RESUMEN
The monoester alkaloids in Aconitum carmichaelii, including benzoylaconitine (BAC), benzoylmesaconine, and benzoylhypaconitine, were found to have anti-hypertensive effects in spontaneously hypertension rats (SHRs), of which BAC is the strongest. However, its antihypertensive target and underlying molecular mechanisms remain unclear. In this study, first, we screened the antihypertensive targets of BAC by using the CVDPlatform (www.cbligand.org/CVD) and found that ACE/ACE2 are the most possible targets. Then, we verified the effect of BAC on ACE/ACE2 by virtual docking, SPR, enzyme activity assay, and HUVECs cell experiment. We found that BAC could bind with ACE/ACE2, inhibit ACE activity and protein expression, and activate ACE2 enzyme activity. Using vascular function test in vitro, we found that BAC could target ACE/ACE2 to enhance endothelium-dependent vasorelaxation. In BAC-treated SHRs, the levels of ACE and AngII in serum were reduced while Ang (1-7) was increased significantly, and the expression of ACE was reduced, which suggested that BAC can inhibit ACE and activate ACE2 to inhibit AngI to AngII and promote AngII to Ang (1-7) to inhibit vasoconstriction and finally attenuate hypertension. Furthermore, the signaling pathways with regard to vasorelaxation and vascular inflammation were investigated. The results showed that BAC could significantly activate Akt/eNOS, increase NO production, and promote endothelial-related vasodilation; BAC could also reduce inflammatory factors TNF-α and IL6, inhibition of COX-2 expression, and IKB-α phosphorylation to reduce vascular inflammation in SHRs. In brief, BAC targets ACE/ACE2 to enhance endothelium-dependent vasorelaxation and reduce vascular inflammation to attenuate hypertension as a potential modulator of the renin-angiotensin system.
RESUMEN
The title compound, C(22)H(32)O(7), a natural ent-kaurane diterpenoid also referred to as Maoyecrystal F, was obtained from the medicinal plant Isodon nervosa. There are four rings with the expected cis and trans junctions. Cyclohexane ring A adopts a chair conformation, rings B and C adopt boat conformations, while the five-membered ring has an envelope conformation. The mol-ecules stack along the a axis in the crystal and are linked together by inter-molecular O-Hâ¯O hydrogen bonds.
RESUMEN
The title compound, C(20)H(30)O(6), a natural ent-kaurane diterpenoid, named nervosanin B, was obtained from the medicinal plant Isodon serra. It is composed of four rings with the expected trans and cis junctions. One of the six-membered rings is in a chair conformation, the other two are in boat conformations and the five-membered ring adopts an evenlope conformation. The mol-ecules stack along the a axis and are linked together by inter-molecular O-Hâ¯O hydrogen bonds. Two intramolecular O-Hâ¯O interactions also occur.
RESUMEN
The title compound, C(24)H(34)O(8), a natural ent-kaurane diterpenoid, is composed of four rings with the expected cis and trans junctions. The crystal structure is stabilized by inter-molecular O-Hâ¯O hydrogen bonds. In addition, an intra-molecular O-Hâ¯O hydrogen bond occurs.
RESUMEN
The title compound, C(21)H(30)O(6), a natural ent-kaurane diterpenoid, was obtained from the medicinal plant Isodon serra. The five rings in the mol-ecule exhibit the expected cis and trans junctions. The three six-membered rings adopt chair, twist-boat and boat conformations, while two five-membered rings adopt envelope conformations. There are two mol-ecules in the asymmetric unit, related by a non-crystallographic twofold screw axis; the main difference is in the different degrees of distortion of ring B. In the crystal, the mol-ecules are linked by inter-molecular O-Hâ¯O hydrogen bonds, forming chains along the b axis.
RESUMEN
The title compound, C(26)H(34)O(9), a natural ent-kaurane diterpenoid, is composed of four rings with the expected cis and trans junctions. In the crystal structure, the mol-ecules stack along the a axis and are linked together by inter-molecular O-Hâ¯O hydrogen bonds.
RESUMEN
The title compound, enmenol, C(20)H(30)O(6), a natural ent-kaurane diterpenoid, comprises five fused rings, four of which are six-membered. Cyclo-hexane ring A adopts a chair conformation, rings B and C adopt boat conformations, while ring D has an envelope conformation, and two intramolecular O-Hâ¯O interactions occur. In the crystal, inter-molecular O-Hâ¯O hydrogen bonds generate a two dimensional network.