Evaluating the Multifunctional Therapeutic Potential of Phycocyanin: Antidiabetic, Antioxidant, Anticancer and Antimicrobial Effects on Metabolic, Oxidative, and Histopathological Parameters in Dithizone-Induced Diabetic Rats

Dithizone, a heavy metal chelator, induces diabetes in animals to model human diabetes. This study evaluates the effects of a phycocyanin extract (PE) from Spirulina platensis on growth, blood indices, oxidative status, gut microbiota, and tissue histology in dithizone-challenged rats, while also assessing its antidiabetic, antioxidant, anticancer, antimicrobial, and antiviral properties against HSV-1 and influenza A (H1N1) viruses. PE is rich in active compounds, notably C-Phycocyanin (1.2 mg/g). The extract demonstrated robust antioxidant activity by scavenging 92% of DPPH radicals, inhibited breast cancer cell line growth by 81%, and suppressed pathogenic microbes. It also reduced α-glucosidase and α-amylase activity by 75% and 80%. Antiviral assays indicated dose-dependent inhibition of HSV-1 (65% reduction in plaque formation, IC50 = 42.5 μg/ mL) and H1N1 (58% viral load reduction, IC50 = 50.3 μg/mL), with suppression of viral entry, neuraminidase activity, and upregulation of antiviral genes (IFN-α and MX1). In vivo, 200 rats were divided into control, dithizone, PE-treated, and dithizone + PE groups for 30 days. PE treatment resulted in improved glucose control, lower HbA1c, enhanced insulin sensitivity, reduced malondialdehyde, increased glutathione, and favorable changes in gut bacteria. Gene expression of proinflammatory cytokines and precancerous markers (BCL-2, Nrf-2, OH, β-actin, IL-1β, TNF-α, BAX, and Casp-3) was significantly reduced. Histological examination showed improved pancreatic and hepatic structure, and overall growth performance and blood profiles were enhanced. Collectively, PE mitigates metabolic disturbances from dithizone and shows promise as an antiviral agent, supporting its potential in functional foods and nutraceuticals.