Aloin

Key Compounds and Metabolic Pathway Responsible for the Browning in Dangshan Pear (Pyrus spp.) Wine.[Pubmed:34431666]

J Agric Food Chem. 2021 Sep 8;69(35):10311-10320.

Based on hydrophilic interaction liquid chromatography (HILIC) liquid chromatography-mass spectrometry (LC-MS), untargeted differential metabolomics analysis was performed on the pear wine samples before and after browning to determine the key compounds that affect the browning of Dangshan pear wine. A total of 196 significantly differential metabolites were found, 22 of which might be related to the browning of Dangshan pear wine. d-(+)-glucose, l-phenylalanine, l-norleucine, methionine, d-(+)-proline, Aloin, and rutin were the key differential metabolites in pear wine before and after browning. The Maillard reaction of d-(+)-glucose, l-norleucine, methionine, and the oxidation of Aloin played critical roles in the browning of Dangshan pear wine. The reaction of Aloin and glucose to form 5-hydroxyAloin A, 7-hydroxyAloin B, and elgonica-dimer A was one of the important metabolic pathways in which the phenolic compounds formed anthraquinone during the browning process of Dangshan pear wine.

Binding Studies of Aloe-Active Compounds with G-Quadruplex Sequences.[Pubmed:34308065]

ACS Omega. 2021 Jul 9;6(28):18344-18351.

G-quadruplex, a unique DNA quartet motif with a pivotal role in regulation of the gene expression, has been established as a potent therapeutic target for the treatment of cancer. Small-molecule-mediated stabilization of the G-quadruplex and thus inhibition of the expression from the oncogene promoter and telomere region may be a promising anticancer strategy. Aloe vera-derived natural compounds like aloe emodin, aloe emodin-8-glucoside, and Aloin have significant anticancer activity. Comparative binding studies of these three molecules with varieties of G-quadruplex sequences were carried out using different biophysical techniques like absorption spectral titration, fluorescence spectral titration, dye displacement, ferrocyanide quenching assay, and CD and DSC thermogram studies. Overall, this study revealed aloe emodin and aloe emodin-8-glucoside as potent quadruplex-binding molecules mostly in the case of c-KIT and c-MYC sequences with a binding affinity value of 10(5) order that is higher than their duplex DNA binding ability. This observation may be correlated to the anticancer activity of these aloe-active compounds and also be helpful in the potential therapeutic application of natural compound-based molecules.

Dihydroisocoumarins, Naphthalenes, and Further Polyketides from Aloe vera and A. plicatilis: Isolation, Identification and Their 5-LOX/COX-1 Inhibiting Potency.[Pubmed:34299499]

Molecules. 2021 Jul 12;26(14). pii: molecules26144223.

The present study aims at the isolation and identification of diverse phenolic polyketides from Aloe vera (L.) Burm.f. and Aloe plicatilis (L.) Miller and includes their 5-LOX/COX-1 inhibiting potency. After initial Sephadex-LH20 gel filtration and combined silica gel 60- and RP18-CC, three dihydroisocoumarins (nonaketides), four 5-methyl-8-C-glucosylchromones (heptaketides) from A. vera, and two hexaketide-naphthalenes from A. plicatilis have been isolated by means of HSCCC. The structures of all polyketides were elucidated by ESI-MS and 2D (1)H/(13)C-NMR (HMQC, HMBC) techniques. The analytical/preparative separation of 3R-feralolide, 3'-O-beta-d-glucopyranosyl- and the new 6-O-beta-d-glucopyranosyl-3R-feralolide into their respective positional isomers are described here for the first time, including the assignment of the 3R-configuration in all feralolides by comparative CD spectroscopy. The chromones 7-O-methyl-aloesin and 7-O-methyl-aloeresin A were isolated for the first time from A. vera, together with the previously described aloesin (syn. aloeresin B) and aloeresin D. Furthermore, the new 5,6,7,8-tetrahydro-1-O-beta-d-glucopyranosyl- 3,6R-dihydroxy-8R-methylnaphtalene was isolated from A. plicatilis, together with the known plicataloside. Subsequently, biological-pharmacological screening was performed to identify Aloe polyketides with anti-inflammatory potential in vitro. In addition to the above constituents, the anthranoids (octaketides) aloe emodin, Aloin, 6'-(E)-p-coumaroyl-Aloin A and B, and 6'-(E)-p-coumaroyl-7-hydroxy-8-O-methyl-Aloin A and B were tested. In the COX-1 examination, only feralolide (10 microM) inhibited the formation of MDA by 24%, whereas the other polyketides did not display any inhibition at all. In the 5-LOX-test, all Aloin-type anthranoids (10 microM) inhibited the formation of LTB4 by about 25-41%. Aloesin also displayed 10% inhibition at 10 microM in this in vitro setup, while the other chromones and naphthalenes did not display any activity. The present study, therefore, demonstrates the importance of low molecular phenolic polyketides for the known overall anti-inflammatory activity of Aloe vera preparations.

