Studi scientifici sull'Aloe Arborescens

The wound-healing effect of a glycoprotein fraction isolated from aloe vera.

Choi SW, Son BW, Son YS, Park YI, Lee SK, Chung MH. Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.

BACKGROUND: Aloe vera has been used as a family medicine for promoting wound healing, but it is not known which component of the plant is effective for this purpose. OBJECTIVES: To isolate and characterize the component effective in wound healing. METHODS: Chromatography, electrophoresis and spectroscopic methods were used. The cell-proliferation activity of each component isolated was measured by a [3H]thymidine uptake assay. The cell-proliferation activity of the effective component was tested on a three-dimensional raft culture (cell culture technique by which artificial epidermis is made from keratinocytes). The effect of the active component on cell migration and wound healing was observed on a monolayer of human keratinocytes and in hairless mice. RESULTS: A glycoprotein fraction was isolated and named G1G1M1DI2. It showed a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, with an apparent molecular weight of about 5.5 kDa. It exhibited significant [3H]thymidine uptake in squamous cell carcinoma cells. The effect of G1G1M1DI2 on cell migration was confirmed by accelerated wound healing on a monolayer of human keratinocytes. When this fraction was tested on a raft culture, it stimulated the formation of epidermal tissue. Furthermore, proliferation markers (epidermal growth factor receptor, fibronectin receptor, fibronectin, keratin 5/14 and keratin 1/10) were markedly expressed at the immunohistochemical level. The glycoprotein fraction enhanced wound healing in hairless mice by day 8 after injury, with significant cell proliferation. CONCLUSIONS: It is considered that this glycoprotein fraction is involved in the wound-healing effect of aloe vera via cell proliferation and migration. PMID: 11703278

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

Somboonwong J, Thanamittramanee S, Jariyapongskul A, Patumraj S. Department of Physiology, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand.

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. PMID: 10808702

Influence of Aloe vera on collagen turnover in healing of dermal wounds in rats.

Chithra P, Sajithlal GB, Chandrakasan G. Department of Biochemistry, Central Leather Research Institute, Adyar, Chennai, India.

Treatment of full-thickness wounds with A. vera, on rats resulted in increased biosynthesis of collagen and its degradation. A corresponding increase in the urinary excretion of hydroxyproline was also observed. Elevated levels of lysyl oxidase also indicated increased crosslinking of newly synthesised collagen. The results suggest that A. vera influences the wound healing process by enhancing collagen turnover in the wound tissue. PMID: 9854430

Influence of Aloe vera on collagen characteristics in healing dermal wounds in rats.

Chithra P, Sajithlal GB, Chandrakasan G. Department of Biochemistry, Central Leather Research Institute, Adyar, Madras, India.

Wound healing is a fundamental response to tissue injury that results in restoration of tissue integrity. This end is achieved mainly by the synthesis of the connective tissue matrix. Collagen is the major protein of the extracellular matrix, and is the component which ultimately contributes to wound strength. In this work, we report the influence of Aloe vera on the collagen content and its characteristics in a healing wound. It was observed that Aloe vera increased the collagen content of the granulation tissue as well as its degree of crosslinking as seen by increased aldehyde content and decreased acid solubility. The type I/type III collagen ratio of treated groups were lower than that of the untreated controls, indicating enhanced levels of type III collagen. Wounds were treated either by topical application or oral administration of Aloe vera to rats and both treatments were found to result in similar effects. PMID: 9562243

Influence of aloe vera on the healing of dermal wounds in diabetic rats.

Chithra P, Sajithlal GB, Chandrakasan G. Department of Biochemistry, Central Leather Research Institute, Adyar, Chennai, India.

The positive influence of Aloe vera, a tropical cactus, on the healing of full-thickness wounds in diabetic rats is reported. Full-thickness excision/incision wounds were created on the back of rats, and treated either by topical application on the wound surface or by oral administration of the Aloe vera gel to the rat. Wound granulation tissues were removed on various days and the collagen, hexosamine, total protein and DNA contents were determined, in addition to the rates of wound contraction and period of epithelialization. Measurements of tensile strength were made on treated/untreated incision wounds. The results indicated that Aloe vera treatment of wounds in diabetic rats may enhance the process of wound healing by influencing phases such as inflammation, fibroplasia, collagen synthesis and maturation, and wound contraction. These effects may be due to the reported hypoglycemic effects of the aloe gel. PMID: 9507904

Influence of Aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats.

