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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 (31 January 2022) | Viewed by 55294

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Dr. Adam Matkowski

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Department of Pharmaceutical Biology and Biotechnology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
Interests: medicinal plants; phytochemistry; pharmaceutical biology; natural product biotechnology; bioactivity; phenolics; alkaloids; terpenoids
Special Issues, Collections and Topics in MDPI journals

Dr. Slavko Komarnytsky

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Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Raleigh, NC 27695, USA
Interests: pharmacogenomics; diet-gene interactions; energy metabolism; microbiome; botanical products; mitochondria; phenolics; cannabinoids; fungi; fermentation; protein isolate
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Live Nature is a vast source of chemical compounds that are produced in various organisms in significant amounts, accumulated, and sometimes excreted to influence other organisms' function, sometimes in a beneficial but sometimes in a harmful way.

Embraced by a broad term of natural products, they include molecules of various sizes and complexity, from simple monoterpenoid hydrocarbons, through more elaborate specialized metabolites such as steroids, polyphenols, nitrogen compounds sch as alkaloids, and finally oligo- and polymeric structures, such as tannins, polyprenoids, branched carbohydrates, including conjugates between different classes.

They are usually playing important roles in stress responses and protection against natural enemies and other challenges. These unique roles are still not fully understood but the enormous diversity of structures and activities has been always exploited by humanity for various purposes.

Traditionally, most of these compounds are obtained from medicinal plants, but other sources have been also used both in traditional or folk and in official pharmacotherapy. An important emerging source of novel and highly active NPs are marine organisms belonging to several kingdoms.

Some of NP-based drugs have reached a major position in medicine, for example the Nobel-wining artemisinin, several essential cytostatic drugs, cardiac glycosides, to name just a few examples. In a wider meaning, even such everyday drugs as antibiotics or statins have originally been natural products isolated from fungi or prokaryotes. There are also numerous examples of natural drugs with wide use in self healing such as tannins used as astringent against bleeding, skin inflammation, wound healing and diarrhea, bitter compounds for digestive complaints, isoflavones and other phytoestrogens used in alleviation of menopause-related complaints, essential oils used in respiratory ways and digestive tract disorders, and many others.

This Special Issue is devoted to gathering and dissemination of high-quality studies on natural products. All classes natural products from natural sources are welcome, including terrestrial and aquatic plants, animals, and fungi, provided they are not the established drugs such as known statins or antibiotics. The semisynthetic derivatives, products of biomimetic syntheses, and analogs of NPs are outside the SI scope.

Papers involving new or less studied compounds/mixtures demonstrating high activity as well as novel properties of well-known substances are welcome. Any kind of bioacivity related to human health is within the scope, provided the reported potency was adequate and molecular mechanisms of action was addressed. Pharmacokinetic investigations on bioavailability of natural products from various matrices and various ways of administration are encouraged, too.

In silico studies accompanying in vitro or in vivo experiments are also very welcome, including molecular docking, modeling, pharmacodynamic and pharmacokinetic predictions, network pharmacology etc. However, a critical interpretation and discussion of the in silico models is essential.

Comprehensive critical reviews on the recent developments and perspectives of various areas of natural products pharmacology will be considered, too. However, it is recommended to send a proposal containing a suggested title, abstract and table of contents to the Guest Editor before final submission. The review can be focused on a certain class of NPs with various activities, or on a type of activity or signaling pathway of various NPs.

Studies with crude extracts can be considered only if the material is thoroughly characterized with state-of-the art techniques and the results are sufficiently sound in terms of therapeutic relevance. However, preference will be given to the purified, fully identified compounds or selectively enriched fractions. Extracts screened only with general quantitative methods, such as total content of a NP class (total polyphenols, flavonols, alkaloids etc) will not be accepted.

Similarly, the studied activity must not be limited to the routine in vitro testing with little physiological relevance, such as antioxidant, chelating, in vitro enzyme inhibition, non-quantitative antimicrobial tests, or others of this kind. The studies on animals with well developed brains such as vertebrates or cephalopods must be ethical and guarantee an important progress in NP pharmacology for human benefit. In general, in vitro or in vivo experiments should not rely solely on superficial screening without insight into the molecular mechanisms of action.

Dr. Adam Matkowski
Dr. Slavko Komarnytsky
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
plants
macrofungi
marine organisms
pharmacokinetics
signaling pathways
metabolites
molecular targets
pharmacodynamics

Published Papers (12 papers)

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20 pages, 49970 KiB

Open AccessArticle

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

by Shahid Karim, Abdulhadi S. Burzangi, Aftab Ahmad, Nasir Ali Siddiqui, Ibrahim M. Ibrahim, Priyanka Sharma, Walaa A. Abualsunun and Gamal A. Gabr

Int. J. Mol. Sci. 2022, 23(4), 2305; https://doi.org/10.3390/ijms23042305 - 19 Feb 2022

Cited by 19 | Viewed by 2720

Abstract

Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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9 pages, 3061 KiB

