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Inhibition of N-ethyl-N'-nitro-N-nitrosoguanidine-induced Duodenal Tumorigenesis in Mice by Whole-leaf Aloe arborescens Miller var. natalensis Berger.

We examined the modifying effects of freeze-dried whole-leaf Aloe arborescens Miller var. natalensis Berger (designated as 'ALOE') on N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-induced duodenal tumorigenesis in C57BL/6 mice. Experiment 1: Male mice were given ENNG in drinking water for the first 4 weeks, and then 10% ALOE in basal diet for 16 weeks. Experiment 2: Female mice were given ENNG for 5 weeks, and then 5%, 1% or 0.2% ALOE in the diet were given for 15 weeks. In Experiment 1, the tumor incidence and tumor multiplicity (tumors per mouse) of the duodenum in the ENNG + 10% ALOE group were significantly decreased compared with that in the ENNG alone group. Erythrocyte polyamine levels in the ENNG + 10% ALOE group were also significantly decreased. In Experiment 2, the incidence of duodenal tumors in the ENNG + 5% ALOE group were significantly decreased compared with that in the ENNG alone group. These results indicated that ALOE, especially at 10% in the diet, inhibits ENNG-induced duodenal tumorigenesis in mice.

Journal Article↗

Inhibition of azoxymethane-induced aberrant crypt foci formation in rat colorectum by whole leaf Aloe arborescens Miller var. natalensis Berger.

We examined the modifying effect of whole-leaf Aloe arborescens Miller var. natalensis Berger (designated as 'ALOE') on azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions, in the rat colorectum. Male F344 rats (4 weeks old) were fed the basal diet, or experimental diets containing 1% or 5% ALOE for 5 weeks. One week later, all rats except those in the vehicle-treated groups were injected s.c. with AOM (15 mg/kg, once weekly for 3 weeks). At 9 weeks of age, all the rats were killed, and the colorectum and liver were evaluated for ACF and cytosolic quinone reductase (QR; a phase 2 enzyme), respectively. In rats given AOM and ALOE (1% or 5% in diet) the numbers of ACF/colorectum, aberrant crypts/colorectum, aberrant crypts/focus and large ACF/colorectum were significantly decreased compared with those of rats given AOM alone (all p < 0.01). No ACF were found in rats treated without AOM. In addition, ALOE significantly increased cytosolic QR activity in the liver (p < 0.01). These results indicated that ALOE inhibited the development of AOM-induced ACF in the rat colorectum, with increased QR activity in the liver, and therefore suggested that ALOE might have a chemopreventive effect against colon carcinogenesis at least in the initiation stage.

Aloe↗

Fractionation of Aloe vera L. inner gel, purification and molecular profiling of activity.

Products derived from the inner gel of the Aloe vera L. plant have demonstrated multiple clinical activities, and are used routinely to accelerate wound healing. However, typical of natural products, the complex nature of Aloe vera gels may contribute to diverse pharmacologic activities. Our focus on the hematopoietic activities of Aloe vera extracts is extended by these functional studies, which used purified fractions from Aloe vera gel and included a preliminary organ-specific in vitro molecular profile. Studies using a >99% pure carbohydrate fraction from Aloe vera extracts revealed increased hematopoietic and hematologic activity compared to the starting material. In addition, this fraction differentially regulated liver and lung cytokine mRNA levels, resulting in significant increases in message for hematopoietic cytokines [granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF)]. This profile of activity differed from another fraction obtained from Aloe vera, suggesting the potential for diverse pharmacologic activity. The molecular studies were undertaken using co-cultures of organ slices to limit the amount of purified material required. In summary, these studies revealed significant hematopoietic activity by both pharmacologic and molecular analysis using a >99% pure carbohydrate fraction from Aloe vera gels.

Aloe↗

Inhibitory effects of aloe carboxypeptidase fraction on streptozotocin-induced enhancement of vascular permeability in the pancreatic islets.

