Table 1.
Protective effects of saffron and its constituents on the different organs mediated by the Nrf2 signaling pathway
| References | Results/mechanisms | Study design | Dosage | Constituents |
|---|---|---|---|---|
| (72) | ↑Anti-colitis effects ↓Nrf2, HO-1, and anti-inflammatory macrophages Pro-inflammatory macrophages |
in vivo /DSS-induced acute colitis C57BL/6 | 7.5, 15, 20, 25 mg/kg/8 days | Aqueous extract of Saffron |
| (58) | ↓LDH, creatine kinase, oxidative stress, apoptosis, inflammation, Bax, Caspase, MDA, and SOD ↑Nrf2 |
in vivo /Isoproterenol-induced myocardial infarction in Wistar rats | 50, 100, and 200 mg/kg/ day/15 days | Crocetin |
| (56) | Heart protective ↓UPR ↑Nrf2, HO-1, NQO1, and NADPH |
ex vivo/IR injury in Sprague-Dawley rats | 10 μM, 20 μM, and 40 μM | Crocetin |
| (70) | ↓Arthritic pain, inflammation, oxidative stress, NF-κB, iNOS, COX-2, IL-6, IL-10, IL-1β, and TNF-α ↑Nrf2 and HO-1 |
in
vitro/ LPS induced arthritis in mouse macrophages (RAW 264.7) And in vivo / CFA-induced arthritis in rats |
in
vitro: 12.5, 25, 50, 100, 200, and 400 mg/ml/24 hours in vivo : 5 mg/kg, 10 mg/kg, and 20 mg/kg/28 days |
Crocetin |
| (62) | ↑Cytotoxicity in cancer cells, ROS, oxidative stress, Nrf2, HO-1, NQO1, and NQO2 ↓LDHA, membrane potential, and ATP level |
in vitro/A549, HepG2, HCT-116, HeLa, and SK-OV-3 cancer cell lines | -6 hours hours | Crocetin and crocin |
| (78) | ↓Toxicity, ROS, oxidative stress, mitochondrial membrane potential loss, and Nrf2 translocation | in vitro/ cyclosporine A-induced toxicity in HEK-293 | 200, 400, and 600 μM/24 hours | Crocetin and crocetin-loaded lipid nanoparticles |
| (50) | Hepatoprotective effects ↑SOD, CAT, GPx, and Nrf2 ↓ROS |
in vivo /Liver ischemia-reperfusion injury in male Wistar rats | 200 mg/kg/7 days | Crocin |
| (51) | Hepatoprotective effects ↓Oxidative stress, and ROS ↑Nrf2, HO-1, and NQO1 |
in vivo /ATO-induced hepatic injury in rats | 25 or 50 mg/kg/7 days | Crocin |
| (52) | ↑Tissue blood flow, rate of survival, hemodynamic parameters, liver function, Nrf2, HO-1, SOD, GSH, and CAT ↓Oxidative stress and ROS |
in vivo /THS-induced hepatic injury Sprague-Dawley rats | 60 mg/kg/- | Crocin |
| (77) | ↓Liver injury and oxidative stress ↑Nrf2, SOD, CAT, and GPx |
in vivo /IR-induced hepatic injury in male Wistar rats | 200 mg/kg/7 days | Crocin |
| (54) | ↓Cardiac injury, ROS, and NF-κB ↑Nrf2, HO-1, NQO1, Bcl-2, SOD, CAT, and GPx |
in vivo /ATO-induced cardiac injury in male adult Sprague-Dawley rats | 40 mg/kg/day and 80 mg/kg/day/7 days | Crocin |
| (57) | ↓Cardioprotective ER stress, GRP78, CHOP, apoptosis, and miR-34a ↑Nrf2, HO-1, and Sirt1 |
in vivo /C57BL/6 mice undergoing ER stress and IR injury | 50 mg/kg/d for 7 days |
Crocin |
| (59) | ↓Malignancy, oxidative stress, inflammation, MDA, and c-JNK ↑TAA, BAX, Bcl-2, TRAIL, p53 expression, Nrf2, HO-1, Keap1, SOD, GPx, GST, and GSH |
in vivo /TAA-induced HCC in Sprague-Dawley rats | 200 mg/kg, IP/daily for 4 weeks | Crocin |
| (60) | ↓Development of adenocarcinoma and colitis, oxidative stress, inflammation, NF-κB, COX-2, iNOS, IL-1β, and TNF-α ↑Nrf2 expression |
