The genus Polygonum: An updated comprehensive review of its ethnomedicinal, phytochemical, pharmacological activities, toxicology, and phytopharmaceutical formulation.

Polygonum is a plant genus that includes annual and perennial species and is found at various temperatures, from northern temperate regions to tropical and subtropical areas. The genus Polygonum has been used for centuries for various disorders, including hypertension, intestinal and stomach pain, dysuria, jaundice, toothaches, skin allergies, hemorrhoids, cardiac disorders, kidney stones, hemostasis, hyperglycemia, and others. Various databases, including Google Scholar, Scifinder, ScienceDirect, PubMed, Scopus, ResearchGate, and Web of Science, were utilized to collect pertinent scientific literature data. According to bibliographic studies, the Polygonum genus possesses various compounds from different families, including phenolic acids (gallic acid, caffeic acid, quinic acid, p-coumaric acid, ferulic acid, protocatechuic acid, chlorogenic acid, and many other compounds), flavonoids (quercetin, catechin, epicatechin, quercitrin, kaempferol, myricetin, etc.), tannins, stilbenes (polydatin and resveratrol), terpenes (α-pinene, ß-caryophyllene and ß-caryophyllene oxide, bisabolene, ß-farnesene, etc.), fatty acids (decanoic acid, lauric acid, linoleic acid, oleic acid, palmitic acid, stearic acid, dodecanoic acid), polysaccharides, and others. Various chemical and biological activities (in vitro and in vivo), such as antioxidant, antimicrobial, anticancer, antitumor, anti-inflammatory, antidiabetic, antiparasitic, hepatoprotective, neuropharmacological, gastroprotective, diuretic, antipyretic, and others, have been described in several biological studies involving this species. An updated summary of Polygonum species and their ethnomedicinal, phytochemical, toxicological, pharmacological, and phytopharmaceutical formulations is necessary. Considering the numerous potentialities of the Polygonum species and their wide-ranging use, it is extremely essential to provide knowledge by compiling the accessible literature to identify the topics of intense investigation and the main gaps to better design future studies. The objective of this review is to give readers a better understanding, greater comprehension, and in-depth knowledge of the genus Polygonum's traditional applications, phytochemistry, pharmacology, toxicological features, and galenic formulation. Several species of this genus have been detailed in this review, including those that were frequently used in traditional medicine (P. minus, P. aviculare, P. hydropiper, P. cuspidatum, and P. multiflorum) and many of the genus' therapeutic species, like P. equisetiforme, which do not get enough attention.

Chitosan-PNIPAM Thermogel Associated with Hydrogel Microspheres as a Smart Formulation for MSC Injection.

Regenerative medicine based on cell therapy has emerged as a promising approach for the treatment of various medical conditions. However, the success of cell therapy heavily relies on the development of suitable injectable hydrogels that can encapsulate cells and provide a conducive environment for their survival, proliferation, and tissue regeneration. Herein, we address the medical need for cyto- and biocompatible injectable hydrogels by reporting on the synthesis of a hydrogel-forming thermosensitive copolymer. The copolymer was synthesized by grafting poly(N-isopropylacrylamide-co-carboxymethyl acrylate) (PNIPAM-COOH) onto chitosan through amide coupling. This chemical modification resulted in the formation of hydrogels that exhibit a sol-gel transition with an onset at approximately 27 °C, making them ideal for use in injectable applications. The hydrogels supported the survival and proliferation of cells for several days, which is critical for cell encapsulation. Furthermore, the study evaluates the addition of collagen/chitosan hybrid microspheres to support the adhesion of mesenchymal stem cells within the hydrogels. Altogether, these results demonstrate the potential of the PNIPAM-chitosan thermogel for cell encapsulation and its possible applications in regenerative medicine.

Dual Cross-Linked Stimuli-Responsive Alginate-Based Hydrogels.

Sodium alginate with different molecular weights (55, 170, and 320 kg mol-1) were chemically modified by grafting methacrylic moieties onto the hydroxyl groups of the alginate backbone. The methacrylation was optimized to obtain different degrees of modification. Chemically cross-linked hydrogels were obtained following UV-light irradiation in the presence of a photoinitiator. The swelling behavior and the mechanical properties were observed to depend on both the degree of methacrylation and the alginate molecular weight. Due to the chain entanglement present in high-viscosity sodium alginate, lower degrees of modification were required to tune the hydrogel properties. Moreover, in the presence of Ca2+, secondary cross-linking was introduced by the coordination of the alginate guluronate moieties with the Ca2+ ions. The addition of this secondary cross-linking caused fast volume shrinkage and a reinforcement of the mechanical properties. The secondary cross-linking was reversible, and the hydrogels regained their original shape for at least three cycles. Additionally, the dual cross-linked network can be used to induce adhesion between hydrogels and serve as a building block for self-folding actuators.