Nutrient uptake and pharmaceutical compounds of Aloe vera as influenced by integration of inorganic fertilizer and poultry manure in soil.[Pubmed:34278036]

Heliyon. 2021 Jul 2;7(7):e07464.

Aloe vera had been used for numerous medical and cosmetic applications since ancient times. The study aimed to investigate the integrated effects of inorganic fertilizer (IF) and poultry manure (PM) on the nutritional and pharmaceutical constituents of A. vera. Eighteen month old A. vera seedlings were used following completely randomized design with three replications. Six combinations of IF [Nitrogen (N), phosphorus (P), potassium (K) and sulphur (S) at the rate of 150, 80, 120 and 30 kg ha(-1), respectively] and PM (at the rate of 5 t ha(-1)) were considered viz., IF00PM00 (IF = 0%, PM = 0%), IF100PM00(IF = 100%, PM = 0%), IF75PM25 (IF = 75%, PM = 25%), IF50PM50 (IF = 50%, PM = 50%), IF25PM75 (IF = 25%, PM = 75%) and IF00PM100 (IF = 0%, PM = 100%) as treatments. Different treatment combinations of IF and PM exerted significant influence on the nutritional and pharmaceutical contents of A. vera. Concentrations and uptake of the concerned nutrients were gradually increased with the increased levels of PM except NPKS which were highest in sole application of IF. The Aloin concentration of leaf was gradually increased with the increased level of PM and by 42.44% over control. The highest chlorophyll, total phenolic and flavonoid concentrations were found in the plants receiving the treatment IF25PM75 except protein content which was obtained from IF100PM00. Significant and positive relationships between N and S with P concentrations and P and S with K concentrations of A. vera leaf were noticed. Aloin, total phenolic and flavonoid concentrations were significantly and positively correlated with Mg, Fe and Mn concentrations of A. vera leaf. Farmers may be advised to cultivate A. vera applying 75% PM at the rate of 5 t ha(-1) along with 25% IF (N, P, K and S at the rate of 150, 80, 120 and 30 kg ha(-1), respectively) for obtaining better quality leaf in terms of nutrients and pharmaceutical compounds under the agro-climatic conditions of the study area.

Analysis of the Composition of Lyophilisates Obtained from Aloe arborescens Gel of Leaves of Different Ages from Controlled Crops.[Pubmed:34071863]

Molecules. 2021 May 27;26(11). pii: molecules26113204.

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.

Graphene oxide exhibited positive effects on the growth of Aloe vera L.[Pubmed:33967464]

Physiol Mol Biol Plants. 2021 Apr;27(4):815-824.

There is increasing evidence for graphene associated plant growth promotion, however, the chronic effects of soil-applied graphene remain largely unexplored. The present study investigated the morphological, physiological and biochemical responses of graphene oxide (GO) on Aloe vera L. over the concentration range of 0-100 mg/L for four months. Our results demonstrated that GO, with the best efficiency at 50 mg/L, could enhance the photosynthetic capacity of leaves, increase the yield and morphological characters of root and leaf, improve the nutrient (protein and amino acid) contents of leaf, without reducing the content of the main bioactive compound Aloin. Compared with leaves, the effect of GO on root growth was more obvious. Although the electrolyte leakage and MDA content were raised at high concentrations, GO treatment did not increase the root antioxidant enzymes activity or decrease the root vigor, which excluding typical stress response. Furthermore, injection experiments showed that the GO in vivo did not change the plant growth state obviously. Taken together, our study revealed the role of GO in promoting Aloe vera growth by stimulating root growth and photosynthesis, which would provide theory basis for GO application in agriculture and forestry. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-00979-3.

