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Article ; Online: San Jie Tong Mai Fang Protects Against Atherosclerosis Progression by Regulating Macroautophagy through the PI3K/AKT/mTOR Signaling Pathway.

Li, Pengfei / Li, Hongyu / Li, Xiaohui / Li, Shuangdi / Xu, Hanying / Cui, Junfeng / Cheng, Guangyu / Liu, Yinghui / Xu, Xiaolin / Xin, Yuning / Liu, Aidong

Journal of cardiovascular pharmacology

2023 Volume 82, Issue 4, Page(s) 333–343

Abstract: ... autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid ...

Abstract	Abstract: Many studies have confirmed that macrophage autophagy injury negatively impacts the pathogenesis of atherosclerosis (AS). Meanwhile, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway affects AS progression by regulating macrophage autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid regulatory and anti-inflammatory properties. Hence, the current study used an ApoE -/- high-fat diet-fed mouse model to determine whether SJTMF elicits protective effects against AS progression by means of the regulation of macrophage autophagy through the PI3K/AKT/mTOR signaling pathway. Our results show that SJTMF reduced the number of atherosclerotic plaques, foam cell formation, and intimal thickness in mouse aorta. In addition, SJTMF improved blood lipid metabolism and inflammatory levels in mice. We also observed that SJTMF caused macrophages to be polarized toward the M2 phenotype through the inhibition of the PI3K/AKT/mTOR signaling pathway. In addition, the abundances of LC3-II/I and beclin1 proteins-key autophagy molecules-were increased, whereas that of p62 was decreased, resulting in the promotion of macrophage autophagy. Taken together, these findings indicate that SJTMF may regulate the polarization of macrophages by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby reducing atherosclerotic plaque damage in ApoE -/- mice, thereby promoting macrophage autophagy and eliciting a significant antiarteriosclerosis effect. Hence, SJTMF may represent a promising new candidate drug for the treatment of AS.
MeSH term(s)	Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Macroautophagy ; TOR Serine-Threonine Kinases/metabolism ; Mice, Knockout, ApoE ; Signal Transduction ; Atherosclerosis/drug therapy ; Atherosclerosis/prevention & control ; Atherosclerosis/genetics ; Plaque, Atherosclerotic ; Autophagy ; Apolipoproteins E/pharmacology ; Mammals/metabolism
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Apolipoproteins E
Language	English
Publishing date	2023-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/FJC.0000000000001452
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Article ; Online: Study on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology Approaches.

Liu, Wen-Rui / Li, Mao-Ting / Zhou, Qi / Gao, Song-Yan / Hou, Jie-Bin / Yang, Guo-Bin / Liu, Nan-Mei / Jia-Yan / Yu, Jian-Peng / Cheng, Jin / Guo, Zhi-Yong

Combinatorial chemistry & high throughput screening

2024 Volume 27, Issue 1, Page(s) 90–100

Abstract: Introduction: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi ... Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal ... pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced ...

Abstract	Introduction: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently. Methods: Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry. Results: Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment. Conclusions: Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.
MeSH term(s)	Mice ; Animals ; Calcium Oxalate/metabolism ; Calcium Oxalate/pharmacology ; Calcium/metabolism ; Chromatography, High Pressure Liquid ; Network Pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Reactive Oxygen Species/metabolism ; Kidney/metabolism ; Autophagy ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/metabolism
Chemical Substances	Calcium Oxalate (2612HC57YE) ; Calcium (SY7Q814VUP) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Reactive Oxygen Species ; Drugs, Chinese Herbal
Language	English
Publishing date	2024-01-12
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2064785-2
ISSN	1875-5402 ; 1386-2073
ISSN (online)	1875-5402
ISSN	1386-2073
DOI	10.2174/1386207326666230515151302
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Zs.A 5577: Show issues

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Article ; Online: BuShen JianGu Fang alleviates cartilage degeneration via regulating multiple genes and signaling pathways to activate NF-κB/Sox9 axis.

