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Natural Medicine in Therapy
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Natural Medicine in Therapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 107477

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Raffaele Capasso

grade E-Mail Website
Guest Editor
Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
Interests: pharmacology; natural products; neurotransmission; behavioral pharmacology; experimental pharmacology; preclinical pharmacology; CB1 receptor; PPARs; cannabinoids; endocannabinoids; CB2 receptor
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

For a long time, natural medicine has been used as a therapeutic therapy based on generations of indigenous practices. Today the rise in natural remedies has been largely driven by public demand and billions of dollars are spent annually on herbal medicines. It is therefore important to document the effectiveness of natural medicine, its potential side effects, and potential interactions.

The development of new natural products can significantly improve the biomedical efficiency of natural medicine. This Special Issue will highlight research based on the evidence of natural medicines, with a particular focus on their use in therapy. I cordially invite authors to contribute original articles, as well as reviews, that unravel new biological activity of naturally-occurring products to help create greater opportunities for their future use.

Prof. Dr. Raffaele Capasso
Guest Editor

Manuscript Submission Information

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Keywords

  • Medicinal plants
  • Flavonoids
  • annabinoids
  • Essential oil
  • Biological activity
  • Medical use
  • Plant side effects
  • Pharmacological interactions

Published Papers (21 papers)

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Editorial

Jump to: Research, Review

4 pages, 198 KiB  
Editorial
Pharmacological Studies on Traditional Plant-Based Remedies
by Giuseppe Lucariello, Donatella Cicia and Raffaele Capasso
Biomedicines 2021, 9(3), 315; https://doi.org/10.3390/biomedicines9030315 - 19 Mar 2021
Cited by 3 | Viewed by 1860
Abstract
For years, plant-based remedies have been used as a traditional practice to treat and prevent a broad range of diseases [...] Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)

