Jundishapur Journal of Natural Pharmaceutical Products
Volume:15 Issue: 2, May 2020

Chemotherapy fails to eradicate cancer cells, mainly due to the lack of selective drug accumulation into the tumor site, which can affect healthy cells, as well. In this research, we studied the magnetite nanostructured lipid carriers (NLCs) for targeted delivery of curcumin into breast cancer cells. Superparamagnetic iron oxide nanoparticles (SPIONs) were prepared using coprecipitation method by mixing FeCl2 and FeCl3 in a suitable ratio in alkaline media. The resultant ferrofluid was very stable and possessed high magnetic properties. To prepare SPIONs containing NLCs (NLC-SPIONs), cetyl palmitate and cod-liver oil, Tween 80 and span60 were used as solid lipid, liquid lipid, surfactant, and co-surfactant, respectively. Curcumin as an anticancer drug was loaded into NLC-SPIONs (CUR-NLC-SPIONs) and its characteristics, including particle size, zeta potential, polydispersity index (PDI), drug entrapment efficacy, drug-loading capacity, and thermal stability were evaluated. The results showed that CUR-NLC-SPIONs had a mean particle size of 166.7 ± 14.20 nm, mean zeta potential of -27.6 ± 3.83 mv, and PDI of 0.24 ± 0.14. Encapsulation efficiency for all prepared nanoparticles (NPs) was 99.95 ± 0.015% and drug-loading capacity was 3.76 ± 0.005%. Morphological studies were carried out by transmission electron microscopy (TEM) indicating spherical morphology of the NPs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay measurements on cell viability proved that the synthesized CUR-NLC-SPIONs possess a better cytotoxic activity against human breast cancer cells compared with free curcumin. This new drug delivery system, which benefits from superparamagnetic properties may serve as a suitable platform for developing new biocompatible drug carriers and with a potential to use in targeted cancer therapy.

 Mushrooms with significant traditional medicine properties are rich sources of vitamins, proteins, fibres, minerals, and polyphenolic compounds.

 Agaricus bisporus (edible white button mushroom) extracts and their purified polyphenolic content were examined in terms of cholesterol esterase (CEase) inhibitory activity.

 Organic solvent-based extraction methodologies were adopted to prepared the extracts. Two dimensional preparative thin layer chromatography (2D PTLC) technique and direct MS/ESI+ method were also used to purify and elucidate the polyphenolic structures. Standard spectrophotometric analyses were employed to determine the flavonoid and phenolic acid contents as well as CEase inhibitory activity in both extract and purified polyphenols.

 The findings supported the strong cholesterol esterase inhibitory activity of aqueous and methanolic extracts (separating funnel: 97.9 ± 1.1% and 97 ± 0.8%), and acetone extract (shake flask: 97.6 ± 0.2%). The investigation also documented the remarkable quantity of flavonoid (32.61 ± 4.1 mg/g tissue) and phenolic acid (12.38 ± 1.32 mg/g tissue). A fraction of strong blue colour phenolic acid was purified using 2D PTLC technique, and the direct MS/ESI+ method adopted for the purified eluate also revealed the presence of p-hydroxy benzoic acid (m/z 136), ferulic acid (m/z 194), cinnamic acid (m/z 146), and protocatechuic acid (m/z 154). The purified phenolic acids represent a moderate cholesterol esterase inhibitory activity (24.7 ± 1.7%; IC50 = 2.61 µg).

 The study revealed the remarkable CEase inhibitory property, implying the cardioprotective attribute of A. bisporus.

Fifty-four endophytic fungal species were isolated from 10 medicinal plants growing on different geographical Egyptian habitats; 48 of them were morphologically identified, at least to genus level and all belonged to ascomycetes. Ethanolic extracts of 49 isolates were screened for their antibacterial activities against three Gram-positive and three Gram-negative bacteria; they were also screened for their antifungal activities against Candida albicans and Fusarium solani. Twenty-six isolates showed antibacterial activities at least against one tested bacterial strain and seven isolates showed antibacterial activities against both Gram-negative and -positive bacteria. Moreover, cytotoxicity of these extracts were tested against one normal cell line MRC-5 and another cancer cell line MCF-7 using MTT assay. It was found that a group of seven isolates exerted a reduced toxicity towards the normal cell line, but had a higher toxic effect on the cancer cell line. These isolates represent a promising source for anticancer compounds with low cytotoxicity against the normal cell lines.