Zhou, Zhenwei / Lv, Cheng / Wang, Yuting / Zhang, Binghua / Liu, Lang / Yang, Jie / Leng, Xiangyang / Zhao, Daqing / Yao, Baojin / Wang, Jianyu / Dong, Haisi

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 113, Page(s) 154742

Abstract: ... herbal formulae BuShen JianGu Fang (BSJGF) has been clinically applied for treating OA-related syndromes ...

Abstract	Background: Osteoarthritis (OA) is an inflammatory response in chondrocytes, causing extracellular matrix (ECM) degradation and cartilage destruction, affecting millions of people worldwide. Chinese herbal formulae BuShen JianGu Fang (BSJGF) has been clinically applied for treating OA-related syndromes, but the underlying mechanism still unclear. Methods: The components of BSJGF were analyzed by liquid chromatography-mass spectrometry (LC-MS). To make a traumatic OA model, the anterior cruciate ligament of 6-8-week-old male SD rats were cut and then the 0.4 mm metal was used to destroy the knee joint cartilage. OA severity was assessed by histological and Micro-CT. Mouse primary chondrocytes were utilized to investigate the mechanism of BSJGF alleviate osteoarthritis, which was examined by RNA-seq technology combined with a series of functional experiments. Results: A total 619 components were identified by LC-MS. In vivo, BSJGF treatment result in a higher articular cartilage tissue area compared to IL-1β group. Treatment also significantly increased Tb.Th, BV/TV and BMD of subchondral bone (SCB), which implied a protective effect on maintaining the stabilization of SCB microstructure. In vitro results indicated BSJGF promoted chondrocyte proliferation, increased the expression level of cartilage-specific genes (Sox9, Col2a1, Acan) and synthesized acidic polysaccharide, while inhibiting the release of catabolic enzymes and production of reactive oxygen species (ROS) induced by IL-1β. Transcriptome analysis showed that there were 1471 and 4904 differential genes between IL-1β group and blank group, BSJGF group and IL-1β group, respectively, including matrix synthesis related genes (Col2a1, H19, Acan etc.), inflammation related genes (Comp, Pcsk6, Fgfr3 etc.) and oxidative stress related genes (Gm26917, Bcat1, Sod1 etc.). Furthermore, KEGG analysis and validation results showed that BSJGF reduces OA-mediated inflammation and cartilage damaged due to modulation of NF-κB/Sox9 signaling axis. Conclusion: The innovation of the present study was the elucidation of the alleviating cartilage degradation effect of BSJGF in vivo and in vitro and discovery of its mechanism through RNA-seq combined with function experiments, which provides a biological rationale for the clinical application of BSJGF for OA treatment.
MeSH term(s)	Male ; Rats ; Animals ; Mice ; NF-kappa B/metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; Osteoarthritis/metabolism ; Inflammation/drug therapy ; Cartilage, Articular ; Interleukin-1beta/metabolism
Chemical Substances	NF-kappa B ; Interleukin-1beta
Language	English
Publishing date	2023-03-05
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.2023.154742
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Zs.A 4115: Show issues

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Article: Huayu Jiedu Fang Protects Ovarian Function in Mouse with Endometriosis Iron Overload by Inhibiting Ferroptosis.

Ding, Jie / Zhao, Qianqian / Zhou, Zhihao / Cheng, Wen / Sun, Shuai / Ni, Zhexin / Yu, Chaoqin

Evidence-based complementary and alternative medicine : eCAM

2022 Volume 2022, Page(s) 1406820

Abstract: ... of ferroptosis. Huayu Jiedu Fang (HYJDF) is an empirical prescription for EM treatment. This study combined ...

