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Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves

  • Abdulhalim S. Serafi EMAIL logo , Muhammad Ahmed , Imran Shahid , Aisha Azmat , Ammar Bader , Mohammed A. Bafail , Shalan Alaamri and Rizwan Ahmad EMAIL logo
Published/Copyright: April 26, 2024
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Open Chemistry
From the journal Open Chemistry Volume 22 Issue 1

Abstract

Aloe species are known for the treatment of various conditions including diabetes mellitus, hypocholesteremia, and glycation end products. Nevertheless, the biological activity of Aloe armatissima is yet to be reported. It is a first-time report to evaluate the Aloe armatissima leaves (AAL) extract for its antioxidant, anti-glycation, anti-hyperglycemic, and anti-hyperlipidemic potential. In vitro tests of 1,1-diphenyl-2-picrylhydrazyl for the antioxidant and HSA for the antiglycation activity whereas in vivo models were used to assess the toxicity, antihyperglycemic, and anti-hypercholesteremic effects. The volatile profile was determined via gas chromatography-mass spectrometry. The IC50 values of 116 ± 0.66 (μg/mL) for antioxidant activity and 0.21 ± 0.009 (mg/mL) for antiglycation activity were observed for the AAL extract. The acute toxicity in the animal model revealed a lack of toxicity for the extract. The in vivo models exhibited a dose-dependent hypoglycemic and anti-hyperglycemic effects with significant (P < 0.01) blood glucose levels reduction. Moreover, a profound decrease in serum cholesterol, triglyceride, and LDL along with a significant (P < 0.05) increase in HDL and serum insulin levels was recorded. The statistical analysis demonstrated the values of F (24,125) = 23.95, P = 0.001, effect size = 1.95 (normoglycemic mice), F (24,125) = 143.21, P = 0.001, effect size = 4.79 (glucose loaded mice), and F (24,125) = 82.69, P = 0.001, effect size = 3.6 (diabetic model). GCMS showed the presence of eleven compounds with tetratetracontane (100%), β-sitosterol (27.76), and vitamin E (18.68) in major amounts. The results underscore the extract’s capacity to effectively combat various ailments; however, the active phytochemicals need to be isolated and the pharmacological activities may be established at the molecular level.

Keywords: Aloe armatissima ; anti-glycation; anti-diabetic; anti-hyperglycemic; GC-MS

Abbreviations

AAL

Aloe armatissima leaves Extract

ANOVA

analysis of variance

BGL

blood glucose level

DPPH

1,1-diphenyl-2-picrylhydrazyl

DM

diabetes mellitus

GLIB

glibenclamide

HAS

human serum albumin

IDF

International Diabetes Federation

OECD

Organization for Economic Cooperation and Development

OGTT

oral glucose tolerance test

STZ

streptozotocin

WHO

World Health Organization

1 Introduction

Diabetes mellitus (DM) is a chronic condition with a substantial impact on an individual, family, and community health. According to The International Diabetes Federation’s 2017 report, 352 M are at risk of developing type II diabetes. The health experts foresee a staggering figure of 439M adults being afflicted by diabetes by the year 2030 [1]. DM disrupts the body’s metabolic processes, impacting carbohydrate and lipid metabolism, consequently giving rise to an array of complications including the macrovascular (neuropathy, retinopathy, and renal issues) and microvascular complications (closely related to cardiovascular diseases) [2]. The adverse health outcomes with diabetes stem from processes driven by oxidative stress, intricately linked to the onset of diabetes and its ensuing complications. Prior investigations have demonstrated that oxidative stress precipitates diminished insulin secretion and compromised glucose metabolism in peripheral tissues during hyperglycemic states. It indicates that blocking or neutralizing the formation of reactive oxygen species (ROS) in the hyperglycemic context holds the potential to mitigate diabetes-related complications [3]. The emergence of ROS in DM arises from disrupted insulin synthesis due to the apoptotic cell death in the pancreas. To bolster the body’s antioxidant defense mechanism, supplements and plant-based compounds are integrated into regimens to mitigate oxidative stress and thwart the disease’s inception at its nascent stages [4]. Moreover, the formation of glycation end products in the body plays a vital role in the pathogenesis of complications in diabetic individuals. Glycation products are the covalent adducts of glucose and plasma proteins produced through a non-enzymatic process in the body where glucose reacts with the free amino group of the amines producing amadori products. These amadori products turn into advanced glycation end products (AGEs) in the later stage where their interaction with the AGEs receptor (RAGE) causes the release of free radicals, pro-inflammatory molecules, altered intracellular-signaling and gene expression. This ultimately turns into diabetic complications of neuropathy, retinopathy, cardiomyopathy, aging, and osteoporosis [5]. The metabolic risk factor of hypercholesteremia is another contributing factor to the development of cataracts and retinopathy in type II DM patients [6]. Though a complete exploratory mechanism is awaited to date, certain lipoproteins in the body have been reported to have a close association with diabetic retinopathy in type II DM [7]. The potential complications posed due to free radicals, glycation end products, and hypercholesteremia necessitate the surge for a therapeutic agent with an established multipurpose role. The widespread belief in the potential of medicinal plants to offer remedies for health issues, characterized by minimal side effects, affordability, and ease of accessibility, prevails within various communities [8]. Hence, a substantial proportion of diabetic patients (80–85%) turn to herbal remedies for managing their condition. Ethnobotanical studies have cataloged the usage of over 1,200 medicinal plants for addressing DM. Plant-derived medicines hold promise in ameliorating metabolic issues and retarding the onset of diabetes-related complications [9]. Throughout history, plants have served as therapeutic agents for humans and other species, administered in various dosages of crude extracts. Herbal medicine has played a significant role in primary care facilities across developing and developed nations and current anti-diabetic drugs strive to achieve optimal hyperglycemia control with minimal side effects and easy availability, but realizing this objective remains a formidable challenge.

