Acid Levels In Mice Research Articles

Structural elucidation of a Acanthopanax senticosus polysaccharide CQ-1 and its hepatoprotective activity via gut health regulation and antioxidative defense

Acanthopanax senticosus has proven health benefits, particularly for liver damage. The objective of this study was to elucidate the protective effects and the underlying mechanisms of action of A. senticosus against metabolic dysfunction-associated fatty liver disease (MAFLD). A novel homogeneous water-soluble polysaccharide, CQ-1, was successfully isolated and purified from A. senticosus root. The main chain structure of CQ-1 was identified as →2)-α-L-Rha-(1 → 4)-α-D-GalAp-(1 → 6)-β-D-Galp-(1→. Additionally, branched chains comprising an arabinosyl residue, galactosyl residue, and galacturonic acidic residue were identified as being attached to →2,4)-α-L-Rha-(1→, →3,6)-β-D-Galp-(1→, and →3,4)-α-D-GalAp-(1→, respectively. CQ-1 exhibited antioxidant and prebiotic activities in vitro. CQ-1 increased antioxidant capacity and reduced serum pro-inflammatory cytokines in mice. Additionally, CQ-1 has been shown to enhance the diversity and composition of the gut microbiota, thereby facilitating the restoration of gut function. These include improving intestinal barrier function and increasing short-chain fatty acid levels in mice. Our study has shown that CQ-1 has a hepatoprotective effect in MAFLD mice, and we have proposed that CQ-1 may be a promising strategy for the treatment of MAFLD.

P054 R. intestinalis improves inflammatory bowel disease by preventing gut uric acid absorption through inhibiting METTL3 mediated m6A modification of SLC2A9

Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease with persistent, recurrent, unsatisfactory response, and a poor prognosis. The incidence of Chinese IBD has increased rapidly, and Westernized diets such as purine-rich foods play an important role in its rapid growth. The alteration of purine-urate metabolism by microbiota may contribute to the development of IBD. Methods In this study, metagenomic and metabolomic analyses were performed on fecal samples from 30 untreated IBD patients and 30 healthy controls. R. intestinalis was used to observe the effect on serum uric acid levels in mice, respectively. Body weight, colon length, disease activity score, serum uric acid levels, and electron microscopy were all assessed. The RNAseq analysis of intestinal tissue from DSS-induced colitis mice intervened with R. intestinalis and co-cultured with R. intestinalis and the normal intestinal epithelial cell line NCM460, combined with m6A antibody dot blot assay, RM2Target database, and MeRIP sequencing data analysis, provided evidence that SLC2A9 was modified by METTL3, and SRAMP database predicted the potential for SLC2A9 mRNA to be modified by m6A after R. intestinalis intervention. Results Multi-omics analysis revealed that the abundance of R. intestinalis was significantly decreased in untreated IBD patients, and metabolomics revealed a correlation between high uric acid levels and disease severity, while the multi-omics integrated analysis suggested a significant negative correlation between R. intestinalis and uric acid. The research team confirmed that R. intestinalis can lower blood uric acid levels in mice and found that R. intestinalis intervention can alleviate the intestinal mucosal inflammation exacerbated by uric acid treatment in a DSS-induced mouse colitis model. Butyric acid has been reported to regulate m6A, and dot blot assays showed that R. intestinalis can reduce the m6A modification level of intestinal epithelial cells, METTL3, and SLC2A9. RM2Target database identified the protein-RNA interaction of the m6A regulator (WER) for SLC2A9 mRNA, and MeRIP sequencing data further indicated that METTL3 can bind to SLC2A9 mRNA through m6A modification. Meanwhile, based on sequence prediction, the research team identified 13 potential m6A modification sites on SLC2A9 mRNA, of which 4 sites had extremely high credibility . The highest credibility site had a score of 0.694, with a modification site sequence of GGACU located on an adenosine nucleotide. Conclusion R. intestinalis inhibit the METTL3 mediated m6A modification of intestinal epithelial SLC2A9, reducing the expression of SLC2A9, preventing the epithelial absorption of uric acid, and relieving IBD-related colitis

Bifidobacterium longum S3 alleviates loperamide-induced constipation by modulating intestinal acetic acid and stearic acid levels in mice.

