Displaying publications 61 - 80 of 121 in total

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  1. Khan AU, Ullah R, Khan A, Mustafa MR, Hussain J, Murugan DD, et al.
    Clin Exp Hypertens, 2012;34(2):132-9.
    PMID: 21967029 DOI: 10.3109/10641963.2011.601383
    This study describes the vasorelaxant potential of some pure compounds isolated from Phlomis bracteosa L. marrubiin, phlomeoic acid, and two new constituents labeled as RA and RB. In rat thoracic aortic rings denuded of endothelium, marrubiin, phlomeoic acid, RA, and RB caused relaxation of high K(+) (80 mM) and phenylephrine (1 μM)-induced contractions at the concentration range of 1.0-1000 μg/mL. Marrubiin, phlomeoic acid, RA, and RB concentration dependently (3.0-10 μg/mL) shifted the Ca(++) curves to the right obtained in Ca(++)-free medium. The vasodilator effect of marrubiin, phlomeoic acid, RA, and RB was partially blocked by N(ω)-nitro-L-arginine methyl ester in endothelium-intact aorta preparations. These results reveal that P. bracteosa constituents: marrubiin, phlomeoic acid, RA, and RB exhibit vasodilator action occurred via a combination of endothelium-independent Ca(++) antagonism and endothelium-dependent N(ω)-nitro-L-arginine methyl ester-sensitive nitric oxide-modulating mechanism.
    Matched MeSH terms: Diterpenes/isolation & purification; Diterpenes/pharmacology
  2. Zakaria NH, Mohamed Tap F, Aljohani GF, Abdul Majid FA
    J Biomol Struct Dyn, 2025 Apr;43(7):3429-3448.
    PMID: 38165434 DOI: 10.1080/07391102.2023.2298726
    Honey-iQfood is an herbal supplement made of a mixture of polyherbal extracts and wild honey. The mixture is traditionally claimed to improve various conditions related to brain cells and functions including dementia and Alzheimer's disease. Glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5) have been identified as being involved in the pathological hyperphosphorylation of tau proteins, which leads to the formation of neurofibrillary tangles and causes Alzheimer's disease. Therefore, this study was conducted to confirm the traditional claims by detection of active compounds, namely curcumin, gallic acid, catechin, rosmarinic acid, and andrographolide in the raw materials of Honey-iQfood through HPLC analysis, molecular docking, and dynamic simulations. Two potential compounds, andrographolide, and rosmarinic acid, produced the best binding affinities following the molecular docking of the active compounds against the GSK-3β and CDK5 targets. Andrographolide binds with GSK-3β at -8.2 kcal/mol, whereas rosmarinic acid binds to CDK5 targets at -8.6 kcal/mol. Molecular dynamics was further carried out to confirm the docking results and clarify their dynamic properties such as RMSD, RMSF, rGyr, SASA, PSA, and binding free energy. CDK5-andrographolide complexes had the best MM-GBSA score (-83.63 kcal/mol) compared to other complexes, indicating the better interaction profile and stability of the complex. These findings warrant further research into andrographolide and rosmarinic acid as efficient inhibitors of tau protein hyperphosphorylation to verify their therapeutic potential in brain-related illnesses.
    Matched MeSH terms: Diterpenes/pharmacology; Diterpenes/chemistry
  3. Koe XF, Tengku Muhammad TS, Chong AS, Wahab HA, Tan ML
    Food Sci Nutr, 2014 Sep;2(5):500-20.
    PMID: 25473508 DOI: 10.1002/fsn3.122
    A multiplex RT-qPCR was developed to examine CYP1A2, CYP2D6, and CYP3A4 induction properties of compounds from food and herbal sources. The induction of drug metabolizing enzymes is an important pharmacokinetic interaction with unique features in comparison with inhibition of metabolizing enzymes. Cytochrome induction can lead to serious drug-drug or drug-food interactions, especially if the coadministered drug plasma level is critical as it can reduce therapeutic effects and cause complications. Using this optimized multiplex RT-qPCR, cytochrome induction properties of andrographolide, curcumin, lycopene, bergamottin, and resveratrol were determined. Andrographolide, curcumin, and lycopene produced no significant induction effects on CYP1A2, CYP2D6, and CYP3A4. However, bergamottin appeared to be a significant in vitro CYP1A2 inducer starting from 5 to 50 μmol/L with induction ranging from 60 to 100-fold changes. On the other hand, resveratrol is a weak in vitro CYP1A2 inducer. Examining the cytochrome induction properties of food and herbal compounds help complement CYP inhibition studies and provide labeling and safety caution for such products.
