Good Bioactivity Research Articles

Magnetic bioactive glass nano-heterostructures: a deeper insight into magnetic hyperthermia properties in the scope of bone cancer treatment.

Primary bone cancers commonly involve surgery to remove the malignant tumor, complemented with a postoperative treatment to prevent cancer resurgence. Studies on magnetic hyperthermia, used as a single treatment or in synergy with chemo- or radiotherapy, have shown remarkable success in the past few decades. Multifunctional biomaterials with bone healing ability coupled with hyperthermia property could thus be of great interest to repair critical bone defects resulting from tumor resection. For this purpose, we designed superparamagnetic and bioactive nanoparticles (NPs) based on iron oxide cores (γ-Fe2O3) encapsulated in a bioactive glass (SiO2-CaO) shell. Nanometric heterostructures (122 ± 12 nm) were obtained through a two-step process: co-precipitation of 16 nm sized iron oxide NPs, followed by the growth of a bioactive glass shell via a modified Stöber method. Their bioactivity was confirmed by hydroxyapatite growth in simulated body fluid, and cytotoxicity assays showed they induced no significant death of human mesenchymal stem cells after 7 days. Calorimetric measurements were carried out under a wide range of alternating magnetic field amplitudes and frequencies, considering clinically relevant parameters, and some were made in viscous medium (agar) to mimic the implantation conditions. The experimental specific loss power was predictable with respect to the Linear Response Theory, and showed a maximal value of 767 ± 77 W gFe-1 (769 kHz, 23.9 kA m-1 in water). An interesting value of 166 ± 24 W gFe-1 was obtained under clinically relevant conditions (157 kHz, 23.9 kA m-1) for the heterostructures immobilized in agar. The good biocompatibility, bioactivity and heating ability suggest that these γ-Fe2O3@SiO2-CaO NPs are a promising biomaterial to be used as it is or included in a scaffold to heal bone defects resulting from bone tumor resection.

Synthesis and Characterization of Sol-Gel derived SiO2-Na2O-CaO-P2O5-SrO-Ag2O Bioglass

Bioactive glass (BG) is known as the third generation of biomaterials due to its well-known properties such as good biocompatibility, high bioactivity and osteoconductive. Therefore, they have received much attention in recent years and synthesized in many different compositions for certain properties. However, bacterial adhesion during implantation and recurrence of infection after implantation is a serious problem, which leads the wound to be slow in healing rate. Silver (Ag) is famous as an antibacterial agent and it has been widely used as an antimicrobial agent because of its highly promising antibacterial and anti-inflammatory properties. Therefore, in this study, the series of silver doped bioactive glass 50.77SiO2–20.39CaO–3SrO–(24.12-x) Na2O–1.72P2O5–xAg2O (x = 0, 1, 2, 3 mol %) were synthesized by the sol-gel method. The structural properties of synthesized bioglass were characterized using X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). XRD results showed that after Ag was doped into the bioglass formulation, the phase transformation from amorphous phase to crystalline phase was detected. This phase transformation occurs due to the decomposition of silver nitrate raw material to metallic silver at 200 °C during the calcination process. However, there is not much difference in FTIR spectra for all synthesized samples (with and without doped Ag2O). Therefore, in this study, it can be concluded that Ag2O doping does not affect the functional groups of bioglass.

In situ preparation of hydroxyapatite in lamellar liquid crystals for joint lubrication and drug delivery.

Arthritis is a disease that seriously affects the quality of human life, which is partly caused by the reduction of joint lubrication performance. Thus, for the treatment of arthritis, how to improve the lubrication performance of joints is important. The lamellar liquid crystals (LLCs) systems have the potential to be used as joint lubrication due to their double-layer structure and good biocompatibility, however, the LLCs system alone could not provide a satisfactory lubrication effect. Herein, this work synthesized hydroxyapatite (HAP) in situ inside Tween 85/Tween 80/H2O LLCs to construct a biocompatible HAP/Tween 85/Tween 80/H2O LLCs (HAP/LLCs) lubrication system with both sustained drug release properties and anti-wear properties. HAP is the main component of bone with good stability and bioactivity. The LLCs have good lubricating and drug-carrying properties. The impact of HAP on the structure and lubrication properties of LLCs, the mechanism of friction, and the anti-wear reduction of HAP/LLCs were investigated. Moreover, the drug release behavior of the ibuprofen-loaded HAP/LLCs during the friction process was also studied. The results indicated that the addition of HAP could improve the lubricity performance of LLCs. The cumulative drug releasing increased with the friction frequency and was less affected by the load. The related studies provided the theoretical basis for HAP/LLCs for joint lubrication and synergistic therapy.