Aloe armatissima Lavr & Collen belongs to the family Aloaceae [10] where a number of species including A. vera, A. perryi, A. arborescens, and A. ferox find widespread applications for addressing diverse ailments. The folkloric use of aloe leaves has been witnessed to combat microbial infections, digestive disorders, and inflammatory conditions. The applications of aloe plants extend even to the food, beverages, and cosmetic sectors. The literature evidence reveals a potential role for the aloe plant in the treatment of gastrointestinal, inflammatory, and detoxification conditions [11,12] however, none of the studies explored the antihyperglycemic and anti-hypercholesteremic effects of Aloe armatissima. To the best of our knowledge, it is a first-time study to assess the potential for Aloe armatissima leaves (AAL) in diabetes and its related comorbidities. This study aims to establish a multidimensional role for AAL in combating free radicals, advanced glycated end products, and hypercholesteremia which may play a substantial role in developing type II DM and the associated complications.

2 Materials and methodology

2.1 Chemicals and reagents

Streptozotocin (STZ), ethanol, methanol, benzene, petroleum ether, ethyl acetate, glibenclamide, human serum albumin (HSA), 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and gallic acid, were all obtained for the research from SIGMA-Aldrich whereas, Lipid Profile kit was obtained from Human Diagnostica (Germany).

2.2 Instruments and equipment

Rota-Vapor® for evaporation and drying of samples (R-100, BUCHI Corporation); microplate reader (Multiskan Go, Thermo Scientific, USA); multi-plate reader (SpectraMax-384, Molecular Devices, USA); Gas Chromatography-Mass Spectrometry (GC-MS) systems with specifications of GC-7890A/MS-5975C model (Agilent Technologies, Santa Clara, CA, USA) equipped with OPTIMA-5 column for separation of volatile components; HumaLyzer-3000 (Germany); Accu-Check Blood Glucose Meter with strips (Roche, Germany; Insulin assay kit Cisbio International, France.

2.3 Plant material collection and extraction

2.3.1 Plant identification and authentication

The plant species of Aloe armatissima was collected in April 2019 from Wadi Thee, Ghazal near Taif City, Saudi Arabia. The identification and authentication were carried out by Prof. A. Badar with a voucher specimen (2019/Folk/1) and submitted to the Laboratory of the Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura, Kingdom of Saudi Arabia.

2.3.2 Extraction from the AAL

For extraction, the previously reported method with slight modification was followed [13]. Briefly, fresh AAL were collected, cleaned with tap water, cut into small pieces, and subjected to lyophilization for drying. A hundred grams (100 g) of the dried leaves were weighed and macerated in 1L hydroalcoholic solvent of ET:water (70:30) for 3 days, followed by filtration (Whatman filter paper; 0.4 mm), and subsequent drying of the sample with the help of rotary evaporator. The AAL extract was weighed, the %yield calculated, and refrigerated till further use.

2.4 In vitro activities

2.4.1 DPPH free radical scavenging assay

The free radical scavenging activity for the AAL extract was evaluated using DPPH as reported [14]. A reaction mixture was prepared (95 µL of 300 µM DPPH with 5 µL of 0.5 mg/mL test solution), incubated in darkness (37°C for 30 min), and finally, the absorbance was measured at 517 nm using the multi-plate reader. The change in color of the solution (violet to pale yellow), due to the reduction reaction, indicative of the scavenging activity was noted, and the %radical scavenging potential was determined using the following formula:

% RSA = 1 − Abs of test Abs of control × 100 .

2.4.2 Anti-glycation activity

The anti-glycation activity was performed using a previously reported spectrophotometric method [14]. Briefly, 20 µL of AAL extract (2 mg/mL) along with 50 µL of HAS solution (10 mg/mL), 50 µL of fructose solution (500 mM), and 80 µL of phosphate buffer (100 mM; pH 7.4) were introduced in a 96-well microtiter plate. The microtiter plate was incubated (37°C for one week) followed by measurement of the fluorescence for the test sample (AAL), at excitation and emission wavelengths of 330 and 440 nm, respectively. The %inhibition was determined by the following formula:

% Inhibition = 1 − Fluorescence of test Fluorescence of control × 100 .

