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Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 3.0

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: closed (30 November 2023) | Viewed by 11689

Special Issue Editor

Special Issue Information

Dear Colleagues,

Natural products are small molecules produced naturally by any organism, including primary and secondary metabolites. Natural products have a wide range of possible applications, such as in biomedicine and pharmacotherapy, and can be useful in the treatment and management various kinds of human diseases due to their outstanding biological properties. Moreover, bioactive compounds and pharmaceuticals derived from natural products have received increasing attention due to their considerable benefits for human health. This Special Issue will shape the future research direction of important natural products as well as related bioactive. Our purpose is to feature high-quality, advanced research and knowledge contributed by various research groups working on natural products from all around the world. This Special Issue invites researchers to contribute reviews and original research reports of their recent work on the functional and medicinal properties of natural products.

This Special Issue will include recent advances in natural products with significant potential benefits for human health, including on the following topics: natural products for preventing and managing human diseases; the importance of nutraceuticals and cosmeceuticals derived from natural products for human health and skin aging; bioactivity and mechanism of action of natural products; new strategies of using natural drugs for promoting human health.

Prof. Dr. Seung-Hong Lee
Guest Editor

Manuscript Submission Information

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Keywords

  • natural products
  • biomedicine
  • pharmacotherapy
  • bioactive compounds
  • human health
  • skin aging

Published Papers (9 papers)

