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Article ; Online: Si-Zhi Wan regulates osteoclast autophagy in osteoporosis through the AMPK signaling pathway to attenuate osteoclastogenesis.

Huang, Yucheng / Yao, Huan / Tjahjono, Adi Wirawan / Xiang, Li / Li, Ke / Tang, Jiahe / Gao, Yongxiang

The Journal of pharmacy and pharmacology

2024 Volume 76, Issue 3, Page(s) 236–244

Abstract: Objectives: The mechanisms underlying the therapeutic effects of Si-Zhi Wan (SZW ...

Abstract	Objectives: The mechanisms underlying the therapeutic effects of Si-Zhi Wan (SZW), a traditional Chinese medicine used to treat osteoporosis (OP), remain unknown. This study investigated the therapeutic effects of SZW on mice that underwent ovariectomy (OVX) and underlying mechanisms thereof. Methods: We established an in vivo model of OP by performing OVX in mice. Microcomputed tomography (Micro-CT) was used to assess changes in bone characteristics of mice following SZW administration for 4 weeks. H&E staining revealed alterations in bone tissues of mice. Osteoclastogenesis in mouse bone tissue was observed using tartrate-resistant acid phosphatase staining and western blotting. Furthermore, we examined the impact of SZW on osteoclastogenesis in vitro using receptor activator of nuclear factor kappa-B ligand (RANKL). Finally, we explored the regulatory effects of SZW on osteoclast autophagy and the AMPK pathway. Key findings: The results demonstrated that high-dose SZW reversed changes in bone density parameters caused by OVX, including bone volume (BV), BV/total volume, trabecular number, and trabecular spacing (P = 0.0007, 0.0035, 0.0114, and 0.0182, respectively), and stimulated the formation of bone trabeculae in mice (P < 0.0001). Furthermore, SZW suppressed osteoclast formation in mice with OVX and inhibited osteoclast formation induced by RANKL. Mechanistically, SZW inhibited osteoclast precursor cell autophagy through the AMPK pathway. Conclusions: SZW effectively inhibited the autophagy of osteoclast precursors by regulating the AMPK pathway, thereby exerting anti-osteoclastogenic effects and serving as an alternative therapy for OP.
MeSH term(s)	Female ; Mice ; Animals ; Humans ; Osteoclasts/metabolism ; Osteogenesis ; AMP-Activated Protein Kinases/metabolism ; X-Ray Microtomography ; Osteoporosis/drug therapy ; Osteoporosis/metabolism ; Signal Transduction ; Autophagy ; RANK Ligand/metabolism ; RANK Ligand/pharmacology ; RANK Ligand/therapeutic use ; Ovariectomy ; Cell Differentiation
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31) ; RANK Ligand
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	3107-0
ISSN	2042-7158 ; 0022-3573 ; 0373-1022
ISSN (online)	2042-7158
ISSN	0022-3573 ; 0373-1022
DOI	10.1093/jpp/rgad126
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Article ; Online: 14-3-3ζ Plays a key role in the modulation of neuroplasticity underlying the antidepressant-like effects of Zhi-Zi-Chi-Tang.

Tao, Weiwei / Yao, Guangda / Yue, Qiyu / Xu, Chunyan / Hu, Yue / Cheng, XiaoLan / Zhao, Tong / Qi, Mingming / Chen, Gang / Zhao, Min / Yu, Yue

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 116, Page(s) 154888

Abstract: Background: Zhi-Zi-Chi-Tang (ZZCT) is an effective traditional Chinese medicinal formula. ZZCT has ...

