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Natural Compounds for Disease and Health

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 45514

Special Issue Editors


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Guest Editor
Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Interests: natural products; cardiovascular pharmacology; regulation of vascular tone; angiogenesis; ischemic injury; nucleoside transporters
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong, China
Interests: phytomedicine; angiogenesis; tumor-associated macrophages; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Even as the world has seen many advancements in medicine, we have more diseases than ever before. Acute and chronic diseases place a heavy burden on the healthcare system since patients are usually required to take medications for a certain period or time, or even for life, to treat or limit the deterioration of their diseases. In addition to drug treatment and lifestyle modification, many people also choose to consume natural products that claim to be safe and have beneficial effects on our health. Therefore, there has been an exponential increase in the number of preclinical and clinical studies related to the pharmacology of natural products. Some interesting active ingredients have been found, which may serve as the lead compounds for the development of novel therapeutic agents.

For this Special Issue on “Natural Compounds for Disease and Health”, we invite researchers to present their novel data on the pharmacological actions of natural products and their active ingredients, which have potential implications for the treatment of various diseases and the promotion of health. Original papers or reviews are welcome.

Dr. George P.H. Leung
Dr. Jingjing Li
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • natural products
  • phytochemistry
  • structure–activity relationship
  • mechanism of action
  • anti-aging
  • cancer
  • cardiovascular diseases
  • digestive diseases
  • endocrine disorders
  • immune diseases
  • infections
  • inflammation
  • liver diseases
  • metabolic diseases
  • musculoskeletal diseases
  • neurodegenerative diseases
  • pain
  • psychiatric diseases
  • renal diseases
  • respiratory diseases

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Published Papers (16 papers)

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Research

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17 pages, 8965 KiB  
Article
Study of the Anti-Inflammatory Mechanism of β-Carotene Based on Network Pharmacology
by Shilin Wu, Ran Chen, Jingyun Chen, Ning Yang, Kun Li, Zhen Zhang and Rongqing Zhang
Molecules 2023, 28(22), 7540; https://doi.org/10.3390/molecules28227540 - 11 Nov 2023
Cited by 1 | Viewed by 1428
Abstract
β-carotene is known to have pharmacological effects such as anti-inflammatory, antioxidant, and anti-tumor properties. However, its main mechanism and related signaling pathways in the treatment of inflammation are still unclear. In this study, component target prediction was performed by using literature retrieval and [...] Read more.
β-carotene is known to have pharmacological effects such as anti-inflammatory, antioxidant, and anti-tumor properties. However, its main mechanism and related signaling pathways in the treatment of inflammation are still unclear. In this study, component target prediction was performed by using literature retrieval and the SwissTargetPrediction database. Disease targets were collected from various databases, including DisGeNET, OMIM, Drug Bank, and GeneCards. A protein–protein interaction (PPI) network was constructed, and enrichment analysis of gene ontology and biological pathways was carried out for important targets. The analysis showed that there were 191 unique targets of β-carotene after removing repeat sites. A total of 2067 targets from the three databases were integrated, 58 duplicate targets were removed, and 2009 potential disease action targets were obtained. Biological function enrichment analysis revealed 284 biological process (BP) entries, 31 cellular component (CC) entries, 55 molecular function (MF) entries, and 84 cellular pathways. The biological processes were mostly associated with various pathways and their regulation, whereas the cell components were mainly membrane components. The main molecular functions included RNA polymerase II transcription factor activity, DNA binding specific to the ligand activation sequence, DNA binding, steroid binding sequence-specific DNA binding, enzyme binding, and steroid hormone receptors. The pathways involved in the process included the TNF signaling pathway, sphingomyelin signaling pathway, and some disease pathways. Lastly, the anti-inflammatory signaling pathway of β-carotene was systematically analyzed using network pharmacology, while the molecular mechanism of β-carotene was further explored by molecular docking. In this study, the anti-inflammatory mechanism of β-carotene was preliminarily explored and predicted by bioinformatics methods, and further experiments will be designed to verify and confirm the predicted results, in order to finally reveal the anti-inflammatory mechanism of β-carotene. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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17 pages, 4134 KiB  
Article
Bilobalide Induces Apoptosis in 3T3-L1 Mature Adipocytes through ROS-Mediated Mitochondria Pathway
by Su Bu, Anran Xiong, Zhiying Yang, Faycal Aissa-Brahim, Ying Chen, Yichun Zhang, Xunyong Zhou and Fuliang Cao
Molecules 2023, 28(17), 6410; https://doi.org/10.3390/molecules28176410 - 2 Sep 2023
Cited by 2 | Viewed by 1385
Abstract
Bilobalide exhibits numerous beneficial bioactivities, including neuroprotective, anti-inflammatory, and antioxidant activity. Our previous study demonstrated that bilobalide inhibits adipogenesis and promotes lipolysis. The dose-dependent cytotoxicity was found to be specific to the mature adipocytes only, indicating the potential for regulating apoptosis in them. [...] Read more.