 AnbarNesa smoke is used to treat skin ulcers and many inflammatory conditions in Iranian traditional medicine. Avicenna used it to treat vaginitis and uteritis and named it Anbar (smoke) Nesa (women).

 The current study aimed at applying the smoke in modern medicine; since it was not soluble in water or in alcohol, it was solved in propylene glycol and the new product called ANNAS. Then the wound healing activity of ANNAS was examined on the incisional wounds created on the dorsum of male Wistar rats.

 By means of biopsy punch, two full-thickness incisions were made on different sides of the rats’ vertebral column and treated daily by one drop of ANNAS or propylene glycol randomly. The wounds were excised on days 14 and 21; then stained with anti-SMA antigen for myofibroblast cell detection. The myofibroblasts were counted at the surface and deep layers of the dermis as indicators of wound scar by optical microscopy.

 The obtained results showed that the number of myofibroblasts was significantly lower in surfaces and deep layers of the dermis and, consequently, in the entire dermis of lesions treated with ANNAS compared to the ones treated with propylene glycol on days 14 (P < 0.002) and 21 (P < 0.0001).

 It seems that AnbarNesa decreases keloid formation and prevents scar creation. Besides, hair follicles, dermal appendages, and sebaceous glands were also observed on day 21 in lesions treated with ANNAS, which was a novel finding reported for the first time and could be a proof for the acceleration of wound healing by the invented drug, ANNAS.

 Melasma is a common disorder of hyperpigmentation affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. Therapeutic goals for hyperpigmentation include the destruction of melanosomes, inhibition of the melanocyte formation, and delay in the spread of melanocytes. Hydroquinone is a commonly used treatment for melasma, but it is combined with other medications due to its low efficacy in single therapy and relapse. Hydroquinone is hydroxy phenol which inhibits melanin by inhibiting tyrosinase. In addition, retinoid is effective in treating melasma and stimulate the cycle of skin cells, thus increasing the rate of loss of color pigmentation. A corticosteroid is used to increase the efficacy of these two drugs.

 The purpose of this study is to formulate an integrated formulation for the treatment of this skin disease.

 The triple cream, which is a combination of hydroquinone (HQ), tretinoin (TRE), and fluocinolone acetonide (FLU) demonstrate better efficacy in decreasing skin pigmentation due to the additive and synergistic effects of these ingredients. As there is no topical generic formulation in combined form in Iran, such cream is prepared that contains 4% HQ, 0.05% TRE and 0.01% FLU as an oil in water (O/W) cream.

 The result of this study was a 6-month accelerated evaluation of physical and physicochemical properties, including pH, electrical conductivity, density, viscosity, active ingredient identification, determination of amount and completely stable and homogeneous microbial tests. A review of the identification of the active ingredient and the determination of the amount conformed to the USP standard (American Pharmacopoeia). Also, material release from the base was well done.

 The prepared cream was completely stable and homogeneous during the accelerated conditions by evaluating of physicochemical and microbial assessments.

Muscari inconstrictum Rech. f. is an ornamental and bulbous species with various medicinal and biological effects.

This study was designed to evaluate the anti-oxidant and anti-malarial activities of M. inconstrictum as one of the Iranian species of Muscari genus. Additionally, preliminary phytochemical investigation of the extracts with different polarity was performed.

M. inconstrictum bulbs were extracted with n-hexane, chloroform, and methanol (MeOH) by Soxhlet apparatus, in the order of their polarity. Next, vacuum liquid chromatography (VLC) was used for the fractionation of extracts. Free radical scavenging and anti-malarial activities were investigated via DPPH (2,2-diphenyl-1-picrylhydrazyl) and cell-free β-hematin formation methods. Thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) were used for the characterization of potent fractions.

Among different extracts of M. inconstrictum, bulbs, chloroform, and n-hexane extracts were the most potent anti-oxidant and anti-malarial extracts, respectively. Moreover, methanolic, 80% and 100% ethyl acetate/n-hexane VLC fractions of chloroform extract showed significant anti-oxidant activities, which can be related to the presence of flavonoid and coumarin structures. Furthermore, 40% ethyl acetate/n-hexane VLC fraction of n-hexane extract with saponin structures is introduced as the most potent anti-malarial part. GC-MS analysis of methanol fraction of chloroform extract, 40% ethyl acetate/n-hexane VLC fraction of n-hexane extract, and the volatile oil of plant demonstrated the presence of phenolic monoterpenoid, fatty acid derivatives, and sesquiterpenoid structures as the main ingredients, respectively.

