Aquaporins as Targets of Dietary Bioactive Phytocompounds

Tesse, Angela; Grossini, Elena; Tamma, Grazia; Brenner, Catherine; Portincasa, Piero; Marinelli, Raúl A.; Calamita, Giuseppe

doi:10.3389/fmolb.2018.00030

Cited by 41 publications

(36 citation statements)

References 113 publications

(135 reference statements)

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“…Recent pharmacological studies indicate that the diuretic effect of drugs depends not only on the activity of ion channels that transport sodium and potassium but also on aquaporins that mediate water transport across cell membranes [12]. Aquaporins (AQPs) were identified as novel target molecule that might explain the efficacy of diuretic traditional Chinese medicines, which was confirmed by a number of quantitative studies on the diuretic effects of AQPs [13,14]. AQPs are intrinsic membrane proteins that are located in the cell membrane and control the ingress and egress of water between cells [15].…”

Section: Discussionmentioning

confidence: 95%

Corallodiscus flabellata B.L. Burtt Extracts Stimulate Diuretic Activity and Regulate the Renal Expression of Aquaporins

Kan

Zeng

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Corallodiscus flabellata B. L. Burtt is a traditional Chinese medicine. Previous studies in our laboratory showed that C. flabellata alleviated symptoms of Alzheimer’s disease (AD) in a rat model of AD and increased healthy rats’ urine volume. The aims of this study were to explore the diuretic activity of different extracts from C. flabellata and to identify the underlying mechanisms of action. Different doses of a C. flabellata extract (CF-L, CF-M, and CF-H) were administered orally to male KM mice in a single dose. In another procedure, C. flabellata (CF), water extract, and 20%, 30%, and 40% ethanol extracts of C. flabellata (CF-WE, CF-20, CF-30, and CF-40) were administered orally daily for 5 days. The urinary excretion rate, osmolality, and electrolyte levels in urine and serum, renal expression of aquaporins (AQPs), apoptosis-related protein, and MAPK-related protein were analyzed. The results showed that single doses of CF-M and CF-H increased urinary volume significantly, as well as daily administration of CF, CF-WE, CF-20, CF-30, and CF-40. Furthermore, CF-20 and CF-30 increased the concentration of Na+ in the urine. Treatment with CF-40 increased the urine osmolality and Na+ and Cl− concentrations and decreased the concentration of Na+ in the serum. Also, CF, CF-WE, CF-20, CF-30, and CF-40 decreased the renal expression of AQPs, as well as the ratios of Bcl-2/Bax, p-ERK/ERK, p-JNK/JNK, and p-p38/p38. In sum, the medium and high doses of the C. flabellata extract and CF-WE, CF-20, CF-30, and CF-40 were found to have a diuretic activity. They may inhibit the renal expression of AQPs and apoptosis-related proteins by inhibiting the MAPK signaling pathway, thereby achieving diuretic effects.

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Section: Discussionmentioning

confidence: 95%

Corallodiscus flabellata B.L. Burtt Extracts Stimulate Diuretic Activity and Regulate the Renal Expression of Aquaporins

Kan

Zeng

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…MR309, a Sigma-1 antagonist is currently in Phase II clinical trial for the treatment of neuropathic pain) [31,49,50]. On the other hand, aquaporins are still largely unexplored from a medicinal chemistry standpoint and have been recognized as druggable molecular targets only recently [17,[51][52][53][54][55]. To the best of our knowledge, this represents the first report involving modulators of both AQP and S1R.…”

Section: Discussionmentioning

confidence: 90%

Dual Aquaporin and Sigma1 Receptor (DAS) Modulators: New Tools for Counteracting Oxidative Stress

Pellavio¹,

Rossino²,

Gastaldi³

et al. 2020

Preprint

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Specific aquaporins (AQP), called peroxyporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasting during oxidative stress. Another target involved in oxidative stress is the Sigma1 Receptor (S1R), since its activation is triggered by oxidative or endoplasmic reticulum stress. Herein we evaluated the effect of S1R modulators on AQP-dependent water permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in Hela cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. All compounds except one were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together, our results support the hypothesis that the investigated compounds act as dual aquaporin and Sigma1 receptor (DAS) modulators. The finding that small molecules can modulate both AQP and S1R opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, like cancer and degenerative diseases.

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“…Aquaporins have been studied extensively in the recent years in terms of their structures, unique functions, and potential applications in various separations . The highly selective nature of aquaporins toward water and their ability to allow water molecules pass through them at a very high permeability value have given rise to new research directions in clinical and biotechnological research , physiological research , membrane materials and synthesis of biomimetic membranes .…”

Section: Fabrication Of Aquaporin‐based Membranesmentioning

confidence: 99%

Biomimetic and bioinspired membranes for water purification: A critical review and future directions

Wagh

Escobar

2019

Env Prog and Sustain Energy

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Various types of channel proteins, broadly named porins, present in the cell membrane of gram‐negative bacteria have specific functionalities depending on their selectivity toward different nutrients or toward water. The high selectivity of porins has led to their incorporation into synthetic systems, in a field called biomimetics. An example is the addition of water channel proteins, or aquaporins, to polymeric separations membranes in order to enhance their performance in terms of selectivity and permeability. The concept of incorporating aquaporins into synthetic membranes has been studied for the last 10 years; however, there are still limitations such as costs, alignment into the membrane assembly, and scalability of membrane fabrication. Therefore, in recent years, there has been an increase in the study of synthesizing molecules with similar structure–function relationships of porins. These artificial channels attempt to mimic the biological porins, while being synthesized using simpler chemistry, being solvent compatible, and requiring less space on the membrane surface which helps to incorporate more channels into the membrane assembly. In summary, the future of biomimetic and bioinspired membranes depends on the design strategies, level of nature imitation, and the performance of these systems on a commercial scale. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13215, 2019

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Aquaporins as Targets of Dietary Bioactive Phytocompounds

Cited by 41 publications

References 113 publications

Corallodiscus flabellata B.L. Burtt Extracts Stimulate Diuretic Activity and Regulate the Renal Expression of Aquaporins

Corallodiscus flabellata B.L. Burtt Extracts Stimulate Diuretic Activity and Regulate the Renal Expression of Aquaporins

Dual Aquaporin and Sigma1 Receptor (DAS) Modulators: New Tools for Counteracting Oxidative Stress

Biomimetic and bioinspired membranes for water purification: A critical review and future directions

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