The neuroprotective potential of turmeric rhizome and bitter melon on aspartame-induced spatial memory impairment in rats.

Aspartame is widely used artificial sweetener. However, chronic exposure to aspartame led to spatial memory impairment and elevated oxidative stress in the brain. Extract of turmeric rhizome (Curcuma longa) (TUR) and extract of bitter melon (Momordica charantia) (BM) is known to have antioxidant activity. The present study was aimed to examine the neuroprotective potential of TUR and BM extracts, either as single or as combination, against the effects of aspartame in the brain. Here, Sprague-Dawley rats fed with aspartame (40 mg/kg BW) for 28 days were compared with rats fed with extract and aspartame. To assess neuroprotective potential, rats were given extract 7 days before and during aspartame treatment. Spatial memory was assessed with Morris water maze test followed with H&E staining of hippocampal region. Brain lipid peroxidation and enzymatic activity of malondialdehyde (MDA), glutathione peroxidase (GPx), and Acetylcholinesterase (AChE) were measured to probe status of oxidative stress in the brain. Aspartame-treated rats demonstrated spatial memory impairment and reduced number of hippocampal cells and elevated levels of MDA, downregulated activity of GPx and elevated activity of AChE. In contrast, animals received both aspartame and extract demonstrated better spatial memory function, higher number of hippocampal areas, increased GPX activity, reduced MDA levels, and decreased AChE activity were observed in the brain of extract-treated rats. Taken together, our results suggest that extract of TUR rhizome and BM fruit exhibit antioxidant activity which may contribute to the neuroprotective effects against aspartame-induced memory impairment in rats.

Brazilin from Caesalpinia sappan L. as a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor: Pharmacophore-Based Virtual Screening, In Silico Molecular Docking, and In Vitro Studies.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of low-density lipoprotein cholesterol (LDL-c) levels, as it binds to and degrades the LDL receptor (LDLR) in the lysosome of hepatocytes. Elevated levels of PCSK9 have been linked to an increased LDL-c plasma levels, thereby increasing the risk of cardiovascular disease (CVD), making it an attractive target for therapeutic interventions. As a way to inhibit PCSK9 action, we searched for naturally derived small molecules which can block the binding of PCSK9 to the LDLR. Methods: In this study, we carried out in silico studies which consist of virtual screening using an optimized pharmacophore model and molecular docking studies using Pyrx 0.98. Effects of the candidate compounds were evaluated using in vitro PCSK9-LDLR binding assays kit. Results: Eleven natural compounds that bind to PCSK9 were virtually screened form HerbalDB database, including brazilin. Next, molecular docking studies using Pyrx 0.98 showed that brazilin had the highest binding affinity with PCSK9 at -9.0 (Kcal/mol), which was higher than that of the other ten compounds. Subsequent in vitro PCSK9-LDLR binding assays established that brazilin decreased the binding of PCSK9 to the EGF-A fragment of the LDLR in a dose-dependent manner, with an IC50 value of 2.19 µM. Conclusion: We have identified brazilin, which is derived from the Caesalpinia sappan herb, which can act as a small molecule inhibitor of PCSK9. Our findings suggest that screening for small molecules that can block the interaction between PCSK9 and the LDLR in silico and in vitro may be a promising approach for developing novel lipid-lowering therapy.

High-Fat Diet Enhances Platelet Activation and Is Associated with Proprotein Convertase Subtilisin Kexin 9: An Animal Study.

