دکتریلدا شکوهی نیا

Alkaloids are important compounds that have a high potential in the treatment of diseases, including types of tumors. Different alkaloids have antiproliferative and antimetastatic effects on different types of cancer in vitro and in vivo. Compounds such as camptothecin, vinblastine, and colchicine have already been successfully developed into anticancer drugs. Colchicine binds to tubulin and interferes with tubulin polymerization, thereby disrupting microtubule formation. This issue leads to inhibiting the migration of leukocytes and other inflammatory cells and inhibiting the mitosis of dividing cells. Colchicine can also increase free cellular tubulin to limit mitochondrial metabolism in cancer cells through the inhibition of mitochondrial membrane voltage-gated anion channels. In addition, extensive research has shown that colchicine has anti-proliferative and anti-cancer properties in a wide variety of cell lines and animals. In addition, recent studies have shown that colchicine, as an anticancer agent, can effectively induce apoptosis. This is shown by its inhibitory effects on the growth of several tumor cell lines in vitro and in vivo, including gastric cell, hepatocellular carcinoma, hepatocellular carcinoma, and cholangiocarcinoma. To Colchicine is highly toxic at high doses, which limits its use in human cell therapy. Apoptosis is a regulated and programmed cell death process that involves the activation of various molecules to initiate cell death. Specific activation of apoptosis in tumor cells is a promising approach for cancer treatment. Considering the role of colchicine in inducing apoptosis, it can be considered a suitable candidate for investigating anticancer effects in the form of in vitro studies on breast cancer cell models and in vivo studies on mouse models with mammary tumors. However, the specific mechanisms of colchicine-induced cytotoxicity are controversial due to the variability of signaling pathways in different cell types. In addition, colchicine is highly toxic at high doses and the exact mechanism of its apoptotic effects in breast cancer cells is still unclear. Colchicine is an alkaloid widely used to treat gout. It also has a therapeutic effect on cancer through the induction of apoptosis, but the pathways involved in this process remain unclear. The present study was conducted to investigate the effect of this drug on mouse Breast cancer cell line in vitro and in vivo.

This research is of a fundamental type that was carried out experimentally. First, mouse mammary cancer cells (4T1) purchased from Pasteur Institute of Iran were cultured. Then, the effect of colchicine on apoptosis and related signaling pathways was determined using various tests including cell viability assay, real-time PCR, annexin V and propidium iodide staining, and western blot analysis. In vivo studies were also performed after tumor induction in mice and then their treatment.Effect of colchicineand related signaling pathways were determined using different tests including cell viability assay, real-time PCR, annexin V and propidium iodide staining and western blot analysis. In vivo studies were investigated through tumor induction with 4T1 cells in mice and then their treatment. After tumor formation, the antitumor activity of colchicine was compared in cancer mice. Tumor tissues after isolation, fixation and staining with hematoxylin and eosin were examined with a microscope for the presence of cancer symptoms.

The results showed that colchicine at a concentration of about 300 μg/ml killed 50% of 4T1 cancer cells. Colchicine significantly increased Bax and P53 mRNA expression and decreased Bcl-2 gene expression. In the in vivo study, it was shown that in the tumor tissue of mice treated with colchicine, the evidence of apoptosis and the area of ​​destruction and necrosis was much wider than that of the untreated group. The in vivo study showed that in the group treated with colchicine, the tumor tissue showed more evidence of apoptosis than the control group, and in the treated group, the area of destruction and necrosis was much wider than in the untreated group. In the tumor tissues of mice in the control group (without treatment), the signs of malignancy were more severe than in the group that had been treated, and abnormal mitotic forms were abundantly seen. Also, no metastases to the liver and spleen were observed in the treated group as well as in the control group. Finally, it can be concluded that the oral intake of pure colchicine reduces the size of induced tumors in mice, prevents further proliferation and metastasis, and induces Apoptotic. Studies have shown that tumors that grow faster, such as tumors from 4T1 cancer cells, are more invasive and metastasize to the surrounding tissues, but the cells of these tumors (with a high proportion of dividing cells) are the most sensitive to toxic compounds of the cell cycle, such as colchicine. They have sin. Continuous use of these compounds causes a high percentage of exposed cells to be destroyed. Reduction in the size of tumors and metastasis of cells to other places in mice treated with colchicine was observed in the present study.

Studies have shown that tumors that grow faster, such as tumors from 4T1 cancer cells, are more invasive and metastasize to the surrounding tissues, but the cells of these tumors (with a high proportion of dividing cells) are the most sensitive to They have cell cycle toxic compounds such as colchicine. Continuous use of these compounds causes a high percentage of exposed cells to be destroyed. Reduction in the size of tumors and metastasis of cells to other places in mice treated with colchicine was clearly observed in the present study. Colchicine had an effective role in inhibiting the proliferation of breast cancer cells, and its oral use reduced the size of induced tumors in mice, prevented further proliferation and metastasis, and induced apoptosis. The mechanism of toxicity of colchicine for cancer treatment is still not clear enough. In the present research, the results of all the tests showed that colchicine has an effective role in inhibiting the proliferation of mouse breast cancer cells and apoptosis through increasing the expression of pro-apoptotic genes and proteins Bax and p53, decreasing the expression of anti-apoptotic Bcl2 genes and proteins, and ultimately induces the activation of caspases.