    Matched MeSH terms: Diterpenes
  4. Ibrahim Abdelwahab S, Syaed Koko W, Mohamed Elhassan Taha M, Mohan S, Achoui M, Ameen Abdulla M, et al.
    Eur J Pharmacol, 2012 Mar 5;678(1-3):61-70.
    PMID: 22227329 DOI: 10.1016/j.ejphar.2011.12.024
    Columbin, a diterpenoid furanolactone, was isolated purely for the first time from the plant species Tinspora bakis. The anti-inflammatory effects of columbin were studied in vitro, in silico and in vivo. The effect of columbin on nitric oxide was examined on lipopolysaccharide-interferon-gamma (LPS/IFN) induced RAW264.7 macrophages. In vitro and in silico cyclooxygenase-1 and cyclooxygenase-2 inhibitory activities of columbin using biochemical kit and molecular docking, respectively, were investigated. Mechanism of columbin in suppressing NF-kappaB-translocation was tested using Cellomics®NF-κB activation assay and ArrayScan Reader in LPS-stimulated RAW264.7 cells. Moreover, effects of columbin in vivo that were done on carrageenan-induced mice paw-oedema were tested. Lastly, the in vitro and in vivo toxicities of columbin were examined on human liver cells and mice, respectively. Treatment with columbin or N(ω)-nitro-l-arginine methyl ester (l-NAME) inhibited LPS/IFN-γ-induced NO production without affecting the viability of RAW264.7. Pre-treatment of stimulated cells with columbin did not inhibit the translocation of NF-κB to the nucleus in LPS-stimulated cells. COX-1 and COX-2 inhibitory activities of columbin were 63.7±6.4% and 18.8±1.5% inhibition at 100μM, respectively. Molecular docking study further helped in supporting the observed COX-2 selectivity. Whereby, the interaction of columbin with Tyr385 and Arg120 signifies its higher activity in COX-2, as Tyr385 was reported to be involved in the abstraction of hydrogen from C-13 of arachidonate, and Arg120 is critical for high affinity arachidonate binding. Additionally, columbin inhibited oedema formation in mice paw. Lastly, the compound was observed to be safe in vitro and in vivo. This study presents columbin as a potential anti-inflammatory drug.
    Matched MeSH terms: Diterpenes/isolation & purification; Diterpenes/pharmacology*; Diterpenes/toxicity
  5. Ahmad W, Jantan I, Bukhari SN
    Front Pharmacol, 2016;7:59.
    PMID: 27047378 DOI: 10.3389/fphar.2016.00059
    Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the rainforests or mixed deciduous forests in Asia and Africa, is used in traditional medicines to treat numerous health conditions. This review summarizes the up-to-date reports about the ethnobotany, phytochemistry, pharmacological activities, toxicology, and clinical trials of the plant. It also provides critical assessment about the present knowledge of the plant which could contribute toward improving its prospect as a source of lead molecules for drug discovery. The plant has been used traditionally in the treatment of jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fracture, scabies, hypertension, reducing thirst, increasing appetite, cooling down the body temperature, and maintaining good health. Phytochemical analyses of T. crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed that the crude extracts and isolated compounds of T. crispa possessed a broad range of pharmacological activities such as anti-inflammatory, antioxidant, immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic activities. Most pharmacological studies were based on crude extracts of the plant and the bioactive compounds responsible for the bioactivities have not been well identified. Further investigations are required to transform the experience-based claims on the use of T. crispa in traditional medicine practices into evidence-based information. The plant extract used in pharmacological and biological studies should be qualitatively and quantitatively analyzed based on its biomarkers. There should be detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more elaborate toxicity study to ensure safety of the plant for human use. More clinical trials are encouraged to be carried out if there are sufficient preclinical and safety data.