Platelet activation and proprotein convertase subtilisin kexin 9 (PCSK9) play pivotal roles in the progression of atherosclerosis to cardiovascular events. It has been reported that hyperlipidemia, a well-documented risk factors for cardiovascular diseases, tends increase platelet activation and PCSK9 expression. However, little is known about this specific mechanism, particularly how nutrition affects platelet activation and PCSK9 levels in hyperlipidemia conditions. This study aimed to assess how a high-fat diet influences platelet activation, its association with PCSK9, and the effects on blood pressure in an animal model. Here, male Wistar rats were divided into four groups, subjected to different high-fat diets for ten weeks with varying nutrient components. The results showed that high-fat diet-induced hypercholesterolemia and hypertriglyceridemia significantly increased the plasma levels of ß-thromboglobulin (ß-TG), p-selectin, and platelet factor 4 (PF-4). The blood pressure readings were also elevated post high-fat diet induction. Interestingly, the group with the highest percentage of saturated fatty acid and trans-fat exhibited the highest PCSK9 levels, along with the highest increase in plasma cholesterol, triglycerides, and platelet activation parameters. These findings confirm that high-fat diet-induced hypercholesterolemia and hypertriglyceridemia stimulate platelet activity and PCSK9 levels. Moreover, our results suggest that PCSK9, implicated in hypercholesterolemia and hypertriglyceridemia, may synergistically mediate platelet hyperactivity, aligning with clinical studies. Notably, our results highlight the association between a high-fat diet and PCSK9, providing insights for drug discovery targeting platelet activation in atherosclerosis-induced cardiovascular diseases.

Platelet Glycoprotein-Ib (GPIb) May Serve as a Bridge between Type 2 Diabetes Mellitus (T2DM) and Atherosclerosis, Making It a Potential Target for Antiplatelet Agents in T2DM Patients.

Type 2 diabetes mellitus (T2DM) is a persistent metabolic condition that contributes to the development of cardiovascular diseases. Numerous studies have provided evidence that individuals with T2DM are at a greater risk of developing cardiovascular diseases, typically two to four times more likely than those without T2DM, mainly due to an increased risk of atherosclerosis. The rupture of an atherosclerotic plaque leading to pathological thrombosis is commonly recognized as a significant factor in advancing cardiovascular diseases caused by TD2M, with platelets inducing the impact of plaque rupture in established atherosclerosis and predisposing to the primary expansion of atherosclerosis. Studies suggest that individuals with T2DM have platelets that display higher baseline activation and reactivity than those without the condition. The expression enhancement of several platelet receptors is known to regulate platelet activation signaling, including platelet glycoprotein-Ib (GPIb). Furthermore, the high expression of platelet GP1b has been reported to increase the risk of platelet adhesion, platelet-leucocyte interaction, and thrombo-inflammatory pathology. However, the study exploring the role of GP1b in promoting platelet activation-induced cardiovascular diseases in T2DM patients is still limited. Therefore, we summarize the important findings regarding pathophysiological continuity between T2DM, platelet GPIb, and atherosclerosis and highlight the potential therapy targeting GPIb as a novel antiplatelet agent for preventing further cardiovascular incidents in TD2M patients.

Recent Update on PCSK9 and Platelet Activation Experimental Research Methods: In Vitro and In Vivo Studies.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial factor in the development and progression of cardiovascular diseases. PCSK9 has been demonstrated to modify LDL plasma levels and increase platelet activation, which promotes atherosclerosis, a defining feature of nearly all cardiovascular diseases. Platelet activation has been shown to promote and maintain the response to atherosclerosis development, from beginning to progression and exacerbation, which can lead to advanced cardiovascular events including myocardial infarction (MI) or death. Research on PCSK9 and platelet activation is currently underway with the main goal of reducing the risk of advanced cardiovascular events by preventing or slowing down atherosclerosis progression. Both in vitro and in vivo studies have been used to explore PCSK9 functions to develop new drugs targeting PCSK9. Finding the most suitable study models that represent the pathological and physiological systems found in humans is very important to achieving the goal. This review aimed to present a current and comprehensive overview of the experimental models that have been used to investigate the role of PCSK9 in platelet activation-induced atherosclerotic cardiovascular diseases.

PCSK9 Promotes Cardiovascular Diseases: Recent Evidence about Its Association with Platelet Activation-Induced Myocardial Infarction.

