Modulation of PI3K/Akt/GSK3ß signaling cascade through G protein-coupled receptor 55 (GPR55) activation: Prenatal lysophosphatidylinositol attenuates valproic acid-induced synaptic abnormalities and mitochondrial dysfunction.

AIMS: Dysregulation of PI3K/Akt/GSK3ß signaling has been implicated in various neurological disorders, including autism spectrum disorder (ASD). G protein-coupled receptor 55 (GPR55) has recently emerged as a potential regulator of this signaling cascade. This study explores the intricate modulation of the PI3K/Akt/GSK3ß signaling cascade via GPR55 activation and its potential therapeutic implications in the context of autism-associated neuronal impairments. MAIN METHODS: Valproic acid (VPA) was administered on embryonic day 12 (E12) to induce ASD, and lysophosphatidylinositol (LPI), a GPR55 agonist, was used prenatally to modulate the receptor activity. Golgi-cox staining was performed to observe neuronal morphology, and Hematoxylin and eosin (H and E) staining was carried out to quantify damaged neurons. Enzyme-linked immunosorbent assay (ELISA) was implemented to identify molecular mediators involved in neuroprotection. KEY FINDINGS: Prenatal VPA exposure resulted in significant abnormalities in synaptic development, which were further evidenced by impairments in social interaction and cognitive function. When LPI was administered, most of the synaptic abnormalities were alleviated, as reflected by higher neuron and dendritic spine count. LPI treatment also reduced cytoplasmic cytochrome c concentration and related neuronal cell death. Mechanistically, GPR55 activation by LPI increases the expression of phospho-Akt and phospho-GSK3ß, leading to the activation of this signaling in the process of rescuing synaptic abnormalities and mitochondria-mediated neuronal apoptosis. SIGNIFICANCE: The observed therapeutic effects of GPR55 activation shed light on its significance as a prospective target for ameliorating mitochondrial dysfunction and dendritic spine loss, offering novel prospects for developing targeted interventions to alleviate the neuropathological causes of ASD.

Dataset concerning effects of stevia (Stevia rebaudiana bertoni), amlodipine, losartan, and valsartan on water consumption, blood glucose and heart tissue in gentamycin-induced nephrotoxicity in the rat model.

This dataset indicates the effect of stevia (Stevia rebaudiana Bertoni); angiotensin-II type-1 receptor (AT1) blockers, losartan and valsartan; and a calcium (Ca2+) channel blocker, amlodipine; on water consumption, fasting blood glucose, and cardiac histology in gentamycin-induced nephrotoxic rat model. Six groups of male Sprague-Dawley rats were selected as sham control group, gentamycin-induced nephrotoxic disease control group; gentamycin-induced disease control groups treated with stevia (200 mg/kg/day); amlodipine (4 mg/kg/day); losartan (15 mg/kg/day) and valsartan (5 mg/kg/day) respectively. Fasting blood glucose level and water consumption were recorded daily for the first week and then weekly for the rest of treatment period. Serum creatinine, blood urea, total protein and lipid profile were determined. Histological examination of the heart tissue was assessed to find out any alteration of cardiac muscle tissue following gentamycin-induced nephrotoxicity. This article provides additional data collected from the same animals previously reported [1] .

Renoprotective effects of stevia (Stevia rebaudiana Bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: Biochemical, hematological and histological approaches.

The current study investigated the renoprotective effects of stevia, angiotensin-II type 1 receptor (AT1) blocker and calcium (Ca2+) channel blocker in gentamycin-induced nephrotoxicity in rat models. Six groups of male Sprague-Dawley rats of eight weeks old were taken for the experiment: sham control, nephrotoxicity, treatment with amlodipine (4 mg/kg/day); stevia (200 mg/kg/day); losartan (15 mg/kg/day) and valsartan (5 mg/kg/day), accordingly. The blood sample was taken for the assessment of renal and hepatic-functional variables like serum creatinine, blood urea, BUN and SGPT, SGOT, and total serum bilirubin. Hematological parameters were also examined. Histological examination has been done on kidneys and liver. Alterations of the body weight and the organ's weight were documented. Treatment with stevia and valsartan significantly decreased serum creatinine levels. A reduction of liver enzymes, and total serum bilirubin levels were observed in all the treatment groups. Treatment with valsartan and amlodipine, remarkably and stevia, mildly reduced the renal tissue damage, inflammation, and tubular necrosis. However, the present study demonstrated that losartan treatment aggravated kidney damage by increasing protein cast, calcification, tubular necrosis, and injury. This comparison indicated that both stevia and valsartan have beneficial renoprotective effect and valsartan offers a better treatment option in renal damage over losartan.

