scholarly journals Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential

2021 ◽  
Vol 22 (5) ◽  
pp. 2664
Author(s):  
Giuseppe Mannino ◽  
Piera Iovino ◽  
Antonino Lauria ◽  
Tullio Genova ◽  
Alberto Asteggiano ◽  
...  
Keyword(s):  
Chemical Characterization ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Therapeutic Strategies ◽  
Human Hepatocytes ◽  
Pentacyclic Triterpenoids ◽  
Cholesterol Lowering ◽  
Health Promoting ◽  
Phytochemical Profile ◽  
Resin Extract

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (HMGCR, PCSK9, LDLR, FXR, IDOL, and PPAR). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds.

Design, Synthesis and Antitubercular Evaluation of New Benzimidazole Scaffolds

2021 ◽  
Vol 18 (4) ◽  
pp. 375-383
Author(s):  
Smriti Yadav ◽  
Bharath Kumar Inturi ◽  
Shrinidhi B.R ◽  
Pooja H.J ◽  
Neenu Ganesh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Lines ◽  
Normal Cell ◽  
Acyl Carrier Protein ◽  
Antitubercular Activity ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Chemical Library ◽  
Activity Data ◽  
Mycobacterium Tuberculosis H37rv

Background: To overcome one of the resistance mechanisms of Isoniazid (INH), there is a need for an antitubercular agent that can inhibit InhA enzyme by circumventing the formation of INH-NAD+ adduct. Objective: The objective of the study is the development of novel antitubercular agents that target Mycobacterium tuberculosis InhA (Enoyl Acyl Carrier Protein Reductase). Methods: A small-molecule chemical library was used for the identification of the novel InhA inhibitors using primary screening and molecular docking studies followed by the scaffold hopping approach. The designed molecules, 2-(2-(hydroxymethyl)-1H- benzo[d] imidazole-1-yl)- N- substituted acetamides were synthesized by reacting (1H- benzo[d]imidazole -2-yl)methanol with appropriate 2-chloro-N-substituted acetamides / dialkylamino carbonyl chlorides respectively in good yields (42-65%). The antitubercular activity of synthesized compounds was determined by Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis H37Rv strain. The selected compounds were screened for cytotoxicity on normal cell lines. Results: The antitubercular activity data revealed that the 4-chlorophenyl substituted derivative (3b) showed good MIC value at 6.25 μg/mL and, dimethylacetamide substituted derivative (3i) showed MIC at 25 μg/mL among the tested compounds. The substitution of dimethylacetamide (3i) group on the 1st position of benzimidazole has good antitubercular activity (25μg/mL) in comparison to the diethyl acetamide group (3j, 100μg/mL). Conclusion: The antitubercular activity data indicated that the tested compounds exhibited well to moderate inhibition of the H37Rv strains. The compounds (3b) with electronegative substitution on the phenyl moiety exhibited better antitubercular activity than that of the other substitutions. The active compounds have displayed a good safety profile on normal cell lines.

scholarly journals Structural and functional insights into esterase-mediated macrolide resistance

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michał Zieliński ◽  
Jaeok Park ◽  
Barry Sleno ◽  
Albert M. Berghuis
Keyword(s):  
Active Site ◽  
Pathogenic Bacteria ◽  
Catalytic Mechanism ◽  
Three Dimensional ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Macrolide Resistance ◽  
Flexible Docking ◽  
Sequence Identity ◽  
Substrate Spectrum

AbstractMacrolides are a class of antibiotics widely used in both medicine and agriculture. Unsurprisingly, as a consequence of their exensive usage a plethora of resistance mechanisms have been encountered in pathogenic bacteria. One of these resistance mechanisms entails the enzymatic cleavage of the macrolides’ macrolactone ring by erythromycin esterases (Eres). The most frequently identified Ere enzyme is EreA, which confers resistance to the majority of clinically used macrolides. Despite the role Eres play in macrolide resistance, research into this family enzymes has been sparse. Here, we report the first three-dimensional structures of an erythromycin esterase, EreC. EreC is an extremely close homologue of EreA, displaying more than 90% sequence identity. Two structures of this enzyme, in conjunction with in silico flexible docking studies and previously reported mutagenesis data allowed for the proposal of a detailed catalytic mechanism for the Ere family of enzymes, labeling them as metal-independent hydrolases. Also presented are substrate spectrum assays for different members of the Ere family. The results from these assays together with an examination of residue conservation for the macrolide binding site in Eres, suggests two distinct active site archetypes within the Ere enzyme family.

scholarly journals Identification of Bioactive Compounds of Asparagus officinalis L.: Permutation Test Allows Differentiation among “Triguero” and Hybrid Green Varieties

