Schisantherin A protects against 6-OHDA-induced dopaminergic neuron damage in zebrafish and cytotoxicity in SH-SY5Y cells through the ROS/NO and AKT/GSK3β pathways

Zhang, Lun Qing; Sa, Fei; Chong, Cheong Meng; Wang, Ying; Zhou, Zhong Yan; Chang, Raymond Chuen‐Chung; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming‐Yuen

doi:10.1016/j.jep.2015.04.040

Cited by 63 publications

(38 citation statements)

References 34 publications

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“…In our previous studies, all our in vitro and in vivo data indicated StA's promising anti-PD activity, but further development of StA was required to address the problem of its poor bioavailability. The high dose of StA, at 300 mg/kg, exhibited significant and comparable effectiveness to 10 mg/kg of the anti-PD drug selegiline in our previous PD mice study [ 9 , 10 ]. In terms of retaining MPTP-induced loss of TH-positive neurons of the SNpc in a PD mice study, the relatively lower potency of StA was probably because of the poor oral bioavailability of this compound.…”

Section: Discussionmentioning

confidence: 86%

“…The neuroprotection of StA, a dibenzocyclooctadiene lignan from the fruit of Schisandra chinensis (Turcz.) Baill, against two neurotoxins 6-OHDA and MPP + was systematically investigated in our completed studies [ 9 , 10 ]. The pharmacokinetic study and optimal formulation of StA are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

“…StA is believed to have a wide variety of therapeutic effects including antihepatotoxic effects, anticarcinogenic effects, and antioxidant effects [ 6 – 8 ]. In our recent completed studies, we systematically investigated the capacity of five dibenzocyclooctadiene lignans (namely, schisandrin A, schisandrin B, schisandrin C, schizandrol A, and schisantherin A) to protect neuroblastoma SH-SY5Y cells from toxicity induced by 6-OHDA or MPP + [ 9 , 10 ]. Among the tested dibenzocyclooctadiene lignans, only StA significantly protected SH-SY5Y cells against 6-OHDA- or MPP + -induced cell death.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A

Guo

et al. 2015

Parkinson's Disease

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Our recent studies showed that schisantherin A (StA) is a promising candidate for PD treatment, but the pharmacokinetic profile of StA is largely unknown. The effects of different formulations on the pharmacokinetics and bioavailability of StA were investigated by HPLC equipped with a vacuum degasser, a quaternary pump, a manual sampler, and an ultraviolet detector. The absolute bioavailability of StA in nanoemulsion formulation was significantly increased from 4.3% to 47.3%. To the best of our knowledge, this is the first report of absolute bioavailability for StA in rats and successful increase of bioavailability of StA by nanoemulsion formulation. The pharmacokinetic profiles of StA could be significantly improved by a safe nanoemulsion formulation. This study provides a successful example of advanced delivery system for improving the bioavailability of potential central nervous system (CNS) drug candidate with poor solubility. This novel approach could be an effective alternative solution to overcome the shortcomings of conventional poor drug delivery of CNS drugs. The results of present study not only indicate that StA has potential to be developed as a promising oral therapeutic agent for the management of PD but also shed light on novel way to improve bioavailability of PD drugs.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A

Guo

et al. 2015

Parkinson's Disease

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“…36 Schisantherin A, schisandrin B, and schisandrin C from Fructus Schisandrae Chinensis attenuate abnormal oxidative stress and modulate the apoptotic signal pathway, exhibiting their neuroprotective function on neurodegenerative diseases. 37,38 β-asarone and eugenol, components of Rhizoma Acori Tatarinowii, have neuroprotective function cells through inhibiting apoptosis against Aβ- induced neurotoxicity. 39 Polygalae radix has neuroprotective effects against toxin-induced neuronal death through its antioxidant and antiapoptotic activities; 40 its ethanol extracts as a novel autophagy inducer modulate neurodegenerative disorders via reducing toxicity and clearing of mutant proteins in the cellular level.…”

Section: Discussionmentioning

confidence: 99%

Dihuang Yinzi, a Classical Chinese Herbal Prescription, for Amyotrophic Lateral Sclerosis

Qiu

Yin

et al. 2016

Medicine

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Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease with no effective treatment and death within 2 to 5 years after symptom onset. Here, we reported a case of ALS patient using modified Dihuang Yinzi (DHYZ), a classical traditional Chinese medicine (TCM) prescription, who has survived 12 years with significant improvement in bulbar paralysis.A 41-year-old Chinese Han nationality woman was admitted to the hospital with complaints of weakened bilateral grip, slurred speech, stumbling, and muscle twitching for 3 years. The electromyography showed neurogenic injury in bilateral upper limbs and tongue. She was diagnosed with ALS according to the revised El escorial criteria. The patient was orally administrated with Riluzole 100 mg daily for 10 months and then stopped. Subsequently, she resorted to TCM. Based on the TCM theory, the patient was diagnosed with Yinfei syndrome because of kidney deficiency. DHYZ was chosen because it has the function of replenishing kidney essence to treat Yinfei syndrome. Up to now, she has been using modified DHYZ continuously for 12 years. The patient survived with ALS and did not require permanent continuous ventilator. In addition, the symptoms of choking on liquids are improved, and the utility of 30 mL water swallow test was improved with grade 2. The symptoms of muscle fibrillations of limbs are also reduced. However, muscle strength worsened slowly. The repeated electromyography showed motor conduction amplitude reducing gradually and velocity not changing more when compared with the initial electromyography.Our findings suggested that DHYZ can be potentially used in ALS patients because of its multi-targeted neuroprotection and general safety, although ALS does not have a cure. In addition, we identified the area that is worthy of further study and DHYZ as a promising candidate for further clinical application and ALS trials. Rigorous randomized controlled trials are needed in the future.

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“…A group of investigators claimed that schisantherin A (a dibenzocyclooctadiene lignan) from Schisandra chinensis fruit protects against 6-hydroxydopamine (6-OHDA) (a PD model) induced dopaminergic neuronal damage in Zebrafish and cytotoxicity in SHSY5Y cells by regulating intracellular ROS accumulation and inhibiting NO production [128]. Weng et al, showed that 6 days daily intraperitonial injection of 10 mg/kg magnolol reversed the neuronal damage associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopaminergic neurotoxicity (the toxin which produces symptoms like PD) in male C57BL/6 mice [129].…”

Section: Lignans With Anti-pd Effectmentioning

confidence: 99%

A Mini Review on the Protective Effect of Lignans for the Treatment of Neurodegenerative Disorders

2019

NFLS

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Nature is a rich source of numerous bioactive compounds that are categorized as secondary metabolites. Lignans are group of such compounds, generally called phytoestrogens widely present in many plants and vegetables, grains, seeds, nuts and tea. They have been used as folk medicine for the treatment of several clinical conditions like asthma, cardiovascular diseases, arthrosclerosis, colitis and many more. Structurally, lignans are characterized by two phenylpropane groups attached by a carbon bond. They have been divided in to several types on the basis of structure of their carbon skeleton, the way of cyclization and oxygen incorporation in the skeleton. Lignans from numerous plant species such as Kadsura

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Schisantherin A protects against 6-OHDA-induced dopaminergic neuron damage in zebrafish and cytotoxicity in SH-SY5Y cells through the ROS/NO and AKT/GSK3β pathways

Cited by 63 publications

References 34 publications

Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A

Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A

Dihuang Yinzi, a Classical Chinese Herbal Prescription, for Amyotrophic Lateral Sclerosis

A Mini Review on the Protective Effect of Lignans for the Treatment of Neurodegenerative Disorders

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