These findings demonstrate that α-BA decreases oxidative stress and that the Nrf2/HO-1 pathway might play a role in the gastroprotective action of α-BA in ethanol-induced gastric injury in rats.

Acetyl‐11‐keto‐β‐boswellic acid (AKBA), an active triterpenoid compound from the extract of Boswellia serrate, has been reported previously in our group to alleviate fibrosis in vascular remodelling. This study aimed to elucidate the in vivo and in vitro efficacy and mechanism of AKBA in renal interstitial fibrosis. The experimental renal fibrosis was produced in C57BL/6 mice via unilateral ureteral obstruction (UUO). Hypoxia‐induced HK‐2 cells were used to imitate the pathological process of renal fibrosis in vitro. Results showed that the treatment of AKBA significantly alleviated UUO‐induced impairment of renal function and improved the renal fibrosis by decreasing the expression of TGF‐β1, α‐SMA, collagen I and collagen IV in UUO kidneys. In hypoxia‐induced HK‐2 cells, AKBA displayed remarkable cell protective effects and anti‐fibrotic properties by increasing the cell viability, decreasing the lactate dehydrogenase (LDH) release and inhibiting fibrotic factor expression. Moreover, in obstructed kidneys and HK‐2 cells, AKBA markedly down‐regulated the expression of TGFβ‐RI, TGFβ‐RII, phosphorylated‐Smad2/3 (p‐Smad2/3) and Smad4 in a dose‐dependent fashion while up‐regulated the expression of Klotho and Smad7 in the same manner. In addition, the effects of AKBA on the Klotho/TGF‐β/Smad signalling were reversed by transfecting with siRNA‐Klotho in HK‐2 cells. In conclusion, our findings provide evidence that AKBA can effectively protect kidney against interstitial fibrosis, and this renoprotective effect involves the Klotho/TGF‐β/Smad signalling pathway. Therefore, AKBA could be considered as a promising candidate drug for renal interstitial fibrosis.

Vascular remodeling is an important complication of hypertension with oxidative stress-related profibrotic pathways involved. The transforming growth factor β1 (TGF-β1) has been shown to be a potential target of vasoprotection, and has multiple roles in vascular remodeling. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is one of the active principles of Boswellic acids, and shows antioxidant activity in many diseases. The study is to determine effects of AKBA on systemic oxidative stress of hypertension and vascular remodeling. In the experiments, spontaneously hypertensive rats (SHR) were used. And in vitro, fibroblast was pretreated with AKBA before Ang II stimuli. In the results, treatment of AKBA markedly reduced oxidative stress, and decreased vascular remodeling by restoring vascular wall parameters and improving vascular reactivity. AKBA dramatically reduced TGF-β1 and Smad3 expression, as shown in immunofluorescence and immunohistochemistry. In cultured fibroblast, AKBA decreased intracellular ROS levels. Cell viability and proliferation, as well as migration were inhibited by AKBA. Additionally, treatment of AKBA significantly decreased TGF-β1 secretion in culture supernatant. Expression of TGF-β1, Smad3, P-Smad3 and Smad7 were also decreased by AKBA in fibroblast. In conclusion, AKBA is able to attenuate oxidative stress and profibrotic mechanisms, and improve vascular remodeling in hypertension through TGF-β1/Smad3 pathway.