Blood-brain barrier permeability study of ginger constituents

Simon, Alexandra; Darcsi, András; Kéry, Ágnes; Riethmüller, Eszter

doi:10.1016/j.jpba.2019.112820

Cited by 47 publications

(48 citation statements)

References 16 publications

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“…Since ginger extract constituents, including 6-GIN, have the ability to pass the blood–brain barrier [ 19 ], we postulated that they might modulate central nervous system functions. Moreover, their beneficial effects were previously reported in Parkinson’s disease, Alzheimer’s disease [ 48 , 49 , 50 , 51 ], depression [ 52 , 53 ], stress [ 54 ], and anxiety [ 55 , 56 ] in animal models.…”

Section: Discussionmentioning

confidence: 99%

“…The aforementioned pharmacological effects of the plant are mainly related to the presence of terpenes and phenolic acid derivatives in its oleoresin. The latter components, called gingerols and shogaols, which are responsible for the pungent taste of the rhizome, were recently proven to cross the blood–brain barrier [ 19 ] and exhibit central activity that includes the monoamine oxidase A (MAO-A) inhibition [ 20 ], migraine relief [ 21 ], dendritic cell activity amelioration [ 22 ], and neuroprotective action [ 23 ]. Previously, Zingiber officinale hydroethanolic extract was shown to exert antiseizure activity in the acute intravenous PTZ test and PTZ-kindling model in mice, but active constituents responsible for this effect have not been determined [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish

Gaweł

Kukuła-Koch

Banono

et al. 2021

IJMS

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Zingiber officinale is one of the most frequently used medicinal herbs in Asia. Using rodent seizure models, it was previously shown that Zingiber officinale hydroethanolic extract exerts antiseizure activity, but the active constituents responsible for this effect have not been determined. In this paper, we demonstrated that Zingiber officinale methanolic extract exerts anticonvulsant activity in the pentylenetetrazole (PTZ)-induced hyperlocomotion assay in larval zebrafish. Next, we isolated 6-gingerol (6-GIN)—a major constituent of Zingiber officinale rhizoma. We observed that 6-GIN exerted potent dose-dependent anticonvulsant activity in the PTZ-induced hyperlocomotion seizure assay in zebrafish, which was confirmed electroencephalographically. To obtain further insight into the molecular mechanisms of 6-GIN antiseizure activity, we assessed the concentration of two neurotransmitters in zebrafish, i.e., inhibitory γ-aminobutyric acid (GABA) and excitatory glutamic acid (GLU), and their ratio after exposure to acute PTZ dose. Here, 6-GIN decreased GLU level and reduced the GLU/GABA ratio in PTZ-treated fish compared with only PTZ-bathed fish. This activity was associated with the decrease in grin2b, but not gabra1a, grin1a, gria1a, gria2a, and gria3b expression in PTZ-treated fish. Molecular docking to the human NR2B-containing N-methyl-D-aspartate (NMDA) receptor suggests that 6-GIN might act as an inhibitor and interact with the amino terminal domain, the glutamate-binding site, as well as within the ion channel of the NR2B-containing NMDA receptor. In summary, our study reveals, for the first time, the anticonvulsant activity of 6-GIN. We suggest that this effect might at least be partially mediated by restoring the balance between GABA and GLU in the epileptic brain; however, more studies are needed to prove our hypothesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish

Gaweł

Kukuła-Koch

Banono

et al. 2021

IJMS

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“…The first is a BBB cellular kit, consisting of co-cultures of endothelial cells, pericytes, and astrocytes (Pervin et al, 2017). The second is a "parallel artificial membrane permeability assay" (PAMPA), which determines the permeability of substances from a donor compartment, through a membrane into an acceptor compartment (Simon et al, 2020). Some natural compounds were instead tested in vivo, administrating the compounds to mice through intraperitoneal or intra venous injection, and by oral administration.…”

Section: Ability Of Inhibitors To Cross Blood Brain Barrier and Stratmentioning

confidence: 99%

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

Pagano¹,

Tomaselli²,

Molinari³

et al. 2020

Front. Neurosci.

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Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, with no cure and preventive therapy. Misfolding and extracellular aggregation of Amyloid-β (Aβ) peptides are recognized as the main cause of AD progression, leading to the formation of toxic Aβ oligomers and to the deposition of β-amyloid plaques in the brain, representing the hallmarks of AD. Given the urgent need to provide alternative therapies, natural products serve as vital resources for novel drugs. In recent years, several natural compounds with different chemical structures, such as polyphenols, alkaloids, terpenes, flavonoids, tannins, saponins and vitamins from plants have received attention for their role against the neurodegenerative pathological processes. However, only for a small subset of them experimental evidences are provided on their mechanism of action. This review focuses on those natural compounds shown to interfere with Aβ aggregation by direct interaction with Aβ peptide and whose inhibitory mechanism has been investigated by means of biophysical and structural biology experimental approaches. In few cases, the combination of approaches offering a macroscopic characterization of the oligomers, such as TEM, AFM, fluorescence, together with high-resolution methods could shed light on the complex mechanism of inhibition. In particular, solution NMR spectroscopy, through peptide-based and ligand-based observation, was successfully employed to investigate the interactions of the natural compounds with both soluble NMR-visible (monomer and low molecular weight oligomers) and NMR-invisible (high molecular weight oligomers and protofibrils) species. The molecular determinants of the interaction of promising natural compounds are here compared to infer the chemical requirements of the inhibitors and the common mechanisms of inhibition. Most of the data converge to indicate that the Aβ regions relevant to perturb the aggregation cascade and regulate the toxicity of the stabilized oligomers, are the N-term and β1 region. The ability of the natural aggregation inhibitors to cross the brain blood barrier, together with the tactics to improve their low bioavailability are discussed. The analysis of the data ensemble can provide a rationale for the selection of natural compounds as molecular scaffolds for the design of new therapeutic strategies against the progression of early and late stages of AD.

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“…6-Gingerol is a key phytochemical of Zingiber officinale. Among the identified phytochemicals, it has been reported that decursin, aconitine, and 6-gingerol, can be delivered across the BBB [62][63][64]. Accumulating evidence suggests that phytochemicals can affect the central nervous system by crossing the BBB.…”

Section: Discussionmentioning

confidence: 99%

JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

Lee

et al. 2021

IJMS

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Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

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Blood-brain barrier permeability study of ginger constituents

Cited by 47 publications

References 16 publications

6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish

6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

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