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Nutrients
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The Benefits of Natural Products for Disease Treatments
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The Benefits of Natural Products for Disease Treatments

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: 5 May 2024 | Viewed by 16119

Special Issue Editors

Prof. Dr. Sang J. Chung

E-Mail Website
Guest Editor
1. School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
2. Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
Interests: bioactive natural products; synthetic analogues of natural products; anti-diabetic agents; targets of bioactive natural products
Dr. Ki Hyun Kim

E-Mail Website
Guest Editor
Natural Product Research Laboratory, School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea
Interests: discovery and structural elucidation of natural products; metabolomics of natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products have long been recognized for their potential therapeutic benefits, and recent advances in research have led to a renewed interest in exploring their therapeutic potential. At our journal, we aim to publish high-quality research on the use of natural products in treating various diseases, with a particular focus on their potential as novel therapeutic agents.

We are pleased to announce that we are now accepting manuscripts related to natural product research for publication in the Special Issue “The Benefits of Natural Products for Disease Treatments”. Our journal welcomes submissions related to bioactive natural products with therapeutic potential, as well as molecular-level studies of pharmacological activity by natural products. Specifically, we are interested in manuscripts that focus on the use of natural products in the treatment and prevention of cancer, metabolic diseases such as diabetes and obesity, and related conditions.

We welcome original research articles and reviews on the use of natural products in disease prevention and treatment. Our goal is to provide a platform for researchers to share their insights, ideas, and findings on natural product research, with the ultimate aim of improving health outcomes for patients worldwide.

Prof. Dr. Sang J. Chung
Prof. Dr. Ki Hyun Kim
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. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • bioactive natural products
  • diabetes
  • obesity
  • cancers
  • molecular level research
  • target identification
  • multi-targeting

Published Papers (10 papers)

