Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism

Yuan, Dan; Ma, Bin; Yang, Jing; Xie, Yuan; Wang, Li; Zhang, Li Jia; Kano, Yoshihiro

doi:10.1016/j.intimp.2009.09.010

Cited by 102 publications

(63 citation statements)

References 38 publications

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“…Uncaria rhynchophylla has long been used in Chinese medicine and Japanese Kampo medicine to treat vascular dementia, stroke, and other neurodegenerative diseases (Yuan et al 2009). Isorhynchophylline, an oxindole alkaloid isolated from the stem with hooks of this plant, is easily absorbed into the body and readily penetrates the blood-brain barrier (Huang et al 2001), rendering it a promising therapeutic agent for the treatment of various neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Isorhynchophylline (the chemical structure shown in Fig. 1), an oxindole alkaloid isolated from Uncaria rhynchophylla, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Kang et al 2004;Yuan et al 2009). Recent studies have demonstrated that isorhynchophylline protects against the ischemia-and glutamate-induced neuronal damage or death (Shimada et al 1999;Kang et al 2004) and suppresses 5-HT receptor function (Kanatani et al 1985;Matsumoto et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Isorhynchophylline Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

et al. 2011

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Beta-amyloid peptide (Aβ), a major protein component of senile plaques, has been considered as a critical cause in the pathogenesis of Alzheimer's disease (AD). Modulation of the Aβ-induced neurotoxicity has emerged as a possible therapeutic approach to ameliorate the onset and progression of AD. The present study aimed to evaluate the protective effect of isorhynchophylline, an oxindole alkaloid isolated from a Chinese herb Uncaria rhynchophylla, on Aβ-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in Aβ(25-35)-treated PC12 cells. In addition, isorhynchophylline significantly suppressed the formation of DNA fragmentation and the activity of caspase-3 and moderated the ratio of Bcl-2/Bax. These results indicate that isorhynchophylline exerts a neuroprotective effect against Aβ(25-35)-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and suppressing the mitochondrial pathway of cellular apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective Effect of Isorhynchophylline Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

et al. 2011

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“…20 It confers neuron protective effects on ischemia-induced neuronal damage in the rat hippocampus, 21 suppresses 5-HT2A receptor function in the mouse brain, 22 inhibits Listeriolysin O-induced nitric oxide and endothelin-1 release in rat intestinal microvascular endothelial cells, 23 prevents angiotensin II-induced proliferation in rat vascular smooth muscle cells, 24 and suppresses lipopolysaccharide-induced inflammation in rat primary microglial cells. 25 These findings suggest that IsoRhy is a multifunctional compound with neuroprotective properties.…”

Section: Do Not Distributementioning

confidence: 93%

Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy

Lu¹,

Tan²,

Durairajan³

et al. 2012

Autophagy

157

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Accumulation of a-synuclein (a-syn) in the brain is a pathogenic feature and also a causative factor of Parkinson disease. Isorhynchophylline (IsoRhy) is a major tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.)Jacks (Gouteng in Chinese), which has been used for the treatment of neurological diseases in East Asia for centuries. Here we report a novel function of IsoRhy as a neuronal autophagy inducer. IsoRhy induced autophagy in different neuronal cell lines, including N2a, SH-SY5Y and PC12 cells, and also in primary cortical neurons. Furthermore, IsoRhy induced autophagy in the fat bodies of Drosophila. IsoRhy promoted clearance of wild-type, A53T and A30P a-syn monomers, a-syn oligomers and a-syn/synphilin-1 aggresomes in neuronal cells via the autophagy-lysosome pathway. More importantly, IsoRhy was able to decrease the expression levels of wild-type and A53T a-syn protein in differentiated human dopaminergic neurons. Notably, IsoRhy-induced autophagy was independent of the mTOR pathway but dependent on the function of Beclin 1. Taken together, data from this study raise the possibility that oxindole alkaloid derivatives may serve as a means to stimulate autophagy in neuronal cells, thereby exerting preventive and therapeutic values against neurodegenerative diseases such as Parkinson disease by reducing pathogenic protein aggregates in neurons.

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“…The usage of URE in treatment of Parkinson's induced rats revealed significant decrement in the levels ofIL-1β, IL-6 and TNF-α than control +ve group There is evidence suggesting the inhibitory function of rhynchophylline-type alkaloids of U. rhynchophylla in microglial activation in vitro [41]. Moreover, Rhynchophylline and isorhynchophylline have been shown to suppress the release of NO and proinflammatory cytokines [42]. Current data confirmed that URE has an anti-inflammatory effect on brain in vivo.…”

Section: Discussionmentioning

confidence: 98%

Anti-Parkinson’s Activity of Uncaria Rhynchophylla Extract on Rotenone Induced Parkinsonism Model in Male Albino Rats

2017

Dec. 25-26, 2017 Bangkok (Thailand) IETCAS-17, EABNS-2017, DBMCE-17, AHSCSR-17 &Amp; LEBL-17

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Present study investigated the curative effects of Uncaria rhynchophylla aqueous extract (URE) on v) S.c for 20 days. Group V, received S.c injection of rotenone (1.5 mg/kg/ 48h) in DMSO/saline 20% (w/v) interval for 20 days and gavaged URE 500 mg/kg daily for the left 15 days. Brain homogenate dopamine (DA), tyrosine hydroxylase (TH), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), Total oxidant status (TOS), nitric oxide (NO) and total antioxidant capacity (TAC) were estimated. URE exerts anti-Parkinson's activity via increasing DA, TH, and TAC as well as reducing TNF-α, IL1-β, IL-6, TOS and NO. URE possesses neurotherapeutic properties against Parkinson's disease.

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Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism

Cited by 102 publications

References 38 publications

Protective Effect of Isorhynchophylline Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

Protective Effect of Isorhynchophylline Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy

Anti-Parkinson’s Activity of Uncaria Rhynchophylla Extract on Rotenone Induced Parkinsonism Model in Male Albino Rats

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