A Comparative Study on Anticancer Effects of the Alhagi maurorum and Amygdalus haussknechtii Extracts Alone and in Combination with Docetaxel on 4T1 Breast Cancer Cells.

Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 µg/ml and 85 µg/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI < 1). A.h reduced DTX IC50 but presented CI > 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-time PCR analysis showed that A.m + DTX (IC50 + IC25) downregulated the mRNA expression of HIF-1α and FZD7. A.m + DTX (IC50 + IC10) group decreased the expression of HIF-1α. Moreover, in A.h + DTX (IC50 + IC25) group, ß-Catenin and FZD7 were downregulated and upregulated, respectively. Generally, our findings suggest that the combination of A.m and DTX possesses synergistic antitumor effects on 4T1 cells, which may be a valuable choice for CAM therapies. A.h has an acceptable antitumor activity but not in combination with DTX.

Phytochemicals impact on osteogenic differentiation of mesenchymal stem cells.

Medicinal plants have always been utilized for the prevention and treatment of the spread of different diseases all around the world. To name some traditional medicine that has been used over centuries, we can refer to phytochemicals such as naringin, icariin, genistein, and resveratrol gained from plants. Osteogenic differentiation and mineralization of stem cells can be the result of specific bioactive compounds from plants. One of the most appealing choices for therapy can be mesenchymal stem cells (MSCs) because it has a great capability of self-renewal and differentiation into three descendants, namely, endoderm, mesoderm, and ectoderm. Stem cell gives us the glad tidings of great advances in tissue regeneration and transplantation field for treatment of diseases. Using plant bioactive phytochemicals also holds tremendous promises in treating diseases such as osteoporosis. The purpose of the present review article thus is to investigate what are the roles and consequences of phytochemicals on osteogenic differentiation of MSCs.

Personalizing the safe, appropriate and effective concentration(s) of ozone for a non-diabetic individual and four type II diabetic patients in autohemotherapy through blood hemoglobin analysis.

BACKGROUND: Diabetes is a chronic disease associated with many problems and high costs. In recent decades, a lot of research has been carried out in order to improve methods of treatment of diabetic patients. One of the currently used complementary therapies for diabetes is ozone therapy or autohemotherapy. The beneficial effects of ozone has been proven in many diseases such as diabetes, but the critical issue is the determination of the safe and effective concentration of ozone reacting with blood and in particular hemoglobin. METHODS: A number of spectroscopic techniques including intrinsic fluorescence, circular dichroism and UV-VIS spectroscopies were used as well as SDS-PAGE, Native-PAGE and dynamic light scattering to analyze the effect of ozonation on hemoglobin of a non-diabetic individual and four diabetic patients in order to find the appropriate concentration(s) of ozone for personalized autohemotherapy. RESULTS: In this study, we determined the personalized concentration(s) for a safe and effective ozonation of a non-diabetic individual and four diabetic type II patients, based on blood hemoglobin analysis. CONCLUSIONS: A number of techniques were used to determine the personalized ozone concentration(s) for a safe and effective autohemotherapy based on blood hemoglobin analysis. SDS-PAGE and dynamic light scattering were identified as the two main techniques needed for personalizing the ozone concentration(s) for each individual as otherwise hemoglobin in blood can oligomerise and cause serious damage if the inappropriate ozone concentration is used.

Molecular insights into the effect of ozone on human hemoglobin in autohemotherapy: Highlighting the importance of the presence of blood antioxidants during ozonation.

Ozone has been known for several decades, with its antiseptic and therapeutic effects determined by the hormesis theory. It is shown that the therapeutic efficacy of ozone therapy may be partly due to the controlled and moderate oxidative stress produced by the reaction of ozone with several biological components. In this study, the effect of ozone on healthy human hemoglobin (Hb) in the whole blood environment (in the presence of antioxidants) and in the purified form (in the absence of antioxidants) is investigated using a number of different techniques including intrinsic fluorescence, circular dichroism and UV-VIS absorption spectroscopy as well as SDS- and Native-PAGE and dynamic light scattering. The results show that the presence of antioxidants prevents damage to Hb while its absence means that as the exposure to ozone is increased, Hb is increasingly damaged. These results highlight the importance for the use of appropriate doses of ozone, for patients with different diseases and hence antioxidant levels, in autohemotherapy.

Chemical composition and antifungal activity of Satureja hortensis L. essentiall oil against planktonic and biofilm growth of Candida albicans isolates from buccal lesions of HIV(+) individuals.

