Neuroprotective Effects of Baicalein, Wogonin, and Oroxylin A on Amyloid Beta-Induced Toxicity via NF-κB/MAPK Pathway Modulation

Ji, Yeongseon; Han, Jin; Lee, Nayoung; Yoon, Ju-Duk; Youn, Kumju; Ha, Hyun Joo; Yoon, Eunju; Kim, Dong Hyun; Jun, Mira

doi:10.3390/molecules25215087

Cited by 39 publications

(22 citation statements)

References 37 publications

(38 reference statements)

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“…Thus, evidence from in vitro studies showed increased oxidative stress-mediated by NF-kB in response to neurons exposed to Aβ; this increased oxidative stress resulted in the accumulation of lipid peroxides and neurodegeneration [ 92 ]. Moreover, many studies confirm that Aβ peptides stimulate NF-kB gene expression and its nuclear translocation [ 93 , 94 , 95 ].…”

Section: Aβ Vs Oxidative Stressmentioning

confidence: 99%

Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

et al. 2021

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The pathogenesis of Alzheimer’s disease involves β amyloid (Aβ) accumulation known to induce synaptic dysfunction and neurodegeneration. The brain’s vulnerability to oxidative stress (OS) is considered a crucial detrimental factor in Alzheimer’s disease. OS and Aβ are linked to each other because Aβ induces OS, and OS increases the Aβ deposition. Thus, the answer to the question “which comes first: the chicken or the egg?” remains extremely difficult. In any case, the evidence for the primary occurrence of oxidative stress in AD is attractive. Thus, evidence indicates that a long period of gradual oxidative damage accumulation precedes and results in the appearance of clinical and pathological AD symptoms, including Aβ deposition, neurofibrillary tangle formation, metabolic dysfunction, and cognitive decline. Moreover, oxidative stress plays a crucial role in the pathogenesis of many risk factors for AD. Alzheimer’s disease begins many years before its symptoms, and antioxidant treatment can be an important therapeutic target for attacking the disease.

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Section: Aβ Vs Oxidative Stressmentioning

confidence: 99%

Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

et al. 2021

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“…Previous studies suggested that PDE2A and PDE4 expression was increased in brains of patients with AD and mouse models of AD, indicating that their involvement in AD pathology ( Nabavi et al, 2019 ; Tibbo et al, 2019 ). Recent studies suggest that baicalein prevents Aβ-induced memory deficits by attenuating inflammatory response and neuronal apoptosis ( Acquarone et al, 2019 ; Ji et al, 2020 ). However, whether the effects of baicalein on AD-related memory deficits are involved in regulation of PDE subtypes and the downstream signaling pathway remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

Shi

Zhang

et al. 2021

Front. Pharmacol.

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Inhibition of phosphodiesterase 2 and 4 (PDE2A and PDE4) increases the intracellular cAMP and/or cGMP levels, which may prevent Amyloid β 42 oligomers (Aβ) related cognitive impairment and dementias. Baicalein, one of natural flavones found in the root of Scutellaria baicalensis Georgi, has a wide range of pharmacological activities including antioxidant and anti-inflammatory effects. However, no studies suggest whether baicalein mediated anti-Alzheimer’s disease (AD) events involve PDEs subtypes-mediated neuroprotective pathways. The present study examined whether memory enhancing effects of baicalein on Aβ- induced cognitive impairment are related to regulating neuroplasticity via PDE2 and PDE4 subtypes dependent cAMP/cGMP neuroprotective pathway. The results suggested that microinjected of Aβ into CA1 of hippocampus induced cognitive and memory impairment in mice, as evidenced by decreased recognition index in the novel object recognition (NOR) task, impaired memory acquisition, retention and retrieval in the Morris water maze (MWM) and shuttle box tests. These effects were reversed by treatment with baicalein for 14 days. Moreover, Aβ-induced neuronal atrophy and decreased expression of two synaptic proteins, synaptophysin and PSD 95, were prevented by baicalein. The increased expression of PDE2A and PDE4 subtypes (PDE4A, PDE4B and PDE4D), and decreased levels of cAMP/cGMP, pCREB/CREB and BDNF induced by Aβ were also blocked by chronic treatment of baicalein for 14 days. These findings suggest that baicalein’s reversal of Aβ-induced memory and cognitive disorder may involve the regulation of neuronal remodeling via regulation of PDE2/PDE4 subtypes related cAMP/cGMP -pCREB-BDNF pathway.

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“…In addition, a recent study showed that SB has potential therapeutic effects on coronavirus disease 2019 [ 26 ]. Moreover, baicalin and baicalein, which are the major bioactive compounds in SB, have demonstrated an important role in inhibiting the production of inflammatory cytokines [ 25 , 27 ], NF- κ B signalling [ 28 , 29 ], and c-fos expression [ 30 ] in multiple experimental models. These mechanisms are crucial in the pathophysiological processes of migraine.…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness of Scutellaria baicalensis on Migraine: Implications from Clinical Use and Experimental Proof

Liao

Lin

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Scutellaria baicalensis (SB), a traditional Chinese medicine, is commonly used for the treatment of inflammatory and painful conditions. The purpose of the present study was to examine the effects of SB on migraine. Materials and Methods. We examined the clinical applications of SB based on the data obtained from Taiwan’s National Health Insurance Research Database and confirmed that it was frequently used in Taiwan for the treatment of headaches. An experimental migraine model was established in rats by an intraperitoneal injection of nitroglycerin (NTG, 10 mg/kg). Pretreatment with SB was given orally 30 min before NTG administration. The rats were subjected to migraine-related behaviour tests that were video-recorded and analysed using EthoVision XT 12.0 software. Results. The frequency of exploratory and locomotor behaviour was comparatively lower in the NTG group than that in the control group, while the frequency of resting and grooming behaviour increased. These phenomena were ameliorated by pretreatment with 1.0 g/kg SB. The total time spent on the smooth surface was longer in the NTG group than that in the control group, but the time was shortened by pretreatment with 1.0 g/kg SB. Conclusions. Pretreatment with 1.0 g/kg SB relieved migraine-related behaviours in the experimental NTG-induced migraine model. The outcome therefore demonstrated that pretreatment with 1.0 g/kg SB is beneficial for migraine treatment.

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Neuroprotective Effects of Baicalein, Wogonin, and Oroxylin A on Amyloid Beta-Induced Toxicity via NF-κB/MAPK Pathway Modulation

Cited by 39 publications

References 37 publications

Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

The Effectiveness of Scutellaria baicalensis on Migraine: Implications from Clinical Use and Experimental Proof

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