Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

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Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

Molecules ◽

10.3390/molecules26061764 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1764

Author(s):

Anna Kaps ◽

Paweł Gwiazdoń ◽

Ewa Chodurek

Keyword(s):

Water Solubility ◽

Biological Activities ◽

Premature Mortality ◽

Delivery Systems ◽

Pentacyclic Triterpenoids ◽

Anticancer Properties ◽

Oncological Patients ◽

Antitumor Potential ◽

Ring Structures

The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids.

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l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells

Molecules ◽

10.3390/molecules26196062 ◽

2021 ◽

Vol 26 (19) ◽

pp. 6062

Author(s):

Luca Sancineto ◽

Carmine Ostacolo ◽

David Ortega-Alarcon ◽

Ana Jimenez-Alesanco ◽

Laura Ceballos-Laita ◽

...

Keyword(s):

Water Solubility ◽

Pharmaceutical Preparations ◽

Experimental Investigations ◽

Active Principle ◽

Pharmacological Activities ◽

Solubility In Water ◽

Solubility Improvement ◽

Starting Point ◽

Pharmacokinetic Properties ◽

Good Starting Point

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with L-arginine. Tests of the rutin/L-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.

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The Protective Effects and Potential Mechanisms of Ligusticum chuanxiong: Focus on Anti-Inflammatory, Antioxidant, and Antiapoptotic Activities

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8205983 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jinhui Shi ◽

Ruiyue Li ◽

Siyu Yang ◽

Yeelin Phang ◽

Changwu Zheng ◽

...

Keyword(s):

Molecular Mechanisms ◽

Biological Activities ◽

Clinical Settings ◽

Protective Effects ◽

Chinese Materia Medica ◽

Ligusticum Chuanxiong ◽

Anticancer Properties ◽

Pharmacokinetic Properties ◽

Anti Inflammatory ◽

Nrf2 Protein

Ligusticum chuanxiong (LC) is a Chinese materia medica which is widely used in clinical settings to treat headaches, blood extravasation, and arthritis. Recent studies demonstrate that LC possesses versatile pharmacological functions, including antiatherosclerosis, antimigraine, antiaging, and anticancer properties. Moreover, LC also shows protective effects in the progression of different diseases that damage somatic cells. Oxidative stress and inflammation, which can induce somatic cell apoptosis, are the main factors associated with an abundance of diseases, whose progresses can be reversed by LC. In order to comprehensively review the molecular mechanisms associated with the protective effects of LC, we collected and integrated all its related studies on the anti-inflammatory, antioxidant, and antiapoptotic effects. The results show that LC could exhibit the mentioned biological activities by modulating several signaling pathways, specifically the NF-κB, Nrf2, protein kinase, and caspase-3 pathways. In future investigations, the pharmacokinetic properties of bioactive compounds in LC and the signaling pathway modulation of LC could be focused.

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Novel Micro- and Nanocellulose-Based Delivery Systems for Liposoluble Compounds

Nanomaterials ◽

10.3390/nano11102593 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2593

Author(s):

Francisca Casanova ◽

Carla F. Pereira ◽

Alessandra B. Ribeiro ◽

Ricardo Freixo ◽

Eduardo Costa ◽

...

Keyword(s):

Bioactive Compounds ◽

Water Solubility ◽

Biological Activities ◽

Aqueous Solubility ◽

Delivery Systems ◽

Great Promise ◽

Gastrointestinal Conditions ◽

Wide Range ◽

State Of Research ◽

The Impact

Poor aqueous solubility of bioactive compounds is becoming a pronounced challenge in the development of bioactive formulations. Numerous liposoluble compounds have very interesting biological activities, but their low water solubility, stability, and bioavailability restrict their applications. To overcome these limitations there is a need to use enabling delivering strategies, which often demand new carrier materials. Cellulose and its micro- and nanostructures are promising carriers with unique features. In this context, this review describes the fast-growing field of micro- and nanocellulose based delivery systems with a focus on the release of liposoluble bioactive compounds. The state of research on this field is reviewed in this article, which also covers the chemistry, preparation, properties, and applications of micro- and nanocellulose based delivery systems. Although there are promising perspectives for introducing these materials into various fields, aspects of safety and toxicity must be revealed and are discussed in this review. The impact of gastrointestinal conditions on the systems and on the bioavailability of the bioactive compounds are also addressed in this review. This article helps to unveil the whole panorama of micro- and nanocellulose as delivery systems for liposoluble compounds, showing that these represent a great promise in a wide range of applications.

