PMID- 36401276 OWN - NLM STAT- MEDLINE DCOM- 20221128 LR - 20221128 IS - 2662-7671 (Electronic) IS - 2662-7671 (Linking) VI - 22 IP - 1 DP - 2022 Nov 18 TI - Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-kappaB pathway. PG - 301 LID - 10.1186/s12906-022-03776-x [doi] LID - 301 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) approximately constitutes 90% of the reported cases. 30-40% of diabetics eventually develop diabetic nephropathy (DN); accounting for one of the major causes of morbidity and mortality. Increased glucose autoxidation and non-enzymatic glycation of proteins in diabetic kidneys lead to the excessive generation of reactive oxygen species (ROS) that results in lipid peroxidation and activation of inflammatory mediators which overwhelms the scavenging capacity of the antioxidant defense system (Nrf2/Keap1/HO-1). Centratherum anthelminticum commonly called as kali zeeri (bitter cumin) and its seeds are well known for culinary purposes in Asia (Pakistan). It has reported anti-inflammatory, antioxidant, and anti-diabetic activities. The present study has attempted to explore the in-vivo anti-inflammatory, antioxidant and antihyperglycemic potential of the C. anthelminticum seed's fixed oil (FO) and its fractions in high fat-high fructose-streptozotocin (HF-HFr-STZ) induced T2DM rat model. METHODS: The T2DM rat model was developed by giving a high-fat and high-fructose diet followed by a single intraperitoneal injection of streptozotocin (STZ 60 mg/kg) on 28th day of the trial. After 72 hours of this injection, rats showing fasting blood glucose (FBG) levels>/=230 mg/dL were recruited into six groups. These groups were orally administered distilled water (1 mL/kg), Gliclazide (200 mg/kg), Centratherum anthelminticum seed (FO) and its hexane (HF), chloroform (CF) and ethanol (EF) soluble fractions (200 mg/kg each), respectively for 4 weeks (i.e. 28 days). Blood, serum, and kidney tissue samples of euthanized animals were used for biochemical, pro-inflammatory, and antioxidant markers (ELISA, qRT-PCR, and spectrophotometric assays) and histology, respectively. RESULTS: C. anthelminticum FO and its fractions reduced the lipid peroxidation, and improved the antioxidant parameters: enzymatic (SOD, CAT, and GPx), non-enzymatic (GSH), and mRNA expression of anti-inflammatory markers (Nrf-2, keap1, and HO-1). mRNA expression of inflammatory and apoptotic markers (TNF-alpha, IL-1beta, COX-1, NF-kappaB, Bax, and Bcl-2) were attenuated along with improved kidney architecture. CONCLUSION: C. anthelminticum can mitigate inflammation and oxidative stress in early DN. The anti-nephropathic effect can be attributed to its ability to down-regulate NF-kappaB and by bringing the Nrf-2 expression levels to near normal. CI - (c) 2022. The Author(s). FAU - Baig, Nida AU - Baig N AD - Clinical Laboratory Sciences, Institute of Medical Technology, Dow University of Health Sciences, OJHA Campus, Karachi, Pakistan. nida.baig@duhs.edu.pk. AD - Department of Biochemistry, University of Karachi, Karachi, Pakistan. nida.baig@duhs.edu.pk. FAU - Sultan, Rabia AU - Sultan R AD - Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, 75270, Karachi, Pakistan. FAU - Qureshi, Shamim Akhtar AU - Qureshi SA AD - Department of Biochemistry, University of Karachi, Karachi, Pakistan. LA - eng PT - Clinical Trial, Veterinary PT - Journal Article DEP - 20221118 PL - England TA - BMC Complement Med Ther JT - BMC complementary medicine and therapies JID - 101761232 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 30237-26-4 (Fructose) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Plant Oils) RN - 0 (RNA, Messenger) RN - 5W494URQ81 (Streptozocin) SB - IM MH - Animals MH - Rats MH - Anti-Inflammatory Agents/pharmacology MH - Antioxidants/pharmacology/therapeutic use MH - *Asteraceae MH - *Diabetes Mellitus, Experimental/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/drug therapy MH - Fructose MH - Kelch-Like ECH-Associated Protein 1/metabolism MH - NF-E2-Related Factor 2/metabolism MH - NF-kappa B/metabolism MH - Plant Oils MH - RNA, Messenger MH - Seeds MH - Streptozocin/therapeutic use PMC - PMC9675141 OTO - NOTNLM OT - Centratherum anthelminticum OT - Diabetes mellitus OT - Fixed oil OT - NF-kappaB OT - Nephropathy OT - Nrf-2/Keap1/HO-1 COIS- None EDAT- 2022/11/20 06:00 MHDA- 2022/11/23 06:00 PMCR- 2022/11/18 CRDT- 2022/11/19 00:10 PHST- 2022/03/15 00:00 [received] PHST- 2022/09/28 00:00 [accepted] PHST- 2022/11/19 00:10 [entrez] PHST- 2022/11/20 06:00 [pubmed] PHST- 2022/11/23 06:00 [medline] PHST- 2022/11/18 00:00 [pmc-release] AID - 10.1186/s12906-022-03776-x [pii] AID - 3776 [pii] AID - 10.1186/s12906-022-03776-x [doi] PST - epublish SO - BMC Complement Med Ther. 2022 Nov 18;22(1):301. doi: 10.1186/s12906-022-03776-x.