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Research

18 pages, 1088 KiB  
Article
Biotransformation of Δ1-Progesterone Using Selected Entomopathogenic Filamentous Fungi and Prediction of Its Products’ Bioactivity
by Anna Panek, Patrycja Wójcik, Alina Świzdor, Maciej Szaleniec and Tomasz Janeczko
Int. J. Mol. Sci. 2024, 25(1), 508; https://doi.org/10.3390/ijms25010508 - 29 Dec 2023
Cited by 1 | Viewed by 529
Abstract
This research aimed at obtaining new derivatives of pregn-1,4-diene-3,20-dione (Δ1-progesterone) (2) through microbiological transformation. For the role of catalysts, we used six strains of entomopathogenic filamentous fungi (Beauveria bassiana KCh J1.5, Beauveria caledonica KCh J3.3, Isaria fumosorosea KCh [...] Read more.
This research aimed at obtaining new derivatives of pregn-1,4-diene-3,20-dione (Δ1-progesterone) (2) through microbiological transformation. For the role of catalysts, we used six strains of entomopathogenic filamentous fungi (Beauveria bassiana KCh J1.5, Beauveria caledonica KCh J3.3, Isaria fumosorosea KCh J2, Isaria farinosa KCh KW1.1, Isaria tenuipes MU35, and Metarhizium robertsii MU4). The substrate (2) was obtained by carrying out an enzymatic 1,2-dehydrogenation on an increased scale (3.5 g/L) using a recombinant cholest-4-en-3-one Δ1-dehydrogenase (AcmB) from Sterolibacterium denitrificans. All selected strains were characterized by the high biotransformation capacity for the used substrate. As a result of the biotransformation, six steroid derivatives were obtained: 11α-hydroxypregn-1,4-diene-3,20-dione (3), 6β,11α-dihydroxypregn-1,4-diene-3,20-dione (4), 6β-hydroxypregn-1,4-diene-3,11,20-trione (5), 6β,17α-dihydroxypregn-1,4-diene-3,20-dione (6), 6β,17β-dihydroxyandrost-1,4-diene-3-one (7), and 12β,17α-dihydroxypregn-1,4-diene-3,20-dione (8). The results show evident variability of the biotransformation process between strains of the tested biocatalysts from different species described as entomopathogenic filamentous fungi. The obtained products were tested in silico using cheminformatics tools for their pharmacokinetic and pharmacodynamic properties, proving their potentially high biological activities. This study showed that the obtained compounds may have applications as effective inhibitors of testosterone 17β-dehydrogenase. Most of the obtained products should, also with a high probability, find potential uses as androgen antagonists, a prostate as well as menopausal disorders treatment. They should also demonstrate immunosuppressive, erythropoiesis-stimulating, and anti-inflammatory properties. Full article
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16 pages, 4869 KiB  
Article
Porcine Placenta Peptide Inhibits UVB-Induced Skin Wrinkle Formation and Dehydration: Insights into MAPK Signaling Pathways from In Vitro and In Vivo Studies
by Woo-Jin Sim, Jinhak Kim, Kwang-Soo Baek, Wonchul Lim and Tae-Gyu Lim
Int. J. Mol. Sci. 2024, 25(1), 83; https://doi.org/10.3390/ijms25010083 - 20 Dec 2023
Cited by 1 | Viewed by 650
Abstract
Excessive exposure to ultraviolet (UV) radiation from sunlight accelerates skin aging, leading to various clinical manifestations such as wrinkles, dryness, and loss of elasticity. This study investigated the protective effects of porcine placenta peptide (PPP) against UVB-induced skin photoaging. Female hairless SKH-1 mice [...] Read more.
Excessive exposure to ultraviolet (UV) radiation from sunlight accelerates skin aging, leading to various clinical manifestations such as wrinkles, dryness, and loss of elasticity. This study investigated the protective effects of porcine placenta peptide (PPP) against UVB-induced skin photoaging. Female hairless SKH-1 mice were orally administered PPP for 12 weeks, followed by UVB irradiation. PPP significantly reduced wrinkle formation, improved skin moisture levels, and prevented collagen degradation. Mechanistically, PPP inhibited the expression of matrix metalloproteinases (MMPs) and upregulated collagen production. Moreover, PPP elevated hyaluronic acid levels, contributing to enhanced skin hydration. Additionally, PPP demonstrated antioxidant properties by increasing the expression of the antioxidant enzyme GPx-1, thereby reducing UVB-induced inflammation. Further molecular analysis revealed that PPP suppressed the activation of p38 MAP kinase and JNK signaling pathways, crucial mediators of UV-induced skin damage. These findings highlight the potential of porcine placental peptides as a natural and effective intervention against UVB-induced skin photoaging. The study provides valuable insights into the mechanisms underlying the protective effects of PPP, emphasizing its potential applications in skincare and anti-aging formulations. Full article
