Compounds Of Natural Origin Research Articles

Fucoidan alleviates the mitochondria and endoplasmic reticulum stresses in ischemic rat livers

BackgroundHepatic ischemia reperfusion (I/R) injury remains a major problem for liver surgery leading to graft dysfunction. The use of compounds of natural origin as fucoidan, a sulfated polysaccharide from brown seaweed, could have a potential clinical benefit in the treatment of ischemic diseases. Nevertheless, the accurate mechanisms of action of fucoidan on endoplasmic reticulum (ER) stress response and mitochondria after warm hepatic ischemia have not been yet investigated. Thus, the present study focused on the modulation of fucoidan effects on the signaling pathways involving the mitochondria and the ER in ischemic rat liver. MethodsMale Wistar rats were subjected to either sham operation or one hour of partial warm ischemia (70%) followed by two hours of reperfusion. Before ischemia, rats were treated with 0.9% NaCl (I/R group), fucoidan (100 mg/kg body weight) orally for 7 consecutive days (I/R-Fuc group), TUDCA (tauroursodeoxycholic acid, inhibitor of ER stress) (100 mg / kg body weight, i.v.) 10 min before ischemia (I/R-TUDCA group) or fucoidan with TUDCA (I/R-Fuc-TUDCA group). ResultsOur results showed that fucoidan and TUDCA reduced cytolysis and induced a significant improvement in antioxidant status, as compared to I/R. Interestingly, preconditioning with fucoidan resulted in significant decreased ER stress, as reflected by GRP78, p-PERK, ATF-6, XBP-1 and TRAF2. Furthermore, the phosphorylation of MAPKs (ERK, JUNK and P38) significantly diminished after fucoidan treatment. Rats undergoing fucoidan treatment protected liver against mitochondrial stress, which was correlated with low induction of apoptosis (caspase-3). Inhibition of ER stress by TUDCA administration boosted all the protective effects of fucoidan. ConclusionIn conclusion, fucoidan treatment may represent an effective strategy in reducing liver I/R injury through mitochondrial stress attenuation and ER inhibition.

Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression.

Receptors are macromolecules that transmit information regulating cell proliferation, differentiation, migration and apoptosis, play key roles in oncogenic processes and correlate with the prognoses of cancer patients. Thus, targeting receptors to constrain cancer development and progression has gained widespread interest. Small molecule compounds of natural origin have been widely used as drugs or adjuvant chemotherapeutic agents in cancer therapies due to their activities of selectively killing cancer cells, alleviating drug resistance and mitigating side effects. Meanwhile, many natural compounds, including those targeting receptors, are still under laboratory investigation for their anti-cancer activities and mechanisms. In this review, we classify the receptors by their structures and functions, illustrate the natural compounds targeting these receptors and discuss the mechanisms of their anti-cancer activities. We aim to provide primary knowledge of mechanistic regulation and clinical applications of cancer therapies through targeting deregulated receptors.

Plant- and Bacteria-Derived Compounds with Anti-Philasterides dicentrarchi Activity.

Philasterides dicentrarchi is a scuticociliate that causes high mortalities in farmed fish. Although vaccination is an effective method to prevent scuticociliatosis caused by the homologous serotype, a universal vaccine has not been developed yet. Many compounds have been shown to be toxic to this ciliate species; moreover, most of them are toxic to aquatic life and cannot be used to prevent the disease. We have evaluated the toxicity to P. dicentrarchi of several compounds of natural origin to be used to reduce parasite levels in the seawater. Ciliates were exposed to several compound concentrations, and the mortality was determined at several incubation times. Tomatine, plumbagin and 2′,4′-dihydroxychalcone displayed the highest anticiliate activity, with a dose-dependent response. The effects of these compounds on the EPC cell line were also evaluated, finding that 2′,4′-dihydroxychalcone displayed the lowest toxicity to fish cells. At 7.54 μM, 2′,4′-dihydroxychalcone inhibited 50% parasite growth but only killed about 10% of EPC cells after 24 h incubation. Finally, we evaluated the toxicity of Pseudomonas H6 surfactant (PS) to P. dicentrarchi, finding that PS was toxic to the ciliate but showed lower toxicity to EPC cells. At a concentration of 7.8 μg/mL (LC50 for the ciliate after 3 h incubation), PS killed 14.9% of EPC cells. We conclude that 2′,4′-dihydroxychalcone, and PS could be used to reduce parasite levels in seawater, thus decreasing the risk of scuticociliatosis infection in cultured fish.

