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Evaluation of anti-inflammatory potential and GC-MS profiling of leaf extracts from Clerodendrum infortunatum L.

ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum infortunatum L. is commonly distributed in tropical and subtropical countries and is widely use … re phenol, 3,5-bis(1,1-dimethylethyl)-, hexadecanoic acid methyl ester, estragole, methyl stearate, lanosterol, 9-methoxybicyclo[6.1.0]nona-2,4,6-triene, benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl) 4 hydroxy methyl ester, 22,23-dibromostigmasterol acetate, 3-methyl-4-(phenylthio)-2-prop-2-enyl-2,5-dihydrothiophene 1,1-dioxide, benzenemethanol, α-methyl …

Assessment of Novel Genome-Wide Significant Gene Loci and Lesion Growth in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

IMPORTANCE: Age-related macular degeneration (AMD) is a common threat to vision loss in individuals older than 50 years. While neovascular c … ansferase 6 gene (PRMT6; chromosome 1; slope, 0.046 [95% CI, 0.026-0.066]; P = 4.09 × 10-8) and the lanosterol synthase gene (LSS; chromosome 21; slope, 0.105 [95% CI, 0.068-0.143]; P = 4.07 × 10-7) as the most likely progression-associated genes. CONCLUSIONS AND RELEVANCE: These data provide further insight into the genetic architecture of geographic atrop …

Phytochemical profiling, spectroscopic identification of active compounds, and mechanism of the anticandidal properties of Datura stramonium L. using SwissADMET prediction and molecular docking analysis.

BACKGROUND: Datura stramonium L., a wild-growing herb, has been traditionally used to treat various ailments, including toothache, asthma, r … for the tested enzymes, with the highest binding scores of -7.084 kcal/mol and -7.030 kcal/mol with Lanosterol 14-alpha demethylase (PDB ID: 5JLC, 5TZ1). The results of the in silico pharmacokinetic and drug-likeness properties indicated that compound 1 is a potential anticandidal drug candidate. CONCLUSION: This study highlights that 23 compounds were repo …

Verazine biosynthesis from simple sugars in engineered Saccharomyces cerevisiae.

Steroidal alkaloids are FDA-approved drugs (e.g., Zytiga) and promising drug candidates/leads (e.g., cyclopamine); yet many of the ≥697 know … es cerevisiae (S. cerevisiae) through the inducible upregulation of the native yeast mevalonate and lanosterol biosynthetic pathways, diversion of biosynthetic flux from ergosterol (i.e., native sterol in S. cerevisiae) to cholesterol (i.e., biosynthetic precursor to verazine), and expression of a refactored five-step verazine biosynthetic pathway. The engin …

Oxysterols: novel biologic roles for the 21st century.

A major focus for the 21st century are the sterol intermediates in cholesterol synthesis and their metabolites. No longer considered inactiv … nsulin-induced genes 1 & 2) in which lack of the protein product results in a greater production of lanosterol compared to cholesterol during fetal life with severe dysmorphic consequences. Further support can be derived from in vitro studies of the Sonic hedgehog signaling pathway, essential for normal morphogenesis in the central nervous system and perhaps …

Ganoderic acid A attenuates Porphyromonas gingivalis-induced adhesion molecule expression in gingival fibroblasts and tissues via inhibition of NLRP6 inflammasome activation.

OBJECTIVES: This study aimed to elucidate the regulatory effects and mechanisms of Ganoderic acid A (GAA) on Porphyromonas gingivalis (P. gingivalis)-induced expression of adhesion molecules in human gingival fibroblasts (hGFs) and periodontal tissues, focusing on NLRP6 inflammasome modulation. DESIGN: HGFs were stimulated with P. gingivalis strain W83. The expression levels of NLRP6, caspase-1, IL-1β,IL-18 and adhesion molecules ICAM-1 & VCAM-1 were analyzed by RT-PCR, Western blotting and ELISA, with or without GAA pretreatment. To further explore the regulatory role of GAA on the NLRP6 inf

