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Antioxidants and Anti-inflammatory, Antiproliferative Activities of Natural Products

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

Deadline for manuscript submissions: closed (30 May 2024) | Viewed by 11657

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Guest Editor
Laboratoires TBC, Laboratory of Pharmacology, Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Lille, 3, Rue du Professeur Laguesse, B.P. 83, F-59000 Lille, France
Interests: clinical phytopharmacology; phytopharmacology; polyphytotherapy
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Special Issue Information

Dear Colleagues,

Bioactive molecules from plants and fungi have been used for centuries as the main source of natural bioactive molecules. Today, these molecules can come from humans and animals. For example, cruor, the main component responsible for the red color of blood in mammals, contains 90% hemoglobin, a protein that is considered a rich source of bioactive peptides. The hydrolysates of human and bovine hemoglobin have made it possible to isolate peptides possessing antioxidant, antibacterial, anti-inflammatory, and antiproliferative properties. Molecules and peptides derived from human and bovine hemoglobin could be the source of bioactive natural products for the development of biological drugs and biosimilars. Comparisons of the activities of bioactive products derived from animals and plants are increasingly carried out by the pharmaceutical industry to develop effective drugs of the future at low costs.

Dr. Bruno Eto
Guest Editor

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Keywords

  • bioactive products
  • anti-infectives
  • antioxidants
  • anti-inflammatory
  • antiproliferative
  • clinical phytopharmacology
  • phytopharmacology
  • polyphytotherapy

Published Papers (10 papers)

