BRITISH JOURNAL OF PHARMACOLOGY
·
2019
·Vol. 176
·期 14
·2627-2641
·
IF 6.583
Zheng Xu,Chunpeng Zou,Weihui Yu,Sujing Xu,Lan Huang,Zia Khan,Jingying Wang,Guang Liang,Yi Wang
Background and Purpose Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II greatly contributes to the progression of hypertensive kidney disease. Angiotensin II has recently been shown to activate STAT3 in cardiovascular cells. However, the underlying mechanisms of STAT3 activation by angiotensin II and downstream functional consequences in the kidneys are not fully understood. Experimental Approach C57BL/6 mice were treated with angiotensin II by subcutaneous infusion for 1 month to develop nephropathy. Mice were treated with either adeno-associated virus expressing STAT3 shRNA or STAT3 inhibitor, S3I-201. Human archival kidney samples from five patients with hypertension and five individuals without hypertension were also examined. In vitro, STAT3 was blocked using siRNA or STAT3 inhibitor S3I-201 in the renal proximal tubular cell line, NRK52E, after exposure to angiotensin II. Key Results Angiotensin II activated STAT3 in kidney epithelial cells through engaging toll-like receptor 4 (TLR4) and JAK2, which was independent of IL-6/gp130 and angiotensin AT 1 receptors. Angiotensin II-mediated STAT3 activation increased fibrotic proteins and resulted in renal dysfunction. Both STAT3 inhibition by the low MW compound S3I-201 and TLR4 deficiency normalized renal fibrosis and dysfunction caused by Ang II in mice, without affecting hypertension. Conclusions and Implications Our study reveals a novel mechanism of STAT3 activation, induced by angiotensin II, in kidney tissues and highlights a translational significance of a STAT3 inhibitor as potential therapeutic agent for hypertensive kidney disease.
研究领域:
肾病学
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药理学
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分子生物学
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心血管疾病
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2022
·Vol. 180
·期 8
·1114-1131
·
IF 9.473
Weiwei Zhu,Minxiu Wang,Leiming Jin,Bin Yang,Bin Bai,Rumbidzai Natasha Mutsinze,Wei Zuo,Nipon Chattipakorn,Joo Young Huh,Guang Liang,Yi Wang
Background and Purpose Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a challenging clinical syndrome that leads to various respiratory sequelae and even high mortality in patients with severe disease. The novel pharmacological strategies and therapeutic drugs are urgently needed. Natural products have played a fundamental role and provided an abundant pool in drug discovery. Experimental Approach A compound library containing 160 natural products was used to screen potential anti-inflammatory compounds. Mice with LPS-induced ALI was then used to verify the preventive and therapeutic effects of the selected compounds. Key Results Licochalcone A was discovered from the anti-inflammatory screening of natural products in macrophages. A qPCR array validated the inflammation-regulatory effects of licochalcone A and indicated that the potential targets of licochalcone A may be the upstream proteins in LPS pro-inflammatory signalling. Further studies showed that licochalcone A directly binds to myeloid differentiation factor 2 (MD2), an assistant protein of toll-like receptor 4 (TLR4), to block both LPS-induced TRIF- and MYD88-dependent pathways. LEU61 and PHE151 in MD2 protein are the two key residues that contribute to the binding of MD2 to licochalcone A. In vivo , licochalcone A treatment alleviated ALI in LPS-challenged mice through significantly reducing immunocyte infiltration, suppressing activation of TLR4 pathway and inflammatory cytokine induction. Conclusion and Implications In summary, our study identified MD2 as a direct target of licochalcone A for its anti-inflammatory activity and suggested that licochalcone A might serve as a novel MD2 inhibitor and a potential drug for developing ALI/ARDS therapy. Graphical Licochalcone A directly binds with MD2 whereas LEU61 and PHE151 are two key residues for conformational stabilization. This interaction blocks the biological function of MD2 in transducing the signalling from the LPS-induced TLR4 pathway, subsequently restrains both TBK1/IRF3 and TAK1/MAPKs/NF-κB activation and inflammatory cytokines, chemokines, interferons, and so on overexpression, thus decreasing the immune cell infiltration in lung tissue and improving the acute lung injury.
研究领域:
药理学
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免疫学
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分子生物学
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药物发现
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2014
·Vol. 171
·期 23
·5252-5264
·
IF 4.99
Jing Han,Lidan Sun,Xun Huang,Zheng Li,Chenyu Zhang,Hai Qian,Wenlong Huang
Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly 8 -GLP-1(7–36)-NH 2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro . In vivo , effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t 1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation.