ETHNOPHARMACOLOGICAL RELEVANCE: Oral candidiasis is an opportunistic infection of the oral cavity which usually occurs in the immunocompromised individuals. Candida albicans (C. albicans) is the most common species of yeast responsible for oral candidiasis. This study investigated the effects of Satureja hortensis L. essentiall oil (EO) on the planktonic, biofilm formation and mature biofilms of C. albicans isolates from buccal lesions of HIV(+) individuals. MATERIALS AND METHODS: MTT reduction assay, broth micro-dilution method and scanning electron microscopy (SEM) were employed to determine the effect of mentioned EO on the C. albicans planktonic and biofilm forms. GC-GC/MS was used to detect the major active compounds of EO. RESULTS: Thymol (45.9%), gamma-terpinen (16.71%), carvacrol (12.81%) and p-cymene (9.61%) were found as the most abundant constituents. MIC values ranged from 250 to 400 µg/ml and MFC values ranged from 350 to 500 µg/ml. All C. albicans isolates formed biofilm on polystyrene plats but the quantity of biofilm mass (optical density) was different for the isolates ranging from 0.850 to 0.559 nm. The mean of biofilm formation by C. albicans isolates was reduced by 87.1 ± 3.7%, 73.6 ± 5.1%, 69.4 ± 5.3% and 67 ± 4.2% at 4800, 3200, 2400 and 1600 µg/ml, respectively. In sub-MIC concentration, SEM analysis revealed loosening of cells, deformity of three dimensional structures of biofilms and shrinkage in cell membranes of sessile cells. CONCLUSIONS: In conclusion, the substantial anti-fungal activity showed by S. hortensis L. EO suggests exploitation of this oil as potential natural anti-biofilm product to deal with the problem of buccal cavity lesion associated with C. albicans.

Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro.

OBJECTIVES: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. One of the hallmarks of AD is an abnormal accumulation of fibril forms of tau protein which is known as a microtubule associated protein. In this regard, inhibition of tau aggregation has been documented to be a potent therapeutic approach in AD and tauopathies. Unfortunately, the available synthetic drugs have modest beneficial efficacy with several side effects. Therefore, pipeline drugs from natural sources with anti-aggregation properties can be useful in the prevention and treatment of AD. Among medicinal plants, saffron (Crocus sativus, L.), as a traditional herbal medicine has different pharmacological properties and can be used as treatment for several nervous system impairment including depression and dementia. Crocin as a major constituent of saffron is the glycosylated form of crocetin. MATERIALS AND METHODS: In this study, we investigated the inhibitory effect of crocin on aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods and cell culture. RESULTS: Results revealed that tau protein under the fibrillation condition and in the presence of crocin had enough stability with low tendency for aggregation. Crocin inhibited tau aggregation with IC50 of 100 µg/ml. Furthermore, transmission electron microscopy images confirmed that crocin could suppress the formation of tau protein filaments. CONCLUSION: Inhibitory effect of crocin could be related to its interference with nucleation phase that led to increases in monomer species of tau protein. Based on our results, crocin is recommended as a proper candidate to be used in AD treatment.

Beneficial Effect of Flavone Derivatives on Aß-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α: A Comparative Study.

In the present study, the neuroprotective effect of 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4'-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aß)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aß injection. Seven days after Aß administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.

Exercise and supraphysiological dose of nandrolone decanoate increase apoptosis in spermatogenic cells.

Anabolic-androgenic steroids are used at high doses by athletes for improving athletic ability, physical appearance and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of anabolic-androgenic steroids may influence the hypothalamic-pituitary-gonadal axis, which can in turn affect testicular apoptosis. However, the effect of the combination of exercise and high dose of anabolic-androgenic steroids on testicular apoptosis is not known. We investigated the combined effects of exercise and high doses of nandrolone decanoate on apoptosis in the spermatogenic cell lineage. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (Sham); nandrolone decanoate (10 mg/kg/weekly) (nandrolone decanoate); exercise (1 hr/day, 5 days a week) (exercise); nandrolone decanoate (10 mg/kg/weekly) and exercise (1 hr/day, 5 days a week) (nandrolone decanoate exercise); and sedentary control without any injection or exercise (Control). Apoptosis in the male germ line was characterized by TUNEL, caspase-3 assay and transmission electron microscopy. The weights of the testis and accessory sex organs, as well as sperm parameters significantly decreased in the experimental groups relative to the sham and control groups (p < or = 0.05). Germ cell apoptosis and a significant decrease in the number of germ cell layers in nandrolone decanoate exercise-treated testes were observed (p < or = 0.05). Exercise training seems to increase the extent of apoptotic changes caused by supraphysiological dose of nandrolone decanoate in rats, which in turn affects fertility.