JOURNAL OF ETHNOPHARMACOLOGY
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2019
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IF 3.414
Xia Gao,Chaojie Huang,Ting Geng,Xialin Chen,Jiajia Wang,Jingying Liu,Kun Duan,Liang Cao,Zhenzhong Wang,Wei Xiao
Ethnopharmacological relevance Reduning injection (RDN), a patented traditional Chinese medicine , has the obvious antipyretic effect and has been widely used in China. Although some previous studies proved its antipyretic effect by animal efficacy experiment or clinical observation, its holistic mechanism in vivo was still unclear. Aim of the study To comprehensively elucidate the antipyretic mechanism of RDN, the investigation of fever-related potential biomarkers and metabolic pathways in the rat fever model is described in this paper. Materials and methods Rat fever model was established by dry yeast. A large number of endogenous metabolites in serum and urine were detected by UPLC-Q-TOF/MS, and fever-related potential biomarkers were screened and identified by multivariate analysis and metabolite databases. The reliability and biological significance of the largely disturbed biomarkers was verified by the metabolic network and the correlation with pharmacodynamic indicators, which contained IL-1β, IL-6, TNF-α, PGE 2 and cAMP. Results The established UPLC-Q-TOF/MS analytical method afforded satisfactory results in terms of precision, repeatability and stability, which met the requirements of biological sample determination. A total of 32 potential biomarkers associated with fever were screened and identified, among which 22 species could be adjusted by RDN. The metabolism pathway analysis revealed that valine , leucine and isoleucine biosynthesis, and sphingolipid metabolism were greatly disturbed. Their biomarkers involved L-leucine, L-valine, sphinganine and phytosphingosine , all of which showed a callback trend after RDN was given. These 4 biomarkers had a certain correlation with some known fever-related small molecules and pharmacodynamic indicators, which indicated that the selected fever-related biomarkers had certain reliability and biological significance. Conclusions RDN has a good regulation of the metabolic disorder of endogenous components in dry yeast-induced fever rats. Its antipyretic mechanism is mainly related to the regulation of amino acid, lipid and energy metabolism. The study is useful to better understand and analyze the pharmacodynamic mechanism of complex systems, such as traditional Chinese medicine.
研究领域:
药理学
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民族药理学
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代谢组学
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中药
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INVESTIGATIVE SURGERY
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2019
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IF 1.642
Damu Lin,Hongqiang Wu,Zongwei Zhou,Zhenyu Tao,Tanghong Jia,Weiyang Gao
Background The therapeutics used to promote perforator flap survival function induces vascular regeneration and inhibit apoptosis. The present study aimed to explore the potential mechanism of the angiogenesis effects of Ginkgolide B (GB) in perforator flaps. Methods: A total of 72 rats were divided into three groups and treated with saline, GB, or GB + tunicamycin (TM; ER stress activator) for seven consecutive days, respectively. Apoptosis was assayed by determining the Bax/Bcl-2 ratio and caspase-3 level. Endoplasmic reticulum (ER) stress markers (CHOP, GRP78, and caspase-12) were detected by Western blot analysis. Oxidative stress was assessed by measuring the superoxide dismutase activity (SOD) and malondialdehyde (MDA), heme oxygenase-1(HO-1), and nuclear factor erythroid-2-related factor 2 (Nrf2) mRNA levels in the flaps. The percentage flap survival area and blood flow were assessed on postoperative day (POD) 7. Angiogenesis was visualized by hematoxylin and eosin and CD34 staining on POD 7. Results: GB increased the survival of perforator flaps, the flap survival area of GB, GB + TM, and control groups was 90.83 ± 1.93%, 70.93 ± 4.13%, and 62.97 ± 6.50%. GB decreased the Bax/Bcl-2 ratio and caspase-3 level. ER stress-related proteins were downregulated by GB. GB also decreased the MDA level and increased SOD activity, HO-1 and Nrf2 mRNA levels in the flaps. Further, GB induced regeneration of vascular vessels in comparison with saline or GB + TM. Conclusions: GB increased angiogenesis and alleviated oxidative stress by inhibiting ER stress, which increased the survival of perforator flaps. In contrast, GB + TM alleviated angiogenesis and induced oxidative stress by activating ER stress and decreasing the survival of perforator flaps.
