Investigating the Effect of The Habitat and Type of Extracted Organ on The Phytochemical Compounds of Caper (Capparis Spinosa L.) As A Medicinal and Pasture Plant

IntroductionWith the increasing world's population, the need for food and medicine, and their continuous supply, are essential for mankind. Medicinal plants are one of the important factors for human life, as they can be used both as food and medicine. The ancients had a long history of using medicinal plants, and they used their many properties extensively. The scientific name for Caper plant is Capparis spinosa L. Due to its resistance to environmental stress and its ability to act as a protector against soil destruction, this valuable medicinal plant is suitable for growing in arid and desert areas. Commercial cultivation of this plant is very valuable because it is rich in bioactive compounds. This plant's compounds can be extremely useful and effective in protecting humans from various diseases or enhancing the treatment of diseases. This study aimed to examine the total phenol and flavonoid composition, antioxidant activity, and extraction efficacy of various parts of this plant in two desert locations in Yazd and Isfahan to select the best cultivation region from these two sites for expanding cultivation. To determine the most effective compounds and the optimal extraction method, various organs of the plant were examined separately in this research. The best extraction efficiency can be achieved by growing the plant in the region and harvesting the desired organ, and the extracted materials can be used to prevent and treat diseases. Material and Methods The caper plant was collected from desert sites in Yazd and Isfahan in different parts, which included leaves, stems, buds, flowers, fruits, and roots. Plants were collected from four different locations on the site, and finally, the plants from four different locations were combined. After the botany expert's approval, extraction was done from different parts of the plant with hydroalcoholic solvent (80% ethanol) by the Soxhlet method. In this research, different experiments of total phenol, total flavonoid, antioxidant content, and extraction efficiency were performed using standard methods. Different dilutions of extract and standard material were made for all experiments. Folin Ciocalto's reagent was used to measure the total phenol, and it was reported according to the Gallic Acid standard per gram dry weight of the plant. Different tests like ABTS, DPPH, CUPRAC, and FRAP were employed to measure the plant's antioxidant content. The standard for milligrams of Trolox per gram of dried plant weight was used to calculate all of them. The number of flavonoids was measured based on the Aluminium Chloride colorimetry method and was expressed in the standard form of milligrams of Quercetin per gram of weight of the dried plant. To determine the extraction efficiency, the weight of the powder extract obtained from the extraction of different organs was calculated with a scale, and then the ratio of the weight of the powder extract of the weight of dried plant was reported as extraction method efficiency. For each of the experiments, 3 repetitions were performed. A two-way analysis of variance was utilized to examine the data's normality, and finally, IBM SPSS Statistics 26 software was utilized to analyse them. Results and DiscussionThe findings demonstrated that phenolic and flavonoid compounds were abundant in various parts of the caper plant from both locations. The leaves demonstrated a higher concentration of phenolic and flavonol compounds, with 48.611 mgGA/gDW and 19.842 mgQE/gDW, respectively. The antioxidant activity of roots was the highest among all parts of the plant. The Yazd site's caper plants were found to have a higher total phenolic and flavonoid content, with 35.572 mgGA/gDW and 14.14.164 mgQE/gDW, when compared to the other regions. The highest antioxidant activity was found in the fruit and root of the caper plant using the DPPH method. The ABTS method's measurement of antioxidant activity resulted in the same results and indicated that fruits had the highest activity. A positive correlation was observed between the amount of phenol and flavonoids. Furthermore, the Yazd site had a higher extraction efficiency than the Isfahan site, measuring 16.754%. The best region between two desert sites is also the best organ for extraction, as per the results of the current investigation. These results can be utilized to cultivate caper plants that contain more effective substances. These findings emphasize the status of the Caper plant as a rich source of secondary metabolites and show its potential as a potent healing agent with highly beneficial compounds, the site of Yazd is a suitable site for the cultivation of this plant. By cultivating this plant, in addition to helping to reduce desertification and prevent soil erosion, it is possible to have a source of secondary metabolites, especially phenol and flavonoid compounds, and use them in many medicinal applications

Ectopic microRNAs used to preserve human mesenchymal stem cell potency and epigenetics

