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1

Warrilow, Andrew G. S., Josie E. Parker, Claire L. Price, W. David Nes, Edward P. Garvey, William J. Hoekstra, Robert J. Schotzinger, Diane E. Kelly, and Steven L. Kelly. "The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme." Antimicrobial Agents and Chemotherapy 60, no. 8 (May 9, 2016): 4530–38. http://dx.doi.org/10.1128/aac.00349-16.

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ABSTRACTCryptococcosis is a life-threatening disease often associated with HIV infection. ThreeCryptococcusspecies CYP51 enzymes were purified and catalyzed the 14α-demethylation of lanosterol, eburicol, and obtusifoliol. The investigational agent VT-1129 bound tightly to all three CYP51 proteins (dissociation constant [Kd] range, 14 to 25 nM) with affinities similar to those of fluconazole, voriconazole, itraconazole, clotrimazole, and ketoconazole (Kdrange, 4 to 52 nM), whereas VT-1129 bound weakly to human CYP51 (Kd, 4.53 μM). VT-1129 was as effective as conventional triazole antifungal drugs at inhibiting cryptococcal CYP51 activity (50% inhibitory concentration [IC50] range, 0.14 to 0.20 μM), while it only weakly inhibited human CYP51 activity (IC50, ∼600 μM). Furthermore, VT-1129 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. Finally, the cellular mode of action for VT-1129 was confirmed to be CYP51 inhibition, resulting in the depletion of ergosterol and ergosta-7-enol and the accumulation of eburicol, obtusifolione, and lanosterol/obtusifoliol in the cell membranes.
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2

Taton, M., and A. Rahier. "Properties and structural requirements for substrate specificity of cytochrome P-450-dependent obtusifoliol 14 α-demethylase from maize (Zea mays) seedlings." Biochemical Journal 277, no. 2 (July 15, 1991): 483–92. http://dx.doi.org/10.1042/bj2770483.

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The biochemical properties of cytochrome P-450-dependent obtusifoliol 14 alpha-demthylase (P-450OBT.14DM) from maize (Zea mays) seedlings were defined. In particular, the enzyme was shown by differential centrifugation to be localized in the endoplasmic reticulum. P-450OBT.14DM had an apparent Km of 160 +/- 5 microM and an apparent Vmax of 65 +/- 5 pmol/min per mg of protein for its best substrate, obtusifoliol. The substrate specificity of P-450OBT.14DM was thoroughly investigated by comparing the demethylation of obtusifoliol with that of a series of 15 natural or novel synthetic analogues of obtusifoliol. The results obtained clearly indicate that three distinct domains of the sterol substrate are governing obtusifoliol demethylation by P-450OBT.14DM. They revealed that (i) P-450OBT.14DM has probably a specific apolar binding site for the side chain, (ii) the delta 8-double bond is an absolute requirement for substrate demethylation and (iii) the 3-hydroxy group plays a critical role in the enzyme-substrate interaction. Interestingly the binding site, beyond the C-3 position, contains a cleft which cannot accommodate a 4 beta-methyl substituent present in lanosterol or eburicol, the precursors of 14-desmethylsterols respectively in mammals and yeast. This result indicates that P-450OBT.14DM is a novel constitutive cytochrome P-450 with a high degree of substrate and product specificity.
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Lepesheva, Galina I., W. David Nes, Wenxu Zhou, George C. Hill, and Michael R. Waterman. "CYP51 fromTrypanosoma bruceiIs Obtusifoliol-Specific†." Biochemistry 43, no. 33 (August 2004): 10789–99. http://dx.doi.org/10.1021/bi048967t.

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Rahier, Alain, and Maryse Taton. "Plant sterol biosynthesis: 7-oxo-obtusifoliol analogues as potential selective inhibitors of cytochrome P-450 dependent obtusifoliol 14α-demethylase." Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1125, no. 2 (April 1992): 215–22. http://dx.doi.org/10.1016/0005-2760(92)90048-z.

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Tanaka, Reiko, Kazuaki Kasubuchi, Shunji Kita, and Shunyo Matsunaga. "Obtusifoliol and related steroids from the whole herb of Euphorbia chamaesyce." Phytochemistry 51, no. 3 (June 1999): 457–63. http://dx.doi.org/10.1016/s0031-9422(99)00041-2.

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6

Falsone, Gioacchino, and Claudia Schneider. "Über Inhaltsstoffe von Euphorbiaceae, 8. Mitt. [1]. Triterpenester und Triterpenalkohole aus Euphorbia biglandulosa Desf. / Constituents of Euphorbiaceae, 8. Comm. [1]. Triterpen Esters and Triterpen Alcohols from Euphorbia biglandulosa Desf." Zeitschrift für Naturforschung B 40, no. 4 (April 1, 1985): 553–55. http://dx.doi.org/10.1515/znb-1985-0420.

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Fatty acids and acetic acid esters of lanosterol and cycloartenol and triterpens alcohols were isolated from the latex of Euphorbia biglandulosa Desf. The triterpenesters were identified as (E,Z)-2,4-decadienoyllanosterol (1a), (E,Z)-2,4-octadienoyllanosterol (1b), (E,Z)-2,4-oc- tadienoylcycloartenol (2a), (2E,4Z)-2,4,6-decatrienoyllanosterol (1c), (2E,4Z)-2,4,6-deca- trienoylcycloartenol (2b), lanosterylacetat (1d) and cycloartenylacetat (2c) by IR-, 1H-NMR- and MS-spectroscopy and hydrolysis. The triterpens alcohols were identified as butyrospermol, cyclo­artenol, 24-methylencycloartanol and obtusifoliol.
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7

Marichal, Patrick, Jos Gorrens, Leen Laurijssens, Karen Vermuyten, Carl Van Hove, Ludo Le Jeune, Peter Verhasselt, et al. "Accumulation of 3-Ketosteroids Induced by Itraconazole in Azole-Resistant Clinical Candida albicans Isolates." Antimicrobial Agents and Chemotherapy 43, no. 11 (November 1, 1999): 2663–70. http://dx.doi.org/10.1128/aac.43.11.2663.