研究领域:
药理学
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外科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2023
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IF 3.9
Xiudan Wang,Weijing Kong,Rui Yang,Chunyan Yang
Ventilator-induced lung injury (VILI) disturbs the disordered immune system and causes persistent inflammatory damage. 4-octyl itaconate (OI) is a synthetic cell-permeable itaconate derivative with antioxidant and anti-inflammatory effects. In this study, we assessed whether OI protects against VILI. OI was intraperitoneally injected for three days before mechanical ventilation (MV; 20 ml/kg at 70 breaths/min) for 2 h. Mouse lung vascular endothelial cells (MLVECs) were pretreated with OI (62.5, 125, and 250 μM) prior to cyclic stretch for 4 h. We found that OI attenuated VILI and inflammatory response. OI also increased superoxide dismutase, nuclear factor E2-related factor 2, and heme oxygenase-1 levels, and decreased reactive oxygen species and malondialdehyde levels. Furthermore, OI inhibited the expression of NLR family pyrin domain-containing 3 (NLRP3), caspase-1 p20, apoptosis-associated speck-like protein containing a CARD, and N-terminal fragment of gasdermin D. Therefore, OI attenuates VILI, potentially by suppressing oxidative stress and NLRP3 activation.
研究领域:
药理学
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免疫学
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呼吸医学
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炎症
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氧化应激
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产品关联
DOI
PubMed
高影响因子
Heliyon
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2024
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IF 3.4
Lina Ba,Mingyao E,Ruixuan Wang,Nan Wu,Rui Wang,Renling Liu,Xiang Feng,Hanping Qi,Hongli Sun,Guofen Qiao
Background Cardiac remodeling is a common pathological feature in many cardiac diseases, characterized by cardiac hypertrophy and fibrosis. Triptolide (TP) is a natural compound derived from Tripterygium wilfordii Hook F. However, the related mechanism of it in cardiac remodeling has not been fully understood. Methods and results Transverse aortic constriction (TAC)-induced cardiac hypertrophic mouse model and angiotensin II (Ang II)-induced cardiomyocytes hypertrophic model were performed. Firstly, the results indicate that TP can improve cardiac function, decreased cardiomyocyte surface area and fibrosis area, as well as lowered the protein expressions of brain natriuretic peptide (BNP), β-major histocompatibility complex (β-MHC), type I and III collagen (Col I and III). Secondly, TP suppressed cardiac pyroptosis, and decreased the levels of Interleukin-1β (IL-1β), Interleukin-18 (IL-18) by Enzyme-linked immunosorbent assay (ELISA), and pyroptosis-associated proteins. Furthermore, TP enhanced the expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). Interestingly, when Nrf2 was silenced by siRNA, TP lost its properties of reducing pyroptosis and cardiac hypertrophy. In addition, in the Transforming Growth Factor β1 (TGF-β1)-induced primary human coronary artery endothelial cells (HCAEC) model, TP was found to inhibit the process of endothelial-to-mesenchymal transition (EndMT), characterized by the loss of endothelial-specific markers and the gain of mesenchymal markers. This was accompanied by a suppression of Slug, Snail, and Twist expression. Meanwhile, the inhibitory effect of TP on EndMT was weakened when Nrf2 was silenced by siRNA. Lastly, potential targets of TP were identified through network pharmacology analysis, and found that Ubiquitin-Specific Protease 14 (USP14) was one of them. Simultaneously, the data indicated that decrease the upregulation of USP14 and Kelch-like ECH-Associated Protein 1 (Keap1) caused by cardiac remodeling. However, Keap1 was decreased and Nrf2 was increased when USP14 was silenced. Furthermore, CoIP analysis showed that USP14 directly interacts with Keap1. Conclusion TP can observably reduce pyroptosis and EndMT by targeting the USP14/Keap1/Nrf2 pathway, thereby significantly attenuating cardiac remodeling.
