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Science Advances Jun 2024Withanolides are a group of naturally occurring C steroids based on an ergostane skeleton. They have a high degree of polyoxygenation, and the abundance of -functional...
Withanolides are a group of naturally occurring C steroids based on an ergostane skeleton. They have a high degree of polyoxygenation, and the abundance of -functional groups has enabled various natural alterations to both the carbocyclic skeleton and the side chain. Consequently, these molecules have intricate structural features that lead to their highly varied display of biological activities including anticancer, anti-inflammatory, and immunomodulating properties. Despite being intriguing leads for further discovery research, synthetic access to the withanolides remains highly challenging-compounds for current biological research are mainly isolated from plants, often inefficiently. Here, we report the divergent synthesis of 11 withanolides in 12 to 20 steps, enabled by a gram-scale route and a series of late-stage functionalizations, most notably a bioinspired photooxygenation-allylic hydroperoxide rearrangement sequence. This approach enables further biological research disconnected from a reliance on minute quantities of the parent natural products or their simple derivatives.
Topics: Withanolides; Chemistry Techniques, Synthetic; Molecular Structure; Biological Products
PubMed: 38941454
DOI: 10.1126/sciadv.adp9375 -
Medicine Jun 2024Species of the genus Codonopsis (Campanulaceae) have a long history of application, acclaimed for its edible and therapeutic attributes. Scholarly inquiries into... (Review)
Review
Species of the genus Codonopsis (Campanulaceae) have a long history of application, acclaimed for its edible and therapeutic attributes. Scholarly inquiries into Codonopsis span botany, phytochemistry, quality assurance, pharmacodynamics, and toxicity, revealing a rich and comprehensive body of knowledge. This study synthesizes information from esteemed scientific databases like SciFinder, PubMed, China National Knowledge Infrastructure, and Chinese herbal classics to create a thorough scientific conceptual and theoretical framework for Codonopsis research. In this article, the phytochemical composition includes saccharides, polyacetylenes, polyenes, flavonoids, alkaloids, lignans, terpenoids, and organic acids was summarized. To date, over 350 monomeric compounds have been isolated and identified from Codonopsis, with recent studies primarily focusing on polysaccharides, aromatic derivatives, lignans, and polyacetylenes. Codonopsis exhibits broad pharmacological activities across various systems, including immune, blood, cardiovascular, central nervous, and digestive systems, with no significant toxicity or adverse effects reported. The existing research, focusing on various extracts and active parts without identifying specific active molecules, complicates the understanding of the mechanisms of action. There is an urgent need to advance research on the chemical composition and pharmacological effects to fully elucidate its pharmacodynamic properties and the basis of its material composition. Such efforts are crucial for the rational development, utilization, and clinical application of this herb.
Topics: Codonopsis; Humans; Phytochemicals; Drugs, Chinese Herbal; Lignans; Alkaloids
PubMed: 38941387
DOI: 10.1097/MD.0000000000038632 -
Current Microbiology Jun 2024Garlic (Allium sativum L.), particularly its volatile essential oil, is widely recognized for medicinal properties. We have evaluated the efficacy of Indian Garlic...
Garlic (Allium sativum L.), particularly its volatile essential oil, is widely recognized for medicinal properties. We have evaluated the efficacy of Indian Garlic Essential Oil (GEO) for antimicrobial and antibiofilm activity and its bioactive constituents. Allyl sulfur-rich compounds were identified as predominant phytochemicals in GEO, constituting 96.51% of total volatile oils, with 38% Diallyl trisulphide (DTS) as most abundant. GEO exhibited significant antibacterial activity against eleven bacteria, including three drug-resistant strains with minimum inhibitory concentrations (MICs) ranging from 78 to 1250 µg/mL. In bacterial growth kinetic assay GEO effectively inhibited growth of all tested strains at its ½ MIC. Antibiofilm activity was evident against two important human pathogens, S. aureus and P. aeruginosa. Mechanistic studies demonstrated that GEO disrupts bacterial cell membranes, leading to the release of nucleic acids, proteins, and reactive oxygen species. Additionally, GEO demonstrated potent antioxidant activity at IC 31.18 mg/mL, while its isolated constituents, Diallyl disulphide (DDS) and Diallyl trisulphide (DTS), showed effective antibacterial activity ranging from 125 to 500 µg/mL and 250-1000 µg/mL respectively. Overall, GEO displayed promising antimicrobial and antibiofilm activity against enteric bacteria, suggesting its potential application in the food industry.
