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While saffron has the potential for eye health, its effects on lens lesions remain understudied. This study aimed to investigate the effect of saffron on the lens changes in atherosclerotic-induced New Zealand white rabbits (NZWR). Thirty-five NZWRs were subjected to four to eight weeks of high-cholesterol diet to induce atherosclerosis, resulting in cataractous lens changes. The rabbits were categorised randomly into three groups: normal diet group, pre-treated group and treated group. The pre-treated group was divided into early atherosclerosis(HC4) and established atherosclerosis (HC8). The saffron-treated group was fed with the HCD diet followed by saffron treatment of 50mg\/kg\/day (TG450, TG840) and 100mg\/kg\/day (TG4100, TG8100) of saffron ethanolic extract (SEE) respectively. The normal diet group was given a normal diet over the 8 weeks. After completing the 16-week experimental protocol, the NZWR were euthanized, and their lenses were extracted for histopathological evaluation. The pre-treated group exhibited cataractous lens changes of grade 2, characterized by increased homogenisation, swollen lens fibers, and intracellular vacuolisation. Interestingly, these cataract changes showed a positive trend from grade 2 to grade 1 post-treatment with SEE. In the saffron-treated group, vacuoles and pinkish homogenised areas were reduced. Additionally, a uniform layer of anterior epithelium and decreased non-swollen lens fibers indicated significant cataract lesion improvement. The normal diet group displayed minimal to zero cataractous changes (Grade 0). HPLC analysis demonstrated the presence of crocin, crocetin, and picocrocin in the saffron ethanolic extract, with peak absorptions at 440nm (12.817min), 440nm (1.620min), and 254nm (6.553min) respectively. The phytochemical screening of saffron ethanolic extract was conducted and showed the presence of phytochemical compounds including saponins, flavonoids, tannins, and steroids. The positive effects on lenses in the TG groups could be due to crocin and crocetin, bioactive components of saffron, and its phytochemical compounds. This study highlights saffron\u2019s potential in managing cataract-induced conditions, emphasizing the importance of further research for its full therapeutic potential in cataract management.<\/jats:p>","DOI":"10.1371\/journal.pone.0315178","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T18:39:20Z","timestamp":1736879960000},"page":"e0315178","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Saffron\u2019s protective role against atherosclerosis-induced cataract progression in New Zealand white rabbits with phytochemical analysis of saffron\u2019s extract"],"prefix":"10.1371","volume":"20","author":[{"given":"Yasmin","family":"Mohd Zainal Abidin Shukri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman Nabilah","family":"Abd 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