Aloin A prevents ulcerative colitis in mice by enhancing the intestinal barrier function via suppressing the Notch signaling pathway.

BACKGROUND: Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered. METHODS: C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days. Concurrently, AA (25, 50 mg/kg) and 5-aminosalicylic (500 mg/kg) were administrated intragastrically from day 1 to day 7. Colitis was evaluated by disease active index (DAI), colon length, inflammation response, and intestinal barrier function. In vitro LS174T cells challenged with 50 ng/ml of lipopolysaccharides (LPS) were used to validate the modulatory action of AA on the Notch signaling pathway. RESULTS: Our results showed that oral administration with AA prominently prevented DSS-induced colitis symptoms in terms of decreased DAI, prevention of colon shortening, and reduced pathological damage. AA mitigated the inflammatory response evidenced by the decreased proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and increased anti-inflammatory cytokine (IL-10). Besides, AA inhibited apoptosis and facilitated proliferation in colons. Moreover, AA treatment up-regulated the expression of tight junction (TJ) proteins (ZO-1, Occludin) and promoted the secretion of MUC2 to decrease colon permeability. Mechanistically, AA inhibited the Notch pathway to promote the secretion of MUC2, which was consistent with LPS-challenged LS174 cells. CONCLUSION: These results suggested that AA could prevent colitis by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Thus, AA might be a prospective remedy for ulcerative colitis.

Characterization of the metabolism of aloin A/B and aloesin in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti-bacterial, anti-tumour, anti-inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin.

Analysis of the Composition of Lyophilisates Obtained from Aloe arborescens Gel of Leaves of Different Ages from Controlled Crops.

The aim of the study is to evaluate the composition of lyophilisates obtained from Aloe arborescens leaf gel at the age of one to four years. The leaves were obtained from controlled crops, which allowed to exclude environmental factors as variables. It was confirmed that the lyophilisates obtained from different years of Aloe arborescens leaf gel varied in chromatographic analyses in terms of aloin A and aloenin A content (high-performance liquid chromatography with diode-array detection HPLC-DAD, high-performance liquid chromatography with tandem mass spectrometric detection HPLC-MS/MS). Similarly, while testing the phenolic acids and the sum of polyphenols content, differences in their levels in leaf gel lyophilisates from plants of individual years were observed (spectrophotometric method UV-VIS). The lyophilisate composition analysis showed that the one-year-old leaves were characterized by the highest content of aloin A and aloenin A. While the content of polyphenols, including phenolic acids, was higher in the leaves of older plants. The antioxidant potential of the tested lyophilisates was assessed simultaneously. Regardless of the research model used (CUPRAC, DPPH, ABTS), an antioxidant effect was noted for Aloe arborescens leaves.

Aloe vera mitigates dextran sulfate sodium-induced rat ulcerative colitis by potentiating colon mucus barrier.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm. f. (Aloe vera) is a medicinal herb that used in Traditional Chinese Medicine (TCM) practice for the treatment of gastrointestinal diseases such as constipation and colitis. Recent studies also reported its beneficial effect in mitigating ulcerative colitis (UC). Nevertheless, the underlying mechanisms of Aloe vera against UC remain largely unknown. AIM OF THE STUDY: This study aimed to explore a relation between the therapeutical effects of Aloe vera in UC and colonic mucus secretion, and further investigate the underlying pathways through which Aloe vera regulates colon mucus as well as preliminarily studied the main active constitute of Aloe vera to alleviate UC. MATERIALS AND METHODS: UPLC-MS/MS were employed to analyze the Aloe vera extract. The rat models of UC were induced by free subjected to fresh 3% dextran sulfate sodium (DSS) solution for 8 days and then accessed to tap water for 2 days. Aloe vera extract (18 mg/kg and 72 mg/kg) or 5-ASA (400 mg/kg) was administered orally from day 1-10. At the end of experiment, rats were sacrificed and the colon tissues were harvested for analysis. UC symptoms was evaluated by disease activity index (DAI), colon length and H&E staining. The Alcian blue stain were determined colon mucus layer. Myeloperoxidase (MPO) activity, mucin and inflammatory cytokines in colon tissues were determined by ELISA. The expression of related proteins on PI3K/AKT and PKC/ERK signaling pathway was analyzed by Western blot. We then evaluated the effects of three main components of Aloe vera (Aloe-emodin, aloin A and B) on mucin secretion and cytokine expression in vitro by ELISA. RESULTS: Oral supplement with Aloe vera extract resulted in a significantly decreased DSS-induced UC symptoms, including decreased DAI, prevention of the colon length shortening, and alleviation of the pathological changes occurring in colon. The expression of colonic pro-inflammatory mediators, including IL-6, IL-1ß and TNF-α were suppressed, yet the expression of IL-10 was up-regulated by Aloe vera treatment. Moreover, Aloe vera significantly up-regulated the expressions of mucin proteins (e.g., MUC2 and MUC5AC) and increased the thickness of mucus layer in the colon. Further, we revealed that Aloe vera significantly upregulated p-PKC and p-ERK expression and downregulated p-PI3K and p-AKT expression. Finally, we discovered that treat with aloin A markedly decreased IL-6 levels and increased MUC2 expression in LPS-stimulated LS174T cell. CONCLUSION: These results support that Aloe vera improved UC by enhancing colon mucus barrier functions in addition to reducing inflammation. Moreover, aloin A might be a main active components of Aloe vera to ameliorate UC.