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1640
Author(s):  
Cecilia Jiménez-Sánchez ◽  
Fabián Pedregosa ◽  
Isabel Borrás-Linares ◽  
Jesús Lozano-Sánchez ◽  
Antonio Segura-Carretero
Keyword(s):  
High Performance ◽  
Permutation Test ◽  
Asparagus Officinalis ◽  
Diode Array ◽  
Reverse Phase ◽  
Phytochemical Content ◽  
Flight Mass Spectrometry ◽  
Rp Hplc ◽  
Health Promoting ◽  
Phytochemical Profile

In this study, we determined the phytochemical profile of the Spanish “triguero” asparagus landrace “verde-morado” (Asparagus officinalis L.), a wild traditional landrace, and the improved “triguero” HT-801, together with two commercial green asparagus varieties. For comparison, we used reverse-phase high-performance liquid chromatography coupled with diode array electrospray time-of-flight mass spectrometry (RP-HPLC-DAD-ESI-TOF/MS) followed by a permutation test applied using a resampling methodology valid under a relaxed set of assumptions, such as i.i.d. errors (not necessarily normal) that are exchangeable under the null hypothesis. As a result, we postulate that “triguero” varieties (the improved HT-801 followed by its parent “verde-morado”) have a significantly different phytochemical profile from that of the other two commercial hybrid green varieties. In particular, we found compounds specific to the “triguero” varieties, such as feruloylhexosylhexose isomers, or isorhamnetin-3-O-glucoside, which was found only in the “triguero” variety HT-801. Although studies relating the phytochemical content of “triguero” asparagus varieties to its health-promoting effects are required, this characteristic phytochemical profile can be used for differentiating and revalorizating these asparagus cultivars.

scholarly journals Mango (Mangifera indica L.) Leaves: Nutritional Composition, Phytochemical Profile, and Health-Promoting Bioactivities

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299 ◽  
Author(s):  
Manoj Kumar ◽  
Vivek Saurabh ◽  
Maharishi Tomar ◽  
Muzaffar Hasan ◽  
Sushil Changan ◽  
...  
Keyword(s):  
Biological Activities ◽  
Mangifera Indica ◽  
The Philippines ◽  
Nutritional Composition ◽  
Lipid Lowering ◽  
Pharmaceutical Drugs ◽  
Beneficial Effects ◽  
Health Promoting ◽  
Phytochemical Profile ◽  
Mango Leaves

Mangifera indica L. belongs to the family of Anacardiaceae and is an important fruit from South and Southeast Asia. India, China, Thailand, Indonesia, Pakistan, Mexico, Brazil, Bangladesh, Nigeria, and the Philippines are among the top mango producer countries. Leaves of the mango plant have been studied for their health benefits, which are attributed to a plethora of phytochemicals such as mangiferin, followed by phenolic acids, benzophenones, and other antioxidants such as flavonoids, ascorbic acid, carotenoids, and tocopherols. The extracts from mango leaves (MLs) have been studied for their biological activities, including anti-cancer, anti-diabetic, anti-oxidant, anti-microbial, anti-obesity, lipid-lowering, hepato-protection, and anti-diarrheal. In the present review, we have elaborated on the nutritional and phytochemical profile of the MLs. Further, various bioactivities of the ML extracts are also critically discussed. Considering the phytochemical profile and beneficial effects of the MLs, they can be used as a potential ingredient for the development of functional foods and pharmaceutical drugs. However, more detailed clinical trials still needed to be conducted for establishing the actual efficacy of the ML extracts.

scholarly journals Custard Apple (Annona squamosa L.) Leaves: Nutritional Composition, Phytochemical Profile, and Health-Promoting Biological Activities

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 614
Author(s):  
Manoj Kumar ◽  
Sushil Changan ◽  
Maharishi Tomar ◽  
Uma Prajapati ◽  
Vivek Saurabh ◽  
...  
Keyword(s):  
Biological Activities ◽  
Lipid Lowering ◽  
Pharmaceutical Drugs ◽  
Annona Squamosa ◽  
Tropical Fruit ◽  
Custard Apple ◽  
Health Promoting ◽  
Phytochemical Profile

Annona squamosa L. (custard apple) belongs to the family Annonaceae and is an important tropical fruit cultivated in the West Indies, South and Central America, Ecuador, Peru, Brazil, India, Mexico, the Bahamas, Bermuda, and Egypt. Leaves of custard apple plants have been studied for their health benefits, which are attributed to a considerable diversity of phytochemicals. These compounds include phenol-based compounds, e.g., proanthocyanidins, comprising 18 different phenolic compounds, mainly alkaloids and flavonoids. Extracts from Annona squamosa leaves (ASLs) have been studied for their biological activities, including anticancer, antidiabetic, antioxidant, antimicrobial, antiobesity, lipid-lowering, and hepatoprotective functions. In the current article, we discussed the nutritional and phytochemical diversity of ASLs. Additionally, ASL extracts were discussed with respect to their biological activities, which were established by in vivo and in vitro experiments. A survey of the literature based on the phytochemical profile and health-promoting effects of ASLs showed that they can be used as potential ingredients for the development of pharmaceutical drugs and functional foods. Although there are sufficient findings available from in vitro and in vivo investigations, clinical trials are still needed to determine the exact effects of ASL extracts on human health.

