The Beneficial Additive Effect of Silymarin in Metformin Therapy of Liver Steatosis in a Pre-Diabetic Model

The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from Silybum marianum, evinces an antioxidative, anti-inflammatory, and hepatoprotective activity. In this study, we investigated whether metformin (300 mg/kg/day for four weeks) supplemented with micronized silymarin (600 mg/kg/day) would be effective in mitigating fatty liver disturbances in a pre-diabetic model with dyslipidemia. Compared with metformin monotherapy, the metformin–silymarin combination reduced the content of neutral lipids (TAGs) and lipotoxic intermediates (DAGs). Hepatic gene expression of enzymes and transcription factors involved in lipogenesis (Scd-1, Srebp1, Pparγ, and Nr1h) and fatty acid oxidation (Pparα) were positively affected, with hepatic lipid accumulation reducing as a result. Combination therapy also positively influenced arachidonic acid metabolism, including its metabolites (14,15-EET and 20-HETE), mitigating inflammation and oxidative stress. Changes in the gene expression of cytochrome P450 enzymes, particularly Cyp4A, can improve hepatic lipid metabolism and moderate inflammation. All these effects play a significant role in ameliorating insulin resistance, a principal background of liver steatosis closely linked to T2DM. The additive effect of silymarin in metformin therapy can mitigate fatty liver development in the pre-diabetic state and before the onset of diabetes.

Trehalose Ameliorates Diabetic Cardiomyopathy: Role of the PK2/PKR Pathway

Ample clinical case reports suggest a high incidence of cardiomyopathy in diabetes mellitus (DM). Recent evidence supports an essential role of trehalose (TLS) in cardiomyocyte survival signaling. Our previous study found that prokineticin2 (PK2) was involved in the process of diabetic cardiomyopathy (DCM). The present study examined the protective effects and mechanisms of TLS on DM-induced cardiomyocyte injury in mice and H9c2 cardiomyocytes. C57BL/6J mice were intraperitoneally injected with 50 mg·kg-1·d-1 streptozotocin for five consecutive days to establish an experimental diabetic model and then administered TLS (1 mg·g-1·d-1, i.p.) for two days every 4 weeks and given 2% TLS in drinking water for 24 weeks. Echocardiography, myocardial structure, apoptosis, pyroptosis, autophagy, and the PK2/PKR pathway were assessed. Cardiomyocytes exposed to high glucose (HG) were treated with TLS in the absence or presence of the PK2 antagonist PKRA7, and proteins involved in apoptosis, autophagy, and pyroptosis and the PK2/PKR pathways were evaluated using Western blot analysis. Diabetic mice demonstrated metabolic disorder, abnormal myocardial zymograms, and aberrant myocardial systolic and diastolic function, which were accompanied by pronounced apoptosis, pyroptosis, and dampened autophagy. TLS treatment relieved these effects. PK2 and receptor expressions were downregulated in diabetic mice, and TLS nullified this effect. PKRA7 eliminated the impact of TLS on cardiomyocytes. This evidence suggests that TLS rescues DM-induced myocardial function, pyroptosis, and apoptosis, likely via the PK2/PKR pathway.

Phytoremedial effect of fruit extract of Moringa oleifera on alloxan induced diabetic model in Swiss albino mice

Diabetes is a metabolic disorder and global health issue. It arises because of an absolute or relative insulin deficiency that causes hyperglycemia. The study aimed to assess the antihyperglycemic, hepatoprotective, and renal protective effects of ethanolic fruit extract of Moringa oleifera, on alloxan-induced diabetic mice. Four mice were assigned to each group. Alloxan was injected at the dose of 10mg/kg/body weight intraperitoneally to make the diabetic model in mice. Control and diabetic control mice received drinking water as a placebo, while the diabetic model mice group was administered with ethanolic extract of moringa fruit at the dose of 150mg/kg/bodyweight for 12 weeks. After that, animals were sacrificed, and their blood and tissue samples were collected for biochemical and histopathological examination. The glucose level markedly (p<0.0001) increased many folds in Group I (80.73± 1.24 to 221.5±13.4) and Group II (80.73 ± 1.24 from to 221.9±6.88). The level of insulin markedly (P< 0.0001) decreased in both groups (6.8±0.42 to1.378±0.19) and (6.8±0.42 to1.138±0.08) respectively. Serum hepatic and renal marker enzymes increased in the diabetic group of mice. Glucose level was meaningfully (p<0.0001) decreased in the M. oleifera administered group while serum insulin level significantly (p<0.0001) increased. The level of liver marker enzyme and renal marker also decreased as compared to the diabetic control group. Histopathological study revealed that alloxan treatment caused damage to the liver, kidney, and pancreatic tissues while the M. oleifera administered group exhibited significant improvement in the architecture of the liver, kidney, and pancreas. Hence, M. oleifera has great potential to rejuvenate the damaged tissue and consequently can restore all the serum enzymatic and hormonal parameters.

EFFECT OF CHANNA MICROPELTES IN THE GRANULATION, FIBROSIS AND NECROSIS OF DIABETIC WOUND HEALING

Background: Diabetes mellitus (DM) is characterized by persistent hyperglycemia. The symptoms of DM is delayed wound healing. Delayed wound healing in diabetes will increase the risk of wound complications that will hinder the healing process, and lead to complications such as fibrosis and necrosis. The use of Channa Micropeltes (CM) extract at a dose of 16 mL/kg BW orally is proven to general optimal wound closure and wound contraction clinically in Wistar rats as diabetic model on day 14.However, the histopathological description of wound healing is yet to be known. Objective: To analyze the effect of 16 mL/kg BW dose of CM extract on histopathological changes of wound healing granulation tissue, fibrosis and necrosis in diabetic Wistar rats on day 14. Materials and Methods: This study was a true experimental design with a post-test only control group design. The samples were divided into two groups, namely the diabetic model group given CM extract at 16 mL/kg BW dose for 14 days, and the diabetic model group given BR2 feed only for 14 days. Results: The results of Mann-Whitney U test showed p = 0.003 for granulation tissue, p = 0.411 for fibrosis and p = 1 for necrosis, with the level of significance was p<0.05. Conclusion: The CM extract at 16 mL/kg BW dose affects the histopathological description of granulation tissue which presents a better result than those in the control group but did not affect the features of fibrosis and necrosis in diabetic Wistar rats on day 14. Keywords: Channa Micropeltes, Diabetic wound, Fibrosis, Granulation tissue, Necrosis.