Abstract	Background: Zhi-Zi-Chi-Tang (ZZCT) is an effective traditional Chinese medicinal formula. ZZCT has been used for the treatment of depression for centuries. Its clinical efficacy in relieving depression has been confirmed. However, the molecular mechanisms of ZZCT regarding neuroplasticity in the pathogenesis of depression have not yet been elucidated. Purpose: The present study aimed to examine the effects of ZZCT on neuroplasticity in mice exposed to chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms. Methods: For this purpose, a murine model of depression was established using the CUMS procedure. Following the intragastric administration of ZZCT or fluoxetine, classic behavioral experiments were performed to observe the efficacy of ZZCT as an antidepressant. Immunofluorescence was used to label and quantify microtubule-associated protein (MAP2) and postsynaptic density protein (PSD95) in the hippocampus. Golgi staining was applied to visualize the dendritic spine density of neurons in the hippocampi. Isolated hippocampal slices were prepared to induce long-term potentiation (LTP) in the CA1 area. The hippocampal protein expression levels of glycogen synthase kinase-3β (GSK-3β), p-GSK-3β (Ser9), cAMP response element binding protein (CREB), p-CREB (Ser133), brain-derived neurotrophic factor (BDNF) and 14-3-3ζ were detected using western blot analysis. The interaction of 14-3-3ζ and p-GSK-3β (Ser9) was examined using co-immunoprecipitation. LV-shRNA was used to knockdown 14-3-3ζ by an intracerebroventricular injection. Results: ZZCT (6 g/kg) and fluoxetine (20 mg/kg) alleviated depressive-like behavior, restored hippocampal MAP2 Conclusion: ZZCT exerted antidepressant effects against CUMS-stimulated depressive-like behavior mice. The knockdown of 14-3-3ζ using lentivirus confirmed that 14-3-3ζ was involved in the ZZCT-mediated antidepressant effects through GSK-3β/CREB/BDNF signaling. On the whole, these results suggest that the antidepressant effects of ZZCT are attributed to restoring damage by neuroplasticity enhancement via the 14-3-3ζ/GSK-3β/CREB/BDNF signaling pathway.
MeSH term(s)	Mice ; Animals ; Glycogen Synthase Kinase 3 beta/metabolism ; Fluoxetine/pharmacology ; Brain-Derived Neurotrophic Factor/metabolism ; 14-3-3 Proteins/metabolism ; 14-3-3 Proteins/pharmacology ; Antidepressive Agents/pharmacology ; Neuronal Plasticity/physiology ; Cyclic AMP Response Element-Binding Protein/metabolism ; Hippocampus ; Stress, Psychological/drug therapy ; Depression/drug therapy ; Depression/metabolism ; Disease Models, Animal
Chemical Substances	Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Fluoxetine (01K63SUP8D) ; Brain-Derived Neurotrophic Factor ; 14-3-3 Proteins ; Antidepressive Agents ; Cyclic AMP Response Element-Binding Protein
Language	English
Publishing date	2023-05-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.154888
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Article ; Online: 14-3-3ζ Plays a key role in the modulation of neuroplasticity underlying the antidepressant-like effects of Zhi-Zi-Chi-Tang

Tao, Weiwei / Yao, Guangda / Yue, Qiyu / Xu, Chunyan / Hu, Yue / Cheng, Xiaolan / Zhao, Tong / Qi, Mingming / Chen, Gang / Zhao, Min / Yu, Yue

Phytomedicine. 2023 July, v. 116 p.154888-

2023

Abstract: Zhi-Zi-Chi-Tang (ZZCT) is an effective traditional Chinese medicinal formula. ZZCT has been used ...