Research

Jump to: Editorial, Review

16 pages, 5475 KiB  
Article
Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis
by Shara Francesca Rapa, Rosanna Di Paola, Marika Cordaro, Rosalba Siracusa, Ramona D’Amico, Roberta Fusco, Giuseppina Autore, Salvatore Cuzzocrea, Hermann Stuppner and Stefania Marzocco
Biomedicines 2021, 9(1), 67; https://doi.org/10.3390/biomedicines9010067 - 12 Jan 2021
Cited by 9 | Viewed by 3018
Abstract
Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with [...] Read more.
Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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14 pages, 11249 KiB  
Article
Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice
by Jung-Yeon Kim, Jungmin Jo, Jaechan Leem and Kwan-Kyu Park
Biomedicines 2020, 8(12), 572; https://doi.org/10.3390/biomedicines8120572 - 06 Dec 2020
Cited by 15 | Viewed by 2731
Abstract
Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. [...] Read more.
Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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13 pages, 1383 KiB  
Article
Chronic Treatment with a Phytosomal Preparation Containing Centella asiatica L. and Curcuma longa L. Affects Local Protein Synthesis by Modulating the BDNF-mTOR-S6 Pathway
by Giulia Sbrini, Paola Brivio, Enrico Sangiovanni, Marco Fumagalli, Giorgio Racagni, Mario Dell’Agli and Francesca Calabrese
Biomedicines 2020, 8(12), 544; https://doi.org/10.3390/biomedicines8120544 - 26 Nov 2020
Cited by 8 | Viewed by 1975
Abstract
Brain derived neurotrophic factor (Bdnf) is the most diffuse neurotrophin in the central nervous system and it is crucial for the proper brain development and maintenance. Indeed, through the binding to its high affinity receptor TRKB and the activation of different intracellular cascades, [...] Read more.
Brain derived neurotrophic factor (Bdnf) is the most diffuse neurotrophin in the central nervous system and it is crucial for the proper brain development and maintenance. Indeed, through the binding to its high affinity receptor TRKB and the activation of different intracellular cascades, it boosts cell survival, neurite growth and spine maturations mechanisms. Here, we evaluated if the chronic oral treatment for 10 days with a phytosomal preparation containing Centella asiatica L. and Curcuma longa L. could improve Bdnf levels in the prefrontal cortex of adult rats. Interestingly we found an increased expression of Bdnf with main effect of the treatment on the mTOR-S6 downstream signaling pathway. Accordingly, we found an increase in the expression of eukaryotic elongation factor (eEF2) with a shift towards the phosphorylated form thus increasing the transcription of Oligophrenin-1, a protein carrying the upstream Open Reading Frame (uORF) which reduction is paralleled by memory dysfunctions. These results show the ability of the phytosome to enhance mTOR-S6 regulated transcription and suggest the possibility to use this preparation in subjects with impairments in neuroplastic mechanisms, memory and cognitive abilities. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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13 pages, 3113 KiB  
Article
Treatment with Luteolin Improves Lipopolysaccharide-Induced Periodontal Diseases in Rats
by Giovanna Casili, Alessio Ardizzone, Marika Lanza, Enrico Gugliandolo, Marco Portelli, Angela Militi, Salvatore Cuzzocrea, Emanuela Esposito and Irene Paterniti
Biomedicines 2020, 8(10), 442; https://doi.org/10.3390/biomedicines8100442 - 21 Oct 2020
Cited by 19 | Viewed by 2943
Abstract
Periodontitis is a dental disease that produces the progressive destruction of the bone surrounding the tooth. Especially, lipopolysaccharide (LPS) is involved in the deterioration of the alveolar bone, inducing the release of pro-inflammatory mediators, which cause periodontal tissue inflammation. Luteolin (Lut), a molecule [...] Read more.