研究领域:
心脏病学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
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IF 2.956
Xiaobao Gong,You Yang,Ligua Huang,Qingyan Zhang,Rong-Zhen Wan,Peng Zhang,Baoshun Zhang
To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/ d -galactosamine ( d -GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/ d -GalN. Catalase , glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/ d -GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E 2 (PGE 2 ). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway , and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/ d -GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/ d -GalN-induced ALF in the future.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL NEUROANATOMY
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2022
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IF 3.097
Liaoxi Tan,Yixin Hu,Xinyi Zhang,Chunlei Zhang,Chuchu Xi,Zhao Yang,Zhengyu Cao,Fang Zhao
Background and purpose Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability . The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms. Experimental approach Neuropathic pain was modeled using chronic constriction sciatic nerve injury (CCI) in rats. Western blot , immunofluorescence, and qRT-PCR were used to evaluate the levels of protein and mRNA. Key results Intraperitoneal administration of Cor G concentration-dependently ameliorates mechanical and thermo allodynia , suppresses CCI-induced p38/ERK phosphorylation and spinal cord microglia activation, and attenuates the expression levels of NO, inos , Tnf-α , Pge 2 in dorsal horn of L4-L6 spinal cord on the ligation side in CCI rats. Pretreatment with 30 μM Cor G decreased LPS-induced BV2 microglia activation, which occurred via the inos , Tnf-α , Il-1β , Il-6 and phospho-p38/ERK pathways. Conclusions and implications Taken together, we suggest that Cor G, the specific phthalide isoquinoline from traditional Chinese medicine Corydalis Decumbentis Rhizoma, may be promising for treatment of neuropathic pain.
研究领域:
药理学
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神经科学
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传统中药
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Dou Peiyuan,Liu Linlin,Jin Mozhu,Huang Jing,Lekhooa Rose Makhotso,Ran Xiaoku,Yan Xiaohui
Introduction: Black ginseng (BG) was processed by “steaming and drying” (generally nine times) repeatedly to produce “rare saponins” and secondary ginsenosides. Both ginseng (GS) and red ginseng (RG) were commonly used in treating heart failure (HF), and the latter was confirmed to be more potent, implying the presence of rare ginsenosides that contribute positively to the treatment of heart failure. Previous research indicated that rare ginsenosides are more abundant in BG than in RG. Consequently, this study aims to investigate the effects of BG and its components on HF to elucidate the active substances and their underlying mechanisms in the treatment of HF.Methods: The effects of BG and its fractions (water-eluted fraction (WEF), total saponin fraction (TSF), and alcohol-eluted fraction (AEF)) on rats with isoproterenol (ISO)-induced HF were explored, and steroids belonging to the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes were determined quantitatively using the ultra-performance liquid chromatography–triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method. In addition, 16S rDNA sequencing was performed on the gut microbiota, followed by GC–MS analysis of short-chain fatty acids (SCFAs), and the biochemical indexes related to energy metabolism and the serum cyclic nucleotide system were also analyzed by ELISA.Results: Based on a thorough evaluation of energy metabolism and the endocrine system, it was observed that the effects of BG components on the hypothalamic–pituitary–thyroid (HPT) and HPA axes were more pronounced. Notably, the treatment efficacy of the low dose of the total saponin fraction (TSFL), water decoction (WD), and high dose of the polysaccharide fraction (PSFH) was superior based on pharmacodynamic indicators such as brain natriuretic peptide (BNP), creatine kinase (CK), and estradiol (E2)/T). Furthermore, the WD and BG components exhibited significant effects on androgens (T and androstenedione (A4)). The TSFL group exerts an anti-inflammatory effect by regulating Lactobacillus/Erysipelotrichales. The WD, PSFH, and TSFL may impact inflammatory cytokines through the gut microbiota (Lactobacillus/Erysipelotrichales) and their metabolites (acetate and butyrate), exerting an anti-inflammatory effect.Discussion: The BG and all its split components demonstrated varying levels of efficacy in alleviating HF, and TSF and PSF exhibited a significant protective effect on HF. The main active components in TSF were revealed to be ginsenosides Rk1, Rk3, 20-(S)-Rg3, and 20-(S)-Rh2 by the H9C2 cell experiment. The decoction of BG and its components exhibited a potent impact on androgen hormones, with an elevation trend. This phenomenon may be attributed to the activation of the eNOS-NO pathway through androgen regulation, thereby contributing to its anti-HF activities. The WD, PSFH, and TSFL may exert anti-inflammatory effects through the intestinal flora (Lactobacillaceae/Erysipelotrichaceae) and its metabolites (acetic acid and butyric acid), which affect the inflammatory factors. The different mechanisms of action of each component of HF also reflect the significance and necessity of the overall role of traditional Chinese medicine (TCM). Our research was the first to report that the E2/T is related to HF and can be used as an indicator to evaluate HF.