2.5 In vivo activity

2.5.1 Experimental animals

For the in vivo studies, Swiss Albino mice (male and female), weighing between 20 and 40 g, were procured from the Department of Biochemistry, College of medicine, Umm Al-Qura University, Kingdom of Saudi Arabia. The animals were grouped (n = 6), fed with a standard diet, and maintained in at standard laboratory environment (temperature = 23 ± 2°C; relative humidity = 55 ± 10%) with consecutive 12-h dark and light cycles. Prior to any laboratory experiment, the animals were properly acclimatized to the laboratory conditions for one week, and any experiment conducted was assured to follow the guidelines for national legislation on the use of animals for research [15]. The study was issued the ethical approval for experimental handling procedures, approved by the Animal Ethics Board of the College of Medicine, with ethical approval number: HAPO-02-K-012-2022-01-385.

2.5.2 Acute toxicity study

The limit test protocols from the Organization for Economic Cooperation and Development (OECD) guideline-425, were followed for the acute toxicity study utilizing the healthy mice [16]. In detail, five female mice (24–30 g) were subjected to fasting (3–4 h; with excess to water and restricted to food) before dosing and 2 h post-extract administration. The animals were administered with a single oral dose of the AAL extract (2,000 mg/kg) with a close observation for any untoward reaction or symptoms for 24 h and with subsequent daily observation. The body weights of the animals were recorded on a daily basis followed by euthanizing of the animals on the 14th day. The internal organs were removed and thoroughly examined for any toxic effects or signs.

2.5.3 Antidiabetic animal models

2.5.3.1 Estimation of hypoglycemic activity for normoglycemic mice

The hypoglycemic activity of AAL extract was evaluated in normoglycemic mice [17]. A total of 30 animals were randomly allocated into five groups (n = 6) with an oral dose administration of 10 mL/kg distilled water for group-I (control group): AAL extracts of 100, 200, and 400 mg/kg, respectively, for groups II, III, and IV (treated groups): and 5 mg/kg GLB for group-V (standard drug group). The mice were subjected to fasting for 16 h with excess water only. For hypoglycemic activity evaluation, blood glucose levels were measured with the help of a glucometer, using a drop of blood from the animal's tail. The baseline Blood glucose level (BGL) (mg/dl: at 0 h) for the data was noted before animal dosing whereas, for the AAL extract effect, the samples from animal tail vein were collected at predetermined time points of 60, 120, and 240 min following treatment [17,18], and BGL was measured.

2.5.3.2 Effect of AAL on oral glucose tolerance test (OGTT)

The oral glucose tolerance assessment (OGTT) test was conducted following the reported experimental protocols [19]. The animals were grouped as previously with an overnight fasting of unrestricted access to water. Following the 30 min post-AAL dosing, the animals were orally administered a glucose solution of 2,000 mg/kg, and the blood samples were collected from the tail vein at 0, 30, 60, 120, and 240 mins in order to evaluate BGLs (mg/dL).

2.5.3.3 Induction of experimental diabetes

The reported method [19,20] with slight modifications was followed to induce diabetes in the experimental animals. Alike previous protocols, the animals were grouped and fasted overnight. Prior to inducing any diabetes, the blood sugar level and weights were recorded for all the animals. For the diabetes induction; streptozotocin (STZ) was diluted with 0.1M sodium citrate buffer (pH = 4.5) and was administered intraperitoneally (i.p.) as a single dose (150 mg/kg body weight). The mice were allowed access to food and water 30 min post-STZ injection whereas, the animals were administered with a 5% glucose solution (6 h post-STZ injection) in order to prevent hypoglycemia. The plasma BGL levels for the animals were evaluated (3 days post-STZ injection) via the tail vein using a glucometer. Any animal with FBG >200 mg/dL was declared diabetic and included for further antidiabetic evaluation.

2.5.3.4 Antidiabetic assessment for AAL extract

To evaluate the antidiabetic potential for AAL extract, the diabetic animals were categorized as previously. The oral doses were administered; distilled water for group-I (control animals), and group-II (diabetic control animals), GLB for group-III (positive control group) whereas group-IV, group-V, and group-VI received AAL extract of 100, 200, and 400 mg/kg, respectively. For BGL determination, the blood drops were obtained from the tail vein at time intervals of 0, 7, 14, and 21 days.

2.5.4 Assessment of the lipid profile and serum insulin levels

The diabetic mice used in the previous model of antidiabetic activity were used to determine the anti-hyperlipidemic activity of AAL extract. In order to determine the lipid profile, the blood was collected (21st day) from retro-orbital sinus of the animals and subjected to HumaLyzer for a complete blood profiling of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) [21].

The blood (21st day) from the AAL-administered diabetic mice was collected, and serum insulin levels were estimated with the help of a radioimmunoassay kit [22].

2.6 GC-MS profiling for the leaves

An Agilent GC-MS system with GC-7890A/MS-5975C model (Agilent Technologies, Santa Clara, CA, USA) equipped with an OPTIMA-5 column was used to characterize the volatile components in the sample. The instrument conditions were as follows: Helium drift (1.0 mL/min), electron ionization (70 eV), OPTIMA-5 column for separation, and inline built NIST mass spectral database. However, the conditions for chromatography and mass determination consisted of an initial temperature of 50°C (3 min) with an incremental rise of 10°C/min for 20 min followed by an incremental increase of 10°C/min till 300°C. The temperature was maintained for 25 min at 300°C, and the mass spectra were recorded. The compounds were detected by mass spectra comparison and similarity index of the compounds with the reference standards in the NIST mass spectral database [23].