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Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

Current Medicinal Chemistry ◽

10.2174/0929867324666170227114648 ◽

2018 ◽

Vol 25 (14) ◽

pp. 1663-1681 ◽

Cited By ~ 9

Author(s):

Chun-Ting Lee ◽

Heng-Chun Kuo ◽

Yung-Hsiang Chen ◽

Ming-Yen Tsai

Keyword(s):

Biological Activity ◽

Therapeutic Potential ◽

Biological Activities ◽

Biological Effects ◽

Herbal Medicines ◽

Research Field ◽

Protective Effects ◽

Pharmacological Effects ◽

The Family ◽

Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

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Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

Current Medicinal Chemistry ◽

10.2174/0929867325666181112093336 ◽

2020 ◽

Vol 27 (12) ◽

pp. 1955-1996 ◽

Cited By ~ 4

Author(s):

Antonio Speciale ◽

Antonella Saija ◽

Romina Bashllari ◽

Maria Sofia Molonia ◽

Claudia Muscarà ◽

...

Keyword(s):

Human Health ◽

Biological Activities ◽

Wide Spectrum ◽

Antioxidant Defenses ◽

Noncommunicable Diseases ◽

Protective Effects ◽

Pathological Conditions ◽

Chronic Pulmonary Diseases ◽

Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

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Tetrazoloquinolines: Synthesis, Reactions, and Applications

Current Organic Chemistry ◽

10.2174/1385272824666200217095341 ◽

2020 ◽

Vol 24 (4) ◽

pp. 439-464 ◽

Cited By ~ 1

Author(s):

Rizk E. Khidre ◽

Tahah A. Ameen ◽

Mounir A. I. Salem

Keyword(s):

Carboxylic Acid ◽

Chemical Reactions ◽

Sodium Azide ◽

Biological Activities ◽

Quinoline Derivatives ◽

Pharmacological Activities ◽

Synthesis Reactions ◽

Intramolecular Cyclocondensation

This review summarizes the synthesis, reactions, and biological activities of tetrazolo[1,5-a]quinoline derivatives. These derivatives were synthesized by several methods such as i) from the reaction of 2-chloroquinoline with sodium azide ii) from diazotization 2-hydrazinylquinoline derivatives, and iii) from intramolecular cyclocondensation of 2-azidoarylidenes. Also, the chemical reactions and pharmacological activities of some tetrazoloquinolines such as tetrazolo[1,5-a]quinoline-4-carbaldehyde, 5-chlorotetrazolo[ 1,5-a]quinoline, 4-(chloromethyl)tetrazolo[1,5-a]quinoline, tetrazolo[1,5- a]quinoline-4-carboxylic acid, and 5-azidotetrazolo[1,5-a]quinoline were discussed.

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Physicochemical Characterization and Antinociceptive Effect of β-cyclodextrin/Lippia pedunculosa Essential Oil in Mice

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180607081742 ◽

2018 ◽

Vol 18 (9) ◽

pp. 797-807 ◽

Cited By ~ 1

Author(s):

Paula dos Passos Menezes ◽

Francielly de Oliveira Araujo ◽

Tatianny Araujo Andrade ◽

Igor Araujo Santos Trindade ◽

Heitor Gomes de Araujo-Filho ◽

...

Keyword(s):

Essential Oil ◽

Physicochemical Properties ◽

Water Solubility ◽

Therapeutic Potential ◽

Biological Activities ◽

Antinociceptive Effect ◽

Physicochemical Characterization ◽

Good Tool ◽

Main Challenge ◽

Higher Temperature

Background: Some research studies have shown that Lippia pedunculosa essential oil (EOLP) has interesting biological activities. However, its low water solubility is the main challenge to achieve its therapeutic potential. In this context, Cyclodextrins (CDs) have been widely used in order to overcome this problem due to your capability to improve the physicochemical properties of drugs. Objective: In this perspective, the main goal of this study was to investigate how the improvement of the physicochemical properties of inclusion complexes (EOLP and β-CD) enhance the antinociceptive effect in mice. Methods: To achieve that, we prepared samples by Physical Mixture (PM), Paste Complexation (PC) and Slurry Complexation (SC) methods, followed by their physicochemical characterization. In addition, it was evaluated if the use of β-CD enhances the antinociceptive effect of EOLP in mice. Results: The analysis showed that rotundifolone (72.02%) was the major compound of EOLP and we found out based on DSC results that β-CD protected it from oxidation. In addition, TG techniques demonstrated that the best inclusion methods were PC and SC, due to their greater weight loss (10.8 and 11.6%, respectively) in the second stage (171-312°C), indicating that more complexed oil was released at the higher temperature than oil free. Other characteristics, such as changes in the typical crystalline form, and reduced particle size were observed by SEM and laser diffraction, respectively. The SC was the most effective complexation method, once the presence of rotundifolone was detected by FTIR. Based on that, SC method was used in all mice tests. In this regard, the number of paw licks was reduced for both compounds (all doses), but EOLP was more effective in reducing the nociceptive behavior. Conclusion: Therefore, CDs seem not to be a good tool to enhance the pharmacological properties of EOs rich in peroxide compounds such as rotundifolone.

