Antihyperuricemia Activity of the Ethyl Acetate Fraction of Bilimbi Leaves (Averrhoa bilimbi L.)

Hyperuricemia is a condition where there is an increase in uric acid levels above normal. An increase in the number of leukocytes is also a biological marker of hyperuricemia. The leaves of bilimbi (Averrhoa bilimbi L.) are one of the traditional medicinal plants which contain alkaloids, tannins, steroids, and flavonoid compounds. Flavonoid compounds are thought to inhibit the formation of uric acid in the body. This study investigates the antihyperuricemia activity of the ethyl acetate fraction of bilimbi leaves. The animals were male white mice grouped into six groups: the normal group, negative control, positive control (allopurinol), and the group was given the ethyl acetate fraction of bilimbi leaves at doses of 100, 200, and 400 mg/kg BW. Hyperuricemia induction is by giving high-purine diets and potassium oxonate. The results showed that the variation of the ethyl acetate fraction of bilimbi leaves significantly reduce uric acid levels and the number of leukocyte cells (sig <0.05). Giving ethyl acetate fraction at a dose of 400 mg/kg BW showed the best reduction in uric acid and leukocyte levels.

Effect of Apium Graveolens (Celery) Seed Extract on Serum Uric Acid Level of Hyperuricemic Rats and its Comparison with Allopurinol

Background: Plant derived medicines are widely used in traditional culture all over the world. Objectives: To determine the effect of Celery Seed Extract (CSE) on uric acid levels in hyperuricemic rats and to compare the effect of allopurinol and CSE. Methods: It was an animal experimental research study. Group A served as negative control whereas Group B served as positive control. CSE was given orally to three groups of rats (C, D, and E). One hour prior to administration of CSE; potassium oxonate was injected intraperitoneally in all groups except negative control to induce hyperuricemia. Similarly, group F was given allopurinol one hour after injection of potassium oxonate. Blood samples were collected for uric acid estimation. Results: It was found that administration of both CSE (group C, D, E) and allopurinol (group F) significantly lowered serum uric acid levels (p<0.001) as compared to positive control (group B). Serum uric acid lowering effect of both drugs CSE and allopurinol was found to be statistically significant on day 3rd and day 7th and was almost comparable. Conclusions: Celery seed extract significantly reduces serum uric acid levels in potassium oxonate-induced hyperuricemic rats and its uric acid lowering effect was comparable with that of allopurinol.

The effect of chayote leaves (Sechium edule)’s flavonoid fraction on the reduction of the serum uric acid levels through the inhibition of xanthine oxidase activity

Uric acid is the final product of purine metabolism and is categorized as hyperuricemia when it reaches >6.0 mg.dL-1 for women and >7.0 mg.dL-1 for men. The chayote leaves (Sechium edule) contain a high amount of flavonoid and might be used as an alternative to reduce hyperuricemia. The purpose of this study is to analyze the effect of chayote leaves (Sechium edule)’s flavonoid fraction on the level of uric acid and the activity of xanthine oxidase (XO) in Sprague Dawley Rats. The flavonoid fraction (FF) was obtained by extracting the chayote leaves, fractionating with n-hexane, hydrolyzing with HCl, and finally re-fractionating with ethyl acetate. Thirty male Sprague Dawley rats were induced for hyperuricemia by potassium oxonate and broth block for 21 days, and the interventions were given orally for 14 days. The rats were divided randomly into five groups: normal control (K-), hyperuricemia control (K+), hyperuricemia with FF dose 50 mg.200g-1 body weight (P1), hyperuricemia with FF dose 100 mg.200g-1 body weight (P2) and hyperuricemia with allopurinol 1.8 mg.200g-1 body weight. Xanthine oxidase activity was measured by CheKineTM Xanthine Oxidase Assay Kit, with simple colorimetry methods. The statistical analysis for XO activity was done using Kruskal-Wallis followed by Mann Whitney. The results showed that chayote leaves (Sechium edule)’s flavonoid fraction contains apigenin, apigenin o-glucoside, and luteolin. It also has antioxidant activity with 98.45% inhibition. There was a significant reduction in xanthine oxidase activity in groups treated with FF (p <0.005). The best dose of FF affecting XO activity was 100 mg.200g-1 body weight. The combination of FF and allopurinol can be more effective in decreasing uric acid levels by inhibiting XO activity.

Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats

Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1β levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.

Impact of Camellia japonica Bee Pollen Polyphenols on Hyperuricemia and Gut Microbiota in Potassium Oxonate-Induced Mice

Camellia japonica bee pollen is one of the major types of bee pollen in China and exhibits antioxidant and anti-inflammatory activities. The aims of our study were to evaluate the effects and the possible mechanism of Camellia japonica bee pollen polyphenols on the treatment of hyperuricemia induced by potassium oxonate (PO). The results showed that Camellia japonica bee pollen ethyl acetate extract (CPE-E) owned abundant phenolic compounds and strong antioxidant capabilities. Administration with CPE-E for two weeks greatly reduced serum uric acid and improved renal function. It inhibited liver xanthine oxidase (XOD) activity and regulated the expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1) and ATP-binding cassette superfamily gmember 2 (ABCG2) in kidneys. Moreover, CPE-E suppressed the activation of the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in PO-treated mice, and related inflammatory cytokines were reduced. CPE-E also modulated gut microbiota structure, showing that the abundance of Lactobacillus and Clostridiaceae increased in hyperuicemic mice. This study was conducted to explore the protective effect of CPE-E on hyperuricemia and provide new thoughts for the exploitation of Camellia japonica bee pollen.

Evaluation of Anti-hyperuricemic Activity of the Alcoholic Extract of Dried Capparis moonii Wight Fruits in Wistar Rats

Evaluation of anti-hyperuricemic activity of alcoholic extract of Capparis moonii Wight fruits in Wistar rats, by utilizing Indian caper typically occurring in the Konkan area which grows full-fledged in the hot and dry atmosphere that can be generally found throughout asia. The dried fruits of Capparis moonii W. were extracted using absolute ethanol to get an alcoholic extract. Acute oral toxicity studies were performed to decide the doses. The anti-hyperuricemic activity was estimated by the phenol red excretion in rats and the potassium oxonate induced hyperuricemia models respectively. The alcoholic extract showed dose-dependent mode of action where the higher concentration of 200 mg/kg showed higher amount of retention of phenol red in the blood suggesting that it has better ability to secrete urate out of the body of rats as compared to 100mg/kg. Also in potassium oxonate induced hyperuricemia, similar results were obtained with significant reduction in serum uric acid levels and serum creatinine levels as compared to 100mg/kg. The conclusion of this study was that; it proved that Capparis moonii W. alcoholic extract of the fruits can be beneficial as anti-hyperuricemic treatment agent. It would be encouraging to undertake further studies in future to decode the exact mechanism.

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

Background Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. Methods A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875 or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Results Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was most affected. These perturbations were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. Conclusions Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.

Malic Acid Attenuates Potassium Oxonate Induced Gouty Inflammation in Wistar Rat

Malic acid is an organic dicarboxylic acid commonly found in vegetables and fruits. Gouty inflammation is a disease characterized by the accumulation of monosodium urate (MSU) crystals around the tissues and joints. Hence, the current study has been conducted to evaluate the anti-inflammatory efficacy of the malic acid against the potassium oxonate (PO) induced animal model. The hematological, biochemical, and histopathological analyses were carried out to evaluate the efficacy of malic acid in treating gouty inflammation. The elevated levels of various biological markers such as liver injury markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin), renal function markers (urea, creatinine, uric acid), inflammatory markers (C-reactive protein and rheumatoid factors) and blood markers (hemoglobin, erythrocyte sedimentation rate) and white blood cells were observed in PO induced rats. Histological analysis also revealed inflammation in the ankle joint of PO-treated rats. The malic acid (25,50,100mg/kg bwt) treatment made the rats regain the biological markers near to their normal values. It was revealed that the malic acid had potential anti-gouty inflammatory activity against PO induced rat model. Hence, malic acid can be proposed as an excellent drug molecule with detailed examinations.