2.7 Statistical analysis

The G*Power (V 3.1.9.2) and Statistical Package for Social Science Students (SPSS V21.0) were used for statistical analysis of the dataset. For one-way analysis of variance (ANOVA), effect size (f) is taken as 0.10, α-error probability at 0.05, and power at 0.80. The variables are displayed in the tables as mean ± SD whereas, the significance level was set at P = 0.05.

3 Results

3.1 Extract yield and %recovery

The extract yield for the AAL was 9 g which resulted in a yield of 9%.

3.2 DPPH activity

The in vitro free radical scavenging for AAL extract was determined by calculating the IC50 values. Gallic acid was used as a reference standard. The IC50 values (μg/mL) for AAL and gallic acid were 116 ± 0.66 and 2.6 ± 1.0, respectively. The %inhibition and IC50 values are shown in Table 1.

Table 1

In vitro free radical scavenging via DPPH and antiglycation activity for AAL extract

Sample %Inhibition IC50 value
DPPH radical scavenging activity (IC 50 = μg/mL)
AAL 82.5 116 ± 0.66
Gallic acid 97.3 2.6 ± 1.0
Antiglycation activity (IC 50 = mg/mL)
AAL 83.14 0.21 ± 0.009
Rutin 99.5 0.02 ± 0.01

3.3 Anti-glycation HSA assay

The AAL extract significant glycation inhibitory effect of 83.14% as compared to the reference drug rutin (99.50%). The IC50 values (mg/mL) for the AAL extract and rutin observed were 0.21 ± 0.009 and 0.02 ± 0.01, respectively. The data for antiglycation activity are shown in Table 1.

3.4 Acute oral toxicity test

The AAL extract showed no mortality and pathological changes at a dose of 2,000 mg/kg. The toxicity results at 2 h, 24 h, and 14 days showed a lack of any adverse effects on the gross behavioral pattern of the animals. Moreover, no significant differences were noted regarding food intake and body weight as compared to the control group.

3.5 Hypoglycemic activity of AAL extract in normoglycemic mice

For the antidiabetic effect in normoglycemic mice, the BGLs were measured immediately prior to any treatment (0 h) and subsequently at 1, 2, 3, and 4 h after treatment. No significant differences were observed for the control group (P > 0.05); however, significant BGL changes (P < 0.05) were observed after administration of glibenclamide and AAL extract (100, 200, and 400 mg/kg). The ANOVA test value showed a statistical significance with F (24,125) = 23.95 at P = 0.00 and an effect size of 1.95, compared to the control (0 h). For the normoglycemic mice groups, the treatment with glibenclamide and AAL extract revealed a significant decrease for BGLs at 2, 3, and 4 h at different doses; 100 mg/kg (P < 0.05), 200 mg/kg (P < 0.01), 400 mg/kg (P < 0.05), and glibenclamide (P < 0.001).

With regard to the intra-group comparisons; AAL extract (400 mg/kg) exhibited pronounced reduction (P < 0.0001) in BGLs at 2 h (22%), 3 h (37%), and 4 h (44%) as compared to the baseline BGLs. The reference drug glibenclamide showed reductions of 14%, 22%, and 31% at the 2 h, 3 h, and 4 h, respectively. The reduction in BGLs at 4 h post-AAL treatment (400 mg/kg: 72.83 ± 7.55) was more pronounced compared to glibenclamide (87.83 ± 4.02).

In terms of inter-group comparisons, glibenclamide and AAL extract (200 and 400 mg/kg) demonstrated a significant reduction in BGLs at 4 h when compared to these values at 2 h of post-treatment. The control group (group 1: DW) exhibited non-significant changes in BGLs throughout the experiment at time 0–4 h. The data for AAL extract effect in normoglycemic mice are shown in Table 2.

Table 2

Effect of AAL extract on BGLs of normoglycemic, postprandial non-diabetic, and diabetic mice

