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1.
J Nat Prod ; 87(4): 675-691, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38442031

Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.


Vasodilator Agents , Vasodilator Agents/pharmacology , Vasodilator Agents/chemistry , Vasodilator Agents/chemical synthesis , Animals , Structure-Activity Relationship , Rats , Molecular Structure , Ficus/chemistry , Aorta/drug effects , Alkaloids/pharmacology , Alkaloids/chemistry , Male , Molecular Dynamics Simulation
2.
Nutrients ; 15(12)2023 Jun 09.
Article En | MEDLINE | ID: mdl-37375598

Geraniin, an ellagitannin, has shown a potent blood pressure-lowering effect in vivo. Therefore, this study aims to further characterize the ability of geraniin to attenuate hypertensive vascular dysfunction, a key feature of cardiovascular disease (CVD) development. Hypertension was induced in male Sprague-Dawley rats through feeding a high-fat diet (HFD) for eight weeks, followed by oral administration of 25 mg/kg/day geraniin for four weeks. The parameters of vascular dysfunction such as the structure and function of blood vessels as well as the vascular oxidative stress and inflammation were evaluated. The outcomes of geraniin-treated rats were compared with those of untreated rats on either a normal diet (ND) or HFD and with HFD-fed rats treated with captopril (40 mg/kg/day). We found that geraniin supplementation effectively ameliorated HFD-induced hypertension and abnormal remodelling of the thoracic aorta by suppressing excessive vascular superoxide (O2-) radical generation and overexpression of pro-inflammatory mediators in the circulating leukocytes. Furthermore, compared to the ND-fed rats, geraniin also independently promoted the significant enlargement of the thoracic aortic lumen for blood pressure reduction. Notably, the vascular benefits of geraniin were comparable to that of captopril. Collectively, these data suggest that geraniin can mitigate hypertensive vascular remodelling caused by overnutrition, which potentially abrogates the further development of CVDs.


Antioxidants , Hypertension , Rats , Male , Animals , Antioxidants/metabolism , Hydrolyzable Tannins/pharmacology , Hydrolyzable Tannins/therapeutic use , Rats, Sprague-Dawley , Captopril , Vascular Remodeling , Hypertension/drug therapy , Hypertension/etiology , Obesity/drug therapy , Diet, High-Fat/adverse effects , Oxidative Stress , Models, Animal , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
3.
Environ Monit Assess ; 195(2): 307, 2023 Jan 18.
Article En | MEDLINE | ID: mdl-36652034

Recent increase in awareness of the extent of microplastic contamination in marine and freshwater systems has heightened concerns over the ecological and human health risks of this ubiquitous material. Assessing risks posed by microplastic in freshwater systems requires sampling to establish contamination levels, but standard sampling protocols have yet to be established. An important question is whether sampling and assessment should focus on microplastic concentrations in the water or the amount deposited on the bed. On three dates, five replicated water and bed sediment samples were collected from each of the eight sites along the upper reach of the Semenyih River, Malaysia. Microplastics were found in all 160 samples, with mean concentrations of 3.12 ± 2.49 particles/L in river water and 6027.39 ± 16,585.87 particles/m2 deposited on the surface of riverbed sediments. Fibres were the dominant type of microplastic in all samples, but fragments made up a greater proportion of the material on the bed than in the water. Within-site variability in microplastic abundance was high for both water and bed sediments, and very often greater than between-site variability. Patterns suggest that microplastic accumulation on the bed is spatially variable, and single samples are therefore inadequate for assessing bed contamination levels at a site. Sites with the highest mean concentrations in samples of water were not those with the highest concentrations on the bed, indicating that monitoring based only on water samples may not provide a good picture of either relative or absolute bed contamination levels, nor the risks posed to benthic organisms.


Microplastics , Water Pollutants, Chemical , Humans , Plastics , Rivers , Water Quality , Geologic Sediments , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Fresh Water
4.
Int J Pharm Pract ; 31(2): 261-265, 2023 Apr 10.
Article En | MEDLINE | ID: mdl-36534990

OBJECTIVE: To assess the knowledge, attitude and practice of community pharmacists (CP) towards household pharmaceutical waste disposal. METHODS: All pharmacists attending the Malaysian Community Pharmacy Guild event held in-person were invited to self-administer a web-based survey. KEY FINDINGS: The response rate was 61% (168/276). Overall, community pharmacists have mixed knowledge (mean ± SD: 5.89 ± 1.38) and positive attitude (mean ± SD: 9.58 ± 0.81) towards household pharmaceutical waste disposal. However, few community pharmacists (18/168, 10.7%) have promotional materials encouraging safe medication disposal in their pharmacies. CONCLUSIONS: Community pharmacists do not proactively promote safe household pharmaceutical waste disposal to mitigate pharmaceutical pollutants entering the environment although they have satisfactory knowledge and attitude.