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13 pages, 2377 KiB  
Article
Protective Effects of Lanostane Triterpenoids from Chaga Mushroom in Human Keratinocytes, HaCaT Cells, against Inflammatory and Oxidative Stresses
by Jihyun Park, Thi Minh Nguyet Nguyen, Hyun-ah Park, My Tuyen Thi Nguyen, Nan-young Lee, So-young Ban, Kyu-been Park, Chang-kyu Lee, Jaehan Kim and Jong-Tae Park
Int. J. Mol. Sci. 2023, 24(16), 12803; https://doi.org/10.3390/ijms241612803 - 15 Aug 2023
Cited by 1 | Viewed by 1250
Abstract
Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushrooms have been investigated for various allergic diseases. However, the anti-aging and anti-inflammatory activities of inotodiol under different types of oxidative stress and the impact of inotodiol on collagen and hyaluronan synthesis have not [...] Read more.
Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushrooms have been investigated for various allergic diseases. However, the anti-aging and anti-inflammatory activities of inotodiol under different types of oxidative stress and the impact of inotodiol on collagen and hyaluronan synthesis have not been sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulations such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced the overexpression of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate the synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role for pure inotodiol/inotodiol concentrate in the prevention of skin aging. These results illuminate the anti-inflammatory and anti-aging effects of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications. Full article
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18 pages, 6946 KiB  
Article
α-Aminobutyric Acid Constrains Macrophage-Associated Inflammatory Diseases through Metabolic Reprogramming and Epigenetic Modification
by Fei Li, Yuting Xia, Shijie Yuan, Xiaorong Xie, Lin Li, Yuan Luo, Qiuyang Du, Yuqi Yuan and Ran He
Int. J. Mol. Sci. 2023, 24(13), 10444; https://doi.org/10.3390/ijms241310444 - 21 Jun 2023
Viewed by 1487
Abstract
Metabolites play critical roles in macrophage polarization and in their function in response to infection and inflammation. α-aminobutyric acid (AABA), a non-proteinogenic amino acid which can be generated from methionine, threonine, serine, and glycine, has not been studied extensively in relation to macrophage [...] Read more.
Metabolites play critical roles in macrophage polarization and in their function in response to infection and inflammation. α-aminobutyric acid (AABA), a non-proteinogenic amino acid which can be generated from methionine, threonine, serine, and glycine, has not been studied extensively in relation to macrophage polarization and function. In this study, we aimed to investigate the immunomodulatory function of AABA in regulating M1 macrophage polarization and function in vitro and in vivo. We stimulated bone-marrow-derived macrophages with lipopolysaccharide (LPS) to generate M1 macrophages. Subsequently, we induced sepsis and colitis in mice, followed by treatment with AABA. We then analyzed the samples using ELISA, real-time PCR, Western blotting, flow cytometry, and histopathological analysis to evaluate cytokine secretion, inflammatory gene expression, macrophage activation, disease progression, and inflammation severity. Additionally, metabolomic and chromatin immunoprecipitation-qPCR were conducted to investigate the function of AABA on metabolic reprogramming and epigenetic modifications of M1 macrophages. Our results revealed that AABA inhibited M1 macrophage polarization and function, which led to prolonged survival in septic mice and reduced disease severity in colitis mice. Mechanically, AABA promoted oxidative phosphorylation (OXPHOS) and glutamine and arginine metabolism while inhibiting glycolysis. Moreover, AABA could increase the occupancy of trimethylation of histone H3K27 at the promoter regions of M1 macrophage-associated inflammatory genes, which contributed to the inhibition of M1 macrophage polarization. These findings suggest that AABA may have therapeutic potential for inflammatory diseases by regulating macrophage polarization and function through metabolic and epigenetic pathways. Full article
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21 pages, 29126 KiB  
Article
AIEE-Active Flavones as a Promising Tool for the Real-Time Tracking of Uptake and Distribution in Live Zebrafish
by Yi Wu, Ying He, Huiqing Luo, Tingting Jin and Feng He
Int. J. Mol. Sci. 2023, 24(12), 10183; https://doi.org/10.3390/ijms241210183 - 15 Jun 2023
Viewed by 1046
Abstract
