Effects of Aqueous Saffron Extract on Glucoregulation As Well As Hepatic Agt and TNF-α Gene Expression in Rats Subjected to Sub-Chronic Stress

Overview

Journal Adv Biomed Res

Specialty Biomedical Engineering

Date 2023 Jul 12

PMID 37434936

Authors

Yeganeh Yazdani

Maryam Radahmadi

Roshanak Roustazade

Affiliations

Soon will be listed here.

Abstract

Background: Stress and saffron seem to affect glucoregulation mechanisms and insulin resistance in different ways. Impacts of the aqueous saffron extract were investigated on serum glucose levels, serum insulin levels, the homeostatic model assessment of β-cell function (HOMA-B), the homeostatic model assessment of insulin resistance (HOMA-IR), adrenal weight, and hepatic gene expression of angiotensinogen (Agt) and tumor necrosis factor-α (TNF-α) in rats under sub-chronic stress.

Materials And Methods: Forty-two male rats were divided into six groups: control, restraint stress (6h/day for seven days), saffron (30 and 60 mg/kg) treatments for seven days, and post-stress saffron (30 and 60 mg/kg) treatments for seven days. The serum glucose and insulin levels, hepatic gene expressions of Agt and TNF-α, HOMA-IR, HOMA-B, and adrenal gland weight were measured.

Results: One-week recovery following sub-chronic stress led to non-significant hyperglycemia, hyperinsulinemia, and insulin resistance. The hepatic Agt and TNF-α mRNA levels increased significantly in this group. Saffron administration led to enhanced hepatic Agt mRNA in the non-stressed subjects. In addition, serum glucose levels, insulin resistance, and hepatic Agt gene expression significantly increased in stress-saffron groups. The hepatic TNF-α gene expression was reduced only in the stress-saffron 60 group.

Conclusion: Saffron treatment after sub-chronic stress not only did not improve glucose tolerance but also enhanced insulin resistance. It indicated the interaction of saffron and sub-chronic stress to promote renin-angiotensin system activity. In addition, the saffron treatment decreased TNF-α gene expression after sub-chronic stress. The synergistic stimulating effect of saffron and sub-chronic stress on gene expression of hepatic Agt led to insulin resistance and hyperglycemia.

References

Vargas Vargas R, Varela Millan J, Fajardo Bonilla E . Renin-angiotensin system: Basic and clinical aspects-A general perspective. Endocrinol Diabetes Nutr. 2021; 69(1):52-62. PMC: 8547789. DOI: 10.1016/j.endinu.2021.05.012. View

Wang Q, Yu K, Wang J, Lin H, Wu Y, Wang W . Predator stress-induced persistent emotional arousal is associated with alterations of plasma corticosterone and hippocampal steroid receptors in rat. Behav Brain Res. 2012; 230(1):167-74. DOI: 10.1016/j.bbr.2012.01.051. View

Bandegi A, Rashidy-Pour A, Vafaei A, Ghadrdoost B . Protective Effects of Crocus Sativus L. Extract and Crocin against Chronic-Stress Induced Oxidative Damage of Brain, Liver and Kidneys in Rats. Adv Pharm Bull. 2015; 4(Suppl 2):493-9. PMC: 4312396. DOI: 10.5681/apb.2014.073. View

Satou R, Penrose H, Navar L . Inflammation as a Regulator of the Renin-Angiotensin System and Blood Pressure. Curr Hypertens Rep. 2018; 20(12):100. PMC: 6203444. DOI: 10.1007/s11906-018-0900-0. View

Lovelock D, Deak T . Repeated exposure to two stressors in sequence demonstrates that corticosterone and paraventricular nucleus of the hypothalamus interleukin-1β responses habituate independently. J Neuroendocrinol. 2017; 29(9). PMC: 5617797. DOI: 10.1111/jne.12514. View

Rameshrad M, Razavi B, Hosseinzadeh H . Saffron and its derivatives, crocin, crocetin and safranal: a patent review. Expert Opin Ther Pat. 2017; 28(2):147-165. DOI: 10.1080/13543776.2017.1355909. View

