ABSTRACT
Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.
ABSTRACT
Diabetic retinopathy is one of the serious microvascular diseases caused by diabetes. It is the leading cause of visual impairment among workers over 40 years old in developed countries. At present, western medicine methods for treating diabetic retinopathy include pan-retinal photocoagulation, vitrectomy, and intravitreal injection of anti-vascular endothelial growth factor and other methods. Traditional Chinese medicine treatment of diabetic retinopathy is mainly to treat patients using oral Chinese herb preparation based on syndrome differentiation and using certain external traditional Chinese medicine methods, such as auricular point therapy. This paper investigates the research progress of diabetic retinopathy treatment with traditional Chinese and western medicine and provides novel ideas for treating diabetic retinopathy with traditional Chinese combined with western medicine.