Plant and Marine-Derived Natural Product Research in Drug Discovery: Strengths and Perspective

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 78882

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Special Issue Editor

iMed.ULisboa—Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Avenida Prof. Gama Pinto, 1649-019 Lisbon, Portugal
Interests: natural products; bioactive compounds; terpenes; phenolics; plant derived compounds; medicinal plants; natural products chemistry; mass spectrometry; multidrug resistance; medicinal chemistry
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Special Issue Information

Dear Colleagues,

Natural products have played a meaningful role in traditional medicine, which is the basis of primary healthcare systems, particularly in developing countries. They have also been of utmost importance in drug discovery and development, despite the reduction of investment of many pharmaceutical companies in research projects in this area.

With the increasing need to develop new drugs that are effective, safe, and affordable, we have recently seen a renewed interest—from the scientific community and pharma—in natural product research. In fact, the vast majority of global biodiversity (plants, marine organisms, and microorganisms) is yet to be explored. Moreover, when compared to synthetic molecules, the large chemical structure variety of secondary metabolites, along with the presence of chirality and functionality, represents an extremely rich biogenetic resource for the discovery of novel drugs, also providing lead compounds for rational drug design.

This Special Issue, “Plant- and Marine-Derived Natural Product Research in Drug Discovery: Strengths and Perspectives”, aims at gathering both original articles and comprehensive reviews related to natural product research, focusing on their vital role in drug discovery. Topics that will be considered include but are not limited to the following: isolation and structural elucidation of bioactive compounds from plants or marine organisms, in vitro or in vivo biological activities of secondary metabolites, synthetic strategies for plant and marine metabolites and/or analogs, hemi-synthesis of natural product derivatives with improved bioactivity, bioactivity of medicinal plant extracts and development of medicines, biological and pharmacological applications, essential oils with pharmaceutical interest, and bioactive compounds against neglected tropical diseases and cancer.

Dr. Noelia Duarte
Guest Editor

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Keywords

  • natural products
  • medicinal plants
  • marine drugs
  • in vitro and in vivo biological activity
  • pharmacological activity
  • drug discovery

Published Papers (19 papers)

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Editorial

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4 pages, 229 KiB  
Editorial
Special Issue on Plant and Marine-Derived Natural Product Research in Drug Discovery: Strengths and Perspective
by Noélia Duarte
Pharmaceuticals 2022, 15(10), 1249; https://doi.org/10.3390/ph15101249 - 11 Oct 2022
Cited by 2 | Viewed by 986
Abstract
For centuries, nature has been an inspirational source for the discovery of traditional remedies and drugs used in modern medicine [...] Full article

