Acetyl-11-Keto-β-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-β1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats.

Peijin Shang,Yuwen Li,Zhihui Zhu,Fei Mu,Xiaohu Zhai,Aidong Wen,Wenxing Liu,Lingfei Liang,Yi Ding,Yikai Zhang,Tianlong Liu

doi:10.1038/srep39809

Abstract

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.

Highlights

Acetyl-11-Keto-β-Boswellic Acid (AKBA) is a pentacyclic triterpene compound from plant Boswellia serrate gum resins[9], one of the most potent active principles
Biochemical detection showed that spontaneously hypertensive rats (SHR) was challenged with higher vascular contractility that manifested with increased angiotensin II (Ang II) and decreased nitric oxide (NO) levels
The protective effect on vascular wall has been highlighted by down-regulating expression of profirotic factor TGF-β133, which could be activated by overexpressed free oxygen radicals

Summary

Introduction

Acetyl-11-Keto-β-Boswellic Acid (AKBA) is a pentacyclic triterpene compound from plant Boswellia serrate gum resins[9], one of the most potent active principles. It is revealed that boswellic acids markedly decrease transforming growth factor-β1 (TGF-β1) and TGF-β1-induced pulmonary fibrosis[15], and notably prevent colonic fibrosis through TGF-β1/Smad[3] pathway[16]. Asiatic acid can alleviate cardiovascular remodeling due to its antioxidant effect[18], and inhibit cardiac hypertrophy by blocking TGF-β1 pathway[19]. TGF-β1 is one of key growth factors in vascular remodeling and formation of hypertension[21,22] It phosphorylates subordinate receptors and transducers, especially canonical Smads pathway, and induces hundreds of genes expression[23]. The underlying mechanism of vasoprotection probably is associated with its good antioxidant effect, and inhibits over-activation of TGF-β1/Smad[3] pathway. Vascular remodeling and profibrotic processes in vivo and in vitro are assessed

Methods

Results

Conclusion