Community Pharmacy Services , Pharmacists , Humans , Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Surveys and Questionnaires , Pharmaceutical Preparations
5.
Int J Med Mushrooms ; 24(10): 1-14, 2022.
Article En | MEDLINE | ID: mdl-36374826

COVID-19 infection has been a key threat to the public health system globally, with an estimated 248 million cases worldwide. COVID-19 patients are subject to a higher risk of developing chronic respiratory disorders that are closely associated with long-term disability, multi-morbidity, and premature mortality. Although there have been recent advancements in respiratory treatment regimens, there has also been increased interest in the use of medicinal mushrooms in bridging the unaddressed pathways of action within the treatment algorithms. In this review, we provide a collection of medicinal mushrooms that are beneficial in promoting respiratory health and potentially reducing COVID-19 symptoms in patients who are newly diagnosed and those who have recovered. While reviewing the use of immunomodulatory pathways, which have shown promising results in tackling side effects and post-COVID syndromes, we also provide insights into how the antioxidant elements present in medicinal mushrooms help to achieve the same results, especially in the prophylactic and therapeutic management of COVID-19 infection. To date, medicinal mushrooms are regarded as a functional food, which, however, need further quality, safety, and efficacy assessments. These requirements are also highlighted in the present review to promote the future development and application of medicinal mushrooms for better respiratory health.


Agaricales , COVID-19 Drug Treatment , COVID-19 , Phytotherapy , Humans , COVID-19/epidemiology , Pandemics
6.
Front Pharmacol ; 13: 932942, 2022.
Article En | MEDLINE | ID: mdl-36249772

Adverse drug reaction (ADR) is one of the leading public health concerns associated with high mortality rate. Healthcare professionals, particularly pharmacists, have a significant role in monitoring and preventing ADRs. This study was conducted on Malaysian Pharmaceutical Society (MPS) pharmacists who worked at the hospitals, health clinics, and community pharmacies to determine if pharmacists' experiences on ADRs are still the same 10 years later. In 2010, a postal survey and in 2020, an online survey were conducted among these pharmacists. A total of 472 pharmacists and 208 participated in 2010 and 2020, respectively. About 82% and 90% of hospital/health clinic pharmacists (HCPs) observed an ADR over the last 6 months in 2010 and 2020, while 60% and 100% community pharmacists in 2010 and 2020 observed an ADR, respectively. Perindopril was the top drug (HCPs: p = 0.657; CPs: p = 0.98), and rash was the top ADR reported by the pharmacists in both years (HCPs: p < 0.001; CPs: p = 0.679). The most common actions taken by HCPs in 2010 were to report the ADR (p = 0.343), while in 2020, most HCPs explained to patients regarding the reaction (p = 0.061), which was also the same in the CP group in 2020 (p = 0.958). The top factor encouraging ADR reporting in both years and both pharmacist groups was the high degree of severity of the reaction (HCPs: p < 0.001; CPs: p = 0.769). While the top factors discouraging ADR reporting were a lack of information from the affected patients (HCPs: p = 0.2; CPs: p = 0.656), reaction is widely known (HCPs: p = 0.001; CPs: p = 0.144) and uncertainty of the causal relationship (HCPs: p = 0.169; CPs: p = 0.609). Majority of the pharmacists agreed that severe reactions should be reported (HCPs: p = 0.158; CPs: p = 0.501) and the main aim for reporting is to measure the incidence of ADRs (HCPs: p = 0.148; CPs: p = 0.762). Despite being able to identify ADRs during the daily practice, many pharmacists especially community pharmacists are not reporting them. There is a misconception on the purpose of reporting ADRs. An interventional program and ADR reporting training would be a useful step in improving ADR reporting practice.