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ABSTRACT The effects of itraconazole on ergosterol biosynthesis were investigated in a series of 16 matched clinical Candida albicans isolates which had been previously analyzed for mechanisms of resistance to azoles (D. Sanglard, K. Kuchler, F. Ischer, J. L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother., 39:2378–2386, 1995). Under control conditions, all isolates contained ergosterol as the predominant sterol, except two strains (C48 and C56). In isolates C48 and C56, both less susceptible to azoles than their parent, C43, substantial concentrations (20 to 30%) of 14α-methyl-ergosta-8,24(28)-diene-3β,6α-diol (3,6-diol) were found. Itraconazole treatment of C43 resulted in a dose-dependent inhibition of ergosterol biosynthesis (50% inhibitory concentration, 2 nM) and accumulation of 3,6-diol (up to 60% of the total sterols) together with eburicol, lanosterol, obtusifoliol, 14α-methyl-ergosta-5,7,22,24(28)-tetraene-3βol, and 14α-methyl-fecosterol. In strains C48 and C56, no further increase of 3,6-diol was observed after exposure to itraconazole. Ergosterol synthesis was less sensitive to itraconazole inhibition, as was expected for these azole-resistant isolates which overexpress ATP-binding cassette transporter genes CDR1 andCDR2. In addition to 3,6-diol, substantial amounts of obtusifolione were found after exposure to itraconazole. This toxic 3-ketosteroid was demonstrated previously to accumulate after itraconazole treatment in Cryptococcus neoformans andHistoplasma capsulatum but has not been reported inCandida isolates. Accumulation of obtusifolione correlated with nearly complete growth inhibition in these azole-resistant strains compared to that found in the susceptible parent strain, although the onset of growth inhibition only occurred at higher concentrations of itraconazole. ERG25 and ERG26 are the only genes assigned to the 4-demethylation process, of which the 3-ketoreductase is part. To verify whether mutations in theseERG25 genes contributed to obtusifolione accumulation, their nucleotide sequences were determined in all three related isolates. No mutations in ERG25 alleles of isolates C48 and C56 were found, suggesting that this gene is not involved in obtusifolione accumulation. The molecular basis for the accumulation of this sterol in these two strains remains to be established.
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8

Kushiro, Masayo, Takeshi Nakano, Ken Sato, Kazutoshi Yamagishi, Tadao Asami, Akihiko Nakano, Suguru Takatsuto, Shozo Fujioka, Yutaka Ebizuka, and Shigeo Yoshida. "Obtusifoliol 14α-Demethylase (CYP51) Antisense Arabidopsis Shows Slow Growth and Long Life." Biochemical and Biophysical Research Communications 285, no. 1 (July 2001): 98–104. http://dx.doi.org/10.1006/bbrc.2001.5122.

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9

Bailen, Maria, Mourad Daoubi Khamlichi, Ahmed Benharref, Rafael A. Martinez-Diaz, and Azucena Gonzalez-Coloma. "New Bioactive Semisynthetic Derivatives of 31-Norlanostenol and Obtusifoliol from Euphorbia Officinarum." Natural Product Communications 11, no. 6 (June 2016): 1934578X1601100. http://dx.doi.org/10.1177/1934578x1601100609.

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Fifteen semisynthetic terpenoid derivatives from the major latex components of Euphorbia officinarum have been evaluated against the insect pest Spodoptera littoralis, two species of protozoan parasites, Trypanosoma cruzi and Leishmania infantum, and also against insect Sf9 and mammalian CHO cells to test their selective cytotoxicity. Our results showed that 40% of the test substances were postingestive toxicants to S. littoralis. All the tested derivatives had cytotoxic effects on insect-derived Sf9 cells, whereas mammalian CHO cells were affected by a lower number of compounds (47%). Furthermore, 87% of the test compounds had antiparasitic effects on bothi. infantum and T. cruzi, with some of them being selective parasite toxicants.
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10

Bargar, Tom M., Jacob Secor, Lowell D. Markley, Brian A. Shaw, and Jon A. Erickson. "A comparative molecular field analysis study of obtusifoliol 14α-methyl demethylase inhibitors." Pesticide Science 55, no. 11 (October 15, 1999): 1059–69. http://dx.doi.org/10.1002/(sici)1096-9063(199911)55:11<1059::aid-ps57>3.0.co;2-j.

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11

Jaramillo-Madrid, Ana Cristina, Raffaela Abbriano, Justin Ashworth, Michele Fabris, Mathieu Pernice, and Peter J. Ralph. "Overexpression of Key Sterol Pathway Enzymes in Two Model Marine Diatoms Alters Sterol Profiles in Phaeodactylum tricornutum." Pharmaceuticals 13, no. 12 (December 21, 2020): 481. http://dx.doi.org/10.3390/ph13120481.

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Sterols are a class of triterpenoid molecules with diverse functional roles in eukaryotic cells, including intracellular signaling and regulation of cell membrane fluidity. Diatoms are a dominant eukaryotic phytoplankton group that produce a wide diversity of sterol compounds. The enzymes 3-hydroxy-3-methyl glutaryl CoA reductase (HMGR) and squalene epoxidase (SQE) have been reported to be rate-limiting steps in sterol biosynthesis in other model eukaryotes; however, the extent to which these enzymes regulate triterpenoid production in diatoms is not known. To probe the role of these two metabolic nodes in the regulation of sterol metabolic flux in diatoms, we independently over-expressed two versions of the native HMGR and a conventional, heterologous SQE gene in the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum. Overexpression of these key enzymes resulted in significant differential accumulation of downstream sterol pathway intermediates in P. tricornutum. HMGR-mVenus overexpression resulted in the accumulation of squalene, cycloartenol, and obtusifoliol, while cycloartenol and obtusifoliol accumulated in response to heterologous NoSQE-mVenus overexpression. In addition, accumulation of the end-point sterol 24-methylenecholesta-5,24(24’)-dien-3β-ol was observed in all P. tricornutum overexpression lines, and campesterol increased three-fold in P. tricornutum lines expressing NoSQE-mVenus. Minor differences in end-point sterol composition were also found in T. pseudonana, but no accumulation of sterol pathway intermediates was observed. Despite the successful manipulation of pathway intermediates and individual sterols in P. tricornutum, total sterol levels did not change significantly in transformed lines, suggesting the existence of tight pathway regulation to maintain total sterol content.
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12

RAHIER, Alain, Maryse TATON, and Pierre BENVENISTE. "Cycloeucalenol - obtusifoliol isomerase. Structural requirements for transformation or binding of substrates and inhibitors." European Journal of Biochemistry 181, no. 3 (May 1989): 615–26. http://dx.doi.org/10.1111/j.1432-1033.1989.tb14768.x.