Open AccessArticle

Evaluation of Wound Healing Activity of Salvianolic Acid B on In Vitro Experimental Model

by Urszula Szwedowicz, Anna Szewczyk, Krzysztof Gołąb and Anna Choromańska

Int. J. Mol. Sci. 2021, 22(14), 7728; https://doi.org/10.3390/ijms22147728 - 20 Jul 2021

Cited by 9 | Viewed by 2111

Abstract

Despite a wide range of bactericides and antiseptics, the treatment of chronic or complicated wounds is still a major challenge for modern medicine. Topical medications are the most sought-after new agents for use as treatment. The therapeutic concentration of their active substances is easy to achieve with the lowest possible burden on the patient’s body. This study assesses the effect of salvianolic acid B (Sal B) on the proliferation, migration, and production of collagen type III by fibroblasts, which are the most important processes in wound healing. The study was conducted on human gingival fibroblasts obtained from primary cell culture. The results showed that Sal B at a dose of 75 µg/mL increases the cell viability with significant stimulation of the cell migration as demonstrated in the wound healing assay, as well as an increase in the expression of collagen type III, which has great importance in the initial stages of wound scarring. The results obtained in the conducted studies and previous scientific reports on the antibacterial properties and low toxicity of Sal B indicate its high potential in wound healing. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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12 pages, 1978 KiB

Open AccessArticle

Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.)

by Nancy Chiang, Shahla Ray, Jade Lomax, Sydney Goertzen, Slavko Komarnytsky, Chi-Tang Ho and John P. Munafo, Jr.

Int. J. Mol. Sci. 2021, 22(14), 7382; https://doi.org/10.3390/ijms22147382 - 9 Jul 2021

Cited by 2 | Viewed by 3055

Abstract

Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-β-D-apiofuranosyl-β-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC₅₀ at 6.46 μM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 μg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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19 pages, 4782 KiB

Open AccessArticle

Ergosta-7, 9 (11), 22-trien-3β-ol Interferes with LPS Docking to LBP, CD14, and TLR4/MD-2 Co-Receptors to Attenuate the NF-κB Inflammatory Pathway In Vitro and Drosophila

by Wen-Tsong Hsieh, Min-Hsien Hsu, Wen-Jen Lin, Yi-Cheng Xiao, Ping-Chiang Lyu, Yi-Chung Liu, Wei-Yong Lin, Yueh-Hsiung Kuo and Jing-Gung Chung

Int. J. Mol. Sci. 2021, 22(12), 6511; https://doi.org/10.3390/ijms22126511 - 17 Jun 2021

Cited by 9 | Viewed by 2841

Abstract

Ergosta-7, 9 (11), 22-trien-3β-ol (EK100) was isolated from Cordyceps militaris, which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the κ light chain enhancer of B cells (NF-κB) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.7 cells and the green fluorescent protein (GFP)-labeled NF-κB reporter gene of Drosophila. EK100 suppressed the release of the cytokine and attenuated the mRNA and protein expression of pro-inflammatory mediators. EK100 inhibited the inhibitor kappa B (IκB)/NF-κB signaling pathway. EK100 also inhibited phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) signal transduction. Moreover, EK100 interfered with LPS docking to the LPS-binding protein (LBP), transferred to the cluster of differentiation 14 (CD14), and bonded to TLR4/myeloid differentiation-2 (MD-2) co-receptors. Compared with the TLR4 antagonist, resatorvid (CLI-095), and dexamethasone (Dexa), EK100 suppressed the TLR4/AKT signaling pathway. In addition, we also confirmed that EK100 attenuated the GFP-labeled NF-κB reporter gene expression in Drosophila. In summary, EK100 might alter LPS docking to LBP, CD14, and TLR4/MD-2 co-receptors, and then it suppresses the TLR4/NF-κB inflammatory pathway in LPS-stimulated RAW264.7 cells and Drosophila. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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17 pages, 2603 KiB

Open AccessArticle

Magnesium Isoglycyrrhizinate Reduces Hepatic Lipotoxicity through Regulating Metabolic Abnormalities

by Li Lu, Kun Hao, Yu Hong, Jie Liu, Jinwei Zhu, Wenjiao Jiang, Zheying Zhu, Guangji Wang and Ying Peng

Int. J. Mol. Sci. 2021, 22(11), 5884; https://doi.org/10.3390/ijms22115884 - 30 May 2021

Cited by 6 | Viewed by 2895

Abstract

The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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11 pages, 2382 KiB

Open AccessArticle

Carnosic Acid and Carnosol Activate AMPK, Suppress Expressions of Gluconeogenic and Lipogenic Genes, and Inhibit Proliferation of HepG2 Cells

by Shun Hasei, Takeshi Yamamotoya, Yusuke Nakatsu, Yukino Ohata, Shota Itoga, Yuji Nonaka, Yasuka Matsunaga, Hideyuki Sakoda, Midori Fujishiro, Akifumi Kushiyama and Tomoichiro Asano

Int. J. Mol. Sci. 2021, 22(8), 4040; https://doi.org/10.3390/ijms22084040 - 14 Apr 2021

