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Aloe (Aloe vera)


Aloe vera Image
Synonyms / Common Names / Related Terms
Acemannan, Aloe africana, Aloe arborescens Miller, Aloe barbadensis, Aloe barbadesis, Aloe capensis, aloe-coated gloves, Aloe ferox, aloe latex, aloe mucilage, Aloe perfoliata, Aloe perryi Baker, Aloe spicata, Aloe vulgari, Barbados aloe, bitter aloe, burn plant, Cape aloe, Carrisyn, hirukattali, Curaçao aloe, elephant's gall, first-aid plant, Ghai kunwar (Indian), Ghikumar (Indian), Hsiang-Dan (Chinese), jelly leek, kumari, lahoi, laloi, lily of the desert, Lu-Hui, medicine plant, Mediterranean aloe, miracle plant, mocha aloes, musabbar, natal aloes, nohwa, plant of immortality, plant of life, rokai, sabilla (Spanish), Savila, Socotrine aloe, subr, true aloe, Venezuela aloe, Za'bila (Swahili), Zanzibar aloe.
Combination product (example): Mepentol Leche (an emulsion based on hyper-oxygenated fatty acids, Aloe barbadensis and Mimosa tenuiflora).


Mechanism of Action
Pharmacology:
  • Aloe gel: The gel or mucilage obtained from the flesh of the leaf is 99% water at pH 4.5. The constituent polysaccharide glucomannan is an effective human skin moisturizer, which accounts for its use in many cosmetics. Acemannan, the major carbohydrate fraction in the gel, is a water-soluble long chain mannose polymer, which has been found in vitro and in animal studies to modulate immune function (particularly macrophage activation and cytokine production) and to accelerate wound healing. The macrophage stimulating principle of acemannan appears to reside in the high molecular weight polysaccharide Aloeride®.12 Acemannan has also been reported to exhibit antineoplastic and antiviral effects in vitro.
  • Other constituents include bradykininase, which possesses anti-inflammatory properties and magnesium lactate, which has antipruritic effects.5 A mannose-rich polysaccharide fraction of aloe gel has been shown in mice to enhance antibody production.13 Salicylic acid and other antiprostaglandin compounds may be responsible for aloe's local anti-inflammatory activity, possibly due to an inhibitory effect on the arachidonic acid pathway via cyclooxygenase.14
  • Maloyl glucan compounds isolated from Aloe barbadensis Miller include 6-O-(1-L-maloyl)-alpha-,beta-D-Glcp (veracylglucan A), alpha-D-Glcp-(1-->4)-6-O-(1-L-maloyl)-alpha,-beta,-D-Glcp (veracylglucan B) and alpha-D-Glcp-(1-->4)-tetra-[6-O-(1-L-maloyl)-alpha-D-Glcp-(1-->4)]-6-O-(1-L-maloyl)-alpha,-beta-D-Glcp (veracylglucan C).15 Based on in vitro study, veracylglucan B demonstrated potent anti-inflammatory and anti-proliferative effects, while veracylglucan C exhibited significant cell proliferative and anti-inflammatory activities. Veracylglucan B and C appeared antagonistic and competitive in their effects on cell proliferation.
  • Antifungal effects: A hydroalcoholic extract of fresh Aloe vera leaves had a minimum fungicidal concentration (MFC) between 80 and 100mcL/mL against the mycelial growth of Botrytis gladiolorum, Fusarium oxysporum f.sp. gladioli, Heterosporium pruneti, and Penicillium gladioli.1
  • Anti inflammatory effects: Topical aloe's anti-inflammatory properties do not appear to interfere with wound healing, but rather increase wound tensile strength16, possibly due to the fibroblast stimulating activity of mannose-6-phosphate.17 In vivo, Aloe vera gel (97.5%) significantly reduced UV-induced erythema after 48 hours, being superior to 1% hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more efficient than Aloe vera gel.18 Aloe also has antithromboxane activity, yet it maintains prostaglandin ratio without causing injured blood vessels to collapse.
  • Antineoplastic effects: Anti-leukemic and anti-mutagenic effects of aloe in vitro have been attributed to di (2-ethylhexyl) phtalate (DEHP).19 Promotion of apoptosis has been reported in vitro as a possible anti-neoplastic mechanism.20 Aloe appears to affect detoxification of reactive metabolites by liver and other organs.3
  • Antioxidant effects: Antioxidant properties have been attributed to aloesin derived from Aloe vera.2,3,4 Based on cell-line research, APS-1, a polysaccharide from Aloe vera var. chinesis, also showed free radical scavenging and other antioxidant properties.21
  • Cardiovascular effects: Calcium isocitrate, isolated from Aloe sponaria, has been shown to be inotropic in rat and rabbit hearts.5
  • Endocrine effects: Constituents of Kitachi aloe leaf pulp and skin have been found to stimulate beta-cells in diabetic mice, thereby lowering blood glucose levels.7
  • Radioprotective effects: Wang et al. suggested that aloe polysaccharides may have a radioprotective effect on non-malignant cells via its ability to modulate the cell cycle.22,23
  • Other effects: In a study of topical application for up two weeks, Aloe barbadensis Miller extracts increased the water content of the stratum corneum of the arms of human volunteers, although transepidermal water loss was not altered.24
  • Aloe latex: Aloe latex contains anthraquinone glycosides (aloin, aloe-emodin and barbaloin) that act as potent stimulant laxatives.25,26,27,28,29,6,30 These water soluble glycosides are split by intestinal bacteria into aglycones, which are believed to exert a more powerful laxative effect than other herbs, including senna, cascara, or rhubarb root. One of these compounds, aloe-emodin-9-anthrone, has been shown to increase the water content in rat large intestines.31 This appears to be a more important cathartic mechanism than increased intestinal motility (which has also been proposed).26,27
  • Cytotoxic effects: The anthraquinone glycosides have been studied for their cytotoxic effects.8 For instance, aloe-emodin induced apoptosis in T24 human bladder cancer cells, which is thought to be mediated through the activation of p53, p21,Fas/APO-1, Bax and caspase-3.9 In human malignant melanoma cells, aloe-emodin inhibited NAT1 activity in intact cells in a dose-dependent manner.10 In human lung carcinoma cells, aloe-emodin is thought to induce DNA damage through generation of reactive oxygen species.11
  • Based on in vivo angiogenesis assays, Cárdenas et al. reported that aloe-emodin may behave as both an anti-tumor and an anti-angiogenic compound32 Aloe-emodin is thought to inhibit endothelial cell proliferation, but this effect is not cell specific, since aloe-emodin also inhibits tumor cell proliferation. Cell migration and invasion are not remarkably affected by aloe-emodin. On the other hand, aloe-emodin has different effects on endothelial and tumor cell gelatinases. Two main targets of the pharmacological action of aloe-emodin as an anti-angiogenic compound seem to be urokinase secretion and tubule formation of endothelial cells.

