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Fulltext Correlation between Chemical Composition of Curcuma domestica and Curcuma xanthorrhiza and Their Antioxidant Effect on Human Low-Density Lipoprotein Oxidation

Jantan I, Saputri FC, Qaisar MN, Buang F

Evid Based Complement Alternat Med, 2012;2012:438356.
PMID: 23243446 DOI: 10.1155/2012/438356

The antioxidant activity of the curcuminoids of Curcuma domestica L. and C. xanthorrhiza Roxb. and eight compounds which are prevalent constituents of their rhizome oils were investigated in an effort to correlate human low-density lipoprotein (LDL) antioxidant activity with the effect of the herbs and their components. The antioxidant activity was examined using thiobarbituric acid reactive substances (TBARSs) assay with human LDL as the oxidation substrate. The methanol extracts and rhizome oils of C. xanthorrhiza and C. domestica showed strong inhibitory activity on copper-mediated oxidation of LDL. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin, isolated from the methanol extracts of both plants, exhibited stronger activity than probucol (IC(50) value 0.57 μmol/L) as reference, with IC(50) values ranging from 0.15 to 0.33 μmol/L. Xanthorrhizol, the most abundant component (31.9%) of the oil of C. xanthorrhiza, showed relatively strong activity with an IC(50) value of 1.93 μmol/L. The major components of C. domestica, ar-turmerone (45.8%) and zerumbone (3.5%), exhibited IC(50) values of 10.18 and 24.90 μmol/L, respectively. The high levels of curcuminoids in the methanol extracts and xanthorrhizol, ar-turmerone and zerumbone in the oils, and in combination with the minor components were responsible for the high LDL antioxidant activity of the herbs.

Matched MeSH terms: Probucol
Probucol modulates iron nitrilotriacetate (Fe-NTA)-dependent renal carcinogenesis and hyperproliferative response: diminution of oxidative stress

Iqbal M, Okazaki Y, Okada S

Mol Cell Biochem, 2007 Oct;304(1-2):61-9.
PMID: 17487455

Probucol is a clinically used cholesterol-lowering drug, with pronounced antioxidant properties. We have reported previously, that dietary supplementation of probucol enhances NAD(P)H:quinone reductase (Iqbal M, Okada S (2003) Pharmacol Toxicol 93:259-263) and inhibits Fe-NTA induced lipid peroxidation and DNA damage in vitro (Iqbal M, Sharma SD, Oakada (2004) Redox Rep 9:167-172). Further to this, in the present study, we evaluated the modulatory effect of probucol on iron nitrilotriacetae (Fe-NTA) dependent renal carcinogenesis, hyperproliferative response and oxidative stress. In Fe-NTA alone treated group, a 20% renal cell tumor incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA promoted animals, the percentage tumor incidence was increased to 70% as compared with untreated controls. No tumor incidence was recorded in DEN-initiated, nonpromoted group. Diet supplemented with 1.0% probucol fed prior to, during and after Fe-NTA treatment in DEN-initiated animals afforded >65% protection in renal cell tumor incidence. Probucol fed diet pretreatment also resulted a significant and dose dependent inhibition of Fe-NTA induced renal ornithine decarboxylase (ODC) activity. In oxidative stress studies, Fe-NTA alone treatment enhanced lipid peroxidation, accompanied by a decrease in the level of GSH, activities of antioxidants and phase II metabolizing enzymes in kidney concomitant with histolopathological changes. These changes were significantly and dose-dependently alleviated by probucol fed diet. From this data, it can be concluded that probucol can modulates toxic and tumor promoting effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant induced tissue injury and carcinogenesis, in addition to being a cholesterol lowering and anti-atherogenic drug.

Matched MeSH terms: Probucol/pharmacology*; Probucol/therapeutic use
An investigation of the antiplatelet effects of succinobucol (AGI-1067)

Houston SA, Ugusman A, Gnanadesikan S, Kennedy S

Platelets, 2017 May;28(3):295-300.
PMID: 27681689 DOI: 10.1080/09537104.2016.1218456

Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet-platelet and platelet-vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10-5-10-4M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress.

Matched MeSH terms: Probucol/analogs & derivatives*; Probucol/pharmacology
Propensity score matched all comers population treated with ultra-thin strut bare metal and sirolimus-probucol coated drug-eluting stents of identical stent architecture

Krackhardt F, Rosli MA, Leschke M, Schneider A, Sperling C, Heang TM, et al.

Catheter Cardiovasc Interv, 2018 06;91(7):1221-1228.
PMID: 28944613 DOI: 10.1002/ccd.27306

OBJECTIVE: The objective of this study was to compare the safety and efficacy of a polymer-free sirolimus coated, ultrathin strut drug eluting stent (PF-SES) to its uncoated bare-metal stent (BMS) platform of identical stent architecture.
BACKGROUND: Recently published randomized trials comparing BMS to DES with a focus on shortened dual-antiplatelet therapy reported incidences of stent thrombosis (ST) and bleeding complications (LEADERS FREE) in favor of drug eluting stents (DES).
METHODS: Data of previously published large-sale, international, single-armed, multicenter, observational studies of ultra-thin PF-SES, and BMS were propensity score (PS) matched for selected lesion morphological and cardiovascular risk factors to compare target lesion revascularization (TLR), myocardial infarction, cardiac death, major adverse cardiac events (MACE), bleeding complications and ST rates. Primary endpoint in both studies was TLR at 9 months.
RESULTS: At 9 months the rates of TLR was significantly lower in the PF-SES group as compared with patients treated with the BMS analogue of identical stent design (1.4% vs. 4.6%, P = 0.005). Likewise the 9-month MACE rates were lower in the PF-SES group (3.2% vs. 8.7%, P = 0.001) whereas there were no differences in the accumulated ST rates (0.5% vs. 1.5%, P = 0.109). Overall accumulated bleeding incidences (BARC 1-5) were not significantly different between PF-SES and BMS patients (1.8% vs. 2.7%, p = 0.388).
CONCLUSIONS: PF-SES are superior over analogue BMS of identical stent architecture in daily clinical routine with lower rates of TLR and MACE in a PS-matched, unselected patient population without differences in accumulated ST rates and bleeding frequencies given the currently favored postprocedural comedication (ClinicalTrials.gov Identifier NCT02629575).

Matched MeSH terms: Probucol/administration & dosage*; Probucol/adverse effects