Drug/Lead Compound Hydroxymethylation as a Simple Approach to Enhance Pharmacodynamic and Pharmacokinetic Properties.

Hydroxymethylation is a simple chemical reaction, in which the introduction of the hydroxymethyl group can lead to physical–chemical property changes and offer several therapeutic advantages, contributing to the improved biological activity of drugs. There are many examples in the literature of the pharmaceutical, pharmacokinetic, and pharmacodynamic benefits, which the hydroxymethyl group can confer to drugs, prodrugs, drug metabolites, and other therapeutic compounds. It is worth noting that this group can enhance the drug’s interaction with the active site, and it can be employed as an intermediary in synthesizing other therapeutic agents. In addition, the hydroxymethyl derivative can result in more active compounds than the parent drug as well as increase the water solubility of poorly soluble drugs. Taking this into consideration, this review aims to discuss different applications of hydroxymethyl derived from biological agents and its influence on the pharmacological effects of drugs, prodrugs, active metabolites, and compounds of natural origin. Finally, we report a successful compound synthesized by our research group and used for the treatment of neglected diseases, which is created from the hydroxymethylation of its parent drug.

Bioprospecting Phenols as Inhibitors of Trichothecene-Producing Fusarium: Sustainable Approaches to the Management of Wheat Pathogens.

Fusarium spp. are ubiquitous fungi able to cause Fusarium head blight and Fusarium foot and root rot on wheat. Among relevant pathogenic species, Fusarium graminearum and Fusarium culmorum cause significant yield and quality loss and result in contamination of the grain with mycotoxins, mainly type B trichothecenes, which are a major health concern for humans and animals. Phenolic compounds of natural origin are being increasingly explored as fungicides on those pathogens. This review summarizes recent research activities related to the antifungal and anti-mycotoxigenic activity of natural phenolic compounds against Fusarium, including studies into the mechanisms of action of major exogenous phenolic inhibitors, their structure-activity interaction, and the combined effect of these compounds with other natural products or with conventional fungicides in mycotoxin modulation. The role of high-throughput analysis tools to decipher key signaling molecules able to modulate the production of mycotoxins and the development of sustainable formulations enhancing potential inhibitors’ efficacy are also discussed.

Pharmacophore screening to identify natural origin compounds to target RNA-dependent RNA polymerase (RdRp) of SARS-CoV2.

Several existing drugs have gained initial consideration due to their therapeutic characteristics against COVID-19 (Corona Virus Disease 2019). Hydroxychloroquine (HCQ) was proposed as possible therapy for shortening the duration of COVID-19, but soon after this, it was discarded. Similarly, known antiviral compounds were also proposed and investigated to treat COVID-19. We report a pharmacophore screening using essential chemical groups derived from HCQ and known antivirals to search a natural compound chemical space. Molecular docking of HCQ under physiological condition with spike protein, 3C-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV2 showed − 8.52 kcal/mole binding score with RdRp, while the other two proteins showed relatively weaker binding affinity. Docked complex of RdRp-HCQ is further examined using 100 ns molecular dynamic simulation. Docking and simulation study confirmed active chemical moieties of HCQ, treated as 6-point pharmacophore to screen ZINC natural compound database. Pharmacophore screening resulted in the identification of potent hit molecule [(3S,3aR,6R,6aS)-3-(5-phenylsulfanyltetrazol-1-yl)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]N-naphthalen-ylcarbamate from natural compound library. Additionally, a set of antiviral compounds with similar chemical scaffolds are also used to design a separate ligand-based pharmacophore screening. Antiviral pharmacophore screening produced a potent hit 4-[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-(2-hydroxyphenyl)methyl]-1,5-dimethyl-2-phenylpyrazol-3-one containing essential moieties that showed affinity towards RdRp. Further, both these screened compounds are docked (− 8.69 and − 8.86 kcal/mol) and simulated with RdRp protein for 100 ns in explicit solvent medium. They bind at the active site of RdRp and form direct/indirect interaction with ASP618, ASP760, and ASP761 catalytic residues of the protein. Successively, their molecular mechanics Poisson Boltzmann surface area (MMPBSA) binding energies are calculated over the simulation trajectory to determine the dynamic atomistic interaction details. Overall, this study proposes two key natural chemical moieties: (a) tetrazol and (b) phenylpyrazol that can be investigated as a potential chemical group to design inhibitors against SARS-CoV2 RdRp.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11030-021-10358-5.