Constipation is a major gastrointestinal (GI) symptom worldwide, with diverse causes of formation, and requires effective and safe therapeutic measures. In the present study, we used loperamide hydrochloride to establish a constipation model and assessed the effect of Bifidobacterium on constipation and its possible mechanism of relief. The results showed that B. longum S3 exerted a constipation-relieving effect primarily by improving the gut microbiota, enriching genera including Lactobacillus, Alistipes, and Ruminococcaceae UCG-007, and decreasing the bacteria Lachnospiraceae NK4B4 group. These changes may thereby increase acetic acid and stearic acid (C18:0) levels, which significantly increase the expression levels of ZO-1 and MUC-2, repair intestinal barrier damage and reduce inflammation (IL-6). Furthermore, it also inhibited oxidative stress levels (SOD and CAT), decreased the expression of water channel proteins (AQP4 and AQP8), significantly elevated the Gas, 5-HT, PGE2, and Ach levels, and reduced nNOS and VIP levels to improve the intestinal luminal transit time and fecal water content. Collectively, these changes resulted in the alleviation of constipation.

Aspartate restrains thermogenesis by inhibiting the AMPK pathway in adipose tissues.

Increasing evidence suggests that brown adipose tissue (BAT) plays an important role in obesity and related diseases. Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we evaluated the potential effects of aspartate on the BAT function. We found that the circulating aspartate level is positively associated with metabolic syndrome and obesity in adults. Acute cold exposure significantly increases BAT aspartate as well as other amino acid levels in mice. In this regard, we speculate that aspartate may play a role in regulating the BAT function and systemic energy homeostasis. To verify the hypothesis, we altered aspartate availability to explore the effects on adipose tissue metabolism. Supplementation of aspartate exogenously inhibits the thermogenic gene expression and cold tolerance in mice. Intriguingly, aspartate bioavailability inhibits mitochondrial biosynthesis essentially through the suppression of mechanistic targeting of the AMPK cascade. Therefore, an evaluation of whether a diet deficient in aspartate will increase oxidative phosphorylation in the mitochondria to reestablish aspartate levels and therefore increase the energy expenditure will be interesting because these effects can prevent or ameliorate the development of obesity.

Correlation between plasma glutamate and adiponectin in patients with type 2 diabetes.

Visceral fat accumulation is a major determinant of type 2 diabetes mellitus and cardiovascular diseases. Recent studies have reported that glutamate is the most elevated amino acid in the plasma amino acid profile in patients with obesity and/or visceral fat accumulation. Here, we show the relationship between plasma glutamate and the clinical features of patients with type 2 diabetes. The study subjects were 62 (28 men and 34 women) Japanese patients with type 2 diabetes. Blood profiles, including glutamate and adiponectin (APN) levels and estimated visceral fat area (eVFA), were measured. We also evaluated the plasma amino acid levels in mice with or without obesity by GC/MS analysis. In patients with type 2 diabetes, plasma glutamate was positively correlated with BMI, eVFA, and fasting insulin but negatively correlated with APN and duration of diabetes. Additionally, multiple regression analysis revealed that plasma glutamate was a significant determinant of APN. The plasma glutamate level was most significantly increased in obese mice compared to control mice, and it was negatively correlated with APN. These results suggest that the level of plasma glutamate could be a strong indicator of adipocyte dysfunction in patients with type 2 diabetes.