Abstract	Zhi-Zi-Chi-Tang (ZZCT) is an effective traditional Chinese medicinal formula. ZZCT has been used for the treatment of depression for centuries. Its clinical efficacy in relieving depression has been confirmed. However, the molecular mechanisms of ZZCT regarding neuroplasticity in the pathogenesis of depression have not yet been elucidated. The present study aimed to examine the effects of ZZCT on neuroplasticity in mice exposed to chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms. For this purpose, a murine model of depression was established using the CUMS procedure. Following the intragastric administration of ZZCT or fluoxetine, classic behavioral experiments were performed to observe the efficacy of ZZCT as an antidepressant. Immunofluorescence was used to label and quantify microtubule-associated protein (MAP2) and postsynaptic density protein (PSD95) in the hippocampus. Golgi staining was applied to visualize the dendritic spine density of neurons in the hippocampi. Isolated hippocampal slices were prepared to induce long-term potentiation (LTP) in the CA1 area. The hippocampal protein expression levels of glycogen synthase kinase-3β (GSK-3β), p-GSK-3β (Ser9), cAMP response element binding protein (CREB), p-CREB (Ser133), brain-derived neurotrophic factor (BDNF) and 14–3–3ζ were detected using western blot analysis. The interaction of 14–3–3ζ and p-GSK-3β (Ser9) was examined using co-immunoprecipitation. LV-shRNA was used to knockdown 14–3–3ζ by an intracerebroventricular injection. ZZCT (6 g/kg) and fluoxetine (20 mg/kg) alleviated depressive-like behavior, restored hippocampal MAP2⁺ PSD95⁺ intensity, and reversed the dendritic spine density of hippocampal neurons and LTP in the CA1 region of mice exposed to CUMS. Both low and high doses of ZZCT (3 and 6 g/kg) significantly promoted the binding of 14–3–3ζ to p-GSK-3β (Ser9) in the hippocampus, and ZZCT (6 g/kg) significantly promoted the phosphorylation of GSK-3β Ser9 and CREB Ser133 in the hippocampus. ZZCT (3 and 6 g/kg) upregulated hippocampal BDNF expression in mice exposed to CUMS. LV-sh14–3–3ξ reduced the antidepressant effects of ZZCT. ZZCT exerted antidepressant effects against CUMS-stimulated depressive-like behavior mice. The knockdown of 14–3–3ζ using lentivirus confirmed that 14–3–3ζ was involved in the ZZCT-mediated antidepressant effects through GSK-3β/CREB/BDNF signaling. On the whole, these results suggest that the antidepressant effects of ZZCT are attributed to restoring damage by neuroplasticity enhancement via the 14–3–3ζ/GSK-3β/CREB/BDNF signaling pathway.
Keywords	Lentivirus ; Western blotting ; animal models ; antidepressants ; dendrites ; fluorescent antibody technique ; fluoxetine ; glycogen (starch) synthase ; hippocampus ; intragastric administration ; neuroplasticity ; pathogenesis ; phosphorylation ; precipitin tests ; protein synthesis ; Zhi-Zi-Chi decoction (ZZCT) ; Anti-depression ; 14-3-3ζ ; BDNF ; ZZCT ; CUMS ; TST ; SPT ; FST ; OFT ; PSD95 ; MAP2 ; LTP ; GSK-3β ; CREB ; fEPSP
Language	English
Dates of publication	2023-07
Publishing place	Elsevier GmbH
Document type	Article ; Online
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.154888
Database	NAL-Catalogue (AGRICOLA)

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Article: Traditional Chinese decoction Si Zhi Wan attenuates ovariectomy (OVX)-induced bone loss by inhibiting osteoclastogenesis and promoting apoptosis of mature osteoclasts.

He, Qingman / Fu, Kanghua / Yao, Huan / Wei, Shujun / Xiang, Li / Liu, Sixian / Chen, Tao / Gao, Yongxiang

Frontiers in pharmacology

2022 Volume 13, Page(s) 983884

Abstract: Si Zhi Wan (SZW) is a traditional Chinese decoction used for osteoporosis treatment. Currently ...

Abstract	Si Zhi Wan (SZW) is a traditional Chinese decoction used for osteoporosis treatment. Currently, the effect of SZW on ovariectomy (OVX)-induced bone loss and the underlying mechanisms remain unknown. Herein, we investigated the therapeutic effect of SZW on osteoporosis and explored the underlying mechanisms
Language	English
Publishing date	2022-09-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.983884
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Article: Yuan-Zhi decoction in the treatment of Alzheimer's disease: An integrated approach based on chemical profiling, network pharmacology, molecular docking and experimental evaluation.

Wu, Qiong / Li, Xiang / Jiang, Xiao-Wen / Yao, Dong / Zhou, Li-Jun / Xu, Zi-Hua / Wang, Nan / Zhao, Qing-Chun / Zhang, Zhou

Frontiers in pharmacology

2022 Volume 13, Page(s) 893244

Abstract: Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical ...

