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dc.contributor.authorTseng, Yu-Ting
dc.contributor.authorJong, Yuh-Jyh
dc.contributor.authorLiang, Wei-Fang
dc.contributor.authorChang, Fang-Rong
dc.contributor.authorLo, Yi-Ching
dc.date.accessioned2020-12-03T01:20:21Z
dc.date.available2020-12-03T01:20:21Z
dc.date.issued2017
dc.identifier.issn0944-7113en_US
dc.identifier.doi10.1016/j.phymed.2017.08.018en_US
dc.identifier.urihttp://hdl.handle.net/10072/399866
dc.description.abstractBackground: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease. Purpose: This study aimed to investigate the potential protection of LWDH-WE on SMN deficiency-induced neurodegeneration and muscle weakness. Study design: The effects of LWDH-WE on SMN deficiency-induced neurotoxicity and muscle atrophy were examined by using SMN-deficient NSC34 motor neuron-like cells and SMA-like mice, respectively. Methods: Inducible SMN-knockdown NSC34 motor neuron-like cells were used to mimic SMN-deficient condition. Doxycycline (1 µg/ml) was used to induce SMN deficiency in stable NSC34 cell line carrying SMN-specific shRNA. SMAΔ7 mice were used as a severe type of SMA mouse model. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Apoptotic cells and neurite length were observed by inverted microscope. Protein expressions were examined by western blots. Muscle strength of animals was evaluated by hind-limb suspension test. Results: LWDH-WE significantly increased SMN protein level, mitochondrial membrane potential and cell viability of SMN-deficient NSC34 cells. LWDH-WE attenuated SMN deficiency-induced down-regulation of B-cell lymphoma-2 (Bcl-2) and up-regulation of cytosolic cytochrome c and cleaved caspase-3. Moreover, LWDH-WE prevented SMN deficiency-induced inhibition of neurite outgrowth and activation of Ras homolog gene family, member A (RhoA)/ Rho-associated protein kinase (ROCK2)/ phospho-LIM kinase (p-LIMK)/ phospho-cofilin (p-cofilin) pathway. Furthermore, in SMA-like mice, LWDH-WE improved muscle strength and body weight accompanied with up-regulation of SMN protein in spinal cord, brain, and gastrocnemius muscle tissues. Conclusion: The present study demonstrated that LWDH-WE protects motor neurons against SMN deficiency-induced neurodegeneration, and it also improves the muscle strength of SMA-like mice, suggesting the potential benefits of LWDH-WE as a complementary prescription for SMN deficiency-related diseases.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom97en_US
dc.relation.ispartofpageto105en_US
dc.relation.ispartofjournalPhytomedicineen_US
dc.relation.ispartofvolume34en_US
dc.subject.fieldofresearchPlant Biologyen_US
dc.subject.fieldofresearchComplementary and Alternative Medicineen_US
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciencesen_US
dc.subject.fieldofresearchcode0607en_US
dc.subject.fieldofresearchcode1104en_US
dc.subject.fieldofresearchcode1115en_US
dc.titleThe water extract of Liuwei dihuang possesses multi-protective properties on neurons and muscle tissue against deficiency of survival motor neuron proteinen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationTseng, Y-T; Jong, Y-J; Liang, W-F; Chang, F-R; Lo, Y-C, The water extract of Liuwei dihuang possesses multi-protective properties on neurons and muscle tissue against deficiency of survival motor neuron protein, Phytomedicine, 2017, 34, pp. 97-105en_US
dc.date.updated2020-12-02T23:23:19Z
gro.hasfulltextNo Full Text
gro.griffith.authorTseng, Tammy


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