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13

O'Brien, Martin, Sier-Ching Chantha, Alain Rahier, and Daniel P. Matton. "Lipid Signaling in Plants. Cloning and Expression Analysis of the Obtusifoliol 14α-Demethylase from Solanum chacoense Bitt., a Pollination- and Fertilization-Induced Gene with Both Obtusifoliol and Lanosterol Demethylase Activity." Plant Physiology 139, no. 2 (September 16, 2005): 734–49. http://dx.doi.org/10.1104/pp.105.066639.

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14

Kahn, Rachel Alice, Søren Bak, Carl Erik Olsen, Ib Svendsen, and Birger Lindberg Møller. "Isolation and Reconstitution of the Heme-Thiolate Protein Obtusifoliol 14α-Demethylase fromSorghum bicolor(L.) Moench." Journal of Biological Chemistry 271, no. 51 (December 20, 1996): 32944–50. http://dx.doi.org/10.1074/jbc.271.51.32944.

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15

Rahier, A., and M. Taton. "The 14α-demethylation of obtusifoliol by a cytochrome P-450 monooxygenase from higher plants microsomes." Biochemical and Biophysical Research Communications 140, no. 3 (November 1986): 1064–72. http://dx.doi.org/10.1016/0006-291x(86)90743-6.

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16

Jiao, Zhengli, Weijuan Xu, Xuan Zeng, Xinlan Xu, Mingyong Zhang, and Kuaifei Xia. "Obtusifoliol 14α-demethylase OsCYP51G1 is involved in phytosterol synthesis and affects pollen and seed development." Biochemical and Biophysical Research Communications 529, no. 1 (August 2020): 91–96. http://dx.doi.org/10.1016/j.bbrc.2020.05.216.

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17

Salmon, Florence, Maryse Taton, Pierre Benveniste, and Alain Rahier. "Plant sterol biosynthesis: Novel potent and selective inhibitors of cytochrome P450-dependent obtusifoliol 14α-methyl demethylase." Archives of Biochemistry and Biophysics 297, no. 1 (August 1992): 123–31. http://dx.doi.org/10.1016/0003-9861(92)90649-h.

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18

Nam, Jiho, Dong-Won Seol, Choong-Gu Lee, Gabbine Wee, Siyoung Yang, and Cheol-Ho Pan. "Obtusifolin, an Anthraquinone Extracted from Senna obtusifolia (L.) H.S.Irwin & Barneby, Reduces Inflammation in a Mouse Osteoarthritis Model." Pharmaceuticals 14, no. 3 (March 10, 2021): 249. http://dx.doi.org/10.3390/ph14030249.

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Osteoarthritis (OA) is an age-related degenerative disease that causes cartilage dysfunction and inflammation. Obtusifolin, an anthraquinone extracted from Senna obtusifolia (L.) H.S.Irwin & Barneby seeds, has anti-inflammatory functions; it could be used as a drug component to relieve OA symptoms. In this study, we investigated the effects of obtusifolin on OA inflammation. In vitro, interleukin (IL)-1β (1 ng/mL)-treated mouse chondrocytes were co-treated with obtusifolin at different concentrations. The expression of matrix metalloproteinase (Mmp) 3, Mmp13, cyclooxygenase 2 (Cox2), and signaling proteins was measured by polymerase chain reaction and Western blotting; collagenase activity and the PGE2 level were also determined. In vivo, OA-induced C57BL/6 mice were administered obtusifolin, and their cartilage was stained with Safranin O to observe damage. Obtusifolin inhibited Mmp3, Mmp13, and Cox2 expression to levels similar to or more than those after treatment with celecoxib. Additionally, obtusifolin decreased collagenase activity and the PGE2 level. Furthermore, obtusifolin regulated OA via the NF-κB signaling pathway. In surgically induced OA mouse models, the cartilage destruction decreased when obtusifolin was administered orally. Taken together, our results show that obtusifolin effectively reduces cartilage damage via the regulation of MMPs and Cox2 expression. Hence, we suggest that obtusifolin could be a component of another OA symptom reliever.
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Bessonova, I. A., �. Kh Batirov, and M. R. Yagudaev. "Obtusifolin ? A new coumarin from roots of Haplophyllum obtusifolium." Chemistry of Natural Compounds 24, no. 2 (1988): 156–58. http://dx.doi.org/10.1007/bf00596740.

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20

TAN, Kun-Ling, Ming-Yu HU, Xian-Bi LI, Shan QIN, De-Mou LI, Xiao-Ying LUO, Juan ZHAO, et al. "Molecular Identification and Expression Analysis of GhCYP51G1 Gene, a Homologue of Obtusifoliol-14Alpha-Demethylase Gene, from Upland Cotton." Acta Agronomica Sinica 35, no. 7 (July 2009): 1194–201. http://dx.doi.org/10.1016/s1875-2780(08)60091-7.

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21

Cabello-Hurtado, Francisco, Alfred Zimmerlin, Alain Rahier, Maryse Taton, Richard DeRose, Svetlana Nedelkina, Yannick Batard, Francis Durst, Kenneth E. Pallett, and Danièle Werck-Reichhart. "Cloning and Functional Expression in Yeast of a cDNA Coding for an Obtusifoliol 14α-Demethylase (CYP51) in Wheat." Biochemical and Biophysical Research Communications 230, no. 2 (January 1997): 381–85. http://dx.doi.org/10.1006/bbrc.1996.5873.

