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Park SJ, An SY, An YJ, Kim KS, Kim H, Cho JH, Lee YC. Promotion of neurite outgrowth by 3,5,7,3',4'-pentamethoxyflavone is mediated through ERK signaling pathway in Neuro2a cells. J Nat Med 2024; 78:599-607. [PMID: 38662302 DOI: 10.1007/s11418-024-01809-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 03/26/2024] [Indexed: 04/26/2024]
Abstract
In this study, the effects of 3,5,7,3',4'-pentamethoxyflavone (KP1), a major bioactive ingredient isolated from the Kaempferia parviflora rhizomes, on a neurite outgrowth in Neuro2a cells and its mechanism have been investigated. KP1 increased concentration-dependently the percentage of neurite-bearing cells. KP1 showed a remarkable capability to elicit neurite outgrowth in Neuro2a cells, as evidenced by morphological alterations and immunostaining using anti-class III β-tubulin and anti-NeuN antibodies. KP1 also displayed a higher neurogenic activity than retinoic acid (RA), a promoter of neurite outgrowth in Neuro2a cells. KP1 treatment caused significant elevation in phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and glycogen synthase kinase-3β (GSK-3β). However, KP1-triggered neurite outgrowth was markedly inhibited by treatment with the ERK inhibitor U0126, whereas p38 MAPK inhibitor SB203580 and GSK-3β inhibitor SB216763 did not influence KP1-induced neurite outgrowth. These results demonstrate that KP1 elicits neurite outgrowth and triggers cell differentiation of Neuro2a cells through ERK signal pathway.
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Affiliation(s)
- Shin-Ji Park
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea
| | - So-Young An
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea
| | - Yeon Jin An
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea
| | - Kyoung-Sook Kim
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea
| | - Hyunju Kim
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea
| | - Jong Hyun Cho
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea.
| | - Young-Choon Lee
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, South Korea.
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Bian LH, Yao ZW, Wang ZY, Wang XM, Li QY, Yang X, Li JY, Wei XJ, Wan GH, Wang YQ, Shi JL, Guo JY. Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways. Biomed Pharmacother 2022; 153:113269. [PMID: 35728354 DOI: 10.1016/j.biopha.2022.113269] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/04/2022] [Accepted: 06/06/2022] [Indexed: 11/02/2022] Open
Abstract
In a rotenone-induced Parkinson's disease (PD) rat model, behavioral investigation, pathological examination, inflammatory factor analysis, and mitochondrial structure and function investigation verified the anti-PD efficacy of nardosinone. A combined transcriptome and proteome analysis proposed that the anti-PD target of nardosinone is the slc38a2 gene and may involve the GABAergic synaptic pathway and cAMP-signaling pathway. Analysis of targeted slc38a2 knockout cells and expression of key enzyme-encoding genes in both pathways verified the target and pathways proposed by the 'omics analysis. This further confirms that nardosinone can regulate the slc38a2 gene, a potential new target for the treatment of Parkinson's disease, and plays an anti-PD role through the GABAergic synaptic and cAMP pathways.
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Affiliation(s)
- Li-Hua Bian
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China; University of Chinese Academy of Sciences, Beijing 100049, China.
| | - Zi-Wei Yao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Zhe-Yi Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China; Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
| | - Xiao-Mei Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Qiu-Yu Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Xue Yang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Jia-Yuan Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Xiao-Jia Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Guo-Hui Wan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Yu-Qing Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Jin-Li Shi
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.
| | - Jian-You Guo
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 4A DatunRoad, Chaoyang District, Beijing 100101, China.