Discovery of Promising Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER), and Phosphatidylinositol-3-kinase a (PI3Ka) for Personalized Breast Cancer Treatment.

Despite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of breast cancer has now become more personalized based on the specific features of the tumor such as overexpression of growth factor receptors (Epidermal growth factor receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2)), hormone receptors (Human Estrogen receptor alpha (ER)) and kinases involved in pivotal signaling associated with growth (Phosphatidylinositol 3-kinase (PI3K)). Several chemotherapeutic agents have been developed to curb the menace, but the associated adverse drug effects cannot be overlooked. To this end, this study employed a molecular modeling approach to identify novel compounds of natural origin that can potentially antagonize the receptors (mentioned above) associated with the pathophysiology of breast cancer and at the same time pose very little or no side effects. The results of the molecular model of biological interactions between a library of 118 anthocyanins and the binding pockets of the protein targets identified 5 compounds (Pelargonin, Delphinidin 3-O-rutinoside, Malvin, Cyanidin-3-(6-acetylglucoside), and Peonidin 3-O-rutinoside) with good binding affinities to the protein targets. Further MM-GBSA calculations returned high binding energies. The specific molecular interactions between the compounds and the targets were analyzed and reported herein. Also, all the compounds exhibited good pharmacokinetic profiles and are therefore recommended for further analyses as they could be explored as new treatment options for a broad range and personalized breast cancer treatments.

Healing potential of nanocarriers containing essential oils: a literature review

Essential oils are compounds of natural origin with numerous therapeutic properties, however, there are limitations regarding their stability, being easily degraded by processes of oxidation, volatilization, heating and light, characteristics that can be overcame with the use of nanotechnology. The aim of this study was to investigate the main types of nanocarriers used to carry essential oils and to assess their healing potential. A research was carried out in the Web of Science database, without a time limit, using the Boolean descriptors and markers: nano* AND essential oils AND wound healing. Articles published in Portuguese and English, with free access to the full article on the online platform, were included in the review. The research resulted in 168 articles, of which 22 were selected to include this review according to the proposed criteria. From the studies included in this review, it was possible to observe that nanocarriers such as nanoemulsions and nanofibers were able to activate the functionality of essential oils effectively and safely, achieving success in healing and antibacterial activity, demonstrating that nanotechnology is a promising alternative to develop nanotechnology-based formulations containing essential oils for wound healing.

Effects of different stevia-to-onion ratios and heating temperatures on physicochemical and sensory attributes of onion-stevia hot water extracts

Increased consumption of artificial and intense natural sweeteners have led to serious health implications and safety issues for intended consumers. Among all natural sweeteners, steviol glycosides (SGs: stevioside & rebaudioside-A) are popularly known as zero-caloric intense sweetening compounds of natural origin. Hot water extraction (HWE) is considered ecofriendly and less expensive, and HWE extracts are safe for human consumption as compared to organic solvents extraction. Onion (Allium cepa L.) and stevia (Stevia rebaudiana) were extracted using a single factor experimental approach to determine the optimal onion-stevia hot water extract (OSHE) extraction conditions. Physicochemical and sensory attributes of onion hot water extract (OHE) and OSHE extracted at varying stevia-to-onion ratios and temperatures were investigated. The results showed that total phenolic content (TPC) increased and total flavonoid content (TFC), L*, a* and b* values decreased with corresponding increases in stevia-to-onion ratio and extraction temperature. In contrast, total soluble solids increased with increase in onion-stevia ratio, whereas pH values declined with increasing temperature. Glucose was the most dominant organic sugar in OSHE followed by sucrose and fructose. In conclusion, OSHE obtained at 115 °C and 1:100 stevia-to-onion ratio (w/w) could be produced as a natural sweetener after concentration or drying and could be exploited in beverages and cooked foods without any deteriorating quality effects with improved thermal and pH stability and fermentation resistance. Furthermore, OSHE can be manufactured as a natural sweetener because it can be extracted at high temperature and pressure using stevia leaves with only the bound water content of onion without any additional moisture from external sources. As an eco-friendly alternative of expensive enzymatic digestion or organic solvent extraction.

