Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane

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

Оцінка in vitro антиглікаційного та антиоксидантного потенціалу дієтичної добавки L-цитруліну

Diabetes mellitus (DM) represents a significant global public health concern. It is a metabolic condition characterized by abnormal glucose levels in the bloodstream, known as hyperglycemia. This condition arises due to irregular insulin secretion, defective insulin receptivity, or a combination of both factors. The primary contributors to diabetic complications are protein glycation and oxidative stress resulting from chronic hyperglycemia. The aim. The increasing incidence of diabetes mellitus has prompted a quest for a novel, cost-effective, and efficacious medication. The objective of the study generally intends to explore and investigate the antiglycation and antioxidant potential of the dietary supplement L-Citrulline Materials and methods. A two-reaction model system was carried out to study and monitor the inhibitory impact of the dietary supplement L-Citrulline against advanced glycation end products (AGEs) formation. This system involved the in vitro glucose bovine serum albumin (BSA-glucose assay) and methylglyoxal bovine serum albumin (BSA-MGO assay). The antioxidant activity of the supplement was assessed by measuring its capacity to chelate metal ions and scavenge reactive oxygen species. The iron chelating activity was evaluated through absorbance measurements, while fluorescence measurements were employed for the remaining assays. Results. According to the findings of the antiglycation assays, it was observed that the dietary supplement L-Citrulline demonstrated inhibitory properties against the development of advanced glycation end products (AGEs) in the BSA-Glucose model at a concentration of 100 ppm. The degree of inhibition with respect to glycation was ascertained to be 52.19 ± 0.39 % through observation. The BSA-MGO model has exhibited inhibitory properties with an observed activity of 49.64 ± 0.27 % at 100ppm concentration with respect to glycation. On the other hand, the supplement demonstrates antioxidant characteristics through the chelation of Fe ions, leading to a percentage difference in activity of 68.58 ± 0.45 % compared to the control at 100 ppm. The utilization of Glucolypotoxixity (GLT) media during the reactive oxygen species assay yielded a significant rise of 173.48 ± 9.37 % in the reactive species levels compared to the control, with statistical significance. The addition of 10 mM dietary supplement L-Citrulline resulted in a noteworthy reduction of 98.42 ± 5.04 % in the escalation. Therefore, it can be deduced that utilizing L-Citrulline as a dietary supplement exhibits potential for its therapeutic applications in eliminating reactive oxygen species (ROS) within skeletal muscle cells. Conclusion. The study results suggest that the dietary supplement L-Citrulline has demonstrated inhibitory capabilities against glycation at varying concentration levels. Furthermore, it was noted to exhibit significant efficacy in both sets of antioxidant tests. Therefore, the supplement exhibits potential in the treatment of diabetes mellitusЦукровий діабет (ЦД) є серйозною проблемою глобальної системи охорони здоров'я. Це метаболічний стан, що характеризується аномальним рівнем глюкози в крові, відомий як гіперглікемія. Цей стан виникає через нерегулярну секрецію інсуліну, недостатню сприйнятливість до інсуліну або поєднання обох факторів. Основними причинами діабетичних ускладнень є глікація білка та окислювальний стрес, що є наслідком хронічної гіперглікемії. Мета. Зростання захворюваності на цукровий діабет спонукало до пошуку нових, економічно ефективних і дієвих ліків. Метою дослідження є вивчення та дослідження антиглікаційного та антиоксидантного потенціалу дієтичної добавки L-цитруліну. Матеріали та методи. Двореакційна модельна система була проведена для вивчення та моніторингу інгібіторного впливу харчової добавки L-цитрулін на утворення кінцевих продуктів глікації (AGE). Ця система включала in vitro глюкозу бичачого сироваткового альбуміну (аналіз BSA-глюкози) і метилгліоксалю бичачого сироваткового альбуміну (аналіз BSA-MGO). Антиоксидантну активність добавки оцінювали шляхом вимірювання її здатності хелатувати іони металів і поглинати активні форми кисню. Хелатоутворювальну активність заліза оцінювали за допомогою вимірювання абсорбції, тоді як вимірювання флуоресценції використовували для інших аналізів. Результати. Згідно з результатами аналізів антиглікації, було помічено, що дієтична добавка L-цитруліну продемонструвала інгібуючі властивості щодо розвитку кінцевих продуктів глікації (AGE) у моделі BSA-Glucose у концентрації 100 ppm. Ступінь інгібування щодо глікації було встановлено як 52,19 ± 0,39 % шляхом спостереження. Модель BSA-MGO продемонструвала інгібіторні властивості з спостережуваною активністю 49,64 ± 0,27 % при концентрації 100 ppm щодо глікації. З іншого боку, добавка демонструє антиоксидантні характеристики через хелатування іонів Fe, що призводить до процентної різниці в активності 68,58 ± 0,45 % порівняно з контролем при 100 ppm. Використання середовищ глюколіпотоксичності (GLT) під час аналізу активних форм кисню дало значне підвищення на 173,48 ± 9,37 % рівнів активних форм порівняно з контролем зі статистичною значущістю. Додавання 10 мМ харчової добавки L-цитруліну призвело до помітного зниження ескалації на 98,42 ± 5,04 %. Таким чином, можна зробити висновок, що використання L-цитруліну як харчової добавки має потенціал для його терапевтичного застосування для усунення активних форм кисню (АФК) у клітинах скелетних м’язів. Висновки. Результати дослідження свідчать про те, що дієтична добавка L-цитруліну продемонструвала здатність пригнічувати глікацію при різних рівнях концентрації. Крім того, було відзначено значну ефективність в обох наборах тестів на антиоксиданти. Таким чином, добавка має потенціал для лікування цукрового діабету

In Vitro Antioxidant and Fibroblast Migration Activities of Fractions Eluded from Dichloromethane Leaf Extract of <i>Marantodes pumilum</i>

(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

Comparative Studies of Palmatine with Metformin and Glimepiride on the Modulation of Insulin Dependent Signaling Pathway In Vitro, In Vivo &amp; Ex Vivo

(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-&alpha;, 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-&alpha; 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

Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane

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