Abstract:A new skeleton of diterpenoid, 1,2,3,4,4α,9,10,10α-octahydro-(4α-hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4αR,9R,10αS)-2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (2-5), were isolated from Salvia plebeia R. Br. Their structures were determined on the basis of spectral analysis. In the bioactivity tests, compounds 1, 2 and 5 showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with IC50 values of 20.0-29.6 µM. In addition, these three compounds had significant inhibitory effects on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-induced macrophages. Compounds 1-3 inhibited nitric oxide (NO) production in LPS-induced macrophages with IC50 values of 18.0-23.6 µM. These results showed that compounds 1, 2 had significant antioxidant and anti-inflammatory activities and might provide basis for the treatment of diseases associated with oxidative lesions and inflammation.
Palmitic acid (PA)-induced vascular endothelial inflammation plays a pivotal role in the occurrence and development of vascular diseases. The present study was conducted to examine the effect of homoplantaginin, a main flavonoid from a traditional Chinese medicine Salvia plebeia R. Br., on PA-treated human umbilical vein endothelial cells inflammation and the underlying molecular mechanism. Firstly, we found that homoplantaginin (0.1, 1, 10 μM) dose-dependently reduced expression of toll-like receptor-4 evoked by PA (100 μM). The inhibitory effect of homoplantaginin was further confirmed under lipopolysaccharide challenge. In addition, downstream adapted proteins including myeloid differentiation primary response gene 88, toll/interleukin-1 receptor-domain containing adaptor-inducing interferon-β and tumor necrosis factors receptor associated factor-6 were successfully inhibited by homoplantaginin under PA treatment. Also, we found that homoplantaginin tightly controlled PA-induced reactive oxygen species to prevent nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome activation by suppressing reactive oxygen species-sensitive thioredoxin-interacting protein, NLRP3, and caspase-1. Meanwhile, protein and mRNA levels of inflammatory mediators (interleukin-1β, intercellular cell adhesion molecule-1, and monocyte chemotactic protein-1) were decreased by homoplantaginin. Furthermore, homoplantaginin restored PA-impaired nitric oxide generation. Taken together, these results indicated that homoplantaginin protected endothelial cells from ameliorating PA-induced endothelial inflammation via suppressing toll-like receptor-4 and NLRP3 pathways, and restoring nitric oxide generation, suggesting it may be a potential candidate for further development in the prevention and treatment of vascular diseases.
Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V–FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.
A new triterpene saponin, 3β,16β,23α,28β,30β-pentahydroxyl-olean-11,13(18)-dien-3β-yl-[β-D-glucopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→3)]-β-D-fucopyranoside, was named Clinoposaponin D (1), together with six known triterpene saponins, buddlejasaponin IVb (2), buddlejasaponin IVa (3), buddlejasaponin IV (4), clinopodisides D (5), 11α,16β,23,28-Tetrahydroxyolean-12-en-3β-yl-[β-D-glucopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→3)]-β-D-fucopyranoside (6) and prosaikogenin A (7), and two known triterpenes, saikogenin A (8) and saikogenin F (9) were isolated from Clinopodium chinense (Benth.) O. Kuntze. Their structures were elucidated on the basis of 1D, 2D NMR and MS analysis. Meanwhile, the effects of all compounds on rabbit platelet aggregation and thrombin time (TT) were investigated in vitro. Compounds 4 and 7 had significant promoting effects on platelet aggregation with EC50 value at 53.4 and 12.2 μM, respectively. In addition, the highest concentration (200 μM) of compounds 2 and 9 shortened TT by 20.6 and 25.1%, respectively.
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