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Research

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22 pages, 3667 KiB  
Article
Berberis vulgaris L. Root Extract as a Multi-Target Chemopreventive Agent against Colon Cancer Causing Apoptosis in Human Colon Adenocarcinoma Cell Lines
by Anna Och, Marta Kinga Lemieszek, Marek Cieśla, Dariusz Jedrejek, Aleksandra Kozłowska, Sylwia Pawelec and Renata Nowak
Int. J. Mol. Sci. 2024, 25(9), 4786; https://doi.org/10.3390/ijms25094786 - 27 Apr 2024
Viewed by 729
Abstract
Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant’s methanolic root [...] Read more.
Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant’s methanolic root extract (BVR) against colon cancer cells. Studies were conducted in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3, 46.1, and 50.2 µg/mL for the LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of the cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. Nuclear double staining revealed the great proapoptotic BVR properties in HT-29 cells and subtle effect in LS180 cells. RT-qPCR with the relative quantification method showed significant changes in the expression of genes related to apoptosis in both the LS180 and HT-29 cells. The genes BCL2L1 (126.86–421.43%), BCL2L2 (240–286.02%), CASP3 (177.19–247.83%), and CASP9 (157.99–243.75%) had a significantly elevated expression, while BCL2 (25–52.03%) had a reduced expression compared to the untreated control. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93 ± 0.01, 122.92 ± 0.01, and 220.29 ± 0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+, and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62.60 ± 0.87% of enzyme inhibition. The chemical composition of BVR was determined using a UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). The results are very promising and encourage the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer, and were widely discussed alongside data from the literature. Full article
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22 pages, 5730 KiB  
Article
Investigating the Anti-Inflammatory Properties and Skin Penetration Ability of Cornelian Cherry (Cornus mas L.) Extracts
by Martyna Zagórska-Dziok, Anna Nowak, Anna Muzykiewicz-Szymańska, Aleksandra Ziemlewska, Zofia Nizioł-Łukaszewska, Agnieszka Mokrzyńska, Magdalena Wójciak and Ireneusz Sowa
Int. J. Mol. Sci. 2024, 25(9), 4763; https://doi.org/10.3390/ijms25094763 - 27 Apr 2024
Viewed by 609
Abstract
Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained [...] Read more.
Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained in dogwood extracts of different fruit colors (yellow, red, and dark ruby red) prepared using different extractants was investigated. These analyses were performed using a Franz chamber and HPLC-UV chromatography. Moreover, the antioxidant properties of the tested extracts were compared and their impact on the intracellular level of free radicals in skin cells was assessed. The cytotoxicity of these extracts towards keratinocytes and fibroblasts was also analyzed and their anti-inflammatory properties were assessed using the enzyme-linked immunosorbent assay (ELISA). The analyses showed differences in the penetration of individual phenolic acids into the skin and different biological activities of the tested extracts. None of the extracts had cytotoxic effects on skin cells in vitro, and the strongest antioxidant and anti-inflammatory properties were found in dogwood extracts with dark ruby red fruits. Full article
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19 pages, 10534 KiB  
Article
The Effects of Body Fat Reduction through the Metabolic Control of Steam-Processed Ginger Extract in High-Fat-Diet-Fed Mice
by Yeong-Geun Lee, Sung Ryul Lee, Hyun Jin Baek, Jeong Eun Kwon, Nam-In Baek, Tong Ho Kang, Hyunggun Kim and Se Chan Kang
Int. J. Mol. Sci. 2024, 25(5), 2982; https://doi.org/10.3390/ijms25052982 - 4 Mar 2024
Viewed by 1032
Abstract
The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through [...] Read more.
The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25–100 μg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome. Full article
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15 pages, 3664 KiB  
Article
Anti-Inflammatory Effect of Fermented Cabbage Extract Containing Nitric Oxide Metabolites with Silica
by Yun-Seong Lee, Byeong-Jun Ji, Hyun-Ock Pae, Mu-Weon Cheon, Guangpeng Xu, Hyun-Soo Chun and Sooah Kim
Int. J. Mol. Sci. 2024, 25(2), 775; https://doi.org/10.3390/ijms25020775 - 8 Jan 2024
Viewed by 1303
Abstract
The aim of this study was to evaluate the anti-inflammatory effect of fermented cabbage extract (FC) containing nitric oxide metabolites with silica (FCS) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) in BALB/c mice. Atopic dermatitis-like allergic contact dermatitis was induced by DNFB challenge in [...] Read more.
The aim of this study was to evaluate the anti-inflammatory effect of fermented cabbage extract (FC) containing nitric oxide metabolites with silica (FCS) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) in BALB/c mice. Atopic dermatitis-like allergic contact dermatitis was induced by DNFB challenge in the ear after DNFB sensitization on the dorsal skin of mice. FCS alleviated the severity of atopic dermatitis-like skin lesions. In addition, epidermis thickness of the ear and penetration of inflammatory cells in atopic dermatitis-like skin lesions were decreased after topical application of FCS. The serum levels of TNF-α and IL-4 were measured in atopic dermatitis mice using ELISA kits, which were observed to be significantly decreased after topical application of FCS. This study demonstrates that the FCS can be used as a potential therapeutic for the treatment and prevention of AD. Full article
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15 pages, 4104 KiB  
Article
Auraptene Enhances AMP-Activated Protein Kinase Phosphorylation and Thereby Inhibits the Proliferation, Migration and Expression of Androgen Receptors and Prostate-Specific Antigens in Prostate Cancer Cells
by Yasuyuki Akasaka, Shun Hasei, Yukino Ohata, Machi Kanna, Yusuke Nakatsu, Hideyuki Sakoda, Midori Fujishiro, Akifumi Kushiyama, Hiraku Ono, Akio Matsubara, Nobuyuki Hinata, Tomoichiro Asano and Takeshi Yamamotoya
Int. J. Mol. Sci. 2023, 24(21), 16011; https://doi.org/10.3390/ijms242116011 - 6 Nov 2023
Viewed by 1307
Abstract