In recent years, aggregation-induced emission enhancement (AIEE) molecules have shown great potential for applications in the fields of bio-detection, imaging, optoelectronic devices, and chemical sensing. Based on our previous studies, we investigated the fluorescence properties of six flavonoids and confirmed that compounds 1 [...] Read more.
In recent years, aggregation-induced emission enhancement (AIEE) molecules have shown great potential for applications in the fields of bio-detection, imaging, optoelectronic devices, and chemical sensing. Based on our previous studies, we investigated the fluorescence properties of six flavonoids and confirmed that compounds 13 have good aggregation-induced emission enhancement (AIEE) properties through a series of spectroscopic experiments. Compounds with AIEE properties have addressed the limitation imposed by the aggregation-caused quenching (ACQ) of classic organic dyes owing to their strong fluorescence emission and high quantum yield. Based on their excellent fluorescence properties, we evaluated their performance in the cell and we found that they could label mitochondria specifically by comparing their Pearson correlation coefficients (R) with Mito Tracker Red and Lyso-Tracker Red. This suggests their future application in mitochondrial imaging. Furthermore, studies of uptake and distribution characterization in 48 hpf zebrafish larvae revealed their potential for monitoring real-time drug behavior. The uptake of compounds by larvae varies significantly across different time cycles (between uptake and utilization in the tissue). This observation has important implications for the development of visualization techniques for pharmacokinetic processes and can enable real-time feedback. More interestingly, according to the data presented, tested compounds aggregated in the liver and intestine of 168 hpf larvae. This finding suggests that they could potentially be used for monitoring and diagnosing liver and intestinal diseases. Full article
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13 pages, 1760 KiB  
Article
Efficacy of a Multicomponent Nutraceutical Formulation for the Prevention and Treatment of Urinary Tract Stones
by Maria Maisto, Elisabetta Schiano, Gianni Luccheo, Luigi Luccheo, Ernesto Alfieri, Vincenzo Piccolo, Fortuna Iannuzzo, Ritamaria Di Lorenzo and Gian Carlo Tenore
Int. J. Mol. Sci. 2023, 24(9), 8316; https://doi.org/10.3390/ijms24098316 - 05 May 2023
Viewed by 1478
Abstract
Urolithiasis is a complex and multifactorial disease characterized by the formation of calculi at the urinary tract level. Conventional therapeutic prophylaxis relies on the use of Ca-blockers, alkalis, diuretics, and anti-edema agents, but their prolonged utilization is often limited by several side effects. [...] Read more.
Urolithiasis is a complex and multifactorial disease characterized by the formation of calculi at the urinary tract level. Conventional therapeutic prophylaxis relies on the use of Ca-blockers, alkalis, diuretics, and anti-edema agents, but their prolonged utilization is often limited by several side effects. In this scenario, the aim of the present work was the design of an innovative multi-component nutraceutical formulation (NF) for the management of urinary stones consisting of a synergistic combination of natural aqueous extracts of Oreganum vulgare L. (1% of saponin), Urtica dioica (0.8% of β-sitosterol), Phyllanthus niruri (15% of tannins w/w), and Ceterach officinarum in association with bromelain, K, and Mg citrate. To assess the potential of NF also in the treatment of uric acid (UA) stones, the effects on the expression of the cellular UA transporters OAT1 and URAT1 were investigated in a renal tubular cell line. In addition, the myorelaxant effect of NF was investigated in a human pulmonary artery smooth muscle cell (HPASMC) model resulting in a decreased muscle contractility of −49.4% (p < 0.01) compared to the control. The treatment with NF also showed a valuable inhibition of in vitro calcium-oxalate crystal formation, both in prevention (−52.3% vs. control, p < 0.01) and treatment (−70.8% vs. control, p < 0.01) experiments. Finally, an ischemic reperfusion rat model was used to evaluate the NF anti-edema effects, resulting in a reduction in the edema-related vascular permeability (Normalized Gray Levels, NGL = 0.40 ± 0.09, p < 0.01, −67.1% vs. untreated rats). In conclusion, the present NF has shown to be a promising natural alternative for managing urinary tract stones. Full article
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17 pages, 3786 KiB  
Article
Antiviral Activity of Quercetin Hydrate against Zika Virus