Research

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14 pages, 1537 KiB  
Article
Enhanced Anticancer Activity of Hymenocardia acida Stem Bark Extract Loaded into PLGA Nanoparticles
by Oluwasegun Adedokun, Epole N. Ntungwe, Cláudia Viegas, Bunyamin Adesina Ayinde, Luciano Barboni, Filippo Maggi, Lucilia Saraiva, Patrícia Rijo and Pedro Fonte
Pharmaceuticals 2022, 15(5), 535; https://doi.org/10.3390/ph15050535 - 26 Apr 2022
Cited by 6 | Viewed by 2638
Abstract
Hymenocardia acida (H. acida) is an African well-known shrub recognized for numerous medicinal properties, including its cancer management potential. The advent of nanotechnology in delivering bioactive medicinal plant extract with poor solubility has improved the drug delivery system, for a better therapeutic value [...] Read more.
Hymenocardia acida (H. acida) is an African well-known shrub recognized for numerous medicinal properties, including its cancer management potential. The advent of nanotechnology in delivering bioactive medicinal plant extract with poor solubility has improved the drug delivery system, for a better therapeutic value of several drugs from natural origins. This study aimed to evaluate the anticancer properties of H. acida using human lung (H460), breast (MCF-7), and colon (HCT 116) cancer cell lines as well as the production, characterization, and cytotoxicity study of H. acida loaded into PLGA nanoparticles. Benchtop models of Saccharomyces cerevisiae and Raniceps ranninus were used for preliminary toxicity evaluation. Notable cytotoxic activity in benchtop models and human cancer cell lines was observed for H. acida crude extract. The PLGA nanoparticles loading H. acida had a size of about 200 nm and an association efficiency of above 60%, making them suitable to be delivered by different routes. The outcomes from this research showed that H. acida has anticancer activity as claimed from an ethnomedical point of view; however, a loss in activity was noted upon encapsulation, due to the sustained release of the drug. Full article
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24 pages, 2382 KiB  
Article
Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties
by Elżbieta Studzińska-Sroka, Aleksandra Majchrzak-Celińska, Przemysław Zalewski, Dominik Szwajgier, Ewa Baranowska-Wójcik, Barbara Kaproń, Tomasz Plech, Marcin Żarowski and Judyta Cielecka-Piontek
Pharmaceuticals 2021, 14(12), 1293; https://doi.org/10.3390/ph14121293 - 10 Dec 2021
Cited by 16 | Viewed by 3347
Abstract
Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, [...] Read more.
Lichens are a source of chemical compounds with valuable biological properties, structurally predisposed to penetration into the central nervous system (CNS). Hence, our research aimed to examine the biological potential of lipophilic extracts of Parmelia sulcata, Evernia prunastri, Cladonia uncialis, and their major secondary metabolites, in the context of searching for new therapies for CNS diseases, mainly glioblastoma multiforme (GBM). The extracts selected for the study were standardized for their content of salazinic acid, evernic acid, and (−)-usnic acid, respectively. The extracts and lichen metabolites were evaluated in terms of their anti-tumor activity, i.e., cytotoxicity against A-172 and T98G cell lines and anti-IDO1, IDO2, TDO activity, their anti-inflammatory properties exerted by anti-COX-2 and anti-hyaluronidase activity, antioxidant activity, and anti-acetylcholinesterase and anti-butyrylcholinesterase activity. The results of this study indicate that lichen-derived compounds and extracts exert significant cytotoxicity against GBM cells, inhibit the kynurenine pathway enzymes, and have anti-inflammatory properties and weak antioxidant and anti-cholinesterase properties. Moreover, evernic acid and (−)-usnic acid were shown to be able to cross the blood-brain barrier. These results demonstrate that lichen-derived extracts and compounds, especially (−)-usnic acid, can be regarded as prototypes of pharmacologically active compounds within the CNS, especially suitable for the treatment of GBM. Full article
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15 pages, 2496 KiB  
Article
Development of a Topical Amphotericin B and Bursera graveolens Essential Oil-Loaded Gel for the Treatment of Dermal Candidiasis
by Lupe Carolina Espinoza, Lilian Sosa, Paulo C. Granda, Nuria Bozal, Natalia Díaz-Garrido, Brenda Chulca-Torres and Ana Cristina Calpena
Pharmaceuticals 2021, 14(10), 1033; https://doi.org/10.3390/ph14101033 - 12 Oct 2021
Cited by 9 | Viewed by 2555
Abstract
The higher molecular weight and low solubility of amphotericin B (AmB) hinders its topical administration. The aim of this study was to incorporate Bursera graveolens essential oil into an AmB topical gel (AmB + BGEO gel) in order to promote the diffusion of [...] Read more.