Bilobalide exhibits numerous beneficial bioactivities, including neuroprotective, anti-inflammatory, and antioxidant activity. Our previous study demonstrated that bilobalide inhibits adipogenesis and promotes lipolysis. The dose-dependent cytotoxicity was found to be specific to the mature adipocytes only, indicating the potential for regulating apoptosis in them. Herein, we aimed to investigate the apoptotic effects of bilobalide on 3T3-L1 mature adipocytes and elucidate the underlying mechanisms thereof. Flow cytometry analysis (FACS) revealed the pro-apoptotic effects of bilobalide on these cells. Bilobalide induced early apoptosis by reducing the mitochondrial membrane potential (MMP). DNA fragmentation was confirmed using TUNEL staining. Additionally, bilobalide increased the intracellular reactive oxygen species (ROS) levels and activities of Caspases 3/9. Pre-treatment with NAC (an ROS scavenger) confirmed the role of ROS in inducing apoptosis. Moreover, bilobalide up- and down-regulated the expression of Bax and Bcl-2, respectively, at the mRNA and protein expression levels; upregulated the Bax/Bcl-2 ratio; triggered the release of cytochrome c from the mitochondria; and increased the protein expression of cleaved Caspase 3, cleaved Caspase 9, and PARP cleavage. These results support the conclusion that bilobalide induces apoptosis in mature 3T3-L1 adipocytes through the ROS-mediated mitochondrial pathway, and offers potential novel treatment for obesity. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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24 pages, 10964 KiB  
Article
A Rational Combination of Cyclocarya paliurus Triterpene Acid Complex (TAC) and Se-Methylselenocysteine (MSC) Improves Glucose and Lipid Metabolism via the PI3K/Akt/GSK3β Pathway
by Xichen Bai, Hong Zhou, Dan Luo, Dan Chen, Jianyuan Fan, Xiaoting Shao, Jun Zhou and Wei Liu
Molecules 2023, 28(14), 5499; https://doi.org/10.3390/molecules28145499 - 19 Jul 2023
Cited by 1 | Viewed by 1254
Abstract
Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid [...] Read more.
Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA), exhibit antihyperglycemic and antihypertensive effects. The response surface methodology was utilized to design and optimize the ratio of UA, OA, and BA based on the inhibition rate of pancrelipase and α-amylase. The proportional mixture of UA, OA, and BA resulted in the formation of a complex known as Cyclocarya paliurus triterpenoid acid (TAC). Se-methylselenocysteine (MSC), a compound with various physiological functions such as antioxidant properties and tumor inhibition, has been used in combination with TAC to form the TAC/MSC complex. Our data demonstrate that TAC/MSC improved palmitic acid (PA)-induced insulin resistance in HepG2 cells through activating the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Moreover, TAC/MSC effectively improved hyperglycemia, glucose intolerance, insulin resistance, and lipid metabolism disorder in mice with type 2 diabetes mellitus (T2DM), attenuated hepatic steatosis, and reduced oxidative stress to alleviate T2DM characteristics. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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15 pages, 3132 KiB  
Article
Differential Activities of the Botanical Extract PBI-05204 and Oleandrin on Innate Immune Functions under Viral Challenge Versus Inflammatory Culture Conditions
by Gitte S. Jensen, Liu Yu, Ifeanyi Iloba, Dina Cruickshank, Jose R. Matos and Robert A. Newman
Molecules 2023, 28(12), 4799; https://doi.org/10.3390/molecules28124799 - 16 Jun 2023
Cited by 2 | Viewed by 2034
Abstract
The Nerium oleander extract PBI 05204 (PBI) and its cardiac glycoside constituent oleandrin have direct anti-viral properties. Their effect on the immune system, however, is largely unknown. We used an in vitro model of human peripheral blood mononuclear cells to document effects under [...] Read more.
The Nerium oleander extract PBI 05204 (PBI) and its cardiac glycoside constituent oleandrin have direct anti-viral properties. Their effect on the immune system, however, is largely unknown. We used an in vitro model of human peripheral blood mononuclear cells to document effects under three different culture conditions: normal, challenged with the viral mimetic polyinosinic:polycytidylic acid Poly I:C, and inflamed by lipopolysaccharide (LPS). Cells were evaluated for immune activation marks CD69, CD25, and CD107a, and culture supernatants were tested for cytokines. Both PBI and oleandrin directly activated Natural Killer (NK) cells and monocytes and triggered increased production of cytokines. Under viral mimetic challenge, PBI and oleandrin enhanced the Poly I:C-mediated immune activation of monocytes and NK cells and enhanced production of IFN-γ. Under inflammatory conditions, many cytokines were controlled at similar levels as in cultures treated with PBI and oleandrin without inflammation. PBI triggered higher levels of some cytokines than oleandrin. Both products increased T cell cytotoxic attack on malignant target cells, strongest by PBI. The results show that PBI and oleandrin directly activate innate immune cells, enhance anti-viral immune responses through NK cell activation and IFN-γ levels, and modulate immune responses under inflamed conditions. The potential clinical impact of these activities is discussed. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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17 pages, 3156 KiB  
Article
Licochalcone A Inhibits Prostaglandin E2 by Targeting the MAPK Pathway in LPS Activated Primary Microglia
by Harsharan Singh Bhatia, Matthias Apweiler, Lu Sun, Julian Baron, Ashwini Tirkey and Bernd L. Fiebich
Molecules 2023, 28(4), 1927; https://doi.org/10.3390/molecules28041927 - 17 Feb 2023
Cited by 1 | Viewed by 1715
Abstract
Neuroinflammation and oxidative stress are conditions leading to neurological and neuropsychiatric disorders. Natural compounds exerting anti-inflammatory and anti-oxidative effects, such as Licochalcone A, a bioactive flavonoid present in a traditional Chinese herb (licorice), might be beneficial for the treatment of those disorders. Therefore, [...] Read more.