Cardiovascular diseases are the leading cause of death worldwide, with the majority of the cases being heart failure due to myocardial infarction. Research on cardiovascular diseases is currently underway, particularly on atherosclerosis prevention, to reduce the risk of myocardial infarction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to play a role in lipid metabolism, by enhancing low-density lipoprotein (LDL) receptor degradation. Therefore, PCSK9 inhibitors have been developed and found to successfully decrease LDL plasma levels. Recent experimental studies have also implicated PCSK9 in platelet activation, having a key role during atherosclerosis progression. Although numerous studies have addressed the role of PCSK9 role in controlling hypercholesterolemia, studies and discussions exploring its involvement in platelet activation are still limited. Hence, here, we address our current understanding of the pathophysiological process involved in atherosclerosis-induced myocardial infarction (MI) through platelet activation and highlight the molecular mechanisms used by PCSK9 in regulating platelet activation. Undoubtedly, a deeper understanding of the relationship between platelet activation and the underlying molecular mechanisms of PCSK9 in the context of MI progression will provide a new strategy for developing drugs that selectively inhibit the most relevant pathways in cardiovascular disease progression.

Peperomia pellucida (L.) Kunth as an angiotensin-converting enzyme inhibitor in two-kidney, one-clip Goldblatt hypertensive rats.

BACKGROUD: Peperomia pellucida (L.) Kunth has been used widely to treat headache, kidney disease, fever, and hypertension. Previous in vitro studies discovered that the flavonoid-rich extract of this plant has potential hypotensive effects, specifically angiotensin-converting enzyme (ACE)-inhibitory activity. However, there is insufficient scientific evidence to validate the result in vivo. PURPOSE: This study investigated the dose dependencies of the effects of the ethyl acetate fraction of the ethanolic extract of this plant on blood pressure and biomarkers associated with the renin-angiotensin-aldosterone systems (RAAS), such as angiotensin II (AII) and the plasma renin concentration (PRC). STUDY DESIGN: In total, 30 two-kidney, one-clip (2K1C) hypertensive model rats were divided into five groups (n = 6 each): model group, captopril 25 mg/kg BW group, and three different ethyl acetate groups (25, 50, and 100 mg/kg BW). Another six rats comprised the sham group. METHODS: Renal hypertensive rats (RHRs) were generated using stainless steel modification clips. Drugs were administered via oral gavage for 2 consecutive weeks. Blood pressure was measured weekly prior to treatment. Blood samples were collected before treatment and after the last dose to measure AII and PRC. The left kidney was isolated for histopathological examination. RESULTS: Blood pressure, AII levels, and PRC were elevated after 6 weeks in RHRs. Treatment with captopril and the ethyl acetate fraction of P. pellucida (L.) Kunth decreased blood pressure, AII levels, and PRC. The ethyl acetate fraction at a dose of 50 mg/kg BW had similar ACE-inhibitory effects as captopril. Histopathological examination disclosed coagulative necrosis in clipped kidneys. Impairment was alleviated in a dose-dependent manner by P. pellucida (L.) Kunth, similarly as observed in the captopril group. CONCLUSION: P. pellucida (L.) Kunth targets the renin-angiotensin-aldosterone system, which might explain its antihypertensive effects.

Two triterpenoids from Rubus fraxinifolius leaves and their tyrosinase and elastase inhibitory activities.

Numerous therapeutic compounds have been isolated from naturally abundant organic resources, which may offer economical and sustainable sources of compounds with safe and efficacious biological activities. In the cosmetics industry, natural compounds with anti-aging activities are eagerly sought. Thus, we prepared various extracts from Rubus fraxinifolius leaves and used enzyme inhibition assays to isolate compounds with protective effects against skin aging. Two triterpenoids were isolated from Rubus fraxinifolius Poir. leaves. The structures were characterized by spectroscopic analyses (LC-ESI-MS, 1D/2D NMR) and comparison to reported data. Compound 1 and 2 were determined as 2,3-O-ethyleneglycol, 19-hydroxyurs-12-en-23,28-dioic acid and 2,3-O-propanediol,19-hydroxyurs-12-en-28-oic acid. Methanol extract and isolates were assessed for their inhibitory effects on elastase and tyrosinase. Compounds 1 and 2 inhibited elastase with IC50 122.199 µg/mL and 98.22 µg/mL, and also inhibited tyrosinase with IC50 207.79 µg/mL and 221.51 µg/mL, respectively. The molecular docking proved that both compounds have affinities toward the enzymes.

Optimization of betaine-sorbitol natural deep eutectic solvent-based ultrasound-assisted extraction and pancreatic lipase inhibitory activity of chlorogenic acid and caffeine content from robusta green coffee beans.