The Ethanol Extract Fractionation (Peperomia Pellucida (L.) Kunth) On Uric Acid Levels Blood Serum Of Male White Mice

Research has been carried out on the effect of fractionating the ethanol extract of the messenger herbs (Peperomia pellucida (L.) Kunth) to reduce blood serum uric acid levels in male white mice. Ordered herbs containing flavonoid compounds are thought to be used as lowering uric acid levels in the blood. The purpose of this study was to determine the effect of giving the ethanol extract fraction (Peperomia pellucida (L.) Kunth) on blood serum uric acid levels of male white mice. Simplicia extraction was carried out with 96% ethanol and extract fractionation was carried out using n-hexane, ethyl acetate, and water as solvents. The chicken liver inductor was used using experimental methods in vivo. Uric acid levels in mice were measured using a test-strip out. The results of the analysis using statistical tests on the decrease in uric acid levels in the blood were significant with a value (p 0.05) on the 14th day of the ethyl acetate fraction. This study concludes that there are compounds in the messenger herbs that have the potential to reduce uric acid levels in the blood.

Structural analysis and attenuates hyperuricemic nephropathy of dextran from the Imperata cylindrica Beauv. var. major (Nees) C. E. Hubb.

ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development.

In Vivo Antihyperuricemic Activities of 3,4,5-Tri-O-caffeoylquinic acid, 4,4',6'-Trihydroxy-2'-Methoxychalcone, and Caffeic Acid from the Aerial Parts of Gnaphalium Affine

The extract of Gnaphalium affine has been reported to have antihyperuricemic and renal protective effects in vivo. The plant could alleviate acute hyperuricemia by inhibiting the activity of xanthine oxidase (XOD). 3,4,5-Tri-O-caffeoylquinic acid (3,4,5-triCQA), 4,4',6'-trihydroxy-2'-methoxychalcone (Chal), and caffeic acid (CA) were identified as the main ingredients of the plant attributed to the potential to retard XOD activity. However, whether the compounds were the effective ingredient of the plant exerting antihyperuricemic activity remained largely unknown. In this study, an experimental mouse model of hyperuricemia was induced by potassium oxonate and hypoxanthine, and orally administered with 3,4,5-triCQA (10 and 20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (40 and 80 mg/kg/d) for 6 consecutive days, respectively. Then, serum urate levels and liver XOD activities were assessed. The liver- or kidney-to body weight ratio was calculated. Allopurinol (AP, 50 mg/kg/d) and benzbromarone (BBR, 10 mg/kg/d) were used as controls. Our data showed that there were 52.7 to 81.0% inhibitions in XOD activities in mice treated with 3,4,5-TriCQA (10 and 20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (80 mg/kg/d), and 38.8 to 72.5% reduction in uric acid levels in mice treated with 3,4,5-TriCQA (20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (40 and 80 mg/kg/d). A larger kidney-to-body weight ratio was observed in hyperuricemic mice and further enhanced by AP treatment. However, the increasing trend was significantly reversed by additional treatment of 3,4,5-triCQA (10 and 20 mg/kg/d) and CA (40 mg/kg/d). Given the above fundings, 3,4,5-triCQA, Chal, and CA may be the key component responsible for the in vivo activities of G. affine for urate-lowering therapy and even promising agents for the treatment of hyperuricemia.

The Effect of Dayak Onion Extract on Lactic Acid Levels in Mice with FST Model

Intense physical exercise can increase lactic acid levels in the blood as a result of the anaerobic metabolism that occurs at that time. The impact of increased levels of lactic acid includes the occurrence of acidosis, damage to body cells, and fatigue which reduces muscle performance. Antioxidants can play a role in preventing body fatigue caused by oxidative stress. Onion Dayak (Eleutherine palmifolia) is a type of medicinal plant that is useful for health. The high content of antioxidants in Dayak onions can be used as an alternative anti-fatigue ingredient. This study aimed to look at the effect of the dose and duration of Dayak onion extract on lactic acid levels and physical activity in mice forced swimming test models. Type of Research Randomized Pre and Post-Test Control Group Design. Male White Mice (Sprague Dawley) 2 months old (weight 150-200g). Divided into 5 groups K- (the experimental group was not given Dayak onion extract, they were still given FST), K+ (the experimental group was given xanthine and FST), P1 (given Dayak onion extract at a dose of 50mg/200gBW), P2 (given the extract onion Dayak dose of 100mg/200gBB), P3 (given onion extract dose of 200mg/200gBW). Dayak onion extract was given for 28 days and given the forced swimming test, then the changes in lactic acid and physical activity endurance in swimming were observed.

Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers.

Rapamycin treatment significantly increases lifespan and ameliorates several aging-related diseases in mice, making it a potential anti-aging drug. However, there are several obvious side effects of rapamycin, which may limit the broad applications of this drug. Lipid metabolism disorders such as fatty liver and hyperlipidemia are some of those unwanted side effects. Fatty liver is characterized as ectopic lipid accumulation in livers, which is usually accompanied by increased inflammation levels. Rapamycin is also a well-known anti-inflammation chemical. How rapamycin affects the inflammation level in rapamycin-induced fatty liver remains poorly understood. Here, we show that eight-day rapamycin treatment induced fatty liver and increased liver free fatty acid levels in mice, while the expression levels of inflammatory markers are even lower than those in the control mice. Mechanistically, the upstream of the pro-inflammatory pathway was activated in rapamycin-induced fatty livers, however, there is no increased NFκB nuclear translocation probably because the interaction between p65 and IκBα was enhanced by rapamycin treatment. The lipolysis pathway in the liver is also suppressed by rapamycin. Liver cirrhosis is an adverse consequence of fatty liver, while prolonged rapamycin treatment did not increase liver cirrhosis markers. Our results indicate that although fatty livers are induced by rapamycin, the fatty livers are not accompanied by increased inflammation levels, implying that rapamycin-induced fatty livers might not be as harmful as other types of fatty livers, such as high-fat diet and alcohol-induced fatty livers.

Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice.

Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surf4 (surfeit locus protein 4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic Surf4 markedly reduces the development of atherosclerosis in different mouse models of atherosclerosis without causing hepatic steatosis. However, the role of Surf4 in chylomicron secretion is unknown. We developed inducible intestinal-specific Surf4 knockdown mice (Surf4IKO) using Vil1Cre-ERT2 and Surf4flox mice. Metabolic cages were used to monitor mouse metabolism. Enzymatic kits were employed to measure serum and tissue lipid levels. The expression of target genes was detected by qRT-PCR and Western Blot. Transmission electron microscopy and radiolabeled oleic acid were used to assess the structure of enterocytes and intestinal lipid absorption and secretion, respectively. Proteomics was performed to determine changes in protein expression in serum and jejunum. Surf4IKO mice, especially male Surf4IKO mice, displayed significant body weight loss, increased mortality, and reduced metabolism. Surf4IKO mice exhibited lipid accumulation in enterocytes and impaired fat absorption and secretion. Lipid droplets and small lipid vacuoles were accumulated in the cytosol and the endoplasmic reticulum lumen of the enterocytes of Surf4IKO mice, respectively. Surf4 colocalized with apoB and co-immunoprecipitated with apoB48 in differentiated Caco-2 cells. Intestinal Surf4 deficiency also significantly reduced serum triglyceride, cholesterol, and free fatty acid levels in mice. Proteomics data revealed that diverse pathways were altered in Surf4IKO mice. In addition, Surf4IKO mice had mild liver damage, decreased liver size and weight, and reduced hepatic triglyceride levels. Our findings demonstrate that intestinal Surf4 plays an essential role in lipid absorption and chylomicron secretion and suggest that the therapeutic use of Surf4 inhibition requires highly cell/tissue-specific targeting.