Neuroinflammation and oxidative stress are conditions leading to neurological and neuropsychiatric disorders. Natural compounds exerting anti-inflammatory and anti-oxidative effects, such as Licochalcone A, a bioactive flavonoid present in a traditional Chinese herb (licorice), might be beneficial for the treatment of those disorders. Therefore, this study aimed to investigate the anti-inflammatory and anti-oxidative effects of Licochalcone A in LPS-activated primary rat microglia. Licochalcone A dose-dependently prevented LPS-induced PGE2 release by inhibiting the arachidonic acid (AA)/cylcooxygenase (COX) pathway decreasing phospholipase A2, COX-1, and COX-2 protein levels. Furthermore, LPS-induced levels of the cytokines IL-6 and TNFα were reduced by Licochalcone A, which also inhibited the phosphorylation and, thus, activation of the mitogen-activated protein kinases (MAPK) p38 MAPK and Erk 1/2. With the reduction of 8-iso-PGF, a sensitive marker for oxidative stress, anti-oxidative effects of Licochalcone A were demonstrated. Our data demonstrate that Licochalcone A can affect microglial activation by interfering in important inflammatory pathways. These in vitro findings further demonstrate the potential value of Licochalcone A as a therapeutic option for the prevention of microglial dysfunction related to neuroinflammatory diseases. Future research should continue to investigate the effects of Licochalcone A in different disease models with a focus on its anti-oxidative and anti-neuroinflammatory properties. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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16 pages, 5800 KiB  
Article
Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from Monodora myristica: A Novel DNA Gyrase Inhibitor
by Sunday Amos Onikanni, Bashir Lawal, Adewale Oluwaseun Fadaka, Oluwafemi Bakare, Ezekiel Adewole, Muhammad Taher, Junaidi Khotib, Deny Susanti, Babatunji Emmanuel Oyinloye, Basiru Olaitan Ajiboye, Oluwafemi Adeleke Ojo and Nicole Remaliah Samantha Sibuyi
Molecules 2023, 28(4), 1593; https://doi.org/10.3390/molecules28041593 - 7 Feb 2023
Cited by 3 | Viewed by 1644
Abstract
The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as [...] Read more.
The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the computational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excretion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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9 pages, 1455 KiB  
Article
Verbenalin Reduces Amyloid-Beta Peptide Generation in Cellular and Animal Models of Alzheimer’s Disease
by Juhee Lim, Seokhee Kim, Changhyun Lee, Jeongwoo Park, Gabsik Yang and Taehan Yook
Molecules 2022, 27(24), 8678; https://doi.org/10.3390/molecules27248678 - 8 Dec 2022
Viewed by 1316
Abstract
Verbenalin, among the major constituents of Verbena officinalis, has been reported to exhibit sleep-promoting and antioxidant activities. This study demonstrates the effects of verbenalin on amyloid-beta (Aβ) peptide generation in Swedish mutant amyloid precursor protein (APP)-overexpressing Neuro2a cells (SweAPP/N2a) and in Alzheimer’s [...] Read more.
Verbenalin, among the major constituents of Verbena officinalis, has been reported to exhibit sleep-promoting and antioxidant activities. This study demonstrates the effects of verbenalin on amyloid-beta (Aβ) peptide generation in Swedish mutant amyloid precursor protein (APP)-overexpressing Neuro2a cells (SweAPP/N2a) and in Alzheimer’s disease (AD) animal models. We further performed molecular biological analyses of these in vitro and in vivo models of AD. The effects of verbenalin were assessed based on the expression of factors related to Aβ peptide production using Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry (IHC). The intracellular expression and release of APP protein were both decreased by verbenalin treatment in SweAPP/N2a cells. Thus, the production of Aβ peptides was decreased. Compared to those in AD transgenic (Tg) mice, IHC revealed that verbenalin-treated animals showed decreased Aβ and tau expression levels in the hippocampus. In addition, verbenalin restored the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of AD animal models. These findings suggest that verbenalin may decrease Aβ formation both in vitro and in vivo. Verbenalin may also help improve the pathological hallmarks of AD. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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13 pages, 2104 KiB  
Article
In Vitro Evaluation of the Interaction of Seven Biologically Active Components in Anemarrhenae rhizoma with P-gp
by Jianying Dai, Yuzhen He, Jiahao Fang, Hui Wang, Liang Chao, Liang Zhao, Zhanying Hong and Yifeng Chai
Molecules 2022, 27(23), 8556; https://doi.org/10.3390/molecules27238556 - 5 Dec 2022
Cited by 2 | Viewed by 1413
Abstract
The efficacy and pharmacokinetics of the biologically active components in Anemarrhenae rhizoma (AR) would be affected by the interaction of P-glycoprotein(P-gp) and effective components in AR. However, little is known about the interaction between them. The goal of this research was to examine [...] Read more.