Chithra P, Sajithlal GB, Chandrakasan G. Department of Biochemistry, Central Leather Research Institute, Madras, India.

The influence of Aloe vera (L.) Burman f. on the glycosaminoglycan (GAG) components of the matrix in a healing wound was studied. Wound healing is a dynamic and complex sequence of events of which the major one is the synthesis of extracellular matrix components. The early stage of wound healing is characterized by the laying down of a provisional matrix, which is then followed by the formation of granulation tissue and synthesis of collagen and elastin. The provisional matrix or the ground substance consists of GAGs and proteoglycans (PGs), which are protein GAG conjugates. In the present work, we have studied the influence of Aloe vera on the content of GAG and its types in the granulation tissue of healing wounds. We have also reported the levels of a few enzymes involved in matrix metabolism. The amount of ground substance synthesized was found to be higher in the treated wounds, and in particular, hyaluronic acid and dermatan sulphate levels were increased. The levels of the reported glycohydrolases were elevated on treatment with Aloe vera, indicating increased turnover of the matrix. Both topical and oral treatments with Aloe vera were found to have a positive influence on the synthesis of GAGs and thereby beneficially modulate wound healing. PMID: 9507902

Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model.

Heggers JP, Elzaim H, Garfield R, Goodheart R, Listengarten D, Zhao J, Phillips LG. University of Texas Medical Branch, Galveston, USA.

PURPOSE: Many systemic and topical therapeutic agents such as growth hormone, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth factor (IGF) have been used as vulnerary agents. However, the role of nitric oxide (NO) as a wound-healing stimulant has been received with mixed reviews. NO is a potent vasodilator that is thought to be an endothelium-dependent relaxing factor, and a regulator of blood pressure and regional blood flow. It affects vascular smooth muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Therefore we compared the effects of several topical substances that have similar or reverse properties. METHODS: Using the excisional rat wound model, we evaluated the topical effects of Dermaide Aloe (D-Aloe, Dermaide Research Corp, Palos Heights, IL), nitroglycerin, Aquaphor (Beuersdorf, Inc., Norwalk, CT) alone, with D-Aloe with nitroglycerin, 2%, and L-NAME (NO inhibitor) with Aquaphor, and L-NAME with Aquaphor and D-Aloe for a 21-day period. All wounds were measured by planimetry at 1, 7, 10, 13, 16, 18, and 21 days. RESULTS: At day 1, all wounds had an average wound size of 2.27 cm2 (SD +/- 0.372) with no significant difference in wound size among the groups. Topically applied D-Aloe appeared to promote wound healing faster than the remaining other topicals (p < .05, Student-Newman-Keuls and Dunn's Method) over the study period. However, topicals combined with D-Aloe, the vehicle Aquaphor, and L-NAME improved the wound healing process when compared with nitroglycerin alone (p < .05). CONCLUSIONS: D-Aloe appears to have a wound-healing advancement factor that can reverse the effects of petrolatum- and nitroglycerin-based products as observed in the remaining groups when compared with nitroglycerin alone. It appears that D-Aloe's effect of preventing dermal ischemia by reversing the effects of thromboxane synthetase (TxA2) may act synergistically with NO or could be an oxygen radical scavenger. PMID: 9395704

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

Heggers JP, Kucukcelebi A, Listengarten D, Stabenau J, Ko F, Broemeling LD, Robson MC, Winters WD. University of Texas Medical Branch, Galveston, USA.

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. PMID: 9395659

Isolation and characterization of the glycoprotein fraction with a proliferation-promoting activity on human and hamster cells in vitro from Aloe vera gel.

Yagi A, Egusa T, Arase M, Tanabe M, Tsuji H. Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.

