rebaudioside-a and Hyperuricemia

Abnormal uric acid level result in the development of hyperuricemia and hallmark of various diseases, including renal injury, gout, cardiovascular disorders, and non-alcoholic fatty liver. This study was designed to explore the anti-inflammatory potential of stevia residue extract (STR) against hyperuricemia-associated renal injury in mice. The results revealed that STR at dosages of 150 and 300 mg/kg bw and allopurinol markedly modulated serum uric acid, blood urea nitrogen, and creatinine in hyperuricemic mice. Serum and renal cytokine levels (IL-18, IL-6, IL-1Β, and TNF-α) were also restored by STR treatments. Furthermore, mRNA and immunohistochemistry (IHC) analysis revealed that STR ameliorates UA (uric acid)-associated renal inflammation, fibrosis, and EMT (epithelial-mesenchymal transition) via MMPS (matrix metalloproteinases), inhibiting NF-κB/NLRP3 activation by the AMPK/SIRT1 pathway and modulating the JAK2-STAT3 and Nrf2 signaling pathways. In summary, the present study provided experimental evidence that STR is an ideal candidate for the treatment of hyperuricemia-mediated renal inflammation. PRACTICAL APPLICATIONS: The higher uric acid results in hyperuricemia and gout. The available options for the treatment of hyperuricemia and gout are the use of allopurinol, and colchicine drugs, etc. These drugs possess several undesirable side effect. The polyphenolic compounds are abundantly present in plants, for example, stevia residue extract (STR) exert a positive effect on human health. From this study results, we can recommend that polyphenolic compounds enrich STR could be applied to develop treatment options for the treatment of hyperuricemia and gout.

Topics: Allopurinol; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Colchicine; Creatinine; Drugs, Chinese Herbal; Gout; Humans; Hyperuricemia; Inflammation; Interleukin-18; Interleukin-6; Kidney; Mice; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; RNA, Messenger; Sirtuin 1; Stevia; Tumor Necrosis Factor-alpha; Uric Acid

The current project was designed to utilize flavonoids and chlorogenic acids enriched stevia residue extract (STVRE) against hyperuricemia (HU). The in vitro results showed that STVRE potently and synergistically inhibits Xanthine oxidase (XO) with allopurinol. The AFM results predicted that STVRE compounds bind with XO and alter its structure which further prevents the entrance of substrate with XO. These in vitro results were further confirmed in fructose-PO-induced hyperuricemic mice model. The results showed that supplementation of STVRE with allopurinol significantly attenuated HU, oxidative stress, and inflammation caused by UA via inhibiting the production of uric acid and lowering cyclooxygenase-2, tumor necrosis factor-alpha, prostaglandin E2, interleukin-6, and interleukin 1-beta levels in serum and renal tissues. Moreover, STVRE and allopurinol treatment attenuated, tubular dilation, infiltration of inflammatory cells, improved structure disorder of podocyte, and foot process fusion, and decreased glomerular basement membrane thickness. These findings suggested that STVRE can be used as an antihyperuricemic agent along with allopurinol. PRACTICAL APPLICATIONS: The results of present study showed that STVRE has a beneficial effect against fructose-PO-induced hyperuricemia by decreasing uric acid level, xanthine oxidase activity, improving oxidative stress and inflammation. These findings suggested that by-product of stevia (STVRE) enriched with polyphenolic compounds can be used as a functional ingredient against hyperuricemia and related diseases.

Topics: Allopurinol; Animals; Fructose; Hyperuricemia; Mice; Plant Extracts; Stevia

Hyperuricemia (HUA) is considered a potent risk factor for the development of gout, renal failure, and cardiovascular disease. The current project was designed to use stevia (Stevia rebaudiana Bertoni) byproduct, named stevia residue extract (STVRE), for the treatment of HUA. Male Kunming mice were divided into six groups: normal control, model control, positive control (allopurinol, 5 mg per kg body weight [bw]), STVRE-1 (75 mg per kg bw), STVRE-2 (150 mg per kg bw), and STVRE-3 (300 mg per kg bw). HUA was induced by the administration of potassium oxonate (100 mg per kg bw), fructose (10% w/v), and yeast extract (100 mg per kg bw) for 8 weeks. STVRE significantly (p < 0.05) decreased uric acid (UA) production and ameliorated UA excretion by interacting with urate transporters. The STVRE remarkably attenuated oxidative stress mediated by UA and downregulated inflammatory-related response markers such as COX-2, NF-κB, PGE2, IL-1β, and TNF-α. Furthermore, STVRE also reversed HUA-induced abnormalities in kidneys compared with the MC group. The results of our study suggest that STVRE has potential to attenuate hyperuricemia and renal protective effects, and may be used as a natural supplement for the possible treatment of UA-related disorders.

Topics: Animals; Disease Models, Animal; Hyperuricemia; Male; Mice; Mice, Inbred Strains; Phytotherapy; Plant Extracts; Stevia

Hyperuricemia (HUA) is a metabolic disorder that occurs due to the overproduction or under-excretion of uric acid (UA) and is directly linked to the development of many life-threatening diseases. There is a growing interest among many researchers regarding how to overcome the encumbrance of HUA because conventional drugs are associated with multiple side effects. Thus, the present project has been designed to utilize flavonoids and chlorogenic acid-enriched stevia residue extract (STVRE) to combat HUA. The results show that supplementation with STVRE (200 and 400 mg per kg bw) inhibits the XOD enzyme in serum, duodenum, jejunum, and ileum tissues. Moreover, UA levels in the STVRE groups were also significantly (p < 0.05) decreased in serum, duodenum, jejunum, and ileum tissues and juices. STVRE also improved the intestinal morphology and oxidative biomarkers in duodenum, jejunum, and ileum tissues. Protein and mRNA expressions of ABCG2 were upregulated, whereas GLUT9 was downregulated in the STVRE-treated groups as compared with the model control group. The supplementation of STVRE significantly attenuated hyperuricemia and oxidative stress, upregulated ABCG2 and downregulated GLUT9 (protein and mRNA) expression in hyperuricemic mice. The results of our study revealed that the by-product of stevia has the potential to combat hyperuricemia, and can be used as a functional ingredient in the development of nutraceutical products.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 2; Chlorogenic Acid; Flavonoids; Glucose Transport Proteins, Facilitative; Humans; Hyperuricemia; Intestinal Elimination; Intestines; Male; Mice; Organic Anion Transporters; Oxidative Stress; Plant Extracts; Stevia; Uric Acid