Displaying publications 1 - 20 of 53 in total

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  1. Zolkeflee NKZ, Wong PL, Maulidiani M, Ramli NS, Azlan A, Abas F
    Planta Med, 2023 Aug;89(9):916-934.
    PMID: 36914160 DOI: 10.1055/a-2053-0950
    Diabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aims to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC is tested on a streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat model by using the 1H-NMR-based metabolomic approach. Serum biochemical analyses reveal that treatment with 250 mg/kg body weight (bw) standardized freeze-dried (FD) 50% ethanolic MC extract (MCE 250) shows favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicates the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate are identified in rats' urinary profile, discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA is due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA-induced diabetic rats shows improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism.
  2. Haque MA, Jantan I, Harikrishnan H, Abdul Wahab SM
    Planta Med, 2018 Nov;84(17):1255-1264.
    PMID: 29906814 DOI: 10.1055/a-0637-9936
    Magnoflorine, a major bioactive metabolite isolated from Tinospora crispa, has been reported for its diverse biochemical and pharmacological properties. However, there is little report on its underlying mechanisms of action on immune responses, particularly on macrophage activation. In this study, we aimed to investigate the effects of magnoflorine, isolated from T. crispa on the pro-inflammatory mediators generation induced by LPS and the concomitant NF-κB, MAPKs, and PI3K-Akt signaling pathways in U937 macrophages. Differentiated U937 macrophages were treated with magnoflorine and the release of pro-inflammatory mediators was evaluated through ELISA, while the relative mRNA expression of the respective mediators was quantified through qRT-PCR. Correspondingly, western blotting was executed to observe the modulatory effects of magnoflorine on the expression of various markers related to NF-κB, MAPK and PI3K-Akt signaling activation in LPS-primed U937 macrophages. Magnoflorine significantly enhanced the upregulation of TNF-α, IL-1β, and PGE2 production as well as COX-2 protein expression. Successively, magnoflorine prompted the mRNA transcription level of these pro-inflammatory mediators. Magnoflorine enhanced the NF-κB activation by prompting p65, IκBα, and IKKα/β phosphorylation as well as IκBα degradation. Besides, magnoflorine treatments concentration-dependently augmented the phosphorylation of JNK, ERK, and p38 MAPKs as well as Akt. The immunoaugmenting effects were further confirmed by investigating the effects of magnoflorine on specific inhibitors, where the treatment with specific inhibitors of NF-κB, MAPKs, and PI3K-Akt proficiently blocked the magnoflorine-triggered TNF-α release and COX-2 expression. Magnoflorine furthermore enhanced the MyD88 and TLR4 upregulation. The results suggest that magnoflorine has high potential on augmenting immune responses.
  3. Chan KL, Choo CY, Abdullah NR
    Planta Med, 2005 Oct;71(10):967-9.
    PMID: 16254833 DOI: 10.1055/s-2005-864188
    Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.
  4. Moideen SV, Houghton PJ, Rock P, Croft SL, Aboagye-Nyame F
    Planta Med, 1999 Aug;65(6):536-40.
    PMID: 10483374
    Dichloromethane extracts of the root bark and stem bark of Kigelia pinnata collected from Zimbabwe exhibited antitrypanosomal activity against Trypanosoma brucei brucei in vitro. Activity-guided fractionation led to the isolation of four naphthoquinones from both the root and stem bark of the plant. The compounds were identified as 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone (1), isopinnatal (2), kigelinol (3), and isokigelinol (4). Subsequently, the compounds were assessed for antitrypanosomal activity against T. brucei brucei and T. brucei rhodesiense bloodstream form trypomastigotes in vitro. Compound 1 with a furanonaphthoquinone structure was found to possess pronounced activity against both parasites with IC50 values of 0.12 and 0.045 microM, respectively, although it was less active than the standard drug pentamidine. Compounds 2, 3, and 4 also exhibited activity against the parasites, although to a lesser extent. The activities of the compounds were further assessed by comparison with the cytotoxic activities obtained against KB cell lines.
  5. Ang KP, Tan HK, Selvaraja M, Kadir AA, Somchit MN, Akim AM, et al.
    Planta Med, 2011 Nov;77(16):1782-7.
