Characterization of Emodin as a Therapeutic Agent for Diabetic Cataract

Abstract

Aldose reductase (AR) in the lens plays an important role in the pathogenesis of diabetic cataract (DC) by contributing to osmotic and oxidative stress associated with accelerated glucose metabolism through the polyol pathway. Therefore, inhibition of AR in the lens may hold the key to prevent DC formation. Emodin, a bioactive compound isolated from plants, has been implicated as a therapy for diabetes. However, its inhibitory activity against AR remains unclear. Our results showed that emodin has good selectively inhibitory activity against AR (IC50 = 2.69 ± 0.90 μM) but not other aldo-keto reductases and is stable at 37 °C for at least 7 days. Enzyme kinetic studies demonstrated an uncompetitive inhibition against AR with a corresponding inhibition constant of 2.113 ± 0.095 μM. In in vivo studies, oral administration of emodin reduced the incidence and severity of morphological markers of cataract in lenses of AR transgenic mice. Computational modeling of the AR–NADP–emodin ternary complex indicated that the 3-hydroxy group of emodin plays an essential role by interacting with Ser302 through hydrogen bonding in the specificity pocket of AR. All the findings above provide encouraging evidence for emodin as a potential therapeutic agent to prevent cataract in diabetic patients.

Antidiabetic potential of anthraquinones: A review

“…Jang et al () have reported that emodin from S. tora L. inhibited aldose reductase activity and advanced glycation end products formation with IC 50 values of 15.9 and 118 μM, respectively. To support the in vitro data, oral administration of emodin prevented the occurrence and severity of cataract in lenses of aldose reductase transgenic mice (Chang et al, ). This study showed the potential role of emodin in attenuating diabetes‐induced complications and cataract formation and could be responsible for the potent amelioration of diabetes‐induced oxidative damages of S. tora (Kumar, Singh, Mahdi, Mahdi, & Singh, ).…”

Cataract as Early Ocular Complication in Children and Adolescents with Type 1 Diabetes Mellitus

“…Previously, studies have been published describing various aldose reductase inhibitors that clearly prevent the onset of cataract on induced diabetic mouse model, but unfortunately most of them have numerous side effects [ 22 ]. Recently, research focus has been shifted to unrefined nutrients extracted from plants, teas, and fruits, which inhibits aldose reductase [ 22 , 51 ]. Other possible preventive supplements are also described in the literature including nutritional antioxidants such as pyruvates and vitamins C and E, but further studies are needed to fully clarify their role [ 52 ].…”

Phytobioactive compound-based nanodelivery systems for the treatment of type 2 diabetes mellitus – current status

“…However, due to the high first pass metabolism and greater hydrophobicity of emodin, it cannot be efficiently delivered through oral means, limiting the bioavailability and bioaccessibility of the compound. [163][164][165][166][167][168][169] A novel delivery approach was carried out using various delivery technologies, including nanoemulsions and nanotransfers, and some showed efficient delivery of emodin through oral means, which in turn enhances its efficacy. Recently, emodin-loaded magnesium hollow silicate nanocarriers were studied for their efficacy in treating angiogenesis associated with diabetic retinopathy.…”