Discovery of ganodecalone A, from Ganoderma calidophilum for the treatment of acute gastric ulcers by binding to ALOX5 via the MAPK/NF-κB/iNOS signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: "Li medicine" Ganoderma calidophilum is a rare and unique medicinal fungus native to Hainan, China, traditionally used to relieve stomach pain and treat gastric diseases. However, its medicinal applications lack scientific validation despite its prominent role in ethnomedicine. AIM OF THE STUDY: This study aimed to evaluate the therapeutic potential of G. calidophilum extract against gastric ulcer (GU), isolate its main bioactive compound (GDA), and elucidate the underlying mechanisms of action. MATERIALS AND METHODS: In vivo, acute gastric mucosal-injured mic

Euphol prevents experimental autoimmune encephalomyelitis in mice: evidence for the underlying mechanisms.

Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to have anti-inflammatory action. However there are no reports about the effects and mechanisms of euphol in experimental autoimmune encephalomyelitis (EAE), an established model of MS. Here we report the effects and the underlying mechanisms of action of

Antidiabetic and Antihyperlipidemic Properties of a Triterpenoid Compound, Dehydroeburicoic Acid, from Antrodia camphorata in Vitro and in Streptozotocin-Induced Mice.

The aim of this study was to examine the effects of dehydroeburicoic acid (TT) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were randomly divided into six groups and given orally by gavage TT (at three dosages), metformin (Metf), fenfibrate (Feno), or vehicle for 4 weeks. STZ-induced diabetic mice showed elevations in blood glucose levels (P < 0.001). TT treatment markedly decreased blood glucose levels by 42.6-46.5%. Moreover, STZ-induced diabetic mice displayed an increase in circulating triglyceride (TG) and total chol

Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections.

BACKGROUND: Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: This study was condu…

Isolation and biological activity of agrostophillinol from kaffir lime (Citrus hystrix) leaves.

The leaves of the kaffir lime (Citrus hystrix) are commonly used in cuisine and folk medicine. The aim of this study was to isolate a bioactive compound in kaffir lime leaves and characterize its biological activity. The compound was isolated from a hexane fractional extract and identified as agrostophillinol. This is the first report of agrostophillinol isolated from kaffir lime leaves. In terms of cytotoxicity, agrostophillinol exhibited IC50 values of 36.27 ± 7.30 and 53.44 ± 10.63 μg/mL against EoL-1 and HL60 cells, respectively. Agrostophillinol also exhibited potent anti-inflammatory act

Triadimefon causes branchial arch malformations in Xenopus laevis embryos.

BACKGROUND, AIMS AND SCOPE: Triazole-derivatives are potent antifungal agents used as systemic agricultural fungicides and against fungal diseases in humans and domestic animals. They act by inhibiting the cytochrome P-450 conversion of lanosterol to ergosterol, thus resulting in faulty fungal cell wall synthesis. Some data have been published about the teratogenic activity of triazoles on rodent embryos: Hypoplasias, abnormal shape, agenesis of the branchial arches, for example, were reported as typical induced malformations. Unfortunately, no data are available on the embryotoxicity of these…

DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.

As an important nutrient in the human body, cholesterol can not only provide structural components for the body's cells, but also can be transformed into a variety of active substances to regulate cell signaling pathways. As an important cholesterol synthase, DHCR24 participates in important regulatory processes in the body. The application of DHCR24 in tumor clinical diagnosis and treatment also attracts much attention. This article reviews the structure and regulatory characteristics of DHCR24, and the research of DHCR24 on tumor progression. We summarize the possible mechanisms of DHCR24 pr

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… Cholesterol synthesis occurs primarily in the liver, and acetyl-CoA or leucine is converted to cholesterol molecules by nearly 30 enzymatic steps, one of which produces lanosterol, followed by another enzymatic reaction to produce cholesterol. 30 The enzymatic process from lanosterol to cholesterol can … Cholesterol biosynthesis from lanosterol: Development of a novel assay method and characterization of rat liver microsomal lanosterol delta 24-reductase. Biochem J. 1997;326(Pt 2):609-616. doi: 10.1042/bj3260609 49. Horton JD, Shah NA, Warrington JA, et al. …