Fractions of leaf gel from Aloe barbadensis Mill. were prepared by gel permeation using DEAE Sephadex A-25, Sepharose 6B, and Sephadex G-50 columns. These were then tested by in vitro assays for proliferation of human normal dermal and baby hamster kidney cells. The glycoprotein fraction promoted cell growth, while the neutral polysaccharide fraction did not show any growth stimulation. Moreover, the polar-colored glycoprotein fraction strongly inhibited the in vitro assays. An active glycoprotein fraction (protein 82%, carbohydrate 11%) examined on polyacrylamide gel electrophoresis (PAGE) and SDS-PAGE showed a single band. Its molecular weight was 29 kD on a Sephadex G-50 column and its isoelectric point was pH 6.8. Immunoblotting after SDS-PAGE showed that the glycoprotein was composed of two subunits (14 kD). Deglycosylation of glycoprotein (Pg21-2b fraction) by trifluoromethanesulphonic acid provided a protein band with a molecular weight of 13 kD on SDS-PAGE. The colored glycoprotein fraction was shown on SDS-PAGE to be a mixture with a molecular weight of 18 kD-15 kD. It was later hydrolyzed with 10% H2SO4 to produce phenolic substances. PMID: 9063091

Hematopoietic augmentation by a beta-(1,4)-linked mannan.

Egger SF, Brown GS, Kelsey LS, Yates KM, Rosenberg LJ, Talmadge JE. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.

CARN 750 (injectable acemannan) is a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe barbadensis plant. It has multiple therapeutic properties including activity in wound repair and as a biological agent for the treatment of neoplasia in animals as well as the ability to activate macrophages. We report herein that CARN 750 directly or indirectly has significant hematoaugmenting properties. We observed that the subcutaneous administration of CARN 750 significantly increases splenic and peripheral blood cellularity, as well as hematopoietic progenitors in the spleen and bone marrow as determined by the interleukin-3-responsive colony-forming unit culture assay and the high-proliferative-potential colony-forming-cell (HPP-CFC) assay (a measure of primitive hematopoietic precursors) in myelosuppressed (7 Gy) C57BL/6 mice. The greatest hematopoietic effect was observed following sublethal irradiation in mice receiving 1 mg CARN 750/ animal, with less activity observed at higher or lower doses. Further, CARN 750, following daily injection, has activity equal to or greater than the injection of an optimal dose of granulocyte-colony-stimulating factor (G-CSF) in myelosuppressed mice. In this comparison, significantly greater activity was observed in the splenic and peripheral blood cellularity, and in the frequency and absolute number of splenic HPP-CFC as compared to the mice receiving G-CSF at 3 micrograms/animal. CARN 750, when administered to myelosuppressed animals, decreased the frequency of lymphocytes with a concomitant significant increase in the frequency of polymorphonuclear leukocytes (PMN). However, owing to the increased cellularity, a significant increase in the absolute number of PMN, lymphocytes, monocytes and platelets was observed, suggesting activity on multiple cell lineages. The latter is the primary difference in activity as compared to G-CSF which has activity predominantly on PMN. PMID: 9003464

Studies on optimal dose and administration schedule of a hematopoietic stimulatory beta-(1,4)-linked mannan.

Egger SF, Brown GS, Kelsey LS, Yates KM, Rosenberg LJ, Talmadge JE. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.

Several complex carbohydrates have been found to significantly stimulate hematopoiesis. CARN 750, a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe vera plant, has been shown to have activity in wound repair, to function as a antineoplastic, and to activate macrophages. We report, herein, the hematoaugmenting properties of CARN 750 and its optimal dose and timing of administration in an animal model of irradiation-induced myelosuppression. We observed that subcutaneous injections of 1 mg/animal of CARN 750 had equal or greater stimulatory activity for white blood cell (WBC) counts and spleen cellularity as well as on the absolute numbers of neutrophils, lymphocytes, monocytes and platelets than did higher or lower doses of CARN 750 or an optimal dose of granulocyte-colony stimulating factor (G-CSF). Hematopoietic progenitors, measured as interleukin-3-supported colony forming units-culture (CFU-C) and high proliferative potential colony-forming cells (HPP-CFC) assays, were similarly increased by CARN 750 in the spleen but not in the bone marrow. The frequency of splenic HPP-CFCs and absolute number of splenic HPP-CFCs and CFU-Cs were optimally increased by 1 mg/animal of CARN 750. In contrast, bone marrow cellularity, frequency and absolute number of HPP-CFCs and CFU-Cs had as a dosage optimum 2 mg/animal of CARN 750. These parameters were similarly increased by G-CSF. In studies to determine the optimal protocol for the administration of CARN 750 we found that the hematopoietic activity of CARN 750 increased with the frequency of administration. The greatest activity in myelosuppressed mice was observed for all hematopoietic parameters except the platelet number in mice receiving daily administration of 1 mg/animal of CARN 750 with activity equal to or greater than G-CSF. PMID: 8799361

Effect of aloe vera gel to healing of burn wound a clinical and histologic study.

