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 for 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 with comorbidities of cardiovascular system and blood disorders. Herein, the effect of AAL extract upon blood serum insulin, weight loss, and lipid profile was evaluated in order to harness the pathogenesis or treat the diabetes and its related complications.
The AAL extract demonstrated a noteworthy antioxidative property in DPPH in vitro model of free radicals. The %inhibition was comparable to the standard drug gallic acid. The 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 for 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, in-depth phytochemical investigation is needed to elaborate the phytochemical composition for 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 current study. (27) This suggest the AAL to be a rich source of phenolic and flavonoids compounds.
For the safety profile of the AAL extract, the in vivo model showed no signs of mortality, any adverse effect, and 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 the reveal the toxicity profile at large doses. This study developed in vivo diabetic mice models where the AAL effect was evaluated in normoglycemic, postprandial, STZ-induced diabetic mice. The STZ-induced diabetic model carries the advantages of hyperglycemia induction which closely mimics human diabetes, (20, 28) have 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 400mg/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’s 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 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 aligns the previous literature reporting the antihyperglycemic effects for Aloe species via stimulation of the 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 for AAL extract. The results declared a noteworthy enhancement for glucose tolerance at 100, 200, and 400 mg/kg of the AAL doses following 1h, 2h, and 4h post-administration. This further support 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 enhances peripheral glucose consumption. (33) Further studies at molecular and receptor levels may help clarify the pharmacological and therapeutic basis for the antihyperglycemic mechanism for 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 an improved blood sugar control and safeguarded against weight reduction. The diabetic mice administered with AAL extract maintained the weight throughout the tested days as compared to the diabetic control mice. Keeping in mind the fact that STZ-triggered diabetes development results heightened muscle wasting and protein depletion from tissues ultimately leading towards a significant weight loss, the observed non-significant changes in weight may be attributed to the effect of AAL extract. The advancement in research elaborated 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 upon 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 aforementioned activities. 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 for 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 for these compounds in the antioxidant, antiglycation, anti-hypercholesteremic, and antihyperglycemic activities of AAL extract.
The data generated and analyzed 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 molecular level in order to establish the pharmacological role for these novel molecules.
CONCLUSION
The outcomes for this study demonstrate the effective use of AAL in improving the 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 the novel drug discovery with less adverse effects and possibly more therapeutic activity at low doses in diabetes.