Periodontitis is a dental disease that produces the progressive destruction of the bone surrounding the tooth. Especially, lipopolysaccharide (LPS) is involved in the deterioration of the alveolar bone, inducing the release of pro-inflammatory mediators, which cause periodontal tissue inflammation. Luteolin (Lut), a molecule of natural origin present in a large variety of fruits and vegetables, possess beneficial properties for human health. On this basis, we investigated the anti-inflammatory properties of Lut in a model of periodontitis induced by LPS in rats. Animal model predicted a single intragingival injection of LPS (10 μg/μL) derived from Salmonella typhimurium. Lut administration, was performed daily at different doses (10, 30, and 100 mg/kg, orally), starting from 1 h after the injection of LPS. After 14 days, the animals were sacrificed, and their gums were processed for biochemical analysis and histological examinations. Results showed that Lut (30 and 100 mg/kg) was equally able to reduce alveolar bone loss, tissue damage, and neutrophilic infiltration. Moreover, Lut treatment reduced the concentration of collagen fibers, mast cells degranulation, and NF-κB activation, as well as the presence of pro-inflammatory enzymes and cytokines. Therefore, Lut implementation could represent valid support in the pharmacological strategy for periodontitis, thus improving the well-being of the oral cavity. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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14 pages, 2351 KiB  
Article
Hemocyanins from Helix and Rapana Snails Exhibit in Vitro Antitumor Effects in Human Colorectal Adenocarcinoma
by Ani Georgieva, Katerina Todorova, Ivan Iliev, Valeriya Dilcheva, Ivelin Vladov, Svetlozara Petkova, Reneta Toshkova, Lyudmila Velkova, Aleksandar Dolashki and Pavlina Dolashka
Biomedicines 2020, 8(7), 194; https://doi.org/10.3390/biomedicines8070194 - 05 Jul 2020
Cited by 19 | Viewed by 2815
Abstract
Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins [...] Read more.
Hemocyanins are oxygen-transporting glycoproteins in the hemolymph of arthropods and mollusks that attract scientific interest with their diverse biological activities and potential applications in pharmacy and medicine. The aim of the present study was to assess the in vitro antitumor activity of hemocyanins isolated from marine snail Rapana venosa (RvH) and garden snails Helix lucorum (HlH) and Helix aspersa (HaH), as well the mucus of H. aspersa snails, in the HT-29 human colorectal carcinoma cell line. The effects of the hemocyanins on the cell viability and proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alterations in the tumor cell morphology were examined by fluorescent and transmission electron microscopy. The results of the MTT assay showed that the mucus and α-subunit of hemocyanin from the snail H. aspersa had the most significant antiproliferative activity of the tested samples. Cytomorphological analysis revealed that the observed antitumor effects were associated with induction of apoptosis in the tumor cells. The presented data indicate that hemocyanins and mucus from H. aspersa have an antineoplastic activity and potential for development of novel therapeutics for treatment of colorectal carcinoma. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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11 pages, 1388 KiB  
Article
A Mechanism by which Ergosterol Inhibits the Promotion of Bladder Carcinogenesis in Rats
by Nobutomo Ikarashi, Motohiro Hoshino, Tetsuya Ono, Takahiro Toda, Yasuharu Yazawa and Kiyoshi Sugiyama
Biomedicines 2020, 8(7), 180; https://doi.org/10.3390/biomedicines8070180 - 27 Jun 2020
Cited by 6 | Viewed by 2112
Abstract
We previously showed that ergosterol has an inhibitory effect on bladder carcinogenesis. In this study, we aimed to elucidate the molecular mechanism by which ergosterol inhibits bladder carcinogenesis using a rat model of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer. The messenger ribonucleic acid (mRNA) expression level [...] Read more.