Hypoglycemic activity for AAL extract in normoglycemic mice
Group 0 h 1 h 2 h 3 h 4 h
Control 122.67 ± 3.93 124.17 ± 3.49 122.33 ± 4.97 119.83 ± 4.07 118.83 ± 4.72
Glibenclamide 127.50 ± 9.12 112.50 ± 3.56 109.67 ± 10.95* 99.17 ± 3.66*** 87.83 ± 4.02***#
AAL 100 mg/kg 122.17 ± 6.27 116.67 ± 9.69 103.50 ± 13.41* 97.33 ± 8.98*** 92.33 ± 7.45***
AAL 200 mg/kg 125.50 ± 9.40 119.83 ± 7.*57 104.17 ± 12.69* 90.67 ± 13.72*** 83.50 ± 13.91***#
AAL 400 mg/kg 129.17 ± 3.97 117.17 ± 4.07 100.17 ± 4.62* 80.17 ± 9.77***# 72.83 ± 7.55***#
F (24, 125) = 23.95, *P = 0.001, effect size = 1.95, power = 0.99
Significant decrease in BGL compared to their control value (at 0 h), *P < 0.05, ***P < 0.001
Significant decrease in BGL compared to their value at 2 h # P < 0.05
Hypoglycemic activity for AAL extract in glucose-loaded mice (OGTT)
Group 0 h 0.5 h 0.5 h (% increase BGL) 1 h 2 h 4 h % Decrease (at 4 h compared to 0.5 h)
Control 105.67 ± 5.79 166.50 ± 8.67* 58% 154.50 ± 6.80* 142.5 ± 8.78*@ 129.33 ± 7.79*@ 22%
Glibenclamide 115.17 ± 5.31 162.67 ± 4.80* 41% 116.83 ± 5.31@ 93.67 ± 4.93#@ 85.17 ± 4.83#@ 47%
Extract (100 mg/kg) 118.67 ± 7.74 171.50 ± 6.89* 44% 125.83 ± 3.76@ 96.33 ± 6.68#@ 89.33 ± 6.25#@ 47%
Extract (200 mg/kg) 117.17 ± 3.87 168.17 ± 5.19* 43% 119.33 ± 12.09@ 94.17 ± 3.60#@ 83.17 ± 6.37#@ 49%
Extract (400 mg/kg) 119.33 ± 5.82 165.33 ± 3.20* 38% 106.33 ± 4.41@ 75.67 ± 7.31#@b 67.83 ± 6.05#@b 59%
F (24, 125) = 143.21, *P = 0.001, effect size = 4.79, power = 0.99
Significantly increased as compared to their control value (at 0 h), *P < 0.001
Significantly decreased as compared to their value (at 30 min), @ P < 0.001
Significantly decreased as compared to their value (at 1 h), # P < 0.001
Significantly decreased as compared to positive value b P < 0.001
Antihyperglycemic activity for AAL extract on BGL in STZ-induced diabetic mice
Group Pre-STZ 0 Day 7 Days 14 Days 21 Days
Normal control 118.50 ± 1.87 120.167 ± 1.472 118.33 ± 4.97 114.50 ± 1.871 115.167 ± 2.37
Diabetic control 127.33 ± 15.56 228.83 ± 5.64* 236.17 ± 6.91* 250.50 ± 10.80* 261.67 ± 11.04*#
Glibenclamide 123.33 ± 8.09 232.17 ± 7.55* 198.00 ± 12.66*# 182.17 ± 9.95*# 147.67 ± 13.56#@
Extract 100 mg/kg 125.67 ± 20.50 221.50 ± 9.48* 206.50 ± 9.01* 190.00 ± 7.77*# 174.33 ± 7.20*#@
Extract 200 mg/kg 126.78 ± 9.85 226.50 ± 9.85* 197.83 ± 13.61*# 175.67 ± 12.21*# 164.00 ± 12.71*#@
Extract 400 mg/kg 129.33 ± 6.89 221.17 ± 16.07* 182.67 ± 5.72*# 154.67 ± 11.36*#@ 142.67 ± 15.29#@
F (24,125) = 82.69, *P = 0.001, effect size = 3.6, power = 0.99
Significantly increased as compared to their control value (before STZ) *P < 0.001
Significantly decreased as compared to the value at 0 day, # P < 0.001
Significantly decreased as compared to the value on 7th day, @ P < 0.001

Results are expressed in mean ± SD, n = 6, Control = distilled water (10 mL/kg); glibenclamide = 5 mg/kg.

3.6 Effects of AAL extract in glucose-loaded/post-prandial mice

The AAL extract and glibenclamide revealed significant (P < 0.05) effects in glucose-loaded mice with statistical values of F (24,125) = 143.21, P = 0.000, and effect size of 4.79. Following glucose administration, a significant increase in glucose level was observed in all the groups producing hyperglycemia at 0.5 h with a pronounced increase in the negative control group (58%). The positive control group of glibenclamide and AAL extract groups exhibited non-significant (P > 0.05) differences at any of the tested doses following post-30 min glucose loading.

The AAL extract (100, 200, and 400 mg/kg) and glibenclamide (5 mg/kg) significantly reduced the BGLs compared to the control group (P < 0.001) at 1 h and onwards. The AAL effect (400 mg/kg) showed a significant rise in glucose level with the passage of time, particularly at 2 h, with a notable decline at 2 h compared to the control and glibenclamide groups (P < 0.001). This effect remained sustained till the end of the experiment. The details for the AAL effect in the postprandial mice model are shown in Table 2.

3.7 Anti-diabetic effect of AAL in STZ-induced diabetic mice

The ANOVA for STZ-induced diabetes in mice revealed a significant result with F (24,125) = 82.69, P = 0.000, and an effect size of 3.6. The BGLs for STZ-induced diabetic mice exhibited profound differences (P < 0.001) compared to the control group. The BGL level for the diabetic control significantly increased starting at day 0 till day 21 (P < 0.001). As compared to the diabetic control, all the doses for AAL extracts revealed a dose-dependent reduction for BGLs on days 7, 14, and 21. Likewise, glibenclamide-treated groups exhibited a significant decrease in BGLs (days 7, 14, and 21) however, no significant differences were observed for AAL extracts and glibenclamide. This indicates a potential antidiabetic role for AAL extract. The data for AAL extracts in the diabetic mice model are shown in Table 2.