研究领域:
药理学
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心脏病学
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传统中药
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内分泌学
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微生物学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yan Lin,Xing-Jun Chen,Jing-Jing Li,Lei He,Ya-Ru Yang,Fei Zhong,Ming-Hui He,Yi-Tong Shen,Bo Tu,Xu Zhang,Zhu Zeng
Ethnopharmacology relevance Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. Aim of the study This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1 ) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4 )-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. Materials and methods The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. Results The lavandulyl flavonoid (kurarinol A, 1 ) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What’s more, we found that treatment with kurarinol A ( 1 ) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. Conclusion These findings demonstrated that the novel compound (kurarinol A, 1 ) possessed notable hepatoprotective activity against CCl 4 . It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.
研究领域:
药理学
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民族药理学
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分子生物学
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细胞生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Ya-Nan Jia,Hai-Peng Lu,Ya-Lin Peng,Bao-Shun Zhang,Xiao-Bao Gong,Jun Su,You Zhou,Min-Hui Pan,Li Xu
Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d -galactosamine (LPS/ d -GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines. Oxy treatment diminished the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway in liver, activated the Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and increased expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1(NQO1). Pretreatment with Oxy decreased LPS/ d -GalN stimulated hepatocyte apoptosis by efficaciously raising the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) ratio, inhibiting the expression and activation of caspases , and activating the phosphoinoside-3-kinase (PI3K)-Akt pathway. Our results demonstrate the hepatoprotective efficacy of Oxy. The protection is mainly due to the prevention of TLR4/NF-κB pathway activation, induced activation of Keap1-Nrf2 signaling pathway, and decreased hepatocyte apoptosis. Oxy warrants further study as a potential therapeutic agent candidate for the management of acute liver injury.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2022
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IF 10.753
Jinhua Jiang,Changpeng Zhang,Luyan Wang,Xiangyun Wang,Hongmei He,Shenggan Wu,Xueping Zhao
Limited literature had focused on the combined effect of triazole fungicides on aquatic organisms at environmental concentrations. In this research, difenoconazole (DIF) and tebuconazole (TEB) mixture exhibited additive effect on the acute toxicity to zebrafish embryos. The transcriptomics and metabolomics demonstrated DIF and TEB mixtures at aquatic life benchmark and environmental concentration simultaneously influenced the lipid metabolism, arachidonic acid metabolism, steroid hormone biosynthesis and tryptophan metabolism, but showed diverse response patterns mediating the combined effects on zebrafish embryos after 120 h exposure. The DIF and TEB mixture at aquatic life benchmark caused combined effect on yolk sac resorption and metabolites, was less than the additive effect of individual DIF and TEB. It was found environmental concentration of DIF and TEB caused much lower levels of IFN and IL6, induced higher levels of PGE 2 , l -kynurenine and formylanthranilate in zebrafish larvae, and their binary mixture caused synergistic effect on the accumulation of metabolites in metabolic pathways, which might cause more negative effect and risk on growth in zebrafish later life stages. Results further demonstrated that adding arachidonic acid (AA) increased the transcripts of Pla 2 , Ptgs1 , Cyp19a and Cxcl8b , allayed the accumulation of PLA 2 and 17 β -E 2 , and induced more PGF2 α , IFN and IL6 levels in zebrafish larvae, indicated AA metabolism might play important regulatory roles on hormone synthesis and immune response caused by DIF and TEB mixtures. Current results indicated the risk assessment of mixtures based on single concentration may not precisely estimate the environmental risk and health effect, it is crucially important to consider the multi-concentration combinations, and more attention should be paid to the environmental concentration.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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药理学
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生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）