Aloin is a chemical in the latex of Aloe Vera that can cause side effects and is banned for consumption. Learn how to avoid aloin and enjoy the benefits of Aloe Vera gel, a superfood with antioxidants and vitamins.

Exploring the therapeutic potential of Aloin

In recent years, there has been growing interest in the potential therapeutic benefits of natural compounds for various health conditions, including cancer and neurodegenerative diseases. Aloin is a bioactive compound derived from Aloe vera leaves that has shown some potential as a drug candidate for several diseases, including cancer and brain injury. Aloin has been proposed to possess neuroprotective effects, such as improving cognitive dysfunction, preventing chronic gliosis, and exhibiting antioxidant and anti-inflammatory properties. Recent studies have also suggested that Aloin could serve as a new neuroprotective compound and caspase inhibitor through its antiaggregating effects and activation of survival mechanisms. Studies have demonstrated that Aloin activates phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling, a pathway involved in promoting cell survival and inhibiting apoptosis. By enhancing this essential pathway, it confers protection against neuronal cell death and reduces the risk of neurodegenerative disorders. An additional area of interest in the study of Aloin is its potential as anticancer agent. Many studies have shown that Aloin inhibits tumor angiogenesis and growth by blocking STAT3 activation, a protein involved in cell growth and survival. Furthermore, Aloin has been found to induce cell cycle arrest and apoptotic cell death in various human cancer cell lines. These findings suggest that it may be a promising therapeutic option for cancer treatment.[1]

The therapeutic potential of Aloins, despite reported benefits in numerous studies, is constrained by their poor stability and rapid degradation in aqueous solutions. Prior research has investigated the stability of Aloins and other anthraquinones across diverse pH and temperature conditions, revealing that dehydration could notably enhance their stability during storage. Nevertheless, there is limited information regarding the stability of Aloin in aqueous solutions over time. To address this gap, we followed by RP-HPLC analysis, the disappearance of the peak relating to the metabolite over time. In this study, we explored the therapeutic potential of two derivatives extracted from the Aloe vera leaves called Aloin A (AloA) and Aloin B (AloB). The separation of the two epimers aimed to establish a structure–activity relationship and the stability of these compounds in water, a critical consideration given the aqueous nature of many pharmaceutical or nutraceutical preparations. Our investigations revealed that both epimers are not stable in neutral aqueous solution and tend to degrade rapidly, with their concentration decreasing by over 50% within approximately 12 h. This information is crucial not only for assessing product efficacy in prevention or therapy but also for validating experimental data obtained in studies employing an incubation period exceeding 12 h. As a consequence, all experiments deemed valid by us were conducted under conditions ensuring that observed effects could be attributed to Aloin rather than its degradation products.

While existing literature highlights the neuroprotective effects of Aloe vera extracts, there was a lack of data regarding their ability to inhibit amyloid aggregation. Our ThT fluorescence studies demonstrated that both products were not significantly effective in inhibiting amyloid aggregation, suggesting that neuroprotection mechanisms may be attributed to their antioxidant properties or other mechanisms. Furthermore, the antiproliferative activity of these encapsulated Aloins in carbon dots was significantly higher. The collective results suggest that, albeit this work is only a preliminary exploration of the effects of these molecules and their mechanism of action needs to be further investigated, the use of CDs nanoparticles can enhance the stability and anticancer activity of equimolar mixtures of Aloin, making them promising candidates for further in vivo studies.