7.
Phytother Res ; 36(7): 2952-2963, 2022 Jul.
Article En | MEDLINE | ID: mdl-35537691

This study investigated the vasorelaxant effects of schwarzinicine A, an alkaloid recently reported from Ficus schwarzii Koord. Regulation of calcium homeostasis in vascular smooth muscle cells (VSMC) is viewed as one of the main mechanisms for controlling blood pressure. L-type voltage-gated calcium channel (VGCC) blockers are commonly used for controlling hypertension. Recently, the transient receptor potential canonical (TRPC) channels were found in blood vessels of different animal species with evidence of their roles in the regulation of vascular contractility. In this study, we studied the mechanism of actions of schwarzinicine A focusing on its regulation of L-type VGCC and TRPC channels. Schwarzinicine A exhibited the highest vasorelaxant effect (123.1%) compared to other calcium channel blockers. It also overtly attenuated calcium-induced contractions of the rat isolated aortae in a calcium-free environment showing its mechanism to inhibit calcium influx. Fluorometric intracellular calcium recordings confirmed its inhibition of hTRPC3-, hTRPC4-, hTRPC5- and hTRPC6-mediated calcium influx into HEK cells with IC50 values of 3, 17, 19 and 7 µM, respectively. The evidence gathered in this study suggests that schwarzinicine A blocks multiple TRPC channels and L-type VGCC to exert a significant vascular relaxation response.


Transient Receptor Potential Channels , Vasodilation , Animals , Calcium/metabolism , Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/pharmacology , Rats , Transient Receptor Potential Channels/pharmacology , Vasodilator Agents/pharmacology
8.
Int J Med Mushrooms ; 24(3): 1-14, 2022.
Article En | MEDLINE | ID: mdl-35467802

Ophiocordyceps sinensis is a popular medicinal mushroom used for various health conditions, including alleviation of frequent urination, which is a major symptom of overactive bladder (OAB) syndrome. This study aimed to investigate the effect of O. sinensis (OCS02 cultivar) cold-water extract (CWE) against bladder contractility using the organ bath technique. The bladder was removed from male Sprague-Dawley rats and cut into longitudinal strips of 2 mm × 8 mm. In some experiments, the urothelium was removed to study its role in CWE-induced responses. CWE elicited a biphasic response consisting of an immediate, transient contraction that was followed by a sustained relaxation in bladder strips precontracted with carbachol, a muscarinic agonist. Removal of urothelium did not alter the magnitude of the contractile response but significantly attenuated the relaxation response. In the presence of L-NAME (nitric oxide synthase inhibitor) and sodium nitroprusside (nitric oxide donor), CWE-induced transient contraction was enhanced, whereas the relaxation response was significantly reduced. Following preincubation with CWE, the amplitude and the frequency of the spontaneous myogenic contractions induced by carbachol, as well as the contractile response toward calcium, were significantly suppressed. Findings from this study show that the urothelium plays a role in the relaxant effect of CWE. Its mechanisms of action include the regulation of nitric oxide and inhibition of calcium influx.


Cordyceps , Urinary Bladder , Animals , Calcium/pharmacology , Carbachol/pharmacology , China , Male , Muscle, Smooth/physiology , Rats , Rats, Sprague-Dawley , Urinary Bladder/physiology , Water
9.
Environ Res ; 210: 112972, 2022 07.
Article En | MEDLINE | ID: mdl-35219629

Information on the relative contributions of microplastics coming from different sources is important to help prioritise measures to reduce river contamination levels and limit human and ecological health risks. This paper reports on work which aimed to quantitatively assess the relative concentrations and types of microplastic delivered from differed sources to a second order river. The study was undertaken in a mixed landuse area within a rapidly urbanising catchment in Malaysia. Over a six-week period, water samples were collected from road culverts and drains in residential and industrial areas across the area to assess microplastic concentrations, while inputs from atmospheric deposition and wastewater treatment plants (WWTPs) were also quantified. Microplastic fibres and fragments were the dominant material in all sources, with the majority consisting of styrene-butadiene rubber and nylon. Culverts draining main roads were the main contributor to riverborne microplastic, delivering 42.20 ± 35.29 particles/L directly to the river channel. Road inputs were up to seven times greater than those from residential (8.53 ± 9.91 particles/L) and industrial (5.67 ± 4.88 particles/L) areas. The five WWTPs had removal efficiencies of between 30.95 ± 5.51% and 69.94 ± 22.17%, with their outflows delivering microplastics to the river in concentrations similar to those in uncontrolled residential and industrial drains. Atmospheric deposition across the study area was estimated to be 76.07 ± 32.85 particles/m2/day (=8.35 ± 5.11 particles/L). Mitigation strategies in the study area should focus on improving management of water draining roads, and re-routing discharges from domestic and industrial areas to WWTPs rather than allowing them to flow directly to the river. The low efficiencies of some of the WWTPs are not unusual, and indicate the need for additional water treatment to deal with microplastic present in wastewater.