Abstract	Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer's disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aβ plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3β/GSK-3β, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These
Language	English
Publishing date	2022-08-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.893244
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Book: Zhejiang yao yong zhi wu zi yuan zhi yao

Yao, Zhensheng

2016

Author's details	zhu bian Yao Zhensheng, Xiong Yaokang
MeSH term(s)	Plants, Medicinal ; Natural Resources
Keywords	China
Language	Chinese
Size	8, 2, 2, 2, 2, 518 pages :, portraits
Edition	Di 1 ban.
Document type	Book
ISBN	9787547829455 ; 7547829457
Database	Catalogue of the US National Library of Medicine (NLM)

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Article: Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats.

Zhang, Hua / Yao, Xiang-Yang / Zhang, Dan-Feng / Guo, Qi-le / Yang, Jun-Jun / Zhu, Bao-Guo / Shen, Dong-Xiao / Ruan, Ke-Feng / Wang, Yuan / Peng, Jun-Liang

Journal of integrative medicine

2020 Volume 19, Issue 1, Page(s) 42–49

Abstract: ... to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate ...

Abstract	Objective: Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats. Methods: HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations. Results: In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α). Conclusion: This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.
MeSH term(s)	Animals ; Drugs, Chinese Herbal/therapeutic use ; Hemorrhoids/drug therapy ; Interleukin-1beta ; Interleukin-6 ; Medicine, Chinese Traditional ; Rats ; Tumor Necrosis Factor-alpha
Chemical Substances	Drugs, Chinese Herbal ; Interleukin-1beta ; Interleukin-6 ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2020-09-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2705612-0
ISSN	2095-4964
ISSN	2095-4964
DOI	10.1016/j.joim.2020.09.006
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Zs.A 6322: Show issues

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Article ; Online: Discovery of potential active ingredients of Er-Zhi-Wan, a famous traditional Chinese formulation, in model rat serum for treating osteoporosis with kidney-yin deficiency by UPLC-Q/TOF-MS and molecular docking.

Gao, Mengting / Xue, Xin / Zhang, Xuemeng / Chang, Yueyue / Zhang, Qiulan / Li, Xin / Wang, Yifei / Zhang, Li / Li, Zhipeng / Dong, Haijuan / Wang, Wei / Yao, Weifeng

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2022 Volume 1208, Page(s) 123397

Abstract: Er-Zhi-Wan (EZW), a classical traditional Chinese formulation, has attracted more and more ...

Abstract	Er-Zhi-Wan (EZW), a classical traditional Chinese formulation, has attracted more and more attention. This study was carried out to analyze the constituents of EZW absorbed into blood and find out the potential active ingredients for treating osteoporosis (OP) with kidney-yin deficiency (KYD). The rat model of OP with KYD was achieved by ovariectomies and using the mixture of thyroxine and reserpine. Then ultra-high performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (UPLC-Q/TOF-MS) combined with statistical analysis was used to analyze the constituents of EZW absorbed into blood and differential components between the normal and OP with KYD rats. Finally, the components identified in OP with KYD rats were docked with targets of OP with KYD found in online databases. The results of molecular docking were adopted to find the potential active ingredients and further verified in vitro experiment. A total of 21 prototype compounds and 69 metabolites were identified in serum. Among them, 63 components in model rats and 50 components in normal rats were summarized, respectively. Most of the identified metabolites in serum of model rats were produced by hydrolysis, oxidation or glucuronidation, while in serum of normal rats were produced by hydrolysis, oxidation and methylation. According to the results of molecular docking, specnuezhenide, salidroside, tyrosol, echinacoside and verbascoside could be classified as potential active ingredients. The activity of salidroside and a metabolite was verified by pharmacodynamics analysis. In summary, UPLC-Q/TOF-MS system was combined with molecular docking to search the potential active ingredients from model rats of OP with KYD, which provided a new idea for the research on the pharmacodynamic material basis of other traditional medicine. Moreover, the result of this study lays the foundation for further study regarding the mechanism of EZW in treating OP with KYD.
MeSH term(s)	Animals ; China ; Chromatography, High Pressure Liquid/methods ; Drugs, Chinese Herbal ; Kidney/chemistry ; Molecular Docking Simulation ; Osteoporosis ; Rats ; Yin Deficiency
Chemical Substances	Drugs, Chinese Herbal ; er-zhi-wan
Language	English
Publishing date	2022-07-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2022.123397
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 813: Show issues

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Article ; Online: Combination of cell metabolomics and pharmacology: A novel strategy to investigate the neuroprotective effect of Zhi-zi-chi decoction.