Aloin Induces Pathological Changes and Modulates the Composition of Microbiota

In a previous study, the oral administration of an Aloe vera whole leaf extract induced dose-related mucosal and goblet cell hyperplasia in the rat colon after 13?weeks and colon cancer after 2?years. The primary goal of this study was to determine whether or not the administration of aloin, a component of the Aloe vera plant leaf, would replicate the pathophysiological effects that were observed in rats in the previous study with an Aloe vera whole leaf extract. Groups of 10 male F344/N rats were administered aloin at 0, 6.95, 13.9, 27.8, 55.7, 111, 223, and 446?mg/kg drinking water for 13?weeks. At the end of study, rat feces were collected, and the composition of fecal bacteria was investigated by next generation sequencing of the PCR-amplified V3/V4 region of the 16S rRNA gene. At necropsy, blood was collected by cardiac puncture and organs and sections of the large intestine were collected for histopathology. Aloin induced dose-related increased incidences and severities of mucosal and goblet cell hyperplasia that extended from the cecum to the rectum, with increased incidences and severities detected at aloin doses?≥55.7?mg/kg drinking water. Analysis of the 16S rRNA metagenomics sequencing data revealed marked shifts in the structure of the gut microbiota in aloin-treated rats at each taxonomic rank. This study highlights the similarities in effects observed for aloin and the Aloe vera whole leaf extract, and points to a potential mechanism of action to explain the observed pathological changes via modulation of the gut microbiota composition.[2]

For this study, doses of aloin were selected to include a low dose that was below the level of aloin used by the IASC in their product certification program and a high dose that was equivalent in it A content to a 2% (wt/wt) dose formulation of the Aloe vera whole leaf extract (～250?mg aloin A/kg water) that was used in the previous 13-week study (Boudreau et al., 2013). In this study, the 446?mg aloin/kg dosed water formulation had an aloin A content of ～250?mg/kg water. Lower doses equated to the aloin content in Aloe vera whole leaf extract doses of 1%, 0.5%, 0.25%, 0.13%, 0.06%, and 0.03% (wt/wt) that were used in the previous study.

The potential health benefits of aloin

Aloin, also known as barbaloin, is the anthraquinone of Aloe. Its chemical formula and molecular weights are C21H22O9 and 418.3940?g/mol, respectively. Aloin is a mixture of two diastereomers: Aloin A(R) and aloin B(S). As presented, the two diastereomers have different C-10 glycosidic bond configurations, which can be converted into each other in an aqueous solution. It tastes bitter and can be hydrolyzed to form Aloe-emodin under the action of microorganisms in the intestinal tract, stimulating the intestinal wall and increasing intestinal peristalsis. Secondary to a change in osmotic pressure, aloin is also conducive to the elimination of intestinal waste, which has led to its use as a laxative drug.[3]

The Aloe species is known for its medicinal and cosmetic properties. Aloin is an active ingredient found in the leaves of medicinal plants of the genus Aloe. It has attracted considerable interest for its antiinflammatory, anticancer, antibacterial, and antioxidant activities. However, since its clinical application is restricted by its unclear mechanism of action, a deeper understanding of its pharmacological activity is required. This review provides an overview of current pharmacological and toxicological studies published in English from February 2000 to August 2021. Herein, we summarized the sources and potential health benefits of aloin from a clinical application perspective to guide for further studies on the sources of aloin, aimed at efficiently increasing production. Importantly, the function and mechanism of action of aloin remain unclarified. In future research, it is necessary to develop new approaches for studying the pharmacological molecular mechanisms underlying the activity of this compound against various diseases.

References

[1]Zimbone S, Romanucci V, Zarrelli A, Giuffrida ML, Sciacca MFM, Lanza V, Campagna T, Maugeri L, Petralia S, Consoli GML, Di Fabio G, Milardi D. Exploring the therapeutic potential of Aloin: unraveling neuroprotective and anticancer mechanisms, and strategies for enhanced stability and delivery. Sci Rep. 2024 Jul 20;14(1):16731.

[2]Boudreau MD, Olson GR, Tryndyak VP, Bryant MS, Felton RP, Beland FA. From the Cover: Aloin, a Component of the Aloe Vera Plant Leaf, Induces Pathological Changes and Modulates the Composition of Microbiota in the Large Intestines of F344/N Male Rats. Toxicol Sci. 2017 Aug 1;158(2):302-318.

[3]Xiao, Jianbin et al. “The potential health benefits of aloin from genus Aloe.” Phytotherapy research : PTR vol. 36,2 (2022): 873-890.