The higher molecular weight and low solubility of amphotericin B (AmB) hinders its topical administration. The aim of this study was to incorporate Bursera graveolens essential oil into an AmB topical gel (AmB + BGEO gel) in order to promote the diffusion of the drug through the skin in the treatment of cutaneous candidiasis. AmB + BGEO gel formulation was determined using a factorial experiment. Physical and chemical parameters, stability, in vitro release profile and ex vivo permeation in human skin were evaluated. In vitro antimicrobial activity was studied using strains of C. albicans, C. glabrata and C. parapsilosis. The tolerability was evaluated using in vitro and in vivo models. AmB + BGEO gel presented appropriate characteristics for topical administration, including pH of 5.85, pseudoplastic behavior, optimal extensibility, as well as high stability and acceptable tolerability. In vitro release studies showed that the formulation releases the drug following a Boltzmann sigmoidal model. Finally, AmB + BGEO gel exhibited higher amount of drug retained inside the skin and lower Minimum Inhibitory Concentration than a formulation sans essential oil. Therefore, these results suggest that the incorporation of B. graveolens essential oil in the formulation could be used as strategy to promote a local effect in the treatment of cutaneous candidiasis. Full article
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12 pages, 2030 KiB  
Communication
Posidonia oceanica (L.) Delile Extract Reduces Lipid Accumulation through Autophagy Activation in HepG2 Cells
by Marzia Vasarri, Emanuela Barletta and Donatella Degl’Innocenti
Pharmaceuticals 2021, 14(10), 969; https://doi.org/10.3390/ph14100969 - 24 Sep 2021
Cited by 4 | Viewed by 2233
Abstract
Posidonia oceanica (L.) Delile is a marine plant traditionally used as an herbal medicine for various health disorders. P. oceanica leaf extract (POE) has been shown to be a phytocomplex with cell-safe bioactivities, including the ability to trigger autophagy. Autophagy is a key [...] Read more.
Posidonia oceanica (L.) Delile is a marine plant traditionally used as an herbal medicine for various health disorders. P. oceanica leaf extract (POE) has been shown to be a phytocomplex with cell-safe bioactivities, including the ability to trigger autophagy. Autophagy is a key pathway to counteract non-alcoholic fatty liver disease (NAFLD) by controlling the breakdown of lipid droplets in the liver. The aim of this study was to explore the ability of POE to trigger autophagy and reduce lipid accumulation in human hepatoma (HepG2) cells and then verify the possible link between the effect of POE on lipid reduction and autophagy activation. Expression levels of autophagy markers were monitored by the Western blot technique in POE-treated HepG2 cells, whereas the extent of lipid accumulation in HepG2 cells was assessed by Oil red O staining. Chloroquine (CQ), an autophagy inhibitor, was used to study the relationship between POE-induced autophagy and intracellular lipid accumulation. POE was found to stimulate an autophagy flux over time in HepG2 cells by lowering the phosphorylation state of ribosomal protein S6, increasing Beclin-1 and LC3-II levels, and decreasing p62 levels. By blocking autophagy with CQ, the effect of POE on intracellular lipid accumulation was clearly reversed, suggesting that the POE phytocomplex may reduce lipid accumulation in HepG2 cells by activating the autophagic process. This work indicates that P. oceanica may be considered as a promising molecule supplier to discover new natural approaches for the management of NAFLD. Full article
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25 pages, 6082 KiB  
Article
A Newfangled Collagenase Inhibitor Topical Formulation Based on Ethosomes with Sambucus nigra L. Extract
by Ana Henriques Mota, Inês Prazeres, Henrique Mestre, Andreia Bento-Silva, Maria João Rodrigues, Noélia Duarte, Ana Teresa Serra, Maria Rosário Bronze, Patrícia Rijo, Maria Manuela Gaspar, Ana Silveira Viana, Lia Ascensão, Pedro Pinto, Pradeep Kumar, António José Almeida and Catarina Pinto Reis
Pharmaceuticals 2021, 14(5), 467; https://doi.org/10.3390/ph14050467 - 15 May 2021
Cited by 9 | Viewed by 3334
Abstract
Sambucus nigra L. (S. nigra) is a shrub widespread in Europe and western Asia, traditionally used in medicine, that has become popular in recent years as a potential source of a wide range of interesting bioactive compounds. The aim of the [...] Read more.