    PMID: 21614753 DOI: 10.1055/s-0030-1271119
    Development of early stage atherosclerosis involves the activation of endothelial cells by oxidized low-density lipoprotein (oxLDL) with subsequent increases in endothelial permeability and expression of adhesion molecules favoring the adherence of monocytes to the endothelium. Cryptotanshinone (CTS), a major compound derived from the Chinese herb Salvia miltiorrhiza, is known for its protective effects against cardiovascular diseases. The aim of this study was to determine whether CTS could prevent the oxLDL-induced early atherosclerotic events. OxLDL (100 µg/mL) was used to increase endothelial permeability and induce monocyte-endothelial cell adhesion in human umbilical vein endothelial cells (HUVECs). Endothelial nitric oxide (NO) concentrations, a permeability-regulating molecule, and expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured. Results show that a) endothelial hyperpermeability was suppressed by 94 % (p 
  6. Rahmani M, Ling CY, Sukari MA, Ismail HB, Meon S, Aimi N
    Planta Med, 1998 Dec;64(8):780.
    PMID: 17253329
  7. Jantan I, Pisar MM, Idris MS, Taher M, Ali RM
    Planta Med, 2002 Dec;68(12):1133-4.
    PMID: 12494345
    Rubraxanthone and isocowanol isolated from Garcinia parvifolia Miq. were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets using 3H-PAF as a ligand. Rubraxanthone showed a strong inhibition with IC 50 value of 18.2 microM. The IC 50 values of macluraxanthone, 6-deoxyjacareubin, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone, 2-(3-methylbut-2-enyl)-1,3,5,6-tetrahydroxyxanthone and 1,3,5-trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)-xanthone were also determined for comparison. In the course of our study on structure-activity relationship of xanthones, the results revealed that a geranyl group substituted at C-8 was beneficial to the binding while a hydroxylated prenyl group at C-4 resulted in a significant loss in binding to the PAF receptor.
  8. Zahari A, Cheah FK, Mohamad J, Sulaiman SN, Litaudon M, Leong KH, et al.
    Planta Med, 2014 May;80(7):599-603.
    PMID: 24723007 DOI: 10.1055/s-0034-1368349
    The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).
  9. Sivasothy Y, Ibrahim H, Paliany AS, Alias SA, Md Nor NR, Awang K
    Planta Med, 2013 Dec;79(18):1775-80.
    PMID: 24356874 DOI: 10.1055/s-0033-1351075
    The rhizomes of Alpinia pahangensis yielded a new bis-labdanic diterpene for which the name pahangensin C (1) was proposed along with twelve known analogues (2-13). The structure of 1 was elucidated via spectroscopic methods including 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 2 and 12 were isolated for the first time from the genus Alpinia. This is the second occurrence of compounds 2 and 12 in the Zingiberaceae family. Selected analogues exhibited moderate to strong inhibitory activity against Staphylococcus aureus and Bacillus cereus.
  10. Khangholi S, Majid FA, Berwary NJ, Ahmad F, Aziz RB
    Planta Med, 2016 Jan;82(1-2):32-45.
    PMID: 26550791 DOI: 10.1055/s-0035-1558086
    Glycation, the non-enzymatic binding of glucose to free amino groups of an amino acid, yields irreversible heterogeneous compounds known as advanced glycation end products. Those products play a significant role in diabetic complications. In the present article we briefly discuss the contribution of advanced glycation end products to the pathogenesis of diabetic complications, such as atherosclerosis, diabetic retinopathy, nephropathy, neuropathy, and wound healing. Then we mention the various mechanisms by which polyphenols inhibit the formation of advanced glycation end products. Finally, recent supporting documents are presented to clarify the inhibitory effects of polyphenols on the formation of advanced glycation end products. Phytochemicals apply several antiglycation mechanisms, including glucose metabolism, amelioration of oxidative stress, scavenging of dicarbonyl species, and up/down-regulation of gene expression. To utilize polyphenols in order to remedy diabetic complications, we must explore, examine and clarify the action mechanisms of the components of polyphenols.
  11. Tan S, Yuen KH, Chan KL
    Planta Med, 2002 Apr;68(4):355-8.
    PMID: 11988862 DOI: 10.1055/s-2002-26751
    A new and simple HPLC method using fluorescence detection was developed to determine 9-methoxycanthin-6-one, an active compound of Eurycoma longifolia Jack in rat and human plasma. The method entailed direct injection of plasma sample after deproteinization using acetonitrile. The mobile phase comprised acetonitrile and distilled water (55 : 45, v/v). Analysis was run at a flow rate of 1.0 ml/min with the detector operating at an excitation wavelength of 371 nm and emission wavelength of 504 nm. The method was specific and sensitive with a detection limit of 0.6 ng/ml and a quantification limit of approximately 1.6 ng/ml. The method was applied in a pilot pharmacokinetic/bioavailability study of the compound in rats. Less than 1 % of the compound was found to be absorbed orally.