3.8 AAL effect on body weight of normal and diabetic mice

The statistical analysis for the AAL extract and glibenclamide revealed a non-significant result for the effect on body weight in STZ-induced diabetic mice, with F (23,120) = 1.28 and P = 0.193 (P > 0.05). The body weight for the diabetic control mice group showed a decline throughout the stud whereas, administration of the AAL extract prevented the weight loss. However, the result was non-significant for AAL and glibenclamide across all the tested doses (100, 200, and 400 mg/kg). The data for the mice models are shown in Table 3.

Table 3

Effect of AAL extract on body weight of normal and diabetic mice

Group 0 day 7 days 14 days 21 days
Normal control 26.733 ± 1.05 26.71 ± 0.85 26.86 ± 0.73 27.08 ± 1.65
Diabetic control 28.25 ± 0.95 27.81 ± 2.31 26.61 ± 1.82 25.82 ± 1.64*
Glibenclamide 27.63 ± 1.23 27.7 ± 1.32 28.41 ± 0.86 29.61 ± 1.49
Extract (100 mg/kg) 27.33 ± 1.57 27.68 ± 1.51 28.11 ± 2.02 28.38 ± 2.32
Extract (200 mg/kg) 27.61 ± 1.02 27.83 ± 2.41 28.3 ± 1.24 28.66 ± 2.01
Extract (400 mg/kg) 28.15 ± 2.05 28.5 ± 1.14 29 ± 1.87 29.66 ± 1.38
F (23,120) = 1.28, P = 0.193

Results are expressed in mean ± SD, n = 6, distilled water (10 mL/kg), glibenclamide (5 mg/kg), AAL; as compared to their control value (before STZ) *P < 0.05.

3.9 AAL effect on lipid profile and serum insulin level

The STZ increased the serum total cholesterol, triglycerides, and LDL cholesterol for diabetic mice as compared to the normal mice; however, low levels of HDL and serum insulin levels were observed (P < 0.05). The administration of AAL extract produced a significant decrease in the serum level of total cholesterol (P < 0.001), triglyceride (P < 0.01), and low-density lipoprotein-cholesterol (P < 0.001).

On the contrary, the administration of AAL extract at 400 mg/kg resulted in a significant increase in serum insulin level and high-density lipoprotein-cholesterol (P < 0.01). The reference drug glibenclamide also improved the lipid profile and insulin levels in diabetic mice (P < 0.05). The data for insulin level and lipid profile are shown in Table 4.

Table 4

Effect of the AAL extract on serum insulin level and lipid profiles

Group TC (mg/dL) TG (mg/dL) HDL (mg/dL) LDL (mg/dL) Serum insulin (µU/mL)
Normal control 91.17 ± 5.15 94.67 ± 3.83 37.00 ± 1.41 32.83 ± 2.04 18.83 ± 5.8
Diabetic control 187 ± 4.13* 177.67 ± 3.01* 26.16 ± 1.72* 129.33 ± 5.01* 10.45 ± 1.22*
Glibenclamide 96.50 ± 1.87# 106.00 ± 3.35# 36.50 ± 1.87 37.83 ± 4.26# 18.60 ± 3.45#
Extract (100 mg/kg) 138.6 ± 2.16# 155.17 ± 3.54# 29.66 ± 1.03# 96.67 ± 2.94# 13.33 ± 3.70
Extract (200 mg/kg) 120.33 ± 3.5# 148.33 ± 4.79# 33.33 ± 2.60# 86.50 ± 7.94# 15.12 ± 3.22
Extract (400 mg/kg) 109.67 ± 3.01# 127.66 ± 1.82# 37.33 ± 2.16# 45.33 ± 4.46# 17.45 ± 1.77#
F (5,30) = 618.2, *P = 0.001, effect size = 5.3, power = 0.99 F (5,30) = 479.2, *P = 0.001, effect size = 4.7, power = 0.99 F (5,30) = 36.79, *P = 0.001, effect size = 1.38, power = 0.99 F (5,30) = 389.5, *P = 0.001, effect size = 4.43, power = 0.99 F (5,30) = 5.29, *P = 0.001, effect size = 0.5, power = 0.99

Results are expressed as mean ± SD, n = 6, NC = normal control, distilled water (10 mL/kg), DC = diabetic control, glibenclamide (5 mg/kg), significantly increased as compared to their control value *P < 0.001, significantly decreased as compared to their positive control value (diabetic), # P < 0.001.

3.10 GC-MS analysis of AAL extract

The GCMS analysis indicated the presence of eleven compounds in the AAL extract as shown in Table 5. These compounds (on the basis of peak area) may be arranged in the descending order of its occurrence; tetratetracontane (100%) > β-sitosterol (27.76%) > vitamin-E (18.68%) > squalene (18.32) > palmitic acid (16.76%) > lupeol (13.89%) > stearic acid (13.06%) > ethyl linolenate (7.7%) > 3,7,11,15-tetramethyl-2-hexadecen-1-ol (7.12) > γ-tocopherol (6.62%) > phytol (6.26%). The details regarding the retention time, molecular weight, and peak area for the eleven compounds are shown in Table 5.