Topics: Garlic; Oils, Volatile; Antioxidants; Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Staphylococcus aureus; Allyl Compounds; Phytochemicals; Sulfides; Bacteria; Pseudomonas aeruginosa; Disulfides; India; Plant Oils; Humans; Plant Extracts
PubMed: 38940852
DOI: 10.1007/s00284-024-03753-2 -
Journal of the Science of Food and... Jun 2024Pomegranate peel waste is a valuable reservoir of heat-sensitive total hydrolysable tannins (THT), with potential applications in food and pharmaceuticals. Preserving...
BACKGROUND
Pomegranate peel waste is a valuable reservoir of heat-sensitive total hydrolysable tannins (THT), with potential applications in food and pharmaceuticals. Preserving THT is challenging due to degradation post-extraction. We explore ionic gelation as an encapsulation method to optimize THT utilization.
RESULTS
Through external gelation, we optimized the process variables using Box-Behnken design. At 40 g kg sodium alginate, 25 g kg calcium chloride, and 300 g kg pomegranate peel extract (PPE), we achieved an 83.65% encapsulation efficiency. Compared to spray drying, external gelation demonstrated superior performance, with enhanced release percentages and stability. Physical, phytochemical, and release profiles of encapsulates were extensively analysed. External gelation achieved an 87.5% release in 30 min, outperforming spray-dried counterparts (69.7% in 25 min). Encapsulated PPE exhibited robust antibacterial activity against Staphylococcus aureus (ATCC 25923) in powdered infant formula, with a 32 ± 0.01 mm zone of inhibition and 300 μg mL minimum inhibitory concentration. Insights into S. aureus growth curves underlined the mechanism of action via membrane potential alterations. The results of carried investigations also showed that the antibacterial activity of the encapsulated PPE extracts against the targeted organism was identical to the antibacterial activity exhibited by synthetic antibiotics used generally to kill microorganisms in food. Therefore, from the findings, it can be concluded that the PPE encapsulate produced using the external gelation technique at the optimized condition displayed superior storage stability possessing strong antimicrobial activity when compared to encapsulate produced using the spray drying technique.
CONCLUSIONS
External gelation emerges as a potent technique for developing effective encapsulates enriched with natural antimicrobials or antibiotics. This approach holds promise for applications in food, pharmaceuticals, and nutraceuticals, enhancing stability and efficacy while reducing reliance on synthetic antibiotics. © 2024 Society of Chemical Industry.
PubMed: 38940545
DOI: 10.1002/jsfa.13698 -
Critical Reviews in Food Science and... Jun 2024Mounting evidence implicates the gut microbiota as a possible key susceptibility factor for atherosclerosis (AS). The employment of dietary phytochemicals that strive to... (Review)
Review
Mounting evidence implicates the gut microbiota as a possible key susceptibility factor for atherosclerosis (AS). The employment of dietary phytochemicals that strive to target the gut microbiota has gained scientific support for treating AS. This study conducted a general overview of the links between the gut microbiota and AS, and summarized available evidence that dietary phytochemicals improve AS manipulating gut microbiota. Then, the microbial metabolism of several dietary phytochemicals was summarized, along with a discussion on the metabolites formed and the biotransformation pathways involving key gut bacteria and enzymes. This study additionally focused on the anti-atherosclerotic potential of representative metabolites from dietary phytochemicals, and investigated their underlying molecular mechanisms. In summary, microbiota-dependent dietary phytochemical therapy is a promising strategy for AS management, and knowledge of "phytochemical-microbiota-biotransformation" may be a breakthrough in the search for novel anti-atherogenic agents.
PubMed: 38940319
DOI: 10.1080/10408398.2024.2369169 -
Natural Product Research Jun 2024The study explored DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known...
The study explored DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known bioactive metabolite glaucarubinone (). Mosquito larvicidal activity of glaucarubinone () against the three vector species viz. and was determined using a modified WHO 2005 protocol. It was observed that larvae were the most susceptible species with LC 13.88 ppm and LC 70.01 ppm followed by and at 24 h of exposure. The mode of action as observed microscopically is the lysis of midgut and thorax cells of the third instar larvae. The crystal structure of the glaucarubinone () is reported for the first time using X-ray crystallography. This phytochemical product has the potential to act as a green alternative to existing chemical-based insecticides for integrated vector management.