Pharmacodynamics/Kinetics:
  • Anthraquinone glycosides, which are absorbed well only after digestion by intestinal bacteria, are eliminated in the urine, bile, feces, and breast milk.
  • The half-life of aloe-emodin is approximately 48-50 hours.33

References
  1. Rosca-Casian, O., Parvu, M., Vlase, L., and Tamas, M. Antifungal activity of Aloe vera leaves. Fitoterapia 2007;78(3):219-222. 17336466
  2. Yagi, A., Kabash, A., Mizuno, K., Moustafa, S. M., Khalifa, T. I., and Tsuji, H. Radical Scavenging Glycoprotein Inhibiting Cyclooxygenase-2 and Thromboxane A2 Synthase from Aloe vera Gel. Planta Med. 2003;69(3):269-271. 12677534
  3. Singh, R. P., Dhanalakshmi, S., and Rao, A. R. Chemomodulatory action of Aloe vera on the profiles of enzymes associated with carcinogen metabolism and antioxidant status regulation in mice. Phytomedicine 2000;7(3):209-219. 11185732
  4. Yagi, A., Kabash, A., Okamura, N., Haraguchi, H., Moustafa, S. M., and Khalifa, T. I. Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera. Planta Med 2002;68(11):957-960. 12451482
  5. Yagi, A., Shibata, S., Nishioka, I., Iwadare, S., and Ishida, Y. Cardiac stimulant action of constituents of Aloe saponaria. J Pharm.Sci 1982;71(7):739-741. 7120054
  6. Krumbiegel G and Schulz HU. Rhein and aloe-emodin kinetics from senna laxatives in man. Pharmacology 1993;47(suppl 1):120-124. 8234418
  7. Beppu H, Nagamura Y, and Fujita K. Hypoglycemic and antidiabetic effects in mice of aloe-arborescens miller var natalensis berger. Phytother Res 1993;7:S37-S42.
  8. Esmat, A. Y., Tomasetto, C., and Rio, M. C. Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: topoisomerase IIalpha coamplification. Cancer Biol Ther 2006;5(1):97-103. 16357514
  9. Lin, J. G., Chen, G. W., Li, T. M., Chouh, S. T., Tan, T. W., and Chung, J. G. Aloe-emodin induces apoptosis in T24 human bladder cancer cells through the p53 dependent apoptotic pathway. J Urol 2006;175(1):343-347. 16406939
  10. Lin, S. Y., Yang, J. H., Hsia, T. C., Lee, J. H., Chiu, T. H., Wei, Y. H., and Chung, J. G. Effect of inhibition of aloe-emodin on N-acetyltransferase activity and gene expression in human malignant melanoma cells (A375.S2). Melanoma Res 2005;15(6):489-494. 16314733
  11. Lee, H. Z., Lin, C. J., Yang, W. H., Leung, W. C., and Chang, S. P. Aloe-emodin induced DNA damage through generation of reactive oxygen species in human lung carcinoma cells. Cancer Lett 7-28-2006;239(1):55-63. 16300878
  12. Pugh, N., Ross, S. A., ElSohly, M. A., and Pasco, D. S. Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity. J Agric Food Chem 2001;49(2):1030-1034. 11262067
  13. 't Hart, L. A., van den Berg, A. J., Kuis, L., van Dijk, H., and Labadie, R. P. An anti-complementary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera. Planta Med 1989;55(6):509-512. 2616669
  14. Vazquez, B., Avila, G., Segura, D., and Escalante, B. Antiinflammatory activity of extracts from Aloe vera gel. J Ethnopharmacol. 1996;55(1):69-75. 9121170
  15. Esua, M. F. and Rauwald, J. W. Novel bioactive maloyl glucans from aloe vera gel: isolation, structure elucidation and in vitro bioassays. Carbohydr Res 2-27-2006;341(3):355-364. 16343466
  16. Davis, R. H., DiDonato, J. J., Johnson, R. W., and Stewart, C. B. Aloe vera, hydrocortisone, and sterol influence on wound tensile strength and anti-inflammation. J Am Podiatr.Med Assoc 1994;84(12):614-621. 7853156
