Beneficial Biological Activities of Cinnamomum osmophloeum and its Potential Use in the Alleviation of Oral Mucositis: A Systematic Review.

The aim of this review was to provide an updated overview of studies on the medical-biological activities of Cinnamomum osmophloeum (C. osmophloeum) in vitro and in vivo and the potential therapeutic use of natural agents prepared from this plant for the alleviation of oral mucositis (OM). Reported articles were collected using web search engine tools. The systematic review was organized according to the preferred reporting items for reviews and meta-analyses (PRISMA) statement. Additional sources were identified through cross-referencing to identify the potential use of C. osmophloeum in the alleviation of OM. The results disclosed that C. osmophloeum is comprised of bioactive ingredients that could act diversely as a reagent in anti-inflammation, antibacterial, antioxidant, anti-hyperglycemic, antidyslipidemia, anti-cancer, renal disease therapy and anti-hyperuricemia capacities. Recent studies revealed that the overall effects on anti-inflammation, wound repair, and the antibacterial and antioxidant activities of its constituents would act as a potential remedy for oral mucositis. Up-to-date in vitro and in vivo studies on the medical-biological activities of C. osmophloeum suggested that C. osmophloeum and its constituents could be promising remedies as adjuvants in OM therapy and warrant further investigation.

Anti-inflammatory effect of cinnamaldehyde and linalool from the leaf essential oil of Cinnamomum osmophloeum Kanehira in endotoxin-induced mice.

Cinnamomum osmophloeum Kanehira is a Taiwan native plant that belongs to genus Cinnamomum and is also known as pseudocinnamomum or indigenous cinnamon. Its leaf is traditionally used by local people in cooking and as folk therapy. We previously demonstrated the chemical composition and anti-inflammatory effect of leaf essential oil of Cinnamomum osmophloeum Kanehira of linalool chemotype in streptozotocin-induced diabetic rats and on endotoxin-injected mice. The aim of the present study is to evaluate whether cinnamaldehyde and linalool the active anti-inflammatory compounds in leaf essential oil of Cinnamomum osmophloeum Kanehira. Before the injection of endotoxin, C57BL/6 mice of the experimental groups were administered cinnamaldehyde (0.45 or 0.9 mg/kg body weight) or linalool (2.6 or 5.2 mg/kg body weight), mice of the positive control group were administered the leaf essential oil (13 mg/kg body weight), and mice of the negative group were administered vehicle (corn oil, 4 mL/kg body weight) by gavage every other day for two weeks. All mice received endotoxin (i.p. 10 mg/mL/kg body weight) the next day after the final administration and were killed 12 h after the injection. Normal control mice were pretreated with vehicle followed by the injection with saline. None of the treatment found to affect body weight or food or water intake of mice before the injection of endotoxin. Cinnamaldehyde and linalool were found significantly reversed endotoxin-induced body weight loss and lymphoid organ enlargement compared with vehicle (P < 0.05). Both compounds also significantly lowered endotoxin-induced levels of peripheral nitrate/nitrite, interleukin (IL)-1ß, IL-18, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and High-mobility group box 1 protein (HMGB-1), and levels of nitrate/nitrite, IL-1ß, TNF-α, and IFN-γ in spleen and mesenteric lymph nodes (MLNs) (P < 0.05). Endotoxin-induced expression of toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88), myeloid differentiation protein 2 (MD2), Nod-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and caspase-1 in spleen and mesenteric lymph nodes (MLNs) were inhibited by all tested doses of cinnamaldehyde and linalool (P < 0.05). Subsequently, the activation of nuclear factor (NF)-κB and the activity of caspase-1 in spleen and MLNs were also suppressed by these two compounds (P < 0.05). In addition, cinnamaldehyde and linalool at the dose equivalent to their corresponding content in the tested dose of the leaf essential oil, which was 0.9 mg/kg and 5.2 mg/kg, respectively, showed similar or slightly less inhibitory activity for most of these inflammatory parameters compared with that of the leaf essential oil. Our data confirmed the potential use of leaf essential oil of Cinnamomum osmophloeum Kanehira as an anti-inflammatory natural product and provide evidence for cinnamaldehyde and linalool as two potent agents for prophylactic use in health problems associated with inflammations that being attributed to over-activated TLR4 and/or NLRP3 signaling pathways.