We previously showed that ergosterol has an inhibitory effect on bladder carcinogenesis. In this study, we aimed to elucidate the molecular mechanism by which ergosterol inhibits bladder carcinogenesis using a rat model of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer. The messenger ribonucleic acid (mRNA) expression level of the cell cycle-related gene cyclin D1 and inflammation-related gene cyclooxygenase-2 in bladder epithelial cells was significantly increased in the carcinogenesis group compared with the control group. In contrast, in ergosterol-treated rats, these increases were significantly suppressed. Ergosterol did not affect the plasma testosterone concentration or the binding of dihydrotestosterone to androgen receptor (AR). The mRNA expression levels of 5α-reductase type 2 and AR were higher in the carcinogenesis group than in the control group but were significantly decreased by ergosterol administration. These results suggest that ergosterol inhibits bladder carcinogenesis by modulating various aspects of the cell cycle, inflammation-related signaling, and androgen signaling. Future clinical application of the preventive effect of ergosterol on bladder carcinogenesis is expected. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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11 pages, 1655 KiB  
Article
β-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors
by Giacomo Picciolo, Giovanni Pallio, Domenica Altavilla, Mario Vaccaro, Giacomo Oteri, Natasha Irrera and Francesco Squadrito
Biomedicines 2020, 8(6), 164; https://doi.org/10.3390/biomedicines8060164 - 17 Jun 2020
Cited by 34 | Viewed by 3392
Abstract
Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet [...] Read more.
Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of β-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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12 pages, 2875 KiB  
Article
Anti-Anaphylactic Activity of Isoquercitrin (Quercetin-3-O-β-d-Glucose) in the Cardiovascular System of Animals
by Jinbong Park
Biomedicines 2020, 8(6), 139; https://doi.org/10.3390/biomedicines8060139 - 29 May 2020
Cited by 9 | Viewed by 3070
Abstract
Effects of isoquercitrin (IQ) on anaphylactic responses were examined in cardiovascular systems of experimental animals. In pithed rats, IQ at 30 and 100 mg/kg (intravenous) significantly blunted both the initial hypertensive and the ensuing hypotensive responses during anaphylaxis. Death rate and tachycardia were [...] Read more.
Effects of isoquercitrin (IQ) on anaphylactic responses were examined in cardiovascular systems of experimental animals. In pithed rats, IQ at 30 and 100 mg/kg (intravenous) significantly blunted both the initial hypertensive and the ensuing hypotensive responses during anaphylaxis. Death rate and tachycardia were also significantly inhibited after the same IQ doses in these rats. In isolated guinea pig hearts, IQ infusion at 30–100 μg/mL markedly reduced anaphylaxis-related coronary flow decrease, contractile force change, and heart rate responses (both tachycardia and arrhythmia). Cardiac histamine and creatine kinase releases were similarly diminished by IQ during anaphylaxis in the isolated guinea pig hearts. In two different isolated guinea pig vasculatures, the pulmonary artery and mesenteric arterial bed, anaphylactic vasoconstriction was reduced by IQ 30 and 100 μg/mL. It was observed that IQ had a marked inhibitory effect on histamine release from rat mast cells, and this mechanism was suggested as the major anti-anaphylactic mechanism. Direct inhibition of histamine-induced muscle contraction did not seem to be relevant, but IQ treatment successfully repressed intracellular calcium influx/depletion in mast cells. Overall, this study provided evidence for the beneficial effect of IQ on cardiac anaphylaxis, thus suggesting its potential applications in the treatment and prevention of related diseases. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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16 pages, 7958 KiB  
Article
Phytogenic Synthesis of Nickel Oxide Nanoparticles (NiO) Using Fresh Leaves Extract of Rhamnus triquetra (Wall.) and Investigation of Its Multiple In Vitro Biological Potentials
by Javed Iqbal, Banzeer Ahsan Abbasi, Riaz Ahmad, Mahboobeh Mahmoodi, Akhtar Munir, Syeda Anber Zahra, Amir Shahbaz, Muzzafar Shaukat, Sobia Kanwal, Siraj Uddin, Tariq Mahmood and Raffaele Capasso