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and

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… By the action of SQS, FPP is converted to squalene ( 60 ), which is converted sequentially to monooxidaosqualene (MOS) and lanosterol by squalene monooxygenase (SM) and lanosterol synthase, respectively ( 18 ). … Lastly, lanosterol is further metabolized to cholesterol by 19 enzymes, including CYP51A (lanosterol-14α demethylase), TM7SF2 (steroid 14 reductase), SC4MOL (4 methyl sterol oxidase), NSDHL (C3 sterol dehydrogenase), HSD17B7 (3-ketoreductase), EBP (phenylalkylamine Ca 2+ antagonist binding protein), …

Ganoderic acid A/DM-induced NDRG2 over-expression suppresses high-grade meningioma growth.

PURPOSE: N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in grade-III meningioma [anaplastic meningioma (AM)] and associated with clinically aggressive behavior. Current therapies in the treatment of high-grade meningioma are lacking with limited success. This study aims to validate the effect of NDRG2-targeted therapy using structurally related bioactive triterpene compounds derived from the edible mushroom Ganoderma lucidum (ganoderic acid A:GA-A/ganoderic acid DM:GA-DM) in human AM in relevant pre-clinical models. METHODS: Tissue samples from the AM tumor regions of three human

Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern.

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with ora

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… These agents target sterol 14α demethylase converts lanosterol to ergosterol in sterol biosynthesis ( Mann et al., 2003 ; Lepesheva and Waterman, 2011 ; Hata et al., 1996 ). … Ro 48-8.071, a new 2, 3-oxidosqualene: lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin. J. Lipid Res. 1997;38(2):373–390. Murer L., Petkidis A., Vallet T., Vignuzzi M., Greber U.F. …

Recent advances in drug repositioning for the discovery of new anticancer drugs.

Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and targ

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… It is known to inhibit cytochrome P450-dependent lanosterol 14-α-demethylation (14DM) in the ergosterol biosynthesis pathway in fungi 14 . Ergosterol is the main sterol in most yeasts and fungi, being responsible for their membrane integrity and function. …

Ось NSDHL/c-Myc/PKM2 ведет гликолитическое перепрограммирование и рост опухоли в множестве миелом.

Множественная миелома (ММ) остается в основном неизлечимой из-за ее сложной биологии и частого рецидива заболеваний. Перепрограммирование метаболических программ все чаще признается в качестве одного из важнейших факторов развития ММ. Зависящий от NAD (P) стероид дегидрогеназный белок (NSDHL) был выделен в качестве неблагоприятного прогностического гена, связанного с метаболизмом, в плазменной клеточной миеломе, но его функциональное значение и метаболическая роль в MM остаются неясными. Для оценки выражения НКПЧС и его клинической значимости были проанализированы общедоступные наборы данных M

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… NAD (P)-dependent steroid dehydrogenase-like protein (NSDHL) is an enzyme involved in post-squalene cholesterol biosynthesis, where it participates in the C4-demethylation process during the conversion of lanosterol-derived sterol intermediates to cholesterol [ 8 ]. …

Липид Метаболизм и статинская терапия нейродегенеративных заболеваний: эндокринный взгляд.

Справочная информация/цели: Растущий объем данных свидетельствует о наличии связи между дислипидемией и нейродегенеративными заболеваниями, подчеркивая решающую роль липидного метаболизма в здоровье центральной нервной системы. Цель нашей работы состояла в том, чтобы представить обновленную информацию по этой теме с уделением особого внимания клинической практике с эндокринологической точки зрения. Эндокринологи, будучи экспертами в области управления дислипидемиями, могут играть ключевую роль в профилактике и лечении нейродегенеративных заболеваний путем предварительной и эффективной оптимиза

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… The detrimental effects of 6-hydroxydopamine on striatal neurons may be inhibited by squalene [ 85 ], whereas lanosterol acted protectively against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity on dopaminergic neurons in the substantia nigra in mouse models of PD [ 86 ]. …

Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabo

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… Then, squalene is cyclized to lanosterol under the action of squalene epoxidase (SQLE) 30 . Finally, lanosterol undergoes oxidation, decarboxylation and reduction reactions to generate cholesterol 31 . …