Nephroprotective Activity of Angelica keiskei (Miq). Koidz. on Cisplatin-Induced Rats: Reducing Serum Creatinine, Urea Nitrogen, KIM-1, and Suppressing NF-kappaB p65 and COX-2.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S481479

Ika Wahyuni, Diah Lia Aulifa, Aziiz Mardanarian Rosdianto, Jutti Levita

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Abstract

Background: The sap of Angelica keiskei (Miq). Koidz. has been reported for its abundance of chalcone contents. Chalcones have been known for their effective nephroprotective activity toward cisplatin-induced renal cells and mice.

Purpose: To investigate the effect of A. keiskei sap extract (ASEE) on kidney function parameters (serum creatinine, urea nitrogen, and kidney injury molecule-1) and the expression of NF-kappaB p65 and COX-2 in cisplatin-induced Wistar rats.

Methods: In vivo nephroprotective activity of ASEE at 1000 and 1500 mg/kg BW/day doses for 10 days on cisplatin (5 mg/kg BW) induced nephrotoxicity was evaluated on Wistar rats. Quercetin 20 mg/kg BW/day was used as the control drug. Cisplatin inducement was given on day 7. The BW was measured every day. On day 11, the rats were euthanized, and their blood was taken intracardially for creatinine and urea nitrogen analysis. Histopathological analysis was carried out on the right kidney, and KIM-1 levels in the left kidney were measured. The Western blot technique evaluated the NF-kappaB p65 and COX-2 expression in the kidney. All data obtained were compared to the cisplatin group (negative control). The total flavonoids and chalcones in ASEE were also determined.

Results: Pretreatment with ASEE reduces the BW of Wistar rats, and significantly reduces creatinine and KIM-1 levels, but does not significantly reduce the levels of urea nitrogen, the expression of NF-kappaB p65, and COX-2 in the kidney of cisplatin-induced Wistar rats. The total flavonoid content in ASEE is 8.755 g QE/100 g extract and the total chalcone content is 5.532 g IBCE/100 g extract.

Conclusion: The sap of Angelica keiskei (Miq). Koidz. reveal the potential to protect the kidneys against cisplatin-induced toxicity. The nephroprotective activity may be attributed to the antioxidant and anti-inflammatory properties of the flavonoids and the chalcones contained in the sap of Angelica keiskei (Miq). Koidz.

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Koidz.Koidz：降低血清肌酸酐、尿素氮和 KIM-1，抑制 NF-kappaB p65 和 COX-2。

背景：Koidz.Koidz. 的汁液中含有丰富的查耳酮。目的：研究 A. keiskei sap extract（ASEE）对顺铂诱导的 Wistar 大鼠肾功能参数（血清肌酐、尿素氮和肾损伤分子-1）以及 NF-kappaB p65 和 COX-2 表达的影响：方法：在 Wistar 大鼠身上评估 ASEE 对顺铂诱导的肾毒性（5 毫克/千克体重）的体内肾保护活性，剂量为 1000 和 1500 毫克/千克体重/天，持续 10 天。槲皮素 20 毫克/千克体重/天作为对照药。第 7 天给予顺铂诱导。每天测量体重。第 11 天，对大鼠实施安乐死，心内抽血进行肌酐和尿素氮分析。对右肾进行组织病理学分析，并测定左肾中的 KIM-1 水平。Western 印迹技术评估了肾脏中 NF-kappaB p65 和 COX-2 的表达。所有数据均与顺铂组（阴性对照）进行了比较。此外，还测定了 ASEE 中的总黄酮和查耳酮含量：结果：用 ASEE 预处理可降低 Wistar 大鼠的体重，显著降低肌酐和 KIM-1 水平，但不能显著降低顺铂诱导的 Wistar 大鼠肾脏中的尿素氮水平、NF-kappaB p65 和 COX-2 的表达。ASEE 中的总黄酮含量为 8.755 克 QE/100 克提取物，总查尔酮含量为 5.532 克 IBCE/100 克提取物：结论：Angelica keiskei (Miq).Koidz.的汁液具有保护肾脏免受顺铂引起的毒性的潜力。这种肾脏保护活性可能归因于当归汁液中所含黄酮类化合物和查耳酮的抗氧化和抗炎特性。Koidz.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.