Background Chemotherapy remains to be the method of choice used by clinicians to treat acute myeloid leukemia (AML) patients. However, the most common problem usually faced in the course of treatment is multidrug resistance (MDR). Nowadays, combination therapy involving natural products as adjuvant therapy to chemotherapy and radiotherapy has been used for many of health problems. Coumarin is a natural compound with known chemotherapeutic activity, as well as other pharmacological properties. We focused on the combination of coumarin and doxorubicin in overcoming of drug-resistance in acute myeloid leukemia. Methods Cell viability, Apoptotic and necrotic cell death with FACS, oxidative stress detection, and protein expression analysis were used in this study. Results Coumarin as a single drug exerts a significant cell death on Human acute myeloid leukemia (HL60); however, it does not show the same effect on drug-resistant acute myeloid leukemia (HL60/ADR). Comparing the effects of doxorubicin and coumarin as single drugs versus a combination of coumarin and doxorubicin showed a significant apoptotic cell death. Conclusion In AML patients, the development of multiple drug resistance (MDR) is the biggest challenge in treating AML patients. Combination therapy with coumarin may be a good choice to overcome the drug resistance in AML patients.

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now.Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger (Zingiber officinale Roscoe) and cinnamon (Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect.Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague–Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA–β cells were performed. Pancreatic gene expression of β-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques.Results: BGL significantly decreased (p = 0.01), while serum insulin and TAC significantly increased (p < 0.001) in both metformin- and ginger plus cinnamon–treated groups compared to the untreated diabetic group. HOMA–β cell index significantly increased (p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated (p < 0.001), while β-catenin was insignificantly downregulated (p = 0.32) in ginger plus cinnamon–treated groups. Insulin immunoexpression in β cells significantly increased (p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon–treated groups, respectively.Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.

Background: Rhazya stricta has been used as a folkloric medicinal herb for treating various diseases such as diabetes, inflammatory disorders, and sore throat. Several studies have revealed the potential of this plant as an important source of phytochemicals with anticancer properties. Objective: The present study was designed to isolate a novel anticancer compound from Rhazya stricta and elucidate its mechanism of action using genomics approach. Methods: Rhazya stricta leaves extract was prepared, and several alkaloids were purified and characterized. These alkaloids were screened for their anticancer potential. One of the alkaloids, termed as isopicrinine, showed efficient cytotoxicity against MCF7 breast cancer cell line and was selected for further analysis. RNA-Seq transcription profiling was conducted to identify the affected genes and cellular pathways in MCF7 cells after treatment with isopicrinine alkaloid. Results: In vitro studies revealed that newly identified isopicrinine alkaloid possess efficient anticancer activity. Exposure of MCF7 cells with isopicrinine affected the expression of various genes involved in p53 signaling pathway. One of the crucial proapoptotic genes, significantly upregulated in MCF7 after exposure to alkaloid, was PUMA (p53 upregulated modulator of apoptosis), which is involved in p53-dependent and -independent apoptosis. Moreover, exposure of sublethal dose of isopicrinine alkaloid in breast cancer cell line led to the downregulation of survivin, which is involved in negative regulation of apoptosis. Besides, several genes involved in mitosis and cell proliferation were significantly downregulated. Conclusion: In this article, we report the determination of a new alkaloid isopicrinine from the aerial parts of Rhazya stricta with anticancer property. This compound has the potential to be developed as a drug for curing cancer.

Background: Hepatocellular carcinoma (HCC) is one of the most serious cancers worldwide.Even with recent developments, there has been slight progress in improving the survival rate of HCC patients. Current therapies are accompanied by marked side effects beside incomplete recovery. Therapy by Herbal products proved effective anticancer. Aim: Screening of the apoptotic and anti-proliferative effects of Rhazya stricta (R. stricta), nanoparticles which locally known as " Harmal" against highly aggressive HCC in vitro study. Procedures: R. Stricta Nano particles was gained by exposing R. Stricta sheets to ball milling process to convert particles into Nano scale diameter which examined by scanning electron microscopy (SEM) . Cytotoxicity of different concentrations of R.stricta nanoparticles (0.0, 100 and 500 µg/ml) was evaluated via its effects on the mRNA expression of Bax and Bcl-2 apoptosis related genes in Hep G-2 and Huh-7cell lines using real-time quantitative PCR analysis, MTT assay and FACS analysis Results: It is clear from SEM images that R.Stricta nanoparticles are predominantly spherical in shape and polydispersity with particle size around 100 nm. After 24 and 48 hours, R.stricta nanoparticles showed a significant cytotoxic effect on all cell lines at 500 μg/ml (p<0.05) but has a high significant effect on decreasing Hep G-2 cell viability with 100 and 500 μg/ml of R.stricta nanoparticles Hr(p<0.001) compared with other cell lines. Conclusion and clinical relevance:Moving on gene expression,MTT assay and FACS analysis, it could concluded that the R. stricta, nanoparticles produced apoptosis in Hep G-2 and Huh-7 cell lines

While chemotherapy remains to be one of the main using approaches in the clinical treatment of acute myeloid leukemia (AML), multidrug resistance (MDR) is considered the major obstacle that limits the therapeutic efficacy. Nowadays, Herbal therapy as an adjuvant therapy has been used for many health problems. Ginger (Zingiber officinale) is considering one of the promising herbal spices showing high therapeutic and preventive effects against many disorders specially cancer. In the current work, we focused on the role of ginger crude extract in fighting drug resistant AML. MTT assay showed a significant decrease in cell viability and clear cytotoxic effect on HL60/ADR and HL60 cell under the high concentrations (100 and 1000 μg/Ml) of ginger extract. The flow cytometry results showed a significant apoptotic cell death by ginger in HL60 and ADR/Hl60 and also confirmed by immunostaining of nucleus by DAPI which showed apoptotic nuclei. Our data clearly declared that the high concentration of ginger extract is promising anticancer drug by induction of apoptotic cell death in HL60/ADR cells especially in drug resistant AML.

Metagenomic approach was used to detect microbial gene abundance and relative abundance in the rhizosphere of Moringa oleifera and surrounding bulk soil and to detect the response of soil microbes to watering. Expectedly, the number and abundance of non-redundant genes were extremely higher in bacteria followed by archaea, eukaryota and viruses. Results demonstrated unexpected high abundance of some microbes (ex., endophyte genus Nocardioides) in the rhizosphere that are supposed to exist mainly in other rhizocompartments. We suggest this differential distribution of microbes is due to the specific pattern of host-microbe interaction. Other endosymbiont microbes, ex., fungi Mucoromycota and Ascomycota, were highly abundant in the bulk soil possibly because they are phytopathogens where plant exudates might inhibit their growth or force these fungi to approach reverse chemotaxis. Our data indicated high abundance of other symbiont microbes in the rhizosphere of M. oleifera at phylum (ex., Actinobacteria) and genus (ex., Streptomyces) levels. Watering experiment indicated that phylum Actinobacteria and the descending genus Streptomyces are among the highest. Rhizobiome of M. oleifera seems to harbor a wealth of new species of the genus Streptomyces that are required to be deciphered for function in order to be eventually utilized in pharmaceutical and agricultural applications.

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