Human mesenchymal stem cells (hMSCs) have remarkable potential for use in regenerative medicine. However, one of the great challenges is preserving their potency for long time. This study investigated the effect of miRNA ectopic expression on their proliferation and also on the expression level of Parp1 as an epigenetic switch preserving pluripotency in hMSCs. A cationic liposome was prepared as an efficient carrier for miRNA delivery. The miRNA loading efficiency and physical stability of vesicles were measured, and their scanning electron microscopic shapes determined. hMSCs were transfected with miR-302a and miR-34a followed by assessment of their proliferation potency with MTT assay and measurement of the expression of Parp1 by quantitative polymerase chain reaction (QPCR). Cell transfection with miR-302a and miR-34a efficiently and differentially affects the proliferation potency of hMSCs and the expression level of Parp1 as the key epigenetic factor involved in pluripotency. While miR-302a increases Parp1 expression, miR-34a suppresses it significantly, showing differential effects. Our results demonstrated that miRNA-based treatments represent efficient therapeutic systems and hold a great promise for future use in regenerative medicine through modification of hMSC pluripotency and epigenome

A new study on synthesize and optimization of PEGylated LipoNiosomal nanocarriers containing curcumin for use in cancer chemotherapy

Introdution: Chemotherapy is one of most effective methods to fight metastatic tumors. Its non- targeting has many side effects. The aim of this study was to investigate various formulations of Lipo-Niosomal hybrid system to achieve an optimized and targeted formulation to provide proper function as a complementary drug in cancer chemotherapy. Methods: The present study was an experimental study. Five Lipo-Niosome systems with different formulations containing DPPC, Cholesterol, and Span60 were synthesized using thin-film method. Three formulations were chosen based on the entrapped efficiency of curcumin and their release profile was investigated in order to choose the final formula. In the following, the final formula was optimized by DSPE-mPEG(2000) and after calculating, the curcumin release profile in simulated environment of healthy and cancerous cells; physiochemical characteristics of the final formula determined by ZetaSizer, FTIR and SEM instruments. Results: Final formulation of curcumin PEGylated lipo-niosome had 147.5 nm size, 98.12%±1.85 entrapment, -8.90 mV zeta potential, and 0.176 of PDI. The maximum release of the drug for this nanosystem in an environment similar to healthy cells was 19.02% and 24.88% in cancerous cells. FTIR and SEM investigations show drug and nanocarrier had no chemical interaction leading to change the functional groups and its particles have a spherical morphology. Conclusion: The findings of this study along with confirming the system to be semi-targeting, shows that carrier released entrapped drug with continuous and controlled rate without any change in chemical nature of the drug. It appears the nanoscale size and the low anionic charge of the system is an indication of its high cellular uptake

Experimental study: experimental evaluation of phospholipid system containing doxorubicin HCL for use in chemotherapy

Introdution: Common cancer treatment methods have many side effects. Therefore, the use of new methods for drug delivery to cancer cells is necessary. In the present study, nano formulations of lipid carriers containing doxorubicin have been synthesized and its physicochemical properties have been investigated. Methods: The present study was an experimental study. The liposomal systems were synthesized by the method of thin-film hydration and using Tween-20, cholesterol and soybean phosphatidylcholine. After loading Doxorubicin drug into the liposomes, physiochemical properties of nano-carriers were determined from the perspective of encapsulation efficiency, drug release profile under healthy and cancerous cells condition, hydrodynamic diameter, zeta potential, morphology and IR spectra. Results: The liposomal system had 132.9 nm in diameter, the encapsulation 93.74% and -38.73±0.18mV zeta potential. The maximum release of drug from the nano-carrier under conditions 37°C, pH=7.4 and 42°C, pH=5.4 and 37°C, pH=5.4 after 72 hours was 36.54% and 74.18% and 55.9% respectively. SEM and IR assessments revealed spherical morphology and the absence of chemical interaction between nano-carrier and drug. Conclusion: The result of this research indicates that the liposomal system, having the appropriate physiochemical properties, has not changed the chemical nature of drug and thus can be a suitable and semi-targeted carrier for doxorubicin

Formulation of a therapeutic cationic liposome-siRNA complex for development to fight osteosarcoma

