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Displaying publications 81 - 100 of 132 in total

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Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract

Maulidiani, Abas F, Khatib A, Perumal V, Suppaiah V, Ismail A, et al.

J Ethnopharmacol, 2016 Mar 2;180:60-9.
PMID: 26775274 DOI: 10.1016/j.jep.2016.01.001

'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the 'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach.
Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract

Mediani A, Abas F, Maulidiani M, Khatib A, Tan CP, Ismail IS, et al.

J Pharm Biomed Anal, 2016 Sep 05;128:302-312.
PMID: 27318080 DOI: 10.1016/j.jpba.2016.06.003

Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.
Fulltext Metabolite Characterization and Correlations with Antioxidant and Wound Healing Properties of Oil Palm (Elaeis guineensis Jacq.) Leaflets via 1H-NMR-Based Metabolomics Approach

Che Zain MS, Lee SY, Nasir NM, Fakurazi S, Shaari K

Molecules, 2020 Nov 30;25(23).
PMID: 33265992 DOI: 10.3390/molecules25235636

Oil palm (Elaeis guineensis Jacq.) leaflets (OPLs) are one of the major agricultural by-products generated from the massive cultivation of Malaysian palm oil. This biomass is also reported to be of potential value based on its health-improving effects. By employing proton nuclear magnetic resonance (1H-NMR) spectroscopy combined with multivariate data analysis (MVDA), the metabolite profile of OPLs was characterized and correlated with their antioxidant and wound healing properties. Principal component analysis (PCA) classified four varieties of extracts, prepared using solvents ranging from polar to medium polarity, into three distinct clusters. Cumulatively, six flavonoids, eight organic acids, four carbohydrates, and an amine were identified from the solvent extracts. The more polar extracts, such as, the ethyl acetate-methanol, absolute methanol, and methanol-water, were richer in phytochemicals. Based on partial least square (PLS) analysis, the constituents in these extracts, such as (+)-catechin, (-)-epicatechin, orientin, isoorientin, vitexin, and isovitexin, were strongly correlated with the measured antioxidant activities, comprising ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and nitric oxide (NO) free radical scavenging activities, as well as with cell proliferation and migration activities. This study has provided crucial evidence on the importance of these natural antioxidant compounds on the wound healing properties of OPL.
Fulltext Metabolite Profiling of the Microalgal Diatom Chaetoceros Calcitrans and Correlation with Antioxidant and Nitric Oxide Inhibitory Activities via ¹H NMR-Based Metabolomics

Azizan A, Ahamad Bustamam MS, Maulidiani M, Shaari K, Ismail IS, Nagao N, et al.

Mar Drugs, 2018 May 07;16(5).
PMID: 29735927 DOI: 10.3390/md16050154

Microalgae are promising candidate resources from marine ecology for health-improving effects. Metabolite profiling of the microalgal diatom, Chaetoceros calcitrans was conducted by using robust metabolomics tools, namely ¹H nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate data analysis (MVDA). The unsupervised data analysis, using principal component analysis (PCA), resolved the five types of extracts made by solvents ranging from polar to non-polar into five different clusters. Collectively, with various extraction solvents, 11 amino acids, cholesterol, 6 fatty acids, 2 sugars, 1 osmolyte, 6 carotenoids and 2 chlorophyll pigments were identified. The fatty acids and both carotenoid pigments as well as chlorophyll, were observed in the extracts made from medium polar (acetone, chloroform) and non-polar (hexane) solvents. It is suggested that the compounds were the characteristic markers that influenced the separation between the clusters. Based on partial least square (PLS) analysis, fucoxanthin, astaxanthin, violaxanthin, zeaxanthin, canthaxanthin, and lutein displayed strong correlation to 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric oxide (NO) inhibitory activity. This metabolomics study showed that solvent extractions are one of the main bottlenecks for the maximum recovery of bioactive microalgal compounds and could be a better source of natural antioxidants due to a high value of metabolites.
Fulltext Metabolite profiling of Andrographis paniculata (Burm. f.) Nees. young and mature leaves at different harvest ages using 1H NMR-based metabolomics approach

