Aloe ferox leaf gel extracts attenuate redox imbalance in oxidative renal injury and stimulates glucose uptake, whilst inhibiting key enzymes linked to diabetes and obesity

The worldwide prevalence of diabetes and obesity is growing rapidly. Both metabolic disorders are linked to chronic adverse complications, which include kidney dysfunctions. Medicinal plants play a crucial role in traditional healthcare, especially in developing countries. Aloe ferox, native to South Africa, has a long history of medicinal use, but its pharmacological potential is less studied compared to other Aloe species, necessitating further investigation. Therefore, the present study was conducted to determine the antioxidative, anti-obesogenic, and antidiabetic effects of A. ferox leaf gel extracts using in vitro, ex vivo, and in silico experimental models, with oxidative renal damage induced by ferrous sulfate (FeSO₄). A. ferox leaf gel extracts exhibited strong antioxidant activity, inhibited carbohydrate and lipid digesting enzymes, and significantly improved glucose uptake in yeast. The aqueous extract demonstrated better antioxidant efficacy, leading to higher reduced glutathione (GSH) level, and superoxide dismutase (SOD) and catalase enzymes activity, along with a concurrent reduction of nitric oxide (NO) and malondialdehyde (MDA) levels. Likewise, the aqueous extract showed more potent in vitro DPPH, NO, and OH• radical scavenging activity with IC₅₀ values of 3.64 ± 0.3 μg/mL, 110.73±0.1 μg/mL, and 331.13 ± 0.7 μg/mL, respectively. The aqueous extract had a better inhibition of the enzyme, α-amylase (IC₅₀ = 25.73±2.5 µg/mL), whilst the ethanolic extract inhibited α-glucosidase (IC₅₀ =663.2 ± 0.3 µg/ml), and pancreatic lipase (IC₅₀ =122.01±5.9 µg/mL) more strongly. Incubation of the extracts with yeast cells stimulated glucose uptake dose dependently, when ethanolic extract (IC₅₀ = 308.01±0.7 µg/mL) showed the better effects compared to the aqueous extract (IC₅₀ = 338.79±7.05 µg/mL). Furthermore, LC-MS analysis led to the identification of many compounds, when chlorogenic acid demonstrated a stronger molecular interaction with the active site amino acids of α-amylase and catalase compared to other compounds. However, Aloin B showed the highest binding affinity with α-glucosidase, when 5-Hydroxyaloin A showed the lowest binding energy with lipase and SOD enzymes. These results suggest the reno-protective effects of A. ferox leaf gel extracts against FeSO₄-induced oxidative stress along with its anti-hyperglycaemic activity. Given these observed effects, A. ferox leaf gel could be valuable in developing natural therapies and potential drug development for the management of these disorders. Further studies in animal models and humans are needed to ascertain the results of this study.