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Abstract

Naturally occurring modulators of carcinogenesis, including dietary compounds, can either stimulate or inhibit cancer development. Mechanisms responsible for these effects are unknown. Garlics used in this study were freshly prepared, and their effectiveness in augmenting natural killer (NK) activity was evaluated. Administration of 20 mg/kg produced an optimum augmentation of NK activity. A glycoprotein with MW of about 14 kDa was isolated from garlic extract and its activity was assessed. It could induce NK augmentation against K562 tumor cell line. In vivo studies also confirmed that Fraction Residue 10 (R10) of garlic extract partially purified by ultra filtration and further purified by chromatography could induce a resistance to the growth of spontaneous mammary carcinoma in Balb/c mice. NK cytotoxic activities were evaluated by flowcytometry.

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... In addition, the effects of garlic on PCOS have been assessed before [22][23][24]. On the other hand, previous studies demonstrated immunomodulatory effects of R10 fraction of garlic in the treatment of inflammatory conditions such as cancer [25,26]. Considering previous studies suggesting immunomodulatory therapy for PCOS [2,9,17], this study presented here aimed to evaluate the potential immunomodulatory effects of R10 fraction of garlic in a mouse model of PCOS. ...
... Preparation of residue 10 (R10) fraction of garlic R10 fraction was prepared from Hamedan province garlic (Allium sativum 1753 No 2-1912No 2- , 14.06.2002 which was previously reported by The Iranian Society of Pharmacognosy [18,19] as described before [25,26]. Briefly, the bulbs of garlic were peel off, washed, chopped in small pieces, added into two parts of distilled water, and homogenized in a blender. ...
... Treatment of PCOS mice with the purified R10 fraction was performed by intraperitoneal injection (20 mg/ kg) based on previous studies and unpublished studies of Professor Hassan [25,26], according to two different strategies including (1) daily treatment during 1 week (R10 Treat 1) and (2) every-other-day treatment for 2 weeks (R10 Treat 2). Three days after the last treatment and at the estrous phase, the mice were sacrificed with ketamine/xylazine and then the blood samples were taken from the myocardial tissue of mice. ...
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Polycystic ovary syndrome (PCOS) is an inflammatory endocrine-metabolic disorder related to reproductive system characterized by polycystic ovarian morphology, androgen excess, and chronic anovulation. Current treatments haven’t been very successful in PCOS treatment and the problem still remains as a challenge. Therefore, new approaches should be applied to overcome the disease. Previous studies demonstrated immunomodulatory effects of R10 fraction of garlic in the treatment of inflammatory conditions such as cancer. Considering previous studies suggesting immunomodulatory therapy for PCOS, therapeutic effects of R10 fraction was evaluated in a mouse model of PCOS. To do so, PCOS was developed by intramuscular injection of estradiol valerate. Treatment with R10 fraction, isolated from garlic, was performed and the alterations in hormonal levels (estradiol, progesterone, and testosterone), T cell polarization markers (IFN-γ, IL-4, and IL-17), and expression of fertility-related genes (Gpx3 and Ptx3) were evaluated. The results showed that hormonal levels were elevated in PCOS model comparing to normal animals but were markedly modulated after treatment with R10 fraction. Moreover, a severe disturbance in T cell polarization with a significant reduction of fertility-related genes expression were detected in PCOS-induced ovaries. Treatment with R10 fraction also represented modulatory effects on T cell polarization by increasing IL-4 and decreasing IL-17 and IFN-γ levels. Accordingly, fertility-related genes were also modulated following treatment with R10 fraction in PCOS. Our study elucidated that R10 fraction of garlic possess immunomodulatory effects alleviating PCOS symptoms. This approach could be adjusted to give rise the optimum therapeutic results and considered as a candidate therapeutic approach for PCOS.
... Recently there has been great interest in possible antiinflammatory property of naturally derived compounds [16][17][18] . Aged garlic extract (AGE) was established to contain one major immunomodulatory protein present in R10 fraction called garlic 14-kDa protein which has been proved to impart a wide range of immunomodulatory properties [19][20][21][22][23] . ...
... Isolation of 14-kDa protein from aged garlic extract Aqueous extract was prepared from dry garlic bulbs (AGE) by a method described previously [19][20][21][22][23] . Briefly, garlic bulbs were homogenized with distilled water in a blender. ...
... Previous studies have shed light on the in vitro anti-inflammatory and immunomodulatory effects of a compound isolated from garlic called garlic 14-kDa protein in peritoneal macrophages. Previous studies have reported immunomodulatory potential of garlic 14-kDa protein which includes enhancement of natural killer (NK) cell activity 19 , induction of T-lymphocyte proliferation, and augmentation of delayed type hypersensitivity (DTH) response 20 . In addition, garlic 14-kDa protein isolated from AGE thought to suppress indoleamin 2,3dioxygenase (IDO) in mononuclear cells 21 . ...
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Context: Garlic 14-kDa protein is purified from garlic (Allium sativum L.) which is used in traditional medicine and exerts various immunomodulatory activities. Objective: The present study investigated the suppressive effect of garlic 14-kDa protein on LPS-induced expression of pro-inflammatory mediators and underlying mechanism in inflammatory macrophages. Materials and methods: J774A.1 macrophages were treated with 14-kDa protein (5-30 μg/ml) with/without LPS (1 μg/ml) and the production of inflammatory mediators such as prostaglandin E2 (PGE2), TNF-α, and IL-1β released were measured using ELISA. Nitric oxide (NO) production was determined using the Griess method. The anti-inflammatory activity of 14-kDa protein was examined by measuring inducible nitric oxide synthase and cyclooxygenase-2 proteins using western blot. The expression of nuclear NF-κB p65 subunit was assessed by western blot. Results: Garlic 14-kDa protein significantly inhibited the excessive production of NO, PGE, TNF-α, and IL-1β in lipopolysaccharide (LPS)-activated J774A.1 macrophages in a concentration-related manner without cytotoxic effect. Western blot analysis demonstrated that garlic 14-kDa protein suppressed corresponding inducible NO synthase expression and activated cyclooxygenase-2 protein expression. The inhibitory effect was mediated partly by a reduction in the activity and expression of transcription factor NF-κB protein. Conclusion: Our results suggested, for the first time, garlic 14-kDa protein exhibits anti-inflammatory properties in macrophages possibly by suppressing the inflammatory mediators via the inhibition of transcription factor NF-κB signaling pathway. The traditional use of garlic as anti-inflammatory remedy could be ascribed partly to 14-kDa protein content. This protein might be a useful candidate for controlling inflammatory diseases and further investigations in vivo.
... Garlic extract and a garlic protein fraction were shown to augment the oxidative burst in peritoneal macrophages of Balb/c mice (21). Ghazanfari et al. showed that garlic extract induces a shift in cytokine pattern in Balb/c mice with a Leishmania major infection and an upshot in the immune response with regard to Th 1 (IFN-γ, IL-2) (22,23). At the same time, a unique garlic preparation called AGE has been reported to have a series of pharmacologic effects including immunomodulation (20). ...
... Garlic has been consumed for food and medicinal purposes worldwide for thousands of years. Garlic's beneficial effects on human health are known to everyone (22,24). Currently, the garlic plant itself, as well as its numerous extracts, are commercially available as dietary supplements (20,22,24). ...
... Garlic's beneficial effects on human health are known to everyone (22,24). Currently, the garlic plant itself, as well as its numerous extracts, are commercially available as dietary supplements (20,22,24). Epidemiological studies suggest garlic consumption has preventive effects in some types of cancer (18). ...
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Objective: Aflatoxin B1 (AFB1) suppresses the immune system. To decrease such suppressive effects on the immune system, a wide range of herbal medicines like garlic are utilized. Biological activities of garlic in vitro and in vivo have also been verified. Our previous studies demonstrated that aged garlic (dry garlic bulbs preserved in the freezer for six months at -20˚C) have increased immunostimulator fractions and reduced immunosuppressor fractions. This study focuses on the immunosuppressor activity of AFB1 and immunostimulator activity of aged garlic extract (AGE) through the evaluation of CD4(+) CD25(+) FoxP(+) regulator cell (Treg) counts and the pattern of cytokine production in Balb/c normal mice. Materials and methods: In this experimental research, AFB1 was separated from Aspergillus flavus (PTCC 5004) by HPLC and AGE prepared using the Mantis method. The Delayed-Type Hypersensitivity (DTH) test was carried out to determinate the effectiveness of different doses of AGE and AFB1, which can both have an effect on the immune system. Subsequent experiments were carried out on 20 Balb/c mice to estimate the effects of AGE and AFB1 on the number of Treg cell in 4 groups: 10 µl/kg/day of AFB1 and AGE diluents were administered for 4 consecutive days to group 1. AFB1, 2. control, 3. AGE + AFB1 and 4. AGE via intraperitoneal (IP) route, respectively. Mice were sacrificed and splenocytes harvested and the percentage of splenic Treg cells was measured by flow cytometry analysis. The ELISA method was utilized to measure Cytokine production. Results: The findings reveal that AGE increased the level of IFN-λ and IL-4 cytokines produced by splenocytes stimulated by specific tumor antigen and decreased the number of Treg cells in the spleen (p<0.05). AFB1 increased the number Treg cells in the spleen and decreased cytokine production (p<0.05). In groups 2 (control) and 4 (AGE) the number of Treg cells decreased (p value<0.05) whereas in groups 1 and 3 the number of Treg cells increased (p<0.05). Conclusion: This study indicated that AGE is able to alter the cytokine production in normal mice into a Th1 protective pattern which is beneficial to the immune system in general and anti-tumor immunity in particular. AFB1 is able to alter the cytokine production into a Th2 protective pattern. Therefore, AGE might be used as herbal medicine with few side effects as compared to chemotherapy in treating cancers caused by substances like AFB1.
... Proteins isolated from garlic modulate NK cell line activity in the mesenteric lymph node of mouse [70], while AGE modulates the number and the activity of NK cells in patients with various advanced cancers [71] and also increases NK activities against different cancerous cell lines [72]. Moreover, in healthy subjects, AGE increases the NK cell population [69]. ...