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22

Taton, M., P. Ullmann, P. Benveniste, and A. Rahier. "Interaction of triazole fungicides and plant growth regulators with microsomal cytochrome P-450-dependent obtusifoliol 14α-methyl demethylase." Pesticide Biochemistry and Physiology 30, no. 2 (February 1988): 178–89. http://dx.doi.org/10.1016/0048-3575(88)90051-x.

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23

Mazoir, Noureddine, Ahmed Benharref, María Bailén, Matías Reina, Azucena González-Coloma, and Rafael A. Martínez-Díaz. "Antileishmanial and Antitrypanosomal Activity of Triterpene Derivatives from Latex of Two Euphorbia Species." Zeitschrift für Naturforschung C 66, no. 7-8 (August 1, 2011): 360–66. http://dx.doi.org/10.1515/znc-2011-7-807.

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The in vitro activity on Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes of 25 semisynthetic terpenoid derivatives has been evaluated. These compounds were obtained through chemical modifications of the major components of Euphorbia resinifera (α-euphol and α-euphorbol) and Euphorbia officinarum (obtusifoliol and 31-norlanosterol). Leishmaniasis and Chagas´ disease are major worldwide health problems. The drugs of choice for their treatment are still problematic in both cases, and therefore there is an urgent need to discover new drugs with high activity and low side effects. Natural products have become a key source of new drugs in the last years. The genus Euphorbia has been the subject of abundant phytochemical and pharmacological research because of its potential medical applications, but the antiparasitic effects of derivatives from plants of this genus are still unknown. Our results showed that 76% and 64% of the test compounds had antiparasitic effects on L. infantum and T. cruzi, respectively. The different activities on both parasites, especially their moderate effects on mammalian cells, indicate an interesting selective toxicity.
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Sanora, Ghea Dionita, Elly Yana Mastura, Muhammad Ongky Muji Handoyo, and Erlix Rakhmad Purnama. "Identification of Anticancer Active Compound from GC-MS Test Results of Zodia Leaves (Evodia suaveolens) Ethanol Extract." Jurnal Biota 5, no. 2 (December 5, 2019): 89–95. http://dx.doi.org/10.19109/biota.v5i2.3374.

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Cancer is estimated to be the second leading cause of death globally in 2018. The background of the study was the prevalence of cancer in Indonesia in 2018 reaching 775.120 people. Treatments such as surgery, chemotherapy, radiotherapy, immunotherapy, and hormone therapy have negative side effects. Herbal medicine is an alternative treatment with lower side effects that can reduce the side effects of existing treatments. The aim of this study was to identify the results of GC-MS active compounds from ethanol extract of zodia leaves which have the potential as anticancer. The method of this research was observational research through scientific literature. GC-MS results showed 22 active compounds contained in ethanol extract of zodia leaves. Based on the literature searching, there are 17 active compounds that have potential to be anticancer. Menthofuran; evodone; Bicyclopentene; Delta-Selinene; 3,5,7-Octatrien-2-Ol, 2,6-Dimethyl; Aromadendrene oxide 2; Alpha-bisabolol; 2,4-Dimethyl-2,4-Heptadienal; Phytol; Squalene; Beta-Tocopherol; D-alpha-Tocopherol; Stigmasta-5,23-dien-3.beta.-ol; (23S)-ethylcholest-5-en-3.beta.ol; 24,25-Dihydrolanosterol; Lanosterol; and Obtusifoliol. The compounds are targeted in breast, lung, and ovarian cancer.
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Kukina, Tat'yana Petrovna, and Irina Vladimirovna Khan. "LIPOPHILIC CONSTITUENTS OF PEDICULARIS STRIATA PALLAS И PEDICULARIS FLAVA PALLAS." chemistry of plant raw material, no. 4 (December 27, 2019): 113–18. http://dx.doi.org/10.14258/jcprm.2019044952.

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Some species of Pedicularis have been widely applied in traditional Chinese medicine. Some plants of Pedicularis genus have a great potential for the discovery of new drugs because most of them have not been studied in detail. Extracts from the plants of genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscles, nootropic effect and other activitiesin vivo and in vitro. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides, lignans glycosides, flavonoids, alkaloids and other polar compounds have been isolated and identified from the genus Pedicularis. Information about lipophilic constituents is too poor. The results of our investigations of aliphatic and triterpenoic substances by GC-MS are identification of 25 neutral and 18 acid compounds including sterols, triterpenoids and unusual branched hydrocarbons. Main components of neutral fraction are β-sitosterol and phytol. Triterpenol fraction is found to content cycloartenol, 24-methylene-cycloartanol, obtusifoliol, stigma-7-en-3-ol and citrostadienol. Cycloartenol prevails in both types of row material. The main components of acids are palmitic, linoleic and linolnic acids. Pedicularis striata contains significant amount of melissic and montanic acids. All compounds were found for the first time in these row materials. Identified compounds could be potential chemotaxonomic markers for the Pedicularis species.
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Yuen, Heidi, Andrew Hung, Angela Wei Hong Yang, and George Binh Lenon. "Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C." International Journal of Molecular Sciences 21, no. 4 (February 16, 2020): 1326. http://dx.doi.org/10.3390/ijms21041326.

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Overweight and obesity is a growing global health concern. Current management of obesity includes lifestyle intervention, bariatric surgery and medication. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Lorcaserin, an appetite control drug, has demonstrated efficacy in appetite control by targeting 5-HT2C but causes undesirable side effects. This study aimed to explore the potential usage of Cassiae semen (CS), a well-known traditional Chinese medicine used to treat obesity. A computational molecular docking study was performed to determine the binding mechanism of CS compounds to the 5-HT2C receptors in both active, agonist-bound and inactive, antagonist-bound conformations. By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists which may mimic the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Overall, this study proposed several CS compounds which may be responsible for exerting anti-obesity effects via appetite suppression by 5-HT2C receptor activation.
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Aghaei, Mahmoud, Zeinab Yazdiniapour, Mustafa Ghanadian, Behzad Zolfaghari, Virginia Lanzotti, and Vahid Mirsafaee. "Obtusifoliol related steroids from Euphorbia sogdiana with cell growth inhibitory activity and apoptotic effects on breast cancer cells (MCF-7 and MDA-MB231)." Steroids 115 (November 2016): 90–97. http://dx.doi.org/10.1016/j.steroids.2016.07.008.