Natural deep eutectic solvent (NADES) is an alternative approach in natural product extraction with various advantages, including low toxicity, biodegradable, and suitable phytochemical compounds in a wide range of polarity. Chlorogenic acid (CGA) and caffeine, a well-known compound in the coffee bean, have various potential health benefits. This study aims to optimize the betaine-sorbitol NADES-based ultrasound-assisted extraction (UAE) method of CGA and caffeine from Robusta green coffee beans and determine the inhibitory activity of robusta green coffee beans extract of the betaine-sorbitol NADES-UAE from the optimum condition on pancreatic lipase in vitro and in silico. The betaine-sorbitol NADES-UAE factors as experimental design variable parameters include betaine-sorbitol ratio (0.5:1.2, 1.25:1.2, and 2:1.2 mol), extraction time (10, 35, and 60 min), and solid-liquid ratio (1:10, 1:20, and 1:30 g/mL). Response surface methodology and Box-Behnken Design were used to optimize the extraction process. The response surface was calculated by using CGA and caffeine content as response values. CGA and caffeine content was determined by High-Performance Liquid Chromatography. Whereas in vitro lipase inhibitory activity assay examined by spectrophotometric measurement and in silico molecular docking analysis on PDB ID: 1LPB. According to the results, the optimum conditions of the betaine-sorbitol NADES-UAE have obtained the betaine-sorbitol ratio of 1.25: 1.2 mol, solid-liquid ratio of 1:30 mg/mL, and 60 min extraction time. Furthermore, obtained Robusta green coffee extract from the optimum condition of the betaine-sorbitol NADES-UAE showed high potential to inhibit lipase activity with IC50 of 18.02 µg/ml, comparable with IC50 of standard CGA (11.90 µg/ml) and caffeine (15.59 µg/ml), where potential interaction of both standards was confirmed using molecular docking analysis. Our finding demonstrated the optimum condition of the betaine-sorbitol NADES-UAE method for CGA and caffeine extraction and the potential pancreatic lipase inhibition activity from the Robusta green coffee bean.

Simultaneous Natural Deep Eutectic Solvent-Based Ultrasonic-Assisted Extraction of Bioactive Compounds of Cinnamon Bark and Sappan Wood as a Dipeptidyl Peptidase IV Inhibitor.

Cinnamon bark (Cinnamomum burmannii) and sappan wood (Caesalpinia sappan) have been reported to be beneficial for Type-2 Diabetes Mellitus (T2DM) and the combination is commonly used by Indonesian herbal industries. In the present study, the simultaneous extraction of bioactive compounds from both plants was conducted using natural deep eutectic solvent (NADES), their content analyzed using high-performance liquid chromatography (HPLC), and their dipeptidyl peptidase IV (DPP IV) inhibitory activity evaluated. An additional in silico molecular docking analysis was conducted to ensure their activity. The results showed that NADES (with a composition of choline chloride-glycerol) extraction from cinnamon and sappan wood had DPP IV inhibitory activity of 205.0 and 1254.0 µg/mL, respectively. Brazilin as a marker substance from sappan wood was responsible for the DPP IV inhibitory activity, while none of the marker substances chosen for cinnamon bark (trans-cinnamaldehyde, coumarin, and trans-cinnamic acid) were found to have significant DPP IV inhibitory activity. These results were confirmed by molecular docking conducted in brazilin, trans-cinnamaldehyde, coumarin, and trans-cinnamic acid.

Pharmacokinetic Herb-Drug Interaction between Hibiscus sabdariffa Calyces Aqueous Extract and Captopril in Rats.