Protective effect of leaf essential oil from Cinnamomum osmophloeum Kanehira on endotoxin-induced intestinal injury in mice associated with suppressed local expression of molecules in the signaling pathways of TLR4 and NLRP3.

Endotoxin is a potent microbial mediator implicated in sepsis. We investigated the anti-inflammatory effect of leaf essential oil from Cinnamomum osmophloeum Kanehira (CO) of the linalool chemotype on endotoxin-injected mice. Mice were administered CO or vehicle by gavage before endotoxin injection and were killed 12 h after injection. Neither growth nor the organ weight or tissue weight to body weight ratio was affected by CO treatment. CO significantly lowered peripheral levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-18, interferon-γ, and nitric oxide and inhibited the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene (88), myeloid differentiation factor 2, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase-1, and Nod-like receptor family, pyrin domain containing 3 (NLRP3). CO also inhibited the activation of nuclear factor-ĸB, inhibited the activity of caspase-1 in small intestine, and ameliorated intestinal edema. Our data provide strong evidence for a protective effect of CO of the linalool chemotype in the endotoxin-induced systemic inflammatory response in close association with suppression of the TLR4 and NLRP3 signaling pathways in intestine.

Noni (Morinda citrifolia L.) Fruit Extracts Improve Colon Microflora and Exert Anti-Inflammatory Activities in Caco-2 Cells.

Intestinal microflora and inflammation are associated with the risk of inflammatory bowel diseases. Noni (Morinda citrifolia L.) has various bioactivities, but its effect on colon health remains unknown. This study focused on the effects of fermented noni fruit extracts on colon microflora and inflammation of colon epithelial cells. The anti-inflammatory activities of ethanol and ethyl acetate extracts on Caco-2 cells were evaluated including interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). The growth of Lactobacillus and Bifidobacterium species was promoted by ethanol extract. Ethyl acetate extract decreased intracellular reactive oxygen species and significantly suppressed COX-2, IL-8, and prostaglandin E2 production and neutrophil chemotaxis by suppressing the translocation of the p65 subunit. Quercetin was the main contributor to the anti-inflammatory activity. The fermented noni fruit promoted probiotic growths and downregulated the intracellular oxidation and inflammation in Caco-2 cells. These results suggest that fermented noni fruit might protect against inflammatory diseases of the colon.

A Comparison of Food-grade Folium mori ( Sang Yè) Extract and 1-Deoxynojirimycin for Glycemic Control and Renal Function in Streptozotocin-induced Diabetic Rats.

Folium mori ( Sang Yè, leaf of Morus alba L.; FM) is known to possess hypoglycemic effects, and 1-deoxynojirimycin (1-DNJ) has been proposed as an important functional compound in FM. However, the hypoglycemic activity of purified 1-DNJ has been rarely studied. It is also not known how FM and 1-DNJ affect the development of DM nephropathy. This study compared the antidiabetic effect of a commercial FM product with that of purified 1-DNJ in streptozotocin-induced diabetic rats. Seven days after induction, the diabetic rats were gavaged with FM (1, 3, 10, and 30 mg/kg/day), 1-DNJ (30 mg/kg/day), or vehicle (distilled deionized water; 2 ml/kg/day) for 7 days. All doses of FM ameliorated fasting and post-prandial blood glucose concomitantly with an increase in peripheral and pancreatic levels of insulin and improved homeostasis model assessment (HOMA-IR) in diabetic rats in a dose-dependent manner. Increased thiobarbituric acid reactive substances (TBARS) and nitrate/nitrite levels in the kidney, liver, and muscle of diabetic rats were reversed by all doses of FM. The renal function of the diabetic rats was normalized by all doses of FM, while blood pressure changes were reversed by FM at doses of 3 mg/kg and above. Moreover, most of the above-mentioned parameters were improved by FM at doses of 3 mg/kg and above to a similar extent as that of 1-DNJ. The results showed superior antidiabetic potential of the commercial FM product for glycemic control and protection against the development of diabetic nephropathy.

Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats.

Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE) and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0-12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide.

Isothiocyanates protect against oxidized LDL-induced endothelial dysfunction by upregulating Nrf2-dependent antioxidation and suppressing NFκB activation.

SCOPE: Oxidative stress plays a pivotal role in the pathophysiology of cardiovascular diseases. Oxidized low-density lipoprotein (oxLDL) is a key contributor to atherogenesis through multiple mechanisms. In this study, we investigated the protection by three structurally related isothiocyanates, i.e., sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isocyanate (PEITC), against oxLDL-induced leukocyte adhesion to vascular endothelium and the mechanism involved. METHODS AND RESULTS: The protection against oxLDL-induced endothelial dysfunction by isothiocyanates was studied in human umbilical vein endothelial cells (HUVECs). oxLDL increased reactive oxygen species (ROS) production, stimulated nuclear factor-kappaB (NFκB) activation, and enhanced intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin expression in HUVECs, which led to promotion of monocyte adhesion to HUVECs. Treatment with SFN, BITC, and PEITC (0-10 µM) dose-dependently induced heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) catalytic and modifier subunit expression, intracellular glutathione content, and antioxidant response element (ARE)-luciferase reporter activity. SFN, BITC, and PEITC pretreatment reversed oxLDL-induced ROS production, NFκB nuclear translocation, κB-reporter activity, ICAM-1, VCAM-1, and E-selectin expression, and monocyte adhesion to endothelial cells. Both heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown attenuated the isothiocyanate inhibition of oxLDL-induced ROS production, κB-reporter activity, and adhesion molecule expression. CONCLUSION: SFN, BITC, and PEITC protect against oxLDL-induced endothelial damage by upregulating Nrf2-dependent HO-1 and GCL expression, which leads to inhibition of NFκB activation and ICAM-1, VCAM-1, and E-selectin expression.

Chemical composition and hypoglycemic and pancreas-protective effect of leaf essential oil from indigenous cinnamon (Cinnamomum osmophloeum Kanehira).

The antidiabetic effect of cinnamon has generated broad interest during the past decade. We investigated the hypoglycemic activity and pancreas-protective effect of leaf essential oil from indigenous cinnamon (CO) in diabetic rats induced with streptozotocin (STZ, iv, 65 mg/(kg bw)) and found linalool to be the major component representing 40.24% of the CO composition. In diabetics, all tested doses of CO significantly lowered fasting blood glucose and fructosamine and are concomitant with elevated plasma and pancreatic insulin levels under a fasting condition. However, during the oral glucose tolerance test (OGTT) period the effect of 25 and 50 mg/(kg bw) of CO was shown to be less effective than that of 12.5 mg/(kg bw) in ameliorating the accumulation of plasma insulin. In addition, at 12.5 mg/(kg bw), CO significantly ameliorated pancreatic values of thiobarbituric acid reactive substances and activities of superoxide dismutase and glutathione reductase in diabetics to an extent greater than that of higher CO doses. At doses 12.5 and 25 but not 50 mg/(kg bw), CO significantly ameliorated pancreatic levels of interleukin-1ß and nitric oxide. In conclusion, appropriate doses of CO of the linalool chemotype exhibited therapeutic potential in glycemic control in diabetes that was at least partially resulted from improved insulin secretion. The ameliorated oxidative stress and proinflammatory environment in the pancreas by CO may provide a protective effect on pancreatic ß cells and warrant further investigation.

Effect of garlic sulfur compounds on neutrophil infiltration and damage to the intestinal mucosa by endotoxin in rats.