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Cabello-Hurtado, Francisco, Maryse Taton, Nathalie Forthoffer, Rachel Kahn, Soren Bak, Alain Rahier, and Daniele Werck-Reichhart. "Optimized expression and catalytic properties of a wheat obtusifoliol 14alpha-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51." European Journal of Biochemistry 262, no. 2 (June 1999): 435–46. http://dx.doi.org/10.1046/j.1432-1327.1999.00376.x.

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29

Maillot-Vernier, Pascale, Hubert Schaller, Pierre Benveniste, and Geneviève Belliard. "Biochemical characterization of a sterol mutant plant regenerated from a tobacco callus resistant to a triazole cytochrome-P-450-obtusifoliol-14-demethylase inhibitor." Biochemical and Biophysical Research Communications 165, no. 1 (November 1989): 125–30. http://dx.doi.org/10.1016/0006-291x(89)91043-7.

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30

Urbina, Julio A., Renee Lira, Gonzalo Visbal, and Javier Bartrolí. "In Vitro Antiproliferative Effects and Mechanism of Action of the New Triazole Derivative UR-9825 against the Protozoan Parasite Trypanosoma (Schizotrypanum)cruzi." Antimicrobial Agents and Chemotherapy 44, no. 9 (September 1, 2000): 2498–502. http://dx.doi.org/10.1128/aac.44.9.2498-2502.2000.

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ABSTRACT We describe the in vitro antiproliferative effects of the new triazole derivative UR-9825 against the protozoan parasiteTrypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease in Latin America. The compound was found to be extremely active against the cultured (epimastigote) form of the parasite, equivalent to that present in the reduviid vector, with a MIC of 30 nM, a concentration 33-fold lower than that required with the reference compound ketoconazole. At that MIC, growth arrest coincided with depletion of the parasite's 4,14-desmethyl endogenous sterols (ergosterol, 24-ethylcholesta-5,7,22-trien-3b-ol, and precursors) and their replacement by methylated sterols (lanosterol, 24-methylenedihydrolanosterol, and obtusifoliol), as revealed by high-resolution gas chromatography coupled with mass spectrometry. This indicated that the primary mechanism of action of UR-9825 was inhibition of the parasite's sterol C14α demethylase, as seen with other azole derivatives. The phospholipid composition of growth-arrested epimastigotes was also altered, when compared to controls, with a significant increase in the content of phosphatidylethanolamine and phosphatidylserine and a concomitant reduction of the content of phosphatidylcholine. The clinically relevant intracellular amastigote form, grown in cultured Vero cells at 37°C, was even more sensitive to UR-9825, with a MIC of 10 nM, comparable to that for ketoconazole. The results showed that UR-9825 is among the most potent azole derivatives tested against this parasite and support in vivo studies with this compound.
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Lepesheva, G. I., T. Y. Hargrove, R. D. Ott, W. D. Nes, and M. R. Waterman. "Biodiversity of CYP51 in trypanosomes." Biochemical Society Transactions 34, no. 6 (October 25, 2006): 1161–64. http://dx.doi.org/10.1042/bst0341161.

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Sterol 14α-demethylases (CYP51) are metabolic cytochromes P450, found in each biological kingdom. They catalyse a single three-step reaction included in all sterol biosynthetic pathways. Plant CYP51s have strict preference towards their physiological substrate O (obtusifoliol), which is C-4-monomethylated. Natural substrates of animal/fungal CYP51 (lanosterol, 24,25-dihydrolanosterol or 24-methylenelanosterol) are C-4-dimethylated. CYP51 from the pathogenic protozoa TB (Trypanosoma brucei) is the first example of O-specific sterol 14α-demethylase in non-photosynthetic organisms. Surprisingly, at 83% amino acid identity to the TB orthologue, CYP51 from TC (Trypanosoma cruzi) clearly prefers C-4-dimethylated sterols. Replacement of animal/fungi-like Ile105 in the B′ helix of TC CYP51 with phenylalanine, the residue found in this position in all plant and other trypanosome CYP51s, dramatically increases the ability of the enzyme to metabolize O, converting it into a more plant-like sterol 14α-demethylase. A more than 100-fold increase in binding and turnover is observed for the 24-desmethyl analogue of O [N (norlanosterol)], which is found in vivo in procyclic forms of TB and is a good TB CYP51 substrate in vitro. We believe that (i) N is a non-conventional CYP51 substrate, preferred in TB and perhaps other Trypanosomatidae and (ii) functional similarity of TC CYP51 to animal/fungal orthologues is a result of evolutionary convergence (including F105I mutation), leading to different pathways for sterol production in TC versus TB.
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Xia, Kuaifei, Xiaojing Ou, Huadan Tang, Ren Wang, Ping Wu, Yongxia Jia, Xiaoyi Wei, et al. "Rice microRNA osa-miR1848 targets the obtusifoliol 14α-demethylase geneOsCYP51G3and mediates the biosynthesis of phytosterols and brassinosteroids during development and in response to stress." New Phytologist 208, no. 3 (June 17, 2015): 790–802. http://dx.doi.org/10.1111/nph.13513.

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Maillot-Vernier, Pascale, Hubert Schaller, Pierre Benveniste, and Geneviève Belliard. "In Vitro Selection of Calli Resistant to a Triazole Cytochrome-P-450-Obtusifoliol-14-Demethylase Inhibitor from Protoplasts of Nicotiana tabacum L. cv Xanthi." Plant Physiology 93, no. 3 (July 1, 1990): 1190–95. http://dx.doi.org/10.1104/pp.93.3.1190.