... Even more allicin induces apoptosis through JNK pathway activation and mitochondrial Bax translocation in cells human ovarian cell line SKOV3 [124]. Other studies have demonstrated the role of protein fractions from garlic bulbs in tumor growth and intratumor-infiltrated T lymphocytes in mice transplanted with mammary tumor cells [66], as well as a significant decrease in the size of mouse mammary tumor [70] and complete suppression of growth of Human erythroleukemia cell line HEL in a dose-dependent manner [125]. Recently, our group evidenced that alliin treatment of 3T3-cell-derived adipocytes is capable of downregulating several cancer-related genes [30]. ...
Article
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The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.
... In vitro cytotoxic studies have revealed that aged garlic extract significantly improves the cytotoxic capability of human peripheral blood NK cells against K562 tumor cells (43,44), which is consistent with the findings of the present study. Thus, the ability of FGE to stimulate immune cell IL-12 release must have aided the generation of INF-γ-producing NK cells. ...
... Thus, the ability of FGE to stimulate immune cell IL-12 release must have aided the generation of INF-γ-producing NK cells. As demonstrated herein and in previous research, the inhibition of tumor cell lines, such as YAc-1 may be further aided by extract-induced NK cells (43). ...
... Results showed that animals treated with different doses of garlic fractions had increased T-cell activation and an increase of intra-tumor infiltration of lymphocytes in all doses [124]. Hassan et al. [125] reported that administration of 20 mg/kg of an isolated fraction of garlic extract caused a significant increase in NK activity in mice. The immunomodulatory effect of fresh garlic compounds has also been evidenced in humans. ...
... [46] Mice Purified fraction of garlic extract 10-40 mg/mL, oral -Increase of NK activity with the 20 mg/mL dose. [125] Mice with colitis Alliin 500 mg/kg, oral -Suppression of LPS-induced AP-1/NF-κB/STAT-1 activation. ...
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Glutathione and aged garlic extract are sulfur-containing products that play important protective and regulatory roles within the immune system and in oxidative processes. Hydrogen sulfide (H2S), an endogenous, gaseous, signaling transmitter, has also been shown to be involved in the regulation of inflammation. Recent studies have shown that sulfur-containing compounds from garlic have beneficial effects in attenuating outcomes associated with cardiovascular disease and inflammation by a mechanism that may be related to the H2S signaling pathway. In this review, we summarize the main functions of glutathione (GSH), garlic derivatives and H2S and their role in the immune response and impact on health and disease.
... Several studies have indicated that intake of garlic reduces both carcinoma and sarcoma risk in different tissues and body organs, such as bladder, colon, prostate, lung, oesophagus, stomach, skin, brain, and liver [84]. Other studies have demonstrated the role of protein fractions from garlic bulbs in tumor growth, since a significant decrease in the size of mouse mammary tumor [85] and complete suppression of growth of Human Erythroleukemia cell line (HEL), in a dose-dependent manner, were found [86]. The mechanisms of these effects are not fully understood. ...
... Other studies showed that proteins isolated from garlic modulate NK cell line activity in the mesenteric lymph node of mouse [43]. Therefore, garlic acts as a proliferation inducer for this cell population [85], while aged garlic extract modulates the number and the activity of NK cells in patients with various advanced cancers [37] and also increases NK activities against different cancer cell lines [96]. However, results differ from one study to another. ...
Article
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Allium Sativum L. (garlic), which is a species of the onion family, Alliaceae, is one of the most used plants in traditional medicine worldwide. More than 200 chemicals with diverse properties have been found in garlic extracts. Several garlic compounds were suggested to be efficient in improving various pathologies including certain types of cancer. This paper is an overview of data about garlic biological activities in vitro and/or in vivo on immune cells, on the development of certain inflammatory diseases, and on different types of carcinomas and sarcomas. Garlic and its compounds were found to have notable antioxidant properties. Garlic therapeutic potential has also been studied in several inflammatory diseases such as allergic-airway inflammation, inflammatory bowel disease, arthritic rheumatism, and atherosclerosis. Furthermore, garlic was found to be able to maintain the immune system homeostasis and to exhibit beneficial effects on immune cells especially through regulation of proliferation and cytokine gene expression. Finally, we will show how major garlic components such as sulfur compounds and polyphenols might be responsible for the garlic biological activities revealed in different situations. If identified, specific compounds present in garlic could potentially be used in therapy.
... Proteins isolated from garlic modulate NK cell line activity in the mesenteric lymph node of mouse [70], while AGE modulates the number and the activity of NK cells in patients with various advanced cancers [71] and also increases NK activities against different cancerous cell lines [72]. Moreover, in healthy subjects, AGE increases the NK cell population [69]. ...
... Even more allicin induces apoptosis through JNK pathway activation and mitochondrial Bax translocation in cells human ovarian cell line SKOV3 [124]. Other studies have demonstrated the role of protein fractions from garlic bulbs in tumor growth and intratumor-infiltrated T lymphocytes in mice transplanted with mammary tumor cells [66], as well as a significant decrease in the size of mouse mammary tumor [70] and complete suppression of growth of Human erythroleukemia cell line HEL in a dose-dependent manner [125]. Recently, our group evidenced that alliin treatment of 3T3-cell-derived adipocytes is capable of downregulating several cancer-related genes [30]. ...
Article
Full-text available
The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.
... After ammonium sulfate precipitation, the mixture is centrifuged at 9000 rpm for 1 h. The pellet is solubilised in (Ghazanfari et al., 2002;Hassan et al., 2003) NIK -NF-κB-inducing kinase; PLA2 -phospholipase A2; IRAK-4 -interleukin-1 receptor-associated kinase 4; COX2 -cyclooxygenase 2; DBP -Diastolic blood pressure; SBP -systolic blood pressure; ACE -angiotensin-converting enzyme; LPI -Lipid peroxidase inhibition; FRP -Ferric reducing power assay; GPH -Garlic protein hydrolysate; SHR -spontaneously hypertensive rats; GPC -Gel permeation chromatography; DPPH-1,1-diphenyl-2picrylhydrazil; DDM -Dose-dependent manner. ...
Article
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Garlic is a popular food spice with diverse and well-established medicinal properties. Many research interests have been directed toward the biological activities of the phytochemical constituents of garlic. However, prospects of its bioactive proteins and peptides have been understudied to date. With the advances in food proteomics/peptide research, a review of studies on garlic bioactive proteins and peptides, especially on their nature, extraction, and biological activities, is timely. Garlic has been reported to express several proteins, endogenous and protein-derived peptides with interesting bioactivities, including antioxidant, anti-inflammatory, antibacterial, antifungal, anti-proliferative, antiviral, anti-hypertensive and immunomodulatory activities, suggesting their therapeutic and pharmacological potentials. Compared to legumes, the low protein contents of garlic bulbs and their low stability are possible limitations that would hinder future applications. We suggest adopting heterologous expression systems for peptide overproduction and stability enhancement. Therefore, we recommend increased scientific interest in the bioactive peptides of garlic and other spice plants.
... Moreover, garlic has been proven to be a practicable immune response transformer [20]. Garlic stimulates the natural killer (NK) activity [24] and T-lymphocyte proliferation [25]. Also, garlic extract was shown to the supplementary and provider of the oxidative burst in peritoneal macrophages of BALB/c mice. ...
Article
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We investigated the effects of garlic extract on the peripheral blood immune cells in mice treated with the extract for twenty days. The study was carried out on ten male ICR mice. The mice were divided into two groups. The control group received a distilled water and garlic extract group in which the mice received garlic extract at a dose of 500 mg/kg. b.w, for twenty days. Blood samples were collected on day ten and day twenty post inoculation (p.i) for differential leucocytic count (WBCs count and Lymphocytes %) and flowcytometric analysis. In comparison to the control group, garlic extract treatment induced a significant increase in WBCs count and lymphocytes percentage on day 10 and day 20 p.i. Furthermore, garlic extract administration to the experimental mice caused significant increase in the expression percentage of CD4, CD8 and γ-δ T cells when analyzed by flowcytometry on day 10 and increased dramatically on day 20 p.i. The WBCs count and lymphocytes percentage as well as the percentage of the expressed cells increased on day 20 more than their levels on day 10 p.i with a fixed dose of garlic extract. In conclusion, inoculation of garlic extract induced an increase in the immune responses of the cellular immunity in the peripheral blood circulation of mice. Scholars Middle East Publishers
... Moreover, garlic has been proven to be a practicable immune response transformer [20]. Garlic stimulates the natural killer (NK) activity [24] and T-lymphocyte proliferation [25]. Also, garlic extract was shown to the supplementary and provider of the oxidative burst in peritoneal macrophages of BALB/c mice. ...
Article
Full-text available
We investigated the effects of garlic extract on the peripheral blood immune cells in mice treated with the extract for twenty days. The study was carried out on ten male ICR mice. The mice were divided into two groups. The control group received a distilled water and garlic extract group in which the mice received garlic extract at a dose of 500 mg/kg. b.w, for twenty days. Blood samples were collected on day ten and day twenty post inoculation (p.i) for differential leucocytic count (WBCs count and Lymphocytes %) and flowcytometric analysis. In comparison to the control group, garlic extract treatment induced a significant increase in WBCs count and lymphocytes percentage on day 10 and day 20 p.i. Furthermore, garlic extract administration to the experimental mice caused significant increase in the expression percentage of CD4, CD8 and γ-δ T cells when analyzed by flowcytometry on day 10 and increased dramatically on day 20 p.i. The WBCs count and lymphocytes percentage as well as the percentage of the expressed cells increased on day 20 more than their levels on day 10 p.i with a fixed dose of garlic extract. In conclusion, inoculation of garlic extract induced an increase in the immune responses of the cellular immunity in the peripheral blood circulation of mice.