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Wang M, Yang TT, Rao Y, Wang ZM, Dong X, Zhang LH, Han L, Zhang Y, Wang T, Zhu Y, Gao XM, Li TX, Wang HY, Xu YT, Wu HH. A review on traditional uses, phytochemistry, pharmacology, toxicology and the analytical methods of the genus Nardostachys. JOURNAL OF ETHNOPHARMACOLOGY 2021; 280:114446. [PMID: 34339792 DOI: 10.1016/j.jep.2021.114446] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/22/2021] [Accepted: 07/21/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The plants of the genus Nardostachys (Caprifoliaceae) have been used for a long history in different cultural systems of medicine, including Chinese, Ayurvedic, Korean folk medicine and Islamic, for treatments of disorders in nervous, digestive, cardiovascular and integumentary systems. AIM OF THE REVIEW This review aims to provide comprehensive information on Nardostachys plants including botany update, traditional uses, data mining of uses in traditional Chinese medicine (TCM) and current Chinese medicinal patents, chemical constituents, pharmacological effects, toxicity and analytical method studies. MATERIALS AND METHODS Studies of the genus Nardostachys were collected via Google Scholar and Baidu Scholar, ScienceDirect, SciFinder, Wiley Online Library, ACS Publications, NLM/NCBI, Web of Science, CNKI, WANFANG DATA, EMBASE, Huabeing database and Traditional Chinese Medicine Resource Network and libraries. Some local books, PhD or MS's dissertations were also included. The literatures cited in this review covered the period from 1962 to March 2021. The Plant List and Kew Herbarium Catalogue databases were used to authenticate the scientific name. RESULTS Botany description of Nardostachys genus is updated. Analysis of the literatures indicates that Nardostachys species are valuable herbs with therapeutic potentials for various disorders. Data mining on ancient TCM prescriptions and current Chinese medicinal patents containing Nardostachys revealed its common compatibility with other herbs in China. Phytochemical studies identified terpenoids and phenolic compounds as the main constituents in the genus Nardostachys and sesquiterpenoids as the major bioactive components. Experimental studies demonstrated that crude extracts, major fractions and the main constituents from Nardostachys species mainly exhibited pharmacological activities on nervous, digestive, cardiovascular and skin systems. Further, in vivo and in vitro toxicological studies demonstrated that Nardostachys plants showed either no or low toxicities, except at high doses. Finally, methods of qualitative and quantitative analyses on chemical constituents of genus Nardostachys were summarized, including TLC/HPTLC, GC and HPLC/UPLC methods, combined with common detectors including PDA, DAD and MS. CONCLUSIONS This review summarizes the progress on phytochemistry, pharmacology, toxicology and analytical methods of the genus Nardostachys. Studies demonstrate traditional uses of the genus Nardostachys, and reveal novel bioactive effects for clinical uses. These achievements expand our knowledge on the genus Nardostachys and its clinical value.
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Affiliation(s)
- Miao Wang
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Tian-Tian Yang
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Yao Rao
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Zhi-Mei Wang
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Xueqi Dong
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Li-Hua Zhang
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Lifeng Han
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Yi Zhang
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Tao Wang
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Yan Zhu
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Xiu-Mei Gao
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Tian-Xiang Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Hai-Ying Wang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China
| | - Yan-Tong Xu
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China; Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, PR China
| | - Hong-Hua Wu
- State Key Laboratory of Component-based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, PR China.
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Nardosinone Alleviates Parkinson's Disease Symptoms in Mice by Regulating Dopamine D2 Receptor. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6686965. [PMID: 34426745 PMCID: PMC8380167 DOI: 10.1155/2021/6686965] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 08/03/2021] [Indexed: 12/12/2022]
Abstract
Nardostachyos Radix et Rhizoma (nardostachys) is the root and rhizome of Nardostachys jatamansi DC. Recent studies have shown that nardostachys may exert an anti-PD effect. In this study, the UHPLC-LTQ-Orbitrap-MS method was used to analyze the brain components of nardostachys in rats. Based on the results of UHPLC-LTQ-Orbitrap-MS analysis, nardosinone was identified to be the most effective anti-PD compound in nardostachys. To further verify this inference, a mouse PD model was established and the effect of nardosinone on PD mice was determined using classic behavioral tests. The results showed that nardosinone was indeed effective for relieving PD symptoms in mice. Moreover, network pharmacology analysis was used to elucidate the mechanism underlying the anti-PD effect of nardosinone. Dopamine receptor D2 (DRD2) was identified as the key target of nardosinone-PD interaction network, which was further verified by molecular docking and Western blotting. The results demonstrated that nardosinone and DRD2 could interact with each other. Furthermore, the expression level of DRD2 was decreased in the brain tissue of PD mice, and nardosinone could restore its expression to a certain extent. In conclusion, our findings suggest that nardosinone may reduce the motor and cognitive symptoms in the animal PD model by regulating DRD2 expression.