Sambucus nigra L. (S. nigra) is a shrub widespread in Europe and western Asia, traditionally used in medicine, that has become popular in recent years as a potential source of a wide range of interesting bioactive compounds. The aim of the present work was to develop a topical S. nigra extract formulation based on ethosomes and thus to support its health claims with scientific evidence. S. nigra extract was prepared by an ultrasound-assisted method and then included in ethosomes. The ethosomes were analyzed in terms of their size, stability over time, morphology, entrapment capacity (EC), extract release profile, stability over time and several biological activities. The prepared ethosomes were indicated to be well defined, presenting sizes around 600 nm. The extract entrapment capacity in ethosomes was 73.9 ± 24.8%, with an interesting slow extract release profile over 24 h. The extract-loaded ethosomes presented collagenase inhibition activity and a very good skin compatibility after human application. This study demonstrates the potential use of S. nigra extract incorporated in ethosomes as a potential cosmeceutical ingredient and on further studies should be performed to better understand the impact of S. nigra compounds on skin care over the time. Full article
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11 pages, 379 KiB  
Article
Preliminary Biological Activity Screening of Plectranthus spp. Extracts for the Search of Anticancer Lead Molecules
by Epole Ntungwe, Eva María Domínguez-Martín, Catarina Teodósio, Silvia Teixidó-Trujillo, Natalia Armas Capote, Lucilia Saraiva, Ana María Díaz-Lanza, Noélia Duarte and Patrícia Rijo
Pharmaceuticals 2021, 14(5), 402; https://doi.org/10.3390/ph14050402 - 23 Apr 2021
Cited by 11 | Viewed by 3186
Abstract
Plectranthus species (Lamiaceae) have been employed in traditional medicine and this is now validated by the presence of bioactive abietane-type diterpenoids. Herein, sixteen Plectranthus acetonic extracts were prepared by ultrasound-assisted extraction and their biological activity was screened. The antimicrobial activity of each extract [...] Read more.
Plectranthus species (Lamiaceae) have been employed in traditional medicine and this is now validated by the presence of bioactive abietane-type diterpenoids. Herein, sixteen Plectranthus acetonic extracts were prepared by ultrasound-assisted extraction and their biological activity was screened. The antimicrobial activity of each extract was screened against yeasts, and Gram-positive and Gram-negative bacteria. The P. hadiensis and P. mutabilis extracts possessed significant activity against Staphylococcus aureus and Candida albicans (microdilution method). Moreover, all extracts showed antioxidant activity using the DPPH method, with P. hadiensis and P. mutabilis extracts having the highest scavenging activities. Selected by the Artemia salina model, P. hadiensis and P.ciliatus possessed low micromolar anti-proliferative activities in human colon, breast, and lung cancer cell lines. Furthermore, the most bioactive extract of P. hadiensis leaves and the known abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone isolated from this plant, were tested against the aggressive type triple negative breast cancer (MDA-MB-231S). P. hadiensis extract reduced the viability of MDA-MB-231S cancer cell line cells, showing an IC50 value of 25.6 µg/mL. The IC50 value of 7α-acetoxy-6β-hydroxyroyleanone was 5.5 µM (2.15 µg/mL), suggesting that this lead molecule is a potential starting tool for the development of anti-cancer drugs. Full article
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9 pages, 1513 KiB  
Article
Isofuranodiene, a Natural Sesquiterpene Isolated from Wild Celery (Smyrnium olusatrum L.), Protects Rats against Acute Ischemic Stroke
by Hasan Yousefi-Manesh, Ahmad Reza Dehpour, Samira Shirooie, Fariba Bagheri, Vida Farrokhi, Seyyedeh Elaheh Mousavi, Massimo Ricciutelli, Loredana Cappellacci, Víctor López, Filippo Maggi and Riccardo Petrelli
Pharmaceuticals 2021, 14(4), 344; https://doi.org/10.3390/ph14040344 - 09 Apr 2021
Cited by 7 | Viewed by 2113
Abstract
The myrrh-like furanosesquiterpene isofuranodiene (IFD) is the main constituent of wild celery (Smyrnium olusatrum L., Apiaceae), an overlooked vegetable that was cultivated during the Roman Empire. In the present study, we investigated the protective effects of IFD pre-treatment against oxidative stress and [...] Read more.
The myrrh-like furanosesquiterpene isofuranodiene (IFD) is the main constituent of wild celery (Smyrnium olusatrum L., Apiaceae), an overlooked vegetable that was cultivated during the Roman Empire. In the present study, we investigated the protective effects of IFD pre-treatment against oxidative stress and inflammatory response in an animal model of ischemic stroke. IFD was isolated by the crystallization of Smyrnium olusatrum essential oil, and its structure and purity were confirmed by NMR and HPLC analyses. Acute pre-treatment of IFD (10 mg/kg i.p.) significantly reduced the levels of the inflammatory cytokines IL-1β and TNF-α, the expression of pNF-κB/NF-κB, and the lipid peroxidation indicator MDA. Finally, IFD boosted a faster recovery and better scores in grid-walking and modified neurological severity scores (mNSS) tests. Taken together, these findings indicate IFD as a promising lead compound for the discovery of new treatments of brain ischemia. Full article
