of Periodontitis and Diabetes Mellitus in Uyghur Adults from Rural Hotan Area in Xinjiang

Background and Aims. This study was designed to explore the relationship between periodontitis and diabetes mellitus (DM) in Uygur adults from Xinjiang. Methods and Results. Data were obtained using questionnaire and oral examination. Participants (48.87 ±13.72 yr) were categorized into periodontitis and non-periodontitis groups in accordance with the chronic periodontitis diagnostic criteria. Based on gum inflammation, bleeding on probing, periodontal pocket depth and attachment loss, patients were further divided into mild, moderate and severe periodontitis groups. Among 962 subjects, 453 (47.1%) suffered from chronic periodontitis with a prevalence of type 2 DM and impaired fasting glucose of 9.5% and 11.4%, respectively. In the periodontitis group, the prevalence of type 2 DM was 75.6% compared with 22.4% in the non-periodontitis group. Likewise, the prevalence of impaired fasting glucose was 71.3% and 28.7% in periodontitis and non-periodontitis groups, respectively. The univariate logistic regression analysis revealed moderate and severe periodontitis as risk factors for DM (OR = 3.4, OR = 2.9). Multivariate logistic regression analysis showed that moderate periodontitis is independently associated with DM (OR = 4). Conclusions. Our data revealed that prevalence of DM is overtly higher in periodontitis patients than in individuals without periodontitis. Furthermore, moderate periodontitis is considered an independent risk factor for type 2 DM.

Protective effects of Munziq and Mushil of Abnormal Savda to mitochondrial oxidative damage

Munziq and Mushil of Abnormal Savda are traditional Uighur herbal medicinal products, which could have antioxidant properties protecting mitochondria against oxidative damage. Mitochondria were isolated from rat livers. A FeSO4/VitC hydroxyl radical‐generating system was used to induce mitochondrial oxidative damage. Alterations in mitochondrial membrane structure were observed by electron microscopy, and mitochondrial superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Ca2+–Mg2+‐ATPase activity were measured. Muziq or Mushil were added, at concentrations ranging from 10−5 to 10−1 g/mL. Mitochondrial membrane structure was damaged after exposure to hydroxyl radical; mitochondrial SOD and Ca2+–Mg2+‐ATPase activities decreased (by 80 and 55%, respectively, both P < 0.01), and MDA level increased 4.6‐fold (P < 0.01). Munziq and Mushil protected mitochondrial membranes from structural damage. They inhibited the changes in mitochondrial functions in a dose‐dependent manner. At the highest concentrations, values were equal to initial normal values. Munziq and Mushil of Abnormal Savda can reduce the oxidative damage induced by hydroxyl radical and protect the mitochondrial membrane structure and its functions.

Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice

BackgroundAbnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system.MethodsKunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2–8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 β and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry.ResultsASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1β and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear.ConclusionsASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity.

Anti-inflammatory, immunomodulatory, and heme oxygenase-1 inhibitory activities of ravan napas, a formulation of uighur traditional medicine, in a rat model of allergic asthma.

Ravan Napas (RN) is a traditional formula used to treat pulmonary symptoms and diseases such as coughing, breathing difficulty, and asthma in traditional Uighur medicine. The purpose of this study was to investigate the anti-inflammatory, and immuno-modulatory activity of RN in a well-characterized animal model of allergic asthma. Rats were sensitized with intraperitoneal (ip) ovalbumin (OVA) and alum, and then challenged with OVA aerosols. The asthma model rats were treated with RN; saline- and dexamethasone- (DXM-) treated rats served as normal and model controls. The bronchoalveolar lavage fluid (BALF) cellular differential and the concentrations of sICAM-1, IL-4, IL-5, TNF-α, INF-γ, and IgE in serum were measured. Lung sections underwent histological analysis. The immunohistochemistry S-P method was used to measure the expression of ICAM-1 and HO-1 in the lung. RN significantly reduced the number of inflammatory cells in BALF and lung tissues, decreased sICAM-1, IL-4, IL-5, TNF-α, and IgE in serum, and increased serum INF-γ. There was a marked suppression of ICAM-1 and HO-1 expression in the lung. Our results suggest that RN may have an anti-inflammatory and immuneregulatory effect on allergic bronchial asthma by modulating the balance between Th1/Th2 cytokines.