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34

Warrilow, Andrew G. S., Claire M. Hull, Nicola J. Rolley, Josie E. Parker, W. David Nes, Stephen N. Smith, Diane E. Kelly, and Steven L. Kelly. "Clotrimazole as a Potent Agent for Treating the Oomycete Fish Pathogen Saprolegnia parasitica through Inhibition of Sterol 14α-Demethylase (CYP51)." Applied and Environmental Microbiology 80, no. 19 (August 1, 2014): 6154–66. http://dx.doi.org/10.1128/aem.01195-14.

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ABSTRACTA candidate CYP51 gene encoding sterol 14α-demethylase from the fish oomycete pathogenSaprolegnia parasitica(SpCYP51) was identified based on conserved CYP51 residues among CYPs in the genome. It was heterologously expressed inEscherichia coli, purified, and characterized. Lanosterol, eburicol, and obtusifoliol bound to purified SpCYP51 with similar binding affinities (Ks, 3 to 5 μM). Eight pharmaceutical and six agricultural azole antifungal agents bound tightly to SpCYP51, with posaconazole displaying the highest apparent affinity (Kd, ≤3 nM) and prothioconazole-desthio the lowest (Kd, ∼51 nM). The efficaciousness of azole antifungals as SpCYP51 inhibitors was confirmed by 50% inhibitory concentrations (IC50s) of 0.17 to 2.27 μM using CYP51 reconstitution assays. However, most azole antifungal agents were less effective at inhibitingS. parasitica,Saprolegnia diclina, andSaprolegnia feraxgrowth. Epoxiconazole, fluconazole, itraconazole, and posaconazole failed to inhibitSaprolegniagrowth (MIC100, >256 μg ml−1). The remaining azoles inhibitedSaprolegniagrowth only at elevated concentrations (MIC100[the lowest antifungal concentration at which growth remained completely inhibited after 72 h at 20°C], 16 to 64 μg ml−1) with the exception of clotrimazole, which was as potent as malachite green (MIC100, ∼1 μg ml−1). Sterol profiles of azole-treatedSaprolegniaspecies confirmed that endogenous CYP51 enzymes were being inhibited with the accumulation of lanosterol in the sterol fraction. The effectiveness of clotrimazole against SpCYP51 activity (IC50, ∼1 μM) and the concentration inhibiting the growth ofSaprolegniaspeciesin vitro(MIC100, ∼1 to 2 μg ml−1) suggest that clotrimazole could be used againstSaprolegniainfections, including as a preventative measure by pretreatment of fish eggs, and for freshwater-farmed fish as well as in leisure activities.
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35

Cao, Tong, and Dale H. Vitt. "A Taxonomic Assessment of Grimmia obtusifolia Gao et Cao and Schistidium obtusifolium Irel. et Crum." Bryologist 88, no. 4 (1985): 362. http://dx.doi.org/10.2307/3242676.

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TAN, Kun-Ling, Ming-Yu HU, Xian-Bi LI, Shan QIN, De-Mou LI, Xiao-Ying LUO, Juan ZHAO, et al. "Molecular Identification and Expression Analysis of GhCYP51G1 Gene, a Homologue of Obtusifoliol-14a-demethylase Gene, from Upland Cotton (Gos-sypium hirsutum L.)." ACTA AGRONOMICA SINICA 35, no. 7 (July 23, 2009): 1194–201. http://dx.doi.org/10.3724/sp.j.1006.2009.01194.

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37

Burger, C. "Virus-induced silencing of sterol biosynthetic genes: identification of a Nicotiana tabacum L. obtusifoliol-14 -demethylase (CYP51) by genetic manipulation of the sterol biosynthetic pathway in Nicotiana benthamiana L." Journal of Experimental Botany 54, no. 388 (May 13, 2003): 1675–83. http://dx.doi.org/10.1093/jxb/erg184.

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38

Grausem, Bernard, Nicole Chaubet, Claude Gigot, John C. Loper, and Pierre Benveniste. "Functional expression of Saccharomyces cerevisiae CYP51A1 encoding lanosterol-14-demethylase in tobacco results in bypass of endogenous sterol biosynthetic pathway and resistance to an obtusifoliol-14-demethylase herbicide inhibitor." Plant Journal 7, no. 5 (May 1995): 761–70. http://dx.doi.org/10.1046/j.1365-313x.1995.07050761.x.

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39

Assumpção, Jorge, and Marcelo T. Nascimento. "Estrutura e composição florística de quatro formações vegetais de restinga no complexo lagunar Grussaí/Iquipari, São João da Barra, RJ, Brasil." Acta Botanica Brasilica 14, no. 3 (December 2000): 301–15. http://dx.doi.org/10.1590/s0102-33062000000300007.

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Foi estudada a vegetação de restinga do complexo lagunar Grussaí/Iquipari (21°44'S; 41°02'O), que compreende a bacia das lagunas de Grussaí e Iquipari, com aproximadamente 4.800ha. Uma transecção de 25ha (2500x100m) foi delimitada no sentido mar/interior e coletas botânicas realizadas entre os anos de 1995 e 1997. As quatro unidades fisionômicas ocorrentes na área foram estudadas e, através do Índice de Valor de Cobertura, foram determinadas as espécies dominantes em cada formação: 1) Formação Praial-Graminóide: Remirea maritima, Ipomoea imperati, Sporobolus virginicus e Chamaecyse thymifolia; 2) Formação Praial com Moitas: Schinus terebinthifolius, Eugenia sulcata, Pilosocereus arrabidae e Cereus fernambucensis; 3) Formação de Clusia: Pera glabrata, Eugenia sulcata, Sideroxylon obtusifolium e Scutia arenicola; 4) Formação Mata de Restinga: Maytenus obtusifolia, Pera glabrata, Protium heptaphyllum e Coccoloba alnifolia. A similaridade florística da área estudada com outras restingas nos Estados do Rio de Janeiro e Espírito Santo não ultrapassou 41%, onde a proximidade geográfica não representou aumento da similaridade. Os resultados ressaltam a variação da flora de restinga ao longo de um pequeno trecho do litoral brasileiro.
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Bak, Soren, Rachel Alice Kahn, Carl Erik Olsen, and Barbara Ann Halkier. "Cloning and expression in Escherichia coli of the obtusifoliol 14alpha-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P450 orthologous to the sterol 14alpha-demethylases (CYP51) from fungi and mammals." Plant Journal 11, no. 2 (February 1997): 191–201. http://dx.doi.org/10.1046/j.1365-313x.1997.11020191.x.