... Hypoglycemic activity-In a human trial, it has been demonstrated that treatment with time-released garlic product (Allicor) resulted in better metabolic control due to the lowering of fasting blood glucose and triglyceride levels. There is a significant reduction in the level of fasting blood glucose in from 1-2 weeks to 24 weeks, as well as significantly decrease in fructosamine and glycated hemoglobin in a clinical study Liu et al., 2005;Liu et al., 2006;Thomson et al., 2006;Jalal et al., 2007;Sobenin et al., 2008;Drobiova et al., 2009;Wang et al., 2017 Brain health-garlic have a protective effect against ischemic brain injury; preclinical in vitro and animal studies suggested garlic could protect neurons from Abeta-induced neurotoxicity and apoptosis Saleem et al., 2006;Borek, 2006;Chauhan & Sandoval, 2007;Gupta et al., 2009;Aguilera et al., 2010 Immunomodulatory activity-In vitro and in vivo (animal) studies have found that garlic have several immune-enhancing effects (stimulation of lymphocyte proliferation and interferon-γ release, and enhancement of macrophage phagocytosis and killer cell activity) Salman et al., 1999;Hassan et al., 2003;Ishikawa et al., 2006;Chandrashekar & Venkatesh, 2009 Bioactives from culinary spices and herbs: a review Embuscado mint, nutmeg, oregano, peppers, rosemary, saffron, sage, savory, sumac, tarragon and thyme): 1.5-3.2% (Tsui et al., 2018). ...
... Hypoglycemic activity-In a human trial, it has been demonstrated that treatment with time-released garlic product (Allicor) resulted in better metabolic control due to the lowering of fasting blood glucose and triglyceride levels. There is a significant reduction in the level of fasting blood glucose in from 1-2 weeks to 24 weeks, as well as significantly decrease in fructosamine and glycated hemoglobin in a clinical study Liu et al., 2005;Liu et al., 2006;Thomson et al., 2006;Jalal et al., 2007;Sobenin et al., 2008;Drobiova et al., 2009;Wang et al., 2017 Brain health-garlic have a protective effect against ischemic brain injury; preclinical in vitro and animal studies suggested garlic could protect neurons from Abeta-induced neurotoxicity and apoptosis Saleem et al., 2006;Borek, 2006;Chauhan & Sandoval, 2007;Gupta et al., 2009;Aguilera et al., 2010 Immunomodulatory activity-In vitro and in vivo (animal) studies have found that garlic have several immune-enhancing effects (stimulation of lymphocyte proliferation and interferon-γ release, and enhancement of macrophage phagocytosis and killer cell activity) Salman et al., 1999;Hassan et al., 2003;Ishikawa et al., 2006;Chandrashekar & Venkatesh, 2009 Bioactives from culinary spices and herbs: a review Embuscado mint, nutmeg, oregano, peppers, rosemary, saffron, sage, savory, sumac, tarragon and thyme): 1.5-3.2% (Tsui et al., 2018). ...
Article
Full-text available
Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification , their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
... Hypoglycemic activity-In a human trial, it has been demonstrated that treatment with time-released garlic product (Allicor) resulted in better metabolic control due to the lowering of fasting blood glucose and triglyceride levels. There is a significant reduction in the level of fasting blood glucose in from 1-2 weeks to 24 weeks, as well as significantly decrease in fructosamine and glycated hemoglobin in a clinical study Liu et al., 2005;Liu et al., 2006;Thomson et al., 2006;Jalal et al., 2007;Sobenin et al., 2008;Drobiova et al., 2009;Wang et al., 2017 Brain health-garlic have a protective effect against ischemic brain injury; preclinical in vitro and animal studies suggested garlic could protect neurons from Abeta-induced neurotoxicity and apoptosis Saleem et al., 2006;Borek, 2006;Chauhan & Sandoval, 2007;Gupta et al., 2009;Aguilera et al., 2010 Immunomodulatory activity-In vitro and in vivo (animal) studies have found that garlic have several immune-enhancing effects (stimulation of lymphocyte proliferation and interferon-γ release, and enhancement of macrophage phagocytosis and killer cell activity) Salman et al., 1999;Hassan et al., 2003;Ishikawa et al., 2006;Chandrashekar & Venkatesh, 2009 Bioactives from culinary spices and herbs: a review Embuscado mint, nutmeg, oregano, peppers, rosemary, saffron, sage, savory, sumac, tarragon and thyme): 1.5-3.2% (Tsui et al., 2018). ...
Article
Full-text available
Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification, their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
... Hypoglycemic activity-In a human trial, it has been demonstrated that treatment with time-released garlic product (Allicor) resulted in better metabolic control due to the lowering of fasting blood glucose and triglyceride levels. There is a significant reduction in the level of fasting blood glucose in from 1-2 weeks to 24 weeks, as well as significantly decrease in fructosamine and glycated hemoglobin in a clinical study Liu et al., 2005;Liu et al., 2006;Thomson et al., 2006;Jalal et al., 2007;Sobenin et al., 2008;Drobiova et al., 2009;Wang et al., 2017 Brain health-garlic have a protective effect against ischemic brain injury; preclinical in vitro and animal studies suggested garlic could protect neurons from Abeta-induced neurotoxicity and apoptosis Saleem et al., 2006;Borek, 2006;Chauhan & Sandoval, 2007;Gupta et al., 2009;Aguilera et al., 2010 Immunomodulatory activity-In vitro and in vivo (animal) studies have found that garlic have several immune-enhancing effects (stimulation of lymphocyte proliferation and interferon-γ release, and enhancement of macrophage phagocytosis and killer cell activity) Salman et al., 1999;Hassan et al., 2003;Ishikawa et al., 2006;Chandrashekar & Venkatesh, 2009 Bioactives from culinary spices and herbs: a review Embuscado mint, nutmeg, oregano, peppers, rosemary, saffron, sage, savory, sumac, tarragon and thyme): 1.5-3.2% (Tsui et al., 2018). ...
Article
Full-text available
Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification, their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
... Among the plants of the genus Allium L. (family Amaryllidaceae), garlic (Allium sativum L.) [9], is one of the most important species of this genus. Its effects have been reported on the immune system [10,11]. For many centuries, garlic has been used as a therapeutic and culinary agent [9,12]. ...
... Among the plants of the genus Allium L. (family Amaryllidaceae), garlic (Allium sativum L.) [9], is one of the most important species of this genus. Its effects have been reported on the immune system [10,11]. For many centuries, garlic has been used as a therapeutic and culinary agent [9,12]. ...
Article
Full-text available
Background: Immune cells perform unique functions against infections and imbalances in immunity associated with various diseases. Applying natural products may control immune responses. Among herbals, much attention has been paid to the immunoregulatory functions of Allium sativum. However, the effects of other Allium species on the immune system have remained undiscovered. Therefore, the current study investigated the effects of A. sativum, A. Iranicum, A. elburzense, and A. asarense bulb extracts on macrophage and lymphocyte viability. Materials and Methods: The different concentrations of aqueous extracts of the aged bulb samples were prepared and used for the incubation of examined immune cells. Macrophages and lymphocytes were isolated and cultured in the presence of different concentrations of bulb extracts of Allium species. Macrophages and lymphocytes viability was followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The applied Allium species had stimulatory or inhibitory effects on the examined immune cells at different concentrations. Allium sativum demonstrated the highest effects on macrophage viability indices at 1 mg/mL. The similar effects were found for A. Iranicum extract on macrophage viability indices at 0.01 mg/mL. The bulb extract of A. sativum at the most used concentrations stimulated lymphocyte viability indices. The bulb extracts of all 4 Allium species inhibited viability indices of lymphocytes at 1 mg/mL. The bulb extracts of A. elburzense, at all of the applied concentrations, slightly affected viability indices of the macrophage and lymphocyte. Conclusion: Besides A. sativum, wild growing Allium species could be introduced to study their immunomodulatory effects on various diseases.
... Immunomodulatory activity.-In vitro and in vivo (animal) studies have found that garlic and its constituents have several immune-enhancing effects such as stimulation of lymphocyte proliferation and interferon-γ release and enhancement of macrophage phagocytosis and killer cell activity (318)(319)(320)(321). However, more studies are needed to understand the significance of these emerging data. ...
Article
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Spices and herbs have been in use for centuries both for culinary and medicinal purposes. Spices not only enhance the flavor, aroma, and color of food and beverages, but they can also protect from acute and chronic diseases. More Americans are considering the use of spices and herbs for medicinal and therapeutic/remedy use, especially for various chronic conditions. There is now ample evidence that spices and herbs possess antioxidant, anti-inflammatory, antitumorigenic, anticarcinogenic, and glucose- and cholesterol-lowering activities as well as properties that affect cognition and mood. Research over the past decade has reported on the diverse range of health properties that they possess via their bioactive constituents, including sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, especially flavonoids and polyphenols. Spices and herbs such as clove, rosemary, sage, oregano, and cinnamon are excellent sources of antioxidants with their high content of phenolic compounds. It is evident that frequent consumption of spicy foods was also linked to a lower risk of death from cancer and ischemic heart and respiratory system diseases. However, the actual role of spices and herbs in the maintenance of health, specifically with regards to protecting against the development of chronic, noncommunicable diseases, is currently unclear. This review highlights potential health benefits of commonly used spices and herbs such as chili pepper, cinnamon, ginger, black pepper, turmeric, fenugreek, rosemary, and garlic.
... Further studies on the extract allowed to identify a fraction with possible stimulatory effect. The R10 fraction, injected daily to mice, significantly reduced tumor growth [72]. In addition, research conducted on patients suffering from liver, pancreatic, or colon cancer, who were treated with aged garlic extract (AGE), demonstrated a significant increase of both NK cell number and NK cell activity in the AGE group; however, the quality of patients' life did not improve [73]. ...
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Natural killer (NK) cells are lymphocytes of the innate immune system that survey the body for stressed and abnormal cells. The integration of signals that they receive through various inhibitory and activating cell surface receptors controls their activation and ability to kill target cells and produce cytokines. In this manner, phenotypically and functionally distinct subsets of NK cells help protect against microbial infections and cancer and shape the adaptive immune response. NK cells can use two different mechanisms to kill their targets, either by cytotoxic granule exocytosis or by induction of death receptor-mediated apoptosis. Death ligands belong to the tumor necrosis factor (TNF) family of ligands. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which granzymes and associated molecules can enter and induce apoptosis. NK cells are also involved in antibody-dependent cellular toxicity via the CD16 receptor. In addition to target recognition, NK cells can be also activated by treatment with multiple compounds with stimulatory properties. Apart from interleukins, which belong to the best characterized group of NK cell-stimulating compounds, vitamins and constituents extracted from plants also display the ability to activate NK cells. The current review characterizes several groups of NK cell-activating compounds: vitamins belonging to classes A, B, C, D, and E, polysaccharides, lectins, and a number of phytochemicals used in cancer research, exhibiting stimulatory properties when applied to NK cells. Although in most cases the exact mechanism of action is not known, constituents described in this review seem to be promising candidates for NK cell-stimulating drugs.