Citrus hassaku extract reportedly activates AMPK. Because this extract contains an abundance of auraptene, we investigated whether pure auraptene activates AMPK and inhibits proliferation using prostate cancer cell lines. Indeed, auraptene inhibited the proliferation and migration of LNCaP cells and induced phosphorylation of [...] Read more.
Citrus hassaku extract reportedly activates AMPK. Because this extract contains an abundance of auraptene, we investigated whether pure auraptene activates AMPK and inhibits proliferation using prostate cancer cell lines. Indeed, auraptene inhibited the proliferation and migration of LNCaP cells and induced phosphorylation of AMPK or its downstream ACC in LNCaP, PC3, and HEK-293 cells, but not in DU145 cells not expressing LKB1. In addition, the mTOR-S6K pathway, located downstream from activated AMPK, was also markedly suppressed by auraptene treatment. Importantly, it was shown that auraptene reduced androgen receptor (AR) and prostate-specific antigen (PSA) expressions at both the protein and the mRNA level. This auraptene-induced downregulation of PSA was partially but significantly reversed by treatment with AMPK siRNA or the AMPK inhibitor compound C, suggesting AMPK activation to, at least partially, be causative. Finally, in DU145 cells lacking the LKB1 gene, exogenously induced LKB1 expression restored AMPK phosphorylation by auraptene, indicating the essential role of LKB1. In summary, auraptene is a potent AMPK activator that acts by elevating the AMP/ATP ratio, thereby potentially suppressing prostate cancer progression, via at least three molecular mechanisms, including suppression of the mTOR-S6K pathway, reduced lipid synthesis, and AR downregulation caused by AMPK activation. Full article
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19 pages, 3471 KiB  
Article
Obtaining New Candidate Peptides for Biological Anticancer Drugs from Enzymatic Hydrolysis of Human and Bovine Hemoglobin
by Ahlam Outman, Mohamed Bouhrim, Codjo Hountondji, Omar M. Noman, Ali S. Alqahtani, Bernard Gressier, Naïma Nedjar and Bruno Eto
Int. J. Mol. Sci. 2023, 24(20), 15383; https://doi.org/10.3390/ijms242015383 - 19 Oct 2023
Viewed by 1141
Abstract
Enzymatic hydrolysis of bovine and human hemoglobin generates a diversity of bioactive peptides, mainly recognized for their antimicrobial properties. However, antimicrobial peptides stand out for their ability to specifically target cancer cells while preserving rapidly proliferating healthy cells. This study focuses on the [...] Read more.
Enzymatic hydrolysis of bovine and human hemoglobin generates a diversity of bioactive peptides, mainly recognized for their antimicrobial properties. However, antimicrobial peptides stand out for their ability to specifically target cancer cells while preserving rapidly proliferating healthy cells. This study focuses on the production of bioactive peptides from hemoglobin and evaluates their anticancer potential using two distinct approaches. The first approach is based on the use of a rapid screening method aimed at blocking host cell protein synthesis to evaluate candidate anticancer peptides, using Lepidium sativum seed germination as an indicator. The results show that: (1) The degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3 to 10% produce a considerably stronger inhibition of radicle growth than DH 0 (the native form of hemoglobin), with an intensity three to four times greater. (2) Certain peptide fractions of bovine hemoglobin have a higher activity than those of human hemoglobin. (3) The structural characteristics of peptides (random coil or alpha helix) play a crucial role in the biological effects observed. (4) The α137–141 peptide, the target of the study, was the most active of the fractions obtained from bovine hemoglobin (IC50 = 29 ± 1 µg/mL) and human hemoglobin (IC50 = 48 ± 2 µg/mL), proving to be 10 to 15 times more potent than the other hemoglobin fractions, attributed to its strong antimicrobial potential. The second approach to assessing anticancer activity is based on the preliminary in vitro analysis of hydrolysates and their peptide fractions, with a focus on the eL42 protein. This protein is of major interest due to its overexpression in all cancer cells, making it an attractive potential target for the development of anticancer molecules. With this in mind, astudy was undertaken using a method for labeling formylase (formyl-methionyl-tRNA transformylase (FMTS)) with oxidized tRNA. This approach was chosen because of the similarities in the interaction between formylase and the eL42 protein with oxidized tRNA. The results obtained not only confirmed the previous conclusions but also reinforced the hypothesis that the inhibition of protein synthesis plays a key role in the anticancer mechanism of these peptides. Indeed, the data suggest that samples containing α137–141 peptide (NKT) and total hydrolysates may have modulatory effects on the interaction between FMTS and oxidized tRNA. This observation highlights the possibility that the latter could influence molecular binding mechanisms, potentially resulting in a competitive situation where the ability of substrate tRNA to bind efficiently to ribosomal protein is compromised in their presence. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer, which affects a large number of people around the world. Full article
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13 pages, 3289 KiB  
Article
Anti-Neuroinflammatory Effect of the Ethanolic Extract of Black Ginseng through TLR4-MyD88-Regulated Inhibition of NF-κB and MAPK Signaling Pathways in LPS-Induced BV2 Microglial Cells
by Kwan-Woo Kim, Young-Seob Lee, Bo-Ram Choi, Dahye Yoon and Dae Young Lee
Int. J. Mol. Sci. 2023, 24(20), 15320; https://doi.org/10.3390/ijms242015320 - 18 Oct 2023
Cited by 3 | Viewed by 1314
Abstract
Korean ginseng (Panax ginseng) contains various ginsenosides as active ingredients, and they show diverse biological activities. Black ginseng is manufactured by repeated steaming and drying of white ginseng, which alters the polarity of ginsenosides and improves biological activities. The aim of [...] Read more.