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Maruoka H, Yamazoe R, Takahashi R, Yatsuo K, Ido D, Fuchigami Y, Hoshikawa F, Shimoke K. Molecular mechanism of nur77 gene expression and downstream target genes in the early stage of forskolin-induced differentiation in PC12 cells. Sci Rep 2020; 10:6325. [PMID: 32286359 PMCID: PMC7156746 DOI: 10.1038/s41598-020-62968-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 03/23/2020] [Indexed: 11/20/2022] Open
Abstract
Forskolin promotes neuronal differentiation of PC12 cells via the PKA-CREB-dependent signaling pathway. Activation of PKA by forskolin phosphorylates CREB, which then binds to CRE sites in numerous gene promoters. However, it is unclear which gene contains the CRE sites responsible for forskolin-induced neuronal differentiation. In this study, we investigated how an immediate early gene, nur77, which has CRE sites in the promoter region, contributes to the early stage of differentiation of forskolin-treated PC12 cells. After treatment with forskolin, expression of Nur77 was upregulated within 1 hr. In addition, knockdown of nur77 inhibited neurite outgrowth induced by forskolin. We also revealed that the specific four CRE sites near the transcriptional start site (TSS) of nur77 were strongly associated with phosphorylated CREB within 1 hr after treatment with forskolin. To analyze the roles of these four sites, reporter assays using the nur77 promoter region were performed. The results showed that nur77 expression was mediated through three of the CRE sites, -242, -222, and -78, and that -78, the nearest of the three to the TSS of nur77, was particularly important. An analysis of neuronal markers controlled by Nur77 after A-CREB-Nur77-Synapsin1 signaling pathway plays a pivotal role in differentiation of forskolin-induced PC12 cells.
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Affiliation(s)
- Hiroki Maruoka
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Ryosuke Yamazoe
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Ryota Takahashi
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Keisuke Yatsuo
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Daiki Ido
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Yuki Fuchigami
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Fumiya Hoshikawa
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan
| | - Koji Shimoke
- Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka, 564-8680, Japan.
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Sesamin Promotes Neurite Outgrowth under Insufficient Nerve Growth Factor Condition in PC12 Cells through ERK1/2 Pathway and SIRT1 Modulation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:9145458. [PMID: 32308720 PMCID: PMC7139881 DOI: 10.1155/2020/9145458] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/15/2020] [Accepted: 02/20/2020] [Indexed: 01/25/2023]
Abstract
The promotion of neurogenesis can be a promising strategy to improve and restore neuronal function in neurodegenerative diseases. Nerve growth factor (NGF) plays a key role in neurite outgrowth and synaptic formation during brain repair stage. Nowadays, there are several studies on the developing methods to enhance the endogenous NGF activity for treatment and restore the neuronal function. In this study, the potentiating effect of sesamin, a major lignan in sesame seeds (Sesamum indicum) and oil, on NGF-induced neurogenesis and its involved mechanisms were firstly reported. Sesamin effectively enhanced the PC12 neuron-like cell differentiation and neurite length under insufficient conditions of NGF. The neuronal markers including synaptophysin and growth-associated protein-43 along with the synaptic connections were significantly increased in combination treatment between sesamin and NGF. Moreover, sesamin also increased the level of phospho-ERK1/2 and SIRT1 protein, an important regulatory protein of the neurogenesis process. The neurogenesis was blocked by the specific SIRT1 inhibitor, JGB1741, suggesting that the neuritogenic effect of sesamin was associated with SIRT1 protein modulation. Taken together, the potentiating effect of sesamin on NGF-induced neurogenesis in this finding could be used for alternative treatment in neurodegenerative diseases, including Alzheimer's disease.