    Matched MeSH terms: Diterpenes, Clerodane
  6. Abd Aziz NA, Hasham R, Sarmidi MR, Suhaimi SH, Idris MKH
    Saudi Pharm J, 2021 Feb;29(2):143-165.
    PMID: 33679177 DOI: 10.1016/j.jsps.2020.12.016
    Medicinal plants have gained much interest in the prevention and treatment of common human disease such as cold and fever, hypertension and postpartum. Bioactive compounds from medicinal plants were synthesised using effective extraction methods which have important roles in the pharmaceutical product development. Orthosiphon aristatus (OA), Eurycoma longifolia (EL) and Andrographis paniculata (AP) are among popular medicinal herbs in Southeast Asia. The major compounds for these medicinal plants are polar bioactive compounds (rosmarinic acid, eurycomanone and andrographolide) which have multiple benefits to human health. The bioactive compounds are used as a drug to function against a variety of diseases with the support of scientific evidence. This paper was intended to prepare a complete review about the extraction techniques (e.g. OA, EL and AP) of these medicinal plants based on existing studies and scientific works. Suitable solvents and techniques to obtain their major bioactive compounds and their therapeutic potentials were discussed.
    Matched MeSH terms: Diterpenes
  7. Mustapha bin Akil, Chong, Saw Peng, Norellia binti Bahari
    MyJurnal
    Stevia rebaudiana has recently gained the attention of the food industry as one of the natural sweeteners. The sweet flavour is contributed by the glycoside compounds, especially the rebaudioside A and stevioside, which are the stevia main chemical markers. The aim of the work reported here was to compare the different extraction techniques of stevia leaves using different technologies such as the high pressure and ultrasonic on the extraction of steviol glycosides. In this paper, the extraction techniques yielding the highest glycosides from the leaves of Stevia rebaudiana were determined using hot water extraction (HWE), pressurised liquid extraction (PLE) and ultrasound-assisted extraction (UAE). The steviol glycoside yields were quantified by two chemical markers, rebaudioside A and stevioside of Stevia rebaudiana using highperformance liquid chromatography (HPLC) analysis. The result showed that the HWE managed to obtain 1,110 mg of steviol glycosides. The PLE obtained 294 mg steviol glycosides and the UAE obtained 427.5 mg steviol glycosides. As a conclusion, the results suggested the most efficient technique for stevia extraction in this study was the HWE.
    Matched MeSH terms: Diterpenes, Kaurane
  8. Saiman MZ, Miettinen K, Mustafa NR, Choi YH, Verpoorte R, Schulte AE
    Plant Cell Tissue Organ Cult., 2018;134(1):41-53.
    PMID: 31007320 DOI: 10.1007/s11240-018-1398-5
    Previous studies showed that geraniol could be an upstream limiting factor in the monoterpenoid pathway towards the production of terpenoid indole alkaloid (TIA) in Catharanthus roseus cells and hairy root cultures. This shortage in precursor availability could be due to (1) limited expression of the plastidial geraniol synthase resulted in a low activity of the enzyme to catalyze the conversion of geranyl diphosphate to geraniol; or (2) the limitation of geraniol transport from plastids to cytosol. Therefore, in this study, C. roseus's geraniol synthase (CrGES) gene was overexpressed in either plastids or cytosol of a non-TIA producing C. roseus cell line. The expression of CrGES in the plastids or cytosol was confirmed and the constitutive transformation lines were successfully established. A targeted metabolite analysis using HPLC shows that the transformed cell lines did not produce TIA or iridoid precursors unless elicited with jasmonic acid, as their parent cell line. This indicates a requirement for expression of additional, inducible pathway genes to reach production of TIA in this cell line. Interestingly, further analysis using NMR-based metabolomics reveals that the overexpression of CrGES impacts primary metabolism differently if expressed in the plastids or cytosol. The levels of valine, leucine, and some metabolites derived from the shikimate pathway, i.e. phenylalanine and tyrosine were significantly higher in the plastidial- but lower in the cytosolic-CrGES overexpressing cell lines. This result shows that overexpression of CrGES in the plastids or cytosol caused alteration of primary metabolism that associated to the plant cell growth and development. A comprehensive omics analysis is necessary to reveal the full effect of metabolic engineering.
