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Functions and Applications of Natural Products
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Functions and Applications 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 (20 April 2025) | Viewed by 11969

Special Issue Editors

Dr. Seung-Hong Lee

E-Mail Website
Guest Editor
Department of Pharmaceutical Engineering and Medical Science, Soonchunhyang University, Asan 31538, Republic of Korea
Interests: bioactive natural products; nutraceuticals; cosmeceuticals; pharmaceuticals
Special Issues, Collections and Topics in MDPI journals
Dr. Seon-Heui Cha

E-Mail Website
Guest Editor
Department of Marine Bio and Medical Sciences, Hanseo University, Seosan 32158, Republic of Korea
Interests: nutraceuticals; cosmeceuticals; functional materials; marine biofoods; marine drugs
Special Issues, Collections and Topics in MDPI journals

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 biomedicine and pharmacotherapy, and they can be useful in the treatment and management of 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 bioactives. 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 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; biotechnology for yielding bioactive components from the natural products.

Dr. Seung-Hong Lee
Dr. Seon-Heui Cha
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

  • natural products
  • biomedicine/phytomedicine
  • biologically active extracts and compounds
  • pharmacological and toxicological mechanisms of action

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Published Papers (6 papers)

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Research

17 pages, 3069 KiB  
Article
Benefits of Camelina sativa Supplementation in Morphine Treatment: Enhanced Analgesia, Delayed Tolerance and Reduced Gut Side Effects Through PPAR-α Receptor Engagement
by Elena Lucarini, Eleonora Pagnotta, Laura Micheli, Samuele Trisolini, Roberto Matteo, Laura Righetti, Alma Martelli, Lara Testai, Vincenzo Calderone, Lorenzo Di Cesare Mannelli and Carla Ghelardini
Int. J. Mol. Sci. 2025, 26(6), 2519; https://doi.org/10.3390/ijms26062519 - 11 Mar 2025
Viewed by 465
Abstract
Long-term opioid therapies are severely limited by the development of analgesic tolerance and gastrointestinal side effects. Camelina sativa, a plant of the Brassicaceae family, modulates the activity of peroxisome proliferator-activated receptor α (PPAR-α receptor), which is involved in the regulation of pain [...] Read more.
Long-term opioid therapies are severely limited by the development of analgesic tolerance and gastrointestinal side effects. Camelina sativa, a plant of the Brassicaceae family, modulates the activity of peroxisome proliferator-activated receptor α (PPAR-α receptor), which is involved in the regulation of pain processing and gut physiology. The aim of this study was to evaluate the efficacy of Camelina sativa defatted seed meal (DSM) supplementation on the development of analgesic tolerance and side effects after repeated treatment with morphine in naïve mice. Co-administering Camelina sativa DSM (1 g kg−1 p.o.) and morphine (10 mg kg−1 s.c.) increased the efficacy and duration of the opioid-induced acute analgesic effect. Camelina supplementation also delayed the onset of tolerance to the morphine analgesic effect. The same result was obtained through either simultaneously administering morphine and camelina or administering camelina 24 h before morphine injection for the entire duration of the experiment. Camelina also counteracted intestinal damage and visceral hypersensitivity caused by morphine treatment. The beneficial effects of camelina on morphine-related analgesic efficacy and gut side effects were prevented via pre-treatment with the PPAR-α antagonist GW6471, though the latter did not influence the development of morphine tolerance. In conclusion, Camelina sativa DSM could be used as a supplement to improve the therapeutic profile of morphine. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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15 pages, 2812 KiB  
Article
Liquid Chromatography Quadrupole Time-of-Flight Tandem Mass Spectrometry Characterization of Ethyl Acetate Fraction from Sargassum pallidum and Its Anti-Melanogenesis Effect in B16F10 Melanoma Cells and Zebrafish Model
