Rhynchophylline downregulates phosphorylated camp response element binding protein, nuclear receptor-related-1, and brain-derived neurotrophic factor expression in the hippocampus of ketamine-induced conditioned place preference rats

Guo, Youli; Luo, Chaohua; Tu, Genghong; Li, Chan; Liu, Yi; Liu, Wei; Yung, Kin Lam; Mo, Zhixian

doi:10.4103/pm.pm_90_17

Cited by 12 publications

(10 citation statements)

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“…In a rat model of epilepsy, kainic acid was found to increase BDNF protein in the cerebral cortex and hippocampus, which was attenuated by Rhy or Uncaria [ 85 ]. Similarly, ketamine-addicted rats were shown to have an increased expression of BDNF in the hippocampus, which was diminished by Rhy [ 21 , 92 ]. Rhy was also observed to reduce the levels of extracellular and intracellular BDNF in human bone marrow mesenchymal cells [ 78 ].…”

Section: Rhy Targets and Links To Sleep Regulationmentioning

confidence: 99%

“…CREB is activated by neuronal activity and acts downstream of numerous other pathways including NMDAR and PI3K/AKT [ 164 , 166 , 187 , 188 ] ( Figure 2 ). Rhy was shown to reduce p-CREB positive cells in the striatum and hippocampus in rats with meth and ketamine-dependent p-CREB increase [ 21 , 90 , 92 ]. Rhy was also found to rescue the meth-induced decrease in the number of c-fos positive cells in the striatum and CA1, which was suggested to depend on CREB [ 90 ].…”

Section: Rhy Targets and Links To Sleep Regulationmentioning

confidence: 99%

“…Although there is no clinical trial investigating the effects of Rhy alone, animal research suggests that Rhy has beneficial properties such as anti-inflammatory, antihypertensive, anti-arrhythmic, anticonvulsant and neuroprotective effects [ 3 , 10 ]. Moreover, it seems to reduce memory impairments, mood dysregulation, and addictive behaviors in rodents [ 17 , 18 , 19 , 20 , 21 ]. Interestingly, one study [ 22 ] and recent unpublished data from our group point to an effect of Rhy on sleep in rodents, which is in line with the beneficial effects of Chotoko and YKS on human sleep time and quality (see details in Section 1.3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Attenuates amph-induced ↑ in CPP, glutamic acid, DA, and NE Attenuates amph-induced ↓ in GABA, endorphin, and ACh[91] Attenuates ketamine-induced ↑ in CPP, Nr4a2 and Bdnf mRNAs, NURR1, BDNF, p-CREB (all hipp. )[21,92] Attenuates amph-induced ↑ in CPP and Grin2b mRNA, and GluN2B protein in mPFC and CA1[20] Attenuates meth-induced ↑ in CPP and GluN2B↓ brain infarction and neurological deficits in a stroke model In cerebral cortex: Accentuates ischemia-induced ↑ in p-AKT and p-mTOR Attenuates ischemia-induced ↑ in TLR2,4, MyD88, caspase 3, and nuclear NF-κB Attenuates stroke-induced ↓ in p-BAD, BDNF, Bdnf p-NF-κB p65, p-IkBα, TLR2, caspase1, MyD88, DA, D2R (in striatum) Attenuates DOI-induced ↓ in p-TrkB, BDNF (in striatum), and cell viability Rats [96,97] Attenuates asthma-induced ↑ in eosinophil recruitment, IL-13, IL-4, IL-5 in serum Attenuates asthma-induced ↑ TGFβ, Smad4, p-Smad2, p-Smad3, p-ERK1/2 and p-38 in lung tissue * Attenuates cardiac hypertrophy-induced ↑ in TGFβ1, cTGF, Collagen 1,3 , p-ERK, p-38, p-JNK, and attenuates the induced ↓ in SOD2 * ↑ NRF2 and accentuates the induced ↑ in SOD3 Mice [101]…”

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Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

et al. 2021

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Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhynchophylline (Rhy) is one of the principal alkaloids in Uncaria species. Although treatment with Rhy alone has not been tested in humans, observations in rodents show that Rhy increases sleep time. However, the mechanisms by which Rhy could modulate sleep have not been comprehensively described. In this review, we are highlighting cellular pathways that are shown to be targeted by Rhy and which are also known for their implications in the regulation of wakefulness and sleep. We conclude that Rhy can impact sleep through mechanisms involving ion channels, N-methyl-d-aspartate (NMDA) receptors, tyrosine kinase receptors, extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT), and nuclear factor-kappa B (NF-κB) pathways. In modulating multiple cellular responses, Rhy impacts neuronal communication in a way that could have substantial effects on sleep phenotypes. Thus, understanding the mechanisms of action of Rhy will have implications for sleep pharmacology.

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Section: Rhy Targets and Links To Sleep Regulationmentioning

confidence: 99%

Section: Rhy Targets and Links To Sleep Regulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

et al. 2021

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“…In the Gou-teng plant, Rhy attributes for 28–50% and IsoRhy for 14% and apart from the above major alkaloids, trace levels of akuammigine, hirsuteine, hirsutine, corynantheine, dihydrocorynantheine, isocorynoxeine, and geissoschizine methyl ether were also seen [ 12 , 13 ]. Rhy exhibited several pharmacological effects such as anti-rhythmic, anti-hypertensive, anti-addictive, anticonvulsant, sedative, anti-anxiety, and neuroprotective activities in different experimental models [ 14 , 15 , 16 , 17 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Anti-Inflammatory Activity of Plant-Derived Alkaloid Rhynchophylline in Neurological and Cardiovascular Diseases

Geetha

Ramachandran

2021

Pharmaceutics

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Rhynchophylline (Rhy) is a plant-derived indole alkaloid isolated from Uncaria species. Both the plant and the alkaloid possess numerous protective properties such as anti-inflammatory, neuroprotective, anti-hypertensive, anti-rhythmic, and sedative effects. Several studies support the significance of the anti-inflammatory activity of the plant as an underlying mechanism for most of the pharmacological activities of the alkaloid. Rhy is effective in protecting both the central nervous system and cardiovascular system. Cerebro-cardiovascular disease primarily occurs due to changes in lifestyle habits. Many previous studies have highlighted the significance of Rhy in modulating calcium channels and potassium channels, thereby protecting the brain from neurodegenerative diseases and related effects. Rhy also has anticoagulation and anti-platelet aggregation activity. Although Rhy has displayed its role in protecting the cardiovascular system, very little is explored about its intervention in early atherosclerosis. Extensive studies are required to understand the cardioprotective effects of Rhye. This review summarized and discussed the various pharmacological effects of Rhy in neuro- and cardioprotection and in particular the relevance of Rhy in preventing early atherosclerosis using Rhy-loaded nanoparticles.

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