Rhynchophylline Loaded-mPEG-PLGA Nanoparticles Coated with Tween-80 for Preliminary Study in Alzheimer's Disease.

PURPOSE: Alzheimer's disease (AD) is a growing concern in the modern society. The current drugs approved by FDA are not very promising. Rhynchophylline (RIN) is a major active tetracyclic oxindole alkaloid stem from traditional Chinese medicine uncaria species, which has potential activities beneficial for the treatment of AD. However, the application of rhynchophylline for AD treatment is restricted by the low water solubility, low concentration in brain tissue and low bioavailability. And there is no study of brain-targeting therapy with RIN. In this work, we prepared rhynchophylline loaded methoxy poly (ethylene glycol)-poly (dl-lactide-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPS-RIN), which coupled with Tween 80 (T80) further for brain targeting delivery (T80-NPS-RIN). METHODS: Preparation and characterization of T80-NPS-RIN were followed by the detection of transportation across the blood-brain barrier (BBB) model in vitro, biodistribution and neuroprotective effects of nanoparticles. RESULTS: The results indicated T80-NPS-RIN could usefully assist RIN to pass through the BBB to the brain. T80-NPS-RIN treatment regulated the activity of neurons in vitro. CONCLUSION: The presented data confirmed that rhynchophylline encapsulated mPEG-PLGA nanoparticles coated with Tween 80 could across through the BBB and exhibited efficient neuroprotective effects. The T80-NPS-RIN nanoparticles have a chance to be an alternative drug to the therapy of AD.

Rhynchophylline attenuates migraine in trigeminal nucleus caudalis in nitroglycerin-induced rat model by inhibiting MAPK/NF-кB signaling.

Migraine causes severe health and social issues worldwide. Rhynchophylline (Rhy) is one of the major active components of Uncaria rhynchophylla that is used for the treatment of headache in Traditional Chinese Medicine. In the current study, the effect of Rhy on nitroglycerin (NTG)-induced migraine was assessed and the associated mechanism was also explored to explain its function. Rats were pre-treated with Rhy of two doses (10 mg/kg and 30 mg/kg) and then subjected to NTG to induce migraine symptoms. Thereafter, the electroencephalogram (EEG) signaling, spontaneous behaviors, levels of indicators related to oxidative stress, and expression of calcitonin gene-related peptide (CGRP) were measured to assess the anti-migraine function of Rhy. Moreover, the activities of MAPK/NF-κB pathway under the administrations of Rhy were also detected. The results showed that NTG induced EEG and behavior disorders in rats, which was associated with the initiation of oxidative stress and increased expression of CGRP. Nevertheless, the pre-treatments with Rhy attenuated the damages induced by NTG by reversing the levels of all the above indicators. The results of western blotting demonstrated that the anti-migraine effect of Rhy was accompanied by the inhibition of MAPK/NF-кB pathway. The findings outlined in the current study revealed an alternative mechanism of Rhy in protecting brain tissues against migraine: the agent exerted its effect by suppressing MAPK/NF-кB pathway, which would ameliorate impairments associated with migraine.

Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-κB pathways.

The aim of this study was designed to investigate the effects of rhynchophyllin (RH) on neuroinflammation in Tourette syndrome (TS) rats. TS model was established in rats by the injection of selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior in DOI-induced rats was tested. Inflammatory cytokines levels such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The expression levels of janus kinase 2 (JAK2)/signal transducer and transcription activator 3 (STAT3) and nuclear factor (NF)-κB pathways in striatum were measured by Western blot. Data indicated that RH can significantly reduce the numbers of nodding experiment of TS rats. RH significantly decreased IL-6, IL-1ß, and TNF-α in serum and striatum of TS rats, with altered expression of P-JAK2, P-STAT3, P-NF-κBp65, and P-IκBα in TS rats, as evidenced by Western blot analysis and immunohistochemistry, suggesting that the regulation of JAK2/STAT3 and NF-κB pathways might be involved in the mechanism of RH on TS.