Abstract	Endometriosis (EM) is a common chronic inflammatory disease in women. Sampson's retrograde menstruation theory is the most widely accepted theory of EM pathogenesis. The periodic bleeding of ectopic lesions is an important pathological feature of this disease, and the occurrence and progression of EM are closely associated with the iron overload caused by ectopic lesions. However, animal models that simulate menstrual-blood reflux and hemorrhage from EM lesions are lacking. In this study, we performed intraperitoneal injection of endometrial fragments and periodic intraperitoneal blood injection to simulate the real cause and disease state of EM and successfully constructed a mouse model of EM iron overload. Our research found that the number, size, and degree of adhesion of EM lesions in the iron-overload model mouse were significantly higher than those in the model mouse. Moreover, the iron concentration in the abdominal fluid and ovary significantly increased, and the level of malondialdehyde (MDA) in the ovary increased. Conversely, GPX4, GSH, and other anti-ferroptosis-related proteins were downregulated, proving the occurrence of ferroptosis. Huayu Jiedu Fang (HYJDF) is an empirical prescription for EM treatment. This study combined animal experiments, UHPLC-QE-MS analysis, and network pharmacology to analyze whether HYJDF can inhibit ferroptosis to slow down the progression of EM and protect ovarian function. Based on the constructed iron-overload model, HYJDF can reduce the volume of EM lesions and the degree of adhesion, downregulate the total iron concentration in the peritoneal fluid and ovary, upregulate GPX4 expression and GSSG in the ovary, downregulate the level of MDA in the ovary, and promote the development of follicles. We further confirmed that HYJDF can inhibit the progression of EM disease and improve the ovarian function of the model mouse by inhibiting ferroptosis. Finally, through UHPLC-QE-MS and network pharmacology analysis, the natural compounds in HYJDF were identified and verified and the regulatory effect of HYJDF on the EM ferroptosis pathway through the IL-6/hepcidin pathway was preliminarily elucidated.
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2022/1406820
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Zs.A 5995: Show issues

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Article: Fu Fang Zhen Zhu Tiao Zhi Capsules Protect against Myocardial Ischemia by Inhibiting Cardiomyocyte Pyroptosis.

Shao, Xiaoqi / Huang, Bingying / Tan, Huiling / Wang, Ruonan / Huang, Xueying / Diao, Hongtao / Cheng, Jiawen / Sun, Mengxian / Wang, Dongwei / Wu, Kaili / Yan, Meiling / Rong, Xianglu / Zhang, Yue / Guo, Jiao

Evidence-based complementary and alternative medicine : eCAM

2022 Volume 2022, Page(s) 4752360

Abstract: Background: Fu Fang Zhen Zhu Tiao Zhi (FTZ) is a traditional Chinese herbal prescription widely ...

Abstract	Background: Fu Fang Zhen Zhu Tiao Zhi (FTZ) is a traditional Chinese herbal prescription widely used to treat dyslipidemia, metabolic diseases, and diabetic coronary disorders. Cardiomyocyte death and loss of regenerative ability cause cardiac dysfunction and heart failure. FTZ can effectively treat diabetic cardiomyopathy and macrovascular diseases; however, the mechanism behind the phenomenon is still unclear. Here, we determined the mechanism of action of FTZ in treating myocardial infarction. Methods: Male C57BL/6 mice were treated with 2.4 or 1.2 g/kg FTZ, or administered saline by oral gavage daily for four weeks, and a 24-hour ligation was administered to the artery. Echocardiography was used to evaluate cardiac function. Hematoxylin and eosin and Evans blue/triphenyltetrazolium chloride staining were carried out by staining the cardiac tissue, used to evaluate cardiac function and infarct size. Using western blotting and reverse transcriptase-polymerase chain reaction, we determined the relative levels of NOD-like receptor protein (NLRP) 3, ASC, cleaved caspase-l (C-Caspase-1), GSDMD, and GSDMD-N. TUNEL, immunohistochemical, and immunofluorescence staining were used to determine cell death and NLRP3 expression. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)-1 Results: FTZ reduced ischemia-induced cardiomyocyte cell death Conclusion: FTZ could preserve cardiac function resulting from ischemic insult by inhibiting pyroptosis, which was partially reversed by NLRP3 overexpression, indicating that NLRP3 could be a potential target of FTZ in treating myocardial infarction.
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2022/4752360
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Article ; Online: Effects of Fang Cang Shelter Hospitals on the Reduction of COVID-19 New Cases in Wuhan

Wang, Ke-Wei / Gao, Jie / Huang, Jiang / Wu, Xiao-Long / Yuan, Qin-Fang / Li, Xiaoshan / Wang, Hua / Cheng, Feng / Cheng, Yang

SSRN Electronic Journal ; ISSN 1556-5068

An Interrupted Time Series Analysis

2020

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.2139/ssrn.3569888
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Article ; Online: Efficacy of Qingre Huayu Fang on atherosclerotic vulnerable plaque in apolipoprotein E knockout mice: proteasome pathway involvement.