Biomedicines 2020, 8(5), 117; https://doi.org/10.3390/biomedicines8050117 - 12 May 2020
Cited by 81 | Viewed by 5456
Abstract
Chemically nickel oxide nanoparticles (NiONPs) involve the synthesis of toxic products, which restrict their biological applications. Hence, we developed a simple, eco-friendly, and cost-efficient green chemistry method for the fabrication of NiONPs using fresh leaf broth of Rhamnus triquetra (RT). The RT leaves [...] Read more.
Chemically nickel oxide nanoparticles (NiONPs) involve the synthesis of toxic products, which restrict their biological applications. Hence, we developed a simple, eco-friendly, and cost-efficient green chemistry method for the fabrication of NiONPs using fresh leaf broth of Rhamnus triquetra (RT). The RT leaves broth was used as a strong reducing, capping, and stabilizing agent in the formation of RT-NiONPs. The color change in solution from brown to greenish black suggests the fabrication of RT-NiONPs which was further confirmed by absorption band at 333 nm. The synthesis and different physicochemical properties of RT-NiONPs were investigated using different analytical techniques such as UV-Vis (ultraviolet−visible spectroscopy), XRD (X-ray powder diffraction), FT-IR (Fourier-transform infrared spectroscopy), SEM (scanning electron microscopy), TEM (transmission electron microscopy), EDS (energy-dispersive X-ray spectroscopy), DLS (dynamic light scattering) and Raman. Further, RT-NiONPs were subjected to different in vitro biological activities and revealed distinctive biosafe and biocompatibility potentials using erythrocytes and macrophages. RT-NiONPs exhibited potential anticancer activity against liver cancer cell lines HUH7 (IC50: 11.3 µg/mL) and HepG2 (IC50: 20.73 µg/mL). Cytotoxicity potential was confirmed using Leishmanial parasites promastigotes (IC50: 27.32 µg/mL) and amastigotes (IC50: 37.4 µg/mL). RT-NiONPs are capable of rendering significant antimicrobial efficacy using various bacterial and fungal strains. NiONPs determined potent radical scavenging and moderate enzyme inhibition potencies. Overall, this study suggested that RT-NiONPs can be an attractive and eco-friendly candidate. In conclusion, current study showed potential in vitro biological activities and further necessitate different in vivo studies in various animal models to develop leads for new drugs to treat several chronic diseases. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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18 pages, 2637 KiB  
Article
Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects
by Dayana da Costa Salomé, Natália de Morais Cordeiro, Tayná Sequeira Valério, Darlisson de Alexandria Santos, Péricles Barreto Alves, Celuta Sales Alviano, Daniela Sales Alviano Moreno and Patricia Dias Fernandes
Biomedicines 2020, 8(5), 111; https://doi.org/10.3390/biomedicines8050111 - 06 May 2020
Cited by 6 | Viewed by 2972
Abstract
Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, [...] Read more.
Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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18 pages, 4890 KiB  
Article
Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy
by Bernhard P. Kaltschmidt, Inga Ennen, Johannes F. W. Greiner, Robin Dietsch, Anant Patel, Barbara Kaltschmidt, Christian Kaltschmidt and Andreas Hütten
Biomedicines 2020, 8(5), 105; https://doi.org/10.3390/biomedicines8050105 - 01 May 2020
Cited by 14 | Viewed by 3367
Abstract
Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce invasomes encapsulating [...] Read more.
Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce invasomes encapsulating thymol, menthol, camphor and 1,8-cineol, characterize them via cryo transmission electron microscopy and assess their bactericidal properties. While control- and cineol-invasomes are similarly distributed between unilamellar and bilamellar vesicles, a shift towards unilamellar invasomes is observable after encapsulation of thymol, menthol or camphor. Thymol- and camphor-invasomes show a size reduction, whereas menthol-invasomes are enlarged and cineol-invasomes remain unchanged compared to control. While thymol-invasomes lead to the strongest growth inhibition of S. aureus, camphor- or cineol-invasomes mediate cell death and S. aureus growth is not affected by menthol-invasomes. Flow cytometric analysis validate that invasomes comprising thymol are highly bactericidal to S. aureus. Notably, treatment with thymol-invasomes does not affect survival of Gram-negative E. coli. In summary, we successfully produce terpenoid-invasomes and demonstrate that particularly thymol-invasomes show a strong selective activity against Gram-positive bacteria. Our findings provide a promising approach to increase the bioavailability of terpenoid-based drugs and may be directly applicable for treating severe bacterial infections such as methicillin-resistant S. aureus. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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16 pages, 2334 KiB  
Article
Orthosiphon stamineus Standardized Extract Reverses Streptozotocin-Induced Alzheimer’s Disease-Like Condition in a Rat Model
by Thaarvena Retinasamy, Mohd. Farooq Shaikh, Yatinesh Kumari, Syafiq Asnawi Zainal Abidin and Iekhsan Othman
Biomedicines 2020, 8(5), 104; https://doi.org/10.3390/biomedicines8050104 - 30 Apr 2020
Cited by 12 | Viewed by 3026
Abstract
Alzheimer’s disease (AD) is a chronic neurodegenerative brain disease that is characterized by impairment in cognitive functioning as well as the presence of intraneuronal neurofibrillary tangles (NFTs) and extracellular senile plaques. There is a growing interest in the potential of phytochemicals to improve [...] Read more.
Alzheimer’s disease (AD) is a chronic neurodegenerative brain disease that is characterized by impairment in cognitive functioning as well as the presence of intraneuronal neurofibrillary tangles (NFTs) and extracellular senile plaques. There is a growing interest in the potential of phytochemicals to improve memory, learning, and general cognitive abilities. The Malaysian herb Orthosiphon stamineus is a traditional remedy that possesses anti-inflammatory, anti-oxidant, and free-radical scavenging abilities, all of which are known to protect against AD. Previous studies have reported that intracerebroventricular (ICV) administration of streptozotocin (STZ) mimics a condition similar to that observed in AD. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel treatment for AD in a rat model and can reverse the STZ- induced learning and memory dysfunction. The results of this study indicate that O. stamineus has the potential to be potentially effective against AD-like condition, as both behavioral models employed in this study was observed to be able to reverse memory impairment. Treatment with the extract was able to decrease the up-regulated expression levels of amyloid precursor protein (APP), microtubule associated protein tau (MAPT), Nuclear factor kappa-light-chain-enhancer of activated B cells (NFᴋB), glycogen synthase kinase 3 alpha (GSK3α), and glycogen synthase kinase 3 beta (GSK3β) genes indicating the extract’s neuroprotective ability. These research findings suggest that the O. stamineus ethanolic extract demonstrated an improved effect on memory, and hence, could serve as a potential therapeutic target for the treatment of neurodegenerative diseases such as AD. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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10 pages, 1688 KiB  
Article
Characterization of the Antinociceptive Activity from Stevia serrata Cav
by Millena S. Cordeiro, Daniel L. R. Simas, Juan F. Pérez-Sabino, Max S. Mérida-Reyes, Manuel A. Muñoz-Wug, Bessie E. Oliva-Hernández, Antônio J. R. da Silva, Patricia D. Fernandes and Thais B. S. Giorno
Biomedicines 2020, 8(4), 79; https://doi.org/10.3390/biomedicines8040079 - 07 Apr 2020
Cited by 8 | Viewed by 2821
Abstract
Background: Stevia serrata Cav. (Asteraceae), widely found in Guatemala, is used to treat gastrointestinal problems. The aim of this study was to demonstrate the antinociceptive and anti-inflammatory effects of the essential oil (EO) and the mechanism of action. Methods: EO was tested in [...] Read more.