Preliminary analysis of the effect of Stevia (Stevia rebaudiana) in patients with chronic kidney disease (stage I to stage III).

BACKGROUND: Stevia, Stevia rebaudiana (Bertoni), has become an important economic plant for its commercial use as a sweetener. Stevia plays a significant role in the healthcare practice of different cultures and in population. Previous animal and clinical studies demonstrated the efficacy of Stevia against chronic diseases like diabetes and hypertension. This study aimed to investigate the beneficial effect of Stevia in chronic kidney disease (CKD) patients after three (3) months of treatment along with the conventional antihypertensive and anti diabetic medications. METHODS: A prospective, interventional, randomized, single-blind, placebo-controlled trial has been done with 97 participants. Stevia capsule (250 mg) or matching placebo was given to the participants twice daily along with Angiotensin-II Receptor Blocker (ARB) and/or Ca2+ Channel Blocker (CCB). First follow up visits were done after 3 months of the interval. Blood and urine samples were collected for the biochemical tests. A structured questionnaire was used for the baseline assessment. Informed consent was taken from each participant. RESULTS: Both hypertension and diabetes were found to be associated with CKD. Most of the participants (52.3%) of Stevia group were in CKD Stage II. Significant changes were found in Serum creatinine (p < 0.027), Serum Uric acid (p < 0.009), Fasting blood sugar (p < 0.041) and Postprandial blood sugar (p < 0.013) and Microalbumin (p < 0.041) level in the treatment group. CONCLUSION: The initial result demonstrated that Stevia has the potential for a significant improvement of some biochemical parameters in CKD patients. After completion of the nine (9) months clinical trial, the constructive effect of Stevia can be confirmed in this group of patients.

Electrophysiological, vasoactive, and gastromodulatory effects of stevia in healthy Wistar rats.

Antihypertensive and antidiabetic effects of stevia, Stevia rebaudiana (Asteraceae), have been demonstrated in several human and animal models. The current study aims to define stevia's role in modifying the electrophysiological and mechanical properties of cardiomyocytes, blood vessels, and gastrointestinal smooth muscle. Tissues from thoracic aorta, mesenteric arteries, ileum, and left ventricular papillary muscles were excised from 8-week-old healthy Wistar rats. The effects of stevia (1 × 10-9 M to 1 × 10-4 M) were measured on these tissues. Stevia's effects in the presence of verapamil, 4-AP, and L-NAME were also assessed. In cardiomyocytes, stevia attenuated the force of contraction, decreased the average peak amplitude, and shortened the repolarisation phase of action potential - repolarisation phase of action potential20 by 25 %, repolarisation phase of action potential50 by 34 %, and repolarisation phase of action potential90 by 36 %. Stevia caused relaxation of aortic tissues which was significantly potentiated in the presence of verapamil. In mesenteric arteries, incubation with L-NAME failed to block stevia-induced relaxation indicating the mechanism of action may not be fully via nitric oxide-dependent pathways. Stevia concentration-dependently reduced electrical field stimulated and carbachol-induced contractions in the isolated ileum. This study is the first to show the effectiveness of stevia in reducing cardiac action potential duration at 20 %, 50 %, and 90 % of repolarisation. Stevia also showed beneficial modulatory effects on cardiovascular and gastrointestinal tissues via calcium channel antagonism, activation of the M2 muscarinic receptor function, and enhanced nitric oxide release.

A comparative study of thyroid hormone levels in diabetic and non-diabetic patients.

Diabetic patients have a higher prevalence of thyroid disorders than the general population, this may influence diabetic management. In this study, we investigated thyroid hormone levels in uncontrolled diabetic patients. This comparative study was conducted at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM). Fifty-two diabetic patients were consecutively selected from diabetic patients attending the out-patient department of BIRDEM. Fifty control subjects were selected from non-diabetic patients who attended the out-patient department of BIRDEM for routine check-ups as advised by their attending physicians. The subjects in both groups were above 30 years of age. The concentration of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and thyroxine (FT4) were evaluated using a Microparticle Enzyme Immunoassay (MEIA) procedure. Patients with type 2 diabetes had significantly lower serum FT3 levels (p = 0.000) compared to the control groups. There were no significant differences observed in serum FT4 (p = 0.339) and TSH (p = 0.216) levels between the control and study subjects. All the diabetic patients had high fasting blood glucose levels (12.15 +/- 2.12). We conclude that FT3 levels were altered in these study patients with uncontrolled diabetes.