Amalgamation of nano hydroxyapatite bioceramics for electrical and optical studies

Calcium phosphate minerals (HAp) are the key component of human bones and teeth. The HAp nanorods can perform a good biocompatibility and bioactivity. In this work, HAp powders are synthesized via a simple route by hydrothermal treatment. The resultant HAp samples are rod-like crystalline, where the morphological and particle dimensions can be customized by changing the pH conditions. The prepared HAp powder samples confirmation results are discussed using FT-IR, scanning electron microscopy, XRD, and impedance spectroscopy. FT-IR investigation confirmed that the occurrence of phosphate, carbonate and water molecules for all the samples and the transmittance decreases with pH. The acidic, base and alkaline nature of the synthesised samples are analysed using XRD studies. It results as the pH increases, significant reduction in crystallites size of HAp occurs. The average crystalline size of HAp nanorod is maximum (43.089 nm) for pH4. The SEM images of the synthesized HAp samples obtained, displays nanorods with excellent uniformity which depends on pH value. The particle diameter is estimated in the range of 10 nm to 45 nm. Electrical conductivity and dielectric function are studied using impedance spectroscopy. It can be massively helpful recognition for the presence of conduction mechanism in the synthesised HAp samples. The electrical and the optical properties may be tuned by altering the pH value which is concluded from the current work.

Dissolution and Bio-compatibility of ZnO Doped Bioactive Glasses after In Vitro Experiment

This work presents the study of 60SiO2-(36-x)CaO-4P2O5-xZnO (x=1, 3, 5 mol.%) glasses synthesized by a modified sol-gel method based on a hydrothermal reaction. The thermal morphology of the glass systems was evaluated by the Thermogravimetric analysis-differential scanning calorimetry (TG-DSC) method. The in vitro assay for dissolution was evaluated by the Inductively coupled plasma-optical emission spectroscopy (ICP-OES) method. Biocompatibility testing was performed with L-929 fibroblast cells. The results show that the ZnO-doped glass systems show good bioactivity and biocompatibility.

In silico, ADMET and Docking Analysis for the Compounds of Chloroform Extract of Tinospora cardifolia (Wild.) Identified by GC-MS and Spectral Analysis for Antidiabetic and Anti-Inflammatory Activity

The present study was aimed to phytochemical and GC-MS analysis for chloroform extract of Tinospora cardifolia. The structure of the compounds was further confirmed by UV-spectroscopy and FTIR study. The in silico study like molecular, physico-chemical and drug likeliness property was carried out by computational approaches for the identified molecules. Further toxicity potential and pharmacokinetic profile were also determined. The study was carried out using OSIRIS data warrior and Swiss ADME tools. The docking analysis was carried out for the antidiabetic and anti-inflammatory profiles. The compounds were targeted for α-glucosidase, peroxisome proliferator-activated receptor, glucose transporter-1, cyclo-oxygenase-1 & 2 inhibitions. There were around 12 compounds identified by GC-MS analysis. All the compounds exhibited moderate to good drug likeliness and pharmacokinetic potentials. The molecules showed a good bioactivity score against enzyme receptors. The ADMET prediction showed PGP and CYP-inhibitory effects with the least toxic profile. The docking analysis showed strong binding affinity of [1S-(1α,3aα,4α,6aα)]-1H,3H-furo[3,4-c]furan tetrahydrophenyl (molecule-7) on targeted proteins under investigation.

Electrospun Polycaprolactone/Hydroxyapatite (PCL/HAp) microfibers as potential biomaterials for tissue engineering

Among several methods to fabricate microfiber based scaffolds, electrospinning is widely used due to its simplicity, low-cost and flexibility. In this study, fabrication of Polycaprolactone/Hydroxyapatite (PCL/HAp) microfibers by one-step electrospinning was investigated. HAp was synthesized via precipitation method using Ca(OH)2 and H3PO4 as the precursors. The effect of the electrospinning process parameters on morphology and diameter of PCL/HAp fibers was studied. Results indicated that precipitated HAp presented in spherical morphology and high crystallinity. The dispersion of HAp into PCL matrix was proved to produce the porous microfibers with interconnected pores. It is expected to improve mechanical performance and good bioactivity due to the incorporation of HAp. Furthermore, PCL/HAp fibrous scaffolds aim to mimic the extracellular matrix (ECM) structure and biological function if they were used in bone tissue regeneration.