by Wook-Chul Kim, Hyeon Kang and Seung-Hong Lee
Int. J. Mol. Sci. 2025, 26(4), 1522; https://doi.org/10.3390/ijms26041522 - 11 Feb 2025
Viewed by 707
Abstract
Melanin overproduction causes various skin diseases, such as spots, freckles, and wrinkles, resulting in the requirement of melanin synthesis inhibitors like 1-phenyl-2-thiourea (PTU) and kojic acid, which have been commonly used in the pharmaceutical industry. However, these inhibitors can cause side effects such [...] Read more.
Melanin overproduction causes various skin diseases, such as spots, freckles, and wrinkles, resulting in the requirement of melanin synthesis inhibitors like 1-phenyl-2-thiourea (PTU) and kojic acid, which have been commonly used in the pharmaceutical industry. However, these inhibitors can cause side effects such as skin irritation and allergies. Therefore, it is necessary to develop safe and effective melanin inhibitors from natural resources. The purpose of this study was to investigate a whitening agent from natural substances using B16F10 melanoma cells and zebrafish model. We investigated the melanogenesis-inhibiting activities of the fractions from Sargassum pallidum extract. The ethyl acetate fraction from S. pallidum extract (SPEF) significantly decreased tyrosinase activity. SPEF also significantly reduced α-melanocyte stimulating hormone (MSH)-induced intracellular tyrosinase activity and melanin content in B16F10 cells. Moreover, SPEF inhibited the expression levels of key melanogenic proteins such as tyrosinase, TRP-1, TRP-2, and MITF by downregulating the phosphorylation levels of CREB and PKA in α-MSH-stimulated melanoma cells. Furthermore, SPEF significantly suppressed melanin synthesis in the zebrafish model with no developmental toxicity. LC-Q-TOF-MS/MS analysis identified that SPEF was composed of 12 phytochemical compounds, including diterpenes, which were the dominant metabolites. These results altogether show that SPEF effectively suppresses melanogenesis in B16F10 melanoma cells and in a zebrafish model, with potential for usage in pharmaceuticals and cosmeceuticals. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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11 pages, 2582 KiB  
Article
Skin Improvement Effects of Ultrasound-Enzyme-Treated Collagen Peptide Extracts from Flatfish (Paralichthys olivaceus) Skin in an In Vitro Model
by Su-Jin Eom, Jae-Hoon Kim, A-Reum Ryu, Heejin Park, Jae-Hoon Lee, Jung-Hyun Park, Nam-Hyouck Lee, Saerom Lee, Tae-Gyu Lim, Min-Cheol Kang and Kyung-Mo Song
Int. J. Mol. Sci. 2024, 25(17), 9300; https://doi.org/10.3390/ijms25179300 - 27 Aug 2024
Viewed by 1885
Abstract
Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for [...] Read more.
Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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15 pages, 1547 KiB  
Article
Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans—A Pilot Study
by Chuck Chang, Yoon Seok Roh, Min Du, Yun Chai Kuo, Yiming Zhang, Mary Hardy, Roland Gahler and Julia Solnier
Int. J. Mol. Sci. 2024, 25(11), 5625; https://doi.org/10.3390/ijms25115625 - 22 May 2024
Cited by 2 | Viewed by 2515
Abstract
We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over [...] Read more.
We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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16 pages, 1923 KiB  
Article
Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats
by Kristina Stavrakeva, Kalina Metodieva, Maria Benina, Anelia Bivolarska, Ivica Dimov, Mariya Choneva, Vesela Kokova, Saleh Alseekh, Valentina Ivanova, Emil Vatov, Tsanko Gechev, Tsvetelina Mladenova, Rumen Mladenov, Krasimir Todorov, Plamen Stoyanov, Donika Gyuzeleva, Mihaela Popova and Elisaveta Apostolova
Int. J. Mol. Sci. 2024, 25(10), 5396; https://doi.org/10.3390/ijms25105396 - 15 May 2024
Cited by 1 | Viewed by 1765
Abstract
Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. Micromeria frivaldszkyana is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of M. [...] Read more.
Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. Micromeria frivaldszkyana is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of M. frivaldszkyana by chromatography–mass spectrometry (GC-MS), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Amino acids, organic acids, sugars, and sugar alcohols were the primary metabolites with the highest levels in the plant extract. Detailed analysis of the sugar content identified high levels of sucrose, glucose, mannose, and fructose. Lipids are primary plant metabolites, and the analysis revealed triacylglycerols as the most abundant lipid group. Potassium (K), magnesium (Mg), zinc (Zn), and calcium (Ca) were the elements with the highest content. The results showed linarin, 3-caffeoil-quinic acid, and rosmarinic acid, as well as a number of polyphenols, as the most abundant secondary metabolites. Among the flavonoids and polyphenols with a high presence were eupatorin, kaempferol, and apigenin—compounds widely known for their bioactive properties. Further, the acute toxicity and potential anti-inflammatory activity of the methanolic extract were evaluated in Wistar rats. No toxic effects were registered after a single oral application of the extract in doses of between 200 and 5000 mg/kg bw. A fourteen-day pre-treatment with methanolic extract of M. frivaldszkyana in doses of 250, 400, and 500 mg/kg bw induced anti-inflammatory activity in the 1st, 2nd, and 3rd hours after carrageenan injection in a model of rat paw edema. This effect was also present in the 4th hour only in the group treated with a dose of 500 mg/kg. In conclusion, M. frivaldszkyana extract is particularly rich in linarin, rosmarinic acid, and flavonoids (eupatorin, kaempferol, and apigenin). Its methanolic extract induced no toxicity in male Wistar rats after oral application in doses of up to 5000 mg/kg bw. Additionally, treatment with the methanolic extract for 14 days revealed anti-inflammatory potential in a model of rat paw edema on the 1st, 2nd, and 3rd hours after the carrageenan injection. These results show the anti-inflammatory potential of the plant, which might be considered for further exploration and eventual application as a phytotherapeutic agent. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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28 pages, 15021 KiB  
Article
Bacillus megaterium: Evaluation of Chemical Nature of Metabolites and Their Antioxidant and Agronomics Properties
by Anna Hur, Mohamed Marouane Saoudi, Hicham Ferhout, Laila Mzali, Patricia Taillandier and Jalloul Bouajila
Int. J. Mol. Sci. 2024, 25(6), 3235; https://doi.org/10.3390/ijms25063235 - 12 Mar 2024
Cited by 2 | Viewed by 3689
Abstract
Bacillus megaterium is particularly known for its abundance in soils and its plant growth promotion. To characterize the metabolites excreted by this specie, we performed successive liquid/liquid extractions from bacteria culture medium with different polarity solvents (cyclohexane, dichloromethane, ethyl acetate and butanol) to [...] Read more.
Bacillus megaterium is particularly known for its abundance in soils and its plant growth promotion. To characterize the metabolites excreted by this specie, we performed successive liquid/liquid extractions from bacteria culture medium with different polarity solvents (cyclohexane, dichloromethane, ethyl acetate and butanol) to separate the metabolites in different polarity groups. The extracts were characterized regarding their total phenolic content, the amount of reducing sugar, the concentration of primary amines and proteins, their chromatographic profile by HPLC-DAD-ELSD and their chemical identification by GC-MS. Among the 75 compounds which are produced by the bacteria, 19 identifications were for the first time found as metabolites of B. megaterium and 23 were described for the first time as metabolites in Bacillus genus. The different extracts containing B. megaterium metabolites showed interesting agronomic activity, with a global inhibition of seed germination rates of soya, sunflower, corn and ray grass, but not of corn, compared to culture medium alone. Our results suggest that B. megaterium can produce various metabolites, like butanediol, cyclic dipeptides, fatty acids, and hydrocarbons, with diverse effects and sometimes with opposite effects in order to modulate its response to plant growth and adapt to various environmental effects. These findings provide new insight into bioactive properties of this species for therapeutic uses on plants. Full article
(This article belongs to the Special Issue Functions and Applications of Natural Products)
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