Pheophorbide <scp>A</scp> from <i>Gelidium amansii</i> improves postprandial hyperglycemia in diabetic mice through α‐glucosidase inhibition

Kim, Min Jung; Kim, Hak Ju; Han, Jiarui

doi:10.1002/ptr.6260

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…In contrast to our in-silico data, Kim et al. ( 15 ) showed that 2 g/kg body weight of pheophorbide A was administered to 4‐week‐old male ICR mice and was found to be non-toxic. Another report suggests that maximum permissible amount of pheophorbide A was determined at 1,000 mg/g and a recommended dosage of 25 mg/day ( 43 ).…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, polyherbal formulation MA, a complex concoction of bioactive compounds, was considered, which showed various lead phytocompounds. Our previous study reported pheophorbide A in the major peak of LC-MS/MS of MA ( 12 ) similar to other supporting studies in the literature with regard to DM management ( 14 , 15 ). These studies suggest that pheophorbide A manages DM by enhancing insulin secretion.…”

Section: Discussionsupporting

confidence: 88%

“…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: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 88%

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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“…The best activity (75.41±0.03%) was obtained at 0.5 mg/mL against α-glucosidase. This is in support of results reported by Kim et al (2019) that pheophorbide A, an unesterified analog isolated from Gelidium amansii caused significant decrease in the activity of α-glucosidase and α-amylase when compared to Acarbose 40 . Palmitic acid showed the best α-glucosidase activity in all the concentrations tested ranging from 324.69-355.89 µM.…”

Section: Discussionsupporting

confidence: 92%

In vitro α-Glucosidase and α-Amylase Activities of Wild and Cultivated Amaranthus spp. and Isolated Compounds

Nkobole¹,

Bodede²,

Hussein³

et al. 2021

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Introduction: Diabetes mellitus is a serious metabolic disorder that affects many South Africans. There is urgent need for alternative and affordable diabetic therapy from edible wild plants which have been used by the indigenous people for many years. This study presents in vitro antidiabetic effects of methanol leaf extracts of wild and cultivated Amaranthus spp. and isolated compounds. Methods: The inhibitory effects against yeast α-glucosidase and porcine α-amylase were determined using a dilution series of ethanolic extracts of wild and cultivated leaf extracts and isolated compounds of Amaranthus spp. The aerial parts of the plant material were subjected to silica gel chromatography to yield three compounds. Results: Wild A. hybridus showed potent α-glucosidase enzyme activity (89.92±0.04%) at the lowest concentration tested (0.125 mg/mL) in comparison to acarbose which exhibited 80.20±0.13% inhibition at the same concentration. Cultivated A. cruentus extracts inhibited α-glucosidase enzyme activity (84.95 ± 0.04%) at the lowest concentration compared to cultivated A. hybridus which exhibited inhibitory activities of 72.28 ± 0.06%. In addition, three compounds namely, α-spinasterol, palmitic acid and pheophorbide A-methyl ester isolated from wild A.cruentus were tested for in vitro antidiabetic activity. Palmitic acid demonstrated the highest inhibition against α-glucosidase for all the concentrations tested. Tested separately, the isolated compounds were weaker α-amylase enzyme inhibitors however, when the compounds were combined, inhibition of α-amylase increased to 58.49± 002% at 0.5 mg/mL. Conclusions: Extracts and compounds of Amaranthus showed strong α-glucosidase activity inhibition and mild α-amylase activity inhibition suggesting that the extracts and compounds slow glucose absorption.

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“…Pheophorbides are commonly produced by most photosynthetic plants and microalgae as breakdown products of chlorophyll upon senescence and/or fruit ripening [17]. Pheophorbide a (PA) exerts antiviral [18], antioxidant [19], anti-inflammatory [20], antidiabetic [21,22], anticancer [23], and antiparasitic effects [24] through regulation of hepatitis C virus, scavenging of the 2,2-diphenyl-1-picryldrazyl-radical, and induction of tumor necrosis factor alpha (TNFα) secretion, α-glucosidase activity, insulin secretion, cancer cell proliferation, and Leishmania amazonensis cell death, respectively. PA is a good photosensitizer and strongly absorbs light energy at 650−700 nm [25].…”

Section: Introductionmentioning

confidence: 99%

Pheophorbide a Derivatives Exert Antiwrinkle Effects on UVB-Induced Skin Aging in Human Fibroblasts

Lee

Park

Jeong

2021

Life

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Pheophorbide a is a chlorophyll metabolic breakdown product. This study investigated the antiwrinkle effect of pheophorbide a (PA) and its derivatives, including pyropheophorbide a (PyroPA) and pyropheophorbide a methyl ester (PyroPA-ME), on ultraviolet (UV) B-stimulated CCD-986sk fibroblasts. PA, PyroPA, and PyroPA-ME effectively suppressed reactive oxygen species accumulation in UVB-exposed CCD-986sk fibroblasts. All three pheophorbides also reduced UVB-induced matrix metalloproteinase (MMP)-1 secretion and mRNA expression of MMP-1, MMP-2, and MMP-9. Treatment with pheophorbides resulted in increased procollagen synthesis, and this required enhancement of procollagen type I C-peptide content and mRNA expression of collagen type I alpha 1 (COL1A1) and COL1A2 in CCD-986sk cells. These antiwrinkle effects were more potent with PA and PyroPA than with PyroPA-ME. Furthermore, PA and PyroPA suppressed UVB-induced phosphorylation of extracellular signal-regulated protein kinase and c-Jun N-terminal kinase but not p38. Moreover, all three pheophorbides inhibited NF-κB p65 phosphorylation. Therefore, these pheophorbides, especially PA and PyroPA, can be used as antiwrinkle agents, and PA- or PyroPA-rich natural resources can be used in functional cosmetics.

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

Cited by 14 publications

References 21 publications

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

In vitro α-Glucosidase and α-Amylase Activities of Wild and Cultivated Amaranthus spp. and Isolated Compounds

Pheophorbide a Derivatives Exert Antiwrinkle Effects on UVB-Induced Skin Aging in Human Fibroblasts

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