Crocin and Nano-Crocin Mitigate Paraquat Hepatotoxicity by Modulating Expression of Genes Involved in Oxidative Stress and Inflammation
Authors: Khaksari Zahra , Mehri Freshteh , Abdolvahab Mohadeseh Haji , Manavi Mohammad Amin , Nasab Mohammad Hosein Fathian , Karbasi Ashkan , Baeeri Maryam , Ranjbar Akram 
Published: February 2025

Introduction:
Crocin, a natural compound found in saffron, has shown promising potential
as an anti-inflammatory and antioxidant agent. Paraquat is a widely used herbicide known to
cause severe oxidative stress and inflammation in the liver, leading to significant tissue damage.
This study explores the potential of crocin and its nanoformulation for mitigating paraquat-induced
liver damage associated with inflammation and oxidative stress.

Materials and Methods:
The experimental design included 30 male Wistar rats divided into a control
group, a paraquat group (5 mg/kg/day for 1 week, i.p.), and four treatment groups: crocin (20
mg/kg/day for 1 week, i.p.), nano-crocin (20 mg/kg/day for 1 week, i.p.), crocin+paraquat, and
nano-crocin+paraquat. The levels of TNF-α, IL-1β, and NF-κB mRNA, reactive oxygen species
(ROS), lipid peroxidation (LPO) generation, thiol level, and superoxide dismutase (SOD) activity
were assessed.

Results:
According to the results, the TNF-α, IL-1β, and NF-κB mRNA levels, as well as LPO and
ROS generation increased following paraquat administration. Furthermore, both treatment groups
showed significantly lower levels compared to the paraquat group (p<0.0001), with the nano-crocin
group showing the most significant reduction (p<0.0001). On the other hand, reduced thiol level and
SOD activity in the paraquat group were significantly attenuated by crocin and nano-crocin administration
(p<0.0001). Notably, nano-crocin exhibited superior protective effects, with a greater reduction
in inflammatory markers and oxidative stress indicators compared to crocin (p<0.01).

Discussion:
This study provides strong evidence that nano-crocin offers superior hepatoprotective
effects over crocin in mitigating paraquat-induced liver injury by reducing oxidative stress and inflammation.
The results suggest that nano-crocin could be a promising candidate for the development
of novel antioxidant therapies targeting liver diseases characterized by oxidative stress. The
study further elucidates the underlying mechanisms of action, highlighting the role of nano-crocin in
modulating inflammatory pathways and enhancing antioxidant defenses, which may be attributed to
its improved bioavailability and targeted delivery. Future studies should focus on the long-term safety
and efficacy of nano-crocin, as well as exploring its potential applications in other models of liver
injury and systemic oxidative stress-related diseases.

Conclusion:
In conclusion, nano-crocin treatment exerted more protective effects than crocin on the
liver against inflammation and oxidative stress induced by paraquat. These findings suggest that
nano-crocin could serve as a promising therapeutic candidate for the management of liver diseases
characterized by oxidative stress and inflammation. Future studies should focus on exploring the
long-term safety and efficacy of nano-crocin, as well as its potential applications in other models of
liver injury and related oxidative stress disorders.