Aloe vera mitigates dextran sulfate sodium-induced rat ulcerative colitis by potentiating colon mucus barrier.[Pubmed:33839199]

J Ethnopharmacol. 2021 Oct 28;279:114108.

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-1beta and TNF-alpha 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.

Efficacy Prediction of Four Pharmaceutical Formulations for Intramammary Administration Containing Aloe vera (L.) Burm. f. Combined With Ceftiofur or Cloxacillin in Lactating Cows as an Alternative Therapy to Treat Mastitis Caused by Staphylococcus aureus.[Pubmed:33829050]

Front Vet Sci. 2021 Mar 22;8:572568.

Synergy or additive effect between Aloe vera (L.) Burm.f. and beta-lactam (beta-lactam) antibiotics has been reported against Staphylococcus aureus, one of the most important etiological agents of cow mastitis. The goal of the present study was to predict the efficacy of intramammary formulations containing the Aloe vera gel extract in the combination with cloxacillin or ceftiofur at low concentrations in lactating cows as an alternative therapy. Each quarter of 20 healthy Holstein Friesian lactating cows were treated with a single dose of one of the following formulations, corresponding to one of these treatment groups: A1, A2, A3, and A4. A1 and A2 contained cloxacillin at 0.25 and 0.5 mg/ml, whereas A3 and A4 contained ceftiofur 0.25 and 0.5 mg/ml, respectively. In addition, all formulations contained 600 mg/ml of an alcoholic extract of Aloe vera. Milk samples were taken at predefined time points. Antibiotics and Aloin (active compound of Aloe vera) concentrations were assessed by liquid chromatography mass spectrometry system (LC-MS/MS). Pharmacokinetic profiles were obtained, and the efficacy index, the fraction of dosing interval in which the antimicrobial concentration remains above the minimum inhibitory concentrations (MICs) (T > MIC) for each formulation, was calculated considering MIC values against Staphylococcus aureus ATCC 29213 as obtained for the combination Aloe vera + antibiotic and Aloin concentration in the extract. Mammary gland safety assessment was performed for each combination. Values of the main efficacy index for this study, T > MIC (h) for Aloe vera were 23.29, 10.50, 27.50, and 13.89, whereas for cloxacillin or ceftiofur were 19.20, 10.9, 19.74, and 15.63, for A1, A2, A3, and A4, respectively. Only A1 and A3 reached Aloin and antibiotic recommended values as predictors of clinical efficacy for cloxacillin, ceftiofur, and Aloin (50, 70, and 60%, respectively), assuming a dose interval of 24 h. The efficacy index values obtained suggest that A1 and A3 might be an effective therapy to treat bovine mastitis caused by S. aureus after a single dose. Nevertheless, further trials in S. aureus mastitis clinical cases are mandatory to confirm the efficacy of Aloe vera formulations.

Non-pharmacologic approach to pediatric constipation.[Pubmed:33737146]

Complement Ther Med. 2021 Jun;59:102711.

