Abstract
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.
Highlights
Hyperglycemia induces the formation and accumulation of advanced glycation end products (AGEs), and these products are present at high levels in the blood and tissue of diabetic patients [1,2].AGEs are accumulated at high levels in the tissues of patients with age-related diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, osteoporosis, and neurodegenerative diseases [3]
We evaluated the efficacy of inhibition of AGE formation with different combinations of the two herbs to obtain the best formulation
The regression equations for the five reference standards, together with the limit of detection (LOD) and limit of quantification (LOQ)
Summary
Hyperglycemia induces the formation and accumulation of advanced glycation end products (AGEs), and these products are present at high levels in the blood and tissue of diabetic patients [1,2]. AGEs are accumulated at high levels in the tissues of patients with age-related diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, osteoporosis, and neurodegenerative diseases [3]. AGEs are formed by oxidative and non-oxidative reactions, and they affect the biochemical and physical properties of proteins in tissues. AGE formation is triggered by high glucose-induced oxidative stress and fluorescent protein cross-linking [4]. Elevated AGE levels increase the breakdown of the blood-retinal barrier (BRB), adhesion of leukocytes, and retinal vascular injury, leading to serious impairment of vision. The BRB consists of Antioxidants 2020, 9, 627; doi:10.3390/antiox9070627 www.mdpi.com/journal/antioxidants
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