Drug Design, Development and Therapy (Oct 2024)
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
Abstract
Ika Wahyuni,1,2,* Diah Lia Aulifa,3,* Aziiz Mardanarian Rosdianto,4,* Jutti Levita5,* 1Master Program in Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia; 2Faculty of Health, Universitas Nahdlatul Ulama, Mataram, West Nusa Tenggara, Indonesia; 3Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 4Veterinary Medicine Study Program, Faculty of Medicine, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 5Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia*These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia, Tel +6222-84288888 Ext. 3510, Email [email protected]: 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.Keywords: antioxidants, apoptosis, chalcones, chemotherapy, Japanese celery, kidney injury