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Rehman T, Ahmad S. Nardostachys chinensis
Batalin: A review of traditional uses, phytochemistry, and pharmacology. Phytother Res 2019; 33:2622-2648. [DOI: 10.1002/ptr.6447] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 05/21/2019] [Accepted: 06/26/2019] [Indexed: 01/06/2023]
Affiliation(s)
- Tayyeba Rehman
- University College of Conventional Medicine, Faculty of Pharmacy and Alternative MedicineThe Islamia University of Bahawalpur Bahawalpur Pakistan
| | - Saeed Ahmad
- University College of Conventional Medicine, Faculty of Pharmacy and Alternative MedicineThe Islamia University of Bahawalpur Bahawalpur Pakistan
- Department of Pharmacy, Faculty of Pharmacy and Alternative MedicineThe Islamia University of Bahawalpur Bahawalpur Pakistan
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Le VNH, Khong TQ, Na MK, Kim KT, Kang JS. An optimized HPLC-UV method for quantitatively determining sesquiterpenes in Nardostachyos Radix et Rhizoma. J Pharm Biomed Anal 2017; 145:406-413. [PMID: 28728067 DOI: 10.1016/j.jpba.2017.06.041] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 06/09/2017] [Accepted: 06/17/2017] [Indexed: 11/24/2022]
Abstract
Nardostachyos Radix et Rhizoma (NR), the root and rhizome from either Nardostachys jatamansi Batal or Nardostachys jatamansi DC, is known to have biological functions including neuro-protective and anti-pancreatitis activity. The main bioactive compounds within NR are all classified as sesquiterpenes, and include desoxo-narchinol A, nardosinonediol, and nardosinone. Although NR is a valuable herb that is widely used in many Asian countries, robust quality control protocols for NR are still in question, especially those that can analyze the three main active compounds. Current quantitative methods within the Chinese Pharmacopoeic use nardosinone as a marker compounds. One compound cannot represent a complicated matrix, and is thus insufficient to control the quality of this herbal medicine. Moreover, there are no high-performance liquid chromatography (HPLC) methods that can simultaneously analyze desoxo-narchinol A (DA), nardosinonediol (NE), and nardosinone (ND) within NR. This study aimed to establish an efficient quality control protocol by developing an analytical method that simultaneously detects the three sesquiterpenes with HPLC using response surface methodology (RSM) to optimize sample preparation. Optimized HPLC conditions included a mobile phase of 0.1% formic acid in water (A), and a 0.1% formic acid in acetonitrile (B) under an elution program of 20% B-80% B for 30min at 254nm. The method was well validated, demonstrating satisfactory linearity, accuracy, precision, recovery, repeatability, and stability. Optimized conditions for creating the analytical sample were predicted by RSM using a Box-Behnken design. These conditions included reflux at 70°C for 3h using 24.98% ethanol as the extraction solvent (solvent: solid ratio=78.81mL/g). The relationship between the results between predicted and experimental conditions was well correlated, and varied between 96.48%-102.11%. Thus, our developed HPLC method, paired with optimized sample preparation conditions, accurately quantified all three sesquiterpenes, and may thus be a prospective means of controlling the quality of NR.
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Affiliation(s)
- Vu Ngoc Han Le
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Trong Quan Khong
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Min Kyun Na
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Kyung Tae Kim
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
| | - Jong Seong Kang
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
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Ohizumi Y. [A new strategy for preventive and functional therapeutic methods for dementia--approach using natural products]. YAKUGAKU ZASSHI 2016; 135:449-64. [PMID: 25759053 DOI: 10.1248/yakushi.14-00245] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Alzheimer's disease (AD) has become a serious social problem in Japan. However, effective preventive and fundamental therapeutic methods for AD have not yet been developed. Using a new strategy in the course of our survey of numerous natural resouces having neurotrophic activity, we isolated a variety of active constituents and proved their pharmacological properties. As a result, we successfully found nobiletin, a compound with anti-dementia activity that comes from citrus peels. Also, we have demonstrated that nobiletin ameliorates cognitive impairment in several dementia model animals such as chronically amyloid β(Aβ) infused rats, amyloid precursor protein transgenic (APPTg) mice, olfactory-bulbectomized (OBX) mice, N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801)-treated mice, senescence-accelated mice and bilaterial common carotid arteries occlusion mice. In a APPTg mouse of AD, nobiletin greatly improved memory impairment, and this was accompanied by a marked decrease in Aβ deposition. Also, in OBX mice memory impairment was markedly recoverd by nobiletin, accompanied by improvement of a decrease indensity of cholinergic neurons. Interestingly, nobiletin improves age-related congnitive impairment and decreased hyperphosphorylation of tau as well as oxidative stress in senescence-accelerated mice. In cultured cells, nobiletin reversed the Aβ-induced inhibition of glutamate-induced increases in cAMP response element binding protein (CREB) phosphorylation and modulated gen expression of thioredoxin-interacting protein and NMDA resceptor subunits. These results suggest that nobiletin prevents memory impairment and exhibits a protecting action against neurodgeneration in AD model animals. Nobiletin and citrus peels thus have potential as functional foods for prevention of dementia.