Tajidin NE, Shaari K, Maulidiani M, Salleh NS, Ketaren BR, Mohamad M

Sci Rep, 2019 11 14;9(1):16766.
PMID: 31727911 DOI: 10.1038/s41598-019-52905-z

Andrographis paniculata (Burm. F.) Nees. is considered as the herb of the future due to its precious chemical compounds, andrographolide (ANDRO), neoandrographolide (NAG) and 14-deoxyandrographolide (DAG). This study aims to profile the metabolites in young and mature leaf at six different harvest ages using 1HNMR-based metabolomics combined with multivariate data analysis. Principal component analysis (PCA) indicated noticeable and clear discrimination between young and mature leaves. A comparison of the leaves stage indicated that young leaves were separated from mature leaves due to its larger quantity of ANDRO, NAG, DAG, glucose and sucrose. These similar metabolites are also responsible for the PCA separation into five clusters representing the harvest age at 14, 16, 18, 20, 22 weeks of leaves extract. Loading plots revealed that most of the ANDRO and NAG signals were present when the plant reached at the pre-flowering stage or 18 weeks after sowing (WAS). As a conclusion, A. paniculata young leaves at pre-flowering harvest age were found to be richer in ANDRO, NAG and DAG compared to mature leaves while glucose and choline increased with harvest age. Therefore, young leaves of A. paniculata should be harvested at 18 WAS in order to produce superior quality plant extracts for further applications by the herbal, nutraceutical and pharmaceutical industries.
Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats

Mediani A, Abas F, Maulidiani M, Abu Bakar Sajak A, Khatib A, Tan CP, et al.

J Physiol Biochem, 2018 May 15.
PMID: 29766441 DOI: 10.1007/s13105-018-0631-3

Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (1H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated. The obese-diabetic model was developed by feeding the rats a high-fat diet and inducing diabetic conditions with a low dose of streptozotocin (STZ) (25 mg/kg bw). However, the normal rats were induced by a high dose of STZ (55 mg/kg bw). A partial least squares discriminant analysis (PLS-DA) model showed the biomarkers of both DM types compared to control. The synthesis and degradation of ketone bodies, tricarboxylic (TCA) cycles, and amino acid pathways were the ones most involved in the variation with the highest impact. The diabetic groups also exhibited a noticeable increase in the plasma glucose level and lipid profile disorders compared to the control. There was also an increase in the plasma cholesterol and low-density lipoprotein (LDL) levels and a decline in the high-density lipoprotein (HDL) of diabetic rats. The normal-diabetic rats exhibited the highest effect of all parameters compared to the obese-diabetic rats in the advancement of the DM period. This finding can build a platform to understand the metabolic and biochemical complications of both types of DM and can generate ideas for finding targeted drugs.
Fulltext Metabolomics for characterization of gender differences in patients infected with dengue virus

Shahfiza N, Osman H, Hock TT, Shaari K, Abdel-Hamid AH

Asian Pac J Trop Med, 2015 Jun;8(6):451-6.
PMID: 26194829 DOI: 10.1016/j.apjtm.2015.05.012

OBJECTIVE: To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of (1)H NMR-spectrometry.
METHODS: The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with (1)H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database, Chenomx Profiler.
RESULTS: The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions; infected with dengue. Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle.
CONCLUSIONS: The (1)H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures, gave an evidence for the existence of distinct metabolic differentiation of individuals, according to their gender, modulates with the infection risk.
Fulltext Microplastics Pollution as an Invisible Potential Threat to Food Safety and Security, Policy Challenges and the Way Forward

Usman S, Abdull Razis AF, Shaari K, Amal MNA, Saad MZ, Mat Isa N, et al.

Int J Environ Res Public Health, 2020 Dec 21;17(24).
PMID: 33371479 DOI: 10.3390/ijerph17249591

Technological advances, coupled with increasing demands by consumers, have led to a drastic increase in plastic production. After serving their purposes, these plastics reach our water bodies as their destination and become ingested by aquatic organisms. This ubiquitous phenomenon has exposed humans to microplastics mostly through the consumption of sea food. This has led the World Health Organization (WHO) to make an urgent call for the assessment of environmental pollution due to microplastics and its effect on human health. This review summarizes studies between 1999 and 2020 in relation to microplastics in aquatic ecosystems and human food products, their potential toxic effects as elicited in animal studies, and policies on their use and disposal. There is a paucity of information on the toxicity mechanisms of microplastics in animal studies, and despite their documented presence in food products, no policy has been in place so far, to monitor and regulates microplastics in commercial foods meant for human consumption. Although there are policies and regulations with respect to plastics, these are only in a few countries and in most instances are not fully implemented due to socioeconomic reasons, so they do not address the problem across the entire life cycle of plastics from production to disposal. More animal research to elucidate pathways and early biomarkers of microplastic toxicity that can easily be detected in humans is needed. This is to create awareness and influence policies that will address this neglected threat to food safety and security.
Fulltext Moringa oleifera hydorethanolic leaf extract induced acute and sub-acute hepato-nephrotoxicity in female ICR-mice

Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan FH, Sithambaram S, Mohamed Mustapha N, et al.

