Pham Thi Hoa, Jin Sun Woo, Lee Gi Ho, Park Jin Song, Kim Ji Yeon, Thai Tuyet Ngan, Han Eun Hee, Jeong Hye Gwang
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
Molecular Microbiology Lab, Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam.
J Agric Food Chem. 2020 Mar 18;68(11):3474-3484. doi: 10.1021/acs.jafc.9b07909. Epub 2020 Mar 4.
Sesamin, the most abundant lignan in sesame seed oil, has many biological activities. However, the underlying molecular mechanisms behind the regulatory effects of sesamin on endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation in endothelial cells (ECs) remain unclear. Sesamin induced the intracellular level of NO and eNOS phosphorylation in ECs in a concentration- and time-dependent manner. Additionally, sesamin induced levels of intracellular calcium, leading to the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) at Thr286, calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) at Ser511, protein kinase A (PKA) at Thr197, Akt at Ser473, and AMP-activated protein kinase (AMPK) at Thr172. In particular, blocking of the transient receptor potential vanilloid type 1 (TRPV1) channel by capsazepine (TRPV1 antagonist), as well as TRPV1 knockdown via TRPV1 silencing RNA, abrogated sesamin-induced PKA, Akt, AMPK, CaMKII, CaMKKβ, and eNOS phosphorylation and NO level in ECs. Furthermore, sesamin inhibited TNF-α-induced NF-κB translocation, intercellular adhesion molecule-1 expression, and monocyte adhesion. Sesamin triggered eNOS activity and NO production via activation of TRPV1-calcium signaling, which involved the phosphorylation of PKA, CaMKII, CaMKKβ, Akt, and AMPK. Sesamin may be useful for treating or preventing the endothelial dysfunction correlated with cardiovascular diseases.
芝麻素是芝麻油中含量最丰富的木脂素，具有多种生物活性。然而，芝麻素对内皮细胞（ECs）中内皮型一氧化氮合酶（eNOS）活性和一氧化氮（NO）生成的调节作用背后的潜在分子机制仍不清楚。芝麻素以浓度和时间依赖性方式诱导ECs中NO的细胞内水平和eNOS磷酸化。此外，芝麻素诱导细胞内钙水平升高，导致钙调蛋白依赖性蛋白激酶II（CaMKII）在Thr286、钙/钙调蛋白依赖性蛋白激酶激酶β（CaMKKβ）在Ser511、蛋白激酶A（PKA）在Thr197、Akt在Ser473以及AMP激活的蛋白激酶（AMPK）在Thr172处发生磷酸化。特别地，辣椒素（TRPV1拮抗剂）阻断瞬时受体电位香草酸受体1（TRPV1）通道以及通过TRPV1沉默RNA敲低TRPV1，均可消除芝麻素诱导的ECs中PKA、Akt、AMPK、CaMKII、CaMKKβ和eNOS磷酸化以及NO水平。此外，芝麻素抑制肿瘤坏死因子-α（TNF-α）诱导的核因子κB（NF-κB）易位、细胞间黏附分子-1表达和单核细胞黏附。芝麻素通过激活TRPV1-钙信号传导触发eNOS活性和NO生成，这涉及PKA、CaMKII、CaMKKβ、Akt和AMPK的磷酸化。芝麻素可能对治疗或预防与心血管疾病相关的内皮功能障碍有用。