  17. Davis, R. H., Donato, J. J., Hartman, G. M., and Haas, R. C. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr.Med Assoc 1994;84(2):77-81. 8169808
  18. Reuter, J., Jocher, A., Stump, J., Grossjohann, B., Franke, G., and Schempp, C. M. Investigation of the anti-inflammatory potential of Aloe vera gel (97.5%) in the ultraviolet erythema test. Skin Pharmacol Physiol 2008;21(2):106-110. 18253066
  19. Lee, K. H., Kim, J. H., Lim, D. S., and Kim, C. H. Anti-leukaemic and anti-mutagenic effects of di(2-ethylhexyl)phthalate isolated from Aloe vera Linne. J Pharm Pharmacol 2000;52(5):593-598. 10864149
  20. Pecere, T., Sarinella, F., Salata, C., Gatto, B., Bet, A., Dalla, Vecchia F., Diaspro, A., Carli, M., Palumbo, M., and Palu, G. Involvement of p53 in specific anti-neuroectodermal tumor activity of aloe-emodin. Int J Cancer 10-10-2003;106(6):836-847. 12918060
  21. Wu, J. H., Xu, C., Shan, C. Y., and Tan, R. X. Antioxidant properties and PC12 cell protective effects of APS-1, a polysaccharide from Aloe vera var. chinensis. Life Sci 1-2-2006;78(6):622-630. 16150464
  22. Wang, Z., Huang, Z., Wu, Q., Zhou, J., Zhu, X., Li, Q., and Liu, Z. [The modulating of aloe polysaccharides on the cell cycle and cycle regulating protein expression in X-ray irradiated non-malignant cells]. Zhong.Yao Cai. 2005;28(6):482-485. 16209264
  23. Wang, Z. W., Huang, Z. S., Yang, A. P., Li, C. Y., Huang, H., Lin, X., Liu, Z. C., and Zhu, X. F. [Radioprotective effect of aloe polysaccharides on three non-tumor cell lines]. Ai.Zheng. 2005;24(4):438-442. 15820066
  24. Dal'Belo, S. E., Gaspar, L. R., and Maia Campos, P. M. Moisturizing effect of cosmetic formulations containing Aloe vera extract in different concentrations assessed by skin bioengineering techniques. Skin Res Technol 2006;12(4):241-246. 17026654
  25. de Witte, P. and Lemli, L. The metabolism of anthranoid laxatives. Hepatogastroenterology 1990;37(6):601-605. 2289777
  26. Ishii, Y., Tanizawa, H., and Takino, Y. Studies of aloe. IV. Mechanism of cathartic effect. (3). Biol.Pharm.Bull. 1994;17(4):495-497. 8069255
  27. Ishii, Y., Tanizawa, H., and Takino, Y. Studies of aloe. V. Mechanism of cathartic effect. (4). Biol.Pharm.Bull. 1994;17(5):651-653. 7920425
  28. Honig J, Geck P, and Rauwald HW. Inhibition of Cl- channels as a possible base of laxative action of certain anthraquinones and anthrones. Planta Med 1992;58(suppl 1):A586-A587.
  29. Koch A. Investigations of the laxative action of aloin in the human colon. Planta Med 1993;59:A689.
  30. Nelemans FA. Clinical and toxicological aspects of anthraquinone laxatives. Pharmacology 1976;14(suppl 1):73-77. 981318
  31. Ishii, Y., Tanizawa, H., and Takino, Y. Studies of aloe. III. Mechanism of cathartic effect. (2). Chem.Pharm.Bull.(Tokyo) 1990;38(1):197-200. 2159853
  32. Cardenas, C., Quesada, A. R., and Medina, M. A. Evaluation of the anti-angiogenic effect of aloe-emodin. Cell Mol.Life Sci 2006;63(24):3083-3089. 17131052
  33. Lang, W. Pharmacokinetic-metabolic studies with 14C-aloe emodin after oral administration to male and female rats. Pharmacology 1993;47 Suppl 1:110-119. 8234417




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