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Atherton, P. (1997, June/July). Aloe vera: Myth or medicine? Positive Health. Issue 20.

Abstract: Author is convinced that there is enough evidence available now to suggest that the properties of this amazing plant should be properly tested, to prove whether or not there is just a myth or real medicine here.

Cassileth, B. (2011, June 13). Aloe vera (aloe barbadensis, aloe capensis). Oncology, 25:7, 1-3

Abstract: In vitro studies indicate that aloe has immunomodulatory, anticancer, antioxidant, and anti-inflammatory properties. Emodin, an extract of aloe, inhibits cell proliferation and induces apoptosis in human liver cancer cell lines via p53- and p21-dependent pathways. One study showed topical aloe vera to be superior to silver sulfadiazine (drug information on silver sulfadiazine) cream, an agent commonly used to treat second-degree burns. A few trials have explored aloe’s anticancer effects. Concurrent oral administration of aloe with chemotherapy was reported to increase the efficacy of chemotherapy in patients with metastatic cancers and to prevent oral mucositis. Data on topical aloe’s role in alleviating radiation therapy-induced skin damage are inconsistent. More research is needed to determine the safety and efficacy of aloe vera in cancer patients.

Farahnejad, Z., Ghazanfari, T., and Yaraee, R. (2011). Immunomodulatory effects of Aloe vera and its fractions on response of macrophages against Candida albicans. Immunopharmacology and Immunotoxicology, 33(4), 676-681. 

Abstract: Natural products are important resources in traditional medicine and have been long used for prevention and treatment of many diseases. Medicinal plants have immunomodulatory properties. Aloe is one of the herbal medicines widely used in natural treatment and alternative therapy for various types of diseases. Aloe vera has been shown to modulate the immune response. Macrophages have been shown to play an essential role as the first line of defense against invading pathogen. Candida albicans is a communal and opportunistic pathogen in humans. In this study, we investigated the effect of A. vera extract and its fractions on infected macrophages with C. albicans. Viability of intraperitoneal macrophages was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Cell viability of infected macrophages was increased by the extract and dose of some isolated fractions dependently. The extract as well as R100, R50, R30, and R10 fractions of A. vera significantly increased cell viability of macrophages in most doses. R5 and F5 fractions showed no significant difference in comparison with control group. Further studies in animal models and human are necessary to clarify the modulatory effects of A. vera on macrophage function. Isolation and purification of A. vera components are also needed to find out the effective molecules.

Fortak, W. (1964). Biostymin, extract of Aloe histologic and histochemical studies on the influence of biostymin on regeneration of hepatic parenchyma in white rats. Archivum Immunologiae El Therapiae Experimentalis,12, 80-95.

Abstract: A study on healing of injured white rats by a product developed in Poland from Aloe juice, called Biostymin, meaning biogenic stimulator, made from Aloe aborescens.

Fortak, W., Karasek, M., and Kolaszynski, J. (1964). Biostymin: Aloe extract histologic and histochemical studies on the mechanism of action of biostymin in the animal body. Archivum Immunologiae El Therapiae Experimentalis, 12, 96-105.

Abstract: This study was undertaken with the idea of elucidating, by means of morphochemical methods, the effect of Biostymin on the reticuleondothelial system of the spleen and the action of the drug on the adrenals in white rats.

Im, S. A., Lee, Y. R., Lee, Y. H., Lee, M. K., Park, Y. I., Lee, S., Kim, K., and Lee, C. K. (2010). In vivo evidence of the immunomodulatory activity of orally administered aloe vera gel. Arch Pharm Res, 33(3), 451-456.

Abstract: The gels of Aloe species contain immunomodulatory components such as aloctin A and acemannan. Most studies on these gels were performed in in vitro cell culture systems. Although several studies examined their immunomodulatory activity in vivo, the route of administration was intraperitoneal or intramuscular. Here, we evaluated the in vivo immunomodulatory activity of processed Aloe vera gel (PAG) in mice. Oral administration of PAG significantly reduced the growth of C. albicans in the spleen and kidney following intravenous injection of C. albicans in normal mice. PAG administration also reduced the growth of C. albicans in streptozotocin-induced diabetic mice. PAG administration did not increase ovalbumin (OVA)-specific cytotoxic T lymphocyte (CTL) generation in normal mice, but did increase it in high-fat-diet induced diabetic mice. These findings provide the first clear evidence for the immuno-modulatory activity of orally administered Aloe vera gel.