We investigated the protective effects of garlic sulfur compounds (GSCs), specifically, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), on endotoxin-induced intestinal damage. Wistar rats received by gavage 0.125 or 0.025 mmol/kg body wt of each GSC or the vehicle (corn oil; 2 mL/kg body wt) every other day for 2 weeks before being injected with endotoxin (ip, 5 mg/kg body wt). Control rats were administered corn oil and were injected with sterile saline. Rats were killed at 18 h after injection. Both doses of DAS suppressed endotoxin-induced neutrophilia, serum levels of sICAM-1 and CINC-1, cellular CD11b on neutrophils, and intestinal contents of ICAM-1, CINC-1, TNF-alpha, and IL-1beta (p<0.05). DADS suppressed endotoxin-induced intestinal contents of ICAM-1, TNF-alpha, and IL-1beta at both doses, but only suppressed the serum sICAM-1 level and cellular CD11b on neutrophils at the low dose (p<0.05). DATS did not ameliorate the endotoxin-induced serum level of sICAM-1 or CINC-1 but suppressed intestinal IL-1beta at both doses. The low but not the high dose of DATS also ameliorated the intestinal contents of ICAM-1 and TNF-alpha (p<0.05). All GSCs reversed endotoxin-induced neutrophil infiltration and damage in the intestine, and the order of the effects of these GSCs to normalize intestinal morphology was DAS>DADS>DATS.

The Antidiabetic Effect of Garlic Oil is Associated with Ameliorated Oxidative Stress but Not Ameliorated Level of Pro-inflammatory Cytokines in Skeletal Muscle of Streptozotocin-induced Diabetic Rats.

Oxidative stress and inflammatory condition has been broadly accepted being associated with the progression of diabetes. On the other hand, garlic ( dà suàn, bulb of Allium sativum) has been shown to possess both antioxidant and anti-inflammatory action in several clinical conditions. Our previous study demonstrated that treatment with garlic oil improves oral glucose tolerance and insulin tolerance and improves the insulin-stimulated utilization of glucose to synthesize glycogen in skeletal muscle in streptozotocin (STZ)-induced diabetes, in vivo and ex vivo, respectively. The aim of the present study is to investigate the antioxidant and anti-inflammatory effects of garlic oil (GO) in the skeletal muscle of diabetic rats. Rats with STZ-induced diabetes received GO (10, 50, or 100 mg/kg body weight) or corn oil by gavage every other day for 3 weeks. Control rats received corn oil only. GO dose-dependently improved insulin sensitivity, as assessed by the insulin tolerance test, and oral glucose tolerance. GO significantly elevated total glutathione and glutathione peroxidase activity and lowered the nitrate/nitrite content in skeletal muscle at 50 and 100 mg/kg and significantly elevated glutathione reductase activity and lowered lipid peroxidation at 100 mg/kg. By contrast, GO did not reverse diabetes-induced elevation of IL-1ß and TNF-α in skeletal muscle at any tested dose. On the other hand, GO elevated the expression of GLUT4 in skeletal muscle along with glycogen content as observed with PAS staining. In conclusion, the antidiabetic effect of garlic oil is associated with ameliorated oxidative stress in skeletal muscle.

Effect of garlic oil on neutrophil infiltration in the small intestine of endotoxin-injected rats and its association with levels of soluble and cellular adhesion molecules.

Garlic ( Allium sativum ) possesses anti-inflammatory effects. This study investigated the effects of garlic oil on endotoxin-induced neutrophil infiltration in the small intestine. Wistar rats received by gavage 10, 50, or 100 mg/kg body wt garlic oil (GO) or the vehicle (corn oil; 2 mL/kg body wt) every other day for 2 weeks before being injected with endotoxin (ip, 5 mg/kg body wt). Control rats were administered corn oil and injected with sterile saline. Blood samples for the measurement of soluble adhesion molecules were collected at various time points after injection, and all other samples were collected 18 h after injection. The 10 and 50 mg/kg doses suppressed endotoxin-induced neutrophilia, serum levels of sL-selectin and sICAM-1, cellular CD11b on neutrophils, intestinal ICAM-1 content, and neutrophil infiltration (P < 0.05). The 100 mg/kg dose significantly lowered local ICAM-1 and cellular CD11b on neutrophils (P < 0.05) but did not have a beneficial effect on neutrophil infiltration. In addition, 100 mg/kg of GO worsened the elevation of the local TNF-α level and neutrophilia. Appropriate doses of garlic oil have a preventive effect on endotoxin-induced neutrophil infiltration and damage to the small intestine.