    Matched MeSH terms: Diterpenes
  9. Al-Khdhairawi AAQ, Low YY, Manshoor N, Arya A, Jelecki M, Alshawsh MA, et al.
    J Nat Prod, 2020 12 24;83(12):3564-3570.
    PMID: 33305943 DOI: 10.1021/acs.jnatprod.0c00618
    Two new diterpene pyrones, asperginols A (1) and B (2), and four known analogues (3-6) were isolated from the endophytic fungus Aspergillus sp. HAB10R12. The structures and absolute configurations of these compounds were elucidated based on the analysis of their NMR, MS, and X-ray diffraction data. The revision of the absolute configurations at C-10, C-11, and C-14 of the known diterpene pyrones (3-6) and the determination of the configuration at the polyene side chain for compounds (4-6) were made using chemical methods and vibrational circular dichroism analysis. This group of diterpene pyrone compounds showed unique structural features including a 7/6/6 tricyclic diterpene moiety with an unusual trans-syn-trans stereochemical arrangement. Compound 6 showed moderate activity against the HT-29 colon cancer cell line.
    Matched MeSH terms: Diterpenes
  10. Haida, Z., Asikin, A., Hakiman, M.
    MyJurnal
    Stevia rebaudiana Bertoni is a perennial herbal species with a number of therapeutic properties. The leaves of S. rebaudiana are the most important part of the plant as they contain high
    level of sweetener compounds known as steviol glycosides; which are known to possess
    antioxidant, antimicrobial, and antifungal activities. Among the steviol glycosides, stevioside
    and rebaudioside A are the most abundant sweetening compounds of interest, documented to
    be 30 - 250 folds sweeter than sucrose or refined sugar. The therapeutic properties of the
    species make it more interesting as they play important roles as anti-hyperglycaemic agent to
    lower glucose levels in the blood, thus commonly used in the treatment of diabetes mellitus
    and obesity. Known to have sweet tasting leaves, its extract which contains antioxidant
    compounds have been used to treat cancer, reduce inflammatory, and hypertension. S. rebaudiana has drawn the attention of health-conscious fitness lovers all over the world as non-caloric sweetener, and has been widely cultivated for being the most suitable sweetening substitution.
    Matched MeSH terms: Diterpenes, Kaurane
  11. Mohammed Abdul KS, Rayadurgam J, Faiz N, Jovanović A, Tan W
    J Cell Mol Med, 2020 09;24(18):10924-10934.
    PMID: 32794652 DOI: 10.1111/jcmm.15721
    In the present study, we have investigated potential cardioprotective properties of Isosteviol analogue we recently synthesized and named JC105. Treatment of heart embryonic H9c2 cells with JC105 (10 μM) significantly increased survival of cells exposed to hypoxia-reoxygenation. JC105 (10 μM) activated ERK1/2, DRP1 and increased levels of cardioprotective SUR2A in hypoxia-reoxygenation, but did not have any effects on ERK1/2, DRP1 and/or SUR2A in normoxia. U0126 (10 μM) inhibited JC105-mediated phosphorylation of ERK1/2 and DRP1 without affecting AKT or AMPK, which were also not regulated by JC105. Seahorse bioenergetic analysis demonstrated that JC105 (10 μM) did not affect mitochondria at rest, but it counteracted all mitochondrial effects of hypoxia-reoxygenation. Cytoprotection afforded by JC105 was inhibited by U0126 (10 μM). Taken all together, these demonstrate that (a) JC105 protects H9c2 cells against hypoxia-reoxygenation and that (b) this effect is mediated via ERK1/2. The unique property of JC105 is that selectively activates ERK1/2 in cells exposed to stress, but not in cells under non-stress conditions.