Imanishi, K.. (1993). Aloctin A, an active substance of Aloe arborescens Miller as immunomodulator. Department of Microbiology and Immunology, Tokyo Women’s Medical College, Tokyo, Japan, 1-4.

Abstract: In this article, I would like to describe the antitumor activity of Aloe A using methylcholanthrene-induced nurine fibrosarcoma (MethA) and lymphocytic leukemia in syngeneic mouse systems.

Ji-eun, S. (2009, September 19). Health ministry scales back measures in schools for flu. JoonAng Daily. 

Abstract: Korea FDA warns against A(H1N1) claims, notes aloe vera is one of only four ingredients allowed to claim immune system enhancement.

Karaca, K., Sharma, J. M., and Nordgren, R. (1995). Nitric oxide production by chicken macrophages activated by Acemannan. International 1. Immuno Pharmacology, 17(3), 183-188.

Abstract: Cultures of normal chicken spleen cells and HD11 line cells produce nitric oxide (NO) in response to Acemannan, a complex carbohydrate derived from the Aloe vera plant. Neither cell type produced detectable amounts of NO in response to similar concentrations of yeast mannan, another complex carbohydrate. Nitric oxide production was dose dependent and inhibitable by the nitric oxide synthase inhibitor N G-methyl-L-arginine. In addition, the production of NO was inhibited by preincubation of ACM with concanavalin A in a dose-dependent manner. These results suggest that ACM-induced NO synthesis may be mediated through macrophage mannose receptors, and macrophage activation may be accountable for some of the immunomodulatory effects of ACM in chickens.

Khaing, T.A. (2011). Evaluation of the antifungal and antioxidant activities of the leaf extract of Aloe vera (Aloe barbbadenisis Miller). World Academy of Science: Engineering and Technology,75.

Abstract: Aloe vera has been used worldwide both for pharmaceutical, food, and cosmetic industries due to the plethora of biological activities of some of its metabolites. The aim of this study was to evaluate the antifungal and antioxidant activities of the leaf extract. The antifungal activity was determined by the agar-well diffusion method against plant and human fungal pathogens. The methanol and ethanol portions of the extracts studies were more bioactive than ethyl acetate portion. It was also observed that the activity was more pronounced on plant pathogen than human pathogen except Candida albicans. This is an indication that the extract has the potential to treat plant fungal infections. The Aloe extract showed the significant antioxidant activity by the DPPH radical scavenging method. Therefore, the Aloe extract provided as natural antioxidant has been used in health foods for medical and preservative purposes.

Lee, J. K., Lee, M. K., Yun, Y. P., Kim, Y., Kim, J. S., Kim, Y. S., Kim, K., Han, S. S., and Lee, C. K. (2001). Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. International Immunopharmacology, 1, 1275-1284.

Abstract: Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.

Lee, C. K., Hana, S. S., Shina, Y. K., Chung, M. H., Park, Y. I., Lee, S. K., and Kim, Y. S. (1999). Prevention of ultraviolet radiation-induced suppression of contact hypersensitivity by Aloe vera gel components. International Journal of Immunopharmacology, 21, 303-310.

Abstract: We have recently reported that Aloe vera gel contains small molecular weight immunomodulators, G1C2F1, that restore ultraviolet B (UVB)-suppressed accessory cell function of epidermal Langerhans cells (LC) in vitro. In the present study we evaluated the UVB-protective activity of G1C2F1 in vivo. Exposure of the shaved abdominal skin of mice to 2.4 KJ/m2 of UVB radiation resulted in suppression of contact sensitization through the skin to 41.1%, compared to normal unirradiated skin. Topical application of G1C2F1 immediately after irradiation reduced this suppression significantly. The percentage recovery of UVB-suppressed contact hypersensitivity (CHS) response was 52.3, 77.3, and 86.6% when the irradiated skin was treated once with 0.1, 0.5, and 2.5 mg/ml of G1C2F1-containing cream, respectively. G1C2F1 did not show nonspecific stimulatory activity on CHS response. The present study, together with the previous observation, show that Aloe vera gel contains small molecular weight immunomodulators that prevent UVB-induced immune suppression in the skin by restoration of UVB-induced damages on epidermal LC.

