Crocin protects against endoplasmic reticulum stress-related tubular injury in diabetic nephropathy via the activation of the PI3K/AKT/Nrf2 pathway.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/IJBMS.2023.73385.15942
Guiying Wang, Jiuhon Deng, Zhou Hua
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Abstract

Objectives: Diabetic nephropathy (DN) is the main cause of end-stage renal disease, but the current treatment is not satisfactory. Crocin is a major bioactive compound of saffron with antioxidant and anti-endoplasmic reticulum stress (ERS) abilities used to treat diabetes. This study specifically investigated whether crocin has a regulatory role in renal injury in DN.

Materials and methods: The experiment was divided into control, (db/m mice), model (db/db mice), and experimental groups (db/db mice were intraperitoneally injected with 40 mg/kg crocin). Renal function-related indicators (Scr, BUN, FBG, UP, TG, TC, ALT, and AST) and oxidative stress-related indicators (ROS, MDA, GSH, SOD, and CAT) were assessed. The pathological changes of renal tissues were confirmed by HE, Masson, PAS, and TUNEL staining. The levels of ERS-related proteins (GRP78 and CHOP), apoptosis-related proteins, and PI3K/AKT and Nrf2 pathways-related proteins in renal tissue were detected.

Results: In db/db mice, renal function-related indicators, apoptotic cells of renal tissues, the contents of ROS and MDA as well as the expressions of CHOP, GRP78, and Bax were increased, the degree of renal tissue damage was aggravated, while the contents of GSH, SOD, and CAT, as well as the protein levels of Nrf2, PARP, anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) were decreased compared to the db/m mice. However, crocin treatment reversed the above-mentioned situation. The expressions of the PI3K/AKT and Nrf2 pathways-related proteins were also activated by crocin.

Conclusion: Crocin inhibited oxidative stress and ERS-induced kidney injury in db/db mice by activating the PI3K/AKT and Nrf2 pathways.

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藏红花苷可通过激活 PI3K/AKT/Nrf2 通路防止糖尿病肾病中与内质网应激相关的肾小管损伤。
目的:糖尿病肾病(DN)是导致终末期肾病的主要原因,但目前的治疗效果并不理想。藏红花苷是藏红花的一种主要生物活性化合物,具有抗氧化和抗内质网应激(ERS)的能力,可用于治疗糖尿病。本研究特别探讨了藏红花苷是否对 DN 肾损伤具有调节作用:实验分为对照组(db/m小鼠)、模型组(db/db小鼠)和实验组(db/db小鼠腹腔注射40 mg/kg巴豆毒素)。评估肾功能相关指标(Scr、BUN、FBG、UP、TG、TC、ALT和AST)和氧化应激相关指标(ROS、MDA、GSH、SOD和CAT)。HE、Masson、PAS和TUNEL染色证实了肾组织的病理变化。检测了肾组织中ERS相关蛋白(GRP78和CHOP)、凋亡相关蛋白、PI3K/AKT和Nrf2通路相关蛋白的水平:结果:与db/m小鼠相比,db/db小鼠肾功能相关指标、肾组织凋亡细胞、ROS和MDA的含量以及CHOP、GRP78和Bax的表达均升高,肾组织损伤程度加重,而GSH、SOD和CAT的含量以及Nrf2、PARP、抗凋亡蛋白(Mcl-1、Bcl-2和Bcl-xl)的蛋白水平降低。然而,羊角霉素治疗逆转了上述情况。PI3K/AKT和Nrf2通路相关蛋白的表达也被巴豆素激活:结论:巴豆素通过激活PI3K/AKT和Nrf2通路,抑制了氧化应激和ERS诱导的db/db小鼠肾损伤。
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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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