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Affiliation(s)
- Yasushi Ohizumi
- Graduate School of Pharmaceutical Sciences, Tohoku University; 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan; Graduate School of Engineering, Tohoku University; 6-6-07 Aoba, Aramaki, Aoba-ku, Sendai 980-8579; Faculty of Pharmaceutical Sciences, University of Shizuoka; 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan; Kansei Research Institute, Tohoku Fukushi University; 1-19-1 Kunimi, Aoba-ku, Sendai 989-3201, Japan; Yokohama College of Pharmacy; 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan
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Lu Z, Zhou P, Zhan Y, Su J, Yi D. Quantification of Nardosinone in Rat Plasma Using Liquid Chromatography–Tandem Mass Spectrometry and Its Pharmacokinetics Application. J Chromatogr Sci 2015; 53:1725-9. [DOI: 10.1093/chromsci/bmv081] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Indexed: 11/13/2022]
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11
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Heo JI, Kim JH, Lee JM, Kim SC, Park JB, Kim J, Lee JY. Mechanism for Antioxidant Activity of Nardostachys chinensis root Extract. ACTA ACUST UNITED AC 2014. [DOI: 10.3839/jabc.2014.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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12
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Li ZH, Li W, Shi JL, Tang MK. Nardosinone improves the proliferation, migration and selective differentiation of mouse embryonic neural stem cells. PLoS One 2014; 9:e91260. [PMID: 24614893 PMCID: PMC3948776 DOI: 10.1371/journal.pone.0091260] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Accepted: 02/10/2014] [Indexed: 11/18/2022] Open
Abstract
In this study, we investigated the impact of Nardosinone, a bioactive component in Nardostachys root, on the proliferation and differentiation of neural stem cells. The neural stem cells were isolated from cerebrums of embryonic day 14 CD1 mice. The proliferation of cells was monitored using the cell counting kit-8 assay, bromodeoxyuridine incorporation and cell cycle analysis. Cell migration and differentiation were investigated with the neurosphere assay and cell specific markers, respectively. The results showed that Nardosinone promotes cells proliferation and increases cells migration distance in a dose-dependent manner. Nardosinone also induces the selective differentiation of neural stem cells to neurons and oligodendrocytes, as indicated by the expression of microtubule-associated protein-2 and myelin basic protein, respectively. Nardosinone also increases the expression of phospho-extracellular signal-regulated kinase and phospho-cAMP response element binding protein during proliferation and differentiation. In conclusion, this study reveals the regulatory effects of Nardosinone on neural stem cells, which may have significant implications for the treatment of brain injury and neurodegenerative diseases.
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Affiliation(s)
- Ze-Hui Li
- Department of Biomedical Science, College of Medicine, University of Toledo, Toledo, Ohio, United States of America
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China
| | - Wei Li
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China
| | - Jin-Li Shi
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China
| | - Min-Ke Tang
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China
- * E-mail:
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13
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Paek JH, Lim SS. Preparative isolation of aldose reductase inhibitory compounds from Nardostachys chinensis by elution–extrusion counter-current chromatography. Arch Pharm Res 2014; 37:1271-9. [DOI: 10.1007/s12272-014-0328-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Accepted: 01/02/2014] [Indexed: 10/25/2022]
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14
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Cragg CL, Kalisch BE. Nerve Growth Factor Enhances Tau Isoform Expression and Transcription in IMR32 Cells. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/nm.2014.52015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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15
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Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy. ACTA ACUST UNITED AC 2013; 33:822-826. [DOI: 10.1007/s11596-013-1205-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 09/12/2013] [Indexed: 10/25/2022]
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16
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Nardokanshone A, a new type of sesquieterpenoid–chalcone hybrid from Nardostachys chinensis. Tetrahedron Lett 2013. [DOI: 10.1016/j.tetlet.2013.05.127] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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17
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Bae GS, Kim MS, Park KC, Koo BS, Jo IJ, Choi SB, Lee DS, Kim YC, Kim TH, Seo SW, Shin YK, Song HJ, Park SJ. Effect of biologically active fraction of Nardostachys jatamansi on cerulein-induced acute pancreatitis. World J Gastroenterol 2012; 18:3223-34. [PMID: 22783046 PMCID: PMC3391759 DOI: 10.3748/wjg.v18.i25.3223] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Revised: 04/16/2012] [Accepted: 05/12/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine if the fraction of Nardostachys jatamansi (NJ) has the potential to ameliorate the severity of acute pancreatitis (AP).
METHODS: Mice were administered the biologically active fraction of NJ, i.e., the 4th fraction (NJ4), intraperitoneally, and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination, measurement of cytokine expression, and examination of neutrophil infiltration.
RESULTS: NJ4 administration attenuated the severity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1 (HO-1). Furthermore, NJ4 and its biologically active fraction, NJ4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells.
CONCLUSION: These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression.