Sci Prog, 2021 Oct;104(4):368504211004272.
PMID: 34886737 DOI: 10.1177/00368504211004272

Moringa oleifera (M. oleifera) Lam belongs to the family Moringaceae. It is an important multipurpose tree that is largely distributed globally and has been used almost in every aspect of traditional medicine for the treatment of various illnesses including cancers, diabetes mellitus, asthma, arthritis, etc. This study investigated the effects of oral acute and sub-acute administration of M. oleifera hydroethanolic leaf extract (MOHE) in ICR-mice. Its major phenolic compounds were also determined. Ten (10) female, 8-week old mice were grouped into control and treatment groups for acute toxicity study. A dose of 2000 mg/kg MOHE was given once to the treatment group via oral gavage. However, for the sub-acute toxicity study, 25 mice were grouped into groups A (control), B (125 mg/kg), C (250 mg/kg), D (500 mg/kg) and E (1000 mg/kg). MOHE was given via oral gavage to groups B, C, D and E daily for 28 days. Group A received only distilled water. The mice were sacrificed at the end of the experiments and samples were collected for evaluation. The results of the chemical profiling of MOHE revealed the presence of glucomoringin, niaziminine, quercetin and kaempferol as the major compounds. The treated mice in the acute toxicity study were slightly anaemic and showed evidence of stress leukogram. Moreover, a slight increase in creatinine, significant increases in AST and CK, hepatic degeneration and necrosis, none-obstructive sinusoidal dilatation, renal tubular necrosis, interstitial nephritis and renal interstitial oedema were observed. It is concluded that the LD50 of MOHE is higher than 2000 mg/kg. However, oral administration of MOHE causes acute mild anaemia and moderate hepato-nephrotoxicity in ICR-mice. Its major phenolic compounds are glucomoringin, niaziminine, quercetin and kaempferol.
Fulltext Multi-Platform Metabolomics Analyses Revealed the Complexity of Serum Metabolites in LPS-Induced Neuroinflammed Rats Treated with Clinacanthus nutans Aqueous Extract

Ahmad Azam A, Ismail IS, Shaikh MF, Abas F, Shaari K

Front Pharmacol, 2021;12:629561.
PMID: 34177565 DOI: 10.3389/fphar.2021.629561

The use of metabolomics as a comprehensive tool in the analysis of metabolic profiles in disease progression and therapeutic intervention is rapidly advancing. Yet, a single analytical platform could not be applied to cover the entire spectrum of a biological sample's metabolome. In the present paper, multi-platform metabolomics approaches were explored to determine the diverse rat sera metabolites extracted from intracerebroventricular lipopolysaccharides (LPS)-induced neuroinflammed rats treated with oral therapeutic interventions of positive drug (dextromethorphan, 5 mg/kg BW); with Clinacanthus nutans (CN) aqueous extract (CNE, 500 mg/kg BW); and with phosphate buffer saline (PBS) as the control group for 14 days. Analyzed by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) techniques, this study depicted the potential of metabolites associated with neuroinflammation and verified by MetDisease. The key observations in the perturbed metabolic pathways that showed ameliorative effects were linked to the class of amino acid and peptide metabolism involving valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Lipid metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, terpenoid backbone biosynthesis, and glycosphingolipid metabolism were also affected. Current findings suggested that the putative biomarkers, especially lysophosphatidic acid (LPA) and 5-diphosphomevalonic acid from glycerophospholipid and squalene/terpenoid and cholesterol biosynthesis, respectively, showed the ameliorative effects of the drug and CN treatments by controlling cell differentiation and proliferation. Our study proved that the complex and dynamic sera profiling affected during the CN treatment was greatly influenced by the analytical platform selection as integration between the two data yielded a more holistic summary of the metabolite pattern changes. Hence, an evidence-based herb, such as CN, can be used for novel diagnostic tools in the quest for ethnopharmacological studies.
Fulltext N-Ethyl-n-Nitrosourea Induced Leukaemia in a Mouse Model through Upregulation of Vascular Endothelial Growth Factor and Evading Apoptosis

Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan MFH, Sithambaram S, Noordin MM, et al.