Cancer development is a multi-stage process in which apoptosis plays an important role. Apoptotic agents from natural products like phenolic compounds can be used effectively in the treatment of cancer. Berberis vulgaris L. fruits are a rich source of natural phenolic compounds and have been evaluated for their apoptotic effects.

this study was carried out to evaluate the apoptotic effect of B. vulgaris fruits in normal and cancerous cells by investigating p53, Bax, and Bcl-2 genes expression and identifying an active compound.

B. vulgaris fruits were extracted with ethanol using maceration method. To yield an active compound, the extract was divided into fractions and subfractions that could be evaluated using chromatography techniques, and the purified compound structure was determined by nuclear magnetic resonance (NMR). The cytotoxic activity of the selected fraction against 3T3 and MCF-7 cell lines along with its effect on the mRNA apoptosis regulating genes like p53, Bax, and Bcl-2 were investigated subsequently.

Results showed that B. vulgaris extract increased the mRNA level of p53 and Bax and decreased Bcl-2 mRNA level in cancer cell lines. The structure of the purified compound was determined as the 3-caffeoylquinic acid (chlorogenic acid).

B. vulgaris fruit has in vitro antineoplastic activity by stimulating cellular apoptosis via increasing the levels of p53 and Bax proteins and decreasing Bcl-2 and comprises chlorogenic acid as one of its phenolic phytochemicals.

Pistacia atlantica subsp. kurdica is an endemic plant of Iran which belongs to Anacardiaceae family. This plant has been proposed as an efficacious remedy for gastrointestinal diseases such as inflammatory bowel disease, colitis, and peptic ulcer.

In this study we decided to evaluate the efficacy and pharmacological mechanisms involved in anti-colitis effect of essential oil of Pistacia atlantica in Wistar rats.

Sixty Wistar rats were selected for this study and were categorized to 6 groups. Experimental colitis was induced with 3% acetic acid solution. Animals of treatment groups received different daily doses of the essential oil (25, 50, and 100 mg/Kg, orally) and.Sulphasalazine (as the standard drug), for 7 days. At the end of the study, the rats were sacrificed and the colon was removed and assessed for macroscopic and microscopic changes. Also, in order to identify the mechanisms involved in anti-colitis effect of this natural drug, the level of cyclooxygenase (COX)-2 were evaluated.

The essential oil of Pistacia atlantica gum significantly reduced macroscopic and microscopic scores of colitis compared with control group (P <0.01). The essential oil with the dose of 100 mg/kg showed the highest anti-colitis effect. The oil of P. atlantica remarkably suppressed the level of COX-2 in colon tissue (P <0.05).

This research has proved the protective effect of oral administration of essential oil of P. atlantica gum on ulcerative colitis in rats. This natural drug performs anti-colitis potential through inhibiting the pro-inflammatory cytokines.

Sulfur compounds in plants can differ in number of sulfur groups، being cyclic or acyclic، and saturation number. They affect the flavor and fragrance of herbal products. Plants rich in sulfides like Allium and Ferula have beneficial effects on skin. Allium sulfides are disinfectant، antifungal، and hair stimulant. Likewise، Ferula sulfides have disinfectant and antifungal properties. Sulfides such as diallyl sulfide have been shown to possess antitumor activities on polycyclic aromatic hydrocarbon-induced mouse skin carcinogenesis and to reduce cell proliferation. Diallyl sulfide also regulates p21/rat sarcoma protein expression in dimethylbenzanthracene-induced neoplastic changes in mouse skin. Moreover، sulfur compounds are antileishmanial agents and improve hair and nail growth. It seems that sulfide derivatives of medicinal plants can be used in some dermatological products and cosmetics.

Leishmaniasis is an infectious disease caused by different strains of Leishmania. The disease affects many people in different countries، particularly in the developing countries. With regard to the symptoms and complications، the disease is categorized into the three types of cutaneous، cutaneous-mucosal، and visceral leishmaniasis. The cutaneous type of the disease is more common، and is prevalent in some countries including Iran. Leishmaniasis is transmitted via the bit of Phlebotomus papatasi and some other species of Phlebotomus. According to the World Health Organization reports، more than 350 million people in 88 countries are at the risk of the disease. Currently، 12 million people around the world are affected by the disease، and it is estimated that 1-2 million new cases of the disease occur each year. Almost 90% of the cutaneous leishmaniasis cases occur in Afghanistan، Brazil، Iran، Peru، Saudi Arabia، and Syria. Considering the several and dangerous adverse effects of currently available drug formulations، many attempts have been carried out to find drugs of plant origin that are more effective and affordable with less adverse effects. Evaluation and identification of medicinal plants used in the traditional medicine and their constituents could facilitate achieving this goal. So far، the anti-leishmaniasis effect of some plants and plant compounds such as quinones، terpenes، alkaloids، coumarins، flavonoids، lactones، chalcones، tetralones، and saponins have been confirmed. In this study، we have reviewed the medicinal plants used in the traditional medicine of countries and the plants’ constituents to introduce new sources to achieve compounds effective against leishmaniasis