The protective actions of components isolated from Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japanese) on streptozotocin (Sz)-induced necrosis of B cells in the pancreatic islets of the mouse were investigated to clarify its action mechanism involved in anti-diabetic effects. In this experiment, phenol low molecular weight components of aloin and aloin A that were anti-oxidants and derived from the leaf skin or pulp extract, an aloe carboxypeptidase fraction that is a inhibitor of enhanced vascular permeability and a glycoprotein component that decreases blood glucose were tested with mice precedently administered with Sz which is known as a cytotoxin specific to B cells. The results showed that the treatment group receiving Sz followed by the aloe carboxypeptidase fraction increased the inhibition of dye leakage by 75.8% (p<0.001) in the extract of whole pancreas in comparison to the control group and the aloe carboxypeptidase fraction group also increased the inhibition effect by 68.4% (p<0.001) in the extract of pancreatic islets as compared to the control group. The carboxypeptidase is an aloe-derived protease known to inhibit the acetic acid-related enhancement of intraperitoneal vascular permeability in mice. Further, the elevation of blood glucose in Sz-induced diabetic mice intraperitoneally given the aloe carboxypeptitase fraction was significantly (p<0.01-0.001) restrained at 3, 7 and 14 days after the injection as compared to the control group given solvent only. The results of this experiment suggested that the inhibitory effect on the enhancement of vascular permeability related to the vascular acute inflammatory response at Sz-induced lesions of pancreatic islets was involved in the action mechanism of this enzyme.

Aloe↗

The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines.

The aim of this study is to investigate the anticancer effect of aloe-emodin in two human liver cancer cell lines, Hep G2 and Hep 3B. We observed that aloe-emodin inhibited cell proliferation and induced apoptosis in both examined cell lines, but with different the antiproliferative mechanisms. In Hep G2 cells, aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax. These findings suggest that aloe-emodin may be useful in liver cancer prevention.

Aloe↗

Radical-scavenging effects of Aloe arborescens Miller on prevention of pancreatic islet B-cell destruction in rats.

We evaluated the possible scavenging effects of Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japanese) on free radicals generated by streptozotocin (Sz) or alloxan (Ax). The components of Kidachi aloe were added to a reaction system in which .OH radicals derived from Sz or Ax as pancreatic islet B-cell toxins and hypoxanthine-xanthine oxidase (HX-XO)-derived O(2) radicals destroy isolated islet B-cells, and we observed its preventive effects. The Kidachi aloe components inhibited the destruction of rat pancreatic islet B-cells by Sz, Ax or HX-XO. These components were prepared in the form of a freeze-dried powder of the boiled leaf skin of Kidachi aloe, and measurement of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity showed higher radical-scavenging activity in this boiled leaf skin powder than the non-boiled leaf skin powder.Furthermore, HPLC chromatograms of the "Boiled leaf skin powder" were similar to those of commercially available aloin (barbaloin content: approximately 20%). Therefore, the main component may be a phenol compound. In addition, the phenolic fraction of the Boiled leaf skin contained large amounts of 2'-O-p-coumaroylaloesin and 2'-O-feruloylaloesin, which have higher DPPH radical-scavenging activity than barbaloin. These results suggest that the action mechanism of Kidachi aloe Boiled leaf skin components, which prevent destruction of the pancreatic islets by specific pancreatic islet toxins such as Sz, Ax, and HX-XO, involves inhibition of free radical-scavenging effects, and may be associated with a thermostable low molecular component. The co-existence of Kidachi aloe-derived 2'-O-p-coumaroylaloesin, 2'-O-feruloylaloesin, and aloin may result in the potentiation of radical-scavenging activity.

Alloxan↗

Aloe exudate: characterization by reversed phase HPLC and headspace GC-MS.