    Matched MeSH terms: Diterpenes, Kaurane/pharmacology; Diterpenes, Kaurane/therapeutic use*; Diterpenes, Kaurane/chemistry
  12. Norazlina Noordin, Rusli Ibrahim, Nur Hidayah Mohd Sajahan, Salmah Moosa, Sobri Hussein
    MyJurnal
    Stevia rebaudiana Bertoni is a perennial herb that belongs to the family of Asteraceae. It is a
    natural sweetener plant known as sweet leaf, which is estimated to be 300 times sweeter than cane
    sugar. In this study, micropropagation and in vitro mutagenesis of this natural herb was
    successfully conducted. It was found that shoot tips on MS medium supplemented with 1 mg/l
    Kinetin showed the highest shoot induction and multiplication after 3 weeks of culture
    (5.50±1.95a). Radiosensitivity test was conducted to identify the dose that killed 50% of the
    irradiated explants (LD50) for in vitro stevia shoots and to select effective doses to be used for the in
    vitro mutagenesis. Shoot tips were irradiated with acute and chronic gamma radiation at 0, 10, 20,
    30, 40, 60, and 80Gy. At 60 Gy and 80 Gy, all treated shoot tips were not survived. In this study,
    LD50 for the stevia was estimated at 29 Gy for acute irradiation and 45 Gy for chronic irradiation.
    The effective doses were selected at 10, 20, 30 and 40 Gy. These selected doses were applied for the
    in vitro mutagenesis of the stevia shoots
    Matched MeSH terms: Diterpenes, Kaurane
  13. Abdul Razak F, Baharuddin BA, Akbar EFM, Norizan AH, Ibrahim NF, Musa MY
    Arch Oral Biol, 2017 Aug;80:180-184.
    PMID: 28448807 DOI: 10.1016/j.archoralbio.2017.04.014
    OBJECTIVE: Compact-structured oral biofilm accumulates acids that upon prolonged exposure to tooth surface, causes demineralisation of enamel. This study aimed to assess the effect of alternative sweeteners Equal Stevia(®), Tropicana Slim(®), Pal Sweet(®) and xylitol on the matrix-forming activity of plaque biofilm at both the early and established stages of formation.

    METHODS: Saliva-coated glass beads (sGB) were used as substratum for the adhesion of a mixed-bacterial suspension of Streptococcus mutans, Streptococcus sanguinis and Streptococcus mitis. Biofilms formed on sGB at 3h and 24h represented the early and established-plaque models. The biofilms were exposed to three doses of the sweeteners (10%), introduced at three intervals to simulate the exposure of dental plaque to sugar during three consecutive food intakes. The treated sGB were (i) examined under the SEM and (ii) collected for turbidity reading. The absorbance indicated the amount of plaque mass produced. Analysis was performed comparative to sucrose as control.

    RESULTS: Higher rate of bacterial adherence was determined during the early compared to established phases of formation. Comparative to the sweeteners, sucrose showed a 40% increase in bacterial adherence and produced 70% more plaque-mass. Bacterial counts and SEM micrographs exhibited absence of matrix in all the sweetener-treated biofilms at the early phase of formation. At the established phase, presence of matrix was detected but at significantly lower degree compared to sucrose (p<0.05).

    CONCLUSION: Alternatives sweeteners promoted the formation of oral biofilm with lighter mass and lower bacterial adherence. Hence, suggesting alternative sweeteners as potential antiplaque agents.

    Matched MeSH terms: Diterpenes, Kaurane
  14. Prakash I, Markosyan A, Bunders C
    Foods, 2014 Feb 27;3(1):162-175.