The efficacy and pharmacokinetics of the biologically active components in Anemarrhenae rhizoma (AR) would be affected by the interaction of P-glycoprotein(P-gp) and effective components in AR. However, little is known about the interaction between them. The goal of this research was to examine the transmembrane absorption of timosaponin AIII(TAIII), timosaponin BII(TBII), sarsasapogenin (SSG), mangiferin(MGF), neomangiferin(NMGF), isomangiferin(IMGF), and baohuosideI(BHI) in AR and their interaction with P-gp. Seven effective components in AR(TAIII, TBII, SSG, MGF, NMGF, IMGF, and BHI) were investigated, and MDCK-MDR1 cells were used as the transport cell model. CCK-8 assays, bidirectional transport assays, and Rhodamine-123 (Rh-123) transport assays were determined in the MDCK-MDR1 cells. LC/MS was applied to the quantitative analysis of TAIII, TBII, MGF, NMGF, IMGF, SSG, and BHI in transport samples. The efflux ratio of MGF, TAIII, TBII, and BHI was greater than 2 and significantly descended with the co-administration of Verapamil, indicating MGF, TAIII, TBII, and BHI as the substrates of P-gp. The efflux ratio of the seven effective components in the extracts (10 mg/mL) of AR decreased from 3.00~1.08 to 1.92~0.48. Compared to the efflux ratio of Rh-123 in the control group (2.46), the efflux ratios of Rh-123 were 1.22, 1.27, 1.25, 1.09, 1.31, and 1.47 by the addition of TAIII, TBII, MGF, IMGF, NMGF, and BHI, respectively, while the efflux ratio of Rh-123 with the co-administration of SSG had no statistical difference compared to the control group. These results indicated that MGF, TAIII, TBII, and BHI could be the substrates of P-gp. TAIII, TBII, MGF, IMGF, NMGF, and BHI show the effect of inhibiting P-gp function, respectively. These findings provide important basic pharmacological data to assist the therapeutic development of AR constituents and extracts. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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16 pages, 3369 KiB  
Article
Amauroderma rugosum Extract Suppresses Inflammatory Responses in Tumor Necrosis Factor Alpha/Interferon Gamma-Induced HaCaT Keratinocytes
by Polly Ho-Ting Shiu, Jingjing Li, Chengwen Zheng, Panthakarn Rangsinth, Renkai Li, Queenie Tze-Lam Cheung, Angel Heng-Yee Lau, Jacqueline Cho-Ki Chan, Yiu-Wa Kwan, Timothy Man-Yau Cheung and George Pak-Heng Leung
Molecules 2022, 27(19), 6533; https://doi.org/10.3390/molecules27196533 - 3 Oct 2022
Cited by 6 | Viewed by 1816
Abstract
Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum [...] Read more.
Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum has been previously reported, it is not known whether the aqueous extract has a similar effect. In addition, the effect of Amauorderma rugosum extract on skin has never been explored. Therefore, the objectives of the present study were to evaluate the anti-inflammatory effects of the aqueous extract of Amauroderma rugosum on HaCaT keratinocytes, to explore its mechanisms of action, and to study the possible active ingredients involved. The results showed that the aqueous extract of Amauroderm rugosum at a concentration of 1.5 mg/mL was non-toxic to HaCaT cells and inhibited the release of cytokine interleukin-1β, and chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-stimulated HaCaT cells. Amauroderma rugosum extract reduced the intracellular levels of reactive oxygen species. In addition, Amauroderma rugosum extract reduced the total protein expression of nuclear factor-kappa B (NF-κB) and B-cells inhibitor alpha in HaCaT keratinocytes and inhibited the phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in TNF-α- and INF-γ-stimulated HaCaT keratinocytes. Chemical analysis revealed that the aqueous extract of Amauroderma rugosum contains polysaccharides, triterpenes, and phenolic compounds. Anti-inflammatory compounds, such as gallic acid, guanosine, and uridine, were also present. The anti-inflammatory effect of Amauroderma rugosum could be mimicked by a combination of gallic acid, guanosine, and uridine. In conclusion, our study suggests that the aqueous extract of Amauroderma rugosum exerts anti-inflammatory effects on keratinocytes through its antioxidant and inhibitory effects on MEK/ERK-, Akt/mTOR-, and NF-κB-dependent signaling pathways. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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8 pages, 1415 KiB  
Article
(+)-Catechin Stereoisomer and Gallate Induce Oxidative Stress in Rat Aorta
by Tamara V. Samokhvalova, Yuri A. Kim, Antonia F. Korystova, Ludmila N. Kublik, Vera V. Shaposhnikova and Yuri N. Korystov
Molecules 2022, 27(11), 3379; https://doi.org/10.3390/molecules27113379 - 24 May 2022
Viewed by 1388
Abstract
The goal of the work was to study changes in the activity of the angiotensin-converting enzyme (ACE) and production of reactive oxygen species (ROS) in the aorta of rats after the intraperitoneal injection of stereoisomers of catechin and gallate. The activity of ACE [...] Read more.