From the leaves of aloe, a succulent plant, a dried exudate commonly called aloe can be obtained, which is used as a natural drug for its cathartic effect and is widely employed as a bittering agent in alcoholic beverages. This investigation provides a tentative characterization of several commercial aloe exudates carried out both by reversed phase HPLC and by headspace GC-MS analysis. By means of HPLC the derivatives were evaluated, and by GC-MS the volatile fraction was investigated. Qualitative and quantitative differences among the constituents in various samples of different origins were found. In particular, these were evident in the HPLC profile of Kenya aloe and an Aloe barbadensis sample, which exuded a high content of isoaloeresin D and aloins, whereas GC-MS analysis showed the presence of anisole exclusively in Kenya aloe samples. Moreover, the results obtained by means of the latter technique suggested a reason for the prevailing use of Mosselbay and Port Elizabeth aloes in bitter spirits formulation.

Alcoholic Beverages↗

Aloe spp.--plants with vertebrate-like telomeric sequences.

Chromosome termini of most eukaryotes end in tracks of short tandemly repeated GC-rich sequences, the composition of which varies among different groups of organisms. Plant species predominantly contain (TTTAGGG)n repeats at their telomeres. However, a few plant species, including members of Alliaceae and Aloe spp. (Asphodelaceae) were found to lack such Arabidopsis-type (T3AG3)n telomeric repeats. Recently, it has been proposed that the lack of T3AG3 telomeric repeat sequences extends to all species forming the Asparagales clade. Here, we analysed the composition of Aloe telomeres by single-primer PCR and fluorescence in-situ hybridization (FISH) with directly labelled Arabidopsis-type (TTTAGGG)28-43 DNA probe, and with vertebrate-type (TTAGGG)33-50 DNA and a (C3TA2)3 peptide nucleic acid (PNA) probe. It was found that Nicotiana tabacum contained Arabidopsis-type telomeric repeats, while Aloe telomeres lacked the corresponding FISH signals. Surprisingly, FISH with the highly specific vertebrate-type (C3TA2)3 PNA probe resulted in strong T2AG3-specific FISH signals at the ends of chromosomes of both Aloe and Nicotiana tabacum, suggesting the presence of T2AG3 telomeric repeats in these species. FISH with a long (TTAGGG)33-50 DNA probe also highlighted Aloe chromosome ends, while this probe failed to reveal FISH signals on tobacco chromosomes. These results indicate the presence of vertebrate-like telomeric sequences at the telomeres of Aloe spp. chromosomes. However, single-primer PCR with (TAG3)5 primers failed to amplify such sequences in Aloe, which could indicate a low copy number of T2AG3 repeats at the chromosome ends and/or their co-orientation and interspersion with other repeat types. Our results suggest that telomeres of plant species, which were thought to lack GC-rich repeats, may in fact contain variant repeat types.

Aloe↗

Beneficial effect of Aloe on wound healing in an excisional wound model.

Recent evidence from in vitro and in vivo experiments suggests that topical antimicrobials may be toxic to fibroblasts and keratinocytes and retard wound healing. The purpose of this study was to determine the effects of Aloe, a potential wound-healing agent, on wound contraction in excisional wounds treated with topical antimicrobials. Sprague-Dawley rats were prepared with four 1.5 cm2 dorsal defects through the skin and panniculus. The animals were divided into five groups (n = 10 per group): (1) Aloe, (2) NaOCl solution (0.025%), (3) mafenide acetate, (4) mafenide acetate + Aloe, and (5) control. Wounds were treated topically for 14 days 3 times a day. Serial standard photographs and serial wound planimetry were performed weekly. Following healing, the breaking strength of each resultant scar was determined using an Instron tensiometer. Kruskal-Wallis, ANOVA, and multiple comparison methods were used for data analysis. Aloe and NaOCl solution significantly accelerated wound contraction (p < 0.05). In the mafenide acetate + Aloe group, contraction was similar to the control, whereas the mafenide acetate alone retarded wound healing. The addition of Aloe in combination and alone in wounds increased the breaking energy when compared to controls (p < 0.05). Aloe appears to expedite wound contraction and neutralize the wound retardant effect seen with the topical mafenide acetate alone. This effect appears to be due to an increased collagen activity, which is enhanced by a lectin, consequently improving the collagen matrix and enhancing the breaking strength.

