Dexmedetomidine is an α₂-adrenoceptor agonist and anesthetic. The present study was designed to characterize the receptor subtypes and the downstream mechanisms of the vascular effects of dexmedetomidine in small (mesenteric artery) and large (aorta) arteries ex vivo. Isometric tension was measured in Sprague-Dawley rat mesenteric and aortic rings (with or without endothelium). To study relaxations, cumulative concentrations of dexmedetomidine, 5-bromo-N-(2-imidazolin-2-yl)-6-quinoxalinamine, (UK14304), or clonidine were added to rings contracted with 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F_2α (U46619) in the presence or absence of indomethacin; N^ω-nitro-l-arginine methyl ester hydrochloride (l-NAME); 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole maleate (BRL44408); 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride (ARC239); l-657,743, (2S-trans)-1,3,4,5′,6,6′,7,12b-octahydro-1′,3′-dimethyl-spiro[2H-benzofuro[2,3-a]quinolizine-2,4′(1′H)-pyrimidin]-2′(3′H)-one hydrochloride hydrate (MK912); rauwolscine; prazosin; or pertussis toxin. To study contractions, dexmedetomidine was added to quiescent rings without endothelium or after incubation with l-NAME, rauwolscine, prazosin, indomethacin, or 3-[(6-amino-(4-chlorobenzensulfonyl)-2-methyl-5,6,7,8-tetrahydronaphth)-1-yl]propionic acid (S18886). Dexmedetomidine evoked relaxation at low concentrations (10 pM–30 nM) followed by contraction at higher concentrations (>30 nM) in the mesenteric artery. In the aorta, the relaxation was significantly smaller. The relaxation to dexmedetomidine depended on nitric oxide, endothelium, and G_i protein, and it was mediated by α_2A/D-adrenoceptors and possibly α_2B-adrenoceptors. The contraction was mediated mainly by α_2B- and α₁-adrenoceptors and involved the action of prostanoids. UK14304 and clonidine induced greater and smaller relaxations, respectively, than dexmedetomidine. In conclusion, depending on the concentration used and the presence of functional endothelium, dexmedetomidine may evoke both relaxation and contraction in isolated arteries. The vascular effects also vary depending on the blood vessel studied. Its vascular effect is different from that of clonidine and UK14304.

The use of medication is effective in managing metabolic syndrome (MetS), but side effects have led to increased attention on using nutraceuticals and supplements. Astaxanthin shows positive effects in reducing the risk of MetS, but results from individual studies are inconclusive. This systematic review summarizes the latest evidence of astaxanthin in adults with risk factors of MetS. A systematic search of English and Chinese randomized controlled trials in 14 electronic databases from inception to 30 June 2021 was performed. Two reviewers independently screened the titles and abstracts, and conducted full-text review, quality appraisal, and extraction of data. Risk of bias was assessed by PEDro. A total of 7 studies met the inclusion criteria with 321 participants. Six studies were rated to have excellent methodological quality, while the remaining one was rated at good. Results show marginal effects of astaxanthin on reduction in total cholesterol and systolic blood pressure, and a significant attenuating effect on low-density lipoprotein cholesterol. Further robust evidence is needed to examine the effects of astaxanthin in adults at risk of MetS.

Despite various therapeutic approaches, colorectal cancer is among the most fatal diseases globally. Hence, developing novel and more effective methods for colorectal cancer treatment is essential. Recently, reactive oxygen species (ROS)/JNK signaling pathway has been proposed as the potential target for the anticancer drug discovery. The present study investigated the anticancer effects of the bioactive xanthone garcinone E (GAR E) in mangosteen and explored its underlying mechanism of action. HT-29 and Caco-2 cancer cells were used as in vitro models to study the anticancer effect of GAR E. The findings demonstrated that GAR E inhibited colony formation and wound healing, whereas triggered the production of ROS, which induced mitochondrial dysfunction and apoptosis, causing cell cycle arrest at the Sub G1 phase. Additionally, GAR E treatment elevated the ratio of Bax/Bcl-2 and activated PARP, caspases 3 and 9, and JNK1/2. These GAR E-induced cytotoxic activities and expression of signaling proteins were reversed by the antioxidant N-acetyl-L-cysteine and JNK inhibitor SP600125, indicating the involvement of ROS/JNK signaling pathways. In vivo experiments using an HT-29 xenograft nude mouse model also demonstrated the antitumor effect of GAR E. In conclusion, our findings showed that GAR E might be potentially effective in treating colorectal cancer and provided insights into the development of xanthones as novel chemotherapeutic agents.

Background: The α₂-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations.l-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role ofl-arginine in modulating the overall vascular response to dexmedetomidine.Methods: Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N^ω-nitro-l-arginine methyl ester hydrochloride (l-NAME; nitric oxide synthase inhibitor), prazosin (α₁-adrenergic antagonist), rauwolscine (α₂-adrenergic antagonist),l-arginine, (S)-(2-boronethyl)-l-cysteine hydrochloride (arginase inhibitor), N^G-hydroxy-l-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed.Results: Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated withl-NAME (E_max50 ± 4%) or after endothelium-removal (E_max74 ± 5%; N = 7 to 12). Exogenousl-arginine augmented the dexmedetomidine-induced contractions in the presence ofl-NAME (E_max75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-l-cysteine hydrochloride (E_max16 ± 4%) and N^G-hydroxy-l-arginine (E_max18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect asl-arginine. Immunoassay measurements demonstrated an upregulation of arginase I byl-arginine treatment in the presence ofl-NAME (N = 4).Conclusions: These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of dexmedetomidine byl-arginine depends on arginase activity and the production of urea and ornithine.