Korean ginseng (Panax ginseng) contains various ginsenosides as active ingredients, and they show diverse biological activities. Black ginseng is manufactured by repeated steaming and drying of white ginseng, which alters the polarity of ginsenosides and improves biological activities. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the ethanolic extract of black ginseng (BGE) in lipopolysaccharide (LPS)-induced BV2 microglial cells. Pre-treatment with BGE inhibited the overproduction of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 cells. In addition, BGE reduced the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) MAPK signaling pathways induced by LPS. These anti-neuroinflammatory effects were mediated through the negative regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) signaling pathway. Among the four ginsenosides contained in BGE, ginsenosides Rd and Rg3 inhibited the production of inflammatory mediators. Taken together, this investigation suggests that BGE represents potential anti-neuroinflammatory candidates for the prevention and treatment of neurodegenerative diseases. Full article
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20 pages, 3101 KiB  
Article
Comparison of the Bioactive Properties of Human and Bovine Hemoglobin Hydrolysates Obtained by Enzymatic Hydrolysis: Antimicrobial and Antioxidant Potential of the Active Peptide α137-141
by Ahlam Outman, Barbara Deracinois, Christophe Flahaut, Mira Abou Diab, Jihen Dhaouefi, Bernard Gressier, Bruno Eto and Naïma Nedjar
Int. J. Mol. Sci. 2023, 24(17), 13055; https://doi.org/10.3390/ijms241713055 - 22 Aug 2023
Cited by 3 | Viewed by 1149
Abstract
This study focuses on the enzymatic hydrolysis of hemoglobin, the main component of cruor that gives blood its red color in mammals. The antibacterial and antioxidant potentials of human hemoglobin hydrolysates were evaluated in comparison to bovine hemoglobin. The results showed strong antimicrobial [...] Read more.
This study focuses on the enzymatic hydrolysis of hemoglobin, the main component of cruor that gives blood its red color in mammals. The antibacterial and antioxidant potentials of human hemoglobin hydrolysates were evaluated in comparison to bovine hemoglobin. The results showed strong antimicrobial activity of the peptide hydrolysates against six bacterial strains, independent of the initial substrate concentration level. The hydrolysates also showed strong antioxidant activity, as measured by four different tests. In addition, the antimicrobial and antioxidant activities of the human and bovine hemoglobin hydrolysates showed little or no significant difference, with only the concentration level being the determining factor in their activity. The results of the mass spectrometry study showed the presence of a number of bioactive peptides, the majority of which have characteristics similar to those mentioned in the literature. New bioactive peptides were also identified in human hemoglobin, such as the antibacterial peptides PTTKTYFPHF (α37-46), FPTTKTYFPH (α36-45), TSKYR (α137-141), and STVLTSKYR (α133-141), as well as the antioxidant TSKYR (α137-141). According to these findings, human hemoglobin represents a promising source of bioactive peptides beneficial to the food or pharmaceutical industries. Full article
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25 pages, 2775 KiB  
Article
Potential of Human Hemoglobin as a Source of Bioactive Peptides: Comparative Study of Enzymatic Hydrolysis with Bovine Hemoglobin and the Production of Active Peptide α137–141
by Ahlam Outman, Barbara Deracinois, Christophe Flahaut, Mira Abou Diab, Bernard Gressier, Bruno Eto and Naïma Nedjar
Int. J. Mol. Sci. 2023, 24(15), 11921; https://doi.org/10.3390/ijms241511921 - 25 Jul 2023
Cited by 2 | Viewed by 1240
Abstract
Cruor, the main component responsible for the red color of mammalian blood, contains 90% haemoglobin, a protein considered to be a rich source of bioactive peptides. The aim of the present study is to assess the potential of human hemoglobin as a source [...] Read more.
Cruor, the main component responsible for the red color of mammalian blood, contains 90% haemoglobin, a protein considered to be a rich source of bioactive peptides. The aim of the present study is to assess the potential of human hemoglobin as a source of bioactive peptides, compared with bovine hemoglobin, which has been extensively studied in recent years. More specifically, the study focused on the α137–141 fragment of bovine haemoglobin (TSKYR), a small (653 Da) hydrophilic antimicrobial peptide. In this work, the potential of human hemoglobin to contain bioactive peptides was first investigated in silico in comparison with bovine hemoglobin-derived peptides using bioinformatics tools. The blast results showed a high identity, 88% and 85% respectively, indicating a high similarity between the α and β chains. Peptide Cutter software was used to predict cleavage sites during peptide hydrolysis, revealing major conservation in the number and location of cleavage sites between the two species, while highlighting some differences. Some peptides were conserved, notably our target peptide (TSKYR), while others were specific to each species. Secondly, the two types of hemoglobin were subjected to similar enzymatic hydrolysis conditions (23 °C, pH 3.5), which showed that the hydrolysis of human hemoglobin followed the same reaction mechanism as the hydrolysis of bovine hemoglobin, the ‘zipper’ mechanism. Concerning the peptide of interest, α137–141, the RP-UPLC analyses showed that its identification was not affected by the increase in the initial substrate concentration. Its production was rapid, with more than 60% of the total α137–141 peptide production achieved in just 30 min of hydrolysis, reaching peak production at 3 h. Furthermore, increasing the substrate concentration from 1% to 10% (w/v) resulted in a proportional increase in α137–141 production, with a maximum concentration reaching 687.98 ± 75.77 mg·L−1, approximately ten-fold higher than that obtained with a 1% (w/v) concentration. Finally, the results of the UPLC-MS/MS analysis revealed the identification of 217 unique peptides in bovine hemoglobin hydrolysate and 189 unique peptides in human hemoglobin hydrolysate. Of these, 57 peptides were strictly common to both species. This revealed the presence of several bioactive peptides in both cattle and humans. Although some had been known previously, new bioactive peptides were discovered in human hemoglobin, such as four antibacterial peptides (α37–46 PTTKTYFPHF, α36–45 FPTTKTYFPH, α137–141 TSKYR, and α133–141 STVLTSKYR), three opioid peptides (α137–141 TSKYR,β31–40 LVVYPWTQRF,β32–40, VVYPWTQRF), an ACE inhibitor (β129–135 KVVAGVA), an anticancer agent (β33–39 VVYPWTQ), and an antioxidant (α137–141 TSKYR). To the best of our knowledge, these peptides have never been found in human hemoglobin before. Full article
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Review