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Research

Jump to: Review, Other

16 pages, 2727 KiB  
Article
Treatment with Glycyrrhiza glabra Extract Induces Anxiolytic Effects Associated with Reduced Salt Preference and Changes in Barrier Protein Gene Expression
by Harald Murck, Peter Karailiev, Lucia Karailievova, Agnesa Puhova and Daniela Jezova
Nutrients 2024, 16(4), 515; https://doi.org/10.3390/nu16040515 - 13 Feb 2024
Viewed by 993
Abstract
We have previously identified that low responsiveness to antidepressive therapy is associated with higher aldosterone/cortisol ratio, lower systolic blood pressure, and higher salt preference. Glycyrrhiza glabra (GG) contains glycyrrhizin, an inhibitor of 11β-hydroxysteroid-dehydrogenase type-2 and antagonist of toll-like receptor 4. The primary hypothesis [...] Read more.
We have previously identified that low responsiveness to antidepressive therapy is associated with higher aldosterone/cortisol ratio, lower systolic blood pressure, and higher salt preference. Glycyrrhiza glabra (GG) contains glycyrrhizin, an inhibitor of 11β-hydroxysteroid-dehydrogenase type-2 and antagonist of toll-like receptor 4. The primary hypothesis of this study is that food enrichment with GG extract results in decreased anxiety behavior and reduced salt preference under stress and non-stress conditions. The secondary hypothesis is that the mentioned changes are associated with altered gene expression of barrier proteins in the prefrontal cortex. Male Sprague-Dawley rats were exposed to chronic mild stress for five weeks. Both stressed and unstressed rats were fed a diet with or without an extract of GG roots for the last two weeks. GG induced anxiolytic effects in animals independent of stress exposure, as measured in elevated plus maze test. Salt preference and intake were significantly reduced by GG under control, but not stress conditions. The gene expression of the barrier protein claudin-11 in the prefrontal cortex was increased in control rats exposed to GG, whereas stress-induced rise was prevented. Exposure to GG-enriched diet resulted in reduced ZO-1 expression irrespective of stress conditions. In conclusion, the observed effects of GG are in line with a reduction in the activity of central mineralocorticoid receptors. The treatment with GG extract or its active components may, therefore, be a useful adjunct therapy for patients with subtypes of depression and anxiety disorders with heightened renin–angiotensin–aldosterone system and/or inflammatory activity. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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15 pages, 2050 KiB  
Article
Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron
by Xiaodi Zhao, Dohee Ahn, Gibeom Nam, Jihee Kwon, Songyi Song, Min Ji Kang, Hyejin Ahn and Sang J. Chung
Nutrients 2023, 15(22), 4774; https://doi.org/10.3390/nu15224774 - 13 Nov 2023
Cited by 1 | Viewed by 1254
Abstract
Crocin, a glycoside of crocetin, has been known as the principal component responsible for saffron’s antidiabetic, anticancer, and anti-inflammatory effects. Crocetin, originating from the hydrolytic cleavage of crocin in biological systems, was subjected to ligand-based virtual screening in this investigation. Subsequent biochemical analysis [...] Read more.
Crocin, a glycoside of crocetin, has been known as the principal component responsible for saffron’s antidiabetic, anticancer, and anti-inflammatory effects. Crocetin, originating from the hydrolytic cleavage of crocin in biological systems, was subjected to ligand-based virtual screening in this investigation. Subsequent biochemical analysis unveiled crocetin, not crocin, as a novel dual GPR40 and GPR120 agonist, demonstrating a marked preference for GPR40 and GPR120 over peroxisome proliferator-activated receptors (PPAR)γ. This compound notably enhanced insulin and GLP-1 secretion from pancreatic β-cells and intestinal neuroendocrine cells, respectively, presenting a dual mechanism of action in glucose-lowering effects. Docking simulations showed that crocetin emulates the binding characteristics of natural ligands through hydrogen bonds and hydrophobic interactions, whereas crocin’s hindered fit within the binding pocket is attributed to steric constraints. Collectively, for the first time, this study unveils crocetin as the true active component of saffron, functioning as a GPR40/120 agonist with potential implications in antidiabetic interventions. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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16 pages, 3464 KiB  
Article
Myogenesis Effects of RGX365 to Improve Skeletal Muscle Atrophy
by Hye-Jin Lee, Hui-Ji Choi, Sang-Ah Lee, Dong Hyuk Baek, Jong Beom Heo, Gyu Yong Song and Wonhwa Lee
Nutrients 2023, 15(19), 4307; https://doi.org/10.3390/nu15194307 - 09 Oct 2023
Viewed by 1398
Abstract
Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the [...] Read more.
Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 µM)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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17 pages, 2612 KiB  
Article
The Circadian Nobiletin-ROR Axis Suppresses Adipogenic Differentiation and IκBα/NF-κB Signaling in Adipocytes
by Eunju Kim, Kazuaki Mawatari, Seung-Hee Yoo and Zheng Chen
Nutrients 2023, 15(18), 3919; https://doi.org/10.3390/nu15183919 - 09 Sep 2023
Cited by 1 | Viewed by 1165
Abstract
Obesity is a known risk factor for metabolic diseases and is often associated with chronic inflammation in adipose tissue. We previously identified the polyethoxylated flavonoid Nobiletin (NOB) as a circadian clock modulator that directly binds to and activates the ROR receptors in the [...] Read more.
Obesity is a known risk factor for metabolic diseases and is often associated with chronic inflammation in adipose tissue. We previously identified the polyethoxylated flavonoid Nobiletin (NOB) as a circadian clock modulator that directly binds to and activates the ROR receptors in the core oscillator, markedly improving metabolic fitness in obese mice. Here, we show that NOB enhanced the oscillation of core clock genes in differentiated 3T3-L1 adipocytes, including ROR target genes such as Bmal1, Cry1, Dec1, and Dec2. NOB inhibited lipid accumulation in 3T3-L1 and SVF cells, concomitant with the dysregulated circadian expression of adipogenic differentiation-related genes including Cebpb, Pparg, Lpl, Scd1, and Fas. Importantly, RORα/RORγ double knockdown in 3T3-L1 cells (Ror DKD) significantly attenuated the effects of NOB on circadian gene expression and lipid accumulation. Furthermore, whereas NOB upregulated the expression of IκBα, a target of RORs, to inhibit NF-κB activation and proinflammatory cytokine expression, Ror DKD cells exhibited a heightened activation of the NF-κB pathway, further indicating a requisite role of RORs for NOB efficacy in adipocytes. Together, these results highlight a significant regulatory function of the NOB–ROR axis in the circadian expression of clock and clock-controlled genes in adipocytes, thereby governing adipogenic differentiation, lipogenesis, and inflammation. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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14 pages, 2724 KiB  
Article
