Abstract:Objectives
To investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia (HUA) mice and explore the potential mechanisms.
Methods
Orthosiphon stamineus extracts were extracted using 50% ethanol and enriched using ethyl acetate, and characterised utilising UPLC/ESI‐MS. A potassium oxonate (PO) induced hyperuricemic mouse model was used to evaluate antihyperuricemia and nephroprotective effects of O. stamineus ethyl acetate extracts (OSE).
Key findings
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“…This could further be correlated with the suppressed XO activity in these groups. Since XO activity is known to trigger inflammatory reactions and consequent tissue damage [ 22 ], the observed results further indicated the tissue protective potential of the triterpene.…”
Section: Discussionmentioning
confidence: 77%
“…Blood UA levels are physiologically regulated by XO activity, an enzyme that catalyzes the formation of UA from xanthine. The XO catalyzed reaction also generates reactive oxygen species (ROS) which can trigger inflammatory reactions and consequent tissue damage [ 22 ]. The reduced serum levels of UA along with decreased XO activity in the triterpene treated groups supported the antihyperuricemic effect of RA-3.…”
Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.
“…This could further be correlated with the suppressed XO activity in these groups. Since XO activity is known to trigger inflammatory reactions and consequent tissue damage [ 22 ], the observed results further indicated the tissue protective potential of the triterpene.…”
Section: Discussionmentioning
confidence: 77%
“…Blood UA levels are physiologically regulated by XO activity, an enzyme that catalyzes the formation of UA from xanthine. The XO catalyzed reaction also generates reactive oxygen species (ROS) which can trigger inflammatory reactions and consequent tissue damage [ 22 ]. The reduced serum levels of UA along with decreased XO activity in the triterpene treated groups supported the antihyperuricemic effect of RA-3.…”
Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.
“…They further investigated the primary mechanisms that indicated O. aristatus probably increases the sensitivity of pancreatic beta cells to insulin or (and) peripheral utilization of glucose by the tissues for lowering plasma glucose [50,53]. Meanwhile, Chen and Xu et al [9,54] evaluated the function of anti-gout in mice. They showed that ethanolic and ethyl acetate fraction of O. aristatus possessed lowering serum uric acid (UA) and relieving pain because of the increasing excretion and the suppressing production of the UA, anti-inflammation, and analgesia.…”
Section: Discussionmentioning
confidence: 99%
“…Meanwhile, Chen and Xu et al . (Xu et al, 2020; Chen et al, 2020) evaluated the function of anti-gout in mice. They showed that ethanolic and ethyl acetate fraction of O. aristatus possessed lowering serum uric acid (UA) and relieving pain because of the increasing excretion and the suppressing production of the UA, anti-inflammation, and analgesia.…”
Section: Discussionmentioning
confidence: 99%
“…So, it is reasonable to conduct a targeted therapy if the Arachidonic acid metabolism has been impacted by O. aristatus . Besides, it seems compelling for O. aristatus to treat nephritis(Xu et al, 2020; Domitrovic et al, 2014; Luo et al, 2018), calculus(Akanae et al, 2010), urinary tract infection, hypertension(Azizan, 2012), liver damage(Yam et al, 2007), atherosclerosis(Mohd et al, 2019), and gastritis(Yuniarto, 2017) in numerous animal experiments. A few investigations also evaluated its neuroprotection in epilepsy, depression, and Alzheimer’s disease(Chung et al, 2020).…”
Background: Orthosiphon stamineus Benth. (OS) was a traditional folk herb with widespread clinical application, but it was lack of comprehensive understanding of its active ingredients and polypharmacological mechanisms. The aim of this work was to systematically study its natural compounds and the molecular mechanisms of the OS via network pharmacology. Methods: Compounds from OS were collected by literature retrieval and evaluated by SwissADME with the physicochemical property (ADMET model) and the likelihood for a natural medicine. The connection of active ingredients and target genes was built and confirmed by Cytoscape and AutoDock vina. Then, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were separately performed to obtain more in-depth understanding of OS. Finally, the relationship among active ingredients, targets, and diseases was built to clarify the polypharmacological mechanisms and found relevant active substances for further drug discovery. Results: A total of 140 compounds of OS were collected, and 16 potentially active ingredients were screened out. The Ingredient-Target Interaction Network was built with 6 flavonoids, 3 diterpenes, 3 phenols, 4 volatile oils, and 64 targets. The Docking analysis indicated that the ingredient-target interaction network was reliable; most ligand-receptor had a strong binding affinity (lowest binding energy: -6.9 kcal/mol). After pathway analysis, 185 significant biological processes and 36 signal pathways were found, and the ingredient-target-disease network of OS was constructed for polypharmacological mechanisms. Conclusion: Our study clarified the polypharmacological mechanisms via the relationship among active ingredients, targets, and diseases and provided better guidance for subsequent experiments and potential active ingredients for drug discovery.
This study aims to investigate the anti-hyperuricemic and nephroprotective effects and the potential mechanisms of the separated gastrointestinal hydrolysates of 𝜶-lactalbumin on hyperuricemic mice. Methods and results: The gastrointestinal hydrolysate of 𝜶-lactalbumin, the hydrolysate fraction with molecular weight (MW) < 3 kDa (LH-3k), and the fragments with smallest MW among LH-3K harvested through dextran gel chromatography (F5) are used. Hyperuricemia mice are induced via daily oral gavage of potassium oxonate and hypoxanthine. F5 displays the highest in vitro xanthine oxidase (XO) inhibition among all the fractions separated from LH-3k. Oral administration of F5 significantly reduces the levels of serum uric acid (UA), creatinine, and urea nitrogen. F5 treatment could ameliorate kidney injury through alleviating oxidative stress and inflammation. F5 alleviates hyperuricemia in mice by inhibiting hepatic XO activity and regulating the expression of renal urate transporters. Gut microbiota analysis illustrates that F5 administration increases the abundance of some SCFAs producers, and inhibits the growth of hyperuricemia and inflammation associated genera. LH-3k exhibits similar effects but does not show significance as those of the F5 fraction. Conclusion: The anti-hyperuricemia and nephroprotective functions of F5 are mediated by inhibiting hepatic XO activity, ameliorating oxidative stress and inflammation, regulating renal urate transporters, and modulating the gut microbiota in hyperuricemic mice.
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