Acetyl-11-Keto-Beta Boswellic Acid (AKBA) Protects Lens Epithelial Cells Against H2O2-Induced Oxidative Injury and Attenuates Cataract Progression by Activating Keap1/Nrf2/HO-1 Signaling

Abstract

Age-related cataract (ARC) is one of the leading blinding eye diseases worldwide. Chronic oxidative stress and the apoptosis of human lens epithelial cells (HLECs) have been suggested to be the mechanism underlying cataract formation. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpene with antioxidative and antiapoptotic effects. In this study, we investigated the potential effects of AKBA on oxidative-induced HLECs injury and cataract formation. H2O2 was used to simulate HLECs oxidative injury in vitro, and Na2SeO3 was applied to establish an in vivo cataract model. In our current study, a cell counting kit-8 (CCK-8) assay was performed to evaluate the effects of H2O2 and AKBA on cell viability in vitro. Intracellular reactive oxygen species (ROS) levels were measured with the ROS assay to verify the antioxidant capacity of AKBA. Apoptotic cells were detected and measured by TUNEL staining and flow cytometry, and quantitative real-time (qRT)-PCR and Western blotting were applied to examine the transcription and expression of apoptosis-related proteins. Furthermore, immunofluorescence staining was performed to locate factor-erythroid 2-related factor 2 (Nrf2), and the protein levels of Nrf2, kelch-like ECH-associated protein 1 (Keap1) and heme oxygenase-1 (HO-1) were determined by Western blotting. Finally, we observed the degree of lens opacity and performed hematoxylin-eosin (H&E) staining to assess the protective effect of AKBA on cataract formation in vivo. AKBA increased HLECs viability under H2O2 stimulation, decreased intracellular ROS levels and alleviated the cell apoptosis rate in vitro. AKBA significantly decreased the expression of caspase-3 and Bax and increased the content of Bcl-2. The results of immunofluorescence and immunohistochemical staining proved that the expression and nuclear translocation of Nrf2 were activated with AKBA treatment in vivo and in vitro. Moreover, computational docking results showed that AKBA could bind specifically to the predicted Keap1/Nrf2 binding sites. After AKBA activation, Nrf2 dissociates from the Nrf2/Keap1 complex, translocates into the nucleus, and subsequently promotes HO-1 expression. In addition, AKBA attenuated lens opacity in selenite-induced cataracts. Overall, these findings indicated that AKBA alleviated oxidative injury and cataract formation by activating the Keap1/Nrf2/HO-1 cascade. Therefore, our current study highlights that AKBA may serve as a promising treatment for ARC progression.

Acetyl‐11‐keto‐beta‐boswellic acid modulates macrophage polarization and Schwann cell migration to accelerate spinal cord injury repair in rats

“…Therefore, the overexpression of Nrf2/HO‐1 will promote the expression of IL‐10, thereby promoting the transition of macrophages to M2. 44 Existing studies have shown that AKBA can significantly promote the expression of Nrf2 and activate HO‐1, 21 , 45 but whether it can promote the transformation of macrophages is unknown. Our experimental results answered, not only verifying that AKBA can activate Nrf2/HO‐1, but also further proving that AKBA can increase the expression level of IL‐10 and promote the transformation of macrophages from M1 to M2.…”

“… 19 It is shown that AKBA can upregulate Nrf2, downregulate NF‐κB, reduce oxidative stress and inflammation. 20 , 21 It has been shown that AKBA can promote sciatic nerve injury and repair. 22 , 23 , 24 It has also been shown to reduce experimental autoimmune encephalomyelitis through Nrf2.…”

The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK

“…In addition, dietary supplementation with B. serrata gum powder was shown to prevent liver and pancreatic damage in STZ-treated rats by suppressing lipid peroxidation and stimulating GSH, SOD, and CAT [ 36 ]. In addition, it has been shown to prevent UV-mediated skin damage, ethidium bromide-induced multiple sclerosis, hydrogen peroxide-induced retinal damage, and amyloid-β-induced cognitive impairment and brain damage by upregulating/activating the Nrf2/HO2/antioxidant axis [ 92 , 93 , 94 ]. Moreover, in vitro, experimental, and clinical studies have confirmed the ability of IKAB and other extracts of B. serrata to ameliorate psoriasis, atherosclerosis, asthma, colitis, rheumatoid arthritis, and osteoclastogenesis by suppressing NF-κB and inflammatory cytokine production [ 95 , 96 , 97 , 98 ], a phenomenon reviewed by Ammon [ 34 ].…”

Fabrication of a 3D bioprinting model for posterior capsule opacification using GelMA and PLMA hydrogel-coated resin

“…The HLEC-SRA01/04 cells were cultured in DMEM (high glucose) (Gibco, USA) supplemented with 10% FBS (Gibco, USA), 100 mg/ml streptomycin and 100 units/ml penicillin. The cells were maintained at 37°C in a humidified atmosphere with 5% CO 2 , following a previously described protocol [ 23 ].…”