Cardiac contractile dysfunction and apoptosis in streptozotocin-induced diabetic rats are ameliorated by garlic oil supplementation.

Previous studies have suggested that garlic oil could protect the cardiovascular system. However, the mechanism by which garlic oil protects diabetes-induced cardiomyopathy is unclear. In this study, streptozotocin (STZ)-induced diabetic rats received garlic oil (0, 10, 50, or 100 mg/kg of body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction examined by echocardiography and apoptosis evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay were observed in diabetic rat hearts. Additionally, a shift in cardiac myosin heavy chain (MHC) gene expression from α- to ß-MHC isoform, decreased levels of superoxide dismutase-1 (SOD-1) and cardiac α-actin, and elevated cardiac thiobarbituric acid reactive substances (TBARS) and caspase- and p38-NFκB-leading apoptosis signaling activities were demonstrated in diabetic hearts. However, these diabetes-related cardiac dysfunctions were almost dose-dependently ameliorated by garlic oil administration. In conclusion, garlic oil possesses significant potential for protecting hearts from diabetes-induced cardiomyopathy.

Effects of garlic oil on the migration of neutrophil-like cell studied by using a chemotactic gradient Labchip.

We have designed and fabricated a novel chemotactic gradient Labchip for studying cell migration quantitatively. Owing to the great potential of garlic and its preparations in developing antiinflammatory drugs, the aim of the present study is to investigate the effect of garlic oil on the locomotion of a neutrophil-like cell by measuring the dynamic features of cell migration including migration direction, average migration speed, chemotactic index (CI), and motility index (MI) with the newly designed Labchip. We found that garlic oil treatment lowered the values of CI and MI and reduced the average speed of cell migration from 13 to 8 microm/min. The results indicate that garlic oil is a potential inhibitor for neutrophil-like cell migration and chemotactic responsiveness. By comparing with the effects of nocodazole and cytochalasin B, we also suggest that the antiinflammatory activity exhibited by garlic oil was mainly through inhibiting the assembly-disassembly processes of the cytoskeleton.

Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein.

Garlic is viewed as an effective health food against atherosclerosis. In this study, we examined whether diallyl disulfide (DADS) and diallyl trisulfide (DATS) protect endothelial nitric oxide synthase (eNOS) activation against oxidized LDL (ox-LDL) insult and through what mechanism. We found that DADS and DATS reversed the suppression of eNOS Ser1177 phosphorylation by ox-LDL, and wortmannin abolished the reversal by DADS and DATS. Similarly, the inhibition of cellular cGMP and nitric oxide production by ox-LDL was reversed by DADS and DATS (p<0.05). This increase in nitric oxide bioavailability by the allyl sulfides was attenuated by wortmannin. Immunoprecipitation assay revealed that DADS and DATS preserved the interaction of eNOS with caveolin-1 in the membrane. In addition, DADS and DATS suppressed the reduction of the cellular eNOS protein content by ox-LDL. When cycloheximide was added to block protein synthesis, DADS and DATS suppressed eNOS protein degradation similarly to that noted by MG132. Ox-LDL increased chymotrypsin-like proteasome activity, and this increase was inhibited by the allyl sulfides and MG132 (p<0.05). These results suggest that DADS and DATS protect eNOS activity against ox-LDL insult. This protection can be attributed partly to their mediation of phosphatidylinositol 3-kinase/protein kinase B signaling and prevention of eNOS degradation.

Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin-induced diabetic rats.

Increased myocyte apoptosis in diabetic hearts has been previously reported. Therefore, the purpose of this study was to evaluate the effects of insulin on cardiac apoptotic, hypertrophic, and survival pathways in streptozotocin (STZ)-induced diabetic rats. Forty-eight male Wistar rats at 8 weeks of age were randomly divided into control group (Control), STZ-induced (65 mg/kg STZ i.v.) Type 1-like diabetic rats (DM), and DM rats with 4 IU insulin replacement (DI) for 4 and 8 weeks, respectively. The levels of protein involved in cardiac apoptotic, hypertrophic, and survival pathways were measured by Western blotting. Cardiac mitochondrial-dependent apoptotic pathways, such as Bad, cytosolic cytochrome c, activated caspase 9 and 3, and calcineurin-nuclear factor activation transcription 3 (NFAT3) hypertrophic pathway in DM were increased compared to Control and attenuated in DI group after 8 weeks whereas those were not found after 4 weeks. Cardiac anti-apoptotic Bcl2 and phosphorylated-Bad were significantly decreased in DM group but not in DI group after 8 weeks. Insulin-like growth factor-I receptor (IGFIR), phosphatidylinositol 3'-kinase (PI3K), and the protein kinase B (Akt) were significantly decreased in DM relative to Control and DI after 8 weeks whereas those were not found after 4 weeks. Insulin replacement not only prevents activation of the cardiac mitochondrial-dependent apoptotic pathway and calcineurin-related NFAT3 hypertrophic pathway in diabetes but it also enhances the cardiac insulin/IGFIR-PI3K-Akt survival pathway, all of which are attenuated with insulin therapeutic duration-dependent manners. The findings may provide possible diabetes-related apoptotic, hypertrophic, and survival pathways for potentially preventing cardiac abnormality in diabetes.

Effect of supplementation with garlic oil on activity of Th1 and Th2 lymphocytes from rats.

Garlic and garlic products are known to induce anti-inflammatory effects, but much of the research to date has focused on the inhibitory effect of garlic on the activity of mononuclear cells/macrophages. The effect of garlic on the balance of the two mutually inhibitory T helper cell subtypes, Th1 and Th2 cells, has hitherto received little attention. We thus studied the effect of supplementation with garlic oil on the activity of Th1 and Th2 cells. Rats were administered by gavage with garlic oil (10 - 200 mg/kg) or corn oil every other day for 2 weeks. Cervical lymph nodes were collected to assay the lymphocyte proliferation rate and the production of Th1 interleukin 2 (IL-2) and interferon gamma (IFN-gamma) and the Th2 cytokines IL-4 and IL-10 upon stimulation with concanavalin A. Garlic oil enhanced the lymphocyte proliferation rate accompanied by an elevated production of all four cytokines when given at a dose of 100 mg/kg. At 200 mg/kg, the production of IL-4 and IL-10 was further enhanced but IFN-gamma production was suppressed. The ratio of IFN-gamma to IL-4 was enhanced by 50 mg/kg garlic oil but suppressed by 200 mg/kg garlic oil. In conclusion, supplemental garlic oil has a dual effect on Th1-Th2 cell balance: an enhanced T cell response towards the Th1 type at low doses and towards the Th2 type at high doses.

The significance of arginase I administration on the survival of mice bearing NS-1 myeloma cells.