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9 pages, 1093 KiB  
Article
Analytical Characterization of an Inulin-Type Fructooligosaccharide from Root-Tubers of Asphodelusramosus L
by Valentina Noemi Madia, Daniela De Vita, Antonella Messore, Chiara Toniolo, Valeria Tudino, Alessandro De Leo, Ivano Pindinello, Davide Ialongo, Francesco Saccoliti, Anna Maria D’Ursi, Manuela Grimaldi, Pietro Ceccobelli, Luigi Scipione, Roberto Di Santo and Roberta Costi
Pharmaceuticals 2021, 14(3), 278; https://doi.org/10.3390/ph14030278 - 19 Mar 2021
Cited by 4 | Viewed by 2750
Abstract
Plant-based systems continue to play a pivotal role in healthcare, and their use has been extensively documented. Asphodelus L. is a genus comprising various herbaceous species, known by the trivial name Asphodelus. These plants have been known since antiquity for both food and [...] Read more.
Plant-based systems continue to play a pivotal role in healthcare, and their use has been extensively documented. Asphodelus L. is a genus comprising various herbaceous species, known by the trivial name Asphodelus. These plants have been known since antiquity for both food and therapeutic uses, especially for treating several diseases associated with inflammatory and infectious skin disorders. Phytochemical studies revealed the presence of different constituents, mainly anthraquinones, triterpenoids, phenolic acids, and flavonoids. Although extensive literature has been published on these constituents, a paucity of information has been reported regarding the carbohydrate composition, such as fructans and fructan-like derivatives. The extraction of water-soluble neutral polysaccharides is commonly performed using water extraction, at times assisted by microwaves and ultrasounds. Herein, we reported the investigation of the alkaline extraction of root-tubers of Asphodelus ramosus L., analyzing the water-soluble polysaccharides obtained by precipitation from the alkaline extract and its subsequent purification by chromatography. A polysaccharide was isolated by alkaline extraction; the HPTLC study to determine its composition showed fructose as the main monosaccharide. FT-IR analysis showed the presence of an inulin-type structure, and NMR analyses allowed us to conclude that A. ramosus roots contain polysaccharide with an inulin-type fructooligosaccharide with a degree of polymerization of 7–8. Full article
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16 pages, 7331 KiB  
Article
Effects of Essential Oils and Some Constituents from Ingredients of Anti-Cellulite Herbal Compress on 3T3-L1 Adipocytes and Rat Aortae
by Ngamrayu Ngamdokmai, Tamkeen Urooj Paracha, Neti Waranuch, Krongkarn Chootip, Wudtichai Wisuitiprot, Nungruthai Suphrom, Kamonlak Insumrong and Kornkanok Ingkaninan
Pharmaceuticals 2021, 14(3), 253; https://doi.org/10.3390/ph14030253 - 11 Mar 2021
Cited by 8 | Viewed by 4145
Abstract
Cellulite is associated with a complex array of adipocytes under the skin and vascular system. A herbal compress that was previously developed was proven to have an anti-cellulite effect in healthy volunteers within 2 weeks of treatment. However, its mechanism and ingredients responsible [...] Read more.
Cellulite is associated with a complex array of adipocytes under the skin and vascular system. A herbal compress that was previously developed was proven to have an anti-cellulite effect in healthy volunteers within 2 weeks of treatment. However, its mechanism and ingredients responsible for reducing cellulite were not known. The purpose of this study was to investigate the activity of eight essential oils in, and two water extracts from, the ingredients of the herbal compress together with nine monoterpenoid constituents on the 3T3-L1 adipocytes. The vasodilatory effect on rat aortae was also studied. The adipocytes were induced by dexamethasone, 3-isobutyl-1-methylxanthine and insulin. At all concentrations tested, all essential oils, water extracts and their monoterpenoid constituents significantly inhibited lipid accumulation activity (p < 0.05) and decreased the amount of triglycerides when compared to untreated cells (p < 0.01). In addition, our results showed that the mixed oil distilled from the herbal compress mixed ingredients could relax the isolated rat aorta (EC50 = 14.74 ± 2.65 µg/mL). In conclusion, all essential oils, extracts and chemical constituents tested showed effects on adipogenesis inhibition and lipolysis induction on the cultured adipocytes with the mixed oil demonstrating vasorelaxation activity, all of which might be the mechanisms of the anti-cellulite effects of the herbal compress. Full article
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14 pages, 1800 KiB  
Article
Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zücker Diabetic Fatty Rat
by Samira Aouichat, Miguel Navarro-Alarcon, Pablo Alarcón-Guijo, Diego Salagre, Marwa Ncir, Lazhar Zourgui and Ahmad Agil
Pharmaceuticals 2021, 14(3), 232; https://doi.org/10.3390/ph14030232 - 08 Mar 2021
Cited by 17 | Viewed by 3751
Abstract
Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetes-related kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound. Previously, our research group showed that [...] Read more.
Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetes-related kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound. Previously, our research group showed that the renoprotective effect of melatonin administration was associated with restoring mitochondrial fission/fusion balance and function in a rat model of diabesity-induced kidney injury. This study was carried out to further investigate whether melatonin could suppress renal endoplasmic reticulum (ER) stress response and the downstream unfolded protein response activation under obese and diabetic conditions. Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight (BW)/day) (M–ZDF and M–ZL) or vehicle (C–ZDF and C–ZL) for 17 weeks. Western blot analysis of ER stress-related markers and renal morphology were assessed. Compared to C–ZL rats, higher ER stress response associated with impaired renal morphology was observed in C–ZDF rats. Melatonin supplementation alleviated renal ER stress response in ZDF rats, by decreasing glucose-regulated protein 78 (GRP78), phosphoinositol-requiring enzyme1α (IRE1α), and ATF6 levels but had no effect on phospho–protein kinase RNA–like endoplasmic reticulum kinase (PERK) level. In addition, melatonin supplementation also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins phospho–c–jun amino terminal kinase (JNK), Bax, and cleaved caspase-3, as well as by upregulation of B cell lymphoma (Bcl)-2 protein. These improvements were associated with renal structural recovery. Taken together, our findings revealed that melatonin play a renoprotective role, at least in part, by suppressing ER stress and related pro-apoptotic IRE1α/JNK signaling pathway. Full article
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17 pages, 3506 KiB  
Article
Antibacterial and Antifungal Activity of Propyl-Propane-Thiosulfinate and Propyl-Propane-Thiosulfonate, Two Organosulfur Compounds from Allium cepa: In Vitro Antimicrobial Effect via the Gas Phase
by Antonio Sorlozano-Puerto, Maria Albertuz-Crespo, Isaac Lopez-Machado, Lidia Gil-Martinez, Juan Jose Ariza-Romero, Alba Maroto-Tello, Alberto Baños-Arjona and Jose Gutierrez-Fernandez
Pharmaceuticals 2021, 14(1), 21; https://doi.org/10.3390/ph14010021 - 29 Dec 2020
Cited by 27 | Viewed by 3445
Abstract
Propyl-propane thiosulfinate (PTS) and propyl-propane thiosulfonate (PTSO) are two volatile compounds derived from Allium cepa with a widely documented antimicrobial activity. The aim of this study was to evaluate their anti-candidiasis activity and the ability of its gaseous phase to inhibit bacterial and [...] Read more.
Propyl-propane thiosulfinate (PTS) and propyl-propane thiosulfonate (PTSO) are two volatile compounds derived from Allium cepa with a widely documented antimicrobial activity. The aim of this study was to evaluate their anti-candidiasis activity and the ability of its gaseous phase to inhibit bacterial and yeast growth in vitro. The minimum inhibitory concentration of various antifungal products (including PTS and PTSO) was determined versus 203 clinical isolates of Candida spp. through broth microdilution assay. Additionally, the antimicrobial activity through aerial diffusion of PTS and PTSO was evaluated over the growth of a collection of bacteria and yeasts cultivated in agar plates. All yeasts were susceptible to the antifungals tested, except C. glabrata and C. krusei, that showed azole resistance. PTSO (MIC50 and MIC90 ranged from 4 to 16 mg/L and 8 to 32 mg/L, respectively) was significantly more active against yeasts than PTS (MIC50 and MIC90 ranged from 16 to 64 mg/L and 32 to 64 mg/L). Values were higher than those obtained for antifungal drugs. Gaseous phases of PTS and PTSO generated growth inhibition zones whose diameters were directly related to the substances concentration and inversely related to the microbial inoculum. The quantification of PTS and PTSO levels reached in the growth media through aerial diffusion displayed a concentration gradient from the central zone to the periphery. Only P. aeruginosa ATCC 27853 showed resistance, while yeasts (C. albicans ATCC 200955 and C. krusei ATCC 6258) presented the higher susceptibility to both compounds. These results suggest that PTS and PTSO display antibacterial and anti-candidiasis activity in vitro through aerial diffusion, having potential use in human therapy. Full article
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Review

