Search results for: genistein

Authors: Tanveer Beg, Yasir H. Siddique, Gulshan Ara, Asfar S. Azmi, Mohammad Afzal

Abstract:

Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apoptosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treatment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Keywords: apoptosis, DNA damage markers, doxorubicin, genistein, genotoxicity, human lymphocyte culture

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Authors: Sanaa AM Elgayar, Sohair A Eltony, Maha Mahmoud Abd El Rouf

Abstract:

Background: Retinopathy remains an important complication of diabetes. Aim of work: This work was carried out to evaluate the protective effects of genistein from diabetic retinopathy in rat. Material and Methods: Fifteen adult male albino rats were divided into two groups; Group I: control (n=5) and Group II: streptozotocin induced diabetic group (n=10), which is equally divided into two subgroups; IIa (diabetic vehicle control) and IIb (diabetic genistein-treated). Specimens were taken from the retina 12 weeks post induction, processed and examined using light, immunohistochemical, ultrastructural techniques. Blood samples were assayed for the levels of glucose. Results: In comparison with the diabetic non-treated group, the histological changes in macro and microglial glial cells reactivity and retinal blood capillaries were improved in genistein-treated groups. In addition, GFAP and iNOS expressions in the retina and the blood glucose level were reduced. Conclusion: Genistein ameliorates the histological changes of diabetic retinopathy reaching healing features, which resemble that of a normal retina.

Keywords: diabetic retinopathy, genistein, glia, capillaries.

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Authors: Niranjani Wickramsinghe, Mario Soares, Stuart Johnson, Ranil Cooray, Vijay Jayasena

Abstract:

Tempeh is a traditional fermented soya bean food in Indonesia which is produced from de-hulled soya fermented with Rhizopusoligosporus. Natto is a traditional Japanese food made from whole soya bean seed fermentation with the bacteriaBacillus subtilis natto. Lupin is a grain legume with a low content of the phytoestrogenic isoflavones genistein and daidzein compared to soya. However due a comparable nutrition profile and increased cost effectiveness relative to soy, lupin has been substituted into various oriental fermented foods such as tempe and natto. Lupin tempeh and lupin natto were prepared using either WS or DHS. Analysis for genistein and daidzein content was conducted using HPLC for time points zero, 12h, 24h, 36h, 48h and 72h after fermentation. Results revealed that the amount of genistein and daidzein significantly increased with time in both tempeh and natto. Both isoflavones peaked at 48h in lupin tempeh and earlier at 36h in lupin natto. WS tempeh and WS natto had significantly more genistein than WHS tempe and WHS natto. Diadzeincontent of WHS tended to be higher than WS across both products. It is concluded that, fermentation time increased the amount of genistein and daidzein content in both lupin tempeh and natto and the form of lupin raw material used affected the genistein level and to some extent the daidzein content of fermented products.

Keywords: lupin, natto, soya, tempeh

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Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

Abstract:

Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: Dina F. Mansour, Dalia O. Saleh, Rasha E. Mostafa

Abstract:

Cyclophosphamide (CP), the most commonly used chemotherapeutic agent, was reported to cause many side effects including urotoxicity, cardiotoxicity, gonadotoxicity, and hepatotoxicity; this limits its clinical practice. In the present study, the protective effect of genistein (GEN), the major phytoestrogen in soy products that possesses various pharmacological activities, has been investigated against CP-induced acute liver damage in rats. Forty adult Sprague-Dawley rats were allocated into five groups. The first group received the vehicles and act as normal control. In the other groups, rats were injected with a single dose of CP (200 mg/kg, i.p). The last three groups were pretreated with subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Forty-eight hours following CP injection, rats of all groups were investigated for the serum levels of alanine transaminase and aspartate transaminase, as well as the liver contents of reduced glutathione, malondialdehyde, nitrite, interleukin-1β, and myeloperoxidase. Histopathological examination of liver tissues was also conducted. CP resulted in acute liver damage in rats as evidenced by alteration of liver function biomarkers, oxidative stress, and inflammatory markers; that was confirmed by the histopathological outcomes. Pretreatment of rats with GEN significantly protected against CP-induced deterioration of liver function and showed marked anti-oxidant and anti-inflammatory properties that were demonstrated by the biochemical and histopathological findings. In conclusion, the present findings demonstrated the protective effects of GEN against CP-induced liver damage and suggested role of its antioxidant and anti-inflammatory activities.

Keywords: cyclophosphamide, genistein, inflammation, interleukin-1β, liver, myeloperoxidase, oxidative stress

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Agatha Swasti Ayuning Tyas

Abstract:

Hyperglycemia in Diabetes Mellitus (DM) is an important factor in cellular and vascular damage, which is caused by activation of C Protein Kinase, polyol and hexosamine track, and production of Advanced Glycation End-Products (AGE). Those mentioned before causes the accumulation of Reactive Oxygen Species (ROS). Oxidative stress increases the expression of proinflammatory factors IL-6 as one of many signs of endothelial disfunction. Genistein in soy milk has a high immunomodulator potential. Goat milk contains amino acids which have antioxidative potential. Fermented kefir has an anti-inflammatory activity which believed will also contribute in potentiating goat milk and soy milk. This study is a quasi-experimental posttest-only research to 30 Wistar mice. This study compared the levels of IL-6 between healthy Wistar mice group (G1) and 4 DM Wistar mice with intervention and grouped as follows: mice without treatment (G2), mice treated with 100% goat milk kefir (G3), mice treated with combination of 50% goat milk kefir and 50% soy milk kefir (G4), and mice treated with 100% soy milk kefir (G5). DM animal models were induced with Streptozotocin & Nicotinamide to achieve hyperglycemic condition. Goat milk kefir and soy milk kefir are given at a dose of 2 mL/kg body weight/day for four weeks to intervention groups. Blood glucose was analyzed by the GOD-POD principle. IL-6 was analyzed by enzyme-linked sandwich ELISA. The level of IL-6 in DM untreated control group (G2) showed a significant difference from the group treated with the combination of 50% goat milk kefir and 50% soy milk kefir (G3) (p=0,006) and the group treated with 100% soy milk kefir (G5) (p=0,009). Whereas the difference of IL-6 in group treated with 100% goat milk kefir (G3) was not significant (p=0,131). There is also synergism between glucose level and IL-6 in intervention groups treated with combination of 50% goat milk kefir and 50% soy milk kefir (G3) and the group treated with 100% soy milk kefir (G5). Combination of 50 % goat milk kefir and 50% soy milk kefir and administration of 100% soy milk kefir alone can control the level of IL-6 remained low in DM Wistar mice induced with streptozocin and nicotinamide.

Keywords: diabetes mellitus, goat milk kefir, soy milk kefir, interleukin 6

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