The goal of the work was to study changes in the activity of the angiotensin-converting enzyme (ACE) and production of reactive oxygen species (ROS) in the aorta of rats after the intraperitoneal injection of stereoisomers of catechin and gallate. The activity of ACE in the aorta sections was determined by measuring the hydrolysis of hippuryl-l-histidyl-l-leucine. The production of ROS in the aorta sections was estimated from the oxidation of dichlorodihydrofluorescein. The time and dose dependences of the effect of catechin stereoisomers and gallate on ACE activity and ROS production in the aorta were studied. It was shown that (+)-catechin and gallate increased the ACE activity and ROS production, and (−)-catechin and (−)-epicatechin did not influence these parameters. The doses of (+)-catechin and gallate that increased the ACE activity to a half-maximal value (AD50) were 0.04 and 0.03 µg/kg, respectively. Fucoidin, a blocker of leukocyte adhesion to the endothelium, reduced the ACE activity to the control level in the aortas of (+)-catechin-treated rats. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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Review

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31 pages, 3667 KiB  
Review
A Critical Review of the Neuropharmacological Effects of Kratom: An Insight from the Functional Array of Identified Natural Compounds
by Rahni Hossain, Abida Sultana, Manit Nuinoon, Kunwadee Noonong, Jitbanjong Tangpong, Kazi Helal Hossain and Md Atiar Rahman
Molecules 2023, 28(21), 7372; https://doi.org/10.3390/molecules28217372 - 31 Oct 2023
Viewed by 5763
Abstract
Kratom (Mitragyna speciosa Korth. Havil) has been considered a narcotic drug for years, barred by the law in many parts of the world, while extensive research over the past few decades proves its several beneficial effects, some of which are still in [...] Read more.
Kratom (Mitragyna speciosa Korth. Havil) has been considered a narcotic drug for years, barred by the law in many parts of the world, while extensive research over the past few decades proves its several beneficial effects, some of which are still in ambiguity. In many countries, including Thailand, the indiscriminate use and abuse of kratom have led to the loss of life. Nonetheless, researchers have isolated almost fifty pure compounds from kratom, most of which are alkaloids. The most prevalent compounds, mitragynine and 7-hydroxy mitragynine, are reported to display agonist morphine-like effects on human μ-opioid receptors and antagonists at κ- and δ-opioid receptors with multimodal effects at other central receptors. Mitragynine is also credited to be one of the modulatory molecules for the Keap1-Nrf2 pathway and SOD, CAT, GST, and associated genes’ upregulatory cascades, leading it to play a pivotal role in neuroprotective actions while evidently causing neuronal disorders at high doses. Additionally, its anti-inflammatory, antioxidative, antibacterial, and gastroprotective effects are well-cited. In this context, this review focuses on the research gap to resolve ambiguities about the neuronal effects of kratom and demonstrate its prospects as a therapeutic target for neurological disorders associated with other pharmacological effects. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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28 pages, 1192 KiB  
Review
Tracing the Path between Mushrooms and Alzheimer’s Disease—A Literature Review
by Ana Margarida Silva, Marco Preto, Clara Grosso, Mónica Vieira, Cristina Delerue-Matos, Vitor Vasconcelos, Mariana Reis, Lillian Barros and Rosário Martins
Molecules 2023, 28(14), 5614; https://doi.org/10.3390/molecules28145614 - 24 Jul 2023
Cited by 5 | Viewed by 2600
Abstract
Alzheimer’s disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial [...] Read more.