Aloe↗

Absence of contact sensitization to Aloe vera (L.) Burm. f.

Aloe vera has been used as a cosmetic and medical remedy since ancient times and has gained increasing popularity in recent years. Despite its widespread use, reports of allergic reactions are rare. We patch tested 702 consecutive patients with an oily extract from the leaves, Aloe pulvis from the entire plant and concentrated Aloe vera gel. A specially designed questionnaire was used for the use of Aloe vera, reasons and location of application, adverse reactions, occupation, hobbies and atopy. None of the subjects showed any reaction to one of the preparations. 2 components of the plant have to be distinguished: the bark of the leaves contains anthrachinones with pro-peristaltic and potential antibiotic and anticancer properties. Constraints have been imposed due to their considerable toxic potential. Today, mostly the Aloe gel from the center of the leaves is processed. It almost exclusively consists of carbohydrates to which also many medical effects have been attributed. Carbohydrates are not likely to induce contact sensitization, which might explain the outcome of our study. However, this does not justify unrestrained promotion of Aloe products, as scientific studies investigating the claims on its constitutional effects are few in number, and the majority of them have been unable to diminish the intuitive scepticism against miracle cures, like Aloe seems to be.

Allergens↗

The stimulation of postdermabrasion wound healing with stabilized aloe vera gel-polyethylene oxide dressing.

Full-face dermabrasion provided an ideal opportunity to document the effects of dressings on wound healing management. Following the procedure, the abraded face was divided in half. One side was treated with the standard polyethylene oxide gel wound dressings. The other side was treated with a polyethylene oxide gel dressing saturated with stabilized aloe vera. The polyethylene oxide dressing provided an excellent matrix for the release of aloe vera gel during the initial 5 days of wound healing. By 24-48 hours there was dramatic vasoconstriction and accompanying reduction in edema on the aloe-treated side. By the third to fourth day there was less exudate and crusting at the aloe site, and by the fifth to sixth day the reepithelialization at the aloe site was complete. Overall, wound healing was approximately 72 hours faster at the aloe site. This acceleration in wound healing is important to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. The exact mechanism of acceleration of wound healing by aloe vera is unknown.

Aloe↗

Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms.

The possibility of natural cancer therapy has been recently suggested by advances in the knowledge of tumor immunobiology. Either cytokines such as IL-2, or neurohormones, such as the pineal indole melatonin (MLT), may activate anticancer immunity. In addition, immunomodulating substances have also been isolated from plants, particularly from Aloe vera. Preliminary clinical studies had already shown that MLT may induce some benefits in untreatable metastatic solid tumor patients, whereas, for the time being, no clinical trial has been performed with aloe products. We have carried out a clinical study to evaluate whether the concomitant administration of aloe may enhance the therapeutic results of MLT in patients with advanced solid tumors for whom no effective standard anticancer therapies are available. The study included 50 patients suffering from lung cancer, gastrointestinal tract tumors, breast cancer or brain glioblastoma, who were treated with MLT alone (20 mg/day orally in the dark period) or MLT plus A. vera tincture (1 ml twice/day). A partial response (PR) was achieved in 2/24 patients treated with MLT plus aloe and in none of the patients treated with MLT alone. Stable disease (SD) was achieved in 12/24 and in 7/26 patients treated with MLT plus aloe or MLT alone, respectively. Therefore, the percentage of nonprogressing patients (PR + SD) was significantly higher in the group treated with MLT plus aloe than in the MLT gorup (14/24 vs. 7/26, p < 0.05). The percent 1-year survival was significantly higher in patients treated with MLT plus aloe (9/24 vs. 4/26, p < 0.05). Both treatments were well tolerated. This preliminary study would suggest that natural cancer therapy with MLT plus A. vera extracts may produce some therapeutic benefits, at least in terms of stabilization of disease and survival, in patients with advanced solid tumors, for whom no other standard effective therapy is available.