Table 5

Volatile profile for AAL extract based on GCMS analysis

S# Compound RT Molecular formula Molecular weight Peak area (%)
1 3,7,11,15-Tetramethyl-2-hexadecen-1-ol 25.5 C20H40O 296 7.12
2 Palmitic acid 27.32 C16H32O2 256 16.76
3 Stearic acid 27.84 C18H36O2 284 13.06
4 Phytol 30.31 C20H40O 296 6.26
5 Ethyl linolenate 31.76 C20H34O2 306 7.7
6 Squalene 60.61 C30H50 410 18.32
7 γ-Tocopherol 63.42 C28H48O2 416 6.62
8 Tetratetracontane 64.23 C44H90 618 100
9 Vitamin-E 64.53 C29H50O2 430 18.68
10 β-Sitosterol 66.4 C29H50O 414 27.76
11 Lupeol 67.27 C30H50O 426 13.89

4 Discussion

Diabetes is a widespread global concern with far-reaching implications for human health. The primary culprits behind diabetes-related issues are endogenous advanced glycation end-product (AGE) formations. The glycation process, a key driver of diabetic symptoms, involves a spontaneous reaction between proteins and reducing sugars where the synthesis of endogenous AGEs plays a pivotal role in initiating a majority of diabetic complications. Current scientific investigation aims to evaluate the in vitro and in vivo antioxidant and antiglycation activity for the AAL extract, to develop a potential source for combating these conditions. To assure the efficacy of the ALL extract in diabetes, in vivo diabetic models in mice were developed to investigate the effect of AAL in normoglycemic, glucose-loaded, and diabetic mice. Diabetes is accompanied by comorbidities of the cardiovascular system and blood disorders. Herein, the effect of AAL extract on blood serum insulin, weight loss, and lipid profile was evaluated in order to harness the pathogenesis or treat diabetes and its related complications.

The AAL extract demonstrated a noteworthy antioxidative property in the DPPH in vitro model of free radicals. The %inhibition was comparable to the standard drug gallic acid. Free radical scavenging plays a pivotal role in safeguarding against free radical-induced damage in various ailments, including hyperglycemia and this phenomenon has been observed for Aloe vera gel [24]. There is no report on the antioxidant potential of AAL extract however, earlier investigations have underscored the antioxidant potential for a number of Aloe species. The results from this study are in line with these reports [25,26]. An effective antiglycation activity was observed for AAL extract where the %inhibition was comparable to the standard drug rutin. Albeit, the in-depth phytochemical investigation is needed to elaborate the phytochemical composition of AAL extract, previous studies suggest potent antioxidant and antiglycation activity for plants enriched with phenolics and flavonoids [27]. In addition, the hydroethanolic extract for the other species of Aloe revealed significant anti-glycation potential which supports the finding in the current study [27]. This suggests that AAL is a rich source of phenolic and flavonoid compounds.

For the safety profile of the AAL extract, the in vivo model showed no signs of mortality, adverse effect, or organ toxicity. The acute toxicity result is self-explanatory evidence for the safe oral administration of the AAL hydroethanolic extract in selected doses however, further chronic or long-term toxicity studies may help reveal the toxicity profile at large doses. This study developed in vivo diabetic mice models where the AAL effect was evaluated in normoglycemic, postprandial, and STZ-induced diabetic mice. The STZ-induced diabetic model carries the advantages of hyperglycemia induction which closely mimics human diabetes, [20,28] has extended half-life, low risk of ketosis, and lower mortality rate [29]. For the normoglycemic and postprandial mice models, a dose-dependent antihyperglycemic activity was observed where a profound effect was observed at 400 mg/kg of the AAL extract. For the STZ-induced mice model, the AAL extract demonstrated a significant (P < 0.01) dose-dependent reduction for BGLs as compared to the diabetic control group. The effect on BGLs was observed for all the doses of AAL, particularly starting from day 7 till day 21. Yet again, it is a first-time report regarding the antihyperglycemic effect of AAL extract in an in vivo mice model. The previous evidences suggest the potent hypoglycemic, anti-hyperglycemic, and glucose-suppressing effects in plants attributed to the presence of phenolics, flavonoids, saponins, and alkaloids [30]. These phytochemicals have the potential to safeguard the pancreatic β-cells, enhance insulin release and synthesis [70], and produce an anti-hyperglycemic effect [31]. Herein, the AAL extract also revealed an increase in serum insulin level which may be linked to the antihyperglycemic effect of AAL extract in normoglycemic mice. This suggests a significant link for the presence of one or more of these naturally occurring phenolics, flavonoids, saponins, and alkaloidal compounds. The findings in this study align with the previous literature reporting the antihyperglycemic effects for aloe species via stimulation of insulin release [18,29,32]. With regard to clinical and research context, oral glucose tolerance is considered a primary approach for assessing insulin secretion and resistance hence, an OGTT test was employed to validate the antihyperglycemic effect of AAL extract. The results declared a noteworthy enhancement for glucose tolerance at 100, 200, and 400 mg/kg of the AAL doses following 1, 2, and 4 h post-administration. This further supports the effect of AAL extract on the beta cells of the pancreas, rendering them more responsive to insulin, probably through the stimulation of PPAR-gamma or via extra-pancreatic mechanisms that enhance peripheral glucose consumption [33]. Further studies at molecular and receptor levels may help clarify the pharmacological and therapeutic basis for the antihyperglycemic mechanism of AAL extract and its phytochemicals.