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Neuroprotective efficacy of Nardostachys jatamansi and crocetin in conjunction with selenium in cognitive impairment. Neurol Sci 2011; 33:1011-20. [DOI: 10.1007/s10072-011-0880-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2011] [Accepted: 12/03/2011] [Indexed: 11/27/2022]
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19
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Otoguro K, Iwatsuki M, Ishiyama A, Namatame M, Nishihara-Tukashima A, Kiyohara H, Hashimoto T, Asakawa Y, Omura S, Yamada H. In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei. PHYTOCHEMISTRY 2011; 72:2024-2030. [PMID: 21843897 DOI: 10.1016/j.phytochem.2011.07.015] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Revised: 07/05/2011] [Accepted: 07/18/2011] [Indexed: 05/31/2023]
Abstract
During the course of screening to discover antitrypanosomal compounds, 24 known plant terpenes (6 sesquiterpenes, 14 sesquiterpene lactones and 4 diterpenes) were evaluated for in vitro antitrypanosomal activity against Trypanosoma brucei brucei. Among them, 22 terpenes exhibited antitrypanosomal activity. In particular, α-eudesmol, hinesol, nardosinone and 4-peroxy-1,2,4,5-tetrahydro-α-santonin all exhibited selective and potent antitrypanosomal activities in vitro. Detailed here in an in vitro antitrypanosomal properties and cytotoxicities of the 24 terpenes compared with two therapeutic antitrypanosomal drugs (eflornithine and suramin). This finding represents the first report of promising trypanocidal activity of these terpenes. Present results also provide some valuable insight with regard to structure-activity relationships and the possible mode of action of the compounds.
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Affiliation(s)
- Kazuhiko Otoguro
- Research Center for Tropical Diseases, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
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Hwang JS, Lee SA, Hong SS, Han XH, Lee C, Lee D, Lee CK, Hong JT, Kim Y, Lee MK, Hwang BY. Inhibitory constituents of Nardostachys chinensis on nitric oxide production in RAW 264.7 macrophages. Bioorg Med Chem Lett 2011; 22:706-8. [PMID: 22079762 DOI: 10.1016/j.bmcl.2011.10.043] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Revised: 10/10/2011] [Accepted: 10/12/2011] [Indexed: 10/16/2022]
Abstract
The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4α,5-dimethyl-1,3-dioxo-1,2,3,4,4α,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.6-21.6 μM.
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Affiliation(s)
- Ji Sang Hwang
- College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea
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21
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Jang JY, Kim HN, Kim YR, Choi WY, Choi YH, Shin HK, Choi BT. Partially purified components of Nardostachys chinensis suppress melanin synthesis through ERK and Akt signaling pathway with cAMP down-regulation in B16F10 cells. JOURNAL OF ETHNOPHARMACOLOGY 2011; 137:1207-1214. [PMID: 21816215 DOI: 10.1016/j.jep.2011.07.047] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Revised: 06/30/2011] [Accepted: 07/19/2011] [Indexed: 05/31/2023]
Abstract
UNLABELLED Ethnopharmacological relevance Nardostachys chinensis has been used in folk medicine to treat melasma and lentigines in Korea. We investigated the inhibitory activities of Nardostachys chinensis in melanogenesis and its related signaling pathway. MATERIALS AND METHODS Bioassay-guided fractionation of Nardostachys chinensis using solvent partitioning and purification with octadecylsilane open-column chromatography resulted in partial purification. The active 20% methanol chromatographic fraction from the ethyl acetate layer (PPNC) was used to investigate melanogenesis by melanin synthesis, tyrosinase activity assay, cAMP assay, Western blot and flow cytometric analyses in B16F10 mouse melanoma cells. RESULTS PPNC markedly inhibits melanin synthesis and tyrosinase activity in a concentration-dependent manner. We also found that PPNC decreases microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and dopachrome tautomerase (Dct) protein expressions and MITF and tyrosinase mRNA levels. Moreover, PPNC reduces intracellular cAMP levels and activates mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt expression in B16F10 cells. The specific MEK/ERK inhibitor PD98059 and PI3K/Akt inhibitor LY294002, block the PPNC-induced hypopigmentation effect, and abrogate the PPNC-suppressed expression of melanogenic proteins such as MITF, tyrosinase, TRP-1, and Dct. Using flow cytometry, we elucidated whether PPNC directly induces ERK phosphorylation at the level of an intact single cell. PPNC shows marked expression of phosphorylated ERK in live B16F10 cells and abrogates PPNC-induced phosphorylated ERK by PD98059 treatment. CONCLUSIONS PPNC stimulates MEK/ERK phosphorylation and PI3K/Akt signaling with suppressing cAMP levels and subsequently stimulating MITF and TRPs down-regulation, resulting in melanin synthesis suppression.