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15 pages, 3072 KiB  
Review
Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin
by Gérard Vergoten and Christian Bailly
Int. J. Mol. Sci. 2024, 25(7), 3597; https://doi.org/10.3390/ijms25073597 - 22 Mar 2024
Viewed by 766
Abstract
Limonoids are extremely diversified in plants, with many categories of products bearing an intact, rearranged or fragmented oxygenated scaffold. A specific subgroup of fragmented or degraded limonoids derives from the tetranortriterpenoid prieurianin, initially isolated from the tree Trichilia prieuriana but also found in [...] Read more.
Limonoids are extremely diversified in plants, with many categories of products bearing an intact, rearranged or fragmented oxygenated scaffold. A specific subgroup of fragmented or degraded limonoids derives from the tetranortriterpenoid prieurianin, initially isolated from the tree Trichilia prieuriana but also found in other plants of the Meliaceae family, including the more abundant species Aphanamixis polystachya. Prieurianin-type limonoids include about seventy compounds, among which are dregeanin and rohitukin. Prieurianin and analogs exhibit insecticidal, antimicrobial, antiadipogenic and/or antiparasitic properties but their mechanism of action remains ill-defined at present. Previous studies have shown that prieurianin, initially known as endosidin 1, stabilizes the actin cytoskeleton in plant and mammalian cells via the modulation of the architecture and dynamic of the actin network, most likely via interference with actin-binding proteins. A new mechanistic hypothesis is advanced here based on the recent discovery of the targeting of the chaperone protein Hsp47 by the fragmented limonoid fraxinellone. Molecular modeling suggested that prieurianin and, to a lesser extent dregeanin, can form very stable complexes with Hsp47 at the protein–collagen interface. Hsp-binding may account for the insecticidal action of the product. The present review draws up a new mechanistic portrait of prieurianin and provides an overview of the pharmacological properties of this atypical limonoid and its chemical family. Full article
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