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Hybrids of Coumarin Derivatives as Potent and Multifunctional Bioactive Agents: A Review

Medicinal Chemistry ◽

10.2174/1573406415666190416121448 ◽

2020 ◽

Vol 16 (3) ◽

pp. 272-306

Author(s):

Ioannis Fotopoulos ◽

Dimitra Hadjipavlou-Litina

Keyword(s):

Pharmacological Activity ◽

Biological Activities ◽

Structural Characteristics ◽

Pharmacokinetic Profile ◽

Biologically Active ◽

Hybridization Technique ◽

Coumarin Derivatives ◽

Hybrid Molecules ◽

Pharmacokinetic Properties ◽

Bioactive Agents

Background: Coumarins exhibit a plethora of biological activities, e.g. antiinflammatory and anti-tumor. Molecular hybridization technique has been implemented in the design of novel coumarin hybrids with several bioactive groups in order to obtain molecules with better pharmacological activity and improved pharmacokinetic profile. Objective: Therefore, we tried to gather as many as possible biologically active coumarin hybrids referred in the literature till now, to delineate the structural characteristics in relation to the activities and to have a survey that might help the medicinal chemists to design new coumarin hybrids with drug-likeness and varied bioactivities. Results: The biological activities of the hybrids in most of the cases were found to be different from the biological activities presented by the parent coumarins. The results showed that the hybrid molecules are more potent compared to the standard drugs used in the evaluation experiments. Conclusion: Conjugation of coumarin with varied pharmacophore groups/druglike molecules responsible for different biological activities led to many novel hybrid molecules, with a multitarget behavior and improved pharmacokinetic properties.

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Development and Evaluation of Sustained Release Lipid Nanocarriers for Curcumin

Current Nanomaterials ◽

10.2174/2405461505999200917122147 ◽

2020 ◽

Vol 5 (3) ◽

pp. 224-235

Author(s):

Harshal A. Pawar ◽

Bhagyashree D. Bhangale

Keyword(s):

Drug Delivery ◽

Sustained Release ◽

Drug Delivery Systems ◽

Biological Activities ◽

Curcuma Longa ◽

Research Work ◽

Elimination Rate ◽

Delivery Systems ◽

Physicochemical Stability ◽

Wide Range

Background: Lipid based excipients have increased acceptance nowadays in the development of novel drug delivery systems in order to improve their pharmacokinetic profiles. Drugs encapsulated in lipids have enhanced stability due to the protection they experience in the lipid core of these nano-formulations. Phytosomes are newly discovered drug delivery systems and novel botanical formulation to produce lipophilic molecular complex which imparts stability, increases absorption and bioavailability of phytoconstituent. Curcumin, obtained from turmeric (Curcuma longa), has a wide range of biological activities. The poor solubility and wettability of curcumin are responsible for poor dissolution and this, in turn, results in poor bioavailability. To overcome these limitations, the curcumin-loaded nano phytosomes were developed to improve its physicochemical stability and bioavailability. Objective: The objective of the present research work was to develop nano-phytosomes of curcumin to improve its physicochemical stability and bioavailability. Methods: Curcumin-loaded nano phytosomes were prepared by using phospholipid Phospholipon 90 H using a modified solvent evaporation method. The developed curcumin nano phytosomes were evaluated by particle size analyzer and differential scanning calorimetry (DSC). Results: Results indicated that phytosomes prepared using curcumin and lipid in the ratio of 1:2 show good entrapment efficiency. The obtained curcumin phytosomes were spherical in shape with a size less than 100 nm. The prepared nano phytosomal formulation of curcumin showed promising potential as an antioxidant. Conclusion: The phytosomal complex showed sustained release of curcumin from vesicles. The sustained release of curcumin from phytosome may improve its absorption and lowers the elimination rate with an increase in bioavailability.

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