Cui B, Gai Z, She X, Wang R, Xi Z . Effects of chronic noise on glucose metabolism and gut microbiota-host inflammatory homeostasis in rats. Sci Rep. 2016; 6:36693. PMC: 5095650. DOI: 10.1038/srep36693. View

Singh B, Mourya A, Sah S, Kumar A . Protective effect of losartan and ramipril against stress induced insulin resistance and related complications: Anti-inflammatory mechanisms. Eur J Pharmacol. 2017; 801:54-61. DOI: 10.1016/j.ejphar.2017.02.050. View

Mobasseri M, Ostadrahimi A, Tajaddini A, Asghari S, Barati M, Akbarzadeh M . Effects of saffron supplementation on glycemia and inflammation in patients with type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical trial study. Diabetes Metab Syndr. 2020; 14(4):527-534. DOI: 10.1016/j.dsx.2020.04.031. View

10.

Dehghan F, Hajiaghaalipour F, Yusof A, Muniandy S, Hosseini S, Heydari S . Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo. Sci Rep. 2016; 6:25139. PMC: 4848502. DOI: 10.1038/srep25139. View

11.

Shahveisi K, Mousavi S, Hosseini M, Khajavi Rad A, Jalali S, Rajaei Z . The role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species production in PC12 cells. Iran J Basic Med Sci. 2014; 17(8):613-21. PMC: 4240797. View

12.

Qu W, Han C, Li M, Zhang J, Jiang Z . Anti-TNF-α antibody alleviates insulin resistance in rats with sepsis-induced stress hyperglycemia. J Endocrinol Invest. 2017; 41(4):455-463. DOI: 10.1007/s40618-017-0742-7. View

13.

Lovelock D, Deak T . Neuroendocrine and neuroimmune adaptation to Chronic Escalating Distress (CED): A novel model of chronic stress. Neurobiol Stress. 2018; 9:74-83. PMC: 6234279. DOI: 10.1016/j.ynstr.2018.08.007. View

14.

Roy M, Kirschbaum C, Steptoe A . Psychological, cardiovascular, and metabolic correlates of individual differences in cortisol stress recovery in young men. Psychoneuroendocrinology. 2001; 26(4):375-91. DOI: 10.1016/s0306-4530(00)00061-5. View

15.

Maggi M, Bisti S, Picco C . Saffron: Chemical Composition and Neuroprotective Activity. Molecules. 2020; 25(23). PMC: 7731018. DOI: 10.3390/molecules25235618. View

16.

Tadaishi M, Toriba Y, Shimizu M, Kobayashi-Hattori K . Adenosine stimulates hepatic glycogenolysis via adrenal glands-liver crosstalk in mice. PLoS One. 2018; 13(12):e0209647. PMC: 6303095. DOI: 10.1371/journal.pone.0209647. View

17.

Bali A, Jaggi A . Preclinical experimental stress studies: protocols, assessment and comparison. Eur J Pharmacol. 2014; 746:282-92. DOI: 10.1016/j.ejphar.2014.10.017. View

18.

Bahem R, Hoffmann A, Azonpi A, Caballero-George C, Vanderheyden P . Modulation of Calcium Signaling of Angiotensin AT1, Endothelin ETA, and ETB Receptors by Silibinin, Quercetin, Crocin, Diallyl Sulfides, and Ginsenoside Rb1. Planta Med. 2014; 81(8):670-8. DOI: 10.1055/s-0034-1383408. View

19.

Shirali S, Bathaie S, Nakhjavani M . Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytother Res. 2012; 27(7):1042-7. DOI: 10.1002/ptr.4836. View

20.

Fasipe O, Ayoade O, Enikuomehin A . Severity Grade Assessment Classifications for Both Insulin Resistance Syndrome and Status of Pancreatic Beta Cell Function in Clinical Practice Using Homeostasis Model Assessment Method Indices. Can J Diabetes. 2020; 44(7):663-669. DOI: 10.1016/j.jcjd.2020.02.003. View