Structural and Functional Insights of Thiazole Derivatives as Potential Anti-inflammatory Candidate: A New Contender on Chronic and Acute SARS-CoV-2 Inflammation and Inhibition of SARS-CoV-2 Proteins

Thiazoles are notable five-membered heterocyclic rings and their moieties can be found in several biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. Inflammation is the common cause that is associated with different disorders and diseases such as psoriasis, arthritis, infections, asthma, cancer, etc. In this article, the synthesis pattern of these novel molecules are discussed and their anti-inflammatory activities against cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) were reviewed and documented. The potent 26 thiazole analogs were validated with molecular docking against main protease (6LU7) and spike binding domain ACE2 receptor (6M0J) to defeat from the COVID-19 infections. Among this, THI-9a showed excellent binding energy and affinity against deadly SAR CoV-2. The reviewed and theoretical study information strongly suggested that thiazole derivatives can be used for the development of futuristic target drugs against death-causing diseases like SAR-CoV-2.

Interleukin-6 and colorectal cancer development

Background. Colorectal cancer (CRC) is one of the most common malignancies in the world. It ranks third in the structure of cancer morbidity and second in the structure of mortality. One of the important factors leading to CRC is chronic inflammation of the intestine, in which pro-inflammatory cytokines play a crucial role. Among proinflammatory cytokines, interleukin-6 occupies one of the leading places in the pathogenesis of CRC. Therefore, it is important to elucidate the role of interleukin-6 (IL-6) in the development and progression of CRC, determine the diagnostic and prognostic value of the cytokine and analyze the application of therapeutic strategies aimed at the IL-6 signaling pathway in CRC. Purpose – to analyze the role of proinflammatory cytokine IL-6 in the development of colorectal cancer, consider the mechanisms of oncogenic action of cytokine, evaluate the results of therapeutic strategies aimed at the IL-6 signaling pathway in colorectal cancer and characterize prognostic and diagnostic value of IL-6. Data sources. Data search for review was performed in databases Pubmed, Cochrane Library, ScienceDirect. The results of research performed before May 2021 are analyzed. Relevant unpublished studies have been found in clinical trial registry of U.S. National Institutes of Health www.clinicaltrials.gov. Results. The assessment of diagnostic and prognostic value of IL-6 in patients with CRC is given. The mechanisms of IL-6 regulation of tumor growth, angiogenesis, apoptosis, metastasis in CRC are elucidated. The results of preclinical and clinical testing of monoclonal antibodies to IL-6, IL-6R, low molecular weight compounds that affect cytokine receptor signaling through gp130 and JAK-STAT, as well as drugs and compounds of natural origin, that are able to inhibit IL-6/STAT3 signal pathway, are presented. Conclusions. Strategies to block IL-6 signaling may be potentially useful in malignancies, most likely as a component of combination therapy, or in preventing adverse symptoms associated with cancer immunotherapy. Further research is needed to elucidate the exact role of classical IL-6 signaling and trans-signaling in the pathogenesis of colorectal cancer, as this may provide a basis for more targeted inhibition of the functions of this pleiotropic cytokine.

Reconceptualization of Hormetic Responses in the Frame of Redox Toxicology.

Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date.

Assessment of the quality of the southern Bug waters within the Khmelnytsky region and biotechnological ways to solve their purification

Water resources are the national wealth of each state, an important natural resource, and determine the development opportunities of most sectors of the economic complex of Ukraine. The Southern Bug River is the largest river, the basin of which is completely located in Ukraine. Due to the intensive growth of anthropogenic impact on the studied reservoir and the economic use of its resources, the quality of water in it has significantly decreased. To improve the quality of water in rivers, it is optimal to use biotechnological methods, which provide many opportunities for effective solutions to issues related to monitoring, assessment, and treatment of polluted watercourses. The aim of our study was to assess water safety, the current ecological status of the Southern Bug River within the Khmelnytsky region in three areas (Maryanivske Reservoir, Kopystyn, Shchedrivske Reservoir) and use in domestic needs, with analysis of potential risks to human health, development of new biotechnological and improvement of existing measures to improve water supply. The experimental part of the work was performed on the basis of the Khmelnytsky Regional Department of Water Resources in the laboratory at the address Khmelnytsky, st. Soborna, 29. We conducted a chemical assessment of the Southern Bug River on three indicators: salt composition (I1), tropho-saprobiological (I2), and specific toxic substances (I3). Research of river waters was carried out in order to control the MPC (maximum permissible concentrations) of substances for use in household and food needs of the population and to propose biotechnological methods of river water purification within the Khmelnytsky region. According to our research on hydrochemical characteristics, the water contained elevated levels of NH4, NO2, NO3, PO4, the average values of HSC (chemical oxygen demand) exceeded the MPC in all areas by 2 to 5 times. This may be due to exposure to organic compounds of natural origin. The content of nitrites, nitrates is within normal limits, but the content of ammonium salt exceeds the MPC up to 20 times in the village Kopystyn and from 2 to 7 times in the village of Letychiv. According to many indicators of the salt block, the maximum concentration limit was not exceeded, except for the village Kopystyn, the concentration of Magnesium (Mg) was 84.33 mg/dm3 at a rate of 40.00 mg/dm3. According to specific toxic substances, the water belonged to the III class 4 quality category, Chromium (Cr) was not detected, Manganese (Mn) and Copper (Cu) were within normal limits, although the Copper content was high. The concentration of Iron (Fe) varies in different areas and during the year, there is a case of excess Iron in the village. Kopistin up to 0.86 mg/dm3 at a rate of 0.30 mg/dm3. Iron affects the intensity of phytoplankton development and the qualitative composition of the microflora, so its concentration is subject to seasonal fluctuations. To improve the quality of water in the Southern Bug River, we have proposed the use of biotechnological methods, including those that provide many opportunities to effectively address issues related to monitoring, assessment, and treatment of polluted watercourses.