研究领域:
药理学
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糖尿病研究
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药物化学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2018
·Vol. 176
·期 3
·416-435
·
IF 6.81
Jingyan Li,Junying Huang,Jing Lu,Zhen Guo,Zhuoming Li,Hui Gao,Panxia Wang,Wenwei Luo,Sidong Cai,Yuehuai Hu,Kaiteng Guo,Luping Wang,Zhenzhen Li,Minghui Wang,Xiaolei Zhang,Peiqing Liu
Background and Purpose Activation of PKC-ζ is closely linked to the pathogenesis of cardiac hypertrophy. PKC-ζ can be activated by certain lipid metabolites such as phosphatidylinositol (3,4,5)-trisphosphate and ceramide. However, its endogenous negative regulators are not well defined. Here, the role of the sirtuin1-PKC-ζ signalling axis and the underlying molecular mechanisms were investigated in cardiac hypertrophy. Experimental Approach Cellular hypertrophy in cultures of cardiac myocytes, from neonatal Sprague-Dawley rats, was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Interaction between sirtuin1 and PKC-ζ was investigated by co-immunoprecipitation and confocal immunofluorescence microscopy. Sirtuin1 activation was enhanced by resveratrol treatment or Ad-sirtuin1 transfection. A model of cardiac hypertrophy in Sprague-Dawley rats was established by abdominal aortic constriction surgery or induced by isoprenaline in vivo . Key Results Overexpression of PKC-ζ led to cardiac hypertrophy and increased activity of NF-κB, ERK1/2 and ERK5, which was ameliorated by sirtuin1 overexpression. Enhancement of sirtuin1 activity suppressed acetylation of PKC-ζ, hindered its binding to phosphoinositide-dependent kinase 1 and inhibited PKC-ζ phosphorylation in cardiac hypertrophy. Consequently, the downstream pathways of PKC-ζ' were suppressed in cardiac hypertrophy. This regulation loop suggests a new role for sirtuin1 in mediation of cardiac hypertrophy. Conclusions and Implications Sirtuin1 is an endogenous negative regulator for PKC-ζ and mediates its activity via regulating the acetylation and phosphorylation in the pathogenesis of cardiac hypertrophy. Targeting the sirtuin1-PKC-ζ signalling axis may suggest a novel therapeutic approach against cardiac hypertrophy.
研究领域:
心脏病学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2017
·Vol. 175
·期 5
·840-854
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IF 5.491
Yali Zhang,Tingting Xu,Zheer Pan,Xiangting Ge,Chuchu Sun,Chun Lu,Hongjin Chen,Zhongxiang Xiao,Bing Zhang,Yuanrong Dai,Guang Liang
Background and Purpose Acute lung injury (ALI) is a challenging clinical syndrome, which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating LPS-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin, a natural naphthoquinone, prevents LPS-induced inflammation. However, little is known about the underlying mechanisms. Experimental Approach The binding affinity of shikonin to MD2 was analysed using computer docking, surface plasmon resonance analysis and elisa . In vitro , the anti-inflammatory effect and mechanism of shikonin were investigated through elisa , real-time quantitative reverse transcription PCR, Western blotting and immunoprecipitation assay. In vivo , lung injury was induced by intratracheal administration of LPS and assessed by changes in the histopathological and inflammatory markers. The underlying mechanisms were investigated by immunoprecipitation in lung tissue. Key Results Shikonin directly bound to MD2 and interfered with the activation of toll-like receptor 4 (TLR4) induced by LPS. In cultured macrophages, shikonin inhibited TLR4 signalling and pro-inflammatory cytokine production. These effects were produced through suppression of key signalling proteins including the NF-κB and the MAPK pathway. We also showed that shikonin inhibits MD2–TLR4 complex formation and reduces LPS-induced inflammatory responses in a mouse model of ALI. Conclusions and Implications Our studies have uncovered the mechanism underlying the biological activity of shikonin in ALI and suggest that the targeting of MD2 may prove to be beneficial as a treatment option for this condition.