Hibiscus sabdariffa L. (Malvaceae) is a traditional medicinal herb widely consumed as a beverage ("hibiscus tea"), and its global popularity is expanding due to health benefits such as blood pressure and cholesterol control. Previous studies showed that Hibiscus sabdariffa is coadministered with antihypertensives and antihyperlipidemics, thus predisposing herb-drug interactions. We investigated the pharmacokinetic interaction between H. sabdariffa L. aqueous extract and captopril, a frequently prescribed antihypertensive. In this study, chemical profile of H. sabdariffa L. aqueous extract was identified using HPLC system equipped with a DAD detector at 360 nm and 520 nm. The male Sprague Dawley rats were divided into two groups of six rats. Group I received a single dose of captopril suspension (4.5 mg/200 g body weight (BW) orally (p.o.)) while group II received H. sabdariffa L. aqueous extract (60 mg/200 g BW; p.o.) daily for two weeks prior to the same captopril dose. Multiple blood samples were collected at predetermined times after captopril administration and the plasma concentration was analyzed using ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Chemical profiling of the H. sabdariffa L. aqueous extract showed that the extract contains chlorogenic acid, myricetin 3-arabinogalactoside, 5-O-caffeoylshikimic acid, quercetin 3-rutinoside, delphinidin 3-sambubioside, and cyanidin 3-sambubioside. Ingestion of the extract significantly reduced the captopril area under the curve (AUC)0-t (0.1745 (0.1254-0.2429)), AUC0-∞ (0.1734 (0.1232-0.2442))], and peak plasma concentration (0.2119 (0.1337-0.3359)) (geometric mean ratio of the coadministration group to the captopril group (90% CI)). The geometric mean ratios were falling outside the 90% CI of 0.8-1.25 bioequivalent range. Conversely, H. sabdariffa L. extract increased the apparent total body clearance (Cl/F, 0.0257 ± 0.0115 vs. 0.1418 ± 0.0338 mL/h·kg) and the apparent volume of distribution (Vd/F, 0.0541 ± 0.0226 vs. 0.3205 ± 0.0790 mL/kg). This study indicated that coadministration of H. sabdariffa L. aqueous extract could change the pharmacokinetic profile of captopril; therefore, its coadministration should be avoided.

Optimization of choline chloride-glycerol based natural deep eutectic solvent for extraction bioactive substances from Cinnamomum burmannii barks and Caesalpinia sappan heartwoods.

Indonesian cassia (Cinnamomum burmannii Blume) is commonly used as a condiment. It reportedly contains a number of major phytochemical constituents such as trans-cinnamaldehyde and coumarin. Sappan wood (Caesalpinia sappan) is a native plant of Southeast Asia that contains brazilin, a widely known red pigment. This study aimed to determine the optimal extraction conditions using a choline chloride-glycerol (ChCl-glycerol)-based natural deep eutectic solvent (NADES) to obtain greater trans-cinnamaldehyde and brazilin levels from Indonesian cassia and sappan wood. The powders of Indonesian cassia and sappan wood were extracted using ChCl-glycerol-based NADES varied at three different levels: ratio of ChCl to glycerol, ratio of powder to NADES, and the amount of water in NADES. All variables were designed using the Box-Behnken design of response surface methodology to provide 15 extraction conditions. The extraction was performed using ultrasonication-assisted extraction for 30 and 50 min for Indonesian cassia and sappan wood, respectively. Determination of the active compound contents was performed using a high-performance liquid chromatography system equipped with a UV-VIS detector at λmax = 280 nm. The optimization results revealed that the highest levels of trans-cinnamaldehyde, coumarin, and brazilin in NADES extracts were 1907.32, 1735.68, and 368.67 µg/ml, respectively, whereas the lowest levels of these compounds were 453.59, 616.76, and 74.21 µg/ml, respectively. The maximal levels exceeded those obtained using a conventional extraction method, in which 5000 µg/ml Indonesian cassia reflux extract contained only 108.45 µg/ml trans-cinnamaldehyde. Similarly, 1000 µg/ml sappan wood contained only 124.64 µg/ml brazilin. ChCl-glycerol-based NADES was suitable for extracting active compounds from Indonesian cassia and sappan wood; moreover, this solvent is more effective than organic ethanolic coventional solvent.

Effects of Hibiscus Sabdariffa Calyces Aqueous Extract on the Antihypertensive Potency of Captopril in the Two-Kidney-One-Clip Rat Hypertension Model.