    PMID: 28234311 DOI: 10.3390/foods3010162
    This work aims to review and showcase the unique properties of rebaudioside M as a natural non-caloric potential sweetener in food and beverage products. To determine the potential of rebaudioside M, isolated from Stevia rebaudiana Bertoni, as a high potency sweetener, we examined it with the Beidler Model. This model estimated that rebaudioside M is 200-350 times more potent than sucrose. Numerous sensory evaluations of rebaudioside M's taste attributes illustrated that this steviol glycoside possesses a clean, sweet taste with a slightly bitter or licorice aftertaste. The major reaction pathways in aqueous solutions (pH 2-8) for rebaudioside M are similar to rebaudioside A. Herein we demonstrate that rebaudioside M could be of great interest to the global food industry because it is well-suited for blending and is functional in a wide variety of food and beverage products.
    Matched MeSH terms: Diterpenes, Kaurane
  15. Aziz AN, Ismail NH, Halim SNA, Looi CY, Anouar EH, Langat MK, et al.
    Phytochemistry, 2018 Dec;156:193-200.
    PMID: 30316148 DOI: 10.1016/j.phytochem.2018.10.002
    A phytochemical investigation of the stem barks of the Malaysian Croton oblongus Burm.f. (Syn. Croton laevifolius Blume) (Euphorbiaceae) yielded seven previously undescribed ent-neo-clerodane diterpenoids, laevifins A - G and the known crovatin (3). Structures were established by a combination of spectroscopic methods including HRESIMS, NMR spectroscopy and X-ray crystallography. The absolute configuration of crovatin and laevifins A-G was established by comparison of experimental ECD and theoretical TDDFT ECD calculated spectra. This is the first report on the occurrence of the sesquiterpenoid cryptomeridiol in a Croton species. In vitro cytotoxicity assays on laevifins A, B and G showed moderate activities against the MCF-7 cancer cell line (IC50 102, 115 and 106 μM, respectively) while β-amyrin and acetyl aleuritolic acid showed good anti-inflammatory activity on the LPS-induced NF-κB translocation inhibition in RAW 264.7 cells assay with IC50 values of 23.5 and 35.4 μg/mL, respectively.
    Matched MeSH terms: Diterpenes, Clerodane/isolation & purification; Diterpenes, Clerodane/pharmacology*; Diterpenes, Clerodane/chemistry
  16. Takahiro Ishii, Takashi Kamada, Chin-soon Phan, Charles S. Vairappan
    Sains Malaysiana, 2018;47:319-322.
    Soft corals are often the research interest organism due to their structural diverse secondary metabolites with wide
    spectrum of biological activities range from antibacterial to anticancer potentials. The Borneo Island is rich in diversity
    of marine organisms including soft coral. Therefore, a population of Bornean soft coral belongs to genus Nephthea
    was collected from Mantanani Island (Sabah, Malaysia) which led to the isolation of a novel norditerpene, chabrolene
    (1) together with three known compounds (2-4). The chemical structure of 1 was determined by NMR and HREIMS data.
    Compound 1 exhibited repellent activity against the maize weevil Sitophilus zeamais.
    Matched MeSH terms: Diterpenes
  17. Agatonovic-Kustrin S, Wong S, Dolzhenko AV, Gegechkori V, Ku H, Tan WK, et al.
    J Pharm Biomed Anal, 2023 Apr 01;227:115308.
    PMID: 36827737 DOI: 10.1016/j.jpba.2023.115308
    Extracts of two Salvia species, Salvia apiana (white sage) and Salvia officinalis (common sage) were screened for phytoconstituents with the ability to act as antidiabetic, cognitive enhancing, or antimicrobial agents, by hyphenation of high-performance thin-layer chromatography with enzymatic and microbial effect directed assays. Two bioactive zones with α-amylase inhibition (zone 1 and zone 2), 3 zones for acetylcholinesterase inhibition (zones 3, 4 and 5), and two zones for antimicrobial activity (zones 4 and 5) were detected. The compounds from the five bioactive zones were initially identified by coelution with standards and comparing the RF values of standards to the bioautograms. Identity was confirmed with ATR-FTIR spectra of the isolated compounds from the bioactive zones. A significantly higher α-amylase and acetylcholinesterase inhibition of S. apiana leaf extract was associated with a higher flavonoid and diterpenoid content. Fermented S. officinalis extract exhibited a significantly higher ability to inhibit α-amylase compared to other non-fermented extracts from this species, due to increased extraction of flavonoids. The ATR-FTIR spectra of 2 zones with α-amylase inhibition, indicated that flavonoids and phenolic acids were responsible for α-amylase inhibition. Multiple zones of acetylcholinesterase inhibition were related to the presence of phenolic abietane diterpenoids and triterpenoid acids. The presence of abietane diterpenoids and triterpenoid acids was also found responsible for the mild antimicrobial activity. Flash chromatography was used to isolate sufficient amounts of bioactive compounds for further characterisation via NMR and MS spectroscopy. Five compounds were assigned to the zones where bioactivity was observed: cirsimaritin (zone 1), a caffeic acid polymer (zone 2), 16-hydroxyrosmanol (zone 3), 16-hydroxycarnosic acid (zone 4), oleanolic and ursolic acids (zone 5).