Lissoni, P., Rovelli, F., Brivio, F., Zago, R., Colciago, M., Messina, G., Mora, A., and Porro, G. (2009). A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus aloe arborescens in patients with metastatic cancer. In Vivo, 23, 171-176.

Abstract: The recent advances in the analysis of tumor immuno-biology suggest the possibility of biologically manipulating the efficacy and toxicity of cancer chemotherapy by endogenous or exogenous immuno-modulating substances. Aloe is one of the of the most important plants exhibiting anticancer activity and its anti-neoplastic property is due to at least three different mechanisms, based on anti-proliferative, immuno-stimulatory and antioxidant effects. The anti-proliferative action is determined by anthracenic and anthraquinonic molecules, while the immuno-stimulating activity is mainly due to acemannan. Patients and Methods: A study was planned to include 240 patients with metastatic solid tumor who were randomized to receive chemotherapy with or without Aloe. According to tumor histotype and clinical status, lung cancer patients were treated with Cisplatin and Etoposide or weekly Vinorelbine, colorectal cancer patients received Oxaliplatin plus 5-fluorouracil (5-FU), gastric cancer patients were treated with weekly 5-FU and pancreatic cancer patients received weekly Gemcitabine. Aloe was given orally at 10 ml thrice/daily. Results: The percentage of both objective tumor regressions and disease control was significantly higher in patients concomitantly treated with Aloe than with chemotherapy alone, as well as the percent of 3-year survival patients. Conclusion: This study seems to suggest that Aloe may be successfully associated with chemotherapy to increase its efficacy in terms of both tumor regression rate and survival time.

Lissoni, P., Rovelli, F., Messina, G., Brivio, F., Boniardi, B., Porro, G., Vigore, L., Fede, D., Marchiori, P., and Brera, G. (2009). Biotherapy with the pineal hormone melatonin plus aloe and myrrh tincture in untreatable metastatic cancer patients as an essence therapy of cancer. Cancer Therapy, 7, 297-401.

Abstract: The recent advances in understanding the immunobiological interactions responsible for cancer progression have allowed us to define the mechanisms of action of some plants, whose antitumor properties were already known by the popular Medicine, in particular Aloe and Myrrha, whose mixture was already therapeutically utilized more than 2000 years ago by the Essence medicine. Moreover, some endogenous natural substances, namely the main hormone produced by the pineal gland melatonin (MLT) may also play anticancer activity. On this basis, a study was performed with a biological regimen consisting of MLT, Aloe and Myrrha in untreatable metastatic cancer patients with life expectancy lower than 1 year. Methods: The study included 35 patients. MLT was given orally at 20 mg/day in the evening and a mixed Aloe and Myrrha tincture was administered at a dose of 5 ml/thrice daily. Results: The clinical response consisted of complete response (CR) in 1, partial response (PR) in 2, stable disease (SD) in 19 patients, whereas the remaining 13 patients had a progressive disease (PD). Thus, a disease control (CR + PR + SD) was achieved in 22/35 (63%)patients. Moreover, a survival longer than 1 year was achieved in 17/35 (49%) patients. Finally, DC was associated with an evident improvement in the immune status, namely consisting of a decrease in the number of T regulatory lymphocytes, which are the main cells responsible for the suppression of the anticancer immunity. Conclusion: This preliminary study shows that a biological anticancer regimen consisting of the pineal hormone MLT in association with Aloe and Myrrha mixture, already known at the times of the Essence medical tradition, may induce a control of the neoplastic disease by stimulating the anticancer immunity, in a relevant percentage metastatic cancer patients, who did not respond to the conventional anticancer treatments and for whom no other standard therapy was available.

Ni, Y., and Tizard, I. (1996). Lectin-carbohydrate interaction in the immune system. Veterinary Immunology and Immunopathology, 55, 205-223.

Abstract: The immune system consists of various types of cells and molecules that specifically interact with each other to initiate the host defense mechanism. Recent studies have shown that carbohydrates and lectins (carbohydrate-binding proteins) play an essential role in mediating such interactions. The development in this area has opened a new aspect in studying the immune system, and at the same time, provided new therapeutic routes for the treatment and prevention of disease.

Pittman, J. C. (1992). Immune enhancing effects of Aloe. Health Conscious,13(1), 2830.