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20 pages, 1602 KiB  
Review
The Use of Shells of Marine Molluscs in Spanish Ethnomedicine: A Historical Approach and Present and Future Perspectives
by José A. González and José Ramón Vallejo
Pharmaceuticals 2023, 16(10), 1503; https://doi.org/10.3390/ph16101503 - 23 Oct 2023
Viewed by 1680
Abstract
Since ancient times, the shells of marine molluscs have been used as a therapeutic and/or prophylactic resource. In Spain, they were part of practical guides for doctors or pharmacists until the 19th century. In general, seashells were prepared by dissolving in vinegar and [...] Read more.
Since ancient times, the shells of marine molluscs have been used as a therapeutic and/or prophylactic resource. In Spain, they were part of practical guides for doctors or pharmacists until the 19th century. In general, seashells were prepared by dissolving in vinegar and were part of plasters or powders used as toothpaste, or to treat dyspepsia, heartburn and leprosy. Thus, the nacre or mother-of-pearl of various molluscs was regularly used in the Royal Colleges of Surgery and in hospitals during the times of the Cortes of Cadiz, as a medicine in galenic preparations based on powders. In contemporary Spanish ethnomedicine, seashells, with a high symbolic value, have been used as an amulet to prevent cracks in the breasts and promote their development during lactation, to avoid teething pain in young children, to eliminate stains on the face or to cure erysipelas. But, as in other countries, products derived from seashells have also been empirically applied. The two resources used traditionally have been the cuttlebone, the internal shell of cuttlefish and the nacre obtained from the external shells of some species. Cuttlebone, dried and pulverised, has been applied externally to cure corneal leukoma and in dental hygiene. In the case of nacre, a distinction must be made between chemical and physical remedies. Certain seashells, macerated in lemon juice, were used in coastal areas to remove spots on the face during postpartum. However, the most common practice in Spain mainland was to dissolve mother-of-pearl buttons in lemon juice (or vinegar). The substance thus obtained has been used to treat different dermatological conditions of the face (chloasma, acne), as well as to eliminate freckles. For the extraction of foreign bodies in the eyes, a very widespread traditional remedy has been to introduce small mother-of-pearl buttons under the lid. These popular remedies and practices are compared with those collected in classic works of medicine throughout history, and data on the pharmacological activity and pharmaceutical applications of the products used are provided. The use of cuttlebone powders is supported by different works on anti-inflammatory, immune-modulatory and/or wound healing properties. Nacre powder has been used in traditional medicines to treat palpitations, convulsions or epilepsy. As sedation and a tranquilisation agent, nacre is an interesting source for further drug development. Likewise, nacre is a biomaterial for orthopaedic and other tissue bioengineering applications. This article is a historical, cultural and anthropological view that can open new epistemological paths in marine-derived product research. Full article
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37 pages, 4090 KiB  
Review
Plant Terpenoids as Hit Compounds against Trypanosomiasis
by Raquel Durão, Cátia Ramalhete, Ana Margarida Madureira, Eduarda Mendes and Noélia Duarte
Pharmaceuticals 2022, 15(3), 340; https://doi.org/10.3390/ph15030340 - 10 Mar 2022
Cited by 4 | Viewed by 4819
Abstract
Human African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas disease) are vector-borne neglected tropical diseases, caused by the protozoan parasites Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases were circumscribed to South American and African countries in the past. However, human migration, [...] Read more.
Human African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas disease) are vector-borne neglected tropical diseases, caused by the protozoan parasites Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases were circumscribed to South American and African countries in the past. However, human migration, military interventions, and climate changes have had an important effect on their worldwide propagation, particularly Chagas disease. Currently, the treatment of trypanosomiasis is not ideal, becoming a challenge in poor populations with limited resources. Exploring natural products from higher plants remains a valuable approach to find new hits and enlarge the pipeline of new drugs against protozoal human infections. This review covers the recent studies (2016–2021) on plant terpenoids, and their semi-synthetic derivatives, which have shown promising in vitro and in vivo activities against Trypanosoma parasites. Full article
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13 pages, 566 KiB  
Review
Pharmacological Activity of Garcinia indica (Kokum): An Updated Review
by Sung Ho Lim, Ho Seon Lee, Chang Hoon Lee and Chang-Ik Choi
Pharmaceuticals 2021, 14(12), 1338; https://doi.org/10.3390/ph14121338 - 20 Dec 2021
Cited by 15 | Viewed by 4396
Abstract
Garcinia indica (commonly known as kokum), belonging to the Clusiaceae family (mangosteen family), is a tropical evergreen tree distributed in certain regions of India. It has been used in culinary and industrial applications for a variety of purposes, including acidulant in curries, pickles, [...] Read more.
Garcinia indica (commonly known as kokum), belonging to the Clusiaceae family (mangosteen family), is a tropical evergreen tree distributed in certain regions of India. It has been used in culinary and industrial applications for a variety of purposes, including acidulant in curries, pickles, health drinks, wine, and butter. In particular, G. indica has been used in traditional medicine to treat inflammation, dermatitis, and diarrhea, and to promote digestion. According to several studies, various phytochemicals such as garcinol, hydroxycitric acid (HCA), cyanidin-3-sambubioside, and cyanidin-3-glucoside were isolated from G. indica, and their pharmacological activities were published. This review highlights recent updates on the various pharmacological activities of G. indica. These studies reported that G. indica has antioxidant, anti-obesity, anti-arthritic, anti-inflammatory, antibacterial, hepatoprotective, cardioprotective, antidepressant and anxiolytic effects both in vitro and in vivo. These findings, together with previously published reports of pharmacological activity of various components isolated from G. indica, suggest its potential as a promising therapeutic agent to prevent various diseases. Full article
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21 pages, 1231 KiB  
Review
Linarin, a Glycosylated Flavonoid, with Potential Therapeutic Attributes: A Comprehensive Review
by Javad Mottaghipisheh, Hadi Taghrir, Anahita Boveiri Dehsheikh, Kamiar Zomorodian, Cambyz Irajie, Mohammad Mahmoodi Sourestani and Aida Iraji