... Anti-proliferative action of garlic compounds to retard the tumor growth has been studied using the epidemiologic studies and animal experiments. Mice transplanted with mammary tumor cells were given supplements of protein extractions from garlic bulb and a significant decrease in the size of mouse mammary tumor was observed [28] . Different studies show that garlic rich in allicin compound inhibits proliferation of human mammary endometrial and colon cancer cells [29] . ...
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Garlic (Allium sativum L.) botanically a member of the Lillaceae family and Allium genus, is considered to be rich in medicinal properties. The undamaged bulbs contain allin which will be enzymatically converted to allicin during cutting. Allicin, is the major bioactive compound found in garlic followed by other organosulfur compounds. Preparation of garlic extractions can be done in liquid form and solid form. The composition and bioactivity of the extraction depend on the strain, age, method of preparation and consumption method. When extracted and isolated, the bioactive compounds of garlic show a wide range of beneficial health effects to treat various infectious diseases, non-communicable diseases as well as metabolic and genetic disorders. An overview is provided on the numerous clinical and experimental investigations done on the reduction of LDL cholesterol level, cardiovascular disease, blood glucose levels by garlic derivative compounds. Furthermore, anti-carcinogenic effect, anti-microbial effect and antioxidant property of garlic are also reviewed.
... Different chemicals were detected in garlic using different extraction procedures. Garlic also shifts polarization of CD4 + T cells toward T helper cells 1 (Th1), [6,7] increases frequency and function of natural killer (NK) cells, [6,[8][9][10][11][12][13] enhances frequency and proliferation potential of lymphocytes, [14,15] improves CD4 + /CD8 + T cell ratio, [16] has anti proliferative and anti-angiogenesis effects on tumor cells, [12,17,18] modifies monocyte/macrophage function upon endotoxin stimulation through involving in the tool like receptor signal transduction events, [19] has anti apoptotic properties [2,20,21] and demonstrates high antioxidant activities. [22] Several purified chemicals from garlic or its crude extracts have been demonstrated to have obvious antitumor activities. ...
Article
Background: Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. Aim: In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. Materials and methods: WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-γ) and interleukin-4 cytokines were measured. Results: The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. Conclusion: Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.
... Since 4T1 cell is a good metastasis model with weak angiogenesis, we induced the tumor via subcutaneous tumor implantation. An invasive ductal carcinoma, a spontaneous mouse mammary tumor (SMMT), which grows in female BALB/c spontaneously (28), was separated from a cancer-bearing female BALB/c, with scalpel cut into small pieces less than 0.5 cm 3 , and was transplanted subcutaneously to the syngeneic female BALB/c mice. After about a week, when the tumor appeared, tumor size was measure two times a week with digital caliper, and total volume was evaluated by the following formula (29): V = LW 2/2, where V is the volume, L is the length, and W is the width. ...
... 77 Garlic extract may enhance lectin-induced lymphocyte proliferation and natural killer cells activity. 96 Furthermore, garlic extract at dose of 20 mg/kg enhance the delayed type hypersensitivity response in mice and histologically lead to hypertrophy and hyperplasia both of the paracortical zone in lymph nodes and periarteriolar sheaths of spleen. The immunopotentiation and immunomodulatory properties of garlic in enhancement of delayed type hypersensitivity and natural killer cells activity can be an excellent mechanism for cell-mediated immunotherapy. ...
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Leishmaniasis is caused by an obligate intracellular protozoa belonging to Leishmania genus. The current drugs for treatment of leishmaniasis possess many disadvantages; therefore, researchers are continuously looking for the more effective and safer drugs. The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. All relevant databases were searched using the terms "Allium sativum," "Garlic," "Allicin," "Ajoene," "Leishmania," "in vitro," "in vivo," and "clinical trial," alone or in combination from 5 English databases (Web of Science, PubMed, Science Direct, Scopus, Google Scholar) and 3 Persian databases (Scientific Information Database, Iran Medex, and Magiran) from 1990 to 2014. In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis.
... [14] Mice tumor model Spontaneous mouse mammary tumor [ Figure 2], as an invasive ductal carcinoma was spontaneously developed in the female BALB/c mice. [15] The diagnosis of ductal carcinoma in tumorized mice was evaluated by the histopathological method as described previously. [16] In brief, the isolated tumors were fixed in 10% formaldehyde, passaged, and embedded in paraffin. ...
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The combination of artemisinin and transferrin exhibits versatile anticancer activities. In previous, we successfully prepared artemisinin and transferrin-loaded magnetic nanoliposomes and evaluated their anti-proliferative activity against MCF-7 and MDA-MB-231 cell lines in vitro. In this study, we investigate the in vivo anti-breast cancer activity of artemisinin and transferrin-loaded magnetic nanoliposome against breast transplanted tumors in BALB/c mice model. Artemisinin and transferrin-loaded magnetic nanoliposomes were prepared and characterized for some physiochemical properties. Pieces of tumor tissue from the breast cancer-bearing BALB/c mice were transplanted subcutaneously to the syngeneic female BALB/c mice. In the presence of the external magnet that placed at the breast tumor site, the tissue distribution and tumor-suppressing effects of prepared nanoliposomes on tumor growth was evaluated. The prepared nanoliposomes have fine spherical shape, rough surface, nano-sized diameter and magnetic properties. At 2 h after treatment, the intravenous administration of artemisinin and transferrin-loaded magnetic nanoliposomes followed using the magnetic field approximately produced 10- and 5.5-fold higher levels of artemisinin and transferrin in the tumors, respectively, compared with free artemisinin and transferrin. Moreover, in the presence of an external magnetic field, the prepared nanoliposomes could significantly induce apoptosis in the mice breast cancer cells as well as could reduce tumor volume in tumorized mice at 15 days after treatment. The data suggested that the artemisinin and transferrin-loaded magnetic nanoliposomes would be a good choice for the breast tumor-targeted therapy, due to its high targeting efficiency.
... NKC cytotoxic activities were evaluated by Hassan et al. in which four garlic preparations significantly enhanced NKC and killer cell activities of the spleen cells of tumorbearing mice [61]. Only AGE inhibited the growth of inoculated tumor cells. ...
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The Natural Killer Cell (NKC) is the cell-mediated cornerstone of innate immunity. The purpose of this reviewis to give a historical perspective of the discovery of the Natural Killer Cell (NKC)and to apply the use of supplements in the enhancement of NKC in human cancers for the developmentof human health and well-being.Since the discovery of the NKC, as observed by Nomarski optics, scanning (SEM)/transmission electron microscopy (TEM) with cellular numeration and enrichment using bovine serum albumin (BSA) continuous gradients, there have been significant research and clinical studies to increase the effectiveness of NKC in the destruction of cancer cells. Based on significant research and clinical studies, at least 16 components have been identified that enhance or may enhance, based on their immune modulator activity, the NKC. These supplements include Alpha LipoicAcid, Arabinoxylin, Curcumin, Garlic, Genistein, Ginseng, Lentinan, Mistletoe, N-Acetylcysteine, Resveratrol, Selenium, Vitamin B, Vitamin C, Vitamin D3, Vitamin E and zinc.
... Tumor transplantation and measurement of the tumor volume: Spontaneous mouse mammary tumor (SMMT), spontaneously developed in female BALB/c mice. SMMT is an invasive ductal carcinoma (Hassan et al., 2003). The tumor tissue from the breast cancer-bearing BALB/c mice was separated and cut into pieces of less than 0.5cm 3 with forceps and scalpel. ...
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The aim of this study was to investigate the immunomodulatory effects of Spirulina platensis (S. platensis) by measuring the levels of serum interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-|γ| in mice suffered from systemic candidiasis and breast cancer. The aqueous extract of S. platensis was selected for this study. Balb/C female mice were inoculated with Candida albicans (C. albicans) and spontaneous mouse mammary tumor (SMMT). Five days after Candida inoculation, the serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed by Enzyme- linked immunosorbent assay (ELISA). The animals were treated daily with S. platensis solution (800 mg/kg, 0.2 ml, orally) for 3 days before IV challenge with C. albicans, and SC challenge with SMMT and continued for 10 days. The survival rate and tumor size of understudy animals were determined, as well. ELISA determined the levels of TNF-α, IFN-γ IFN T γ-4, IL-10 and IL-17 cytokines in supernatants. The results demonstrated that S. platensis decreased the secretion of IL-4 (45.1 pg/ml) and IL-10 (208.4 pg/ml) in tumor-bearing mice infected with C. albicans, whereas the levels of IL-17, TNF-α and IFN-γ increased to nearly 93.4 p/ml, 316.2 pg/ml and 137.1 pg/ml in this group, respectively. These findings clearly suggest that S. platensis has a remarkable immunomodulatory effect, which provides a scientific validation for the popular use of this natural substance, and assisted in the additional investigation of their complete mechanism of action.
... SMMT is an invasive ductal carcinoma [10]. Tumor transplants were surgically removed from a mature breast cancer-bearing Balb/C mouse and cut into pieces of less than 0.5 cm 3 with forceps and scalpel. ...
Article
Objective This study was aimed at investigating the effect of propolis on immunosurveillance by measuring the levels of serum interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in tumor-bearing mice with disseminated candidiasis. Methods The ethanol extract of propolis was selected for this study. Balb/C female mice were infected with Candida albicans (C. albicans) and inoculated with spontaneous mouse mammary tumor (SMMT). The serum levels of tissue inhibitor of metalloproteinase-1(TIMP-1) were assessed by enzyme- linked immunosorbent assay (ELISA). Mice were treated daily with propolis solution (100 mg/kg, 0.1 mL, orally) for 3 days before IV challenge with C. albicans and SC challenge with SMMT and continued for 10 days. The rates of survival and tumor growth of understudy mice were investigated as well. The levels of TNF-α, IFN-γ, IL-4, IL-10 and IL-17 cytokines in culture supernatants were determined by ELISA. Results The mean tumor size was significantly increased in tumor-bearing mice infected with C. albicans (16.98 ± 0.49 mm2) as compared to other mice groups (P < 0.05). The results showed a significant decline of IL-4 and IL-10 levels after propolis administration to tumor-bearing mice infected with C. albicans (53.41 pg/mL, 156.81 pg/mL and 63.45 pg/mL) (P < 0.05). The increment of TNF-α (433.85 pg/mL) and IFN-γ (120.43 pg/mL) levels were also observed. Conclusion Data revealed that propolis has remarkable immunomodulatory effect, which provides a scientific validation for the popular use of this natural substance, and further investigation will help to understand propolis usefulness during immunosuppressive conditions.