Hibiscus sabdariffa aqueous extract (HS) is often used as complementary therapy for hypertension. However, some studies have shown that coadministration with a conventional antihypertensive drug can affect drug potency. We compared the effects of HS plus captopril (CAP) coadministration to HS and CAP administration alone on blood pressure and renin-angiotensin-aldosterone system (RAAS) biomarkers in the rat two-kidney-one-clip (2K1C) model of hypertension. Male Sprague Dawley rats were randomly divided into seven groups (n=6/group), a normal control (SHAM) group, and six 2K1C groups. In 2K1C animals, hypertension was induced using a stainless microclip (inner diameter of 0.20 mm). Four weeks after 2K1C surgery, blood pressure was significantly higher than in the SHAM group. Then, model rats were randomly divided into negative control (2K1C, no treatment), positive control (4.5 mg captopril/200 g body weight [BW] orally [p.o.]), HS alone (30 mg/200 g BW; p.o.), and 3 co-treatment groups receiving HS (15, 30, or 60 mg/200 g BW; p.o.) plus 4.5 mg/200 g BW captopril. The treatments were performed for two weeks. Blood pressure was significantly reduced by all the drug treatments to near the level of SHAM controls. Plasma renin level, serum angiotensin converting enzyme (ACE) activity, and plasma angiotensin II level were also significantly elevated in the 2K1C group compared to the SHAM group. Both serum ACE activity and plasma angiotensin II level were significantly reduced to near SHAM group levels by all the drug treatments. Hibiscus sabdariffa aqueous extract alone can reduce blood pressure. This extract appears could be used as a supplement with captopril but may not provide any additional benefit.

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

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.

Benzophenones and xanthones from Garcinia cantleyana var. cantleyana and their inhibitory activities on human low-density lipoprotein oxidation and platelet aggregation.

Three benzophenones, 2,6,3',5'-tetrahydroxybenzophenone (1), 3,4,5,3',5'-pentahydroxybenzophenone (3) and 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone (4), as well as a xanthone, 1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'-enyl)xanthone (9), were isolated from the twigs of Garcinia cantleyana var. cantleyana. Eight known compounds, 3,4,5,3'-tetrahydroxy benzophenone (2), 1,3,5-trihydroxyxanthone (5), 1,3,8-trihydroxyxanthone (6), 2,4,7-trihydroxyxanthone (7), 1,3,5,7-tetrahydroxyxanthone (8), quercetin, glutin-5-en-3ß-ol and friedelin were also isolated. The structures of the compounds were elucidated by spectroscopic methods. The compounds were investigated for their ability to inhibit low-density lipoprotein (LDL) oxidation and platelet aggregation in human whole blood in vitro. Most of the compounds showed strong antioxidant activity with compound 8 showing the highest inhibition with an IC50 value of 0.5 µM, comparable to that of probucol. Among the compounds tested, only compound 4 exhibited strong inhibitory activity against platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen. Compounds 3, 5 and 8 showed selective inhibitory activity on platelet aggregation induced by ADP.

Inhibitory activities of compounds from the twigs of Garcinia hombroniana Pierre on human low-density lipoprotein (LDL) oxidation and platelet aggregation.

The methanol extract of the twigs of Garcinia hombroniana, which showed strong LDL antioxidation and antiplatelet aggregation activities, was subjected to column chromatography to obtain 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone, 1,7-dihydroxyxanthone and eight triterpenoids, garcihombronane B, D, E and F, friedelin, glutin-5-en-3ß-ol, stigmasterol and lupeol. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit copper-mediated LDL oxidation and arachidonic acid (AA)-, adenosine diphosphate (ADP)-, collagen-induced platelet aggregation in vitro. Among the compounds tested, 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone and 1,7-dihydroxyxanthone showed strong inhibitory activity on LDL oxidation with half-maximal inhibitory concentration (IC(50)) values of 6.6 and 1.7 µM, respectively. 3,5,3',5'-Tetrahydroxy-4-methoxybenzophenone exhibited strong activity on AA-, ADP- and collagen-induced platelet aggregation with IC(50) values of 53.6, 125.7 and 178.6 µM, respectively, while 1,7 dihydroxyxanthone showed significant and selective inhibitory activity against ADP-induced aggregation with IC(50) value of 5.7 µM. Of the triterpenoids tested, garcihombronane B showed moderate activity against LDL oxidation and garcihombronane D and F showed selective inhibition on ADP-induced platelet aggregation.