Introdution: Cationic liposomes have been presented for gene delivery as an alternative vector instead of viral vectors. A major challenge associated with siRNA delivery is the instability of liposomes, which is still a serious problem. The aim of this study was to provide an appropriate formulation to overcome this instability. Methods: In the present study (Scientific-Fundamental, Experimental-Laboratory Study), liposomal formulation containing soy phosphatidylcholine, cationic DOTAP, cholesterol and polyethylene glycole was synthesized by thin-film hydration method and the siRNA were loaded on liposomes through incubation. In the following; the optimization of siRNA loading was on the agenda. Then the parameters related to size, zeta potential, polydispersity index and lon-term stability of siRNA-liposomes complex were reported. The Data were analyzed by GraphPad Prism version 7 Software. All data were repeated three times and reported as mean±standard deviation. Results: In this study we were able to produce siRNA lipoplex with high loading efficiency of siRNA. The produced nanoparticles did not agglomerate and were stable at 4 oC for 3 months. This nanosystem could successfully deliver siRNA to normal bone cells. Studies have shown that the blank system (no gene) had no toxicity. Conclusion: The prepared PEGylated liposomes have a great potential for delivery of siRNA to bone cell

A new approach to the development and assessment of doxorubicin-loaded nanoliposomes for the treatment of osteosarcoma in 2D and 3D cell culture systems

Doxorubicin (DOX) is an effective anticancer drug used for the treatment of osteosarcoma. Liposomal nanocarriers for doxorubicin administration are now regarded as one of the most promising approaches to overcome multiple drug resistance and adverse side effects. The use of hydrogel as a 3D scaffold to mimic the cellular environment and provide comparable biological conditions for deeper investigations of cellular processes has attracted considerable attention. This study aimed to evaluate the impact of liposomal doxorubicin on the osteosarcoma cell line in the presence of alginate hydrogel as a three-dimensional scaffold. Different liposomal formulations based on cholesterol, phospholipids, and surfactants containing doxorubicin were developed using the thin-layer hydration approach to improve therapeutic efficacy. The final selected formulation was superficially modified using DSPE-mPEG2000. A three-dimensional hydrogel culture model with appropriate structure and porosity was synthesized using sodium alginate and calcium chloride as crosslinks for hydrogel. Then, the physical properties of liposomal formulations, such as mechanical and porosity, were characterized. The toxicity of the synthesized hydrogel was also assessed. Afterward, the cytotoxicity of nanoliposomes was analyzed on the Saos-2 and HFF cell lines in the presence of a three-dimensional alginate scaffold using the MTT assay. The results indicated that the encapsulation efficiency, the amount of doxorubicin released within 8 h, the mean size of vesicles, and the surface charge were 82.2%, 33.0%, 86.8 nm, and −4.2 mv, respectively. As a result, the hydrogel scaffolds showed sufficient mechanical resistance and suitable porosity. The MTT assay demonstrated that the synthesized scaffold had no cytotoxicity against cells, while nanoliposomal DOX exhibited marked toxicity against the Saos-2 cell line in the 3D culture medium of alginate hydrogel compared to the free drug in the 2D culture medium. Our research showed that the 3D culture model physically resembles the cellular matrix, and nanoliposomal DOX with proper size could easily penetrate into cells and cause higher cytotoxicity compared to the 2D cell culture

Synthesis and optimization of niosomal carriers containing doxorubicin in order to achieve a final formulation with high potential in cancer cells temperature and acidity

Introdution: Doxorubicin is one of the most commonly used drugs in chemotherapy with many side effects; this fact has limited its use. In the present study, based on the knowledge of pharmaceutical nanocarriers, various formulations of the niosomal form of this drug were synthesized and surface optimizations were applied to the final selected formulation. Methods: The present study was an experimental study. Various formulations of niosomal systems were synthesized by the method of thin-film hydration and using Tween60 and cholesterol. Doxorubicin was encapsulated through niosome inactively. In the following, optimizations were made based on choosing two formulas out of six experimentally, then the effects of adding Tween20, DSPE-mPEG(2000) polymer and cationic phospholipid of DOTAP (respectively) was investigated. Then, physiochemical properties of nanocarriers were determined from the perspective of encapsulation efficiency, drug release profile under healthy and cancerous cells condition, hydrodynamic diameter, Poly Dispersity Index, zeta potential, morphology and Infrared spectroscopy(IR) spectrum. To plot the graphs and express the data Origin and Excel software were used, respectively. Results: The optimized final niosome formula had 98.59 nm in diameter, 91.8±0.43, -3.5mV zeta potential and 0.196 PDI. The maximum release of drug from the nanocarrier under conditions of healthy and cancerous cells (37°C, pH=7.4 and 42°C, pH=5.4) after 48 hours was 62.3% and 76.5% respectively. Field Emission Scanning Electron Microscope and IR assessments revealed spherical morphology and the absence of chemical interaction between nanocarrier and drug. Conclusion: The findings of this study prove this drug carrier to be semi-targeting. It also shows that niosome by specializing the drug delivery increases the effectiveness of drug and the life quality of patient while reducing the side effects, all without any change in the chemical nature of the drug

