Phenolic Content Analysis of Aloe vera Gel and Evaluation of the Effect of Aloe Gel Supplementation on Oxidative Stress and Fibrosis in Isoprenaline-Administered Cardiac Damage in Rats

Lasker

et al. 2020

Sci Rep

Self Cite

Diabetes is a leading cause of chronic kidney disease, and the high prevalence of sympathetic nervous system (SNS) hyperactivity in diabetic patients makes them further susceptible to SNS-mediated oxidative stress and accelerated kidney damage. Here, we investigated if canagliflozin can reverse isoprenaline (ISO)-induced renal oxidative damage in rats, a model that mimics SNS overstimulationinduced organ injuries in humans. We found that ISO administration elevates renal oxidative stress markers including malondialdehyde (MDA), advanced protein oxidation product (APOP), myeloperoxidase (MPO) and nitric oxide (NO), while depleting levels of endogenous antioxidants such as catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH). Strikingly, canagliflozin treatment of ISO-treated rats not only prevents elevation of oxidative stress markers but also rescues levels of depleted antioxidants. Our results also show that canagliflozin stimulates antioxidant/antiinflammatory signaling pathways involving AMP-activated protein kinase (AMPK), Akt and eNOS, and inhibits iNOS and NADPH oxidase isoform 4 (NOX4), all of which are associated with oxidative stress and inflammation. Further, canagliflozin prevents ISO-induced apoptosis of kidney cells by inhibiting Bax protein upregulation and caspase-3 activation. Histological examination of kidney sections reveal that canagliflozin attenuates ISO-mediated increases in inflammatory cell infiltration, collagen deposition and fibrosis. Finally, consistent with these findings, canagliflozin treatment improves kidney function in ISO-treated rats, suggesting that the antioxidant effects may be clinically translatable. Diabetic kidney disease is a major risk factor for the development of chronic kidney disease affecting approximately 40% of global diabetic population 1. Diabetic kidney disease is associated with vascular inflammation, loss of renal vascular integrity and hypertension, leading to a progressive loss of renovascular function and renal failure 1. Importantly, there is a high prevalence of sympathetic nervous system (SNS) hyperactivity in diabetic patients associated with autonomic neuropathy and concomitant vagal impairment, making diabetic patients twice as likely to develop hypertension 2. Diabetic patients are also highly susceptible to chronic kidney disease due to renal oxidative damage and inflammation 2. High SNS drive stimulates β1 adrenergic receptors (β1-AR) in juxtaglomerular cells, increasing renin secretion and subsequent activation of the renin-angiotensin-aldosterone system (RAAS). RAAS creates a feed-forward mechanism that accelerates renovascular dysfunction and kidney

Section: Discussionsupporting

confidence: 92%

Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK–Akt–eNOS pathway in the isoprenaline-induced oxidative stress model

Lasker

et al. 2020

Sci Rep

Self Cite

“…It is well established that ISO stimulates β-AR, primarily β2-AR, to cause oxidative stress leading to inflammation and tissue damage 22 , 27 , 34 , 35 . ISO-induced oxidative stress is characterized by elevation of various oxidative and nitrative stress markers including MDA, NO, MPO and APOP, with concurrent reduction of cellular reserves of naturally occurring antioxidants such as CAT, SOD and glutathione 36 , 37 . Our data showed that canagliflozin potently reduced MDA, NO, MPO and APOP in heart tissue homogenate (Fig.…”

Section: Discussionmentioning

confidence: 99%

Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways

Lasker

et al. 2020

Sci Rep

Self Cite

The antidiabetic drug canagliflozin is reported to possess several cardioprotective effects. However, no studies have investigated protective effects of canagliflozin in isoprenaline (ISO)-induced cardiac oxidative damage-a model mimicking sympathetic nervous system (SNS) overstimulation-evoked cardiac injuries in humans. Therefore, we investigated protective effects of canagliflozin in ISOinduced cardiac oxidative stress, and their underlying molecular mechanisms in Long-Evans rat heart and in HL-1 cardiomyocyte cell line. Our data showed that ISO administration inflicts pro-oxidative changes in heart by stimulating production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In contrast, canagliflozin treatment in ISO rats not only preserves endogenous antioxidants but also reduces cardiac oxidative stress markers, fibrosis and apoptosis. Our Western blotting and messenger RNA expression data demonstrated that canagliflozin augments antioxidant and anti-inflammatory signaling involving AMP-activated protein kinase (AMPK), Akt, endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In addition, canagliflozin treatment attenuates pro-oxidative, pro-inflammatory and proapoptotic signaling mediated by inducible nitric oxide synthase (iNOS), transforming growth factor beta (TGF-β), NADPH oxidase isoform 4 (Nox4), caspase-3 and Bax. Consistently, canagliflozin treatment improves heart function marker in ISO-treated rats. In summary, we demonstrated that canagliflozin produces cardioprotective actions by promoting multiple antioxidant and antiinflammatory signaling. Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, belongs to a new class of antidiabetic drugs prescribed for the management of type 2 diabetes mellitus (T2DM) 1. Accumulating evidence suggests that canagliflozin exhibits a range of cardiovascular effects that are independent of glucose lowering. According to recent preclinical and clinical data, canagliflozin treatment significantly reduced risk of cardiovascular death, myocardial infarction (MI), stroke and hospitalization due to heart failure in both diabetic and non-diabetic subjects 2-5. Proposed mechanisms for cardiovascular benefits of canagliflozin include improvement of cardiac metabolism and diastolic function, reduction of vascular stiffness, and an overall reduction of blood pressure 5-9. A growing body of evidence suggests that canagliflozin possess antioxidant and anti-inflammatory actions in various cellbased and animal models 10-14. Canagliflozin was shown to reduce vascular inflammation and atherosclerosis by

“…The oxidation reaction of skin lesions is also one of the main reasons that prolongs the process of lesion repair. Glutathione peroxide activity, superoxide dismutase enzymes, and phenolic antioxidants were found to be present in AVG, which may be responsible for the antioxidant effects (36). AVG can inhibit tyrosinase and dihydroxyphenylalanine (DOPA), a priming agent in the enzymatic conversion of tyrosine into melanin that reduces pigmentation (37).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of a New Non-drug Acne Therapy: Aloe Vera Gel Combined With Ultrasound and Soft Mask for the Treatment of Mild to Severe Facial Acne

Zhong

Zhang

et al. 2021

Front. Med.

Background: Acne is a chronic disorder that affects almost 80% of adolescents and young adults, causing psychological and emotional distress. However, the current treatments for acne are either ineffective or have many side effects. This study was designed to confirm and objectively quantify the effect of a new non-drug combined therapy on acne.Methods: This study innovatively utilized ultrasound, which enhanced the absorption of aloe vera gel, and soft mask to make a purely physical method without any drugs. In both the treatment group and control group, the number of papules/pustules and the area of hyperpigmented lesions were counted, and a smart mirror intelligent face system was used before and after the combined therapy. Alterations in the skin functional index were recorded and analyzed statistically.Results: In the treatment group, the combined therapy significantly reduced the number of papules and the area of hyperpigmented lesions and improved skin roughness and local blood circulation. In the control group, there was no obvious improvement over 2 months.Conclusion: This study suggests that the new non-drug combined therapy significantly improved acne, which provided experimental evidence and treatment guidance for patients with mild to severe acne, especially patients with moderate acne. This new therapy may possibly be an appropriate method for patients who seek topical treatments with mild side effects and low antibiotic resistance rates.