Functional constipation (FC) is a pervasive problem in pediatrics. Although pharmaceuticals are commonly used for FC, parents and patients show reluctance or find dissatisfaction with available medications at times. Further, patients often have interest in utilizing nutraceutical supplements and botanicals that are available over the counter. This literature review aims to summarize research studies performed on non-pharmacologic approaches to constipation and to evaluate the safety and efficacy of these modalities. Overall data on non-pharmacologic treatments for childhood constipation were sparse, and though some studies were available for adult populations, pediatrics studies were generally limited, lacking or flawed. Certain supplements, such as prebiotics, probiotics and fiber, are safe and are without significant side effects. Though fiber supplements such as glucomannan, green banana mass, cocao husk and various fiber blends have emerging evidence in children, evidence for psyllium, cellulose and flaxseed only have supportive studies in adults. Other than senna, studies of botanicals indicate significant safety concerns (in particular with Aloe vera with Aloin and Cascara sagrada) and insufficient evidence. For patients with a significant behavioral or anxiety component to their FC and exhibit dyssynergia, mind-body interventions (e.g. diaphragmatic breathing, biofeedback, cognitive behavioral therapy, and behavioral modifications) are certainly safe and effective. Finally, movement and manipulative interventions such as abdominal massage, reflexology, acupuncture and transcutaneous nerve stimulation show promise in the field of pediatric constipation, and data is accumulating for efficacy. These modalities require further study to determine mechanisms of action and which populations may benefit the most from these therapies.

Aloin antagonizes stimulated ischemia/reperfusion-induced damage and inflammatory response in cardiomyocytes by activating the Nrf2/HO-1 defense pathway.[Pubmed:33502605]

Cell Tissue Res. 2021 Jun;384(3):735-744.

Myocardial ischemia/reperfusion injury (I/RI) frequently incurs in acute myocardial infarction with high morbidity and mortality worldwide and is characterized with cardiomyocyte apoptosis and inflammatory response. Aloin is a major anthraquinone from Aloe species and fulfills pleiotropic protective functions in several disease models including hepatic injury. Nevertheless, the potential of Aloin in MI/RI remains elusive. Intriguingly, Aloin had modest cytotoxicity in H9c2 cardiomyocytes. Importantly, Aloin dose-dependently ameliorated cell viability that was inhibited in response to simulated ischemia/reperfusion (SI/R) stimulation. Moreover, the enhanced apoptosis in cells under SI/R conditions were reduced after Aloin treatment, concomitant with the decrease in pro-apoptotic Bax protein levels and increase in anti-apoptotic Bcl-2 protein expression. Of interest, Aloin administration attenuated SI/R-induced oxidant stress by decreasing reactive oxygen species (ROS) production, lactate dehydrogenase (LDH), and malondialdehyde (MDA) release and increasing activity of anti-oxidant stress enzyme superoxide dismutase (SOD). Additionally, the elevated pro-inflammatory cytokine levels were counteracted after Aloin treatment in cells under SI/R conditions, including TNF-alpha, IL-6, and IL-1beta. Mechanically, Aloin further enforced the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Noticeably, blockage of this pathway by si-Nrf2 transfection blunted Aloin-mediated cardioprotective efficacy against SI/R-evoked oxidative stress injury and inflammatory response. Thus, these findings corroborate that Aloin may antagonize SI/R-induced cardiomyocyte injury by attenuating excessive oxidative stress and inflammation, thereby endorsing its potential as a promising therapeutic agent against myocardial infarction.

Two Cases of Thyrotoxicosis due to Redotex Ingestion, a Mexican Weight Loss Drug.[Pubmed:33414048]

J Emerg Med. 2021 Apr;60(4):495-497.

BACKGROUND: Redotex is a Mexican weight-loss supplement that is not U.S. Food and Drug Administration-approved. It consists of the following five ingredients: tri-iodothyronine 75 mug, atropine 0.36 mg, diazepam 8 mg, Aloin 16 mg, and d-norpseudoephedrine 50 mg per tablet. There are few case reports with clinically severe ingestions. We report two cases of clinical thyrotoxicosis due to use of Redotex. CASE REPORTS: A 29-year-old woman presented to the emergency department (ED) with anxiety and palpitations. She reported taking Redotex daily for 1 week. Her temperature was 37.1 degrees C, blood pressure (BP) was 166/104 mm Hg, and heart rate (HR) was 140 beats/min. Laboratory analysis was significant for a bicarbonate level of 20 mmol/L (reference 22-29 mmol/L), free T4 0.75 ng/dL (reference 0.93-1.70 ng/dL), and thyroid-stimulating hormone (TSH) 0.05 uIU/mL (reference 0.27-4.20 uIU/mL). She was treated with 2 mg i.v. lorazepam and 20 mg oral propranolol. A 37-year-old woman presented with chest pain, palpitations, and nausea after taking Redotex 1 to 2 tablets daily for 6 weeks. Her HR was 134 beats/min and BP was 130/66 mm Hg. Thyroid function tests on initial presentation showed a TSH of 0.013 uU/mL, free T4 of 0.24 ng/dL, and free T3 of >30 pg/mL. She was treated with propranolol 1 mg i.v. twice per day and 2 doses of lorazepam 1 mg. Both patients had resolution of their symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When taken chronically and at recommended doses, Redotex can present with clinically significant T3 thyrotoxicosis. This has not been seen in prior reports.