by Marielena Vogel Saivish, Gabriela de Lima Menezes, Roosevelt Alves da Silva, Marina Alves Fontoura, Jacqueline Farinha Shimizu, Gislaine Celestino Dutra da Silva, Igor da Silva Teixeira, Natalia Franco Bueno Mistrão, Victor Miranda Hernandes, Paula Rahal, Lívia Sacchetto, Carolina Colombelli Pacca, Rafael Elias Marques and Maurício Lacerda Nogueira
Int. J. Mol. Sci. 2023, 24(8), 7504; https://doi.org/10.3390/ijms24087504 - 19 Apr 2023
Cited by 3 | Viewed by 1329
Abstract
Zika virus (ZIKV) has re-emerged in recent decades, leading to outbreaks of Zika fever in Africa, Asia, and Central and South America. Despite its drastic re-emergence and clinical impact, no vaccines or antiviral compounds are available to prevent or control ZIKV infection. This [...] Read more.
Zika virus (ZIKV) has re-emerged in recent decades, leading to outbreaks of Zika fever in Africa, Asia, and Central and South America. Despite its drastic re-emergence and clinical impact, no vaccines or antiviral compounds are available to prevent or control ZIKV infection. This study evaluated the potential antiviral activity of quercetin hydrate against ZIKV infection and demonstrated that this substance inhibits virus particle production in A549 and Vero cells under different treatment conditions. In vitro antiviral activity was long-lasting (still observed 72 h post-infection), suggesting that quercetin hydrate affects multiple rounds of ZIKV replication. Molecular docking indicates that quercetin hydrate can efficiently interact with the specific allosteric binding site cavity of the NS2B-NS3 proteases and NS1-dimer. These results identify quercetin as a potential compound to combat ZIKV infection in vitro. Full article
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21 pages, 4140 KiB  
Article
Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition
by Myung-Ji Kang, Hyung Won Ryu, Eun Sol Oh, Yu Na Song, Yang Hoon Huh, Ji-Yoon Park, Seon Min Oh, Su-Yeon Lee, Yhun Jung Park, Doo-Young Kim, Hyunju Ro, Sung-Tae Hong, Su Ui Lee, Dong-Oh Moon and Mun-Ock Kim
Int. J. Mol. Sci. 2023, 24(8), 7057; https://doi.org/10.3390/ijms24087057 - 11 Apr 2023
Cited by 3 | Viewed by 1651
Abstract
The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent [...] Read more.
The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells. Full article
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23 pages, 6827 KiB  
Article
Extract of Aster koraiensis Nakai Leaf Ameliorates Memory Dysfunction via Anti-inflammatory Action
by Seung-Eun Lee, Saetbyeol Park, Gwi Yeong Jang, Jeonghoon Lee, Minho Moon, Yun-Jeong Ji, Ji Wook Jung, Yunkwon Nam, Soo Jung Shin, Yunji Lee, Jehun Choi and Dong Hwi Kim
Int. J. Mol. Sci. 2023, 24(6), 5765; https://doi.org/10.3390/ijms24065765 - 17 Mar 2023
Cited by 4 | Viewed by 1641
Abstract
Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the [...] Read more.
Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, phosphorylated-tau (p-tau), and the expression of inflammatory proteins in lipopolysaccharide- or amyloid-β-treated cells. AK extract exhibited inhibitory activity of control specific binding on N-methyl-D-aspartate (NMDA) receptors. Scopolamine-induced AD models were used chronically in rats and acutely in mice. Relative to negative controls (NC), hippocampal choline acetyltransferase (ChAT) and B-cell lymphoma 2 (Bcl2) activity was increased in rats chronically treated with scopolamine and fed an AK extract-containing diet. In the Y-maze test, spontaneous alterations were increased in the AK extract-fed groups compared to NC. Rats administered AK extract showed increased escape latency in the passive avoidance test. In the hippocampus of rats fed a high-AK extract diet (AKH), the expression of neuroactive ligand–receptor interaction-related genes, including Npy2r, Htr2c, and Rxfp1, was significantly altered. In the Morris water maze assay of mice acutely treated with scopolamine, the swimming times in the target quadrant of AK extract-treated groups increased significantly to the levels of the Donepezil and normal groups. We used Tg6799 Aβ-overexpressing 5XFAD transgenic mice to investigate Aβ accumulation in animals. In the AD model using 5XFAD, the administration of AK extract decreased amyloid-β (Aβ) accumulation and increased the number of NeuN antibody-reactive cells in the subiculum relative to the control group. In conclusion, AK extract ameliorated memory dysfunction by modulating ChAT activity and Bcl2-related anti-apoptotic pathways, affecting the expression of neuroactive ligand–receptor interaction-related genes and inhibiting Aβ accumulation. Therefore, AK extract could be a functional material improving cognition and memory. Full article
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