... Spontaneous mouse mammary tumor (SMMT) is an invasive ductal carcinoma, which develops spontaneously in female BALB/c mouse after transplantation with tumor cells. SMMT is regarded to be similar to the invasive ductal carcinoma observed in human samples (16). In our study, mice were subcutaneously transplanted with 0.5 mm 3 of tumor tissue taken from SMMT-bearing BALB/c mice. ...
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Background: Chemo-immunotherapy is one of the new achievements for treatment of cancer, by which the success of anti-cancer therapy can be increased. In vitro studies have been shown that Arteether (ARE) induces apoptosis in tumor cells, but not in normal cells. Objective: To investigate the cytotoxic and immunomodulatory properties of Arteether in-vivo and in-vitro. Methods: In this study, we used MTT assay for evaluation of cytotoxicity of Arteether on tumor cell line and Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals. Balb/c mice were subcutaneously transplanted with tumor tissue taken from Spontaneous Mouse Mammary Tumor (SMMT) bearing female mice. Arteether was administered to breast tumor-bearing Balb/c mice at a dose of 6mg/kg/day intraperitoneally. Tumor sizes, lymphocyte proliferation, cytokines production, and the percentage of splenic T-reg cells were measured. Results: We observed that ARE could reduce the cell growth of 4T1 cell line in a dose-dependent manner but it had no cytotoxic effect on the growth of peripheral blood lymphocytes. ARE administered intraperitoneally to tumor-bearing Balb/c mice could reduce the tumor growth rate and splenic T-reg cells. No difference in the IFN-γ, IL-10 and IL-4 production was observed between tumor antigen-stimulated splenocytes of mice treated with ARE and control mice. Conclusion: These results underscore antitumor properties of Arteether that may aid in development of more effective antitumor agents.
... It has been reported that organosulfides (19), fructans (20), lectins (21), and Sallyl- L-cysteine sulfoxide (22) in fresh and old garlic are responsible for immunomodulatory potential. However, few studies (23-25) have addressed the effect of garlic proteins on the immune system. ...
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Garlic (Allium sativum) has anti-inflammatory, anti-mutagenesis, and immunomodulatory properties that modulate anti-tumor immunity and inhibit tumor growth. In this study we have examined the effect of a protein fraction isolated from fresh garlic on anti-tumor response and intra-tumor lymphocyte infiltration. In this experimental study a protein fraction was purified from fresh garlic bulbs using ultra-filtration, followed by chromatofocusing, and SDS-PAGE analysis. Anti-tumor activity was assessed by intra-tumor injection of the protein fraction and garlic extract, itself, into groups of 5 mice each. The percentage of peripheral blood and intra-tumor CD4(+) and CD8(+) cells were assessed by flow cytometry. Unpaired student's t test using the SPSS program was applied for all statistical analyses. Garlic extract included different type of proteins with different molecular weight. One of protein's fraction was immunomodeulator and was composed of three single polypeptides, with molecular masses of ~10-13 kDa and different isoelectric points (pI). These molecules augmented the delayed type hypersensitivity (DTH) response compared to the control group. Intra-tumor injection of the fraction provoked a significant increase in the CD8(+) subpopulation of T-lymphocytes, as well as a decrease in tumor size. The fraction increased peripheral blood CD8(+) T-lymphocytes in treated animals. The data confirms that protein fractions purified from fresh garlic bulbs augment CD8(+) T-cell infiltration into the tumor site, inhibiting tumor growth more efficiently than garlic extract. These findings provide a basis for further investigations on the purified polypeptide as a useful candidate for immunomodulation and tumor treatment.
... Furthermore, garlic has been shown to be a possible immune response modifier (4). According to our previous studies, it has been demonstrated that garlic enhances natural killer (NK) activity (8) and T-lymphocyte proliferation (9). Also, garlic extract and a garlic protein were shown to augment the oxidative burst in peritoneal macrophages of BALB/c mice (4). ...
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Garlic (Allium sativum) is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, and anticoagulant. One of the major purified garlic protein components is the 47 kDa protein. In this study, the effect of 47 kDa protein extracted from aged garlic (AGE) was evalua. Forty seven kDa protein was purified from AGE by ammonium sulfate precipitation and gel filtration. SDS-PAGE was used to determine the molecular weight and purity of the isolated protein. DCs were purified from spleen of BALB/c mice by Nycodenz centrifugation and their adhesiveness to the plastic dish. The 47 kDa protein isolated from AGE was added to DCs medium during the overnight culture and the expression of DC surface markers was assessed via flowcytometry. The 47 kDa protein-treated DCs lowered the expression of DC maturation markers including: CD40, CD86 and MHC-II in comparison with non-treated DCs; (median of 41% versus 47%, 84% versus 91% and 83% versus 90%, respectively) but we observed no statistical difference between the two groups. Upon treatment with DCs with 47 kDa protein, DCs down regulated the expression of costimulatory and MHC-II surface molecules, which is similar to tolerogenic DC phenotype. According to the results of the present study, we found that 47 kDa protein purified from AGE can be considered as a potential candidate to generate tolerogenic DCs in vitro.
... SMMT is regarded to be similar to the invasive ductal carcinoma observed in human samples. 9 In our study, mice were subcutaneously transplanted with 0.5mm 3 of tumor tissue that was separated from SMMT-bearing Balb/C mice. Tumors were authorized to reach approximately 500 mm 3 . ...
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Recent studies have indicated the profound anti-tumor activity of artemisinin's compounds, among which; arteether is an oil-soluble derivative of artemisinin with an endoperoxide bridge that can induce apoptosis in tumor cells but not in the normal cells. An experiment was carried out on tumor-bearing Balb/c mice to estimate the effects of Arteether on tumor growth and antitumor immune responses. Briefly, 6mg/kg/day of Arteether and diluents were administered to two groups of mice. Tumor sizes were measured using digital verniercallipers. Mice were sacrificed and splenocytes were harvested for lymphocyte proliferation assay, the level of IL-4 and IFN-γ cytokines, and the percentage of splenic T regulatory cells were measured. According to the findings, there were no statistical differences between the groups with respect to the level of IFN-γ, IL-4 and proliferation assay; while our results showed that Arteether is effective in the reduction of tumor growth rate. In general, intra-tumoral injection of Arteether as an oil-soluble derivative of artemisinin brings to light some antitumor properties that may aid in development of more effective antitumor agents.
... SMMT is regarded to be similar to the invasive ductal carcinoma observed in human samples. 9 In our study, mice were subcutaneously transplanted with 0.5mm 3 of tumor tissue that was separated from SMMT-bearing Balb/C mice. Tumors were authorized to reach approximately 500 mm 3. 10 tumor-bearing mice were randomly divided into two groups, each consisting of five mice. ...
Article
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Recent studies have indicated the profound anti-tumor activity of artemisinin's compounds, among which; arteether is an oil-soluble derivative of artemisinin with an endoperoxide bridge that can induce apoptosis in tumor cells but not in the normal cells. An experiment was carried out on tumor-bearing Balb/c mice to estimate the effects of Arteether on tumor growth and antitumor immune responses. Briefly, 6mg/kg/day of Arteether and diluents were administered to two groups of mice. Tumor sizes were measured using digital verniercallipers. Mice were sacrificed and splenocytes were harvested for lymphocyte proliferation assay, the level of IL-4 and IFN-+ cytokines, and the percentage of splenic T regulatory cells were measured. According to the findings, there were no statistical differences between the groups with respect to the level of IFN-+, IL-4 and proliferation assay; while our results showed that Arteether is effective in the reduction of tumor growth rate. In general, intra-tumoral injection of Arteether as an oil-soluble derivative of artemisinin brings to light some antitumor properties that may aid in development of more effective antitumor agents. Keywords: Anti-tumor; Arteether; Breast Cancer
... SMMT is an invasive ductal carcinoma. Previous studies have shown that this tumor develops spontaneously in normal BALB/c mice (Hassan et al. 2003). Tumor transplants were surgically removed from a mature breast cancer-bearing BALB/c mouse and cut into pieces of less than 0.5 cm 3 with forceps and scalpel. ...
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Invasive aspergillosis increases in chronic immunosuppressive diseases such as cancer. There is little information about the mechanisms by which Aspergillus infection affects the immune regulation and microenvironment of cancer cells. Hence, this study was aimed at investigating the effect of invasive aspergillosis on immunosurveillance, metastasis, and prognosis of cancer in tumor-bearing mice. After implantation of mouse mammary tumor in BALB/c mice, they were infected with Aspergillus conidia intravenously. For comparison, groups of mice were experimentally infected with Aspergillus conidia or implanted with tumor cells separately. Seven days after Aspergillus infection, the serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and subsequently regulatory T lymphocytes were analyzed by flow cytometry. The survival of animals and mean tumor size were then determined. Our results indicated that tumor sizes in mice increased significantly after infection with Aspergillus conidia. Moreover, invasive aspergillosis enhanced the population of regulatory lymphocytes and level of TIMP-1. This study supports the idea that massive Aspergillus infection could stimulate tumor growth and increases the possibility of a bad prognosis. As a result, treatment of Aspergillus infection could be considered an important issue for efficient cancer therapy.Les maladies immunosuppressives chroniques comme le cancer augmentent l'incidence d'aspergillose invasive. Il n'y a que peu d'informations disponibles sur les mécanismes par lesquels l'infection à Aspergillus affecte la régulation immune et le microenvironnement des cellules cancéreuses. Ainsi, cette étude visait à examiner l'effet de l'aspergillose invasive sur l'immunosurveillance, la métastase et le pronostic du cancer chez des souris porteuses de tumeurs. Après l'implantation de tumeurs mammaires chez la souris BALB/c, celles-ci ont été infectées par des conidies d'Aspergillus de façon intraveineuse. Pour fins de comparaison, des groupes de souris ont été séparément infectés par des conidies d'Aspergillus ou implantés avec des cellules tumorales. Sept jours après l'infection à Aspergillus, les niveaux sériques de TIMP-1 (tissue inhibitor of metalloproteinase-1) ont été mesurés par ELISA et les lymphocytes T régulateurs (Treg) ont été analysés subséquemment par cytométrie de flux. La survie des animaux et la taille moyenne des tumeurs ont ensuite été déterminées. Nos résultats indiquent que la taille des tumeurs des souris augmentait significativement à la suite de l'infection par les conidies d'Aspergillus. Parallèlement, l'aspergillose invasive augmentait la population de lymphocytes régulateurs et le niveau de TIMP-1. Cette étude appuie l'idée que l'infection massive par Aspergillus puisse stimuler la croissance tumorale et détériorer le pronostic. Conséquemment, le traitement de l'infection à Aspergillus devrait être considéré comme un problème important à prendre en compte pour l'efficacité de la thérapie anticancéreuse chez les patients.
