The herbal combination cpa4‐1 inhibits changes in retinal capillaries and reduction of retinal occludin in db/db mice

Increased formation of advanced glycation end products (AGEs) plays an important role in the development of diabetic retinopathy (DR) via blood‐retinal barrier (BRB) dysfunction, and reduction of AGEs has been suggested as a therapeutic target for DR. In this study, we examined whether CPA4‐1, a herbal combination of Cinnamomi Ramulus and Paeoniae Radix, inhibits AGE formation. CPA4‐1 and fenofibrate were tested to ameliorate changes in retinal capillaries and retinal occludin expression in db/db mice, a mouse model of obesity‐induced type 2 diabetes. CPA4‐ 1 (100 mg/kg) or fenofibrate (100 mg/kg) were orally administered once a day for 12 weeks. CPA4‐ 1 ( the half maximal inhibitory concentration, IC₅₀ = 6.84 ± 0.08 μg/mL) showed approximately 11.44‐ fold higher inhibitory effect on AGE formation than that of aminoguanidine (AG, the inhibitor of AGEs, IC₅₀ = 78.28 ± 4.24 μg/mL), as well as breaking effect on AGE‐bovine serum albumin crosslinking with collagen (IC₅₀ = 1.30 ± 0.37 μg/mL). CPA4‐1 treatment ameliorated BRB leakage and tended to increase retinal occludin expression in db/db mice. CPA4‐1 or fenofibrate treatment significantly reduced retinal acellular capillary formation in db/db mice. These findings suggested the potential of CPA4‐1 as a therapeutic supplement for protection against retinal vascular permeability diseases.