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Type 2 diabetes is a disease characterized by dysregulation of glucose homeostasis, with numerous diabetic complications attributable to the resulting chronic exposure of cells and tissues to elevated concentrations of glucose and fatty acids. This in part results from formation of advanced glycation end-products and advanced lipidation end-products that can form adducts with proteins, lipids, or DNA and disrupt their normal cellular function. There is, however, growing evidence that supplementation with the endogenous histidine-containing dipeptide, carnosine, or its rate-limiting precursor, β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and related conditions. Here we investigated the scavenging potential of β-alanine in INS-1 pancreatic β-cells and C2C12 skeletal muscle myotubes, and show a significant reduction of >60% in reactive species that were generated by glucolipotoxic metabolic stress in both cell types following incubation with β-alanine for 5 days. Furthermore, β-alanine supplementation resulted in a protective action that helped prevent the damaging action of metabolic stress that otherwise leads to inhibition of mitochondrial function in both cell types. This in turn resulted in >60% preservation of insulin secretion and glucose uptake, in INS-1 cells and C2C12 cells respectively, which would otherwise be inhibited by metabolic stress. This suggests potential therapeutic benefit to taking β-alanine supplements as an alternative to carnosine.

(1) The complexity of diabetes and diabetic wound healing remains a therapeutic challenge because proper and systematic wound care and management are essential to prevent chronic microbial infection and mechanical damage to the skin. Marantodes pumilum, locally known as ‘Kacip Fatimah’, is an herb that has been previously reported to possess anti-inflammatory, analgesic, antinociceptive and antipyretic properties. The current study aims to assess the antioxidant and fibroblast cell migration activities of the fractions eluded from the dichloromethane extract of M. pumilum leaves. (2) The total antioxidant capacity of M. pumilum was assessed using the total proanthocyanidins and phosphomolybdenum assays, while DPPH, nitric oxide, hydrogen peroxide and superoxide free radical scavenging assays were tested to determine the antioxidant potential of M. pumilum. An in vitro scratch wound assay was performed to measure the fibroblast cell migration rate using normal and insulin-resistant human dermal fibroblast cells. (3) All M. pumilum fractions exhibited good antioxidant and fibroblast cell migration activity, among which fractions A and E displayed the greatest effect. (4) M. pumilum’s fibroblast migration activity could be attributed to its strong antioxidant properties along with its previously reported properties.

1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of Marantodes pumilum (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of M. pumilum and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP.

(1) Insulin resistance, a symptom of type 2 diabetes mellitus (T2DM), is caused by the inactivation of the insulin signaling pathway, which includes IRS-PI3K-IRS-1-PKC-AKT2 and GLUT4. Metformin (biguanide) and glimepiride (sulfonylurea) are both drugs that are derivatives of urea, and they are widely used as first-line drugs for the treatment of type 2 diabetes mellitus. Palmatine has been previously reported to possess antidiabetic and antioxidant properties. (2) The current study compared palmatine to metformin and glimepiride in a type 2 diabetes model for ADME and insulin resistance via the PI3K/Akt/GLUT4 signaling pathway: in vitro, in vivo, ex vivo, and in silico molecular docking. (3) Methods: Differentiated L6 skeletal muscle cells and soleus muscle tissue were incubated in standard tissue culture media supplemented with high insulin and high glucose as a cellular model of insulin resistance, whilst streptozotocin (STZ)-induced Sprague Dawley rats were used as the diabetic model. The cells/tissue/animals were treated with palmatine, while glimepiride and metformin were used as standard drugs. The differential gene expression of PI3K, IRS-1, PKC-α, AKT2, and GLUT4 was evaluated using qPCR. (4) Results: The results revealed that the genes IRS-PI3K-IRS-1-PKC-AKT2 were significantly down-regulated, whilst PKC-α was upregulated significantly in both insulin-resistant cells and tissue animals. Interestingly, palmatine-treated cells/tissue/animals were able to reverse these effects. (5) Conclusions: Palmatine appears to have rejuvenated the impaired insulin signaling pathway through upregulation of the gene expression of IRS-1, PI3K, AKT2, and GLUT4 and downregulation of PKC-expression, according to in vitro, in vivo, and ex vivo studies.