Alzheimer’s disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and β-secretase (BACE 1); the prevention of amyloid beta (Aβ) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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18 pages, 1976 KiB  
Review
Oligosaccharides as Potential Therapeutics against Atherosclerosis
by Siarhei A. Dabravolski, Vasily N. Sukhorukov, Alexandra A. Melnichenko, Victoria A. Khotina and Alexander N. Orekhov
Molecules 2023, 28(14), 5452; https://doi.org/10.3390/molecules28145452 - 17 Jul 2023
Cited by 2 | Viewed by 1447
Abstract
Atherosclerosis is the major cause of cardiovascular-disease-related death worldwide, resulting from the subendothelial accumulation of lipoprotein-derived cholesterol, ultimately leading to chronic inflammation and the formation of clinically significant atherosclerotic plaques. Oligosaccharides have been widely used in biomedical research and therapy, including tissue engineering, [...] Read more.
Atherosclerosis is the major cause of cardiovascular-disease-related death worldwide, resulting from the subendothelial accumulation of lipoprotein-derived cholesterol, ultimately leading to chronic inflammation and the formation of clinically significant atherosclerotic plaques. Oligosaccharides have been widely used in biomedical research and therapy, including tissue engineering, wound healing, and drug delivery. Moreover, oligosaccharides have been consumed by humans for centuries, and are cheap, and available in large amounts. Given the constantly increasing number of obesity, diabetes, and hyperlipidaemia cases, there is an urgent need for novel therapeutics that can economically and effectively slow the progression of atherosclerosis. In this review, we address the current state of knowledge in oligosaccharides research, and provide an update of the recent in vitro and in vivo experiments that precede clinical studies. The application of oligosaccharides could help to eliminate the residual risk after the application of other cholesterol-lowering medicines, and provide new therapeutic opportunities to reduce the associated burden of premature deaths because of atherosclerosis. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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16 pages, 1228 KiB  
Review
A Review on the Sources, Structures, and Pharmacological Activities of Lucidenic Acids
by Chengwen Zheng, Panthakarn Rangsinth, Polly H. T. Shiu, Wen Wang, Renkai Li, Jingjing Li, Yiu-Wa Kwan and George P. H. Leung
Molecules 2023, 28(4), 1756; https://doi.org/10.3390/molecules28041756 - 12 Feb 2023
Cited by 8 | Viewed by 2317
Abstract
Ganoderma lucidum has long been used as a multi-purpose plant and functional food. The pharmacological properties of G. lucidum are primarily attributed to its polysaccharides and triterpenoids. Ganoderic and lucidenic acids are the two major triterpenoids groups in G. lucidum. Despite the [...] Read more.
