Browsing by Subject "Natural products"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases
    (PNAS Online, 2016-07-26) Salmon, Melissa; Thimmappa, Ramesha B.; Minto, Robert E.; Melton, Rachel E.; Hughes, Richard K.; O’Maille, Paul E.; Hemmings, Andrew M.; Osbourn, Anne; Department of Chemistry & Chemical Biology, School of Science
    Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.
  • Thumbnail Image
    Item
    Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature
    (MDPI, 2025-01-20) Diaz, Michael J.; Tran, Jasmine T.; Rose, Drake; Wei, Aria; Lakshmipathy, Deepak; Lipner, Shari R.; Medicine, School of Medicine
    Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact. Emerging evidence suggests that macronutrient and micronutrient-level changes could be beneficial for managing progression and, in some cases, facilitating repigmentation. Antioxidant-rich foods, such as apples, green tea, Indian gooseberry, onions, and peppers, may help mitigate oxidative stress, while inflammatory foods, such as gluten and high-phenol nuts and berries, may exacerbate the condition. Certain supplements, including high-dose vitamin D, vitamin C, vitamin E, and selenium, may enhance phototherapy outcomes. Omega-3 and other unsaturated fatty acids, in addition to prebiotics and probiotics, are under active investigation for their roles in gut health and immune regulation. Notably, plant-derived compounds, i.e., Ginkgo biloba, have demonstrated promise in promoting repigmentation and managing disease progression. However, it must be emphasized that these nutritional interventions remain exploratory, and more research is needed to establish their efficacy, safety, and optimal usage before they can be recommended as part of a standard treatment regimen.
  • Thumbnail Image
    Item
    HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules
    (Elsevier, 2019-05-01) Stevens, Mckayla; Abdeen, Sanofar; Salim, Nilshad; Ray, Anne-Marie; Washburn, Alex; Chitre, Siddhi; Sivinski, Jared; Park, Yangshin; Hoang, Quyen Q.; Chapman, Eli; Johnson, Steven M.; Biochemistry and Molecular Biology, School of Medicine
    All living organisms contain a unique class of molecular chaperones called 60 kDa heat shock proteins (HSP60 - also known as GroEL in bacteria). While some organisms contain more than one HSP60 or GroEL isoform, at least one isoform has always proven to be essential. Because of this, we have been investigating targeting HSP60 and GroEL chaperonin systems as an antibiotic strategy. Our initial studies focused on applying this antibiotic strategy for treating African sleeping sickness (caused by Trypanosoma brucei parasites) and drug-resistant bacterial infections (in particular Methicillin-resistant Staphylococcus aureus - MRSA). Intriguingly, during our studies we found that three known antibiotics - suramin, closantel, and rafoxanide - were potent inhibitors of bacterial GroEL and human HSP60 chaperonin systems. These findings prompted us to explore what other approved drugs, natural products, and known bioactive molecules might also inhibit HSP60 and GroEL chaperonin systems. Initial high-throughput screening of 3680 approved drugs, natural products, and known bioactives identified 161 hit inhibitors of the Escherichia coli GroEL chaperonin system (4.3% hit rate). From a purchased subset of 60 hits, 29 compounds (48%) re-confirmed as selective GroEL inhibitors in our assays, all of which were nearly equipotent against human HSP60. These findings illuminate the notion that targeting chaperonin systems might be a more common occurrence than we previously appreciated. Future studies are needed to determine if the in vivo modes of action of these approved drugs, natural products, and known bioactive molecules are related to GroEL and HSP60 inhibition.
  • Thumbnail Image
    Item
    Nature-Guided Synthesis of Advanced Bio-Lubricants
    (Springer Nature, 2019-08-12) Romsdahl, Trevor; Shirani, Asghar; Minto, Robert E.; Zhang, Chunyu; Cahoon, Edgar B.; Chapman, Kent D.; Berman, Diana; Chemistry and Chemical Biology, School of Science
    Design of environmentally friendly lubricants derived from renewable resources is highly desirable for many practical applications. Here, Orychophragmus violaceus (Ov) seed oil is found to have superior lubrication properties, and this is based on the unusual structural features of the major lipid species-triacylglycerol (TAG) estolides. Ov TAG estolides contain two non-hydroxylated, glycerol-bound fatty acids (FAs) and one dihydroxylated FA with an estolide branch. Estolide branch chains vary in composition and length, leading to their thermal stability and functional properties. Using this concept, nature-guided estolides of castor oil were synthesized. As predicted, they showed improved lubrication properties similar to Ov seed oil. Our results demonstrate a structure-based design of novel lubricants inspired by natural materials.
  • Thumbnail Image
    Item
    Preventing Oral Dual Biofilm Development with Innovative Bioactive Varnishes
    (MDPI, 2025-02-18) Costa, Tainá de Lima; Puppin-Rontani, Regina Maria; de Castilho, Aline Rogéria Freire; Pediatric Dentistry, School of Dentistry
    This study introduces innovative varnishes incorporating natural bioactive compounds to inhibit the formation of oral dual biofilms, a critical contributor to dental caries and other oral diseases. The purpose of this study was to evaluate the effectiveness of bioactive varnishes containing tt-farnesol, quercetin, and theobromine in inhibiting the formation of mixed Streptococcus mutans and Candida albicans biofilms. Mixed biofilms of Streptococcus mutans UA159 and Candida albicans SC5314 were grown in 96-well plates containing a specialized culture medium. Approximately 0.2 mL of experimental varnishes with A-1.5% or B-4.5% concentrations of tt-farnesol, quercetin, and theobromine were separately added to the wells using a disposable applicator, with a vehicle varnish (lacking bioactives) serving as the control. Biofilms were incubated at 37 °C with 5% CO2 for 24 h. Microbial viability was determined in terms of colony-forming units per milliliter (CFU/mL), and biofilm morphology was evaluated qualitatively via scanning electron microscopy (SEM). Statistical analyses were performed using ANOVA/Tukey tests at a 5% significance level. Varnishes A and B achieved significant reductions in microbial populations within the biofilms (p < 0.05) compared to the vehicle control (C). SEM imaging revealed marked structural disruptions in the biofilms, validating the quantitative results. Higher bioactive concentrations demonstrated enhanced inhibitory effects. Bioactive varnishes enriched with theobromine, quercetin, and tt-farnesol represent a novel and effective strategy for inhibiting oral dual biofilm development, offering a promising advancement in preventive dentistry.