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Affiliation(s)
- Ji Yeon Jang
- Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Gyeongnam, Republic of Korea
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22
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Williams AL, Dandepally SR, Gilyazova N, Witherspoon SM, Ibeanu G. Microwave-assisted synthesis of 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B-355252): a new potentiator of Nerve Growth Factor (NGF)-induced neurite outgrowth. Tetrahedron 2010; 66:9577-9581. [PMID: 22973068 PMCID: PMC3437539 DOI: 10.1016/j.tet.2010.09.028] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The synthesis of 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B-355252) using a MW-assisted nucleophilic aromatic substitution (S(N)Ar) reaction will be discussed. Utilization of this method allowed for the rapid generation of B-355252 heteroaryl ether core structure in the presence of cesium carbonate in dimethylformamide or tripotassium phosphate in N-methyl-2-pyrrolidone in 94% yield. Evaluation of B-355252 enhancement of nerve growth factor's ability to stimulate neurite outgrowths was determined using NS-1 cells.
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Affiliation(s)
- Alfred L Williams
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707 USA 2
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23
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Gundimeda U, McNeill TH, Schiffman JE, Hinton DR, Gopalakrishna R. Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species. J Neurosci Res 2010; 88:3644-55. [PMID: 20936703 PMCID: PMC2965808 DOI: 10.1002/jnr.22519] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2010] [Revised: 08/11/2010] [Accepted: 08/20/2010] [Indexed: 12/21/2022]
Abstract
Exogenously administered nerve growth factor (NGF) repairs injured axons, but it does not cross the blood-brain barrier. Thus, agents that could potentiate the neuritogenic ability of endogenous NGF would be of great utility in treating neurological injuries. Using the PC12 cell model, we show here that unfractionated green tea polyphenols (GTPP) at low concentrations (0.1 μg/ml) potentiate the ability of low concentrations of NGF (2 ng/ml) to induce neuritogenesis at a level comparable to that induced by optimally high concentrations of NGF (50 ng/ml) alone. In our experiments, GTPP by itself did not induce neuritogenesis or increase immunofluorescent staining for β-tubulin III; however, it increased expression of mRNA and proteins for the neuronal markers neurofilament-L and GAP-43. Among the polyphenols present in GTPP, epigallocatechin-3-gallate (EGCG) alone appreciably potentiated NGF-induced neurite outgrowth. Although other polyphenols present in GTPP, particularly epigallocatechin and epicatechin, lack this activity, they synergistically promoted this action of EGCG. GTPP also induced an activation of extracellular signal-regulated kinases (ERKs). PD98059, an inhibitor of the ERK pathway, blocked the expression of GAP-43. K252a, an inhibitor of TrkA-associated tyrosine kinase, partially blocked the expression of these genes and ERK activation. Antioxidants, catalase (cell-permeable form), and N-acetylcysteine (both L and D-forms) inhibited these events and abolished the GTPP potentiation of NGF-induced neuritogenesis. Taken together, these results show for the first time that GTPP potentiates NGF-induced neuritogenesis, likely through the involvement of sublethal levels of reactive oxygen species, and suggest that unfractionated GTPP is more effective in this respect than its fractionated polyphenols.
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Affiliation(s)
- Usha Gundimeda
- Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Thomas H. McNeill
- Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California
- Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Jason E. Schiffman
- Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - David R. Hinton
- Departments of Pathology and Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Rayudu Gopalakrishna
- Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California
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Abstract
OBJECTIVES Nardostachys jatamansi belonging to the family Valerianaceae has been used as a remedy for stomach and skin ailments in Korea. The effect of N. jatamansi on acute pancreatitis (AP) has not been defined. Therefore, we investigated the effect of N. jatamansi on cerulein-induced AP. METHODS In the pretreatment group, N. jatamansi was administered orally to mice at 10 and 20 mg/kg for 5 days, and the mice were intraperitoneally injected with the stable cholecystokinin analogue cerulein hourly for 6 hours. In the posttreatment group, cerulein was injected hourly for 6 hours, and N. jatamansi was administered at the indicated time (1, 3, and 5 hours after the first cerulein injection) and dose (10 and 20 mg/kg) during the cerulein injection. Blood samples were taken 6 hours later to determine the serum amylase, the lipase, and the cytokine levels. The pancreas and the lung were rapidly removed for morphologic examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. RESULTS Nardostachys jatamansi treatment attenuated the AP, as shown by the histological examination results of the pancreas and the lung, reductions in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and messenger RNA expressions of inflammatory mediators. CONCLUSIONS These results suggest that N. jatamansi attenuates the severity of AP and pancreatitis-associated lung injury.
