Biomed Research International
·
2021
·
IF 3.411
Xuehua Piao,Xiaodan Sui,Baohai Liu,Tingfang Cui,Zinan Qi
Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.
研究领域:
药理学
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分子生物学
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传统中药研究
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Qian Wu,A-Ling Tang,Qing-Qing Dong,Bing-Qing Chen,Yi Shi,Xiao-Ling Xu,Wei Chen,Wei Chen
Sepsis still remains the leading cause of morbidity and mortality in clinical settings, characterized by pyroptosis-induced cytokine release syndrome, multiple organ dysfunction, and gut microbiota disturbances. Inhibiting the pyroptosis pathway by nanosystems represents a potential therapeutic strategy for the treatment of sepsis. However, current pharmacological interventions primarily focus on blocking reactive oxygen species (ROS)/NOD-like receptor pyrin domain-containing 3 (NLRP3)/Caspase-1-based pyroptosis rather than lipopolysaccharide (LPS)-triggered pyroptosis. Besides, given the importance of microbiota disturbances in a second wave of cytokine storms, the assessment of the composition of intestinal flora after treatment was also missing. Herein, picroside II-encapsulated, palmitic acid-modified nanoformulations were prepared as a pyroptosis modulator to inhibit cytokine release syndrome, accompanied by reprogramming the composition of intestinal flora. Results demonstrated that the modification of palmitic acid on nanoformulations promotes the cellular uptake of nanoparticles via Toll-like receptor-mediated specific recognition. The sustained release of picroside II scavenged the massive reactive oxygen species, reduced the levels of inflammatory factors, and downregulated the pyroptosis-related proteins. Furthermore, the interaction between palmitic acid and Toll receptors reduced the combination site of LPS, providing a positive loop in drug delivery and inhibiting pyroptosis. Consequently, the obtained nanoformulations exerted a better antioxidant, anti-inflammatory, and antiproptosis activity than other treatment groups, thereby alleviating LPS-stimulated multiorgan damage, especially the kidney and colon. Interestingly, it also improved the abundance of intestinal flora, contributing to enhanced intestinal barrier function and improved immune system. Thus, palmitic acid-anchored, picroside II-encapsulated nanoformulations potentiated a systematic and desirable therapeutic outcome in sepsis treatment.
研究领域:
纳米医学
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免疫学
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微生物学
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药理学
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Tingting Li,Lijie Xu,Rongyao Zheng,Xinjie Wang,Liwen Li,Hui Ji,Qinghua Hu
Backgroud Cholestasis , accompanied by the accumulation of bile acids in body, may ultimately cause liver failure and cirrhosis. There have been limited therapies for cholesteric disorders. Therefore, development of appropriate therapeutic drugs for cholestasis is required. Picroside II is a bioactive component isolated from Picrorhiza scrophulariiflora Pennell , its mechanistic contributions to the anti-cholestasis effect have not been fully elucidated, especially the role of picroside II on bile acid homeostasis via nuclear receptors remains unclear. Purpose This study was designed to investigate the hepatoprotective effect of picroside II against alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury and elucidate the mechanisms in vivo and in vitro . Methods The ANIT-induced cholestatic mouse model was used with or without picroside II treatment. Serum and bile biochemical indicators, as well as liver histopathological changes were examined. siRNA , Dual-luciferase reporter, quantitative real-time PCR and Western blot assay were used to demonstrate the farnesoid X receptor (FXR) pathway in the anti-cholestasis effects of picroside II in vivo and in vitro . Results Picroside II exerted hepatoprotective effect against ANIT-induced cholestasis by impaired hepatic function and tissue damage. Picroside II increased bile acid efflux transporter bile salt export pump (Bsep), uptake transporter sodium taurocholate cotransporting polypeptide (Ntcp), and bile acid metabolizing enzymes sulfate transferase 2a1 (Sult2a1) and UDP-glucuronosyltransferase 1a1 (Ugt1a1), whereas decreased the bile acid synthesis enzymes cholesterol 7α-hydroxylase (Cyp7a1) and oxysterol 12α-hydroxylase (Cyp8b1). In addition, expression of FXR and the target gene Bsep was increased, whereas aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor alpha (PPARα) and their corresponding target genes were not significantly influenced by picroside II under cholestatic conditions. Furthermore, regulation of transporters and enzymes involved in bile acid homeostasis by picroside II were abrogated by FXR silencing in mouse primary cultured hepatocytes. Dual-luciferase reporter assay performed in HepG2 cells demonstrated FXR activation by picroside II. Conclusion Our findings demonstrate that picroside II exerts protective effect on ANIT-induced cholestasis possibly through FXR activation that regulates the transporters and enzymes involved in bile acid homeostasis. Picroside II might be an effective approach for the prevention and treatment of cholestatic liver diseases.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
TALANTA
·
2015
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IF 3.545
Wenjing Wang,Lu Wang,Lina Zou,Gaiping Li,Baoxian Ye
A novel voltammetric sensor was constructed by simple dripping single-walled carbon nanotubes (SWCNTs) on to the glass carbon electrode (GCE) firstly and electro-polymerizing l -Citrulline film subsequently. The resulting poly( l -Citrulline)/SWCNTs/GCE showed a significant voltammetric response to picroside II due to the synergistic effect of SWCNTs and poly( l -Citrulline) film. The first electroanalytical method of picroside II was proposed with detection linear range from 8.0×10 −8 to 5.0×10 −6 mol L −1 and a detection limit of 3×10 −8 mol L −1 .The high sensitivity, selectivity and long-term stability made the sensor suitable for the determination of picroside II. Moreover, based on the systematically investigation and some kinetics parameters calculated in the experimentation, the reaction mechanism of picroside II at the poly( l -Citrulline)/SWCNTs modified GCE was obtained reliably. Lastly, the proposed sensor was used for the determination of picroside II in real sample with satisfactory results. This work promoted the potential applications of amino acid materials and SWCNTs in electro-chemical sensors.
研究领域:
分析化学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 5
·1058-1066
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IF 2.772
Nong Xiaolian,Lan Yuyan
Reactive astrocyte-mediated neuroinflammatory responses in the spinal dorsal horn have been reported to play a pivotal role in pathological pain. Chronic constriction injury (CCI) enhances the activation of nuclear factor kappa B (NF-κB), which is involved in neuropathic pain (NP). Picroside II (PII), a major active component of Picrorhiza scrophulariiflora, has been investigated for its anti-oxidative, anti-inflammatory, and anti-apoptotic activities. Here, we explored the analgesic effects of PII on a model of CCI-induced NP and investigated the levels of the GFAP protein and the mRNA and protein levels of pro-inflammatory cytokines in the spinal cord, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). CCI significantly induced mechanical allodynia and thermal hyperalgesia. Intraperitoneal administration of PII remarkably reversed the CCI-induced mechanical allodynia and thermal hyperalgesia and reduced the mRNA and protein levels of IL-1β, IL-6, and TNF-α in the spinal cord. Additionally, according to the in vitro data, the PII treatment inhibited LPS-induced increases in the mRNA and protein levels of IL-1β, IL-6, and TNF-α and suppressed the NF-κB pathway by inhibiting the phosphorylation of NF-κB/p65 and the degradation of inhibitor of NF-κB (IκB) in astrocytes without toxicity to astrocytes. Overall, the analgesic effect of PII correlated with the inhibition of spinal reactive astrocyte-mediated neuroinflammation through the NF-κB pathway in rats with NP.
研究领域:
药理学
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神经科学
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疼痛研究
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炎症
✓ 已验证
DOI
PubMed
高影响因子
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