研究领域:
药理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2016
·Vol. 173
·期 10
·1693-1702
·
IF 5.259
Qing Zhu,Yuehua Sun,Lina Mao,Chengpeng Liu,Bo Jiang,Wei Zhang,Jun-Xu Li
Background and Purpose This study examined the antinociceptive effects of sinomenine in a rat model of postoperative pain. Experimental Approach Male and female rats were subjected to a surgical incision in the right hind paw, and the von Frey filament test was used to measure mechanical hypersensitivity after drug or vehicle treatment (p.o. or i.p.). Rats were treated daily with sinomenine before or after the surgery and the AUCs of the antinociceptive effects measured during a 4 h period were calculated to determine the ED 50 values of sinomenine. The anti-hyperalgesic effects of different doses of a combination of sinomenine and acetaminophen (paracetamol) were assessed in another group of rats. Dose combinations were determined by using a fixed ratio dose-addition analysis method. Key Results Sinomenine (5–80 mg·kg −1 ) produced dose-dependent antinociceptive effects in rats that had been subjected to surgery and this effect lasted for 4 h. The potency of sinomenine, given i.p. or p.o., did not differ between male and female rats. However, sinomenine was fourfold more potent when given i.p. than p.o. The GABA A receptor antagonist bicuculline blocked the antinociceptive effects of sinomenine. The antinociceptive effect of a daily treatment with sinomenine remained stable throughout the course of postoperative pain. Pretreatment with sinomenine did not alter the mechanical hypersensitivity post-surgery. The combination of sinomenine with acetaminophen produced an infra-additive interaction. Conclusions and Implications Sinomenine demonstrated significant antinociceptive activity against postoperative pain and may be a useful novel pharmacotherapy for the management of postoperative pain.
研究领域:
药理学
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疼痛研究
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2022
·Vol. 179
·期 18
·4563-4574
·
IF 9.473
Rongcai Ye,Chunlong Yan,Huiqiao Zhou,Chuanhai Zhang,Yuanyuan Huang,Meng Dong,Hanlin Zhang,Jun Lin,Xiaoxiao Jiang,Shouli Yuan,Li Chen,Rui Jiang,Ziyu Cheng,Kexin Zheng,Anni Yu,Qiaoli Zhang,Lin-hu Quan,Wanzhu Jin
Background and Purpose Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disease affecting women of reproductive age. Due to its complex aetiology, there is no currently effective cure for PCOS. Brown adipose tissue (BAT) activity is significantly decreased in PCOS patients, and BAT activation has beneficial effects in animal models of PCOS. Here, we investigated the effect of ginsenoside compound K (CK) in an animal model of PCOS and its mechanism of BAT activation. Experimental Approach Primary brown adipocytes, Db/Db mice and dehydroepiandrosterone (DHEA)-induced PCOS rats were used. The core body temperature, oxygen consumption, energy metabolism related gene and protein expression were assessed to identify the effect of CK on overall energy metabolism. Oestrous cycle, serum sex hormone, ovarian steroidogenic enzyme gene expression and ovarian morphology were also evaluated following CK treatment. Key Results Our results indicated that CK treatment could significantly protect against body weight gain in Db/Db mice via BAT activation. Furthermore, we found that CK treatment could normalize hyperandrogenism, oestrous cyclicity, normalize steroidogenic enzyme expression and decrease the number of cystic follicles in PCOS rats. Interestingly, as a potential endocrine intermediate, C-X-C motif chemokine ligand-14 protein (CXCL14) was significantly up-regulated following CK administration. In addition, exogenous CXC14 supplementation was found to reverse DHEA-induced PCOS in a phenotypically similar manner to CK treatment. Conclusion and Implications In summary, CK treatment significantly activates BAT, increases CXCL14 expression and ameliorates PCOS. These findings suggest that CK might be a potential drug candidate for PCOS treatment.