Hibiscus Flower and Olive Leaf Extracts Activate Apoptosis in SH-SY5Y Cells

Compounds of natural origin may constitute an interesting tool for the treatment of neuroblastoma, the most prevalent extracranial solid tumor in children. PRES is a commercially available food supplement, composed of a 13:2 (w/w) extracts mix of Olea europaea L. leaves (OE) and Hibiscus sabdariffa L. flowers (HS). Its potential towards neuroblastoma is still unexplored and was thus investigated in human neuroblastoma SH-SY5Y cells. PRES decreased the viability of cells in a concentration-dependent fashion (24 h IC50 247.2 ± 31.8 µg/mL). Cytotoxicity was accompanied by an increase in early and late apoptotic cells (AV-PI assay) and sub G0/G1 cells (cell cycle analysis), ROS formation, reduction in mitochondrial membrane potential, and caspases activities. The ROS scavenger N-acetyl-L-cysteine reverted the cytotoxic effects of PRES, suggesting a key role played by ROS in PRES-mediated SH-SY5Y cell death. Finally, the effects of OE and HS extracts were singularly tested and compared to those of the corresponding mixture. OE- or HS-mediated cytotoxicity was always significantly lower than that caused by PRES, suggesting a synergic effect. In conclusion, the present findings highlight the potential of PRES for the treatment of neuroblastoma and offers the basis for a further characterization of the mechanisms underlying its effects.

Potential Phytochemicals for Cancer Treatment: A Review

Today, cancer had been described as one of the deadliest diseases worldwide. It has been estimated that cancer causes about 9.9 million deaths in the year 2020. The conventional treatment for the disease involves single chemotherapy or a combination of mono-chemotherapy and or a combination of mono-chemotherapy and radiotherapy. However, there are negative sides to these approaches which have prompted the search for new therapeutic drugs. In view of this, scientific communities have started looking for innovative sources of anticancer compound of natural origin which include traditional plants. Nowadays, several studies have evaluated the anticancer properties of bioactive components (phytochemicals) derived from the plants both in vivo and in vitro. The phytochemicals are secondary metabolites or chemical compound produced during metabolic process in plants which are useful in the protection of plants. Most of these phytochemicals such as alkaloid, flavonoids, phenolic compounds, cyanidin, fisetin, genistein, gingerol kaempferol, quercetin, resveratrol possessed certain medicinal properties and found to have numerous applications in pharmaceutical industries for treatment of cancer. The paper was aimed to review some plants bioactive components (phytochemicals) used in cancer treatment.

Preparation and determination of the physical and chemical properties of the nano-gel film of bacterial cellulose

Currently, updated compounds of natural origin are becoming more and more popular as an alternative to synthetic materials. In this work, the physicochemical properties of the nanogel film of bacterial cellulose obtained by culturing the symbiosis of acetic acid bacteria Gluconacetobacter xylinus C-3 and the Hestrin-Schramm culture medium were investigated. The sorption properties in relation to goose fat were determined. It was found that the process of desorption of goose fat from the obtained nanogel film of bacterial cellulose into the buffer solution is completed after 24 hours, which indicates the optimal desorption rate for applications with prolonged action, namely, anti-burn action. The pH value of human skin changes from slightly acidic to neutral, and this confirms the possibility of manufacturing transdermal therapeutic systems based on nanogel film of bacterial cellulose impregnated with oil solutions of drugs. Thus, the prospects of using nanogel films of bacterial cellulose for creating transdermal therapeutic systems are evaluated.