Cancers (Basel), 2020 Mar 13;12(3).
PMID: 32183192 DOI: 10.3390/cancers12030678

Chemical carcinogens are commonly used to investigate the biology and prognoses of various cancers. This study investigated the mechanism of leukaemogenic effects of n-ethyl-n-nitrosourea (ENU) in a mouse model. A total of 14 3-week-old male Institute of Cancer Research (ICR)-mice were used for the study. The mice were divided into groups A and B with seven mice each. Group A served as the control while group B received intraperitoneal (IP) injections of 80 mg/kg ENU twice with a one-week interval and were monitored monthly for 3 months for the development of leukaemia via blood smear examination. The mice were sacrificed humanely using a CO2 chamber. Blood, spleen, lymph nodes, liver, kidney and lung samples were collected for blood smear examination and histopathological evaluation. The expression of angiogenic protein (VEGF), and pro and anti-apoptotic proteins (BCL2 and BAX), was detected and quantified using Western blot technique. Leukaemia was confirmed by the presence of numerous blast cells in the peripheral blood smear in group B. Similarly, the VEGF and BCL2 proteins were significantly (p < 0.05) upregulated in group B compared to A. It is concluded that IP administration of 80 mg/kg ENU induced leukaemia in ICR-mice 12 weeks post administration through upregulation of angiogenic and anti-apoptotic proteins: VEGF and BCL2.
Naturally occurring labdane diterpene and benzofuran from Globba pendula

Maulidiani, Shaari K, Paetz C, Stanslas J, Abas F, Lajis NH

Nat Prod Commun, 2009 Aug;4(8):1031-6.
PMID: 19768978

Phytochemical investigation on Globba pendula resulted in the isolation of a new naturally occurring 16-oxo-(8)17-12-labdadien-15,11-olide 1 and benzofuran-2-carboxaldehyde 2. Other known compounds including isoandrographolide, indirubin, vanillin, vanillic acid, 2(3H)-benzoxazolone, as well as beta-sitosteryl-beta-D-glucopyranoside, beta-sitosterol, and 7alpha-hydroxysitosterol were also isolated. The structures were established based on spectroscopic data and comparison with the literature. Furthermore, the compound isoandrographolide has demonstrated strong cytotoxic properties towards a panel of cancer cell lines (MCF-7, PC-3, and H-460) with the IC50 values of 7.9, 8.7, and 9.0 microM, respectively.
Neuroprotective effects of glucomoringin-isothiocyanate against H2O2-Induced cytotoxicity in neuroblastoma (SH-SY5Y) cells

Jaafaru MS, Nordin N, Rosli R, Shaari K, Bako HY, Saad N, et al.

Neurotoxicology, 2019 12;75:89-104.
PMID: 31521693 DOI: 10.1016/j.neuro.2019.09.008

Neurodegenerative diseases (NDDs) are pathological conditions characterised by progressive damage of neuronal cells leading to eventual loss of structure and function of the cells. Due to implication of multi-systemic complexities of signalling pathways in NDDs, the causes and preventive mechanisms are not clearly delineated. The study was designed to investigate the potential signalling pathways involved in neuroprotective activities of purely isolated glucomoringin isothiocyanate (GMG-ITC) against H2O2-induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. GMG-ITC was isolated from Moringa oleifera seeds, and confirmed with NMR and LC-MS based methods. Gene expression analysis of phase II detoxifying markers revealed significant increase in the expression of all the genes involved, due to GMG-ITC pre-treatment. GMG-ITC also caused significant decreased in the expression of NF-kB, BACE1, APP and increased the expressions of IkB and MAPT tau genes in the differentiated cells as confirmed by multiplex genetic system analysis. The effect was reflected on the expressed proteins in the differentiated cells, where GMG-ITC caused increased in expression level of Nrf2, SOD-1, NQO1, p52 and c-Rel of nuclear factor erythroid factor 2 (Nrf2) and nuclear factor kappa-B (NF-kB) pathways respectively. The findings revealed the potential of GMG-ITC to abrogate oxidative stress-induced neurodegeneration through Nrf2 and NF-kB signalling pathways.
New alkaloids from Phoebe scortechinii

Awang K, Mukhtar MR, Mustafa MR, Litaudon M, Shaari K, Mohamad K, et al.

Nat Prod Res, 2007 Jul 10;21(8):704-9.
PMID: 17616898

The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.
Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives

Leong SW, Mohd Faudzi SM, Abas F, Mohd Aluwi MF, Rullah K, Lam KW, et al.