Cited by 21 | Viewed by 2724

Abstract

Carnosic acid (CA), carnosol (CL) and rosmarinic acid (RA), components of the herb rosemary, reportedly exert favorable metabolic actions. This study showed that both CA and CL, but not RA, induce significant phosphorylation of AMP-dependent kinase (AMPK) and its downstream acetyl-CoA carboxylase 1 (ACC1) in HepG2 hepatoma cells. Glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), rate-limiting enzymes of hepatic gluconeogenesis, are upregulated by forskolin stimulation, and this upregulation was suppressed when incubated with CA or CL. Similarly, a forskolin-induced increase in CRE transcriptional activity involved in G6PC and PCK1 regulations was also stymied when incubated with CA or CL. In addition, mRNA levels of ACC1, fatty acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP-1c) were significantly reduced when incubated with CA or CL. Finally, it was shown that CA and CL suppressed cell proliferation and reduced cell viability, possibly as a result of AMPK activation. These findings raise the possibility that CA and CL exert a protective effect against diabetes and fatty liver disease, as well as subsequent cases of hepatoma. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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14 pages, 3988 KiB

Open AccessArticle

Pseurotin D Inhibits the Activation of Human Lymphocytes

by Daniela Rubanova, Petra Dadova, Ondrej Vasicek and Lukas Kubala

Int. J. Mol. Sci. 2021, 22(4), 1938; https://doi.org/10.3390/ijms22041938 - 16 Feb 2021

Cited by 4 | Viewed by 2356

Abstract

Background: Pseurotins, a family of secondary metabolites of different fungi characterized by an unusual spirocyclic furanone-lactam core, are suggested to have different biological activities including the modulation of immune response. Purpose: Complex characterization of the effects of pseurotin D on human lymphocyte activation in order to understand the potential of pseurotin to modulate immune response in humans. Methods: CD4+ and CD8+ T cells and CD19+ B cells isolated from human blood were activated by various activators simultaneously with pseurotin D treatment. The effects of pseurotin were tested on the basis of changes in cell viability, apoptosis, activation of signal transducers and activators of transcription (STAT) signaling pathways, production of tumor necrosis factor (TNF)-α by T cells, expression of activation markers CD69 and CD25 on T cells and Human Leukocyte Antigen–DR isotype (HLA-DR) on B cells, and the differentiation markers CD20, CD27, CD38, and immunoglobulin (Ig) D on B cells. Results: Pseurotin D significantly inhibited the activation of both CD4+ and CD8+ human T cells complemented by the inhibition of TNF-α production without significant acute toxic effects. The Pseurotin D-mediated inhibition of T-cell activation was accompanied by the induction of the apoptosis of T cells. This corresponded with the inhibited phosphorylation of STAT3 and STAT5. In human B cells, pseurotin D did not significantly inhibit their activation; however, it affected their differentiation. Conclusions: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of lymphocytes and suggest pseurotins as new attractive chemotypes for future research in the context of immune-modulatory drugs. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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12 pages, 2331 KiB

Open AccessArticle

Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model

by Mickey Wilson, Veera Konda, Kathryn Heidt, Thirumurugan Rathinasabapathy, Anuradha Desai and Slavko Komarnytsky

Int. J. Mol. Sci. 2021, 22(3), 1032; https://doi.org/10.3390/ijms22031032 - 21 Jan 2021

Cited by 6 | Viewed by 5089

Abstract

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (T_skin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E₂ withdrawal helped maintain body temperature similarly to E₂ alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/T_skin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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14 pages, 1560 KiB

Open AccessReview

The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

by Maciej Danielewski, Agnieszka Matuszewska, Adam Szeląg and Tomasz Sozański

Int. J. Mol. Sci. 2021, 22(11), 6074; https://doi.org/10.3390/ijms22116074 - 4 Jun 2021

Cited by 17 | Viewed by 2577

Abstract

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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16 pages, 1278 KiB

Open AccessReview

Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils

by Slavko Komarnytsky, Thirumurugan Rathinasabapathy, Charles Wagner, Brandon Metzger, Carolina Carlisle, Chinmayee Panda, Sara Le Brun-Blashka, John P. Troup and Saradhadevi Varadharaj

Int. J. Mol. Sci. 2021, 22(11), 5479; https://doi.org/10.3390/ijms22115479 - 22 May 2021

Cited by 19 | Viewed by 5754

Abstract

The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state. Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation. While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress. Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states. Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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11 pages, 655 KiB

Open AccessReview

Pseudoephedrine—Benefits and Risks

by Krystyna Głowacka and Anna Wiela-Hojeńska

Int. J. Mol. Sci. 2021, 22(10), 5146; https://doi.org/10.3390/ijms22105146 - 13 May 2021

Cited by 28 | Viewed by 15138

Abstract

Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse. Full article

(This article belongs to the Special Issue Natural Product Pharmacology)

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14 pages, 288 KiB

Open AccessReview

Nephrotoxicity of Herbal Products in Europe—A Review of an Underestimated Problem

by Katarzyna Kiliś-Pstrusińska and Anna Wiela-Hojeńska

Int. J. Mol. Sci. 2021, 22(8), 4132; https://doi.org/10.3390/ijms22084132 - 16 Apr 2021

Cited by 19 | Viewed by 5812

Abstract

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases. Full article

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