  12. Low BS, Ng BH, Choy WP, Yuen KH, Chan KL
    Planta Med, 2005 Sep;71(9):803-7.
    PMID: 16206032
    A validated HPLC analysis of eurycomanone (1), a bioactive quassinoid, in rat plasma following oral and intravenous administration of Eurycoma longifolia Jack extract was developed for pharmacokinetic and bioavailability studies. Relatively high plasma eurycomanone concentrations were detected after an intravenous injection of 10 mg/kg extract F2 containing 1.96 mg/kg of the quassinoid. However, it declined rapidly to zero after 8 h. Its mean elimination rate constant (k(e)), biological half-life (t(1/2)), volume of distribution (V(d)) and clearance (CL) were 0.88 +/- 0.19 h (-1), 1.00 +/- 0.26 h, 0.68 +/- 0.30 L/kg and 0.39 +/- 0.08 L/h/kg, respectively. Following oral administration of eurycomanone, its Cmax and Tmax values were detected as 0.33 +/- 0.03 microg/mL and 4.40 +/- 0.98 h, respectively. The plasma concentration of the quassinoid after oral administration was much lower than after intravenous application in spite of the oral dose being 5 times higher. The results indicate that eurycomanone is poorly bioavailable when given orally. A comparison of the AUC (0-->infinity) obtained orally to that obtained after an intravenous administration (normalized for dose differences) revealed that the absolute bioavailability of the compound was low with 10.5 %. Furthermore, the compound appeared to be well distributed in the extravascular fluids because of its relatively high V(d) value. The poor oral bioavailability was not attributed to instability problems because eurycomanone has been shown to be stable under different pH conditions. Thus, its poor oral bioavailability may be due to poor membrane permeability in view of its low P value and/or high first-pass metabolism.
  13. Murugaiyah V, Chan KL
    Planta Med, 2006 Nov;72(14):1262-7.
    PMID: 16953466 DOI: 10.1055/s-2006-947224
    The methanol extract from the leaves of Phyllanthus niruri L. showed oral antihyperuricemic activity in potassium oxonate- and uric acid-induced hyperuricemic rats. Fractionation of the extract by resin chromatography led to the isolation of a less polar fraction which exhibited the highest reduction of plasma uric acid. Further antihyperuricemic-guided purification of the fraction afforded three lignans, phyllanthin (1), hypophyllanthin (2) and phyltetralin (3), of which 1 significantly reversed the plasma uric acid level of hyperuricemic animals to its normal level in a dose-dependent manner, comparable to that of allopurinol, benzbromarone and probenecid which are used clinically for the treatment of hyperuricemia and gout. Thus, the lignans of P. niruri are potential antihyperuricemic agents worthy of further investigation.
  14. Teh CH, Abdulghani M, Morita H, Shiro M, Hussin AH, Chan KL
    Planta Med, 2011 Jan;77(2):128-32.
    PMID: 20665368 DOI: 10.1055/s-0030-1250159
    13 α,21-Dihydroeurycomanone (1), a known quassinoid of Eurycoma longifolia Jack was recrystallized from chloroform into a novel crystal structure in space group P2 (1). Its X-ray data were compared with those of eurycomanone ( 2). Following intraperioneal injections at similar doses of 2.44 µmol/kg/day for 3 consecutive days, 2 displayed comparable potency with tamoxifen but was more potent than 1 in the anti-estrogenic effect against 17 α-ethynylestradiol (EE)-induced uterotrophy of immature rats.
  15. Ng KW, Salhimi SM, Majid AM, Chan KL
    Planta Med, 2010 Jun;76(9):935-40.
    PMID: 20112179 DOI: 10.1055/s-0029-1240813
    Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation.
  16. Hazni H, Ahmad N, Hitotsuyanagi Y, Takeya K, Choo CY
    Planta Med, 2008 Dec;74(15):1802-5.