BACKGROUND: Arginase I blood levels elevate in cancerous patients and correlate with cancer stages and poor prognosis. Since arginase is capable of enhancing cell growth, it is unclear whether its ominous effect on cancer progression is through the inhibition of immunity or through direct enhancement of cancer cell growth. We tried to clarify this question. METHODS: NS-1 mouse myeloma cells were inoculated intraperitoneally (i.p.) into mice. Purified mouse arginase I was injected daily either intravenously (i.v.) or i.p. for 6 d. A tumor-only control group received i.p. tumor cells without arginase. The survival rates of all mice were recorded. RESULTS: Survival rates were significantly lower in the i.v. group than in the i.p. group (P=0.017) or in the tumor-only control group (P=0.034). As spleen is readily exposed to i.v. arginase, its natural killer cells were studied and were found to have been significantly suppressed by arginase in vitro (P<0.005). CONCLUSION: Our results indicate that the direct inhibition of the immune system by i.v. arginase is more significant in shortening the survival of tumor-bearing mice than localized (i.p.) arginase promotion of tumor cell growth. Thus, an elevation of arginase in a patient's blood is very harmful to the host immune system, e.g. splenic natural killer cells.

Does garlic have a role as an antidiabetic agent?

Diabetes affects a large segment of the population worldwide, and the prevalence of this disease is rapidly increasing. Despite the availability of medication for diabetes, traditional remedies are desirable and are currently being investigated. Garlic (Allium sativum), which is a common cooking spice and has a long history as a folk remedy, has been reported to have antidiabetic activity. However, there is no general agreement on the use of garlic for antidiabetic purposes, primarily because of a lack of scientific evidence from human studies and inconsistent data from animal studies. The validity of data from previous studies of the hypoglycemic effect of garlic in diabetic animals and the preventive effects of garlic on diabetes complications are discussed in this review. The role of garlic as both an insulin secretagogue and as an insulin sensitizer is reviewed. Evidence suggests that garlic's antioxidative, antiinflammatory, and antiglycative properties are responsible for garlic's role in preventing diabetes progression and the development of diabetes-related complications. Large-scale clinical studies with diabetic patients are warranted to confirm the usefulness of garlic in the treatment and prevention of diabetes.

Antidiabetic effect of garlic oil but not diallyl disulfide in rats with streptozotocin-induced diabetes.

We investigated the effects of garlic oil and diallyl disulfide (DADS) on glycemic control and renal function in rats with streptozotocin-induced diabetes. Rats received by gavage garlic oil (100 mg/kg body wt) or DADS (40 or 80 mg/kg body wt) every other day until 16 weeks after the induction of diabetes. The control rats were treated with corn oil only. Neither garlic oil nor DADS significantly affected fasting blood glucose concentrations throughout the investigation period. Garlic oil did not affect oral glucose tolerance in diabetes acutely but significantly improved oral glucose tolerance at 4, 8, 12, and 16 weeks and significantly ameliorated proteinuria at the end of 16 weeks. DADS did not significantly affect oral glucose tolerance or renal function. Diabetic rats fed 80 mg DADS/kg body wt had a significantly lower rate of body weight gain and a significantly lower ratio of muscle weight to body weight than did vehicle-treated diabetic rats. In conclusion, long-term treatment of diabetes with garlic oil can improve oral glucose tolerance and renal function in diabetes but not through the action of DADS. High doses of DADS may further complicate the metabolic disturbances in diabetes.

Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin.

Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg body weight diallyl disulfide or diallyl trisulfide, or the vehicle (corn oil; 2 ml/kg body weight) every other day for 2 weeks before being injected with endotoxin (i.p., 5 mg/kg body weight). Control rats were administered with corn oil and were injected with sterile saline. Samples for the measurement of proinflammatory cytokines were collected 3 h after injection, and all other samples were collected 18 h after injection. The low dose of GO suppressed endotoxin-induced inducible nitric oxide synthase (iNOS) activity, ulceration, and apoptosis in the intestinal mucosa (P < 0.05). The high dose of GO significantly lowered the peripheral level of nitrate/nitrite and endotoxin-induced iNOS activity in the intestinal mucosa (P < 0.05) but worsened intestinal mucosal damage accompanied by elevated peripheral proinflammatory cytokines. Diallyl trisulfide but not diallyl disulfide showed similar toxic effect as that of high-dose GO. These results suggest the preventive effect and possible toxicity of garlic oil and its organosulfur compounds in endotoxin-induced systemic inflammation and intestinal damage.