Adjuvants, Immunologic↗

The antidiabetic activity of aloes: preliminary clinical and experimental observations.

The dried sap of the aloe plant (aloes) is one of several traditional remedies used for diabetes in the Arabian peninsula. Its ability to lower the blood glucose was studied in 5 patients with non-insulin-dependent diabetes and in Swiss albino mice made diabetic using alloxan. During the ingestion of aloes, half a teaspoonful daily for 4-14 weeks, the fasting serum glucose level fell in every patient from a mean of 273 +/- 25 (SE) to 151 +/- 23 mg/dl (p less than 0.05) with no change in body weight. In normal mice, both glibenclamide (10 mg/kg twice daily) and aloes (500 mg/kg twice daily) induced hypoglycaemia after 5 days, 71 +/- 6.2 and 91 +/- 7.6 mg/dl, respectively, versus 130 +/- 7 mg/dl in control animals (p less than 0.01); only glibenclamide was effective after 3 days. In the diabetic mice, fasting plasma glucose was significantly reduced by glibenclamide and aloes after 3 days. Thereafter only aloes was effective and by day 7 the plasma glucose was 394 +/- 22.0 versus 646 +/- 35.9 mg/dl, in the controls and 726 +/- 30.9 mg/dl in the glibenclamide treated group (p less than 0.01). We conclude that aloes contains a hypoglycaemic agent which lowers the blood glucose by as yet unknown mechanisms.

Aloe↗

Possible interaction between sevoflurane and Aloe vera.

OBJECTIVE: To describe a patient with massive intraoperative bleeding after oral consumption of Aloe vera tablets. CASE SUMMARY: A 35-year-old woman lost 5 L of blood during surgery as a result of a possible herb-drug interaction between Aloe vera and sevoflurane. DISCUSSION: Aloe vera is a common herb used for antiinflammatory and antiarthritic activity, as well as antibacterial, hypoglycemic, and lipid-lowering effects. Compounds contained within Aloe vera can cause a reduction in prostaglandin synthesis, which may inhibit secondary aggregation of platelets. Sevoflurane inhibits thromboxane A(2) formation by suppression of cyclooxygenase activity, impairs platelet aggregation, and prolongs bleeding. Although the vascularity and size of the hemangioma were the most important factors for the massive intraoperative blood loss, concomitant use of sevoflurane and Aloe vera played a contributory role. An objective causality assessment revealed that this adverse event was possible as a result of the sevoflurane and Aloe vera interaction. CONCLUSIONS: There is a potential herb-drug interaction between Aloe vera and sevoflurane based on the antiplatelet effects of these 2 agents. Herbal medications with antiplatelet potential should be discontinued before anesthesia and surgery.

Adult↗

Therapeutic effects of Aloe vera on cutaneous microcirculation and wound healing in second degree burn model in rats.