It seems that more studies on M. inconstrictum are necessary to focus on pure compounds and their biological activities.

 Terpenoids are produced by a wide variety of plants, animals and microorganisms, which effectively plays a role in the survival of the organisms by means of functional, defensive and communicational attitudes.

 The main purpose of the present study was isolation and elucidation of the natural terpenoids from the aerial parts of Tripleurospermum disciforme (Compositae/Asteraceae family).

 The phytochemical investigation of the dichloromethane extract of T. disciforme was carried out by various chromatographical methods such as column chromatography and thin layer chromatography. The major compounds were purified and their structures were established by using nuclear magnetic resonance and electron impact mass spectroscopic data. Moreover, the cytotoxic ability of the isolated compounds were measured on the human gastric carcinoma (AGS) and the mouse skin fibrosarcoma (WEHI-164) cell lines by using MTT assay. Molecular docking studies of the specialized metabolites were performed with Bcl-2, Bcl-xl, CDK2 accompanied by tubulin proteins using AutoDock Vina.

 Three triterpenoids including (1) taraxasterol; (2) lupeol; and (3) betulinic acid were isolated and elucidated. Our cytotoxic results exhibited that compound 2 could be considered as an anti-tumor component with an IC50 value of 3.2 µM on WEHI-164 cell lines. Likewise, 3 displayed the potent cytotoxic activity, with an IC50 value of 5.6 μM on AGS cell lines. It is noteworthy to mention that the triterpenes 1 - 3, newly reported in T. disciforme impacted on the prevention of tubulin polymerization because of the strong interaction with the vinblastine binding site of tubulin.

 Our data suggested that the isolated triterpenoides from T. disciforme possess anti-tumor properties, and may be included among the effective natural anti-tumors.
 

 Human ABCC3 (hABCC3) or multidrug resistance protein 3 (MRP3), third member of the subfamily C of the ABC proteins, is associated with multidrug resistance and treatment failure in acute leukemia. Hence, targeting this protein might be a useful approach to provide more effective drugs to overcome cancer drug resistance.

 The present study aimed at predicting the possible ligand binding sites (PBSs) on hABCC3 and examining the possible binding of different chemotherapeutic drugs to this protein.

 To predict the PBSs on the hABCC3 transporter, a three-dimensional homology model of hABCC3 was generated in the current study based on bovine ABCC1 (bABCC1) using SWISS-MODEL and MODELLER programs, and then a molecular docking was qualified. Finally, binding affinities of 14 ligands including chemotherapeutic and immunosuppressive drugs, in addition to hABCC3 inhibitors, for hABCC3 were evaluated using binding free energies and the corresponding scores. Molecular docking was performed using AutoDock. Furthermore, Chimera, LigPlot, and Swiss PDB viewer (SPDBV) were used for interactive visualization and analysis of molecular structures.

 The two PBSs on hABCC3 were predicted using the blind docking method. Docking results in both PBSs showed that vincristine, doxorubicin, and daunorubicin had the highest binding affinities, respectively, with vincristine having the highest docking score.

 In the current study, three drugs with the highest affinity for hABCC3 were introduced in order to take a step toward the possible hABCC3 targeting in drug-resistant acute leukemia. Furthermore, the application of in-silico methods in targeted cancer therapy, especially leukemia treatment, was highlighted.

 Acinetobacter baumannii is one of the most common and important causes of hospital-acquired infections. Due to its intrinsic resistance to antibiotics, A. baumannii can survive in the hospital environment for a long time and target hospitalized patients. Therefore, treatment and prevention of hospital-acquired infection with these bacteria require identification of new antibacterial agents with no or fewer side effects and toxicity.

 The aim of this study was to investigate and compare the antibacterial effects of the aqueous and ethanolic extracts of Peganum harmala on multidrug-resistant, extensively drug-resistant and pandrug-resistant Acinetobacter baumannii isolates.