... Mice were 6–8 weeks old at the beginning of the experiments. A fragment (4 mm3) of a spontaneous mouse mammary tumor (an invasive ductal carcinoma) was transplanted subcutaneously into the flank of each animal.30,31 Two weeks after the implantation, when the tumors reached approximately 630 mm3 in volume (12–15 mm in diameter), the mice were randomly divided into the experimental groups (8–10 animals for each control and each experimental group). ...
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The aim of this study was to investigate the antitumor effectiveness of electrochemotherapy with cisplatin combined with suboptimal radiotherapy doses. Tumor radiosensitization was evaluated on large invasive ductal carcinoma tumors in Balb/C mice. Tumors of an average volume of 630 mm(3) were treated with cisplatin, electric pulses, radiotherapy, electrochemotherapy, alone as well as in appropriate combinations. Tumors were irradiated with Cobalt-60 γ-rays at doses 3 Gy and 5 Gy in combination with electrochemotherapy using cisplatin. Controls included each of the treatments alone as well as the combination of the radiotherapy with electric pulses alone or with cisplatin alone. Antitumor effectiveness was evaluated by tumor growth delay, tumor-doubling time, inhibition ratio and the objective response rates. As anticipated, electrochemotherapy was more effective than the treatment with cisplatin alone or the application of the electric pulses alone. When treatments were combined with tumor irradiation at either 3 or 5 Gy, the combination with electrochemotherapy was more effective: at 5 Gy, 2 animals out of 8 were in complete remission 100 days later. In general the higher 5 Gy dose of γ-radiation was more effective than the lower one of 3 Gy. The results of our study demonstrate that irradiation doses, 3 Gy or 5 Gy, increase the antitumor effectiveness of electrochemotherapy with cisplatin on invasive ductal carcinoma tumors. Good antitumor results were achieved in experimental tumors with a size comparable to clinical lesions, demonstrating that this three-modality combined treatment is useful for the treatment of large lesions even at sub-optimal radiotherapy doses.
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Purpose Traditional medicine and herbal therapy, as a health-care approach of traditional medicine, are receiving increased attention from both the public and scientific society. The number of articles presented on traditional medicine and its applications is increasing rapidly. However, compared with extensive ongoing herbal research, achievements are not remarkable. The objective of the present article is to highlight some existing research gaps, which bridging the gaps will increase the quality and validity of the results of herbal research. Methods Iranian and non-Iranian articles on Allium sativum L. were reviewed for compliance with standards and requirements for herbal research. Results Botanical nomenclature, the processing and the extraction procedures, and the history of traditional medicine were the most important gaps in the herbal research. Conclusions Traditional and herbal medicines are rich and promising sources for drug development. Researchers and authors should consider that the familiarity with the history, characteristics, and potentials of traditional medicine systems is an important factor, accelerating the process of natural-based drug development. Moreover, essential standards with a high impact on the validity and reliability of the results of herbal research must not be ignored. Also, numerous fields remain to be considered by scientists and researchers, including the status of medicinal herbs, toxicological assessments, biological and pharmacological mechanisms of disease, and research questions.
Article
Garlic is an ancient plant whose medicinal usage has a long traditional history. It has been always advocated as a suitable candidate for immunomodulation. The purpose of the present study was to assess the immunomodulatory effects of Low Molecular Weight Garlic Proteins (LMWGP) on the proliferation of peripheral blood mononuclear cells (PBMCs), induction of regulatory T cells (Tregs), as well as cytokine secretion in the co-culture of PBMCs and colon cancer cell lines, SW48. Garlic cloves were initially extracted and then protein fractions were separated using gel filtration chromatography and analyzed with mass spectrometry (MS). The effects of LMWGP on the proliferation of PBMCs and induction of Tregs were later analyzed by flow cytometry. Cytokine secretion was also evaluated using the ELISA test. The findings revealed that the proliferation of PBMCs had significantly augmented in the presence of LMWGP (p ≤ 0.05). Moreover, this fraction had reduced induction of Tregs in the co-culture medium (p ≤ 0.05). ELISA results had further demonstrated a decline in cytokines, IL-10, and galectin-3, but an increment in IL-6 in the presence of LMWGP (p ≤ 0.05). According to co-culture study results, it was concluded that LMWGP could be assumed as a beneficial immunomodulatory supplement in herbal medicine for cancer.
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Background & Aims: In recent years, the emergence of multidrug resistance in gastric cancer has been a major challenge in treatment of gastric cancer. To deal with the problem, studies and researches were conducted on Sclareol and have turned up the anti-cancer effect of the compound and have also determined the molecular mechanism of it to some extent. Therefore, the main purpose of this study was to investigate the effect of the substance extracted from Salvia Officinalis called Sclareol on MDR-1 gene expression and consequently on the rate of P-glycoprotein in human gastric cancer cell line MKN-45. Materials and Methods: Cell line MKN-45 was purchased from the Pasteur Institute of Iran and cultured in complete RPMI 1640 Medium with Fetal Bovine Serum, with 20, 40, 60, 80 and 100 μM concentrations of Sclareol treatment for 5 hours. The rate of expression of MDR-1 gene was assessed by Real Time-PCR method and that of P-GP was assessed by Western blotting method. Results: The expression of MDR-1 gene was significantly reduced at doses of 20, 40 and 60 μmol of Sclareol, while at doses of 80 and 100 μmol there was not seen much effect (p <0.0001). Also, P-glycoprotein showed a very high decrease at doses of 40 and 60 μmol of Sclareol, but no decrease was seen at doses of 80 and 100 μmol (p <0.0001). Conclusion: From the results of this study, it seems that doses between 20 and 60 μmol of Sclareol can be useful in reducing drug resistance, but doses above 60 mmol do not have such an effect.
Article
It has been proven that olive associated products such as olive leaf extract (OLE) causes significant reduction in cancer cells viability and proliferation. Female BALB/c adult mice were divided into four groups. Three days prior to oral treatments, tumors were transplanted. First group were treated with distilled water and other three groups were received, respectively, 75, 150, and 225 mg/kg/day of OLE for three weeks. For assessment of anti-angiogenesis and pro-apoptotic effect of OLE on tumor tissue, tumor volume, cell mitosis and apoptosis, and also vascular endothelial growth factor (VEGF) and endostatin levels were assessed. OLE treatment with 150 and 225 mg/kg/day lead to significant reduction in tumor volume and cell mitosis compared with the control group, while the same doses significantly increase tumor cell apoptosis. OLE treatment with 150 mg/kg/day increase endostatin levels, while the same dose did not significantly decrease VEGF levels. The VEGF level is significantly reduced by the treatment with OLE 225 mg/kg/day for three weeks. Although, further studies are needed to clarify anti-angiogenesis and anti-apoptotic mechanism of OLE, consumption of OLE polyphenols after tumor transplantation reduced spontaneous mouse mammary tumor growth.
Chapter
For more than five centuries, garlic (Allium sativum L.) has acquired a reputation as a prophylactic and therapeutic agent in folklore and traditional medicine. Besides possessing various pharmacological activities, garlic has been shown to be a biological response modifier. Several laboratory and animal studies have shown that garlic stimulates a variety of immune-responder cells (dendritic cells, lymphocytes, macrophages, and natural killer cells). In the past, the immunomodulatory properties of garlic have been ascribed to its organosulfur (OS) compounds, the principal of which is allicin in crushed garlic. Based on recent findings, the immunomodulatory properties are also contributed by other major constituents of raw garlic, viz., the lectins or agglutinins and water-soluble fructans. Garlic has also shown promise as an antitumor agent against various tumors in animal and limited human studies. An odorless preparation of garlic, aged garlic extract (AGE), which shows as much potency as raw garlic, has been investigated intensively during the last three decades. In this review, the immunomodulatory attributes of garlic extract and its components are described first, followed by the immunomodulatory attributes of AGE and its components. The principal transformed OS compounds in AGE are S-allyl cysteine and S-allyl methylcysteine; the effects of these and other OS compounds in producing immunomodulation are covered in detail. Although AGE contains fructans, it represents only a small fraction (0.22%) of the total amount of fructans (~14. g/100. g) in raw garlic. In comparison with raw garlic extract, AGE contains mainly garlic lectins (ASA I and ASA II). The yield of immunomodulatory proteins from raw garlic and AGE is 28.5 and 25. mg/100. g fresh garlic, respectively. Lectins and fructans from AGE display lymphoproliferative activity and activation of macrophages including phagocytosis. In conclusion, it appears that the complete immunomodulatory potential of garlic or AGE is contributed by OS compounds, immunomodulatory proteins (mainly lectins), fructans, and fructosyl-arginine.
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Thin-layer chromatography (TLC) methods coupled with densitometric detection were employed in analyses for the presence of non-hallucinogenic indole compounds in methanol extracts from the garlic (Allium sativum L.) bulbs originating from China, Georgia, Spain, Mexico, and Poland, and from granulated garlic in the form of seasoning (commercial product). Four indole compounds for which the garlic bulbs were analyzed, were detected: 5-methyltryptamine, L-tryptophan, 5-hydroxy-L-tryptophan, and melatonin, the amounts of which ranged from 4.2 to 199.6 mg kg(-1) dry weight. In contrast, only 3 indole compounds were found in the garlic bulbs from Spain: 5-methyltryptamine, L-tryptophan and melatonin (85.7, 120.1, and 9.6 mg kg(-1) dry weight, respectively). The total amount of indole compounds in the extracts from the garlic bulbs from China was the highest (415.4 mg kg(-1) dry weight), while the amounts in the others (from Georgia, Spain, Mexico, Poland) were similar and ranged from 215.4 to 283 mg kg(-1) dry weight. The granular, freeze-dried garlic contained the lowest content of indole compounds, and their total amount was only 207 mg kg(-1) dry weight.
