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Nutrients, Natural Products and Nanoparticles for the Development of New Therapeutic Agents

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 4254

Special Issue Editors

Dr. Gabriella Calviello

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Guest Editor
Department of Translational Medicine and Surgery, Section of General Pathology, School of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito, 1-00168 Rome, Italy
Interests: cancer; nutrition; omega-3 fatty acids; antioxidants; phenolic compounds; inflammation; neurodegenerative diseases; metabolic diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Simona Serini

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Guest Editor
Department of Translational Medicine and Surgery, Section of General Pathology, School of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito, 1-00168 Rome, Italy
Interests: cancer; nutrition; omega-3 fatty acids; antioxidants; phenolic compounds; inflammation; neurodegenerative diseases; nutrition; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since ancient times, nutrients and other natural products have been widely used for their ability to alleviate symptoms and cure diseases. In the last two decades, we have been witnessing an upsurge of interest in the possible use of these bioactive compounds for the development of new therapeutic agents for many diseases. The main aim is to obtain new formulations that are safer and more effective than the traditional ones that are already available, often characterized by low target selectivity, rapid clearance and dangerous systemic side-effects. Nanotechnology appears to play a crucial role in this field of research, and one main strategy in this area is the inclusion of the bioactive natural compounds in nano-formulations, alone or in combination with other therapeutic agents. This approach makes it possible to increase the bioavailability of both drugs and natural bioactive products by protecting them from enzymatic and oxidative degradation and, often, to overcome their poor water solubility. In addition, the external layers of these nanoparticles are often designed to target them toward specific locations. Finally, it is worth noting that nutrients and natural products are currently also regarded as interesting and possible unlimited sources of lead compounds for the development of new drug entities with improved pharmacodynamic and pharmacokinetic properties with respect to the original natural compounds.

Therefore, this Special Issue is inviting review and original research papers that provide state-of-the-art insight on:

- Inclusion in nanomaterials of nutrients and other bioactive natural products known for their beneficial health properties.

- Health benefits deriving from the inclusion of nutrients and other bioactive natural products in new nano-formulations.

- Development of nanomaterials for therapeutic combinations with nutrients and other natural bioactive compounds of conventional forms of therapy (chemotherapy, radiotherapy, or phototherapy) or more innovative ones (target therapy or immunotherapy).

- Nutrients and natural products as sources of lead compounds for development of new drug entities.

Dr. Gabriella Calviello
Dr. Simona Serini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nanomedicine
  • nanoparticles
  • natural products
  • nutraceuticals
  • nanomaterials in chemotherapy
  • nanomaterials in radiotherapy
  • antioxidants
  • phenolic compounds
  • cancer
  • inflammation
  • neurodegeneration
  • natural products as lead compounds nanotherapeutic agent development

Published Papers (4 papers)

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Research

14 pages, 4766 KiB  
Article
Investigation of the General Molecular Mechanisms of Gallic Acid via Analyses of Its Transcriptome Profile
by Jiyeon Kim, Bo Kyung Kim, Sang Hyun Moh, Goo Jang and Jae Yong Ryu
Int. J. Mol. Sci. 2024, 25(4), 2303; https://doi.org/10.3390/ijms25042303 - 15 Feb 2024
Viewed by 534
Abstract
Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS [...] Read more.
Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase β and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses. Full article
(This article belongs to the Special Issue Nutrients, Natural Products and Nanoparticles for the Development of New Therapeutic Agents)
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16 pages, 4380 KiB  
Article
Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models
by Wei-Chieh Huang, Lan-Hsin Shu, Yu-Ju Kuo, Kevin Shu-Leung Lai, Chih-Wei Hsia, Ting-Lin Yen, Chih-Hsuan Hsia, Thanasekaran Jayakumar, Chih-Hao Yang and Joen-Rong Sheu
Int. J. Mol. Sci. 2024, 25(4), 2098; https://doi.org/10.3390/ijms25042098 - 08 Feb 2024
Viewed by 704
Abstract
Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and [...] Read more.
Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 μM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2–PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs. Full article
(This article belongs to the Special Issue Nutrients, Natural Products and Nanoparticles for the Development of New Therapeutic Agents)
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20 pages, 3023 KiB  
Article
EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression
by Wei Wang, Taimei Di, Weiwei Wang and Heyuan Jiang
Int. J. Mol. Sci. 2023, 24(13), 11017; https://doi.org/10.3390/ijms241311017 - 03 Jul 2023
Cited by 4 | Viewed by 1310
Abstract
Without affecting cell viability, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), theaflavine-3,3′-digallate (TFDG), or theasinensin A (TSA) have been found to effectively reduce intracellular melanin content and tyrosinase (TYR) activity. However, studies on the anti-melanogenic mechanism of the above samples remain weak, and the [...] Read more.
Without affecting cell viability, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), theaflavine-3,3′-digallate (TFDG), or theasinensin A (TSA) have been found to effectively reduce intracellular melanin content and tyrosinase (TYR) activity. However, studies on the anti-melanogenic mechanism of the above samples remain weak, and the activities of these samples in regulating melanogenesis at the molecular level lack comparison. Using B16F10 cells with the α-melanocyte-stimulating hormone (α-MSH) stimulation and without the α-MSH stimulation as models, the effects of EGCG, GCG, TFDG, or TSA on cell phenotypes and expression of key targets related to melanogenesis were studied. The results showed that α-MSH always promoted melanogenesis with or without adding the four samples. Meanwhile, the anti-melanogenic activities of the four samples were not affected by whether the α-MSH was added in the medium or not and the added time of the α-MSH. On this basis, the 100 µg/mL EGCG, GCG, TFDG, or TSA did not affect the TYR catalytic activity but inhibited melanin formation partly through downregulating the melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), and the TYR family. The downregulation abilities of catechins on the TYR family and MITF expression were stronger than those of dimers at both the transcription and translation levels, while the ability of dimers to downregulate the MC1R expression was stronger than that of catechins at both the transcription and translation levels to some extent. The results of molecular docking showed that these four samples could stably bind to MC1R protein. Taken together, this study offered molecular mechanisms for the anti-melanogenic activity of the EGCG, GCG, TFDG, and TSA, as potential effective components against the UV-induced tanning reactions, and a key target (MC1R) was identified. Full article
(This article belongs to the Special Issue Nutrients, Natural Products and Nanoparticles for the Development of New Therapeutic Agents)
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15 pages, 2964 KiB  
Article
Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy
by Wiwit Nurhidayah, Eva Maria Widyasari, Isti Daruwati, Isa Mahendra, Toto Subroto, Nur Kusaira Khairul Ikram and Muchtaridi Muchtaridi
Int. J. Mol. Sci. 2023, 24(10), 8678; https://doi.org/10.3390/ijms24108678 - 12 May 2023
Viewed by 1254
Abstract
The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows [...] Read more.
The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including −20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at −20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at −20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer. Full article
(This article belongs to the Special Issue Nutrients, Natural Products and Nanoparticles for the Development of New Therapeutic Agents)
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