Pharmaceuticals 2021, 14(11), 1104; https://doi.org/10.3390/ph14111104 - 29 Oct 2021
Cited by 33 | Viewed by 4836
Abstract
Many flavonoids, as eminent phenolic compounds, have been commercialized and consumed as dietary supplements due to their incredible human health benefits. In the present study, a bioactive flavone glycoside linarin (LN) was designated to comprehensively overview its phytochemical and biological properties. LN has [...] Read more.
Many flavonoids, as eminent phenolic compounds, have been commercialized and consumed as dietary supplements due to their incredible human health benefits. In the present study, a bioactive flavone glycoside linarin (LN) was designated to comprehensively overview its phytochemical and biological properties. LN has been characterized abundantly in the Cirsium, Micromeria, and Buddleja species belonging to Asteraceae, Lamiaceae, and Scrophulariaceae families, respectively. Biological assessments exhibited promising activities of LN, particularly, the remedial effects on central nervous system (CNS) disorders, whereas the remarkable sleep enhancing and sedative effects as well as AChE (acetylcholinesterase) inhibitory activity were highlighted. Of note, LN has indicated promising anti osteoblast proliferation and differentiation, thus a bone formation effect. Further biological and pharmacological assessments of LN and its optimized semi-synthetic derivatives, specifically its therapeutic characteristics on osteoarthritis and osteoporosis, might lead to uncovering potential drug candidates. Full article
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34 pages, 2870 KiB  
Review
Dietary Effects of Anthocyanins in Human Health: A Comprehensive Review
by Ana C. Gonçalves, Ana R. Nunes, Amílcar Falcão, Gilberto Alves and Luís R. Silva
Pharmaceuticals 2021, 14(7), 690; https://doi.org/10.3390/ph14070690 - 18 Jul 2021
Cited by 94 | Viewed by 10423
Abstract
In recent years, the consumption of natural-based foods, including beans, fruits, legumes, nuts, oils, vegetables, spices, and whole grains, has been encouraged. This fact is essentially due to their content in bioactive phytochemicals, with the phenolic compounds standing out. Among them, anthocyanins have [...] Read more.
In recent years, the consumption of natural-based foods, including beans, fruits, legumes, nuts, oils, vegetables, spices, and whole grains, has been encouraged. This fact is essentially due to their content in bioactive phytochemicals, with the phenolic compounds standing out. Among them, anthocyanins have been a target of many studies due to the presence of catechol, pyrogallol, and methoxy groups in their chemical structure, which confer notable scavenging, anti-apoptotic, and anti-inflammatory activities, being already recommended as supplementation to mitigate or even attenuate certain disorders, such as diabetes, cancer, and cardiovascular and neurological pathologies. The most well-known anthocyanins are cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside. They are widespread in nature, being present in considerable amounts in red fruits and red vegetables. Overall, the present review intends to discuss the most recent findings on the potential health benefits from the daily intake of anthocyanin-rich foods, as well as their possible pharmacological mechanisms of action. However, before that, some emphasis regarding their chemical structure, dietary sources, and bioavailability was done. Full article
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34 pages, 8859 KiB  
Review
Flavonoids from the Genus Euphorbia: Isolation, Structure, Pharmacological Activities and Structure–Activity Relationships
by Douglas Kemboi Magozwi, Mmabatho Dinala, Nthabiseng Mokwana, Xavier Siwe-Noundou, Rui W. M. Krause, Molahlehi Sonopo, Lyndy J. McGaw, Wilma A. Augustyn and Vuyelwa Jacqueline Tembu
Pharmaceuticals 2021, 14(5), 428; https://doi.org/10.3390/ph14050428 - 02 May 2021
Cited by 22 | Viewed by 4841
Abstract
Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure–activity relationship [...] Read more.
Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure–activity relationship of Euphorbia flavonoids for the period covering 2000–2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Of the investigated species, over 80 different types of flavonoids have been isolated to date. Most of the isolated flavonoids were flavonols and comprised simple O-substitution patterns, C-methylation and prenylation. Others had a glycoside, glycosidic linkages and a carbohydrate attached at either C-3 or C-7, and were designated as d-glucose, l-rhamnose or glucorhamnose. The structure–activity relationship studies showed that methylation of the hydroxyl groups on C-3 or C-7 reduces the activities while glycosylation loses the activity and that the parent skeletal structure is essential in retaining the activity. These constituents can therefore offer potential alternative scaffolds towards development of new Euphorbia-based therapeutic agents. Full article
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17 pages, 1982 KiB  
Review
Mycosporine-Like Amino Acids (MAAs): Biology, Chemistry and Identification Features
by Vanessa Geraldes and Ernani Pinto
Pharmaceuticals 2021, 14(1), 63; https://doi.org/10.3390/ph14010063 - 14 Jan 2021
Cited by 70 | Viewed by 9646
Abstract
Mycosporines and mycosporine-like amino acids are ultra-violet-absorbing compounds produced by several organisms such as lichens, fungi, algae and cyanobacteria, especially upon exposure to solar ultraviolet radiation. These compounds have photoprotective and antioxidant functions. Mycosporine-like amino acids have been used as a natural bioactive [...] Read more.
Mycosporines and mycosporine-like amino acids are ultra-violet-absorbing compounds produced by several organisms such as lichens, fungi, algae and cyanobacteria, especially upon exposure to solar ultraviolet radiation. These compounds have photoprotective and antioxidant functions. Mycosporine-like amino acids have been used as a natural bioactive ingredient in cosmetic products. Several reviews have already been developed on these photoprotective compounds, but they focus on specific features. Herein, an extremely complete database on mycosporines and mycosporine-like amino acids, covering the whole class of these natural sunscreen compounds known to date, is presented. Currently, this database has 74 compounds and provides information about the chemistry, absorption maxima, protonated mass, fragments and molecular structure of these UV-absorbing compounds as well as their presence in organisms. This platform completes the previous reviews and is available online for free and in the public domain. This database is a useful tool for natural product data mining, dereplication studies, research working in the field of UV-absorbing compounds mycosporines and being integrated in mass spectrometry library software. Full article
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