Microplastics , Water Pollutants, Chemical , Environmental Monitoring , Humans , Plastics , Rivers , Water Pollutants, Chemical/analysis
10.
Nat Prod Res ; 36(15): 3972-3978, 2022 Aug.
Article En | MEDLINE | ID: mdl-33749454

A concise synthesis of the 1,4-diarylbutanoid-phenethylamine alkaloids, schwarzinicines A (1) and B (2), recently isolated from Ficus schwarzii, is reported. Key steps include a Claisen condensation to assemble the 1,4-diaryl-2-butanone intermediate, followed by a reductive amination to furnish the core skeleton of the target compounds. The overall synthetic yields of 1 and 2 were 9.1% and 3.5%, respectively. Synthetic (-)-1, (+)-1 and (±)-1 exhibited comparable vasorelaxation as natural schwarzinicine A on rat isolated aortic rings, suggesting that the observed vasorelaxant effects were not influenced by the chirality at C-2.


Alkaloids , Ficus , Alkaloids/pharmacology , Animals , Rats , Stereoisomerism , Vasodilator Agents/pharmacology
11.
Am J Physiol Heart Circ Physiol ; 321(4): H770-H783, 2021 10 01.
Article En | MEDLINE | ID: mdl-34506226

Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.


Cell Proliferation , Cellular Senescence , Exosomes/metabolism , Gene Expression Profiling , MicroRNAs/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Transcriptome , Cells, Cultured , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , Exosomes/genetics , High-Throughput Nucleotide Sequencing , Humans , MicroRNAs/genetics , Protein Processing, Post-Translational , Sequence Analysis, RNA , Transcription Factors/genetics , Transcription Factors/metabolism , Whole Genome Sequencing
12.
J Nat Prod ; 84(8): 2272-2281, 2021 08 27.
Article En | MEDLINE | ID: mdl-34342431

Seven new tropane alkaloids, including five monomeric (1-5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8 and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6 and 7 showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9 induced a smooth muscle relaxation effect comparable to that of atropine (Emax 106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.


Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Muscle, Smooth/drug effects , Rhizophoraceae/chemistry , Tropanes/pharmacology , Alkaloids/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Humans , In Vitro Techniques , Malaysia , Male , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Bark/chemistry , Plant Leaves/chemistry , Rats , Rats, Sprague-Dawley , Trachea/drug effects , Tropanes/isolation & purification
13.
Environ Pollut ; 289: 117895, 2021 Nov 15.
Article En | MEDLINE | ID: mdl-34364115

Microplastic pollution is widely recognised as a global issue, posing risks to natural ecosystems and human health. The combination of rapid industrial and urban development and relatively limited environmental regulation in many tropical countries may increase the amount of microplastic entering rivers, but basic data on contamination levels are lacking. This is especially the case in tropical South East Asian countries. In this paper, the abundance, composition and spatio-temporal variation of microplastic in the Langat River, Malaysia, were assessed, and the relationship between microplastic concentration and river discharge was investigated. Water samples were collected over a 12-month period from 8 sampling sites on the Langat, extending from forested to heavily urbanised and industrial areas. All 508 water samples collected over this period contained microplastic; mean concentration across all sites and times was 4.39 particles/L but extended up to 90.00 particles/L in some urban tributaries. Most microplastics were secondary in origin, and dominated by fibres. Microplastic counts correlated directly with river discharge, and counts increased and decreased in response to changes in flow. A time-integrated assessment of the microplastic load conveyed by the Langat suggested that the river is typically (50 % of the time) delivering around 5 billion particles per day to the ocean. The positive correlation between the concentration of microplastics and suspended sediments in the Langat suggested that continuously logging turbidity sensors could be used to provide better estimates of microplastic loads and improve assessment of human and ecological health risks.