Influence of Extraction Techniques and Solvents on the Antioxidant and Biological Potential of Different Parts of Scorzonera undulata.

The genus Scorzonera has various medicinal values. Species belonging to this genus were traditionally used as drugs or in food. The current study aimed to determine the phytochemical composition, antioxidant activity, and biological properties of the tuber, leaf, and flower of Scorzonera undulata extracts, collected from the southwest of Tunisia. Phenolic compounds from the three parts were extracted using two solvents (water and ethanol) and two extraction techniques (maceration and ultrasound). The total phenolic content was measured by the Folin-Ciocalteu assay. Furthermore, the chemical composition of Scorzonera undulata extract was also investigated by the LC-ESI-MS method using phenolic acid and flavonoid standards. The variation of the extraction methods induced a variation in the real potentialities of the three parts in terms of bioactive molecules. However, the aerial part of S. undulata (leaves and flowers) showed, in general, the highest phenolic contents. Twenty-five volatile compounds have been detected by GC-MS in S. undulata extracts; among them, fourteen were identified before derivatization. The DPPH test showed that the aerial part of the plant has a higher antioxidant activity compared to the tuber (25.06% at 50 µg/mL for the leaf ethanolic extract obtained by ultrasound extraction). For most biological activities (anti-Xanthine, anti-inflammatory, and antidiabetic (alpha-amylase and alpha-glucosidase)), the aerial parts (flowers and leaves) of the plant showed the highest inhibition than tubers.

In Vitro and In Silico Studies of Two 1,4-Naphthoquinones and Their Topical Formulation in Bigels.

BACKGROUND: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving diffusion and bioavailability of NQs into the skin. OBJECTIVE: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application. METHODS: Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as the non-polar solvent and span 65 as an organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a "Franz cell" in vitro permeation model. RESULTS: Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds with LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC50 value: 2.6 and 9.8 µM). The M1 release from bigels was faster and more efficient than that of M2. CONCLUSION: M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.

Bio-inspired apatite particles limit skin penetration of drugs for dermatology applications.

Most treatments of skin pathologies involve local administration of active agents. One issue can however be the partial transcutaneous diffusion of the drug to blood circulation, leading to undesirable effects. In this work, the original use of submicron mineral particles based on bio-inspired calcium phosphate apatite was explored for the first time as drug carriers for favoring topical delivery. The permeation of a model drug across synthetic and biological membranes was investigated in both static and dynamic conditions. Our data show that adsorption of the drug on the apatite particles surface drastically limits its permeation, with lower effective diffusion coefficients (Peff) and smaller total released amounts. The retention of the apatite colloidal particles on porcine ear skin explants surface was demonstrated by combining histological observations and Raman confocal microscopy. All results converge to show that association of the drug to apatite particles favors skin surface effects. These findings point to the relevance of mineral-based particles as drug carriers for local delivery to the skin, and open the way to novel applications of bio-inspired apatites in dermatology. STATEMENT OF SIGNIFICANCE: Calcium phosphates (CaP) are major biomaterials in orthopedics and dentistry. Their resemblance to bone mineral allows new applications beyond bone repair, e.g. in nanomedicine. In 2018, a 14-page detailed review (M. Epple, Acta Biomaterialia 77 (2018) 1-14) provided clear facts in favor of the non-toxicity of nanosized CaP as an answer to discussions from EU and US study groups, thus clarifying the path to novel applications of nano CaP. In the present paper, bio-inspired apatite nanoparticles are used for the first time as drug carriers for dermatology for drastically limiting drug transcutaneous permeation and retaining a topical effect. We demonstrate this proof of concept via permeation cell tests, histology, Raman microscopy and photoluminescence after application on porcine ear skin.

The antioxidant 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone inhibits acetyl-cholinesterase activity and amyloid ß42 aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease.