Lactic acid bacteria with anti-hyperuricemia ability: Screening in vitro and evaluating in mice

Hyperuricemia has become the increasing public health burden, which is a risk factor for gout, chronic kidney, cardiovascular diseases and diabetes. Lactic acid bacteria have been attracting considerable interest for the safe and effective treatment of hyperuricemia in recent years. In this study, Limosilactobacillus fermentum NCUH003018, Limosilactobacillus reuteri NCUH064056 and Lactobacillus gasseri NCUH066006 were preliminarily selected from sixty strains of lactic acid bacteria isolated from infant feces and fermented vegetables, and showed the ability of efficient degradation of inosine and guanosine, inhibition of xanthine oxidase activity, the tolerance to acid and bile salt, adhesion to epithelium cells, antibacterial activity, and antibiotic susceptibility in vitro. Then hyperuricemia mice model was established by high-yeast diet and intraperitoneal injection of potassium oxonate to analyze the uric acid-lowering effect of the three Lactobacillus in vivo. The results showed that Limosilactobacillus fermentum NCU003018 was the most effective in lowering uric acid level in mice, which prompted the decrease of serum uric acid by 30.77% compared with hyperuricemia model group. Therefore, the Limosilactobacillus fermentum NCU003018 is considered as a probiotic with anti-hyperuricemia ability, which could be used as a promising candidate in preventing and treating hyperuricemia, and the uric-acid lowering mechanism merits further investigation.

Abstract 1500: An engineered bacteria expressing an n3-fatty acid desaturase altered polyunsaturated fatty acid levels in mice

Abstract 1500: An engineered bacteria expressing an n3-fatty acid desaturase altered polyunsaturated fatty acid levels in mice

PENGARUH INFUSA REBUSAN DAUN KELOR (Moringa oleifera) TERHADAP PENURUNAN KADAR ASAM URAT DALAM DARAH PADA HEWAN COBA MENCIT JANTAN (Mus musculus)

Gout is the result of metabolism in the body whose levels should not be excessive, everyone has uric acid in their body, because every normal metabolism will produce uric acid while the trigger is food factors and other compounds that contain lots of purines. The purpose of this study was to determine the effect of giving Moringa oleifera leaf infusion on blood uric acid levels in mice using 25 mice which were divided into 5 groups, namely the positive control group, the infusion 20%, and the infusion 40%, infusion 60% and negative control with treatment for 3 weeks. Measurement of uric acid levels using an autocheck tool. The results of the measurement of uric acid levels in the infusion group 20% showed an average decrease of 0.16 mg/dl, in the 40% group the infusion showed an average value of 0.62 mg/dl and in the infusion group 60% showed an average value of 0.92 mg/dl. The higher the concentration of Moringa oleifera infusion, the lower the uric acid level

Antihyperuricemia Activity of Vanilla (Vanilla planifolia Andrews) Fruits Ethanol Extract to Male Mice (Mus musculus L.)

Hyperuricemia is a disease caused by an increase in uric acid levels in the blood over the normal level. Increased uric acid levels happen because the levels of purines in the body are quite high, so that the breakdown of purines into uric acid increases. This study used dried vanilla fruit extract using 60% ethanol solvent. The test animals used were 24 mice which were divided into 6 groups namely group Kn (standard feed), group K- (induced with suspension of chicken liver), group K + (induced by suspension of chicken liver and given allopurinol 10 mg / kgBB), group treatments P1, P2, and P3 were induced by suspension of chicken liver and vanilla fruit extract with doses of 50 mg / kgBB, 100 mg / kgBB, and 200 mg / kgBB respectively. Statistical data analysis using ANOVA (Analysis of Variance) through the SPSS 15.0 program with a level of α = 5% and continued with Duncan test at the level of α = 5%. The results of this study showed that vanilla fruit extract treatment P1, P2, and P3 had potential activity of antihyperuricemia, because it can reduce blood uric acid levels in mice induced by the chicken liver. The antihyperuricemia activity of vanilla fruit extract is comparable to the standard allopurinol chemical drug in reducing blood uric acid levels in mice statistically.