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41

Rahier, A. "Inhibition of δ8 → δ7-sterol isomerase and of cycloeucalenol—obtusifoliol isomerase by N-benzyl-8-aza-4α, 10-dimethyl-trans-decal-3β-ol, an analogue of a carbocationic high energy intermediate." Phytochemistry 24, no. 6 (1985): 1223–32. http://dx.doi.org/10.1016/s0031-9422(00)81106-1.

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42

Strnad, L., M. Hejcman, V. Křišťálová, P. Hejcmanová, and V. Pavlů. "Mechanical weeding of Rumex obtusifolius L. under different N, P and K availabilities in permanent grassland." Plant, Soil and Environment 56, No. 8 (August 19, 2010): 393–99. http://dx.doi.org/10.17221/83/2010-pse.

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In Europe, Rumex obtusifolius L. is the most problematic grassland weed species, especially under the conditions of organic farming. The aims of this study were (1) to investigate the effectiveness of repeated mechanical weeding of R. obtusifolius from the permanent sward, cut two or three times per year, by digging the plants out from 5 cm below the soil surface, and (2) to test the effect of nutrient availability on the effectiveness of mechanical weeding. In 2007, the manipulative experiment was established on permanent grassland infested by R. obtusifolius using the following fertilizer treatments: control, P, N, NP and NPK. Plants of R. obtusifolius were removed eight times during three vegetation seasons. No significant decrease in the density of R. obtusifolius was recorded after three vegetation seasons and density was not significantly affected by fertilizer treatment. The cover of R. obtusifolius decreased slightly, but significantly, over the study period from 7.5% to 4.5%. The cover of R. obtusifolius was only marginally affected by fertilizer treatment. Mechanical weeding by digging the plants out from 5 cm below the ground is not a sufficient method of control for R. obtusifolius in infested fertile grasslands, even when applied eight times during three vegetation seasons.
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Augustine, C., I. D. Kwari, J. U. Igwebuikwe, S. B. Adamu, C. I. Medugu, and D. I. Mojaba. "Laying performance and cost-benefits of feeding brown laying hens with raw or processed tropical sickle pod (Senna obtusifolia) seed meal based-diets." Agricultural Science and Technology 10, no. 4 (2018): 297–301. http://dx.doi.org/10.15547/10.15547/ast.2018.04.056.

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Abstract. A feeding trial was conducted for 16 weeks to evaluate the effects and cost-benefits of feeding raw or processed Senna obtusifolia (S. obtusifolia) seed meal based-diets on the laying performance of ISA brown laying hens. Six experimental diets were compounded to contain 0% S. obtusifolia seed meal (T1) and 20% each of the raw, boiled, soaked, sprouted and fermented S. obtusifolia seed meals designated as T2, T3, T4, T5 and T6, respectively. One hundred and eighty (180) ISA brown laying hens aged 36 weeks were housed in battery cages (5 birds/0.95m2) and assigned to the six (6) dietary treatments in groups of thirty (30) birds in a completely randomized design. Each replicate cage contains 10 laying hens. Data were collected on feed intake, hen-day egg production (HDEP), hen-house egg production (HHEP), egg weight, egg mass, feed conversion ratio per egg mass, feed cost per kilogram, feed cost per egg mass and mortality. The results indicated that the group of laying hens fed raw S. obtusifolia seed meal based diet recorded the lowest HDEP (52.42%), egg weight (53.08g) and egg mass (2782.45g). Among the hens fed the processed S. obtusifolia seed meal based diets, the laying hens fed the fermented S. obtusifolia seed meal based diet indicated significantly (p<0.05) better HDEP (64.05%), egg weight (58.45g) and egg mass (3743.72g). On economic grounds, the use of raw S. obtusifolia is not cost effective because feed cost per kilogram egg was relatively high (N317.47 or $0.82) in the group of laying hens fed raw S. obtusifolia seed meal based diet. However, the processed S. obtusifolia seed meal based diets showed some economic advantage. In conclusion, 20% of fermented S. obtusifolia seed meal can be incorporated in the diets of laying hens with little or no depreciation in laying performance and economic-benefits.
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Lam, Melville, Dogotari, Prüm, Vithlani, Roers, Becker, and Zimmer. "Mapping Invasive Rumex obtusifolius in Grassland Using Unmanned Aerial Vehicle." Proceedings 30, no. 1 (December 23, 2019): 34. http://dx.doi.org/10.3390/proceedings2019030034.

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Silva, Fabrício Francisco Santos da, and Bárbara França Dantas. "Quantification of storage proteins during seed imbibition of native species from the brazilian caatinga vegetation." Semina: Ciências Agrárias 37, no. 4 (August 30, 2016): 1733. http://dx.doi.org/10.5433/1679-0359.2016v37n4p1733.

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Poincianella pyramidalis (Fabaceae), Schinopsis brasiliensis (Anacardiaceae) and Sideroxylon obtusifolium (Sapotaceae) are native species of the Caatinga vegetation from northeastern Brazil and have both biological importance and potential economic uses. Little is known about the water uptake and degradation of storage proteins during seed germination of these species. The aim of this study was to evaluate the imbibition and quantify the amount of storage proteins during seed germination of P. pyramidalis, S. brasiliensis and S. obtusifolium. Two lots of S. obtusifolium seeds with different vigour were used. Four replicates of 20 seeds of P. pyramidalis, S. brasiliensis and S. obtusifolium, were sown onto gerboxes with blotting paper soaked in distilled water and incubated during 72, 200 and 624 hours. Before and after imbibition seeds were weighed and frozen at until the sequential extraction and analysis of the seed storage proteins. Based on our results, we conclude that seed germination of P. pyramidalis, S. brasiliensis and S. obtusifolium has a well-defined triphasic imbibition. All storage proteins content of P. pyramidalis and S. brasiliensis seeds degraded along with the seed imbibition. Likewise, the content of albumins, globulins and glutelins decreased as S. obtusifolium seeds absorbed water.
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Hartika, Meitri, Syamsuardi Syamsuardi, and Nurainas Nurainas. "Kerapatan Dua Populasi Tumbuhan Invasif Lokal Arenga obtusifolia Mart. di Cagar Alam, Sumatera Barat." Metamorfosa: Journal of Biological Sciences 6, no. 2 (December 23, 2019): 259. http://dx.doi.org/10.24843/metamorfosa.2019.v06.i02.p17.

