PEG modification of Amorfrutin B from Amorpha fructicosa increases gastric absorption, circulation half-life and glucose uptake by T3T-L1 adipocytes

Samad, Mehdi Bin; Hasan, Nazmul; Banarjee, Sudipta; Rahman, Mizanur; Raihan, Sabbir; Banti, Faika Laz; Sayfe, Sania Sarker; Hasan, S.M. Nageeb; Akhter, Farida; Kabir, Ashraf Ul; Hannan, J. M. A.

doi:10.1016/j.biopha.2017.08.113

Cited by 4 publications

(3 citation statements)

References 53 publications

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“…In the present study, we have provided evidence on the neuroprotective effect of post-treatment with amorfrutin B, the compound with proven properties of a selective PPARγ modulator [ 14 , 15 ]. The effect of amorfrutin B was estimated in terms of LDH, MTT, ROS activity, ROS-related 8-OHdG, and FJ-C, which suggests that amorfrutin B promotes mitochondrial integrity and is capable of inhibiting ROS activity and ROS-mediated DNA damage to prevent hypoxia- and ischemia-induced neural degeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Amorfrutin B is a plant-derived compound that belongs to SPPARγMs first isolated from the edible parts of legumes Glycyrrhiza foetida and Amorpha fruticosa [ 13 ]. Amorfrutin B has a PPARγ-binding affinity similar to that of the standard PPARγ-targeting drug rosiglitazone, and it can cross the blood–brain barrier and accumulate in brain tissue [ 14 , 15 ]. Unlike TZDs, amorfrutin B treatment showed liver-protecting properties, did not induce weight gain, and had no adverse effects on osteoblastogenesis or fluid retention.…”

Section: Introductionmentioning

confidence: 99%

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Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia

et al. 2021

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In this study, we demonstrate for the first time that amorfrutin B, a selective modulator of peroxisome proliferator-activated receptor gamma—PPARγ, can protect brain neurons from hypoxia- and ischemia-induced degeneration when applied at 6 h post-treatment in primary cultures. The neuroprotective effect of amorfrutin B suggests that it promotes mitochondrial integrity and is capable of inhibiting reactive oxygen species—ROS activity and ROS-mediated DNA damage. PPARγ antagonist and Pparg mRNA silencing abolished the neuroprotective effect of amorfrutin B, which points to agonistic action of the compound on the respective receptor. Interestingly, amorfrutin B stimulated the methylation of the Pparg gene, both during hypoxia and ischemia. Amorfrutin B also increased the protein level of PPARγ during hypoxia but decreased the mRNA and protein levels of PPARγ during ischemia. Under ischemic conditions, amorfrutin B-evoked hypermethylation of the Pparg gene is in line with the decrease in the mRNA and protein expression of PPARγ. However, under hypoxic conditions, amorfrutin B-dependent hypermethylation of the Pparg gene does not explain the amorfrutin B-dependent increase in receptor protein expression, which suggests other regulatory mechanisms. Other epigenetic parameters, such as HAT and/or sirtuins activities, were affected by amorfrutin B under hypoxic and ischemic conditions. These properties position the compound among the most promising anti-stroke and wide-window therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia

et al. 2021

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“…Among many compounds, amorfrutin B has the lowest binding affinity constant ( K i ) to purified PPARγ, which makes this compound the most selective and potent SPPARγM [ 22 ]. Moreover, amorfrutin B is a highly lipophilic molecule that crosses the blood–brain barrier (BBB) and accumulates in brain tissue, which is a desirable feature of potential drugs directed against diseases of the central nervous system [ 23 ]. Despite the aforementioned studies, little is known about the potential of amorfrutin B in the treatment of neural degeneration caused by hypoxia and ischemia.…”

Section: Introductionmentioning

confidence: 99%

Amorfrutin B Protects Mouse Brain Neurons from Hypoxia/Ischemia by Inhibiting Apoptosis and Autophagy Processes Through Gene Methylation- and miRNA-Dependent Regulation

et al. 2022

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Amorfrutin B is a selective modulator of the PPARγ receptor, which has recently been identified as an effective neuroprotective compound that protects brain neurons from hypoxic and ischemic damage. Our study demonstrated for the first time that a 6-h delayed post-treatment with amorfrutin B prevented hypoxia/ischemia-induced neuronal apoptosis in terms of the loss of mitochondrial membrane potential, heterochromatin foci formation, and expression of specific genes and proteins. The expression of all studied apoptosis-related factors was decreased in response to amorfrutin B, both during hypoxia and ischemia, except for the expression of anti-apoptotic BCL2, which was increased. After post-treatment with amorfrutin B, the methylation rate of the pro-apoptotic Bax gene was inversely correlated with the protein level, which explained the decrease in the BAX/BCL2 ratio as a result of Bax hypermethylation. The mechanisms of the protective action of amorfrutin B also involved the inhibition of autophagy, as evidenced by diminished autophagolysosome formation and the loss of neuroprotective properties of amorfrutin B after the silencing of Becn1 and/or Atg7. Although post-treatment with amorfrutin B reduced the expression levels of Becn1, Nup62, and Ambra1 during hypoxia, it stimulated Atg5 and the protein levels of MAP1LC3B and AMBRA1 during ischemia, supporting the ambiguous role of autophagy in the development of brain pathologies. Furthermore, amorfrutin B affected the expression levels of apoptosis-focused and autophagy-related miRNAs, and many of these miRNAs were oppositely regulated by amorfrutin B and hypoxia/ischemia. The results strongly support the position of amorfrutin B among the most promising anti-stroke and wide-window therapeutics.

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PEG-PCL modification and intestinal sustained-release of solid lipid nanoparticles for improving oral bioavailability of 2-methoxyestradiol

Xing

Liu

et al. 2018

Journal of Liposome Research

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PEG modification of Amorfrutin B from Amorpha fructicosa increases gastric absorption, circulation half-life and glucose uptake by T3T-L1 adipocytes

Cited by 4 publications

References 53 publications

Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia

Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia

Amorfrutin B Protects Mouse Brain Neurons from Hypoxia/Ischemia by Inhibiting Apoptosis and Autophagy Processes Through Gene Methylation- and miRNA-Dependent Regulation

PEG-PCL modification and intestinal sustained-release of solid lipid nanoparticles for improving oral bioavailability of 2-methoxyestradiol

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