Ganoderma lucidum has long been used as a multi-purpose plant and functional food. The pharmacological properties of G. lucidum are primarily attributed to its polysaccharides and triterpenoids. Ganoderic and lucidenic acids are the two major triterpenoids groups in G. lucidum. Despite the discovery of 22 types of lucidenic acids, research on lucidenic acids is significantly less extensive compared to that on ganoderic acid. To the best of our knowledge, for the first time, in this review, we aimed to summarize the sources, contents, chemical structures, and pharmacological effects, including anti-cancer, anti-inflammatory, antioxidant, anti-viral, neuroprotective, anti-hyperlipidemic, anti-hypercholesterolemic, and anti-diabetic properties, of lucidenic acids. Studies on lucidenic acids are still preliminary and have several limitations. Therefore, more in-depth studies with optimal designs are essential for the development of lucidenic acids as medicines, functional foods, and nutraceuticals. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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13 pages, 3279 KiB  
Review
Effect of Ginger on Inflammatory Diseases
by Pura Ballester, Begoña Cerdá, Raúl Arcusa, Javier Marhuenda, Karen Yamedjeu and Pilar Zafrilla
Molecules 2022, 27(21), 7223; https://doi.org/10.3390/molecules27217223 - 25 Oct 2022
Cited by 43 | Viewed by 13973
Abstract
Ulcerative colitis, Crohn’s disease, rheumatoid arthritis, psoriasis, and lupus erythematosus are some of common inflammatory diseases. These affections are highly disabling and share signals such as inflammatory sequences and immune dysregulation. The use of foods with anti-inflammatory properties such as ginger (Zingiber [...] Read more.
Ulcerative colitis, Crohn’s disease, rheumatoid arthritis, psoriasis, and lupus erythematosus are some of common inflammatory diseases. These affections are highly disabling and share signals such as inflammatory sequences and immune dysregulation. The use of foods with anti-inflammatory properties such as ginger (Zingiber officinale Roscoe) could improve the quality of life of these patients. Ginger is a plant widely used and known by its bioactive compounds. There is enough evidence to prove that ginger possesses multiple biological activities, especially antioxidant and anti-inflammatory capacities. In this review, we summarize the current knowledge about the bioactive compounds of ginger and their role in the inflammatory process and its signaling pathways. We can conclude that the compounds 6-shoagol, zingerone, and 8-shoagol display promising results in human and animal models, reducing some of the main symptoms of some inflammatory diseases such as arthritis. For lupus, 6-gingerol demonstrated a protective attenuating neutrophil extracellular trap release in response to phosphodiesterase inhibition. Ginger decreases NF-kβ in psoriasis, and its short-term administration may be an alternative coadjuvant treatment. Ginger may exert a function of supplementation and protection against cancer. Furthermore, when receiving chemotherapy, ginger may reduce some symptoms of treatment (e.g., nausea). Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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11 pages, 3686 KiB  
Review
Atheroprotective Effects of Glycyrrhiza glabra L.
by Yuliya V. Markina, Tatiana V. Kirichenko, Alexander M. Markin, Irina Y. Yudina, Antonina V. Starodubova, Igor A. Sobenin and Alexander N. Orekhov
Molecules 2022, 27(15), 4697; https://doi.org/10.3390/molecules27154697 - 22 Jul 2022
Cited by 10 | Viewed by 2274
Abstract
Cardiovascular diseases associated with atherosclerosis are the major cause of death in developed countries. Early prevention and treatment of atherosclerosis are considered to be an important aspect of the therapy of cardiovascular disease. Preparations based on natural products affect the main pathogenetic steps [...] Read more.
Cardiovascular diseases associated with atherosclerosis are the major cause of death in developed countries. Early prevention and treatment of atherosclerosis are considered to be an important aspect of the therapy of cardiovascular disease. Preparations based on natural products affect the main pathogenetic steps of atherogenesis, and so represent a perspective for the long-term prevention of atherosclerosis development. Numerous experimental and clinical studies have demonstrated the multiple beneficial effects of licorice and its bioactive compounds—anti-inflammatory, anti-cytokine, antioxidant, anti-atherogenic, and anti-platelet action—which allow us to consider licorice as a promising atheroprotective agent. In this review, we summarized the current knowledge on the licorice anti-atherosclerotic mechanisms of action based on the results of experimental studies, including the results of the in vitro study demonstrating licorice effect on the ability of blood serum to reduce intracellular cholesterol accumulation in cultured macrophages, and presented the results of clinical studies confirming the ameliorating activity of licorice in regard to traditional cardiovascular risk factors as well as the direct anti-atherosclerotic effect of licorice. Full article
(This article belongs to the Special Issue Natural Compounds for Disease and Health)
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