Zhang, Yin / Yao, Yuan / Shi, Xiaolei / Fan, Jun / Huang, Taohong / Wen, Jun / Zhou, Tingting

Journal of ethnopharmacology

2019 Volume 236, Page(s) 302–315

Abstract: Ethnopharmacological relevance: Zhi-zi-chi Decoction(ZZCD), a traditional Chinese medicine formula ...

Abstract	Ethnopharmacological relevance: Zhi-zi-chi Decoction(ZZCD), a traditional Chinese medicine formula, has been reported its potential protective effect on psychological sub-health diseases. However, there still remains a lack of molecular mechanism interpretation. Aim of the study: This study was aimed at investigating the mechanism of glutamate-induced toxicity in PC12 cells and the neuroprotective effect of ZZCD based on a novel strategy of the combination of cell metabolomics and pharmacology. Materials and methods: The PC12 cells were treated with glutamate to simulate neurotoxic cell model. Gas chromatography coupled with mass spectrometry based on cell metabolomics approach was performed to comprehensively investigate the molecular mechanism of glutamate-induced toxicity The cell viability and cytotoxicity analysis, the determination of glutathione reductase(GR), superoxide dismutase(SOD) and reactive oxygen species(ROS), apoptosis analysis and western blot analysis were performed to evaluate the neuroprotection of ZZCD. Results: Forty metabolites were identified as potential biomarkers in model cells by principal components analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Glutamate decreased the GR and SOD activities, increased the level of intracellular ROS, activated the apoptotic pathway, and induced the changes of energy metabolism, amino acid metabolism and lipid metabolism. In addition, the extract of ZZCD could reverse the disturbed metabolic pathways by regulating those potential biomarkers and exerted anti-oxidation and anti-apoptosis. Conclusion: ZZCD has neuroprotective effect and the novel strategy can be applicable for other traditional Chinese medicine formulas.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Survival/drug effects ; Drugs, Chinese Herbal/pharmacology ; Fruit/chemistry ; Gardenia/chemistry ; Glutamic Acid/toxicity ; Glutathione Reductase/metabolism ; Medicine, Chinese Traditional ; Metabolic Networks and Pathways/drug effects ; Metabolomics/methods ; Neuroprotective Agents/pharmacology ; PC12 Cells ; Rats ; Reactive Oxygen Species/metabolism ; Seeds/chemistry ; Glycine max/chemistry ; Superoxide Dismutase/metabolism
Chemical Substances	Drugs, Chinese Herbal ; Neuroprotective Agents ; Reactive Oxygen Species ; Glutamic Acid (3KX376GY7L) ; Superoxide Dismutase (EC 1.15.1.1) ; Glutathione Reductase (EC 1.8.1.7)
Language	English
Publishing date	2019-03-11
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2019.03.021
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Article: Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis

Shi, Zheng / Li, Ting / Liu, Yuwen / Cai, Tiantian / Yao, Wendong / Jiang, Jianping / He, Yinghua / Shan, Letian

Frontiers in pharmacology

2020 Volume 11, Page(s) 483

Abstract: Nonalcoholic steatohepatitis (NASH) is a liver disease defined as the dynamic condition of hepatocellular injury during the progress of nonalcoholic fatty liver disease (NAFLD). Total flavonoids from the dry and immature fruits ... ...

Abstract	Nonalcoholic steatohepatitis (NASH) is a liver disease defined as the dynamic condition of hepatocellular injury during the progress of nonalcoholic fatty liver disease (NAFLD). Total flavonoids from the dry and immature fruits of
Language	English
Publishing date	2020-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.00483
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