N,N-Dimethyl-anthranilic Acid from Calvatia nipponica Mushroom Fruiting Bodies Induces Apoptotic Effects on MDA-MB-231 Human Breast Cancer Cells
by Dahae Lee, Seulah Lee, Yoon Seo Jang, Rhim Ryoo, Jung Kyu Kim, Ki Sung Kang and Ki Hyun Kim
Nutrients 2023, 15(14), 3091; https://doi.org/10.3390/nu15143091 - 10 Jul 2023
Cited by 1 | Viewed by 1369
Abstract
Breast cancer ranks among the most prevalent malignancies affecting women worldwide, and apoptosis-targeting drugs are attractive candidates for the treatment of cancer. In the current study, we investigated the in vitro cytotoxicity of the mushroom Calvatia nipponica in human breast cancer cells (MDA-MB-231), [...] Read more.
Breast cancer ranks among the most prevalent malignancies affecting women worldwide, and apoptosis-targeting drugs are attractive candidates for the treatment of cancer. In the current study, we investigated the in vitro cytotoxicity of the mushroom Calvatia nipponica in human breast cancer cells (MDA-MB-231), identified potential antitumor compounds through bioactivity-guided isolation, and elucidated the antitumor, pro-apoptotic molecular mechanisms of the identified bioactive compounds. C. nipponica is edible when young, and it has been used as a food source as well as a traditional medicine in wound dressings. However, only a limited number of studies have reported its chemical composition and biological activities. In the screening test, the methanol extract of C. nipponica fruiting bodies exhibited cytotoxicity against MDA-MB-231 cells. Bioactivity-guided fractionation of the methanol (MeOH) extract and chemical investigation of the active fractions resulted in the isolation of fourteen compounds (1–14), including six alkaloids (1–3, 5, 7, and 8), two phenolic compounds (4 and 6), one fatty acid (9), and five steroids (10–14). The structures of the isolated compounds were determined using NMR spectroscopic methods, liquid chromatography–mass spectrometry, and comparison of data with previously reported values. The isolated compounds (1–14) were tested for cytotoxicity against MDA-MB-231 cells, where compound 1, i.e., N,N-dimethyl-anthranilic acid, exhibited the most significant cytotoxicity against MDA-MB-231 cells, with an IC50 value of 90.28 ± 4.23 μM and apoptotic cell death of 56.01% ± 2.64% at 100 μM. Treatment with compound 1 resulted in an upregulation of protein levels, including cleaved caspase-8, cleaved poly (ADP-ribose) polymerase, Bcl-2-associated X protein (Bax), cleaved caspase-3, cleaved caspase-9, Bad, and Cytochrome c, but decreased the levels of B-cell lymphoma 2 (Bcl-2). Overall, these results indicate that N,N-dimethyl-anthranilic acid (1) may have anti-breast cancer activity and is probably involved in the induction of apoptosis mediated by extrinsic and intrinsic signaling pathways. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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22 pages, 21325 KiB  
Article
Bean Leaves Ameliorate Lipotoxicity in Fatty Liver Disease
by Adriana Araceli Becerril-Campos, Minerva Ramos-Gómez, Ericka Alejandra De Los Ríos-Arellano, Perla Viridiana Ocampo-Anguiano, Adriana González-Gallardo, Yazmín Macotela, Teresa García-Gasca and Santiaga Marisela Ahumada-Solórzano
Nutrients 2023, 15(13), 2928; https://doi.org/10.3390/nu15132928 - 28 Jun 2023
Cited by 2 | Viewed by 1823
Abstract
Bioactive compounds in plant-based food have protective effects against metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Bean leaves are widely cultivated in the world and are a source of dietary fiber and polyphenols. High fat/high fructose diet animal models promote deleterious effects [...] Read more.
Bioactive compounds in plant-based food have protective effects against metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Bean leaves are widely cultivated in the world and are a source of dietary fiber and polyphenols. High fat/high fructose diet animal models promote deleterious effects in adipose and non-adipose tissues (lipotoxicity), leading to obesity and its comorbidities. Short-term supplementation of bean leaves exhibited anti-diabetic, anti-hyperlipidemic, and anti-obesity effects in high-fat/high-fructose diet animal models. This study aimed to evaluate the effect of bean leaves supplementation in the prevention of lipotoxicity in NAFLD and contribute to elucidating the possible mechanism involved for a longer period of time. During thirteen weeks, male Wistar rats (n = 9/group) were fed with: (1) S: Rodent Laboratory Chow 5001® (RLC); (2) SBL: 90% RLC+ 10% dry bean leaves; (3) H: high-fat/high-fructose diet; (4) HBL: H+ 10% of dry bean leaves. Overall, a HBL diet enhanced impaired glucose tolerance and ameliorated obesity, risk factors in NAFLD development. Additionally, bean leaves exerted antioxidant (↑serum GSH) and anti-inflammatory (↓mRNA TNFα in the liver) effects, prevented hepatic fat accumulation by enhanced ↑mRNA PPARα (β oxidation), and enhanced lipid peroxidation (↓liver MDA). These findings suggest that bean leaves ameliorated hepatic lipotoxicity derived from the consumption of a deleterious diet. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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12 pages, 10192 KiB  
Article
Prokinetic Activity of Mulberry Fruit, Morus alba L.
by Tae Sik Sung, Seung-Bum Ryoo, Chang-Hyun Lee, Seon-Min Choi, Joo-Won Nam, Hyun-Bok Kim, Ji young Lee, Jung-Dae Lim, Kyu Joo Park and Hyun-Tai Lee
Nutrients 2023, 15(8), 1889; https://doi.org/10.3390/nu15081889 - 14 Apr 2023
Cited by 1 | Viewed by 1509
Abstract
The fruit of Morus alba L. (MAF) has been consumed as a food worldwide. MAF has also been widely used in traditional medicine for thousands of years in East Asia, and its diverse bioactivities have been reported in numerous publications. However, no prokinetic [...] Read more.
The fruit of Morus alba L. (MAF) has been consumed as a food worldwide. MAF has also been widely used in traditional medicine for thousands of years in East Asia, and its diverse bioactivities have been reported in numerous publications. However, no prokinetic activity has been reported for MAF or its components. In the present study, therefore, we investigated the effects of MAF on gastrointestinal motor function by measuring the intestinal transit rate (ITR) of Evans blue in mice in vivo. The ITR values accelerated by MAF were significantly higher than those accelerated by cisapride or metoclopramide, suggesting that MAF has potential as a new prokinetic agent to replace cisapride and metoclopramide. We also investigated the effects of MAF on myogenic and neurogenic contractions in human intestinal smooth muscles by measuring spontaneous contractions of smooth muscle strips, smooth muscle contractions induced by neural stimulation, and migrating motor complexes from intestinal segments in the human ileum and sigmoid colon in situ. MAF increased both myogenic and neurogenic contractions to enhance ileal and colonic motility in the human intestine. Taken together, these results indicate that MAF enhanced intestinal motility by increasing both myogenic and neurogenic contractions, thereby accelerating the ITR. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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Review