Background: Stevia serrata Cav. (Asteraceae), widely found in Guatemala, is used to treat gastrointestinal problems. The aim of this study was to demonstrate the antinociceptive and anti-inflammatory effects of the essential oil (EO) and the mechanism of action. Methods: EO was tested in chemical (capsaicin- and glutamate-induced licking response) or thermal (hot plate) models of nociception at 10, 30 or 100 mg/kg doses. The mechanism of action was evaluated using two receptor antagonists (naloxone, atropine) and an enzyme inhibitor (L-NAME). The anti-hyperalgesic effect was evaluated using carrageenan-induced nociception and evaluated in the hot plate. Results: All three doses of EO reduced licking response induced by glutamate, and higher doses reduced capsaicin-induced licking. EO also increased area under the curve, similar to the morphine-treated group. The antinociceptive effect induced by EO was reversed by pretreatment of mice with naloxone (1 mg/kg, ip), atropine (1 mg/kg, ip) or L-NAME (3 mg/kg, ip). EO also demonstrated an anti-hyperalgesic effect. The 100 mg/kg dose increased the latency time, even at 1 h after oral administration and this effect has been maintained until the 96th hour, post-administration. Conclusions: Our data suggest that essential oil of S. serrata presents an antinociceptive effect mediated, at least in part, through activation of opioid, cholinergic and nitrergic pathways. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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15 pages, 3687 KiB  
Article
Comparative Study of Piper sylvaticum Roxb. Leaves and Stems for Anxiolytic and Antioxidant Properties Through In Vivo, In Vitro, and In Silico Approaches
by Md. Adnan, Md. Nazim Uddin Chy, A.T.M. Mostafa Kamal, Md Obyedul Kalam Azad, Kazi Asfak Ahmed Chowdhury, Mohammad Shah Hafez Kabir, Shaibal Das Gupta, Md. Ashiqur Rahman Chowdhury, Young Seok Lim and Dong Ha Cho
Biomedicines 2020, 8(4), 68; https://doi.org/10.3390/biomedicines8040068 - 25 Mar 2020
Cited by 14 | Viewed by 5328
Abstract
Piper sylvaticum Roxb. is traditionally used by the indigenous people of tropical and subtropical countries like Bangladesh, India, and China for relieving the common cold or a variety of chronic diseases, such as asthma, chronic coughing, piles, rheumatic pain, headaches, wounds, tuberculosis, indigestion, [...] Read more.
Piper sylvaticum Roxb. is traditionally used by the indigenous people of tropical and subtropical countries like Bangladesh, India, and China for relieving the common cold or a variety of chronic diseases, such as asthma, chronic coughing, piles, rheumatic pain, headaches, wounds, tuberculosis, indigestion, and dyspepsia. This study tested anxiolytic and antioxidant activities by in vivo, in vitro, and in silico experiments for the metabolites extracted (methanol) from the leaves and stems of P. sylvaticum (MEPSL and MEPSS). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MEPSL and MEPSS (200 and 400 mg/kg, body weight) exhibited a significant and dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MEPSL and MEPSS demonstrated dose-dependent increases in locomotion and CNS simulative effects in open field test. In addition, both extracts (MEPSL and MEPSS) also showed moderate antioxidant activities in DPPH scavenging and ferric reducing power assays compared to the standard, ascorbic acid. In parallel, previously isolated bioactive compounds from this plant were documented and subjected to a molecular docking study to correlate them with the pharmacological outcomes. The selected four major phytocompounds displayed favorable binding affinities to potassium channel and xanthine oxidoreductase enzyme targets in molecular docking experiments. Overall, P. sylvaticum is bioactive, as is evident through experimental and computational analysis. Further experiments are necessary to evaluate purified novel compounds for the clinical evaluation. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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Review