Visuthikosol V, Chowchuen B, Sukwanarat Y, Sriurairatana S, Boonpucknavig V. Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

In a study of twenty-seven patients with partial thickness burn wound, they were treated with aloe vera gel compared with vaseline gauze. It revealed the aloe vera gel treated lesion healed faster than the vaseline gauze area. The average time of healing in the aloe gel area was 11.89 days and 18.19 days for the vaseline gauze treated wound. Statistical analysis by using t-test and the value of P < 0.002 was statistically significant. In histologic study, it showed early epithelialization in the treated aloe vera gel area. Only some minor adverse effects, such as discomfort and pain were encountered in the 27 cases. This study showed the effectiveness of aloe vera gel on a partial thickness burn wound, and it might be beneficial to do further trials on burn wounds. PMID: 7561562

Treatment of experimental frostbite with pentoxifylline and aloe vera cream.

Miller MB, Koltai PJ. Division of Otolaryngology, Albany (NY) Medical College, USA.

OBJECTIVE: To compare the therapeutic effects of systemic pentoxifylline and topical aloe vera cream in the treatment of frostbite. DESIGN: The frostbitten ears of 10 New Zealand white rabbits were assigned to one of four treatment groups: untreated controls, those treated with aloe vera cream, those treated with pentoxifylline, and those treated with aloe vera cream and pentoxifylline. MAIN OUTCOME MEASURES: Tissue survival was calculated as the percent of total frostbite area that remained after 2 weeks. RESULTS: The control group had a 6% tissue survival. Tissue survival was notably improved with pentoxifylline (20%), better with aloe vera cream (24%), and the best with the combination therapy (30%). CONCLUSION: Pentoxifylline is as effective as aloe vera cream in improving tissue survival after frostbite injury. PMID: 7772322

Aloe vera, hydrocortisone, and sterol influence on wound tensile strength and anti-inflammation.

Davis RH, DiDonato JJ, Johnson RW, Stewart CB. Pennsylvania College of Podiatric Medicine, Philadelphia.

Aloe vera at doses of 100 and 300 mg/kg daily for 4 days blocked the wound healing suppression of hydrocortisone acetate up to 100% using the wound tensile strength assay. This response was because of the growth factors present in A. vera masking the wound healing inhibitors such as sterols and certain amino acids. The sterols showed good anti-inflammatory activity (-36%) in reducing the croton oil-induced ear swelling. This activity displayed a dose-response relationship. PMID: 7853156

Anti-inflammatory and wound healing activity of a growth substance in Aloe vera.

Davis RH, Donato JJ, Hartman GM, Haas RC. Department of Biomedical Sciences, Pennsylvania College of Podiatric Medicine, Philadelphia.

Aloe vera improves wound healing and inhibits inflammation. Since mannose-6-phosphate is the major sugar in the Aloe gel, the authors examined the possibility of its being an active growth substance. Mice receiving 300 mg/kg of mannose-6-phosphate had improved wound healing over saline controls. This dose also had anti-inflammatory activity. PMID: 8169808

Administration of air under the skin produced a pouch wall that closely resembled a synovium in that the inner lining was made up of macrophages and fibroblasts. Administration of 1% carrageenan directly into the 7-day-old air pouch produced an inflammation characterized by an increased number of mast cells in pouch fluid as well as an increase in wall vascularity. A punch biopsy weight of the pouch wall did not reveal an increase in 1% carrageenan-treated animals. However, a 10% Aloe vera treatment of carrageenan-inflamed synovial pouches reduced the vascularity 50% and the number of mast cells in synovial fluid 48%. The pouch wall punch biopsy weight was increased by A. vera, which was verified by histologic examination of the inner synovial lining. Aloe vera stimulated the synovial-like membrane, as evidenced by an increased number of fibroblasts, suggesting that A. vera stimulated fibroblasts for growth and repair of the synovial model. The synovial air pouch can be used to study simultaneously the acute anti-inflammatory and fibroblast stimulating activities of A. vera. PMID: 1578350

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