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Background: Cangshan County of Shandong Province has one of the lowest rates of gastric cancer (GC) in China. While intestinal metaplasia (IM) and dysplasia (DYS) are less common in Cangshan than in areas of Shandong at high risk of GC, these precursor lesions nevertheless affect about 20% of adults age > or = 55. Subjects and setting: In order to evaluate determinants of IM and DYS in Cangshan County, a low risk area of GC a survey was conducted among 214 adults who participated in a gastroscopic screening survey in Cangshan County in 1994. Method: A dietary interview and measurement of serum Helicobacter pylori antibodies were performed. Results: The prevalence of H. pylori was lowest (19%) among those with normal gastric mucosa, rising steadily to 35% for superficial gastritis (SG), 56% for chronic atrophic gastritis (CAG), 80% for IM, and 100% for DYS. The prevalence odds of precancerous lesions were compared with the odds of normal histology or SG. The odds ratio (OR) or CAG associated with H. pylori positivity was 4.2 (95% confidence interval [CI] : 1.7-10.0), while the OR of IM/DYS associated with H. pylori positivity was 31.5 (95% CI: 5.2-187). After adjusting for H. pylori infection, drinking alcohol was a risk factor for CAG (OR = 3.2, 95% CI: 1.1-9.2) and IM/DYS (OR = 7.8, 95% CI: 1.3-47.7). On the other hand, consumption of garlic showed non-significant protective effects and an inverse association with H. pylori infection. Conclusions: The findings of this study suggest that infection with H. pylori is a risk factor and garlic may be protective, in the development and progression of advanced precancerous gastric lesions in an area of China at relatively low risk of GC.
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Alliums have been grown for many centuries for their characteristic, pungent flavor and medicinal properties. The present review, which includes references published up to the middle of 1984, is primarily concerned with the chemical composition, flavor, and physiological properties of these crops, their extracts, and processed products. Special emphasis is placed upon the relationship between the organoleptically and biologically active components of onion and garlic. Following a brief historical introduction, current production of commercially important alliums is described and their botanical origins and interrelationships are explained. Following consideration of the major economic diseases and pests of alliums, the agronomic, husbandry, and practices associated with their cultivation are described, particular emphasis being placed upon the storage and processing of onion and garlic. The detailed, overall chemical composition and nutritional value of members of the genus Allium are presented in Section 7; after an outline of the origin and nature of flavor components and precursors, the flavor volatiles of individual members are presented. The effects of agronomic, environmental, and processing practices on chemical and flavor content and quality are considered in Section 9. The following section deals critically with the human and animal studies which have been conducted into the medical and therapeutic properties of alliums, emphasis being placed upon the studies into the antiatherosclerotic effect of onion and garlic and their essential oils. After a study of antimicrobial properties of alliums and their effects on insects and animals, an overview is presented which highlights unexplored or inadequately studied areas and suggests rewarding areas for future research.
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Division of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada ( Received 13 June 1977) Several lines of circumstantial evidence suggest that the neurohypophysial hormones may be biosynthesized in the form of larger peptides (prohormones) which are degraded to the free hormones during passage of the neurosecretory granules from the hypothalamus to the neurohypophysis (Vogt, 1953; Sachs & Takabatake, 1964; Pickering, Jones & Burford, 1971). Furthermore, it has been suggested that the hormone carrier proteins, the neurophysins, may at some stage in the biosynthesis, form part of the putative prohormones (Hope & Pickup, 1974). In cattle, arginine-vasopressin (AVP) is associated with bovine neurophysin II (Dean, Hope & Kazič, 1968), the complete amino acid sequence of which has been elucidated by Schlesinger, Capra & Walter (1974) and Wuu & Crumm (1976). In the present study, two dodecapeptide analogues of AVP in which the peptide chain was elongated
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A variety of yeast-like fungi representing the genera Candida, Cryptococcus, Rhodotorula, Torulopsis, and Trichosporon was inhibited in vitro in the presence of an aqueous extract of garlic. Fungi associated with vaginitis were inhibited and killed by an aqueous garlic extract diluted to 1: 1024 when incubated at 37 C. The antimycotic activity of the garlic preparation appeared greater at 37 C than at 30 C. The aqueous garlic extract maintained its fungistatic properties at 4, -10, -60 C for the test period of 30 da, but decreased in fungicidal ability within one wk at the same storage temperatures. Twenty-two isolates of C. albicans isolated from active vaginitis cases were all inhibited by the garlic extract.
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Morphological changes that occur in K562 cells after natural killing produce profound changes in cellular light scattering properties. The possibility of gating out all the effector cells by thresholding on perpendicular light scatter and the subsequent identification of two distinct clusters of cells, which correspond to dead and viable targets, have permitted the measurement of natural killer activity in vitro. The changes in scattering properties after cell death are mainly determined by the variation of internal refractive index of the dying cell. A comparison of the scattering and propidium iodide staining procedures showed good correlation. The morphological detection and measurement of cellular death is therefore used to estimate NK lytic activity. This methodology permits the measurement of NK activity without staining the target and the measurement of perpendicular light scatter provides an alternative approach to the study of lytic processes in vitro.
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Interviews with 564 patients with stomach cancer and 1,131 controls in an area of China where gastric cancer rates are high revealed a significant reduction in gastric cancer risk with increasing consumption of allium vegetables. Persons in the highest quartile of intake experienced only 40% of the risk of those in the lowest. Protective effects were seen for garlic, onions, and other allium foods. Although additional research is needed before etiologic inferences can be made, the findings are consistent with recent reports of tumor inhibition following administration of allium compounds in experimental animals.
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Flow cytometry has been employed to establish an NK assay using the K562 target cell line. These cells show a perpendicular light scatter (PLS) characteristically different from lymphocytes. Other physical parameters, such as forward light scatter (FLS), do not discriminate between the two populations, since dead K562 cells display similar FLS characteristics as effector cells. Killed cells are stained with propidium iodide and followed by flow analysis. It was advisable to add the dye in the medium so that, as long as the target cells are killed they will also be stained. Moreover the flow cytometric and trypan blue evaluation of target cell death rate showed a stronger correlation than did either test with the conventional 51Cr release assay, the first two methods both being based on the same biological mechanism.
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Immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum (CP), keyhole limpet hemocyanin (KLH) and an extract of Allium sativum (AS) was studied in a transitional cell carcinoma (MBT-2) in mice. Comparison was made between intraperitoneal (IP) versus intralesional (IL) administration of these agents. C3H/He mice were transplanted subcutaneously in the hind limb with 5 X 10(4) tumor cells. After transplantation, mice were randomized into groups to receive either IP or IL treatments with BCG (2 X 10(6) CFU), CP (250 micrograms.), KLH (50 micrograms.) or AS (25 mg.). At weekly intervals the tumor volume was determined. To assess the local cellular events following these treatments, histopathological studies were performed 10 days after tumor transplant with tissues removed from the injected sites. IL route was much more effective than IP route in inhibiting tumor growth. CP and AS exhibited more significant therapeutic effect than BCG or KLH. No tumor developed in mice which received five IL treatments of CP or AS. The data indicate that CP or AS may serve as effective biological response modifiers in controlling transitional cell carcinoma. The study further emphasizes that route and frequency of administration are crucial variables determining efficacy of immunotherapy.
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Alliums have been grown for many centuries for their characteristic, pungent flavor and medicinal properties. The present review, which includes references published up to the middle of 1984, is primarily concerned with the chemical composition, flavor, and physiological properties of these crops, their extracts, and processed products. Special emphasis is placed upon the relationship between the organoleptically and biologically active components of onion and garlic. Following a brief historical introduction, current production of commercially important alliums is described and their botanical origins and interrelationships are explained. Following consideration of the major economic diseases and pests of alliums, the agronomic, husbandry, and practices associated with their cultivation are described, particular emphasis being placed upon the storage and processing of onion and garlic. The detailed, overall chemical composition and nutritional value of members of the genus Allium are presented in Section 7; after an outline of the origin and nature of flavor components and precursors, the flavor volatiles of individual members are presented. The effects of agronomic, environmental, and processing practices on chemical and flavor content and quality are considered in Section 9. The following section deals critically with the human and animal studies which have been conducted into the medical and therapeutic properties of alliums, emphasis being placed upon the studies into the antiatherosclerotic effect of onion and garlic and their essential oils. After a study of antimicrobial properties of alliums and their effects on insects and animals, an overview is presented which highlights unexplored or inadequately studied areas and suggests rewarding areas for future research.
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Study of 220 Japanese stomach cancer patients and 440 hospital controls in Hawaii revealed that migrants (Issei) from prefectures with the highest stomach cancer risks in Japan continued to display an excess risk in Hawaii, but this effect did not persist among their Nisei offspring. Lower risks were suggested for Nisei, but not Issei adhering to Western-style diets. These nativity distinctions are consistent with other studies suggesting that early exposures are critical. Associations of stomach cancer with consumption of specific foods were noted. Elevated risks were described for Issei and Nisei users of pickled vegetables and dried/salted fish, the most frequent consumers having the highest risks. Since similar associations did not appear for raw fish and unprocessed vegetables, suspicion is directed to methods of preparation. Low risks were suggested for several Western vegetables, many of which are eaten raw. The associations for uncooked vegetables appeared independent of those found for pickled vegetables,- both persisted after control for other facets of vegetable consumption. Associations for tobacco, liquor, coffee, and milk were observed only in the Issei population. Points of consistency between the Hawaii findings and those assembled in Japan are cited. Experimental evidence bearing on the epidemiologic data for processed fish and vegetables is mentioned.
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The tumor yield and incidence of phorbol-myristate-acetate promotion were inhibited in a dose-dependent manner over the range of 10– 10 000 μg onion oil, applied three times per week. Garlic oil was also inhibitory but was less effective.