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25
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Clement CM, Dandepally SR, Williams AL, Ibeanu GC. A synthetic analog of verbenachalcone potentiates NGF-induced neurite outgrowth and enhances cell survival in neuronal cell models. Neurosci Lett 2009; 459:157-61. [PMID: 19427363 PMCID: PMC2726784 DOI: 10.1016/j.neulet.2009.05.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2009] [Revised: 04/30/2009] [Accepted: 05/05/2009] [Indexed: 10/20/2022]
Abstract
This study uses NeuroScreen-1 (NS-1) cells, a derivative of pheochromocytoma (PC12) cells, to examine neurite outgrowth induced by a novel synthetic verbenachalcone derivative, DSRB20-022 (C22). We treated NS-1 cells with varying concentrations of C22 in the presence of 2ng/mL nerve growth factor (NGF). A dose-dependent effect of C22 was observed at concentrations of 2microM and above, resulting in significant enhancement of NGF-dependent neurite outgrowth in NS-1 cells. C22 did not exhibit neuritogenic activity in the absence of NGF, but promoted a concentration-dependent increase in neurite-bearing cells without inducing cytotoxicity. Cell viability assays showed that C22 and the parent compound verbenachalcone (VC) are neuroprotective and enhanced survival of NS-1, PC12, and the murine neuro-2A (N2a) cell lines under conditions of serum deprivation. The results show that augmentation of NGF-induced neurite outgrowth by C22 in NS-1 was dependent on MAP kinase. Furthermore, the neuroprotective function of C22 and VC was accompanied by suppression of caspase-3/7 activation. However, C22 and VC exerted their antagonistic effects on caspase-3/7 activation through potentially different mechanisms of action.
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Affiliation(s)
- Ceiléssia M Clement
- Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, NC 27707, USA
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Vinutha B, Prashanth D, Salma K, Sreeja SL, Pratiti D, Padmaja R, Radhika S, Amit A, Venkateshwarlu K, Deepak M. Screening of selected Indian medicinal plants for acetylcholinesterase inhibitory activity. JOURNAL OF ETHNOPHARMACOLOGY 2007; 109:359-63. [PMID: 16950584 DOI: 10.1016/j.jep.2006.06.014] [Citation(s) in RCA: 152] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2005] [Revised: 03/29/2006] [Accepted: 06/21/2006] [Indexed: 05/11/2023]
Abstract
Seventy-six plant extracts including methanolic and successive water extracts from 37 Indian medicinal plants were investigated for acetylcholinesterase (AChE) inhibitory activity (in vitro). Results indicated that methanolic extracts to be more active than water extracts. The potent AChE inhibiting methanolic plant extracts included Withania somnifera (root), Semecarpus anacardium (stem bark), Embelia ribes (Root), Tinospora cordifolia (stem), Ficus religiosa (stem bark) and Nardostachys jatamansi (rhizome). The IC(50) values obtained for these extracts were 33.38, 16.74, 23.04, 38.36, 73.69 and 47.21mug/ml, respectively. These results partly substantiate the traditional use of these herbs for improvement of cognition.
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Affiliation(s)
- B Vinutha
- Department of Pharmacognosy, Al-Ameen College of Pharmacy, Hosur Road, Bangalore, India
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Liu JH, Yin F, Zheng XX. Nardostachys chinensis Glycoside Induces Characteristics of Neuronal Differentiation in Rat Pheochromocytoma PC12 Cells. Biol Pharm Bull 2005; 28:768-71. [PMID: 15802829 DOI: 10.1248/bpb.28.768] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Rat pheochromocytoma PC12 cells undergo neuronal differentiation in response to nerve growth factor. We show here that exposure of PC12 cells to Nardostachys chinensis glycoside induces the outgrowth of neurites, increases the activity of AChE, triggers cell cycle arrest in G1 and enhances the expression of growth associated protein 43 (GAP-43). Both the outgrowth of neurites and the increase in AChE activity are prevented partly by PD98059, a specific inhibitor of MEK1. These results suggest that N. chinensis glycoside induces the characteristics of neuronal differentiation in PC12 cells via the mitogen-activated protein kinase (MAPK)-related signal cascade.
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Affiliation(s)
- Jian Hui Liu
- Natural Medicine Research Center, Chongqing Technology and Business University, Chongqing, China.
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