ETHANOL EXTRACT ON BLACK GARLIC (Allium sativum L.) REDUCES URIC ACID LEVELS IN MALE MICE HYPERURISEMIA MODEL

Black garlic is garlic that goes through a heating process and has a higher bioactivity of substances. The purpose of this study was to determine the effect of black garlic extract on the reduction of uric acid in male mice with hperuricemia induced by 25 ml / kg of chicken liver juice and 250 mg / kg of potassium oxonate. The mice used were male mice with uric acid levels above 3.3 mg / dL or 6.3-6.8 mg / dL. This research is an experimental study with the method of Pre Test - Post Test Control Group Design. The treatment group was K +: Giving allopurinol suspension 10 mg / kg BW, K-: Giving aquabides to the negative control group of mice, P1: Giving black garlic ethanol extract 4.2 mg / 20gr bb, P2: Giving black garlic ethanol extract 8.4 mg / 20gr bb, P3: Provision of black garlic ethanol extract 12.4 mg / 20gr bb. Measurement of uric acid levels was carried out at D-10 after induction of a high uric acid diet, as well as D-26 after treatment of each group. Data were analyzed by One Way Anova test and post hoc LSD test. The results showed that the ethanol extract of black garlic was able to reduce uric acid levels in the blood of mice with the highest percentage reduction in the P3 group (12.4 mg / 20gr bb) by 31,2%, followed by P2 (8.4 mg / 20gr. bb) of 18,03%. The lowest percentage reduction in uric acid levels was in the P1 group (4.2 mg / 20gr bb) by 10,2%. Black garlic ethanol extract has an effect on reducing total uric acid levels in mice due to its antioxidant content such as flavonoids, polyphenols, 5-hydroxymethylfurfural (5-HMF), leucine, and isoleucine.
 Key words: Black garlic, hyperuricemia, antioxidants, flavonoids.

Skin Dryness Induced in the KK-Ay/TaJcl Type 2 Diabetes Mouse Model Deteriorates Following Dapagliflozin Administration.

Various diabetic drugs have been developed as the number of patients with type 2 diabetes has increased. Sodium-glucose cotransporter (SGLT)-2 inhibitors have been developed as novel therapeutic agents. However, SGLT-2 inhibitors cause skin dryness. The mechanism through which SGLT-2 inhibitors cause skin dryness is unknown. The purpose of this study was to investigate the mechanism through which dapagliflozin, a SGLT-2 inhibitor, induces skin dryness. Specific pathogen-free KK-Ay/TaJcl (type 2 diabetes model) mice were orally administered with SGLT-2 inhibitor (dapagliflozin) daily for 4 weeks at a dose of 1 mg/kg/d. Skin dryness induced in KK-Ay/TaJcl mice became severe after dapagliflozin administration. Dapagliflozin treatment decreased collagen type I and hyaluronic acid levels in mice; additionally, it affected the transforming growth factor (TGF)-β/hyaluronan synthase pathway, further reducing hyaluronic acid levels. The results indicate that the reduction in hyaluronic acid levels plays an important role in the occurrence of dry skin in diabetes.

POTENSI INFUSA BUNGA KEMBANG SEPATU (Hibiscus rosa-sinensis) SEBAGAI ANTI HIPERURISEMIA PADA MENCIT (Mus musculus)

Uric acid levels in the blood can be lowered by taking anti-hyperuricemic drugs, but long-term use can have serious effects on the body. Therefore, we need medicines made from natural ingredients that have a compound that can reduce uric acid levels with a low effect. The purpose of this study was to determine the effect of hibiscus flower infusion on uric acid levels. The research method is experimental research with a Completely Randomized Design (CRD). Mice were divided into 6 treatment groups, the negative control group (normal) A0 was given 0.5% Na-CMC, A1 was hyperuricemia control (induction of potassium oxonate 250mg/kgBW and chicken liver juice), A2-A5 was treated with hyperuricemia. The treatment group A2 was given allopurinol 10mg/kgBW, A3-A5 was given hibiscus flower infusion at a dose of 20%, 30%, and 40%, respectively. The results showed that hibiscus flower infusion at doses of 20%, 30%, and 40% was able to reduce blood uric acid levels in male white mice induced by potassium oxonate and chicken liver juice. Hibiscus flower infusion has the potential to reduce uric acid levels in mice optimally at a dose of 20%, which is 80.8% of hyperuricemia control.

