TABLE 2.

Brief summary of studies on crocin and RA.

Reference	Models/Crocin doses	Main results	Conclusion
Hemshekhar et al. (2012)	Rats/10–20 mg/kg daily for 15 days	Decreased MMP-13, MMP-3, MMP-9, HAases, TNF-a, IL-1b, NF-κB, IL-6, COX-2, PGE2 and ROS.	Reduced RA symptoms by regulating oxidative stress, inflammation, and the levels of exoglycosidases, cathepsin-D and tartrate-resistant acid phosphatase
		Impression GSH, SOD, CAT, and GST. Inhibited levels of the exoglycosidases cathepsin-D, and tartrate-resistant acid phosphatase
Rathore et al. (2015)	Mice/25, 50 and 100 mg/kg for 47 days	Reduction in TNF-α and IL-1β levels, increase in SOD and GR activity in 50 and 100 mg/kg treatments	Reduced inflammation and oxidative stress in 50 and 100 mg/kg treatments
Hu et al. (2019)	Rats/160 mg/kg for 14 days	Decreased paw swelling and ankle diameters, joint, spleen, and thymus inflammation, and levels of TNF-α and TGF-β1	Reduced RA symptoms and complications by reducing inflammation
Liu et al. (2018)	Rats/40 mg/kg for 15 days	MMP-1, -3, and -13 protein expression levels were decreased and decreasing inflammatory cytokines similar to previous studies	Reduced RA by reducing inflammation
Li X et al. (2017)	Rats/6.25–25 mg/kg	Reduction in iNOS and decrease in inflammatory cytokines similar to previous studies	Crocin has positive effects on RA-induced rats
Li L et al. (2018)	Synoviocytes/500 µM (5,000 mg/ml)	Reduced TNF-α, IL-1β, IL-6, p-IκBα, p-IκB kinase α/β, and p65 expression	Crocin had anti-inflammatory and anti-arthritic effects in-vitro and in-vivo through NF-κB signaling
( Wang et al., 2020 )	Rats/50 and 100 mg/kg	Reduced pain-related cytokines and glial activation by affecting Wnt/β-catenin and the Wnt signaling pathway	Reduced neuropathic pain in RA-induced rats