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Cagar Alam lembah Anai dan Cagar alam Rimbo Panti merupakan suatu kawasan konservasi yang diduga diinvasi oleh tumbuhan Langkap (Arenga obtusifolia Mart.). Adanya kecendrungan invasi tumbuhan Langkap terhadap kawasan konservasi maka perlu dilakukan penelitian mengenai kerapatan tumbuhan Langkap di Cagar Alam Lembah Anai dan Cagar Alam Rimbo Panti. Penempatan plot dilakukan secara acak di kedua lokasi cagar alam. Langkap kerapatan A. obtusifolia Mart. di Cagar Alam Rimbo Panti Lebih Tinggi daripada di Cagar Alam Lembah Anai. Hal ini dikarenakan vegetasi di Cagar Alam Rimbo Panti sedikit sehingga A. obtusifolia Mart. lebih mendominasi kawasan tersebut. Kata Kunci : Spesies invasif, Arenga obtusifolia Mart., Cagar Alam Lembah Anai, Cagar Alam Rimbo Panti, Kerapatan.
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Sawicki, Jakub, Vítězslav Plášek, and Monika Szczecińska. "Recent data on occurrence the sporophytes in populations of dioecious moss, Nyholmiella obtusifolia in North-Eastern Poland." Casopis slezského zemského muzea (A) 60, no. 1 (January 1, 2011): 7–10. http://dx.doi.org/10.2478/v10210-011-0002-y.

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Recent data on occurrence the sporophytes in populations of dioecious moss, Nyholmiella obtusifolia in North-Eastern Poland Moss Nyholmiella obtusifolia is relatively common in Poland, but mostly sterile specimens are found in herbarium collections. Sporogenes were created very rare. During bryological explorations conducted in NE Poland in 2009 - 2011, sporophytes were found in four populations of N. obtusifolia, which account for approximately 7% of the surveyed populations.
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Alfred Maroyi. "Medicinal uses, phytochemistry and biological activities of Ehretia obtusifolia Hochst. ex DC. (Ehretiaceae)." International Journal of Research in Pharmaceutical Sciences 12, no. 2 (May 1, 2021): 1345–52. http://dx.doi.org/10.26452/ijrps.v12i2.4688.

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Ehretia obtusifolia Hochst. ex DC. is a shrub or small tree which occurs naturally in tropical Africa and Asia. This study aims to provide some information about the medicinal uses, phytochemistry and biological activities of E. obtusifolia. This review examines the existing literature on the medicinal uses, phytochemistry and biological activities of E. obtusifolia. This study revealed that the bark, branch, fruit, leaf, root, stem, stem bark and twig decoction or infusion of E. obtusifolia are mainly used to treat and manage sore throat, retained placenta in both humans and animals, teething pain, toothache, abdominal pains, menstrual problems and pain. Phytochemical research revealed that the species is characterized by alkaloids, flavonoids, glycosides, phenolics, phlobatannin, saponin, steroids, tannins and terpenoids. Ethnopharmacological research revealed that the extracts and phytochemical compounds isolated from the species showed antibacterial, anti-diarrhoeal, anti-inflammatory, antinociceptive, antioxidant, cytotoxicity and phytotoxicity activities. Ehretia obtusifolia should be subjected to detailed phytochemical, biological and toxicological studies.
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Harsha N, Madhuri, Piyushika Dulloo, Piyushika Dulloo, Rupachandra S, Rupachandra S, Jagadeeshwari S, Jagadeeshwari S, et al. "ISOLATION AND IDENTIFICATION OF ANTIMICROBIAL PROTEINS FROM THE LEAVES OF VALERIANA HARDWICKII AND SENNA OBTUSIFOLIA." Asian Journal of Pharmaceutical and Clinical Research 11, no. 3 (March 1, 2018): 438. http://dx.doi.org/10.22159/ajpcr.2018.v11i3.23009.

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Objective : The aim of this study was to screen the antimicrobial activity of trypsin-digested peptides isolated from the protein extracts of Valeriana hardwickii and Senna obtusifolia. Methods: The proteins were extracted from the leaves of V. hardwickii and S. obtusifolia which were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein extracts were digested using trypsin which was identified using reverse-phase high-performance liquid chromatography analysis. Further, the antimicrobial efficacy of the digested peptides was investigated.Result: Peptide extracts of V. hardwickii exhibited potent antifungal and antibacterial activity at the maximum concentration of 1.5 mg/ml. Similarly, S. obtusifolia exhibited increased antifungal and antibacterial activity at the concentration of 1.44 mg/ml.Conclusion: The trypsinized extracts of V. hardwickii and S. obtusifolia were plated against Bacillus subtilis which is a promising antibacterial agent.
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Kim, Dong Hyun, Sook Kyung Hyun, Byung Hoon Yoon, Ji-Hyung Seo, Kyung-Tae Lee, Jae Hoon Cheong, Seo Yun Jung, Changbae Jin, Jae Sue Choi, and Jong Hoon Ryu. "Gluco-obtusifolin and Its Aglycon, Obtusifolin, Attenuate Scopolamine-Induced Memory Impairment." Journal of Pharmacological Sciences 111, no. 2 (2009): 110–16. http://dx.doi.org/10.1254/jphs.08286fp.

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