ANTIHYPERURICEMIA ACTIVITY OF ETHANOL EXTRACT AND FRACTIONS OF AZADIRACHTA INDICA LEAF IN VIVO AND MECHANISM OF ACTION OF ACTIVE FRACTIONS IN VITRO

Azadirachta indica , A.,Juss is a medicinal plant that is used traditionally for some disease, especially its leaves to treat a rheumatic diseases and lower blood uric acid levels. This study was carried out to examine antihyperuricemia activity of ethanol extract, water fraction, ethyl acetat fraction and n-hexane fraction of the A. Indica leaves in male mice of Swiss-Webster strain. Extract and fraction doses used were 250 and 500 mg/kg of body weight and the doses of allopurinol as a standard drug was 13 mg/kg of body weight. The tests were conducted on mice suffering from hyperuricemia induced by potassium oxonat at adose of 300 mg/kg of body weight intraperitoneally and chicken liver juice orally. Measurement of blood uric acid levels were performed using an Easy Touch® every hour for 4 hours after being given test preparations. The results showed that the ethanol extract and the fractions lowered blood uric acid levels in the same way as allopurinol did. The n-hexane fractions at the all doses showed the highest activity, followed by ethanol fraction, and water fraction at the dose of 250 mg/kg at the 4th hour. These results illustrated that the A. Indica leaves might be potential to be used as antihyperuricemia. The active compounds which possibly reduce blood uric acid levels in mice are believed to be flavonoid or polyphenolic compounds because they are reported to be able to inhibit the action of the xanthine oxidase enzyme that converts purines into uric acid. Then, the most active fraction, n-hexane fraction, was tested for its inhibitory activity on xanthine oxidase enzyme to determine its mechanism of action. The results showed that the n-hexane fraction, like allopurinol, inhibited uric acid biosynthesis through inhibiting the activity of xanthine oxidase enzyme with the IC 50 value of 132 μg/mL lower than that of allopurinol IC 50 58.35 μg/mL. Key words: A. indica leaves, antihyperuricemia, chicken liver juice, potassium oxonat, xanthine oxidase.

Aktivitas Antihiperurisemia Ekstrak Etanol Daun Sungkai (Peronema canescens Jack) Pada Mencit Putih Jantan

Hyperuricemia is a disease caused by an increase in uric acid levels in the blood. Currently, various treatments are developed by utilizing natural ingredients as an anti-hyperuricemia. Sungkai (Peronema canescens Jack) is one of the plants that contain a natural compound that can use as an anti-hyperuricemia treatment is the leaves of sungkai (Peronema canescens Jack.). The aim of this study to determine the anti-hyperuricemia activity of the ethanol extract of Sungkai leaves. The test animals used in this study were male white mice Wistar strain. This study used a completely randomized design (CRD) with 5 groups consisting of negative control (Na CMC 0.5%) positive control (allopurinol 10 mg / kg BW), treatment 1 (extract 125 mg / kg BW), treatment 2 (extract 250 mg / kg BW) and treatment 3 (extract 500 mg / kg BW). The parameters seen were uric acid levels measured using the POCT (Point of Care Test) method and analyzed using One Way Anova statistical analysis and Duncan's continued test. Our results showed that the treatment group with a dose of 125-500 mg / Kg BW reduce uric acid levels in mice. The best dose was a dose of 500 mg / Kg BW in reducing uric acid levels in mice with percent decline of 38.66%.