Table 1.

Saffron and its bioactive compounds with a variety of pharmacological effects.

Bioactive Compound	Pharmacological Effect	Health Benefits	References
Crocetin	(1)Antioxidant, anti-inflammatory, and immunomodulatory (2)Increases the mRNA expression of anti-inflammatory cytokines (TGF, IL-10, and IL-4) (3)Inhibits COX-2 and NO production in macrophages by modulating the crosstalk between the MEK1/JNK/NF-B/iNOS pathway and the Nrf2/HO-1 pathway (4)Inhibits platelet activity and thrombosis by partially inhibiting calcium elevation in stimulated platelets (5)Stimulates Treg and Th1 cell differentiation by reducing MCP-1 and IL-8 expression and inhibiting immune cell adhesion and infiltration (6)Regulates the Keap1/Nrf2 signaling pathway via inhibition of apoptosis (7)Reduces reactive oxygen species production and cell apoptosis in skin cells (8)Partially agonizes and selectively desensitizes the TRPA1 channel (9)Reports showed that it inhibits Escherichia coli cell growth by binding and inhibiting ATP synthase	(1)Cardioprotective/hepatoprotective (2)Reduces diabetic complications (3)Induces neurite growth and facilitates the recovery of motor and sensorimotor functions after spinal cord injury (4)Studies have reported it acts as an enhancer for learning memory and reduces neuropathic pain after spinal nerve transection in rats (5)Shows potential for antiaging, antihypertensive, and anticataract effects (6)Studies have shown neuroprotective effects in ocular diseases, such as age-related macular degeneration, glaucoma, and diabetic maculopathy, and Alzheimer’s and Parkinson’s diseases (7)Protects against UV-A-induced skin damage (8)Exerts analgesic properties (9)Effectively improves insulin sensitivity and related disorders in fructose-fed rats, suggesting its potential as a preventive strategy for insulin resistance-associated diseases	[127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152]
Crocin	(1)Higher solubility and safety, and enhanced inhibitory effects on tumor cell proliferation via inhibiting the angiogenesis-VEGF/VEGFR2 signaling pathway	(1)Potential in treating bone and cartilage diseases (2)Potential for managing diseases associated with abnormal blood vessel growth and inhibiting the growth of human cancer cells in vitro	[150,151,152,153,154,155]
Safranal	(1)Suppresses free radical production and increases antioxidant activity (2)Reduces cardiac injury markers (LDH and CK-MB) caused by sympathetic hyperactivation and decreased TNF-α l, PTGS2, MMP9, and pRELA levels in a model system (3)Potential as a preclinical candidate drug against NLRP3 inflammasome-triggered chronic inflammation by suppressing IL-1 release and preventing ASC oligomerization. (4)Increases the IFN-/IL-4 ratio (5)Reduces oxidative stress and inflammation in a high-fat diet and low-dose streptozotocin-induced type 2 diabetes rat model (6)Reduces inflammation and pain in mice with dextran-sulfate-sodium-induced colitis by suppressing nitric oxide production, iNOS, and COX-2	(1)Reduces diabetic complications (2)Protective effects on ischemic reperfusion injury (3)Cardioprotective (4)Potential therapeutic applications for asthma and allergic reactions (5)Suggests potential therapeutic effects in inflammatory diseases associated with Th1/Th2 imbalance (6)Shows gastro-protective effects against indomethacin-induced gastric ulcers, with similar effects to lansoprazole	[132,133,134,135,144,145,146,147,148,149,156,157,158,159]

Note: CCl4 (carbon tetrachloride); MSCs (mesenchymal stem cells); TGF (transforming growth factor-β); IL-4/10/1 (interleukin-4/10/1); COX-2 (cyclooxygenase-2); NO (nitric oxide); MEK1 OR MAP2K1/JNK/NF-B/iNOS Nrf2/HO-1 (MAP2K1—mitogen-activated protein kinase kinase 1; c-Jun N-terminal kinase; nuclear factor kappa-light-chain-enhancer of activated B cells; inducible nitric oxide synthase; nuclear factor erythroid 2-related factor 2; heme oxygenase-1); LDH (lactate dehydrogenase); CK-MB (creatine kinase-MB); TNF-α (tumor necrosis factor-alpha); NLRP3 (NOD-like receptor family pyrin domain-containing protein 3); ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)); OVA (ovalbumin); LTC4 (leukotriene C4); VEGF/VEGFR2 (vascular endothelial growth factor/vascular endothelial growth factor receptor 2); Treg (regulatory T cells); Th1/Th2 (T helper type 1/type 2 cells); IFN (interferon); Keap1 (Keap1 (Kelch-like ECH-associated protein 1); Nrf2 (nuclear factor erythroid 2-related factor 2); TRPA1 (transient receptor potential ankyrin 1); IBD (inflammatory bowel disease); and UC (ulcerative colitis).