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13 pages, 996 KiB  
Review
Novel Key Ingredients in Urinary Tract Health—The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®)
by Felice Crocetto, Raffaele Balsamo, Ugo Amicuzi, Luigi De Luca, Alfonso Falcone, Benito Fabio Mirto, Gaetano Giampaglia, Gianpiero Ferretti, Federico Capone, Fabio Machiella, Domenico Varriale, Enrico Sicignano, Giovanni Pagano, Alessandro Lombardi, Giuseppe Lucarelli, Francesco Lasorsa, Gian Maria Busetto, Francesco Del Giudice, Matteo Ferro, Ciro Imbimbo and Biagio Baroneadd Show full author list remove Hide full author list
Nutrients 2023, 15(16), 3573; https://doi.org/10.3390/nu15163573 - 14 Aug 2023
Viewed by 2655
Abstract
Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine [...] Read more.
Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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23 pages, 4047 KiB  
Review
Therapeutic Potential of Bioactive Compounds from Brugmansia suaveolens Bercht. & J. Presl
by Sandro Pinheiro da Costa, Raphaela Aparecida Schuenck-Rodrigues, Verônica da Silva Cardoso, Simone Sacramento Valverde, Alane Beatriz Vermelho and Eduardo Ricci-Júnior
Nutrients 2023, 15(13), 2912; https://doi.org/10.3390/nu15132912 - 27 Jun 2023
Viewed by 1578
Abstract
Brugmansia suaveolens Bercht. & J. Presl has been widely used due to the presence of different bioactive compounds. This review summarizes the latest advances and perspectives of the B. suaveolens plant species; it is a systematic literature review on aspects of botany, traditional [...] Read more.
Brugmansia suaveolens Bercht. & J. Presl has been widely used due to the presence of different bioactive compounds. This review summarizes the latest advances and perspectives of the B. suaveolens plant species; it is a systematic literature review on aspects of botany, traditional uses, phytochemistry, pharmacology, and toxicology as therapeutic potential. In addition, 120 compounds are described, including alkaloids, flavonoids, terpenoids, steroids, amino acids, aromatics, and aliphatics. As for the therapeutic potential, it is described in extracts and compounds in the antitumor, anti-inflammatory, antioxidant, antimicrobial, antispasmodic, anticoagulant, and analgesic aspects, as well as the effects on the central nervous system. The toxicity of the genus stands out, especially the potential for organ toxicity. Therefore, this review evidenced the knowledge related to the traditional use based on the scientific research of Brugmansia suaveolens, highlighting an overview of bioactive compounds and biological and toxicological activities in order to provide a scientific basis for future studies on the value of this species for the development of new natural products. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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Other

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41 pages, 2472 KiB  
Systematic Review
Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis
by Preetha Iyengar, Gala Godoy-Brewer, Isha Maniyar, Jacob White, Laura Maas, Alyssa M. Parian and Berkeley Limketkai
Nutrients 2024, 16(7), 934; https://doi.org/10.3390/nu16070934 - 23 Mar 2024
Viewed by 1421
Abstract
Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used [...] Read more.
Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97–6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99–2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71–1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18–5.63), but not for AP (RR 1.31, 95% CI 0.86–2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08–2.26) and remission (RR 19.37, 95% CI 2.71–138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed. Full article
(This article belongs to the Special Issue The Benefits of Natural Products for Disease Treatments)
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