Pang, Jun / Cheng, Wen-Li / Peng, Jingbing / Li, Hong / Wu, Qiang / Li, Ling / Liu, Cheng-Ming / Liu, Wei / Huang, Jing

Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan

2021 Volume 41, Issue 3, Page(s) 432–437

Abstract: Objective: To investigate the efficacy and mechanism of the Qingre Huayu Fang ... a proteasome inhibitor), bortezomib combined with Qingre Huayu Fang, and Qingre Huayu Fang alone. Aortic sections were ... all reduced in the group that received combination bortezomib + Qingre Huayu Fang.: Conclusion: The Qingre ...

Abstract	Objective: To investigate the efficacy and mechanism of the Qingre Huayu Fang () on atherosclerotic vulnerable plaque in apolipoprotein E (ApoE) knockout mice through the ubiquitin proteasome pathway. Methods: Sixty 8-week-old C57BL/6J ApoE knockout mice were fed a high-fat for 12 weeks and randomly divided into four treatment groups (n = 15 each): high-fat control, bortezomib (a proteasome inhibitor), bortezomib combined with Qingre Huayu Fang, and Qingre Huayu Fang alone. Aortic sections were examined for plaque development, inflammatory cell infiltration, type Ⅰ/Ⅲ collagen expression and immunohistochemical staining of CD40L, nuclear factor-kappa B (NF-κB)/P65 and ubiquitin. Results: Mice in the high-fat control group had obvious atherosclerosis, with increased aortic plaque area. The degree of atherosclerosis of the atherosclerotic plaque was reduced in all of the treatment groups that received bortezomib and/or Duzhong (Cortex Eucommiae) Qingre Huayu. The expression of NF-?B, CD40L and ubiquitin were all reduced in the group that received combination bortezomib + Qingre Huayu Fang. Conclusion: The Qingre Huayu Fang inhibited aortic atherosclerosis in mice through a mechanism that may involve inhibition of the ubiquitin proteasome pathway.
MeSH term(s)	Animals ; Apolipoproteins E/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plaque, Atherosclerotic/drug therapy ; Plaque, Atherosclerotic/genetics ; Proteasome Endopeptidase Complex/genetics
Chemical Substances	Apolipoproteins E ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2021-06-10
Publishing country	China
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603186-9
ISSN	2589-451X ; 0254-6272 ; 0255-2922
ISSN (online)	2589-451X ; 0254-6272
ISSN	0255-2922
DOI	10.19852/j.cnki.jtcm.2021.03.011
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Zs.B 2564: Show issues

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Article ; Online: A multiomics and network pharmacological study reveals the neuroprotective efficacy of Fu-Fang-Dan-Zhi tablets against glutamate-induced oxidative cell death.

Gu, Yu / Huang, Pengli / Cheng, Taofang / Yang, Jian / Wu, Gaosong / Sun, Yuting / Liu, Aijun / Li, Houkai / Zhao, Jing / Ye, Ji

Computers in biology and medicine

2022 Volume 148, Page(s) 105873

Abstract: ... still insufficient. The Fu-Fang-Dan-Zhi tablet (FFDZT) is a proprietary Chinese medicine clinically ...