研究领域:
内分泌学
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代谢学
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药理学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2022
·Vol. 179
·期 17
·4440-4456
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IF 9.473
Mengru Bai,Mingyang Chen,Qingquan Zeng,Shuanghui Lu,Ping Li,Zhiyuan Ma,Nengming Lin,Caihong Zheng,Hui Zhou,Su Zeng,Dongli Sun,Huidi Jiang
Background and Purpose Plasma triglyceride (TG) levels increase as gestation proceeds, and abnormal elevation of TG increases the risk of pregnancy complications. The current study explored the mechanisms involved in hypertriglyceridaemia during pregnancy. Experimental Approach Lipid profile and expression levels of key genes involved in liver TG metabolism in non-pregnant and pregnant mice were studied. The effects of pregnancy-related hormones on key genes and the underlying mechanisms were uncovered in vitro and in vivo. Key Results Plasma and hepatic TG levels were elevated, while hepatic fatty acid translocase (FAT/CD36) was up-regulated in pregnant mice. Corticosterone and cortisol (endogenous glucocorticoids that are elevated during pregnancy), but not oestradiol or progesterone, significantly up-regulated CD36 in hepatocytes, and this was abolished after knockdown of the glucocorticoid receptor (GR) using a siRNA or in the presence of GR antagonists, RU486 and AL082D06. The luciferase reporter gene and chromatin immunoprecipitation assay further revealed that corticosterone/cortisol promoted the direct binding of GR to the CD36 promoter and up-regulated its transcription. Chronic corticosterone exposure induced liver lipid accumulation and increased plasma TG levels in mice, which were attenuated by RU486 via inhibition of the GR-CD36 pathway. Conclusions and Implications Increased corticosterone/cortisol induces liver lipid accumulation and hypertriglyceridaemia during pregnancy by accelerating fatty acid uptake into hepatocytes via activation of GR and its target gene, CD36. Our results may be useful for the prevention of severe hypertriglyceridaemia and associated pregnancy complications. Graphical
研究领域:
内分泌学
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肝病学
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药理学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2021
·Vol. 178
·期 24
·4808-4825
·
IF 8.74
Yan-Fei Yang,Hui Dong,Yan Shen,Lei Li,Michael Lazarus,Wei-Min Qu,Zhi-Li Huang
Background and Purpose Modafinil is a potent eugeroic (wakefulness-promoting) drug that is prescribed to treat narcolepsy and has a low incidence of abuse. Although previous studies have shown that modafinil-induced arousal depends on the dopamine receptors and transporters, the specific part/s of the dopamine transmitter system underlying this mechanism remained unclear. Here, we investigated the role of mesencephalic dopamine neurons in modafinil-evoked arousal. Experimental Approach A dopamine indicator (dLight1.1) was employed to detect dopamine changes in the nucleus accumbens (NAc) and dorsal striatum. We specifically lesioned mesencephalic dopamine neurons via diphtheria toxin (DTA) in the dopamine transporter (DAT)-Cre mice. Then, the sleep–wake states were recorded to evaluate the effect of modafinil on arousal. Finally, the extent of DTA-induced lesions was determined by immunohistochemistry. Key Results Modafinil promptly increased dopamine levels in the NAc and dorsal striatum in a dose-dependent manner. Lesioning of dopamine neurons in the substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) had no significant effects on physiological sleep–wake cycles. Modafinil at 90 mg·kg −1 increased continuous wakefulness for 355 min in control mice. However, these effects were slightly decreased by 6.7% in the SNc-lesioned mice and were prominently diminished by 32.8% in VTA-lesioned mice. Furthermore, the modafinil-induced arousal was completely blocked in the SNc-VTA-lesioned mice, whereas lesions of the dorsal raphé nucleus had no effect. Conclusion and Implications Taken together, our findings indicate that mesencephalic dopamine neurons are essential for modafinil-induced arousal. Graphical
研究领域:
神经科学
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药理学
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睡眠医学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2023
·
IF 7.3
Fangfang Wang,Meng Zhang,Meng Yuan,Zixuan Xia,Fengge Yang,Sihao Zhang,Tengyu Lin,Lianxiang Luo,Jinshan Tang,Youwei Zhang