 Antimicrobial susceptibility of the isolates was determined using the Kirby-Bauer method according to the Clinical and Laboratory Standards Institute document M100-S25 (2015). Antimicrobial activity of the ethanolic and aqueous extracts of P. harmala against drug-resistant A. baumannii isolates was determined by the agar well diffusion method. In addition, broth microdilution susceptibility testing was carried out to determine the minimum inhibitory concentrations (MICs) of the extracts. Finally, active compounds with antimicrobial activity were identified by gas chromatography-mass spectrometry.

 The frequencies of the multidrug-resistant, extensively drug-resistant and pandrug-resistant A. baumannii isolates were 37.2%, 58.2% and 61%, respectively. The MIC90 of the aqueous extract of P. harmala was 1024 μg/mL, which was four times less than that of its ethanolic extract (4096 μg/mL). Similarly, the MIC50 of the aqueous extract of P. harmala was significantly smaller than that of the ethanolic extract (P < 0.05). According to the results, vasicine/peganine and 8-hydroxy deoxy peganine were the most abundant (39.94%) bioactive compounds in the aqueous extract of P. harmala.

 The aqueous extract of P. harmala had excellent antimicrobial effects on the resistant A. baumannii isolates.
 

 The potential antidiabetic effects of medicinal plants are investigated since long ago by researchers in medicine. Ferula asafoetida, as a medicinal herb, is traditionally used for the treatment of asthma, epilepsy, stomach pain, bloating, and diabetes.

 The current study aimed at investigating the effect of ethyl acetate extract of F. asafoetida on the glucose level and lipid profile in streptozotocin-induced diabetic rats.

 The F. asafoetida extract (25, 50, and 100 mg/kg) was injected intraperitoneally to diabetic rats once daily for a 28-day period. The diabetic control group received the extract solvent as a vehicle by the same manner. Serum levels of glucose, triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured on the days 0, 17, and 31 of the intervention. In addition, animals’ weight changes were monitored during the experiment.

 The F. asafoetida extract significantly reduced serum glucose, triglycerides, cholesterol, and LDL levels in diabetic rats, compared to the controls. Moreover, the weight-loss observed in diabetic animals receiving the extract was insignificant. The extract had no effect on the serum HDL level.

 Ferula asafoetida influenced serum glucose decrease and improved lipid profile in diabetic animals. However, further research should be conducted on the mechanisms of actions of F. asafoetida extract.

Vancomycin-resistant Staphylococcus aureus has emerged as a multidrug-resistant pathogen responsible for mortality, particularly among ICU patients. This study reports a case of bacteremia associated with mortality in ICU ward in a major referral hospital in Karaj. Although antibiotic treatment was started, the patient died. This report describes the clinical course of the illness. To the best of our knowledge, no case of multidrug-resistant Staphylococcus aureus has been reported previously in Karaj.

Due to the presence of many antimicrobial-resistant pathogens, researchers are trying to substitute antibacterial drugs with other nanostructures and medicinal plants.

This study aimed to assess the antibacterial/antifungal and DNA cleavage characteristics of Pulicaria undulate and Echinacea purpurea extracts with/without Ni:FeO(OH) nanowires and NiS nanoparticles.

The antimicrobial activities of extracts in combination with nanostructures were assessed using MIC, MBC, and disc diffusion methods against Aspergillus oryzae, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis and DNA electrophoresis methods against E. coli. Also, the chemical constituents of extracts and the structures of nanowires/nanoparticles were analyzed by GC-MS and X-ray/SEM, respectively.

The main constituents of Pulicaria undulate and Echinacea purpurea extracts were Nonadecane (13.8%) and phytol (17.7%), respectively, in GC analysis. In the disc diffusion method, Ni:FeO (OH)-NW had more effects on Gram-positive bacteria and NiS-NP showed antibacterial effects on Gram-negative bacteria. Also, the combination of Echinacea purpurea and NiFeO(OH) had the most antibacterial effects on Pseudomonas aeruginosa and Staphylococcus aureus (19 and 20 mm, respectively). The lowest MIC effects were seen for Pulicaria undulate and NiS (0.195 mg/mL) against E. coli. Also, the lowest MBC effects were seen for Echinacea purpurea and Ni-doped FeO(OH) against Staphylococcus aureus (0.195 mg/mL). The combination of NiS-NP and Pulicaria undulate had the most DNA cleavage effect.

The combination of Pulicaria undulate and Echinacea purpurea extracts with nanostructures was effective to eliminate the bacteria. Therefore, the synergistic effect of the combination of plant extracts and nanoparticles brings about new options for the treatment of microbial diseases.