Hepato-protective and anti-diabetic effects of Capsosiphon fulvescens and pheophorbide A in streptozotocin-induced diabetic rats

Lee, Kwang Won; Kim, Se-Wook; Oh, Jisun; Nam, Mi‐Hyun; Hong, Chung-Oui

doi:10.1016/j.toxlet.2014.06.807

Cited by 2 publications

(3 citation statements)

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“…Our data also showed strong binding affinity and stability of the complex. We observed that pheophorbide A further potentiates glucose uptake, which may lead to insulin secretion reported in previous studies ( 11 , 13 ). In every metric, pheophorbide A showed better efficiency of binding with GLUT1 to improve glucose transport.…”

Section: Discussionsupporting

confidence: 82%

“…Pheophorbide A is primarily investigated for its anti-oxidant and anti-inflammatory activity; it has the potential to lower blood glucose levels, thus could be explored for its use in diabetes management. Studies show that it could enhance insulin secretion and manage high-glucose levels during hyperglycemia ( 13 – 15 ), although its mechanism of action in pancreatic β cells is not known. Previous studies on various plant extracts and a few bioactive compounds have reported their anti-diabetic properties with respect to increasing GLUT expression ( 16 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

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Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis

Paul,

Pallavi,

Gandasi

2024

Front. Endocrinol.

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IntroductionPheophorbide A, a chlorophyll-breakdown product, is primarily investigated for its anti-oxidant and anti-inflammatory activity. Recent reports on pheophorbide A have shown its potential in lowering blood glucose levels, thus leading to the exploration of its use in diabetes management. Literature has also shown its effect on enhanced insulin secretion, whereas its mechanism on glucose stimulated insulin secretion (GSIS) in pancreatic β cells remains unexplored.MethodsIn-silico and in-vitro investigations were used to explore the effect of pheophorbide A on class I glucose transporters (GLUTs). In-silico studies include - Molecular docking studies and stability assessment using GROMACS. In-vitro studies include - MTT assay, Glucose uptake assay, Live-cell imaging and tracking of GLUTs in presence of Pheophorbide A compared to control.ResultsMolecular docking studies revealed better binding affinity of pheophorbide A with GLUT4 (−11.2 Kcal/mol) and GLUT1 (−10.7 Kcal/mol) when compared with metformin (−5.0 Kcal/mol and −4.9 Kcal/mol, respectively). Glucose levels are largely regulated by GLUTs where GLUT1 is one of the transporters that is ubiquitously present in human β cells. Thus, we confirmed the stability of the complex, that is, pheophorbide A-GLUT1 using GROMACS for 100 ns. We further assessed its effect on a pancreatic β cell line (INS-1) for its viability using an MTT assay. Pheophorbide A (0.1–1 µM) showed a dose-dependent response on cell viability and was comparable to standard metformin. To assess how pheophorbide A mechanistically acts on GLUT1 in pancreatic β cell, we transfected INS-1 cells with GLUT1–enhanced green fluorescent protein and checked how the treatment of pheophorbide A (0.50 µM) modulates GLUT1 trafficking using live-cell imaging. We observed a significant increase in GLUT1 density when treated with pheophorbide A (0.442 ± 0.01 µm−2) at 20 mM glucose concentration when compared to GLUT1 control (0.234 ± 0.01 µm−2) and metformin (0.296 ± 0.02 µm−2). The average speed and distance travelled by GLUT1 puncta were observed to decrease when treated with pheophorbide A. The present study also demonstrated the potential of pheophorbide A to enhance glucose uptake in β cells.ConclusionThe current study’s findings were validated by in-silico and cellular analyses, suggesting that pheophorbide A may regulate GLUT1 and might be regarded as a potential lead for boosting the GSIS pathway, thus maintaining glucose homeostasis.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis

Paul,

Pallavi,

Gandasi

2024

Front. Endocrinol.

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“…Subsequently, free glucose is absorbed by the gut and causes postprandial hyperglycemia (Tadera, Minami, Takamatsu, & Matsuoka, 2006). The inhibition of these enzymes effectively delays carbohydrate digestion and glucose absorption, which controls postprandial hyperglycemia (Lee, Kim, Oh, Nam, & Hong, 2014). Hence, many studies have searched for natural materials that inhibit the activity of α-glucosidase and α-amylase.…”

Section: Figure 4 Effect Of Pheophorbide a On Cell Viability In 3t3-l1mentioning

confidence: 99%

Pheophorbide A from Gelidium amansii improves postprandial hyperglycemia in diabetic mice through α‐glucosidase inhibition

Kim

Han

2019

Phytotherapy Research

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This study was designed to determine the inhibitory effects of pheophorbide A on carbohydrate digesting enzymes and its ability to improve postprandial hyperglycemia in streptozotocin (STZ)‐induced diabetic mice. Pheophorbide A caused noticeable inhibitory effects on α‐glucosidase and α‐amylase, with half‐maximal inhibitory concentrations (IC50) of 80.65 ± 5.90 and 76.48 ± 6.31 μM, respectively. The pheophorbide‐mediated inhibition of α‐glucosidase and α‐amylase was significantly more effective than that of the positive control, acarbose. The increase in postprandial blood glucose levels was more significantly suppressed in the pheophorbide A group than in the control group of STZ‐induced diabetic mice. In addition, the area under the curve was decreased by pheophorbide A intake in STZ‐induced diabetic mice. Our results suggested that pheophorbide A may help to improve postprandial hyperglycemia by inhibiting the activity of carbohydrate digesting enzymes.

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Hepato-protective and anti-diabetic effects of Capsosiphon fulvescens and pheophorbide A in streptozotocin-induced diabetic rats

Cited by 2 publications

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Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis

Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis

Pheophorbide A from Gelidium amansii improves postprandial hyperglycemia in diabetic mice through α‐glucosidase inhibition

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