scholarly journals Exopolysaccharides Produced by Lactic Acid Bacteria: From Biosynthesis to Health-Promoting Properties

Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 156
Author(s):  
Dominika Jurášková ◽  
Susana C. Ribeiro ◽  
Celia C. G. Silva
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Meat Products ◽  
Fermented Foods ◽  
Cholesterol Lowering ◽  
Beneficial Effects ◽  
Composition And Structure ◽  
Health Promoting

The production of exopolysaccharides (EPS) by lactic acid bacteria (LAB) has attracted particular interest in the food industry. EPS can be considered as natural biothickeners as they are produced in situ by LAB and improve the rheological properties of fermented foods. Moreover, much research has been conducted on the beneficial effects of EPS produced by LAB on modulating the gut microbiome and promoting health. The EPS, which varies widely in composition and structure, may have diverse health effects, such as glycemic control, calcium and magnesium absorption, cholesterol-lowering, anticarcinogenic, immunomodulatory, and antioxidant effects. In this article, the latest advances on structure, biosynthesis, and physicochemical properties of LAB-derived EPS are described in detail. This is followed by a summary of up-to-date methods used to detect, characterize and elucidate the structure of EPS produced by LAB. In addition, current strategies on the use of LAB-produced EPS in food products have been discussed, focusing on beneficial applications in dairy products, gluten-free bakery products, and low-fat meat products, as they positively influence the consistency, stability, and quality of the final product. Highlighting is also placed on reports of health-promoting effects, with particular emphasis on prebiotic, immunomodulatory, antioxidant, cholesterol-lowering, anti-biofilm, antimicrobial, anticancer, and drug-delivery activities.

scholarly journals Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 615 ◽  
Author(s):  
Erin Dobrange ◽  
Darin Peshev ◽  
Bianke Loedolff ◽  
Wim Van den Ende
Keyword(s):  
Potential Role ◽  
Antiviral Agents ◽  
Human Microbiome ◽  
Modern Medicine ◽  
Historical Knowledge ◽  
Multifunctional Compounds ◽  
Health Promoting ◽  
Medicinal Properties ◽  
Phytochemical Profile

Throughout history, medicinal purposes of plants have been studied, documented, and acknowledged as an integral part of human healthcare systems. The development of modern medicine still relies largely on this historical knowledge of the use and preparation of plants and their extracts. Further research into the human microbiome highlights the interaction between immunomodulatory responses and plant-derived, prebiotic compounds. One such group of compounds includes the inulin-type fructans (ITFs), which may also act as signaling molecules and antioxidants. These multifunctional compounds occur in a small proportion of plants, many of which have recognized medicinal properties. Echinacea is a well-known medicinal plant and products derived from it are sold globally for its cold- and flu-preventative and general health-promoting properties. Despite the well-documented phytochemical profile of Echinacea plants and products, little research has looked into the possible role of ITFs in these products. This review aims to highlight the occurrence of ITFs in Echinacea derived formulations and the potential role they play in immunomodulation.

scholarly journals Targeting Oncogenic BRAF: Past, Present, and Future

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1197 ◽  
Author(s):  
Zaman ◽  
Wu ◽  
Bivona
Keyword(s):  
Kinase Inhibitors ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
Wild Type ◽  
Braf Mutations ◽  
Molecular Alterations ◽  
Mutant Braf

Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies.

scholarly journals Nongenetic Mechanisms of Drug Resistance in Melanoma

2020 ◽  
Vol 4 (1) ◽  
pp. 315-330
Author(s):  
Vito W. Rebecca ◽  
Meenhard Herlyn
Keyword(s):  
Drug Resistance ◽  
Metastatic Melanoma ◽  
Metastatic Disease ◽  
Resistance Mechanisms ◽  
Melanoma Cells ◽  
Therapeutic Strategies ◽  
Therapeutic Resistance ◽  
Primary Resistance ◽  
Future Design ◽  
The Future

Resistance to targeted and immune-based therapies limits cures in patients with metastatic melanoma. A growing number of reports have identified nongenetic primary resistance mechanisms including intrinsic microenvironment- and lineage plasticity–mediated processes serving critical functions in the persistence of disease throughout therapy. There is a temporally shifting spectrum of cellular identities fluidly occupied by therapy-persisting melanoma cells responsible for driving therapeutic resistance and metastasis. The key epigenetic, metabolic, and phenotypic reprogramming events requisite for the manifestation and maintenance of so-called persister melanoma populations remain poorly understood and underscore the need to comprehensively investigate actionable vulnerabilities. Here we attempt to integrate the field's observations on nongenetic mechanisms of drug resistance in melanoma. We postulate that the future design of therapeutic strategies specifically addressing therapy-persisting subpopulations of melanoma will improve the curative potential of therapy for patients with metastatic disease.

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