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Lipids of Aspergillus
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
P. Chakrabarti, M. Kundu, J. Basu
Sterols are constituents of biomembranes of eukaryotic cells. They maintain membrane stability by modulating membrane fluidity. Ergosterol has been reported as the major sterol of Aspergillus species.13 However, in A. oryzae, brassicasterol is the main sterol.14 Lanosterol is also found in A. nidulans.15 Unlike other yeasts and fungi, A. nidulans contains sterol mostly in the free form and not as the steryl esters.16 In addition to ergosterol, 14-dehydroergosterol, ergosterol peroxide and cervisterol are also present in A. niger.17 Sterol esters formed from sterol and fatty acids are the storage forms of sterols in fungi.
Ketoconazole
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
At low concentrations, ketoconazole, similar to the other azole antifungal agents, has a fungistatic effect on susceptible fungi by inhibiting sterol synthesis in the cell membrane. It inhibits the 14 alpha-demethylation of lanosterol, resulting in reduction in ergosterol synthesis. It differs from its antifungal analogs in that at higher concentrations it is not usually fungicidal to susceptible fungi. Ketoconazole can exert a fungicidal effect at very high concentrations, but such high levels are usually unattainable in tissues after oral dosing (Borgers et al., 1983).
Examples of single Chinese and botanical medicines derived from TCM
Published in Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang, Chinese and Botanical Medicines, 2017
Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang
In two separate studies, solvent-extracted garlic and sulfur compounds given to patients with hyperlipidemia lowered cholesterol levels and the researchers suggested that the effects resembled those of HMG-CoA reductase inhibitors. One of the constituents in fresh garlic and in solvent extracts is S-allyl-l-cysteine, which is also present in a large amount in aged garlic extract. This material typically contains 19% of the S-allyl cysteine found in the original cloves. This compound is a potent inhibitor of hepatic cholesterol synthesis. Recent research suggests that the site of inhibition is downstream of lanosterol synthesis, as HMG CoA reductase does not appear to be affected. The accumulation of methyl sterols was detected using gas chromatography in cultured hepatoma cells treated with fresh garlic macerates, suggesting that 4a-methyl oxidase is the principal enzyme inhibited in cholesterol synthesis. It has been concluded that all garlic compounds sharing an allyl-disulfide or allyl sulfhydryl group appear to be inhibitors of the enzyme.
Ginsenoside Rg1 Prevents H2O2-induced Lens Opacity
Published in Current Eye Research, 2021
Guowei Zhang, Min Zhang, Jianfeng Yu, Lihua Kang, Huaijin Guan
As there is no single universally accepted pharmacological agent that has emerged to either inhibit or reverse the progression of cataract, it is important to look for alternative pharmacological measures for the treatment of this disorder. In recent years, there has been breakthrough progress in the pharmaceutical research of cataract therapy. Lanosterol, a kind of tetracyclic triterpenoid, was found to have the ability to reverse protein aggregation in cataract lens. This chemical substance showed an obvious and remarkable effect in the cataract model of rabbits ex vivo and dogs in vivo.35 5-cholesten-3b, 25-diol, functioned as a pharmacological chaperone, could improve lens transparency in the hereditary cataract mouse by binding and stabilizing the more soluble forms of a-crystallins.36 But both of these two substances have very limited water solubility, which brings difficulties in the further clinical application. The good water solubility and low toxicity of Rg1 make it as suitable candidate pharmacological intervention to prevent or delay cataract formation.
Protective Effects of Nicotinamide Riboside on H2O2-induced Oxidative Damage in Lens Epithelial Cells
Published in Current Eye Research, 2021
Biting Zhou, Guangyu Zhao, Yihua Zhu, Xiaole Chen, Nanwen Zhang, Juhua Yang, Hong Lin
Given the limitations of cataract surgery, drug treatment, which may delay the opacity of the lens and reduce the incidence and medical costs, has been ahot research topic in the field of cataract treatment. However, due to the extremely poor permeability of the lens to these drugs, they do not specifically target the signalling pathways in the lens, thus reducing their protective effects on the lens.3 Some natural substances, including aspirin, aspirin analogues, protein stabilizers and exogenous antioxidants, have been reported to delay or prevent experimental protein aggregation, oxidation, and insolubility in the lens.8,9 However, the ocular transport, long-term safety and tolerability of most drugs have not been evaluated. Zhao etal.10 found that children with congenital cataracts carry amutation in the LSS gene that blocks lanosterol synthase activity. Furthermore, invivo and invitro studies have suggested vital roles for lanosterol in preventing and treating cataracts, which is good news for patients who are unable to undergo surgical therapy. However, the safety and effectiveness of lanosterol in patients with cataract require further clinical verification. Moreover, the effect of lanosterol on other types of cataract is unclear. Therefore, the identification or development of effective therapeutic drugs remains an urgent problem.
Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Fabrice Pagniez, Nicolas Lebouvier, Young Min Na, Isabelle Ourliac-Garnier, Carine Picot, Marc Le Borgne, Patrice Le Pape
Several events are involved in the membrane biosynthesis, especially the production of lipids as sterols and phospholipids. We demonstrated that 8 g inhibits Candida ergosterol synthesis as observed with other azole drugs. This inhibition led to membrane integrity perturbations through ergosterol depletion, precursor accumulation (lanosterol) and production of alternative 14α-methyl sterols (14α-methyl-fecosterol, 14α-methyl-episterol and 14α-methyl-3,6-diol). Identification of 14α-methylated sterols evidenced a blockage of CYP51 as a way of action of 8 g. Interestingly, the effects of 8 g on sterol metabolism are observed in CAAL93 (fluconazole susceptible strain) at 4 ng/mL whereas the same results are observed after fluconazole treatment at a 1000-fold higher concentration (4 µg/mL). Moreover, the same effects are seen when fluconazole-resistant strains (CAKR7 and CAGL2) were treated by 8 g at 4 µg/mL whereas nothing happened after treatment with the same dose of fluconazole. These results show the potency of this new indole-triazole derivative compound.