Background and Purpose Chronic inflammation is pathogenic and contributes to human diseases, causing a significant threat to public health. The NLR family pyrin domain-containing protein 3 (NLRP3) is the best-characterized factor regulating inflammation. Therefore, targeting NLRP3 has the potential to treat inflammatory diseases and improve human health. Experimental Approach Lipopolysaccharide was used to induce inflammation in cell cultures. Lipopolysaccharide/ d -galactosamine and dextran sulfate sodium salt were used to induce acute liver inflammation and ulcerative colitis respectively in C57BL/6J mice. Western blotting, immunofluorescence, immunoprecipitation, quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the activation of the inflammatory response in cell cultures and in mice. Key Results JNUTS013, a novel sorbicillinoid compound recently synthesized by us, significantly inhibited inflammation both in cell cultures and in mouse models. Mechanistically, JNUTS013 induced proteasome-dependent degradation of NLRP3. Hence, it suppressed the formation of the NLRP3 inflammasome and the production of downstream inflammatory cytokines and chemokines. The inhibitory effect of JNUTS013 on NLRP3 protein expression was confirmed in mice. Importantly, JNUTS013 failed to ameliorate bowel inflammation in Nlrp3 -/- knockout mice, supporting NLRP3 as the biological target by which JNUTS013 inhibits inflammation. Further studies revealed critical chemical moieties of JNUTS013 required for inducing NLRP3 degradation. Conclusion and Implications This study identifies a novel compound JNUTS013 that inhibits inflammation through inducing NLRP3 protein degradation in vitro and in vivo , which not only supports the development of JNUTS013 as an anti-inflammation agent but also creates a new way for the treatment of inflammation by chemically inducing NLRP3 degradation. Graphical
研究领域:
药理学
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免疫学
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炎症研究
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2023
·
IF 7.3
Rui-Fang Dong,Cheng-Jiao Qin,Yong Yin,Liang-Liang Han,Cheng-Mei Xiao,Kai-Di Wang,Rong-Yuan Wei,Yuan-Zheng Xia,Ling-Yi Kong
Background and Purpose Chaperone-mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered. Experimental Approach Levels of CMA in non-small cell lung cancer (NSCLC) tissue samples were confirmed by tyramide signal amplification dual immunofluorescence assay. High-content screening was performed based on CMA activity, to identify potential inhibitors of CMA. Inhibitor targets were determined by drug affinity responsive target stability-mass spectrum and confirmed by protein mass spectrometry. CMA was inhibited and activated to elucidate the molecular mechanism of the CMA inhibitor. Key Results Suppression of interactions between HSC70 and LAMP2A blocked CMA in NSCLC, restraining tumour growth. Polyphyllin D (PPD) was identified as a targeted CMA small-molecule inhibitor through disrupting HSC70–LAMP2A interactions. The binding sites for PPD were E129 and T278 at the nucleotide-binding domain of HSC70 and C-terminal of LAMP2A, respectively. PPD accelerated unfolded protein generation to induce reactive oxygen species (ROS) accumulation by inhibiting HSC70–LAMP2A–eIF2α signalling axis. Also, PPD prevented regulatory compensation of macroautophagy induced by CMA inhibition via blocking the STX17–SNAP29–VAMP8 signalling axis. Conclusions and Implications PPD is a targeted CMA inhibitor that blocked both HSC70–LAMP2A interactions and LAMP2A homo-multimerization. CMA suppression without increasing the regulatory compensation from macroautophagy is a good strategy for NSCLC therapy. Graphical
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2023
·Vol. 180
·期 13
·1690-1709
·
IF 7.3
Weimin Kong,Xueying Sun,Siyu Yu,Peihua Liu,Xiaoke Zheng,Jiaxin Zhang,Liang Zhu,Tianxin Jiang,Mengmeng Jin,Jinghui Gao,Xiaomin Fan,Xiaodong Liu,Li Liu
Background and Purpose Liver failure is associated with psychiatric alterations, partly resulting from the increased brain dopamine levels. We investigated the relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and the mechanism by which liver failure increased dopamine levels in SH-SY5Y cells. Behavioural tests were carried out on day 13 and 27 following BDL, along with measurements of dopamine and metabolites, expressions of enzymes and transporters related to dopamine metabolism, and its transport into the cortex and the hippocampus. SH-SY5Y cells were used to investigate whether NH 4 Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase or not. Tyrosine hydroxylase (TH) expression in SH-SY5Y cells co-incubated with bilirubin and signal pathway inhibitors was measured. Key Results Open-field test results demonstrated BDL rats showed anxiety-like behaviour, accompanied by increased dopamine levels and expression of TH protein in the cortex. Membrane bound long form (MB)-COMT, slightly but significantly decreased. SH-SY5Y cells indicated that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF-κB pathway BAY 11-7082 and silencing NF-κB p65 reversed bilirubin-induced upregulation of TH protein. NF-κB activator TNF-α increased expression of TH protein. Roles of bilirubin in increases of TH protein expressions and dopamine levels were measured using hyperbilirubinemia rats. Anxiety-like behaviour, was associated with increased dopamine levels and TH protein expressions in hyperbilirubinemia rats. Conclusion and Implications BDL significantly increased dopamine levels in rat cortex partly due to bilirubin-mediated TH induction. Increased bilirubin induced TH expression via activating NF-κB signalling pathway.
研究领域:
神经科学
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药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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