Sanguiins-Promising Molecules with Broad Biological Potential.

Compounds of natural origin, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovering new medicines. In this review, we summarize the naturally occurring ellagitannins, sanguiins, which are bioactive constituents of various traditional medicinal plants, especially from the Rosaceae family. In-depth studies of sanguiin H-6 as an antimicrobial, antiviral, anticancer, anti-inflammatory, and osteoclastogenesis inhibitory agent have led to potent drug candidates. In addition, recently, virtual screening studies have suggested that sanguiin H-6 might increase resistance toward SARS-CoV-2 in the early stages of infection. Further experimental investigations on ADMET (absorption, distribution, metabolism, excretion, and toxicity) supplemented with molecular docking and molecular dynamics simulation are still needed to fully understand sanguiins’ mechanism of action. In sum, sanguiins appear to be promising compounds for additional studies, especially for their application in therapies for a multitude of common and debilitating ailments.

Phytoprogestins: Unexplored Food Compounds with Potential Preventive and Therapeutic Effects in Female Diseases.

In recent years, there has been an increasing interest in natural therapies to prevent or treat female diseases. In particular, many studies have focused on searching natural compounds with less side effects than standard hormonal therapies. While phytoestrogen-based therapies have been extensively studied, treatments with phytoprogestins reported in the literature are very rare. In this review, we focused on compounds of natural origin, which have progestin effects and that could be good candidates for preventing and treating female diseases. We identified the following phytoprogestins: kaempferol, apigenin, luteolin, and naringenin. In vitro studies showed promising results such as the antitumoral effects of kaempferol, apigenin and luteolin, and the anti-fibrotic effects of naringenin. Although limited data are available, it seems that phytoprogestins could be a promising tool for preventing and treating hormone-dependent diseases.

Addressing the Osteoporosis Problem-Multifunctional Injectable Hybrid Materials for Controlling Local Bone Tissue Remodeling.

Novel multifunctional biomimetic injectable hybrid systems were synthesized. The physicochemical as well as biological in vitro and in vivo tests demonstrated that they are promising candidates for bone tissue regeneration. The hybrids are composed of a biopolymeric collagen/chitosan/hyaluronic acid matrix and amine group-functionalized silica particles decorated with apatite to which the alendronate molecules were coordinated. The components of these systems were integrated and stabilized by cross-linking with genipin, a compound of natural origin. They can be precisely injected into the diseased tissue in the form of a viscous sol or a partially cross-linked hydrogel, where they can serve as scaffolds for locally controlled bone tissue regeneration/remodeling by supporting the osteoblast formation/proliferation and maintaining the optimal osteoclast level. These materials lack systemic toxicity. They can be particularly useful for the repair of small osteoporotic bone defects.

CARDIOPROTECTIVE EFFECT OF CYANIDIN-3-O-GLUCOSIDE IN ISCHEMIC HEART IS MEDIATED VIA INHIBITION OF AUTOPHAGY

Abstract It is elevated proves that the polyphenolic compounds of natural origin, such as anthocyanins, being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed anthocyanins, may control ischemia/reperfusion (I/R) injury although how much sheltering occurs is not obvious. In the present study, the role of cyanidin-3-O-glucoside pretreatment of cardiac ischemia and dysfunction was studied. Cyanidin-3-O-glucoside in 3 doses (5, 10, and 15 mg/kg body weight), was introduced in vivo 5 min before a 45 min closure of the left anterior descending artery, followed by a 120 min reperfusion in male Wistar rats. Blood samples and cardiac tissue specimens were obtained for studying the cardiac markers and the expression of lncRNA-CTC-448F2.4, miR1273a, and mRNA-DCN (Decorin), Specimens of left ventricles were obtained and prepared for histopathological criteria. Specimens of pretreated rats showed minimal cardiac edema, hemorrhage, cellular inflammatory infiltration, and fibrosis in cardiac tissue samples. Notably, this protective administration of cyanidin-3-O-glucoside also produced a dose-dependent downregulation in lncRNA- CTC-448F2.4 and mRNA-DCN (Decorin, an important gene involved in the regulation of autophagy) with elevation in miR-1273a expressions. Cyanidin-3-O-glucoside pretreatment leads to improvements in cardiac function tests, enzymes, and myocytes. In conclusion, Cyanidin-3-O-glucoside is promising for the protection of the heart from injury following ischemia-reperfusion in the rat examination.