Abstract	Neuroprotective therapy after ischemic stroke remains a significant need, but current measures are still insufficient. The Fu-Fang-Dan-Zhi tablet (FFDZT) is a proprietary Chinese medicine clinically employed to treat ischemic stroke in the recovery period. This work aims to systematically investigate the neuroprotective mechanism of FFDZT. A systems strategy that integrated metabolomics, transcriptomics, network pharmacology, and in vivo and in vitro experiments was used. First, middle cerebral artery occlusion (MCAO) model rats were treated with FFDZT. FFDZT treatment significantly reduced the infarct volume in the brains of middle cerebral artery occlusion (MCAO) model rats. Then, samples of serum and brain tissue were taken for metabolomics and transcriptomics studies, respectively; gene expression profiles of MCF7 cells treated with FFDZT and its 4 active compounds (senkyunolide I, formononetin, drilodefensin, and tanshinone IIA) were produced for CMAP analysis. Computational analysis of metabolomics and transcriptomics results suggested that FFDZT regulated glutamate and oxidative stress-related metabolites (2-hydroxybutanoic acid and 2-hydroxyglutaric acid), glutamate receptors (NMDAR, KA, and AMPA), glutamate involved pathways (glutamatergic synapse pathway; d-glutamine and d-glutamate metabolism; alanine, aspartate and glutamate metabolism), as well as the reactive oxygen species metabolic process. CMAP analysis indicated that two active ingredients of FFDZT (tanshinone ⅡA and senkyunolide I) could act as glutamate receptor antagonists. Next, putative therapeutic targets of FFDZT's active ingredients identified in the brain were collected from multiple resources and filtered by statistical criteria and tissue expression information. Network pharmacological analysis revealed extensive interactions between FFDZT's putative targets, anti-IS drug targets, and glutamate-related enzymes, while the resulting PPI network exhibited modular topology. The targets in two of the modules were significantly enriched in the glutamatergic synapse pathway. The interactions between FFDZT's ingredients and important targets were verified by molecular docking. Finally, in vitro experiments validated the effects of FFDZT and its ingredients in suppressing glutamate-induced PC12 cell injury and reducing the generation of reactive oxygen species. All of our findings indicated that FFDZT's efficacy for treating ischemic stroke could be due to its neuroprotection against glutamate-induced oxidative cell death.
MeSH term(s)	Animals ; Cell Death ; Drugs, Chinese Herbal ; Glutamic Acid ; Infarction, Middle Cerebral Artery ; Ischemic Stroke ; Molecular Docking Simulation ; Neuroprotection ; Oxidative Stress ; Rats ; Reactive Oxygen Species ; Tablets
Chemical Substances	Drugs, Chinese Herbal ; Reactive Oxygen Species ; Tablets ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2022-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2022.105873
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Zs.A 653: Show issues

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Article ; Online: Mechanisms of Xiong-Pi-Fang in treating coronary heart disease associated with depression: A systematic pharmacology strategy and in vivo pharmacological validation.

Deng, Fangjuan / Li, Xiaofeng / Tang, Cheng / Chen, Jinhong / Fan, Boya / Liang, Jiayu / Zhen, Xin / Tao, Rui / Zhang, Shaoqiang / Cong, Zidong / Du, Wuxun / Zhao, Hucheng / Xu, Liang

Journal of ethnopharmacology

2022 Volume 298, Page(s) 115631

Abstract: ... disorders. Xiong-Pi-Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has ...

Abstract	Background: Coronary heart disease (CHD) and depression are very common and often co-existing disorders. Xiong-Pi-Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has shown satisfactory efficacy in treating CHD associated with depression. However, its mechanism of action is still unknown. Purpose: To employ a systematic pharmacology approach for identifying the action mechanisms of XPF in treating CHD associated with depression. Methods: We used a systematic pharmacology approach to identify the potential active mechanisms of XPF in treating CHD with depression. Potential active compounds in XPF and the diseases targets were screened using relevant databases to build corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. Results: Network pharmacology predicted 42 key targets and 20 signaling pathways involved in XPF-mediated treatment, with IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway significantly affected. The common influences were hypothalamic-pituitary-adrenal axis (HPA axis) and glucocorticoid signaling, validated through chronic unexpected mild stress (CUMS) with isoprenaline (ISO) for inducing CHD within the depression model in rats. In addition, XPF intake reduced depressive-like behaviors and improved ECG ischemic changes. Furthermore, XPF exerted some anti-inflammatory effects by inhibiting the interleukin-6 (IL-6) induced phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), ultimately downregulating hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) activation. The dysfunctional HPA axis feedback loop was also regulated, which enhanced the glucocorticoid receptor (GR) expression. In contrast, it improved glucocorticoid resistance by reducing the mineralocorticoid receptor expression. Conclusions: Suppressing IL-6 release and maintaining the HPA feedback loop balance could be the primary mechanism of XPF against CHD with depression. The significance of the IL-6 and HPA axis identified indicates their potential as essential targets for CHD therapy with depression.
MeSH term(s)	Animals ; Coronary Disease/drug therapy ; Coronary Disease/metabolism ; Depression/drug therapy ; Depression/metabolism ; Drugs, Chinese Herbal/metabolism ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Hypothalamo-Hypophyseal System ; Interleukin-6/metabolism ; Network Pharmacology ; Pituitary-Adrenal System ; Rats ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Drugs, Chinese Herbal ; Interleukin-6 ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2022-08-18
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.2022.115631
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Zs.A 1494: Show issues