    Matched MeSH terms: Diterpenes, Abietane
  18. Jada SR, Matthews C, Saad MS, Hamzah AS, Lajis NH, Stevens MF, et al.
    Br J Pharmacol, 2008 Nov;155(5):641-54.
    PMID: 18806812 DOI: 10.1038/bjp.2008.368
    BACKGROUND AND PURPOSE: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.
    EXPERIMENTAL APPROACH: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.
    KEY RESULTS: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis.
    CONCLUSION AND IMPLICATIONS: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle arrest, coupled with induction of apoptosis.
    Matched MeSH terms: Diterpenes/chemical synthesis; Diterpenes/pharmacokinetics*; Diterpenes/chemistry
  19. Jayakumar T, Hsieh CY, Lee JJ, Sheu JR
    PMID: 23634174 DOI: 10.1155/2013/846740
    Andrographis paniculata (Burm. F) Nees, generally known as "king of bitters," is an herbaceous plant in the family Acanthaceae. In China, India, Thailand, and Malaysia, this plant has been widely used for treating sore throat, flu, and upper respiratory tract infections. Andrographolide, a major bioactive chemical constituent of the plant, has shown anticancer potential in various investigations. Andrographolide and its derivatives have anti-inflammatory effects in experimental models asthma, stroke, and arthritis. In recent years, pharmaceutical chemists have synthesized numerous andrographolide derivatives, which exhibit essential pharmacological activities such as those that are anti-inflammatory, antibacterial, antitumor, antidiabetic, anti-HIV, antifeedant, and antiviral. However, what is noteworthy about this paper is summarizing the effects of andrographolide against cardiovascular disease, platelet activation, infertility, and NF- κ B activation. Therefore, this paper is intended to provide evidence reported in relevant literature on qualitative research to assist scientists in isolating and characterizing bioactive compounds.
    Matched MeSH terms: Diterpenes
  20. Rajaratinam H, Nafi SNM
    Malays J Med Sci, 2019 Sep;26(5):6-20.
    PMID: 31728115 MyJurnal DOI: 10.21315/mjms2019.26.5.2
    Oestrogen receptor (ER)-positive breast cancer is one of the common forms of breast cancer affecting women worldwide. ER-positive breast cancer patients are subjected to anti-oestrogen therapy such as selective oestrogen receptor modulator (SERM) and aromatase inhibitors (AIs). Recently, the emergence of resistance to anti-oestrogen treatment is under intensive focus. The different mechanisms postulated to explain the occurrence of resistance in ER-positive breast cancer treatment include the loss of ER function and the crosstalk between signalling pathways in cancer cells. Recent literature highlighted that the cholesterol biosynthesis pathway acts as a novel mechanism underlying resistance to oestrogen deprivation. The present study aimed to highlight the role of cholesterol biosynthesis in anti-oestrogen treatment resistance, putatively suggesting an alternative plant-based treatment using andrographolide from Andrographis paniculata. The hypolipidaemic effect of andrographolide can be utilised to prevent the resistance in the treatment of ER-positive breast cancer contributed by cholesterol biosynthesis.
    Matched MeSH terms: Diterpenes
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