Jump to: Editorial, Research

22 pages, 1092 KiB  
Review
Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders
by Shweta Devi, Vijay Kumar, Sandeep Kumar Singh, Ashish Kant Dubey and Jong-Joo Kim
Biomedicines 2021, 9(2), 99; https://doi.org/10.3390/biomedicines9020099 - 20 Jan 2021
Cited by 56 | Viewed by 6792
Abstract
Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, [...] Read more.
Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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24 pages, 1308 KiB  
Review
Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
by Tapan Behl, Aditi Sharma, Lalit Sharma, Aayush Sehgal, Gokhan Zengin, Roxana Brata, Ovidiu Fratila and Simona Bungau
Biomedicines 2020, 8(12), 571; https://doi.org/10.3390/biomedicines8120571 - 06 Dec 2020
Cited by 52 | Viewed by 5089
Abstract
Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a “hopeless case and the leading cause of death worldwide, and [...] Read more.
Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a “hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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27 pages, 2431 KiB  
Review
Molecular Insights into the Multifunctional Role of Natural Compounds: Autophagy Modulation and Cancer Prevention
by Md. Ataur Rahman, MD. Hasanur Rahman, Md. Shahadat Hossain, Partha Biswas, Rokibul Islam, Md Jamal Uddin, Md. Habibur Rahman and Hyewhon Rhim
Biomedicines 2020, 8(11), 517; https://doi.org/10.3390/biomedicines8110517 - 19 Nov 2020
Cited by 31 | Viewed by 4821
Abstract
Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, [...] Read more.
Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancies. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects. In the current review, we discuss the promising role of natural compounds in modulating the autophagy pathway to control and prevent cancer, and provide possible therapeutic options. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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30 pages, 2041 KiB  
Review
Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review
by Francisco Javier Álvarez-Martínez, Enrique Barrajón-Catalán and Vicente Micol
Biomedicines 2020, 8(10), 405; https://doi.org/10.3390/biomedicines8100405 - 11 Oct 2020
Cited by 87 | Viewed by 14126
Abstract
Drug-resistant bacteria pose a serious threat to human health worldwide. Current antibiotics are losing efficacy and new antimicrobial agents are urgently needed. Living organisms are an invaluable source of antimicrobial compounds. The antimicrobial activity of the most representative natural products of animal, bacterial, [...] Read more.
Drug-resistant bacteria pose a serious threat to human health worldwide. Current antibiotics are losing efficacy and new antimicrobial agents are urgently needed. Living organisms are an invaluable source of antimicrobial compounds. The antimicrobial activity of the most representative natural products of animal, bacterial, fungal and plant origin are reviewed in this paper. Their activity against drug-resistant bacteria, their mechanisms of action, the possible development of resistance against them, their role in current medicine and their future perspectives are discussed. Electronic databases such as PubMed, Scopus and ScienceDirect were used to search scientific contributions until September 2020, using relevant keywords. Natural compounds of heterogeneous origins have been shown to possess antimicrobial capabilities, including against antibiotic-resistant bacteria. The most commonly found mechanisms of antimicrobial action are related to protein biosynthesis and alteration of cell walls and membranes. Various natural compounds, especially phytochemicals, have shown synergistic capacity with antibiotics. There is little literature on the development of specific resistance mechanisms against natural antimicrobial compounds. New technologies such as -omics, network pharmacology and informatics have the potential to identify and characterize new natural antimicrobial compounds in the future. This knowledge may be useful for the development of future therapeutic strategies. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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25 pages, 1289 KiB  
Review
Resveratrol Modulates Transforming Growth Factor-Beta (TGF-β) Signaling Pathway for Disease Therapy: A New Insight into Its Pharmacological Activities
by Milad Ashrafizadeh, Masoud Najafi, Sima Orouei, Amirhossein Zabolian, Hossein Saleki, Negar Azami, Negin Sharifi, Kiavash Hushmandi, Ali Zarrabi and Kwang Seok Ahn
Biomedicines 2020, 8(8), 261; https://doi.org/10.3390/biomedicines8080261 - 31 Jul 2020
Cited by 36 | Viewed by 6652
Abstract
Resveratrol (Res) is a well-known natural product that can exhibit important pharmacological activities such as antioxidant, anti-diabetes, anti-tumor, and anti-inflammatory. An evaluation of its therapeutic effects demonstrates that this naturally occurring bioactive compound can target different molecular pathways to exert its pharmacological actions. [...] Read more.
Resveratrol (Res) is a well-known natural product that can exhibit important pharmacological activities such as antioxidant, anti-diabetes, anti-tumor, and anti-inflammatory. An evaluation of its therapeutic effects demonstrates that this naturally occurring bioactive compound can target different molecular pathways to exert its pharmacological actions. Transforming growth factor-beta (TGF-β) is an important molecular pathway that is capable of regulating different cellular mechanisms such as proliferation, migration, and angiogenesis. TGF-β has been reported to be involved in the development of disorders such as diabetes, cancer, inflammatory disorders, fibrosis, cardiovascular disorders, etc. In the present review, the relationship between Res and TGF-β has been investigated. It was noticed that Res can inhibit TGF-β to suppress the proliferation and migration of cancer cells. In addition, Res can improve fibrosis by reducing inflammation via promoting TGF-β down-regulation. Res has been reported to be also beneficial in the amelioration of diabetic complications via targeting the TGF-β signaling pathway. These topics are discussed in detail in this review to shed light on the protective effects of Res mediated via the modulation of TGF-β signaling. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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26 pages, 1192 KiB  
Review
Trametes versicolor (Synn. Coriolus versicolor) Polysaccharides in Cancer Therapy: Targets and Efficacy
by Solomon Habtemariam
Biomedicines 2020, 8(5), 135; https://doi.org/10.3390/biomedicines8050135 - 25 May 2020
Cited by 73 | Viewed by 20470
Abstract
Coriolus versicolor (L.) Quél. is a higher fungi or mushroom which is now known by its accepted scientific name as Trametes versicolor (L.) Lloyd (family Polyporaceae). The polysaccharides, primarily two commercial products from China and Japan as PSP and PSK, respectively, have been [...] Read more.
Coriolus versicolor (L.) Quél. is a higher fungi or mushroom which is now known by its accepted scientific name as Trametes versicolor (L.) Lloyd (family Polyporaceae). The polysaccharides, primarily two commercial products from China and Japan as PSP and PSK, respectively, have been claimed to serve as adjuvant therapy for cancer. In this paper, research advances in this field, including direct cytotoxicity in cancer cells and immunostimulatory effects, are scrutinised at three levels: in vitro, in vivo and clinical outcomes. The level of activity in the various cancers, key targets (both in cancer and immune cells) and pharmacological efficacies are discussed. Full article
(This article belongs to the Special Issue Natural Medicine in Therapy)
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