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Article ; Online: Effects of Bushen-Tiaojing-Fang on the pregnancy outcomes of infertile patients with repeated controlled ovarian stimulation.

Ma, Yu-Cong / Hao, Gui-Min / Zhao, Zhi-Ming / Cui, Na / Fan, Yan-Li / Zhang, Shuan-Cheng / Chen, Jing-Wei / Cao, Yu-Cong / Guan, Feng-Li / Geng, Jing-Ran / Gao, Bu-Lang / Du, Hui-Lan

Scientific reports

2021 Volume 11, Issue 1, Page(s) 15233

Abstract: Bushen-Tiaojing-Fang (BSTJF) is commonly used to treat infertility. This study investigated ...

Abstract	Bushen-Tiaojing-Fang (BSTJF) is commonly used to treat infertility. This study investigated the effects of BSTJF on the pregnancy outcomes of patients with repeated controlled ovarian stimulation (COS), on mitochondrial function, and on oxidative stress in ovarian granulosa cells (GCs) and follicular fluid (FF). The samples and clinical data of 97 patients, including 35 in the control group, 29 in the placebo group and 33 in the BSTJF group, were collected for this study. The mitochondrial ultrastructure, ATP content, mitochondrial DNA (mtDNA) number, 8-hydroxy-2-deoxyguanosine (8-OHdG), Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) activity levels, and mRNA expression levels of Mn-SOD, GSH-Px, and nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) were analyzed. The high-grade embryo (P < 0.001), implantation (P = 0.033), and clinical pregnancy (P = 0.031) rates, as well as the ATP content (P = 0.014), mtDNA number (P = 0.035), GSH-Px activity (P = 0.004 in GCs and P = 0.008 in FF) and mRNA expression levels (P = 0.019), were significantly lower in the placebo group than in the control group, whereas the 8-OHdG content was significantly (P = 0.006 in FF) higher in the placebo group than in the control group. Compared with those in the placebo group, the high-grade embryo rate (P = 0.007), antioxidant enzyme activity (P = 0.037 and 0.036 in Mn-SOD; P = 0.047 and 0.030 in GSH-Px) and mRNA level (P < 0.001 in Nrf2, P = 0.039 in Mn-SOD and P = 0.002 in GSH-Px) were significantly higher in the BSTJF group, as were changes in mitochondrial ultrastructure, ATP (P = 0.040) and mtDNA number (P = 0.013). In conclusion, BSTJF can improve oxidative stress in patients with repeated COS and pregnancy outcomes.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Adult ; Drugs, Chinese Herbal/therapeutic use ; Embryo Implantation/physiology ; Female ; Follicular Fluid/metabolism ; Glutathione Peroxidase/metabolism ; Humans ; Infertility, Female/metabolism ; Infertility, Female/therapy ; Mitochondria/metabolism ; NF-E2-Related Factor 2/metabolism ; Ovulation Induction/methods ; Pregnancy ; Pregnancy Outcome ; Superoxide Dismutase/metabolism
Chemical Substances	Bushen formula ; Drugs, Chinese Herbal ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Adenosine Triphosphate (8L70Q75FXE) ; Glutathione Peroxidase (EC 1.11.1.9) ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2021-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-94366-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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