in vivo /AOM and DSS-induced colonic adenocarcinoma | 0, 50, 100, and 200 ppm/15 weeks | Crocin |
| (63) | ↓Lung injury and oxidative stress ↑Nrf2, P21, HO-1, CAT, and SOD |
in vivo / MCT-induced PAH in Sprague-Dawley rats | 7.5, 15, and 30 mg/kg, intraperitoneal, 21 days | Crocin |
| (64) | ↓Lung damage, oxidative stress, inflammation, ROS, IL-6, and TNF-α ↑Nrf2, HO-1, PI3K, MAPK, PKC, GCLc, and GSH |
in vivo /Cigarette smoke-induced COPD in Sprague-Dawley rats | 50 mg/kg/2 months | Crocin |
| (65) | ↓Inflammation, oxidative stress, fibrosis, TLR4, IL-10, TNF-α, TGF-β1 ↑HO-1, and Nrf2 |
in vivo /BLM-induced pulmonary fibrosis in Sprague-Dawley rats | 20 mg/kg, orally/5 weeks | Crocin |
| (71) | Anti-ulcerogenic and colon-protective properties ↓Inflammation, oxidative stress, apoptosis, TNF-α, Ca2+, and lipid peroxidation ↑Nrf2, HO-1, and GSH |
in vivo /AA-induced UC in Sprague Dawley rats | 20 mg/kg/8 days | Crocin |
| (73) | ↓Hypoglycemic, hypolipidemic, and renal protective effects ↓Fasting blood glucose, hemoglobin A1, ROS, MDA, and NF-κB ↑SOD, GSH, CAT, Nrf2 |
in vivo /Old db/db mice | 50 mg/kg/8 weeks | Crocin |
| (2) | Pancreas protective effects ↓Inflammation, oxidative stress, amylase, lipase, MDA, IL-1β, IL-17, TNF-α, IL-6, and NF-κB ↑GSH and Nrf2 signaling pathway |
in vivo /Cerulein-induced AP in male Swiss albino mice | 30 mg/kg and 100 mg/kg/7 days | Crocin |
| (75) | ↓Blood pressure, urine proteins, and symptoms of gestational hypertension ↑Nrf2/HO-1 signaling pathway |
in vivo /L-NAME-induced gestational hypertension in rats | 50, 100, and 200 mg/kg/day | Crocin |
| (61) | ↓Invasion, migration, malignancy, TAZ, and YAP ↑Nrf2, Bcl-2/Bax ratio, and Caspase |
in vitro/Human gastric mucosa epithelial cell line GES-1 induced by MNNG | 0–100 μM/6 weeks | Crocin |
| (66) | ↓Oxidative stress, inflammation, lipid peroxidation, ROS, 4-HNE, and O2·- and ·OH ↑Nrf2 and GCL |
in vitro/Cigarette smoke-induced lung cellular toxicity in A549 cells | 500 μM/48 hours | Crocin |
| (74) | ↓Inflammation ↑HO-1, [Ca2+]i, Ca2+/calmodulin dependent protein kinase IV, Akt, and Nrf2 signaling pathway ↓iNOS and NF-κB |
in vitro/LPS- stimulated RAW 264.7 macrophages | 500 𝜇M/24 hours- | Crocin |
| (67) | ↓Neurotoxicity, Keap1, apoptosis, and oxidative stress ↑Nrf2 |
in vitro/Rotenone-induced neurotoxicity dopaminergic neurons | - | Safranal |
| (68) | ↓Neurotoxicity, oxidative stress, ROS, and cell apoptosis ↑Nrf2, GST, NQO1, GCLc, and HO-1 |
in vitro/Rotenone-induced PD in Sprague-Dawley rats | 10, 15, 20, and 50 μg/ml/7 days | Safranal |
| (76) | Anti-NLRP3 inflammasome properties ↓IL-6, TNF-α, NF-κB, and pro-IL-1β ↑Nrf2 signaling pathway |
in vitro/ATP and LPS primed stimulated J774A.1 cells | 6.25, 12.5, 25, 50 mg/kg/0.5 hours | Safranal |
| (55) | ↓Cardiac injury, Inflammation, ROS, MDA, NT, and GSK3b ↑Nrf2, HO-1, NQO1, MnSOD, GSH, NADPH, Akt, and ERK1/2 |
in vivo and in vitro/IR-induced injury in Wild-Type (WT) and ischemic myocardial tissue | 60 µg/kg bolus 15 min and 60 mg/kg/day/4 weeks | Saffron aqueous extract |
| (53) | ↓Liver injury and ROS ↑keap1, Nrf2, HO-1, SOD, GSH, and CAT |
in vitro/Rat liver cell line (BRL-3A) | 300 μg/ml/1 day | TFESP, TFESS, and TFEMS |