Identification of Antidiabetic and Anti-inflammatory Potential Compounds of Ethylacetate Extract of Tinospora cardifolia (Wild) Identified by GC-MS and Spectral Analysis: A Computational Approach

The present study was aimed to the phytochemical and GC-MS analysis for ethyl acetate extract of Tinospora cardifolia. The structure of the compounds was further confirmed by UV-spectroscopy and FTIR study. The in silico study like molecular, physico-chemical and drug likeliness property was carried out by computational approaches for the identified molecules. Further toxicity potential and pharmacokinetic profile were also determined. The study was carried out using OSIRIS data warrior and Swiss ADME tools. The docking analysis was carried out for the antidiabetic and anti-inflammatory profiles. The compounds were targeted for α-glucosidase, peroxisome proliferator-activated receptor, glucose transporter-1, cyclo-oxygenase-1 & 2 inhibitions. About 12 compounds were identified by GC-MS analysis. All the compounds exhibited moderate to good drug likeliness and pharmacokinetic potentials. The molecules showed a good bioactivity score against enzyme receptors. The ADMET prediction showed PGP and CYP-inhibitory effects with the least toxic profile. The docking analysis showed good binding affinity of that 1,4-bis(3,4,5-trimethoxy phenyl)hexahydrofuro[3,4-c]furan (Molecule-10) have strong binding affinity on targeted proteins under investigation.

Dynamic biological interfaces functionalized fructose-responsive immunomagnetic beads for high-efficient and high-purity exosome enrichment

Enrichment of exosomes with high structural and functional integrity is a critically important step before downstream applications in biological and clinical domains. In this work, dynamic biological interfaces functionalized fructose-responsive immunomagnetic beads (Fr-IMBs) were fabricated by incorporating the dynamic biological interfaces composed of dopamine and 4-carboxyphenylboronic acid with immunomagnetic beads. These fabricated Fr-IMBs were successfully applied to capture the MCF-7 exosomes with a high capture efficacy of 91.0%. After incubation with fructose, the molecular structure of the dopamine-boronic acid complexation can be rearranged and the antibody (anti-CD63) bound exosomes were released competitively, with a yield greater than 79.8%. Those exosomes that underwent both immunomagnetic separation and fructose triggered release remained their good bioactivity to promote MCF-7 cell migration. Better yet, exosomes enriched by Fr-IMBs possessed higher purity and better preservation of tumor-related molecular information of the exosomal proteins than those obtained through the ultracentrifugation approach, as proved by the comparative proteomics. These proposed sugar-responsive immunomagnetic beads may serve as biofriendly candidates in enriching useful biomarkers (e.g., cells, nucleic acids, proteins, etc.) efficiently from complex biological samples with high purity.

Mechanistic Validation of an Ergogenic T. arjuna Standardized Extract (Oxyjun®) Using a Molecular Docking Approach

The bark of the tree Terminalia arjuna commonly referred as Arjuna is widely used in Ayurveda as a therapeutic agent for heart disease. More recently, a proprietary botanical extract of T. arjuna with tradename, Oxyjun®, demonstrated cardiotonic and ergogenic benefits for the first time in a younger and healthier population. However, the mechanism of action and biological actives of this novel sports ingredient were not clear. A molecular docking approach was adopted to understand the protein-ligand interactions and establish the most probable mechanism(s) of cardio vascular actions of the phytoconstituents of the T. arjuna standardized extract (TASE). Twenty-one phytochemicals (ligands) were chosen from Arjuna and their binding affinities against eight proteins serving cardiovascular functions (target proteins) were investigated. Autodock Vina was used to carry out the molecular docking studies. Potential efficacy in humans was assessed on the basis of ADMET properties and Lipinski’s Rule of 5. We found that arjunic acid, arjungenin, arjunetin, arjunglucoside1, chrysin, kaempferol, luteolin, rhamnetin and taxifolin demonstrated good docking scores and bioactivity.