Alzheimer's disease is characterized by amyloid ß aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Aß42 aggregation. Such investigation was encouraged by the in vitro high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC50 values of 9.8 and 4.3 µM for ABTS and reducing power, respectively. The ability of DDN to counteract Aß42 aggregation was evaluated by thioflavine-T assay. Strong inhibition of Aß42 aggregation of more than 90% at 25 µM was measured. Moreover, results showed that DDN inhibited AChE (IC50 = 14.5 µM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood-brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.

Nanomedicine: Interaction of biomimetic apatite colloidal nanoparticles with human blood components.

This contribution investigates the interaction of two types of biomimetic-apatite colloidal nanoparticles (negatively-charged 47nm, and positively-charged 190nm NPs) with blood components, namely red blood cells (RBC) and plasma proteins, with the view to inspect their hemocompatibility. The NPs, preliminarily characterized by XRD, FTIR and DLS, showed low hemolysis ratio (typically lower than 5%) illustrating the high compatibility of such NPs with respect to RBC, even at high concentration (up to 10mg/ml). The presence of glucose as water-soluble matrix for freeze-dried and re-dispersed colloids led to slightly increased hemolysis as compared to glucose-free formulations. NPs/plasma protein interaction was then followed, via non-specific protein fluorescence quenching assays, by contact with whole human blood plasma. The amount of plasma proteins in interaction with the NPs was evaluated experimentally, and the data were fitted with the Hill plot and Stern-Volmer models. In all cases, binding constants of the order of 10(1)-10(2) were found. These values, significantly lower than those reported for other types of nanoparticles or molecular interactions, illustrate the fairly inert character of these colloidal NPs with respect to plasma proteins, which is desirable for circulating injectable suspensions. Results were discussed in relation with particle surface charge and mean particle hydrodynamic diameter (HD). On the basis of these hemocompatibility data, this study significantly complements previous results relative to the development and nontoxicity of biomimetic-apatite-based colloids stabilized by non-drug biocompatible organic molecules, intended for use in nanomedicine.

Adsorption of nucleotides on biomimetic apatite: The case of cytidine 5' monophosphate (CMP).

The chemical interaction between DNA macromolecules and hard tissues in vertebrate is of foremost importance in paleogenetics, as bones and teeth represent a major substrate for the genetic material after cell death. Recently, the empirical hypothesis of DNA "protection" over time thanks to its adsorption on hard tissues was revisited from a physico-chemical viewpoint. In particular, the existence of a strong interaction between phosphate groups of DNA backbone and the surface of apatite nanocrystals (mimicking bone/dentin mineral) was evidenced on an experimental basis. In the field of nanomedicine, DNA or RNA can be used for gene transport into cells, and apatite nanocarriers then appear promising. In order to shed some more light on interactions between DNA molecules and apatite, the present study focuses on the adsorption of a "model" nucleotide, cytidine 5' monophosphate (CMP), on a carbonated biomimetic apatite sample. The follow-up of CMP kinetics of adsorption pointed out the rapidity of interaction with stabilization reached within few minutes. The adsorption isotherm could be realistically fitted to the Sips model (Langmuir-Freundlich) suggesting the influence of surface heterogeneities and adsorption cooperativity in the adsorption process. The desorption study pointed out the reversible character of CMP adsorption on biomimetic apatite. This contribution is intended to prove helpful in view of better apprehending the molecular interaction of DNA fragments and apatite compounds, independently of the application domain, such as bone diagenesis or nanomedicine. This study may also appear informative for researchers interested in the origins of life on Earth and the occurrence and behavior of primitive biomolecules.

Synthesis, texture, and photoluminescence of lanthanide-containing chitosan-silica hybrids.

Three different types of photoluminescent hybrid materials containing trivalent lanthanide (Ln(3+) = Eu(3+), Tb(3+)) ions, chitosan, and silica have been prepared with different structural features. The different silica sources lead to diverse microstructures of hybrid materials, with silica being homogeneously dispersed in the chitosan materials (LnChS-H), or forming a core-shell morphology. Postsynthesis treatment is necessary for embedding the luminescent probe. The Ln(3+)-based materials have been investigated by photoluminescence spectroscopy (12-300 K). The chitosan-Eu(3+)-related local environment is maintained in the EuChS-H hybrid material. The emission features of the core-shell materials are characterized by the presence of two Eu(3+) distinct local environments, one associated with the chitosan core and the other with the silica shell.