Abstract: Galactomannans are a class of long-chain sugars derived from plants, which have been shown in laboratory and clinical studies to have a wide variety of immune stimulating and protective effects within the body. In studying the different sources of this polymer, it has been discovered that the Aloe barbadensis plant contains the greatest concentration of acetylated mannan which is also the most active form of mannans. This "acemannan" has been shown to have many effects in the body, mostly impacting on the gastrointestinal and immune systems, which are intricately related. Super-Strength aloe vera is strongly recommended in the treatment of immune deficiency disorders. It plays a prominent role in the treatment of these illnesses.

Plaskett, L. G. (1996, December). Aloe vera against infections. Aloe Vera Information Services (newsletter). Camelford, Cornwall, UK: Biomedical Information Services Ltd.

Abstract: Aloe vera has been tested against a variety of infections--viral, bacterial, and fungal. The exudate of Aloe has been confirmed again and again as having direct antimicrobial effects, killing invading pathological organisms. However, the principal benefits of Aloe with regard to infective agents comes from aloin-free or dealoinized extracts, which work by strengthening the body's own defenses. This newsletter closely examines these functions of Aloe.

Plaskett, L. G. (1996, April). Aloe vera and the human immune system. Aloe Vera Information Services (newsletter). Camelford, Cornwall, UK: Biomedical Information Services, Ltd.

Abstract: Specialized molecules in Aloe vera whole leaf extract interact with some special "receptor" substances that are embedded into the outer membrane of our immune system cells. The result is that the immune system cells are galvanized into action. In particular, the class of cells known as "phagocytes" increase the activities by which they attack and then engulf bacteria, waste products and debris. This increase in scavenging activities cleanses and protects the body, with knock-on benefits for a whole cascade of different medical conditions. The literature indicates that a common mechanism in this respect probably exists in both humans and animals and that both can benefit enormously from the use of Aloe vera.

Plaskett, L. G. (1996, May). Aloe vera eases inflammation. Aloe Vera Information Services (newsletter). Camelford, Cornwall, UK: Biomedical Information Services Ltd.

Abstract: Preparations of Aloe Vera have long been used to ease inflammatory processes originating from a wide variety of triggering causes. This article sets out the nature of inflammation, how Aloe Vera works to influence it, and what clinical problems can be helped as a result.

Russiyan, M., and Khlopushina, A. (n.d.) On the biogenic stimulators of Aloe arborescens. Extract of Aloe, Supplement to Clinical Data, Medexport, USSR, Moscow, Tashkent Pharmaceutical Institute, Russia.

Abstract: Test was conducted to study the effect of cinnamic and salicylic acids in combination with extracts from fresh and preserved Aloe arborescens leaves.

Simoes, J., Nunes, F. M., Domingues, P., Coimbra, M. A., and Domingues, M. R. (2012). Mass spectrometry characterization of an Aloe vera mannan presenting immunostimulatory activity. Carbohydrate Polymers, 90, 229-236. 

Abstract: Aloe vera acemannan is a polysaccharide composed by a backbone of (1-4)-linked d-mannose residues interspersed by few glucose residues, acetylated in O-2, O-3, and O-6 containing side chains constituted by 0-6-linked single α-D-galactose and α-L-arabinose residues. This structural features are rather similar to mannans from other sources, namely coffee and locust bean gum. However, Aloe vera acemannan and coffee mannans present immunostimulatory activity but locust bean gum does not. In order to know more about the structural features of a commercial preparation of Aloe vera presenting comparable immunostimulatory activity to that observed for coffee mannans, this preparation was submitted to sugar and methylation analysis. To gain further insight to the structural details of the mannans, focusing in the study of acetylation pattern, a specific hydrolysis with an endo-β-(1→4)-d-mannanase was performed and the resulting oligosaccharides (OS) were fractionated by size exclusion chromatography and characterized by ESI-MS, ESI-MS/MS and MALDI-MS. The majority of the OS obtained for acemannan had a ratio of two acetyl groups per sugar residue. The observation of OS highly acetylated as well as non-acetylated OS, allowed to infer a non-homogeneous distribution of the acetyl groups. Also, it was observed OS presenting fully acetylated arabinose residues. The occurrence of a high abundance of acetylated residues shows that this polysaccharide contains odd acetylation content. These unusual features are reinforced by the presence of acetylated side chains, only previously observed in chemically acetylated mannans with immunostimulatory activity prepared from coffee residue. The comparison with other galactoman-nans allowed to infer that lower branching, shorter chains, and higher acetylation seems to promote the immunostimulatory activity attributed to these polysaccharides.

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