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Gynura divaricata Water Extract Presented the Possibility to Enhance Neuronal Regeneration.

ABSTRACT: Gynura divaricata (GD) is an Asian herb widely used as an alternative medicine and functional food for type 2 diabetes. Diabetic neuropathy is considered as an important complication of diabetic patients. This study focused on neuroregenerative effects of GD for use in the prevention of diabetic neuropathy. GD leaves were cut and boiled in water to mimic real-life cooking. The boiled content was filtered through white gauze and lyophilized to preserve as dried powder. Antioxidant assay was performed using DPPH assays. UHPLC-QTOF-MS/MS was employed to test for important compounds in the extract of these herbs. MTT assay was used to test for cell viability. The extracts at concentration of 250??g/mL were tested with human gingival cell to observe the change of gene expression. The DPPH assay showed that GD water extract at the concentration of 5000??g/mL could inhibit DPPH radical for 39.2%. The results showed that 5000?µg of GD water extract contained total phenolic content equivalent to 310.9?µg standard gallic acid. UHPLC-QTOF-MS/MS result found phenolic acids and flavonoids as the main components. Human gingival cells treated with 250??g/mL of GD water extract for 10 days showed upregulation of some neuronal differentiation markers. Staining with Cdr3 dye confirmed the presentation of neuronal progenitors. The extract at the concentration of 250??g/mL was also tested with apical papilla cells to screen for change of gene expression by RNA sequencing. The result also showed significant upregulation of alpha-internexin (INA). These results indicated that GD water extract might have an inductive effect for neural regeneration and could be used as functional food and supplementation for the prevention or treatment of diabetic neuropathy. This work provided the basic knowledge for further investigations into the benefits of GD for diabetic neuropathy.

SUBMITTER: Kantawong F

PROVIDER: S-EPMC7904343 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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<i>Gynura divaricata</i> Water Extract Presented the Possibility to Enhance Neuronal Regeneration.

Kantawong Fahsai F Saisuwan Chanakarn C Soeratanapant Pirakorn P Wanachantararak Phenphichar P Nan Jiang J Wu Jianming J Chang Young-Tae YT

Evidence-based complementary and alternative medicine : eCAM 20210217

<i>Gynura divaricata</i> (GD) is an Asian herb widely used as an alternative medicine and functional food for type 2 diabetes. Diabetic neuropathy is considered as an important complication of diabetic patients. This study focused on neuroregenerative effects of GD for use in the prevention of diabetic neuropathy. GD leaves were cut and boiled in water to mimic real-life cooking. The boiled content was filtered through white gauze and lyophilized to preserve as dried powder. Antioxidant assay wa ...[more]

PMID: 33680064

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Project description:Gynura divaricata (L.) DC (Compositae) (GD) could be found in various parts of Asia. It has been used as a traditional medicine to treat diabetes, high blood pressure, and other diseases, but its effects have not yet been scientifically confirmed. Therefore, we aimed at determining whether GD could affect renal function regulation, blood pressure, and the renin-angiotensin-aldosterone system (RAAS). Cardio-renal syndrome (CRS) is a disease caused by the interaction between the kidney and the cardiovascular system, where the acute or chronic dysfunction in one organ might induce acute or chronic dysfunction of the other. This study investigated whether GD could improve cardio-renal mutual in CRS type 4 model animals, two-kidney one-clip (2K1C) renal hypertensive rats. The experiments were performed on the following six experimental groups: control rats (CONT); 2K1C rats (negative control); OMT (Olmetec, 10 mg/kg/day)-treated 2K1C rats (positive control); and 2K1C rats treated with GD extracts in three different doses (50, 100, and 200 mg/kg/day) for three weeks by oral intake. Each group consisted of 10 rats. We measured the systolic blood pressure weekly using the tail-cuff method. Urine was also individually collected from the metabolic cage to investigate the effect of GD on the kidney function, monitoring urine volume, electrolyte, osmotic pressure, and creatinine levels from the collected urine. We observed that kidney weight and urine volume, which would both display typically increased values in non-treated 2K1C animals, significantly decreased following the GD treatment (###p < 0.001 vs. 2K1C). Osmolality and electrolytes were measured in the urine to determine how renal excretory function, which is reduced in 2K1C rats, could be affected. We found that the GD treatment improved renal excretory function. Moreover, using periodic acid-Schiff staining, we confirmed that the GD treatment significantly reduced fibrosis, which is typically increased in 2K1C rats. Thus, we confirmed that the GD treatment improved kidney function in 2K1C rats. Meanwhile, we conducted blood pressure and vascular relaxation studies to determine if the GD treatment could improve cardiovascular function in 2K1C rats. The heart weight percentages of the left atrium and ventricle were significantly lower in GD-treated 2K1C rats than in non-treated 2K1C rats. These results showed that GD treatment reduced cardiac hypertrophy in 2K1C rats. Furthermore, the acetylcholine-, sodium nitroprusside-, and atrial natriuretic peptide-mediated reduction of vasodilation in 2K1C rat aortic rings was also ameliorated by GD treatment (GD 200 mg/kg/day; p < 0.01, p < 0.05, and p < 0.05 vs. 2K1C for vasodilation percentage in case of each compound). The mRNA expression in the 2K1C rat heart tissue showed that the GD treatment reduced brain-type natriuretic peptide and troponin T levels (p < 0.001 and p < 0.001 vs. 2K1C). In conclusion, this study showed that GD improved the cardiovascular and renal dysfunction observed in an innovative hypertension model, highlighting the potential of GD as a therapeutic agent for hypertension. These findings indicate that GD shows beneficial effects against high blood pressure by modulating the RAAS in the cardio-renal syndrome. Thus, it should be considered an effective traditional medicine in hypertension treatment.

Project description:ObjectivesThe study aimed to examine the anti-diabetic effects of Gynura divaricata (GD) and the underlying mechanism.MethodsInformation about the chemical compositions of GD was obtained from extensive literature reports. Potential target genes were predicted using PharmMapper and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). To validate the results from bioinformatics analyses, an aqueous extract of GD was administered to type 2 diabetic rats established by feeding a high-fat and high-sugar diet followed by STZ injection. Key proteins of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway were investigated by immunoblotting.ResultsThe blood glucose of the rats in the GD treatment group was significantly reduced compared with the model group without treatment. GD also showed activities in reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CREA). The levels of urine sugar (U-GLU) and urine creatinine (U-CREA) were also lowered after treatment with GD. Bioinformatics analysis showed that some pathways including metabolic pathways, insulin resistance, insulin signaling pathway, PPAR signaling pathway, bile secretion, purine metabolism, etc. may be regulated by GD. Furthermore, GD significantly increased the protein expression levels of PKM1/2, p-AKT, PI3K p85, and GLUT4 in the rat liver. In addition, the expression levels of key proteins in the fatty acid metabolism signaling pathway including AMPK, p-AMPK, PPARα, and CPT1α were significantly upregulated. The anti-apoptotic protein BCL-2/BAX expression ratio in rats was significantly upregulated after GD intervention. These results were consistent with the bioinformatics analysis results.ConclusionsOur study suggests that GD can exert hypoglycemic effects in vivo by regulating the genes at the key nodes of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway.

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Gynura divaricata Water Extract Presented the Possibility to Enhance Neuronal Regeneration.

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<i>Gynura divaricata</i> Water Extract Presented the Possibility to Enhance Neuronal Regeneration.

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