Microplastics , Water Pollutants, Chemical , Ecosystem , Environmental Monitoring , Humans , Plastics , Rivers , Water Pollutants, Chemical/analysis
14.
Environ Sci Pollut Res Int ; 28(39): 54222-54237, 2021 Oct.
Article En | MEDLINE | ID: mdl-34386926

Plastics are synthetic polymers known for their outstanding durability and versatility, and have replaced traditional materials in many applications. Unfortunately, their unique traits ensure that they pose a major threat to the environment. While literature on freshwater microplastic contamination has grown over the recent years, research undertaken in rapidly developing countries, where plastic production and use are increasing dramatically, has lagged behind that in other parts of the world. In the South East Asia (SEA) region, basic information on levels of contamination is very limited and, as a consequence, the risk to human and ecological health remains hard to assess. This review synthesises what is currently known about microplastic contamination of freshwater ecosystems in SEA, with a particular focus on Malaysia. The review 1) summarises published studies that have assessed levels of contamination in freshwater systems in SEA, 2) discusses key sources and transport pathways of microplastic in freshwaters, 3) outlines what is known of the impacts of microplastic on freshwater organisms, and 4) identifies key knowledge gaps related to our understanding of the transport, fate and effects of microplastic.


Microplastics , Plastics , Ecosystem , Fresh Water , Humans , Malaysia
15.
J Nat Prod ; 83(1): 152-158, 2020 01 24.
Article En | MEDLINE | ID: mdl-31935094

Schwarzinicines A-G (1-7), representing the first examples of 1,4-diarylbutanoid-phenethylamine conjugates, were isolated from the leaves of Ficus schwarzii. The structures of these compounds were determined by detailed analysis of their MS, 1D and 2D NMR data. Compounds 1-4 exhibited pronounced vasorelaxant effects in the rat isolated aorta (Emax 106-120%; EC50 0.96-2.10 µM). However, compounds 1 and 2 showed no cytotoxic effects against A549, MCF-7, and HCT 116 human cancer cells (IC50 > 10 µM).


Antineoplastic Agents, Phytogenic/chemistry , Ficus/chemistry , Phenethylamines/chemistry , Plant Leaves/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , HCT116 Cells , Humans , Molecular Structure , Phenethylamines/isolation & purification , Phenethylamines/pharmacology , Rats
16.
BMC Complement Altern Med ; 19(1): 169, 2019 Jul 10.
Article En | MEDLINE | ID: mdl-31291936

BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known. METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays. RESULTS: The 50% cytotoxicity concentration (CC50) values obtained were 237.5, 555.0, and < 1.25 µg/mL for 45 L Ea, 45 L Et, and 45 L H, respectively. The 45 L Ea showed the greatest viral inhibition potency of 75% at 125 µg/mL. Both 45 L Ea and 45 l Et caused 100% residual viral inhibition at 250 µg/mL. The selectivity index values for 45 L Ea, 45 L Et, and 45 L H were 2.65, 1.75, and 0.10 showing that 45 L Ea had the greatest antiviral activity among the three extracts. CONCLUSION: This study showed that ethyl acetate is the best solvent to be used to obtain extract from G. parvifolia leaves with potent antiviral activities.


Antiviral Agents/pharmacology , Garcinia/chemistry , Herpesvirus 1, Suid/drug effects , Plant Extracts/pharmacology , Acetates , Animals , Antiviral Agents/isolation & purification , Antiviral Agents/toxicity , Chlorocebus aethiops , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Vero Cells , Viral Plaque Assay
17.
Lipids ; 54(6-7): 369-379, 2019 06.
Article En | MEDLINE | ID: mdl-31124166

Dysregulated hepatic gluconeogenesis is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Although existing drugs have been proven to improve gluconeogenesis, achieving this objective with functional food is of interest, especially using conjugated linoleic acid (CLA) found in dairy products. Both cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12) isomers of CLA were tested in human (HepG2) and rat (H4IIE) hepatocytes for their potential effects on gluconeogenesis. The hepatocytes exposed for 24 h with 20 µM of c9,t11-CLA had attenuated the gluconeogenesis in both HepG2 and H4IIE by 62.5% and 80.1%, respectively. In contrast, t10,c12-CLA had no effect. Of note, in HepG2 cells, the exposure of c9,t11-CLA decreased the transcription of gluconeogenic enzymes, cytosolic phosphoenolpyruvate carboxykinase (PCK1) by 87.7%, and glucose-6-phosphatase catalytic subunit (G6PC) by 38.0%, while t10,c12-CLA increased the expression of G6PC, suggesting the isomer-specific effects of CLA on hepatic glucose production. In HepG2, the peroxisome proliferator-activated receptor (PPAR) agonist, rosiglitazone, reduced the glucose production by 72.9%. However, co-administration of c9,t11-CLA and rosiglitazone neither exacerbated nor attenuated the efficacy of rosiglitazone to inhibit glucose production; meanwhile, t10,c12-CLA abrogated the efficacy of rosiglitazone. Paradoxically, PPARγ antagonist GW 9662 also led to 70.2% reduction of glucose production and near undetectable PCK1 expression by abrogating CLA actions. Together, while the precise mechanisms by which CLA isomers modulate hepatic gluconeogenesis directly or via PPAR warrant further investigation, our findings establish that c9,t11-CLA suppresses gluconeogenesis by decreasing PEPCK on hepatocytes.