Amino acid ionic liquid-catalyzed synthesis, anti-Leishmania activity, molecular docking, molecular dynamic simulation, and ADME study of 3,4-dihydropyrimidin-2(1H)-(thio)ones

The synthesis of 3,4-dihydropyrimidin-2(1H)-(thio)one (DHPM) derivatives involving aromatic aldehyde, β-ketoesters and urea/thiourea using prolinium hydrogen sulfate (ProHSO4) as a catalyst has been studied. A variety of DHPM derivatives were obtained in high yield under solvent-free conditions in a short reaction time. The in-vitro screening of antileishmanial activity of both the oxo and the thioxo compounds showed significant activity against extracellular promastigotes. The aldehyde substituted at C-4 position with methyl (4g) in the oxo series and chloro (4m), methyl (4n) in the thioxo series imparted good bioactivity, with >80% reduction in viability at 50 µg/mL, with IC50 values 29.3, 29.3, and 28.3 µg/mL, respectively. Molecular docking study of the compound 4m displayed −6.4 kcal/mol binding energy. According to 50 ns molecular dynamics simulation study Leishmania major pteridine reductase 1 (PTR1) interacts well with the amino acid residues Phe-109, Leu-222, and Val-226. The in silico ADME study showed good drug-likeness properties.

Effects of a novel self-assembling peptide scaffold on bone regeneration and controlled release of two growth factors.

RADA16 is a self-assembling peptide material with good bioactivity. To improve the bioactivity of a material, some specific functional motifs can be added to its peptide sequence. Here, we report a self-assembling peptide nanogel, RADA16-RGD, that has better bioactivity than RADA16 and can simultaneously carry and control the release of two growth factors, VEGF and BMP-2, which have synergistic effects on bone formation. The peptide materials were characterized by transmission electron microscopy and scanning electron microscopy. The mechanical properties of the peptides were evaluated by the rheology test. The biocompatibility of the materials was evaluated via the use of the CCK-8 test, live/dead staining and confocal laser scanning microscopy. Osteogenesis capability in vitro was evaluated by means of ALP staining, extracellular matrix mineralization and detection of osteogenic markers. The controlled release of growth factors was examined by ELISA. The results showed that RADA16-RGD exhibited a better ability than RADA16 to promote cell proliferation, adhesion and bone formation. In addition, RADA16-RGD had good biocompatibility and exhibited effective controlled release of VEGF and BMP-2. More importantly, compared with RADA16-RGD loaded with single growth factor or without growth factors, RADA16-RGD loaded with two growth factors exhibited a stronger ability to promote cell proliferation and osteogenesis. This study provides a promising strategy for the application of self-assembling peptides to promote osteogenesis and controlled release of proteins.

Metformin-loaded \u03b2-TCP/CTS/SBA-15 composite scaffolds promote alveolar bone regeneration in a rat model of periodontitis

Periodontitis is a progressive infectious inflammatory disease, which leads to alveolar bone resorption and loss of periodontal attachment. It is imperative for us to develop a therapeutic scaffold to repair the alveolar bone defect of periodontitis. In this study, we designed a new composite scaffold loading metformin (MET) by using the freeze-drying method, which was composed of β-tricalcium phosphate (β-TCP), chitosan (CTS) and the mesoporous silica (SBA-15). The scaffolds were expected to combine the excellent biocompatibility of CTS, the good bioactivity of β-TCP, and the anti-inflammatory properties of MET. The MET-loaded β-TCP/CTS/SBA-15 scaffolds showed improved cell adhesion, appropriate porosity and good biocompatibility in vitro. This MET composite scaffold was implanted in the alveolar bone defects area of rats with periodontitis. After 12 weeks, Micro-CT and histological analysis were performed to evaluate different degrees of healing and mineralization. Results showed that the MET-loaded β-TCP/CTS/SBA-15 scaffolds promoted alveolar bone regeneration in a rat model of periodontitis. To our knowledge, this is the first report that MET-loaded β-TCP/CTS/SBA-15 scaffolds have a positive effect on alveolar bone regeneration in periodontitis. Our findings might provide a new and promising strategy for repairing alveolar bone defects under the condition of periodontitis.

Development of an Efficient Immunosensing Platform by Exploring Single-Walled Carbon Nanohorns (SWCNHs) and Nitrogen Doped Graphene Quantum Dot (N-GQD) Nanocomposite for Early Detection of Cancer Biomarker.