PubMed: 38940013
DOI: 10.1080/14786419.2024.2371569 -
Current Developments in Nutrition Jun 2024This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central... (Review)
Review
This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central nervous system and the enteric nervous system. Phytochemicals, which are compounds derived from plants, have been shown to interact with the gut microbiota, immune system, and neurotransmitter systems, thereby influencing brain function. Phytochemicals such as polyphenols, carotenoids, flavonoids, and terpenoids have been identified as having potential therapeutic implications for various neurological disorders. The GBA plays a critical role in the development and progression of various neurological disorders, including Parkinson's disease, multiple sclerosis, depression, anxiety, and autism spectrum disorders. Dysbiosis, or an imbalance in gut microbiota composition, has been associated with a range of neurological disorders, suggesting that modulating the gut microbiota may have potential therapeutic implications for these conditions. Although these findings are promising, further research is needed to elucidate the optimal use of phytochemicals in neurological disorder treatment, as well as their potential interactions with other medications. The literature review search was conducted using predefined search terms such as phytochemicals, gut-brain axis, neurodegenerative, and Parkinson in PubMed, Embase, and the Cochrane library.
PubMed: 38939650
DOI: 10.1016/j.cdnut.2024.103785 -
Experimental and Therapeutic Medicine Aug 2024Inflammation serves as a multifaceted defense mechanism activated by pathogens, cellular damage and irritants, aiming to eliminate primary causes of injury and promote...
Inflammation serves as a multifaceted defense mechanism activated by pathogens, cellular damage and irritants, aiming to eliminate primary causes of injury and promote tissue repair. Miq (), prevalent in Vietnam and southern China, has a history of traditional use for treating cough, fever and asthma. Previous studies on its phytochemicals have shown their potential as anti-inflammatory agents, yet underlying mechanisms remain to be elucidated. The present study investigated the regulatory effects of on the anti-inflammatory pathways. The methanol extracts of (PDME) were found to inhibit nitric oxide (NO) production and induce heme oxygenase-1 (HO-1) expression in murine macrophages. While MAPKs inhibitors, such as SP600125, SB203580 and U0126 did not regulate HO-1 expression, the treatment of cycloheximide, a translation inhibitor, reduced HO-1. Furthermore, PDME inhibited lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and TNF-α expression at both the mRNA and protein levels. The activity of NOS and the expression of TNF-α, iNOS and COX-2 decreased in LPS-stimulated Raw 264.7 cells treated with PDME and this effect was regulated by inhibition of HO-1 activity. These findings suggested that PDME functions as an HO-1 inducer and serves as an effective natural anti-inflammatory agent in LPS-induced inflammation.
PubMed: 38939180
DOI: 10.3892/etm.2024.12606 -
BioMedicine 2024Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and...
BACKGROUND
Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient's quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer.
METHODS
Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline.
RESULTS
Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from justified the Lipinski's Rule of 5.
CONCLUSION
Viscosalactone obtained from may act as promising drug candidate to fight against metastatic breast cancer.
PubMed: 38939099
DOI: 10.37796/2211-8039.1448 -
and evaluation of ethanolic crude extracts on fatty acid synthase expression on breast cancer cells.BioMedicine 2024Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This...
BACKGROUND
Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This overexpression has been affiliated with poor prognosis and resistance to chemotherapeutics. Consequently, FASN has come into focus as an appealing potential target for breast cancer treatment. Available FASN inhibitors, however, are unstable and have been correlated with adverse side effects.
OBJECTIVE
This present study aims to investigate the potential of ethanolic crude extract (AP) as a potent FASN inhibitor in breast cancer cells.
MATERIALS & METHODS
This study used MTT assay and flow cytometry analysis to measure cell viability and apoptosis following AP treatment (0-500 μg/mL). Furthermore, FASN protein expression was evaluated using immunocytochemistry whereas lipid droplet formation was quantified using Oil Red O staining. Literature-based identified AP phytochemicals were subjected to the prediction of molecular docking and ADMET properties.
RESULTS
This study demonstrated that AP significantly reduced cell viability while inducing apoptosis in breast cancer cells. In addition, for the first time, exposure to AP was demonstrated to drastically reduce intracellular FASN protein expression and lipid droplet accumulation in EMT6 and MCF-7 breast cancer cells. Docking simulation analysis demonstrated AP phytochemicals may have exerted an inhibitory effect by targeting the FASN Thioesterase (TE) domain similarly to the known FASN inhibitor, Orlistat. Moreover, all AP phytochemicals also possessed drug-likeness properties which are in accordance with Lipinski's rule of five.
CONCLUSIONS
These results highlight the potential of ethanolic crude extract as a FASN inhibitor and hence might have the potential to be further developed as a potent chemotherapeutic drug for breast cancer treatment.
PubMed: 38939097
DOI: 10.37796/2211-8039.1444