RESUMO
Diabetes is often associated with increased oxidative stress caused by an imbalance between detoxification and ROS production. Unfortunately, many commercial drugs available today for treating this disease have adverse side effects and ultimately fail to restore glucose homeostasis. Therefore, finding a dietary anti-diabetic remedy that is safe, effective, and economical is crucial. In this study, GC-MS analysis, subsequent HPLC-assisted fractionation, and SPE-based purification led to identifying and purifying of key components such as phloroglucinol and total procyanidin dimer (procyanidin dimer and procyanidin dimer gallate) from methanolic seed extract of Vitis vinifera. In-vitro anti-diabetic screening of various fractions derived from methanolic extract along with individual components and their combinations revealed the potential synergistic behaviour of phloroglucinol and total procyanidin dimer with the lowest IC50 of 48.21 ± 3.54 µg/mL for α-glucosidase and 63.06 ± 5.38 µg/mL for α-amylase inhibition which is found to be superior to the effect shown by the standard Epigallocatechin gallate. Later Glucose utilization studies demonstrated the concentration-dependent effect of Phloroglucinol and total procyanidin dimer, and that has raised the glucose uptake by approximately 36-57% in HepG2 cells and 35-58% in L6 myocytes over a concentration of 50-100 µg/mL. The superior anti-diabetic effect of Phloroglucinol and total procyanidin dimer was proved by the suppression of oxidative stress with an IC50 of 7.92 ± 0.36 µg/mL for DPPH scavenging and 16.87 ± 1.24 µg/mL for SOD scavenging which is competent with the standard ascorbic acid. According to this study, suppressing ROS levels by phloroglucinol and total procyanidin dimer would be the underlying mechanism for the synergistic anti-diabetic effect of this combination. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03929-4.
RESUMO
Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.