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Natural killer cells are a recently discovered subpopulation of lymphoid cells that are present in most normal individuals of a range of mammalian and avian species. Natural killer cells have spontaneous cytolytic activity against a variety of tumor cells and some normal cells, and their reactivity can be rapidly augmented by interferon. They have characteristics distinct from other types of lymphoid cells and are closely associated with large granular lymphocytes, which comprise about 5 percent of blood or splenic leukocytes. There is increasing evidence that natural killer cells, with the ability to mediate natural resistance against tumors in vivo, certain virus and other microbial diseases, and bone marrow transplants, may play an important role in immune surveillance.
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Fraction 4 (F4), a protein fraction isolated from aged garlic extract, enhanced cytotoxicity of human peripheral blood lymphocytes (PBL) against both natural-killer (NK)-sensitive K562 and NK-resistant M14 cell lines. Although F4 treatment alone increased cytotoxicity, the effect was more remarkable when F4 was administered together with suboptimal doses of interleukin-2 (IL-2); combination treatment of 5 micrograms/ml F4 plus 10 U/ml IL-2 for 72 h generated lymphokine-activated killer activity equivalent to that produced by 100 U/ml IL-2 alone against M14. F4 enhanced IL-2-induced proliferation and IL-2 receptor (Tac) expression of PBL without significant increase of IL-2 production. The enhancement of cytotoxicity both by F4 alone and by F4 plus IL-2 was abolished by anti-IL-2 antibody. F4 also enhanced concanavalin-A(ConA)-induced proliferation of PBL. Radiolabeled-ConA binding assays revealed that F4 treatment greatly augmented the affinity and slightly increased the number of ConA binding sites in PBL. F4 also enhanced ConA-induced IL-2 receptor (Tac) expression and IL-2 production of PBL. Anti- IL-2 antibody inhibited the effect of F4 on ConA-induced proliferation. These data suggest that IL-2 is involved in augmentative effects of F4. Our results indicate that F4 is a very efficient immunopotentiator and may be used for immunotherapy.
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The present studies examined the anti-proliferative effects of diallyl disulfide (DADS) on the growth of human colon tumor cell line, HCT-15, xenografts in 6-wk-old female NCr nu/nu mice with an initial body weight of 20-22 g. Intraperitoneal injection of 1 mg DADS thrice weekly reduced tumor volume by 69% (P < 0.05) without apparent ill consequences such as altered growth of the host. Providing this quantity of DADS intragastrically also inhibited growth of the HCT-15 tumor. At equivalent DADS dosages, intraperitoneal treatment was proportionately more effective (P < 0.05) in reducing tumor growth than gastric intubation. Tumor inhibition caused by DADS (0.5 mg thrice weekly) was similar to that occurring with 5-fluorouracil (5-FU) treatment (0.5 mg thrice weekly). Combining DADS and 5-FU was no more effective in inhibiting tumor growth than using either compound alone. However, concurrent DADS treatment significantly (P < 0.05) inhibited the depression in leukocyte counts and spleen weight and prevented the elevated plasma urea caused by 5-FU treatment. These data suggest that DADS, a constituent of garlic oil, reduces the toxicity of 5-FU and is an effective antitumorigenic agent against xenografts resulting from an established human colon tumor cell line.
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Arylamine N-acctyltransferase (NAT) activities with p-aminobenzoic acid (PABA) and 2-aminofluorene (2-AF) were determined in the bacterium Helicobacter pylori collected from peptic ulcer patients. Two assay systems were performed, one with cellular cytosols, the other with intact cell suspensions. Cytosols or suspensions of H. pylori with or without specific concentrations of diallyl sulfide (DAS) or diallyl disulfide (DADS) co-treatment showed different percentages of 2-AF and PABA acetylation. The data indicated that there was decreased NAT activity associated with increased levels of DAS or DADS in H. pylori cytosols and suspensions. Viability studies on H. pylori demonstrated that DAS or DADS elicited dose-dependent bactericide affects on H. pylori cultures. The data also indicated that DAS and DADS decreased the apparent values of K(m) and Vmax of NAT enzyme from H. pylori in both systems examined. This report is the first demonstration that garlic components can affect H. pylori growth and NAT activity.
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In order to study the effect and mechanism of garlic on preventing oral precancer, we divided randomly 32 Wistar rats into two groups. The garlic group was painted with garlic solution on the hard palatal mucosae. The control group was applied with distilled water that is equal in quantity. Then, chemical carinogen 4-nitroquinoline 1-oxide (4NQO) was painted on the same sites for both groups, three times weekly. Eight rats were randomly killed in the 10th, 13th week. The hard palatal mucosae were examined with light microscope. Meanwhile, lymphocytes were isolated from the rat spleens. The activation of natural killer (NK) cells and T-lymphocytes, and level of interleukin-2 were determined by radioimmunoassay. The results revealed that garlic effectively prevented oral precancer induced by 4NQO. This effect may be related to the following factors that garlic can improve the activation of NK cells, the function of T-lymphocytes, and the level of IL-2.
Article
Diallyl sulfide (DAS), a flavor component of garlic that has been used as a food additive, exerts chemopreventive effects at several organ sites in rodents after administration of chemical carcinogens possibly by inhibiting carcinogen activation via cytochrome P450-mediated oxidative metabolism. In this study, we investigated the protective effect of DAS on the N-nitrosodimethylamine (NDMA)-induced immunosuppression of humoral and cellular responses in BALB/c mice and the possible mechanisms involved in this protection. We observed that oral administration of DAS prior to NDMA treatment for 14 consecutive days blocked the NDMA-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes, and the lymphoproliferative response to the T-cell and the B-cell mitogens in dose-dependent manners. Treatment of mice with DAS resulted in a significant decrease of cytochrome P450 2E1-dependent p-nitrophenol hydroxylase and NDMA demethylase activities. The results show that the protective effects of DAS against the NDMA-induced immunotoxicity may, at least in part, be due to its ability to block bioactivation of NDMA mainly by the inhibition of cytochrome P450 2E1.
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To study the relation between allium vegetable intake and cancer of the esophagus (EC) and stomach (SC) in Yangzhong city, which is one of the highest-risk areas for these cancers in Jiangsu province, China, a simultaneous case-referent study was conducted using histopathologically confirmed cases (EC: n = 81, SC: n = 153) and population-based referents (n = 234). A questionnaire was used to collect information on the general status of subjects, their dietary habits, frequency intake of allium vegetables and other foods, tea consumption, smoking and alcohol drinking. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by a multiple logistic regression model. The results showed that frequent intake of allium vegetables (including garlic, onion, Welsh onion and Chinese chives), raw vegetables, tomatoes and snap beans, and tea consumption were inversely associated with the risk for EC and SC. In the highest consumption category (> or = 1 time/week) of garlic, onion, Welsh onion and Chinese chives, the adjusted ORs compared with the lowest category (< 1 time/month) were 0.30 (CI = 0.19-0.47), 0.25 (CI = 0.11-0.54), 0.15 (CI = 0.08-0.26), and 0.57 (CI = 0.23-1.42) for EC, and 0.31 (CI = 0.22-0.44), 0.17 (CI = 0.08-0.36), 0.22 (CI = 0.15-0.31) and 0.40 (CI = 0.17-0.94) for SC, respectively. The main results in the present study suggested that allium vegetables, like raw vegetables, may have an important protecting effect against not only stomach cancer, but also esophageal cancer.
Article
The regulation of T helper (Th)1- and Th2-type cytokine patterns is important in the final outcome of leishmaniasis in human and murine models. We examined the efficacy of garlic therapy or a combination of garlic and an antimonial drug (glucantime) in promoting healing and regulation of Th1/Th2 cytokine patterns in highly susceptible BALB/c mice infected with Leishmania major. Separate groups of infected mice received 20 mg/kg/day garlic, 60 mg/kg/day glucantime or a combination of the two, from day 30 after infection for 2 weeks. An enzyme-linked immunosorbant assay (ELISA) was performed on spleen cell culture supernatants for interferon(IFN)-gamma interleukin(IL)-2, IL-4 and IL-10. The results indicate that garlic therapy is more effective than the usual antileishmanial drug in curing the infection. Garlic-treated mice developed Th1-type cytokine responses. In contrast, glucantime therapy led to a Th2-type response in the control group with a lower level of IL-2. However, a combination of garlic and glucantime treatment was more effective than either treatment alone, and resulted in a Th1-type response similar to that which developed with garlic treatment. These results suggest that garlic extract in combination with an antimonial drug, may provide effective therapy against L. major. The immunomodulatory properties of garlic were elucidated in terms of shifting the cytokine response to a Th1-type pattern and therefore causing the protective response.
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Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, and anticoagulant. One major protein has been isolated and purified; it is the 14-kDa glycoprotein. This protein has shown to have immunomodulatory effects. In this study, two sources of garlic (freshly prepared and commercial tablet) were used. Both sources of garlic were augmented delayed type hypersensitivity (DTH) response, the optimum enhancement were detected at 20 mg/kg. Histological studies indicate that 20 mg/kg caused a hyperplasia and hypertrophy of periarteriolar lymphoid sheath of spleen and paracortical zone of lymph nodes. Partial purified fraction could increase the DTH response comparing to garlic extract, and purified protein could highly increase the DTH response comparing to both garlic extract and partial purified fraction. Garlic at all doses employed did not exhibit any effect on enhancement of antibody titer to SRBC.
A lectin with mitogenic activity in garlic Abstract book of 10th International Congress of Immu-nology
  • T Ghazanfari
  • Hassan
  • Zm
Ghazanfari T, Hassan ZM. A lectin with mitogenic activity in garlic. Abstract book of 10th International Congress of Immu-nology, India, vol. 493. New Delhi: Bruce Robinson publica-tion; 1998.
All rights reserved. doi:10.1016/S1567-5769(03)00161-9 * Corresponding author. E-mail address: hasan _ zm@modares.ac.ir (Z.M. Hassan)
  • B V Elsevier
1567-5769/$ -see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S1567-5769(03)00161-9 * Corresponding author. E-mail address: hasan _ zm@modares.ac.ir (Z.M. Hassan). www.elsevier.com/locate/intimp International Immunopharmacology 3 (2003) 1483 – 1489 References
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