Protective Effects of Ursolic Acid in the Kidneys of Diabetic Rats

Abstract

Amaç: Metabolik ve kronik bir hastalık olan diyabetin birçok ülkede önemli sağlık sorunu olma durumu artış göstermektedir. Diyabetin artmış serbest radikallerin üretimi ve azalmış antioksidan kapasiteyle ilişkili olduğu iddia edilmektedir. Diyabette oluşan oksiatif stres dokularda DNA hasarına neden olabilir. Antioksidan, antikanser, antiülser özellikler gibi sağlığa yararlı etkileri nedeniyle geleneksel Çin halk tıbbında yaygın olarak kullanılan ursolik asit çok iyi tanımlanmış pentasiklik triterpendir. Bu çalışmanın amacı, streptozotosin ile diyabet oluşturulmuş Wistar albino sıçanların böbreklerine ursolik asidin etkisini değerlendirmektir. Gereç ve Yöntemler: Bu amaçla, böbrek hücrelerindeki DNA hasarı alkali comet yöntemiyle araştırılmıştır. KAT, SOD, GR ve GSH-Px enzim aktiviteleri ve toplam GSH ve MDA düzeyleri gibi oksidatif stres parametreleri de ölçülmüştür. Bulgular: Ursolik asit tedavisinin, DNA hasarını, GR enzim aktivitelerini ve MDA seviyelerini önemli ölçüde azalttığı ve diyabetik sıçanlarda GSH düzeylerini ve CAT, SOD ve GSH-Px enzim aktivitelerini önemli ölçüde artırdığı bulundu. Sonuç: Sonuçlarımıza göre, ursolik asidin diyabetin neden olduğu böbrek hasarında yararlı olabileceği görülmüştür. Anahtar kelimeler: Diyabet, DNA hasarı, oksidatif stres, böbrek Objectives: Diabetes, a heteregenous metabolic and chronic disease, is a growing health problem in most countries. It has been claimed that diabetes is associated with the increased formation of free radicals and decreased in antioxidant potential. Oxidative stress formed in diabetes may cause DNA damage in the tissues. Ursolic acid, a well-known pentacylic triterpene, is commonly used in traditional Chinese medicine due to its beneficial health effects such as antioxidant, anticancer, and antiulcer properties. The aim of this study was to investigate the effects of ursolic acid in the kidneys of Wistar albino rats with streptozotocin-induced diabetes. Materials and Methods: DNA damage was evaluated in the kidney cells of rats using alkaline comet assays. Oxidative stress parameters such as CAT, SOD, GR, and GSH-Px enzyme activities and total GSH and MDA levels were also evaluated. Results: Ursolic acid treatment was found to significantly decrease DNA damage, GR enzyme activities, and MDA levels, and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities in diabetic rats. Conclusion: According to our results, it seems that ursolic acid may be beneficial against diabetes-induced renal damage.

A Systematic Review of Orthosiphon stamineus Benth. in the Treatment of Diabetes and Its Complications

“…Arjunolic acid, oleanolic acid, and ursolic acid have antioxidant activities to scavenge free radicals, while oleanolic acid and ursolic acid also have anti-inflammatory activities [100,[132][133][134]. α, β-Amyrin, arjunolic acid, tormentic acid, oleanolic acid, and ursolic acid lower the levels of TC, TG, LDL-C and leptin, increase serum HDL-C level to regulate the lipid metabolism [133,[135][136][137][138]. Maslinic acid, oleanolic acid, and ursolic acid improve insulin resistance and enhance insulin sensitivity respectively by a higher expression of IR, IRS, Akt, and PIP1B inhibitory activity [132,133,139].…”

“…Oleanolic acid inhibits gluconeogenesis by decreasing expression of glucose-6-phosphatase [133]. Maslinic acid and ursolic acid increase the hepatic glycogen accumulation [135,139]. α, β-Amyrin, arjunolic acid, and betulinic acid protect islet cells and decrease cell death [138,140,141].…”

Oleanolic acid and its analogues: promising therapeutics for kidney disease

“…Nephrin↑, VEGF↓, ESAM↑, TGF-β↓, p-smad2/3↓, p-ERK↓, p-eIF2α↓, ATF6↓, Bip↓, CHOP↓, Bcl2↑, Bax↓, Caspase 3↓, Nrf2↑, HO-1↑, α-SMA↓ [124] In vivo IR in Wistar rats OA (12.5, 25, 50 mg/kg) KIM-1↓, MDA↓, SOD↑, CAT↑, GPx↑, GSH↑, IFN-γ↓, IL-6↓, IL-10↑, MPO↓, Caspase 3↓, Nrf2↑, GCLc↑ [18] In vivo IR in SD rats UA (10 mg/kg) TNF-α↓, IL-1β↓, IL-6↓, IL-10↑, p-STAT3↓, P65↓, Caspase-3↓ [101] In vivo STZ-induced DN in SD rats UA (20 mg/kg) GR enzyme↓, MDA↓, GSH↑, CAT↑, SOD↑ [161] In vitro NRK-52E cell stimulated with TGF-β1 OA (2, 4, 8 μM) E-cadherin↑, FN↓,α-SMA↓, Nrf2↑, klotho↑, p-Smad2/3↓, ILK↓, Snail↓ [133] In vivo STZ-induced DN in Wistar rats UA (25 mg/kg) TNF-α↓, IL-1β↓, IL-6↓, IL-18↓, TLR4↓,NF-κB↓, MyD88↓ [105] In vivo Adenine-induced CKD in Wistar rats UA (30 mg/kg) TGF-β↓, CTGF↓, FN↓, CoL-I↓ [162] In vivo STZ-induced DN in SDrats UA (35 mg/kg) SOD ↑, MDA↓,TNF-α↓, MCP-1↓, IL-1β↓ [163] In vivo CLP in mice UA (2, 20 mg/kg) ROS↓, 8-OHdG↓, SOD1↑, SOD2↑, TNF-α↓, IL-1β, IL-6↓, NF-κB↓ [164] In vitro NRK-52E cell stimulated with HG OA (10 μM) miR-142-5p↓, PTEN↑, p62↓, LC3-II/ LC3-I↑, a-SMA↓, CoL-IV↓, PI3K↓, pAKT↓, p-mTOR↓ [21] Immunoregulatory effect…”

Molecular Mechanistic Pathways Targeted by Natural Antioxidants in the Prevention and Treatment of Chronic Kidney Disease

“…The ursolic acid treatment induces the antioxidant defenses in renal tissue as exemplified by increased GSH levels and CAT, SOD, and GSH-Px enzyme activities in diabetic rats. Moreover, treatment by this bioactive compound reduced oxidative stress as shown by decreased tissue lipid peroxidation [ 144 ]. Interestingly, ursolic acid alleviated renal injury in the alloxan-induced diabetes model through the reduction in proinflammatory cytokines [ 145 ].…”