The STZ-induced diabetic mice were subjected to weight loss activity. The effect on weight loss was assessed for 21 days where the AAL extract exhibited improved blood sugar control and safeguarded against weight reduction. The diabetic mice administered with AAL extract maintained their weight throughout the tested days as compared to the diabetic control mice. Keeping in mind the fact that STZ-triggered diabetes development results in heightened muscle wasting and protein depletion from tissues ultimately leading towards significant weight loss, the observed non-significant changes in weight may be attributed to the effect of AAL extract. The advancement in research elaborated on the state of diabetic dyslipidemia in diabetic patients, therefore this study included the antihyperlipidemic effects of AAL extract on the lipid profile of the diabetic mice. The results showed the potential for the AAL extract to maintain the BGLs along with a solid impact on the blood lipid profile in diabetic mice. Such phenomenon has been reported in numerous previous studies for Aloe species and our data is in agreement with these reports [34]. Interestingly, these studies also reported the presence of phenolics, flavonoids, and alkaloids responsible for the aforementioned activities. The current study used the leaves extract where the volatile components were expected hence, GCMS profiling was performed for the AAL extract. A total of eleven compounds were identified via GCMS; 3,7,11,15-tetramethyl-2-hexadecen-1-ol, palmitic acid, stearic acid, phytol, ethyl linolenate, squalene, γ-tocopherol, tetratetracontane, vitamin-E, β-sitosterol, and lupeol. Literature reports indicate alike volatile components in Aloe species such as palmitic acid, ethyl linolenate, and squalene [35,36]. It is noteworthy to mention the antihyperglycemic and antioxidant activity of phytol, and 3,7,11,15-tetramethyl-2-hexadecen-1-ol [37], palmitic acid [38], squalene [39], and lupeol [40]. The GCMS data for the AAL extract presented similar compounds in significant concentration, suggesting the correlation and possible role of these compounds in the antioxidant, antiglycation, anti-hypercholesteremic, and antihyperglycemic activities of AAL extract.

The data generated and analysed in this research proves the antioxidant, antiglycation, anti-hypercholesteremic, and antihyperglycemic effects of AAL extract in different in vitro and in vivo models due to the presence of volatile components. The potential applications for AAL extract urge the need for an in-depth phytochemical and metabolomic exploration to isolate the novel active moieties with mechanistic activities at the molecular level in order to establish the pharmacological role of these novel molecules.

5 Conclusion

The outcomes of this study demonstrate the effective use of AAL in improving oral glucose tolerance, hypoglycemia, and body weight. This corroborates the traditional uses of AAL for treating various ailments. As this species is yet to be explored, particularly in terms of phytochemistry, further research holds promise in establishing a robust foundation for an in-depth exploration in order to comprehensively grasp the mechanisms underlying the phytochemical in AAL. To harness these potentials effectively, the subsequent investigation is essential for isolating and identifying the bioactive compounds responsible for pharmacological activities. This may lead towards novel drug discovery with less adverse effects and possibly more therapeutic activity at low doses in diabetes.

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Acknowledgments

The authors thank the Deanship of Scientific Research for providing financial support through grant no. 18-MED-1-01-0030, Umm Al-Qura University, Makkah, KSA.

  1. Funding information: The research was financial support through grant no. 18-MED-1-01-0030, Umm Al-Qura University, Makkah, KSA.

  2. Author contributions: ASS (study conception, data acquisition, drafting of the manuscript); MA, AA (study design, experimental work, manuscript write-up); MIS, SAA (literature assessment, analysis and interpretation of the data); AB, MAB (plant identification, collection, and availability of plant and resources for experimental work); RA (revision and proof-reading of the manuscript, journal, and reference formatting of the manuscript).

  3. Conflict of interest: The authors state that they have no potential conflicts of interest.

  4. Ethical approval: The Institutional Biomedical Research Ethics Committee of the College of Medicine at Umm Al-Qura University approved the research protocol with reference number: HAPO-02-K-012-2022-01-385.

  5. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-03-05
Revised: 2024-03-30
Accepted: 2024-04-04
Published Online: 2024-04-26

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
https://doi.org/10.1515/chem-2024-0023
Keywords for this article
Aloe armatissima; anti-glycation; anti-diabetic; anti-hyperglycemic; GC-MS
Creative Commons
BY 4.0

Articles in the same Issue

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  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
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  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
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  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
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  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
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  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
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  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
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  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
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  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
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  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
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  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
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  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
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  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
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  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
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