A new strategy in improving therapeutic indexes of medicinal herbs: preparation and characterization of nano-liposomes containing Mentha piperita essential oil

Introduction: Herbal Compound and their essential oils possess high antimicrobial, antioxidant, and anti-tumor properties, but conventional prescribing of them faces serious challenges. Liposomal nano-carrier is one of the common pharmaceutical strategies to overcome these challenges. In this study, slow-released liposomal system containing Mentha piperita’s essential oil was prepared in order to improve its antimicrobial, antioxidant and antitumor properties. Methods: Liposomal vesicles were prepared using phosphatidylcholine (80%) and cholesterol (20%) by thin-film method. Mentha piperita’s essential oil were loaded into the liposomes using inactive loading method. Their physico-chemical features were assayed using Zeta-Sizer, FTIR and SEM, and at the end, the essential oil release amount was calculated at 37° C. Results: Liposomal vesicles containing Mentha piperita’s essential oil showed the size of 247  13.39 nm, 61.38% ± 2.7 essential oil encapsulation efficiency, -34.54  0.74 mV of zeta potential and polydispersity index (PDI) of 0.32  .01. The prepared liposomal system presented essential oil controlled release and FTIR and SEM investigation showed no interaction between nanocarrier and the essential oil and the carriers have spherical structures. Conclusion: In the present study, Mentha piperita’s essential oil encapsulated in liposomal carriers and its physicochemical properties investigated. The results confrimed the slow-releasing ability of system and also showed that the anionic nanosystem increased the essential oil’s stability without any change in its chemical nature. Taken together, liposomal nanocarrier could be a potent and suitable carrier for the essential oil

Study of anti-cancer effects of Curcumin; formulation of Curcumin-loaded nano carrier and its toxicity effect on MCF-7 Cell line.

Introdution: Nanotechnology introduced new methods to chemotherapy drugs delivery into cancer cells to reduce the side effect of drugs it increases the quality of cancer treatment and reduces the side effects of chemotherapy. . In this study, different lipid formulations of nucliposomes containing curcumin was prepared by thin-layer method and evaluated for chemical-physical evaluation on MCF-7 cell line. Methods: This study was a descriptive-analytic. Various formulations of liposomes prepared from Span 60, SPC and cholesterol. Curcumin was loaded in the liposomes. Final liposome formulation selected and PEGylated. The Optimal formulation characterized by DLS, FT-IRT, Fe-SEM and SEM. Statistical analysis was performed with Prism6 software. Results: The average size of liposomes, encapsulation efficacy of liposomal loaded curcumin and Zeta potential was about 63.9 nm, -41mV and %95.58, respectively. Liposomes exhibited the slowest release rate in normal and turmeric cell culture condition. To compare the function of free curcumin in similar concentrations, liposomal curcumin formulation was %63 toxic to MCF7 Cell line. Conclusion: The present study shows that an optimally optimized nanoliposome with curcumin having appropriate physicochemical properties, improving drug toxicity in cancerous cell lines and increasing drug stability can be a good vector for drug delivery to breast cancer cells. Conclusion: The present study shows that an optimally optimized nanoliposome with curcumin having appropriate physicochemical properties, improving drug toxicity in cancerous cell lines and increasing drug stability can be a good vector for drug delivery to breast cancer cells

Using chitosan-stabilized, hyaluronic acid-modified selenium nanoparticles to deliver CD44-targeted PLK1 siRNAs for treating bladder cancer Supplementary data

Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs (siPLK1) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CSSeNP@ siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro. HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.</p