PMID- 34725640 OWN - NLM STAT- MEDLINE DCOM- 20220121 LR - 20240404 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2021 DP - 2021 TI - Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools. PG - 6978450 LID - 10.1155/2021/6978450 [doi] LID - 6978450 AB - BACKGROUND: Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. METHODS: HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7alpha, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba. RESULTS: In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways. CONCLUSION: The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation. CI - Copyright (c) 2021 Md. Atiar Rahman et al. FAU - Rahman, Md Atiar AU - Rahman MA AUID- ORCID: 0000-0002-4902-8923 AD - Department of Biochemistry & Molecular Biology, University of Chittagong, Chittagong4331, Bangladesh. FAU - Uddin, Md Nazim AU - Uddin MN AUID- ORCID: 0000-0001-6586-5636 AD - Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research, Dhaka 1205, Bangladesh. FAU - Babteen, Nouf Abubakr AU - Babteen NA AUID- ORCID: 0000-0002-7836-5398 AD - Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia. FAU - Alnajeebi, Afnan M AU - Alnajeebi AM AUID- ORCID: 0000-0002-5670-1688 AD - Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia. FAU - Zakaria, Zainul Amiruddin AU - Zakaria ZA AUID- ORCID: 0000-0001-5525-7821 AD - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, (Jalan UMS), 88400 Kota Kinabalu, Sabah, Malaysia. AD - Halal Product Development Unit, Halal Product Research Institute, Universiti Putra Malaysia, (UPM), 43400 Serdang, Selangor, Malaysia. FAU - Aboelenin, Salama Mostafa AU - Aboelenin SM AD - Biology Department, Turabah University College, Taif University 21995, Saudi Arabia. LA - eng PT - Journal Article DEP - 20211023 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Antioxidants) RN - 0 (Hypoglycemic Agents) RN - 0 (Plant Extracts) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Alanine Transaminase/blood MH - Animals MH - Antioxidants/pharmacology MH - Aspartate Aminotransferases/blood MH - Diabetes Mellitus, Experimental/*drug therapy MH - Glutathione Peroxidase/metabolism MH - Hypoglycemic Agents/pharmacology MH - Liver/pathology MH - Male MH - Medicine, Traditional/methods MH - Network Pharmacology/methods MH - Oxidative Stress/drug effects MH - Plant Extracts/chemistry/pharmacology MH - Rats MH - Rats, Wistar MH - Superoxide Dismutase/metabolism MH - Vitaceae/*chemistry/*metabolism PMC - PMC8557063 COIS- The authors declare no conflict of interest. EDAT- 2021/11/03 06:00 MHDA- 2022/01/22 06:00 PMCR- 2021/10/23 CRDT- 2021/11/02 06:18 PHST- 2021/05/18 00:00 [received] PHST- 2021/09/29 00:00 [accepted] PHST- 2021/11/02 06:18 [entrez] PHST- 2021/11/03 06:00 [pubmed] PHST- 2022/01/22 06:00 [medline] PHST- 2021/10/23 00:00 [pmc-release] AID - 10.1155/2021/6978450 [doi] PST - epublish SO - Biomed Res Int. 2021 Oct 23;2021:6978450. doi: 10.1155/2021/6978450. eCollection 2021.