Glucose/biosynthesis , Hepatocytes/metabolism , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Linoleic Acids, Conjugated/pharmacology , Phosphoenolpyruvate Carboxykinase (GTP)/antagonists & inhibitors , Animals , Cell Survival/drug effects , Dose-Response Relationship, Drug , Gene Expression Profiling , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Hep G2 Cells , Hepatocytes/chemistry , Humans , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Linoleic Acids, Conjugated/chemistry , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Phosphoenolpyruvate Carboxykinase (GTP)/metabolism , Rats , Reverse Transcriptase Polymerase Chain Reaction , Stereoisomerism , Structure-Activity Relationship
18.
Org Lett ; 20(24): 8014-8018, 2018 12 21.
Article En | MEDLINE | ID: mdl-30543301

Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.


Alstonia/chemistry , Cycloheptanes/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Indoles/pharmacology , Lactones/pharmacology , Oxepins/pharmacology , Secologanin Tryptamine Alkaloids/pharmacology , Animals , Aorta/drug effects , Cell Line, Tumor , Crystallography, X-Ray , Cycloheptanes/chemistry , Cycloheptanes/isolation & purification , Dose-Response Relationship, Drug , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Humans , Indoles/chemistry , Indoles/isolation & purification , Lactones/chemistry , Lactones/isolation & purification , Male , Models, Molecular , Molecular Conformation , Oxepins/chemistry , Oxepins/isolation & purification , Rats , Secologanin Tryptamine Alkaloids/chemistry , Secologanin Tryptamine Alkaloids/isolation & purification , Structure-Activity Relationship
19.
Front Pharmacol ; 9: 461, 2018.
Article En | MEDLINE | ID: mdl-29867469

Lignosus rhinocerotis has a long history of use by the indigenous community within East Asia to treat a range of health conditions including asthma and chronic cough. To date, there is limited scientific evidence to support its therapeutic effects in relieving these airways conditions. In this study, we examined the effects of the different molecular weight fractions [high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW)] obtained from the cold water sclerotial extract (CWE) of L. rhinocerotis on airways patency using airway segments isolated from Sprague Dawley rat in an organ bath set-up. It is demonstrated that the HMW and MMW fractions exhibited higher efficacy in relaxing the pre-contracted airways when compared to the CWE and LMW fraction. In addition, the HMW fraction markedly supressed carbachol-, 5-hydroxytrptamine-, and calcium-induced airway contractions. CWE demonstrated a lower efficacy than the HMW fraction but it also significantly attenuated carbachol- and calcium-induced airway contractions. Results showed that the bronchorelaxation effect of CWE and fractions is mediated via blockade of extracellular Ca2+ influx. The composition analysis revealed the following parts of carbohydrate and proteins, respectively: HMW fraction: 71 and 4%; MMW fraction: 35 and 1%; and LMW fraction: 22 and 0.3%. Our results strongly suggest that the polysaccharide-protein complex or proteins found in the HMW and MMW fractions is likely to contribute to the bronchorelaxation effect of CWE.

20.
Data Brief ; 18: 1322-1326, 2018 Jun.
Article En | MEDLINE | ID: mdl-29900310

The data in this article contain supporting evidence for the research manuscript entitled "Bronchodilator effects of Lignosus rhinocerotis extract on rat isolated airways is linked to the blockage of calcium entry" by Lee et al. (2018) [1]. The data were obtained by calcium imaging technique with fluorescent calcium indicator dyes, Fura 2-AM, to visualize calcium ion movement in the rat dorsal ganglion (DRG) cells. The effects of L. rhinocerotis cold water extract (CWE1) on intracellular calcium levels in the DRG cells were presented.

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