Aloin protects mice from diet-induced non-alcoholic steatohepatitis via activation of Nrf2/HO-1 signaling.[Pubmed:33410857]

Food Funct. 2021 Jan 21;12(2):696-705.

Aloin, a naturally occurring anthraquinone glycoside derived from the Aloe species, has antioxidant and anti-inflammatory activities, but its role in non-alcoholic steatohepatitis (NASH) remains unknown. This study was designed to investigate the anti-inflammatory, antioxidant, and anti-apoptotic effects of Aloin and the underlying mechanisms during NASH. Wild-type or nuclear erythroid 2-related factor 2 (Nrf2) knock-out (KO) mice were fed a choline-deficient, l-amino acid-defined, high-fat (CDAAH) diet and treated with Aloin (10, 20 or 40 mg per kg bw per day) by gavage for twelve weeks. Liver and blood samples were collected to evaluate liver function, protein abundance, and histopathological status. Supplementing Aloin at 20 mg kg(-1) was optimal for mitigating liver damage during NASH, as evidenced by reduced alanine transaminase and aspartate aminotransferase activity in serum. Supplementation with Aloin significantly reduced serum concentration or liver protein abundance of malondialdehyde, tumor necrosis factor alpha, Interleukin (IL)-1beta and IL-6. Aloin treatment enhanced hepatic superoxide dismutase activity, glutathione and serum IL-10 levels in mice with NASH. Furthermore, supplementation with Aloin inhibited hepatocyte apoptosis caused by Bcl-2 up-regulation and cleaved caspase-3 and Bax down-regulation. Mechanistically, by using Nrf2 KO mice, the protective effects of Aloin were associated with enhanced antioxidant, anti-inflammatory and anti-apoptotic activity, all of which were mediated by Nrf2/heme oxygenase-1 (HO-1) signaling activation. Data suggested that Aloin activates the Nrf2/HO-1 pathway and has protective potential against liver injury during NASH. Therefore, Aloin supplementation might contribute to the prevention and treatment of NASH via activation of the Nrf2/HO-1 pathway.

Fast and easily applicable LC-UV method for analysis of bioactive anthrones from Aloe leaf latex.[Pubmed:33402271]

J Pharm Biomed Anal. 2021 Feb 20;195:113834.

Aloe leaf latex is a commonly used plant preparation in traditional medicine. However, quality control on the content of medicinally important constituents is often limited. Hence, establishing a reliable quality control method to identify and quantify bioactive markers is important to ensure safety and efficacy. In the present study, a novel liquid chromatographic (LC) method was developed and validated for efficient analysis of bioactive markers to evaluate the quality of aloe leaf latex. Quantification of marker compounds was possible in only 7 min on a monolithic column using gradient elution with 0.1 % formic acid in acetonitrile and water as mobile phases. The major compounds (Aloins A and B) could be baseline separated together with related compounds within 10 min. The method showed excellent linearity with determination coefficients (r(2)) of 0.9999. Detection limits were 0.017 and 0.013 mug/mL, while quantification limits were 0.057 and 0.043 mug/mL for Aloin A and Aloin B, respectively. Relative standard deviation (RSD) values for intra- and inter-day precision were less than 2% and recoveries for both Aloins were close to 100 %. The robustness was evaluated using an experimental design. The method was applied to some aloe leaf latex samples from Ethiopia. Aloin contents varied from 14 to 35 % and two unknown peaks were tentatively identified as Aloinoside and microdontin.