In this work, a novel electrochemical immunosensor based on nitrogen doped graphene quantum dot (N-GQD) and single-walled carbon nanohorns (SWCNHs) was developed for the detection of α-fetoprotein (AFP), a cancer biomarker. Thus, to fabricate the platform of the immunosensor, nanocomposite architecture was developed by decorating N-GQD on the surface of the SWCNHs. The resulting hybrid architecture (N-GQD@SWCNHs) functioned as an exceptional base for the immobilization of antibody (Anti-AFP) through carbodiimide reaction with good stability and bioactivity. The immunosensor was prepared by evenly distributing the bioconjugates (N-GQD@SWCNHs/Anti-AFP) dispersion on the surface of the glassy carbon electrode, and subsequently blocking the remaining active sites by bovine serum albumin to prevent the nonspecific adsorption. Cyclic voltammetry and electrochemical impedance spectroscopy technique was employed to investigate the assembly process of the immunosensor. Under optimal conditions, the immunosensor exhibited a broad dynamic range in between 0.001 ng/mL to 200 ng/mL and a low detection limit of 0.25 pg/mL. Furthermore, the sensor showed high selectivity, desirable stability, and reproducibility. Measurements of AFP in human serum gave outstanding recovery within 99.2% and 102.1%. Thus, this investigation and the amplification strategy exhibited a potential role of the developed nanocomposite based sensor for early clinical screening of cancer biomarkers.

Hydrothermal treatment of the silver-incorporated MAO coated Ti6Al7Nb alloy

In this study, Ti6Al7Nb titanium alloy has been subjected to micro-arc oxidation (MAO) process and hydrothermal (HT) treatment sequentially. MAO process was conducted in calcium acetate hydrate (Ca(CH3COO)2.H2O) and disodium hydrogen phosphate anhydrous (Na2HPO4) containing reference electrolyte with and without the addition of silver acetate (AgC2H3O2) to provide antibacterial efficiency along with good bioactivity. Subsequently, HT treatment was employed to MAO’ed samples in an alkaline solution (pH = 11) at 230°C. HT treatment induced the covering of the titanium oxide (TiO2)-based MAO coatings with 1–2 µm thick exterior layer composed of nano-rods of titanium oxide and hexagonal columns of hydroxyapatite (HA). The presence of silver (Ag) in the MAO coating refined the structure of the HT treatment-induced exterior layer. As the primary indication of enhancement of the bioactivity, HT treatment accelerated apatite formation in the SBF solution irrespective of the silver presence, which delayed the apatite formation on the untreated MAO coatings. Moreover, HT treatment reduced the release of silver from the coatings into the SBF solution.

Neuroinflammation and Modulation Role of Natural Products After Spinal Cord Injury.

Spinal cord injury (SCI) is a severe traumatic injury of the central nervous system, characterized by neurological dysfunction and locomotor disability. Although the underlying pathological mechanism of SCI is complex and remains unclear, the important role of neuroinflammation has been gradually unveiled in recent years. The inflammation process after SCI involves disruption of the blood–spinal cord barrier (BSCB), activation of gliocytes, infiltration of peripheral macrophages, and feedback loops between different cells. Thus, our first aim is to illustrate pathogenesis, related cells and factors of neuroinflammation after SCI in this review. Due to the good bioactivity of natural products derived from plants and medicinal herbs, these widely exist as food, health-care products and drugs in our lives. In the inflammation after SCI, multiple natural products exert satisfactory effects. Therefore, the second aim of this review is to sum up the effects and mechanisms of 25 natural compounds and 7 extracts derived from plants or medicinal herbs on neuroinflammation after SCI. Clarification of the SCI inflammation mechanism and a summary of the related natural products is helpful for in-depth research and drug development.

Effective drug delivery system based on hydrophobin and halloysite clay nanotubes for sustained release of doxorubicin

Halloysite clay nanotubes (HNTs), which are natural nano-clays with a hollow tubular structure, have been widely studied for drug delivery and sustained release while largely limited by the complexity of surface modification. Hydrophobins are small surface-active proteins produced by filamentous fungi that self-assemble into nanolayers at hydrophobic/hydrophilic interfaces. In this study, hydrophobins including HGFI-his and a mutant MGF6-his were used as unique biomaterials to modify HNTs to construct drug delivery systems. Water contact angle and HNT dispersion assays demonstrated that MGF6-his performed better surface activity and rendered HNT more lasting stability than HGFI-his. MGF6-his-coated HNTs loaded with the anticancer drug doxorubicin hydrochloride ([email protected]) were further prepared and characterized by dynamic light scattering, fluorescence microscopy and transmission electron microscopy. This composite was found to form nanoparticles in size of 375.62 ± 17.85 nm and possess better dispersion stability owing to the coating of the MGF6-his. Excellent sustained release was observed at pH 3.3 and 5.0 but not at pH 7.4 in in vitro release assay. Moreover, an in vitro cytotoxicity assay showed that this system exhibited good bioactivity, killing about 70% of HeLa cells at a concentration of 150 μg/mL. Herein, the hydrophobin MGF6-his was designed as a novel approach for HNT surface modification, facilitating the dispersion and prolonging drug release simultaneously. These findings suggested that coating with hydrophobins has potential as a novel approach to develop HNT-based drug delivery systems.