Characterization and Evaluation of Antioxidant Activity of Aloe schelpei Reynolds.

BACKGROUND: The role of free radical reactions in disease pathology is well known to be involved in many acute and chronic disorders in human beings, such as diabetes, atherosclerosis, aging, immunosuppression and neurodegeneration. The search for new drugs of plant origin becomes increasingly urgent due to drug resistance. Aloe schelpei is an endemic Aloe species traditionally used for the treatment of infectious and chronic diseases. AIM: This study was conducted to evaluate free radical scavenging activities of leaf latex of Aloe schelpei and its isolated compounds. METHODS: The leaf latex of A. schelpei was subjected to preparative thin-layer chromatography to afford three compounds. Free radical scavenging activities of the leaf latex and its constituents was carried out using a 2, 2-diphenyl-1-picrylhydrazyl method. RESULTS: Phytochemical investigation of the leaf latex Aloe schelpei by prepartive thin layer chromatography led to the isolation of three compounds, identified as microdontin A/B (1), aloin A/B (2) and aloinoside A/B (3). The results showed that the leaf latex had a strong free radical scavenging activity reaching a maximum of 84.3% at a concentration of 100 µg/mL, and with an IC50 value of 25.3 ± 2.45 µg/mL (p < 0.05). Among the isolated compounds, microdontin A/B (1) was found to have the strongest free radical scavenging activity with an IC50 value of 0.07 ± 0.005 mµ, followed by aloinoside A/B (IC50 = 0.13 ± 0.01 mM) and aloin A/B (IC50 = 0.15 ± 0.02 mM). CONCLUSION: The traditional medicinal practice of the leaf latex may be due to the antioxidant activities of the leaf latex of A. schelpei and the isolated compounds.

UHPLC-MS/MS method for the quantification of aloin-A in rat plasma and its application to a pharmacokinetic study.

Aloin-A (also known as barbaloin), the main bioactive anthraquinone-C-glycoside of Aloe species, exhibits various beneficial pharmacological effects. However, the determination and pharmacokinetic study of aloin-A in rat plasma need to be improved and systematically demonstrated. In the present study, a simple, robust and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for rapid quantification of aloin-A in rat plasma was developed. Plasma preparation was conducted by a single step protein precipitation with obtusin serving as an internal standards (IS) followed by separation of the analytes using an Agilent C18 column with a gradient mobile phase comprised of acetonitrile and formic acid aqueous solution. Negative ion electrospray was used and multiple reaction monitoring transitions were m/z 417.1 → 297.0 for aloin-A and m/z 343.1 → 328.1 for IS, respectively. The developed method was validated with linear range of 1-1000 ng/mL. All validation parameters were well within the acceptance criteria based on the guidance of FDA. The validated approach was successfully applied to analyze samples from a pharmacokinetic study in healthy rats following intravenous and oral administration. Aloin-A was found to be quickly absorbed, extensively distributed and rapidly eliminated. The absolute bioavailability of aloin-A was 5.79%.

Natural phosphodiesterase-4 inhibitors from the leaf skin of Aloe barbadensis Miller.

The ethanolic extract of Aloe barbadensis Miller leaf skin showed inhibitory activity against phosphodiesterase-4D (PDE4D), which is a therapeutic target of inflammatory disease. Subsequent bioassay-guided fractionation led to the isolation of two new anthrones, 6'-O-acetyl-aloin B (9) and 6'-O-acetyl-aloin A (11), one new chromone, aloeresin K (8), together with thirteen known compounds. Their chemical structures were elucidated by spectroscopic methods including UV, IR, 1D and 2D NMR, and HRMS. All of the isolates were screened for their inhibitory activity against PDE4D using tritium-labeled adenosine 3',5'-cyclic monophosphate ((3)H-cAMP) as substrate. Compounds 13 and 14 were identified as PDE4D inhibitors, with their IC50 values of 9.25 and 4.42 µM, respectively. These achievements can provide evidences for the use of A. barbadensis leaf skin as functional feed additives for anti-inflammatory purpose.

Chemical constituents of Aloe barbadensis Miller and their inhibitory effects on phosphodiesterase-4D.

Aloe barbadensis Mill has been used as food and medicine for a long time. In order to investigate the chemical constituents of A. barbadensis and their inhibitory activities towards phosphodiesterase-4D (PDE4D), 70% methanol extract of the dried A. barbadensis powder was employed. Phytochemical investigation has led to the isolation of three new chromones, 5-(hydroxymethyl)-7-methoxy-2-methylchromone (4), 5-((4E)-2'-oxo-pentenyl)-2-hydroxymethylchromone (6), and 7-hydroxy-5-(hydroxymethyl)-2-methylchromone (7), together with eighteen known compounds. Their chemical structures were determined based on spectroscopic methods including UV, IR, 1D and 2D NMR, and HRMS spectrometry. In addition, their inhibition against PDE4D was evaluated using tritium-labeled adenosine 3',5'-cyclic monophosphate ((3)H-cAMP) as the substrate. Inhibition was calculated by the variation of radioactivity after the reaction, and compounds 1-4, 10, and 21 exhibited certain inhibitory activities towards PDE4D, which can provide an explanation why A. barbadensis can serve as anti-inflammatory agents.