    PMID: 18991205 DOI: 10.1055/s-0028-1088340
    The methanolic extract of the leaves of CASSIA ALATA was sequentially partitioned in increasing polarity to afford the hexane, chloroform, butanol and residual extract. Crude extracts were evaluated against MRSA using the agar well diffusion assay. The butanol and chloroform extracts both exhibited inhibition against MRSA with inhibition indexes of 1.03 +/- 0.16 and 0.78 +/- 0.07 at the concentration of 50 mg/mL. The butanol extracts were further purified using silica gel and reverse phase chromatography to afford kaempferol ( 1), kaempferol 3- O-beta-glucopyranoside ( 2), kaempferol 3- O-gentiobioside ( 3) and aloe emodin ( 4). The four constituents showed varying degrees of inhibition against MRSA. Both 1 and 4 exhibited MIC (50) values of 13.0 +/- 1.5 microg/mL and 12.0 +/- 1.5 microg/mL, respectively. The kaempferol glycosides 2 and 3 were less active with MIC (50) values of 83.0 +/- 0.9 microg/mL and 560.0 +/- 1.2 microg/mL, respectively. A free hydroxyl group at C-3 of the flavonol structure is a structural requirement for the inhibition of MRSA.
  17. Porter GC, Safii SH, Medlicott NJ, Duncan WJ, Tompkins GR, Coates DE
    Planta Med, 2021 Mar;87(3):253-266.
    PMID: 33434939 DOI: 10.1055/a-1330-8765
    Manuka oil, an essential oil derived from the Leptospermum scoparium, has been traditionally used for wound care and as a topical antibacterial, antifungal, and anti-inflammatory. However, the essential oil is not well retained at mucosal sites, such as the oral cavity, where the benefits of the aforementioned properties could be utilized toward the treatment of persistent biofilms. Within this study, L. scoparium essential oil was incorporated into a semisolid emulsion for improved delivery. The safety profile of L. scoparium essential oil on human gingival fibroblasts was determined via cell viability, cytotoxicity, and caspase activation. The minimal bactericidal concentration of L. scoparium essential oil was determined, and the emulsion's antibiofilm effects visualized using confocal laser scanning microscopy. L. scoparium essential oil demonstrated a lower IC50 (0.02% at 48 h) when compared to the clinical control chlorhexidine (0.002% at 48 h) and displayed lower cumulative cytotoxicity. Higher concentrations of L. scoparium essential oil (≥ 0.1%) at 6 h resulted in higher caspase 3/7 activation, suggesting an apoptotic pathway of cell death. A minimal bactericidal concentration of 0.1% w/w was observed for 6 oral bacteria and 0.01% w/v for Porphyromonas gingivalis. Textural and rheometric analysis indicated increased stability of emulsion with a 1 : 3 ratio of L. scoparium essential oil: Oryza sativa carrier oil. The optimized 5% w/w L. scoparium essential oil emulsion showed increased bactericidal penetrative effects on Streptococci gordonii biofilms compared to oil alone and to chlorhexidine controls. This study has demonstrated the safety, formulation, and antimicrobial activity of L. scoparium essential oil emulsion for potential antibacterial applications at mucosal sites.
  18. Rahmani M, Toia RF, Croft KD
    Planta Med, 1995 Oct;61(5):487-8.
    PMID: 7480216
  19. Balz JP, Das NP
    Planta Med, 1979 Jun;36(2):174-7.
    PMID: 461570
  20. Razali NNM, Ng CT, Fong LY
    Planta Med, 2019 Nov;85(16):1203-1215.
    PMID: 31539918 DOI: 10.1055/a-1008-6138
    Centella asiatica, a triterpene-rich medicinal herb, is traditionally used to treat various types of diseases including neurological, dermatological, and metabolic diseases. A few articles have previously reviewed a broad range of pharmacological activities of C. asiatica, but none of these reviews focuses on the use of C. asiatica in cardiovascular diseases. This review aims to summarize recent findings on protective effects of C. asiatica and its active constituents (asiatic acid, asiaticoside, madecassic acid, and madecassoside) in cardiovascular diseases. In addition, their beneficial effects on conditions associated with cardiovascular diseases were also reviewed. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords "Centella asiatica," "asiatic acid," "asiaticoside," "madecassic acid," and "madecassoside." The articles published between 2004 and 2018 that are related to the aforementioned topics were selected. A few clinical studies published beyond this period were also included. The results showed that C. asiatica and its active compounds possess potential therapeutic effects in cardiovascular diseases and cardiovascular disease-related conditions, as evidenced by numerous in silico, in vitro, in vivo, and clinical studies. C. asiatica and its triterpenes have been reported to exhibit cardioprotective, anti-atherosclerotic, antihypertensive, antihyperlipidemic, antidiabetic, antioxidant, and anti-inflammatory activities. In conclusion, more clinical and pharmacokinetic studies are needed to support the use of C. asiatica and its triterpenes as therapeutic agents for cardiovascular diseases. Besides, elucidation of the molecular pathways modulated by C. asiatica and its active constituents will help to understand the mechanisms underlying the cardioprotective action of C. asiatica.
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