Screening of compounds from Nigerian antidiabetic plants as protein tyrosine phosphatase 1B inhibitor

Several studies have established the antidiabetic properties of several traditional Nigerian plants, but only limited studies have elucidated their mechanism of action. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of the insulin signalling pathway, is a drug target for the management of diabetes. However, to date, there is no available commercial drug with specificity for targeting PTP1B. This study sought to investigate compounds identified in Nigerian medicinal plants with therapeutic potential as inhibitors of PTP1B. A chemical library comprising more than a thousand compounds identified from Nigerian medicinal plants was docked with PTP1B; The prepared compounds were filtered using Lipinski's rule of five (RO5) and consequently used for molecular docking analysis. The binding free energy of the best ten (10) drug-like compounds was computed, then their pharmacokinetic and toxicological features were determined and compared with three standard PTP1B inhibitors. A 2D-QSAR model was constructed from an experimental dataset retrieved from literature before confirming its robustness through external validation. Finally, the reactivity and stability of the compounds, coupled with atomic regions rich in electron acceptor and donor capacity, were investigated using Jaguar fast engine. The ten top-scoring compounds had a more favourable binding affinity with PTP1B than the standard inhibitors, and they interacted with crucial residues that enhance inhibition of the protein. Generally, the natural compounds had remarkable pharmacokinetic properties and minor unwanted toxicities compared with the reference inhibitors. The external validated QSAR model (KPLS_Molprint2D_9) demonstrated that the compounds had good bioactivity against PTP1B. Through DFT calculation, blighinone was found to be the most chemically reactive compound, and electron deficit and rich regions of the compounds accepted and donated hydrogen to PTP1B amino acid residues during intermolecular interaction. The knowledge obtained in this study may help reveal natural compounds that can become potent inhibitors of PTP1B.

Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.

Allosteric modulators (AMs) of G-protein coupled receptors (GPCRs) are desirable drug targets because they can produce fewer on-target side effects, improved selectivity, and better biological specificity (e.g., biased signaling or probe dependence) than orthosteric drugs. An underappreciated source for identifying AM leads are peptides and proteins—many of which were evolutionarily selected as AMs—derived from endogenous protein-protein interactions (e.g., transducer/accessory proteins), intramolecular receptor contacts (e.g., pepducins or extracellular domains), endogenous peptides, and exogenous libraries (e.g., nanobodies or conotoxins). Peptides offer distinct advantages over small molecules, including high affinity, good tolerability, and good bioactivity, and specific disadvantages, including relatively poor metabolic stability and bioavailability. Peptidomimetics are molecules that combine the advantages of both peptides and small molecules by mimicking the peptide’s chemical features responsible for bioactivity while improving its druggability. This review 1) discusses sources and strategies to identify peptide/peptidomimetic AMs, 2) overviews strategies to convert a peptide lead into more drug-like “peptidomimetic,” and 3) critically analyzes the advantages, disadvantages, and future directions of peptidomimetic AMs. While small molecules will and should play a vital role in AM drug discovery, peptidomimetics can complement and even exceed the advantages of small molecules, depending on the target, site, lead, and associated factors.

Research progress on therapeutic potential of quercetin

Quercetin is a naturally occurring phytochemical with good bioactivity, which mainly exists in the form of glycoside in vegetables, fruits, tea, and wine and exhibits beneficial health effects. Quercetin is a dietary polyphenol that exerts the protective effects through diet or use as a food supplement. Compared with chemical agents, quercetin is widely available and safe. Quercetin has been extensively studied for its anti-diabetic, anti-hypertensive, anti-Alzheimer's disease, anti-arthritic, anti-influenza virus, anti-microbial infection, anti-aging, autophagy-regulating, and cardiovascular protective effects. Studies on its activities against different can-cer cell lines have also been reported recently. However, the poor water solubility, rapid in vivo metabolism, and short half-life of quercetin have led to its low bioavailability, thus limiting its application in the field of medicine. Quercetin nanoparticles and nanoparticle drug delivery system have been effectively utilized for enhancing its bioavailability. This paper reviewed the therapeutic potential of quercetin from both preclinical and clinical aspects and proposed solutions to improve its bioavailability, so as to provide a reference for the therapeutic application of natural compounds in the field of medicine.