Bioorg Med Chem Lett, 2015 Aug 15;25(16):3330-7.
PMID: 26071636 DOI: 10.1016/j.bmcl.2015.05.056

A series of twenty-four 2-benzoyl-6-benzylidenecyclohexanone analogs were synthesized and evaluated for their nitric oxide inhibition and antioxidant activity. Six compounds (3, 8, 10, 17, 18 and 19) were found to exhibit significant NO inhibitory activity in LPS/IFN-induced RAW 264.7 macrophages, of which compound 10 demonstrated the highest activity with the IC50 value of 4.2 ± 0.2 μM. Furthermore, two compounds (10 and 17) displayed antioxidant activity upon both the DPPH scavenging and FRAP analyses. However, none of the 2-benzoyl-6-benzylidenecyclohexanone analogs significantly scavenged NO radical. Structure-activity comparison suggested that 3,4-dihydroxylphenyl ring is crucial for bioactivities of the 2-benzoyl-6-benzylidenecyclohexanone analogs. The results from this study and the reports from previous studies indicated that compound 10 could be a candidate for further investigation on its potential as a new anti-inflammatory agent.
Novel 2-Benzoyl-6-(2,3-Dimethoxybenzylidene)-Cyclohexenol Confers Selectivity toward Human MLH1 Defective Cancer Cells through Synthetic Lethality

Song DSS, Leong SW, Ng KW, Abas F, Shaari K, Leong CO, et al.

SLAS Discov, 2019 06;24(5):548-562.
PMID: 30897027 DOI: 10.1177/2472555219831405

DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.
Nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics studies on non-organic soybeans versus organic soybeans (Glycine max), and their fermentation by Rhizopus oligosporus

Chong SG, Ismail IS, Ahmad Azam A, Tan SJ, Shaari K, Tan JK

J Sci Food Agric, 2023 Apr;103(6):3146-3156.
PMID: 36426592 DOI: 10.1002/jsfa.12355

BACKGROUND: Soybeans (Glycine max) are high in proteins and isoflavones, which offer many health benefits. It has been suggested that the fermentation process enhances the nutrients in the soybeans. Organic foods are perceived as better than non-organic foods in terms of health benefits, yet little is known about the difference in the phytochemical content that distinguishes the quality of organic soybeans from non-organic soybeans. This study investigated the chemical profiles of non-organic (G, T, U, UB) and organic (C, COF, A, R, B, Z) soybeans (G. max [L.] Merr.) and their metabolite changes after fermentation with Rhizopus oligosporus.
RESULTS: A clear separation was only observed between non-organic G and organic Z, which were then selected for further investigation in the fermentation of soybeans (GF and ZF). All four groups (G, Z, GF, ZF) were analyzed using nuclear magnetic resonance (NMR) spectroscopy along with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this way a total of 41 and 47 metabolites were identified respectively, with 12 in common. A clear variation (|log1.5 FC| > 2 and P
Fulltext Pellitorine, a potential anti-cancer lead compound against HL6 and MCT-7 cell lines and microbial transformation of piperine from Piper Nigrum

Ee GC, Lim CM, Rahmani M, Shaari K, Bong CF

Molecules, 2010 Apr;15(4):2398-404.
PMID: 20428051 DOI: 10.3390/molecules15042398

Pellitorine (1), which was isolated from the roots of Piper nigrum, showed strong cytotoxic activities against HL60 and MCT-7 cell lines. Microbial transformation of piperine (2) gave a new compound 5-[3,4-(methylenedioxy)phenyl]-pent-2-ene piperidine (3). Two other alkaloids were also found from Piper nigrum. They are (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (4) and 2,4-tetradecadienoic acid isobutyl amide (5). These compounds were isolated using chromatographic methods and their structures were elucidated using MS, IR and NMR techniques.
Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by 1H Nuclear Magnetic Resonance-Based Metabolomics

Zakaria F, Akhtar MT, Wan Ibrahim WN, Abu Bakar N, Muhamad A, Shohaimi S, et al.

Zebrafish, 2021 02;18(1):42-54.
PMID: 33538644 DOI: 10.1089/zeb.2020.1895

Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), β-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.
Fulltext Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry

Alkhateeb Y, Jarrar QB, Abas F, Rukayadi Y, Tham CL, Hay YK, et al.

Molecules, 2020 Jul 06;25(13).
PMID: 32640512 DOI: 10.3390/molecules25133069

2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5-80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0-24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0-24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.

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