OBJECTIVE: To demonstrate the microcirculatory and wound healing effects of Aloe vera on induced second degree burn wounds in rats. METHOD: A total of 48 male Wistar rats were equally divided into 4 groups as follows: sham controls, untreated burn-wound rats, those treated with once-daily application of normal saline (NSS) and those treated with once-daily application of lyophilized Aloe vera gel. The animals in each group were equally subdivided into 2 subgroups for the study of cutaneous microcirculation and wound healing on day 7 and 14 after burn. Dorsal skinfold chamber preparation and intravital fluorescence microscopic technique were performed to examine dermal microvascular changes, including arteriolar diameter, postcapillary venular permeability and leukocyte adhesion on postcapillary venules. RESULTS: On day 7, the vasodilation and increased postcapillary venular permeability as encountered in the untreated burn were found to be reduced significantly (p < 0.05) in both the NSS- and Aloe vera-treated groups, but to a greater extent in the latter. Leukocyte adhesion was not different among the untreated, NSS- and Aloe vera-treated groups. On day 14, vasoconstriction occurred after the wound had been left untreated. Only in the Aloe vera-treated groups, was arteriolar diameter increased up to normal condition and postcapillary venular permeability was not different from the sham controls. The amount of leukocyte adhesion was also less observed compared to the untreated and NSS- treated groups. Besides, the healing area of the Aloe vera-treated wound was better than that of the untreated and NSS- treated groups during 7 and 14 days after burn. CONCLUSION: Aloe vera could exhibit the actions of both anti-inflammation and wound healing promotion when applied on a second degree burn wound.

Administration, Topical↗

Induced expression of the gene for NADP-malic enzyme in leaves of Aloe vera L. under salt stress.

A cDNA fragment for NADP-malic enzyme, catalyzing the reversible oxidative decarboxylation of L-malate to produce CO(2), pyruvate and NADPH, was isolated from the leaves of a 2-month-old Aloe vera L., The level of expression of NADP-ME mRNA and accumulation of NADP-ME (AvME) protein under salt stress conditions were compared between a tolerant aloe, Aloe vera L. and a sensitive aloe, Aloe saponarea Haw. The results suggested that both the expression of the gene and the accumulation of the protein were induced in the two kinds of aloe, and the strength was related to the degree of salt tolerance. Northern blot analysis revealed that the gene for NADP-malic enzyme in Aloe vera L.( AvME) was induced by high salt, dehydration, and exogenous abscisic acid (ABA), but not by cold treatment. To further confirm whether the synthesis of AvME protein was induced with hours of treatment, Western blot analysis of the samples was conducted. The results indicated that the induction of AvME protein expression was obvious after 48 h at high salt and the level was increased with the hours of treatment.

Abscisic Acid↗

[Relationship between antibacterial activity of aloe and its anthaquinone compounds].

OBJECTIVE: To investigate the relationship between the antibacterial activity of aloe and its contents of anthaquinone compounds, measure and compale antibacterial activities of aloin and aloe-emodin, and analyse the effect of glycoside on the antibacterial activity of aloin. METHOD: The antibacterial activities of the extracts from the outer leaf of Aloe saponaria Haw, aloin and aloe-emodin against three Gram-negative and two Gram-positive bacteria were investigated with the method of agar diffusion. The antibacterial effect of aloin on E. coli was further studied with scanning electron microscopy. RESULT: The antibacterial activities of aloe showed to be dependent on the dose of anthraquinone, aloin (1 g x L(-1)) exhibited higher antibacterial activity [inhibition diameter > (7. 1 +/- 0.15) mm] than Aloe-emodin (inhibition diameter < 5.0 mm), and aloin changed the morphology of E. coli and damaged the outer cell structrue. CONCLUSION: Anthraquinone compounds are the active antibacterial components in aloe and aloin is the main active compound. The glycoside makes it easy for aloin to invade cells and enhances its activity.

Aloe↗

Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma.

Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G(1) formation). Aloe-emodin-induced apoptosis of CH27 cells involved modulation of the expression of Bcl-2 family proteins, such as BclX(L), Bag-1, and Bak, and was associated with the translocation of Bak and Bax from cytosolic to particulate fractions. Aloe-emodin-treated CH27 cells had an increased relative abundance of cytochrome c in the cytosolic fraction. Results demonstrated that the activation of caspase-3, caspase-8, and caspase-9 is an important determinant of apoptotic death induced by aloe-emodin. These results suggest that aloe-emodin induces CH27 cell death by the Bax and Fas death pathway.

Anthraquinones↗