FOOD AND CHEMICAL TOXICOLOGY
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2022
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IF 5.572
Wenshu Zou,Kai Zhang,Zhengying Qiu,Ruihua Xin,Guibo Wang,Jingyan Zhang,Jianxi Li
Damage caused by Salmonella is not only limited to the gastrointestinal tract, but also occurs in the central nervous system (CNS). The aim of this study was to explore the protective effects of asiatic acid (AA) and andrographolide (AD) on the CNS through simulating common infection in mice by oral administration of Salmonella typhimurium (S. typhimurium) . The results showed that the neurons in the hippocampus of mice were damaged after S. typhimurium invaded CNS in mice, and the inflammation was increased, which was manifested by the increased expression of inflammatory factors interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, interferon (IFN)-γ and IL-12b and the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes . The damage and inflammatory response of mouse hippocampal neurons were effectively reduced by AA or AD pretreatment . Furthermore, we observed the significant activation of microglia after S. typhimurium infection. AA and AD attenuated S. typhimurium -induced hippocampal injury by reducing the inflammatory response on microglia. The findings suggest that the AA and AD protect CNS from injury caused by S. typhimurium infection through inhibiting over expression of multiple neuroinflammatory mediators and NLRP3 inflammasome in mice.
研究领域:
神经科学
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免疫学
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药理学
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传染病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2022
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IF 5.589
Sicheng Yao,Naiying Chen,Mingming Li,Qiuyue Wang,Xinxing Sun,Xun Feng,Yang Chen
The study aimed to explore the size effect on the in vitro-in vivo correlation (IVIVC) in the oral absorption of andrographolide nanosuspensions (Ag-NS). Ag-NS with controllable particle sizes were prepared by ultrasonic dispersion method, and the formulation and process parameters were optimized through single factor experiments using mean particle size, polydispersity index, and stability as evaluation indicators. The morphology of Ag-NS was observed by scanning electron microscopy (SEM), and the crystalline state of the nanosuspensions was characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The dissolution tests were carried out with the paddle method in two different mediums simulating the pH conditions in intestinal fluid (pH 6.8) and gastric fluid (pH 1.2), respectively. The pharmacokinetic behaviors were investigated in rats after oral administration, and a deconvolution approach was introduced to determine the correlation between in vitro dissolution and in vivo absorption (IVIVC). The formulation with the use of lecithin and PEG-800 as stabilizers showed its potential in the size-controllable preparation of Ag-NS. Via altering the ultrasonication amplitude and time, three Ag-NS suspensions with three particle sizes, i.e., Ag-NS 250 (249.8 ± 1.3 nm), Ag-NS 450 (485.2 ± 3.7 nm), Ag-NS 1000 (1015 ± 36.1 nm) were prepared. Their morphological and crystal characteristics were not changed during the size reduction process, but both of their in vitro dissolution and in vivo absorption were improved. Relatively better IVIVC performance was observed with the in vitro dissolution data at pH 6.8 ( r > 0.9). With the reduction of particle size, the in vivo absorption fraction was more closed to the level of the in vitro dissolution. In conclusion, the decrease in particle size would improve the dissolution and absorption of Ag-NS, and also affect their IVIVC performance. The study would facilitate the design and quality control of Ag-NS in terms of particle size and dissolution specifications.
研究领域:
药剂学
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药理学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Journal of Bionic Engineering
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2026
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IF 4.4
Hao Jingbin,Shen Ding,Liu Siyu,Wang Shuaihang,Shi Xi,Qiao Yuehua,Naveena Konduru,Zhang Gaorong,Sun He,Zhang Zuoli
Given the poor efficacy of conventional oral medications in treating inner ear disorders due to the presence of the Blood-Labyrinth Barrier (BLB) in the inner ear, we designed an inner ear injectable Andro@GelMA hydrogel for the repair of Diabetic Hearing Loss (DHL). Natural protein-derived materials, such as collagen and gelatin, hold broad prospects in tissue engineering and regenerative medicine. Specifically, Gelatin Methacryloyl Acetate (GelMA), a photosensitive polymer obtained by modifying gelatin with methacrylic anhydride, inherits the high biocompatibility of collagen, making it an ideal drug delivery carrier. In this study, FTIR, XRD, SEM, and rheological tests demonstrated that hydrogen-bonding linkages formed between Andrographolide (Andro) and GelMA, thereby enhancing cross-linking degree and structural stability. Additionally, in vitro and in vivo tests confirmed that the Andro@GelMA hydrogel could achieve controllable sustained release by adjusting the cross-linking degree. Furthermore, in vitro cellular experiments showed strong protective effects on auditory cells, while animal experiments verified that this local delivery system significantly improved the therapeutic efficacy of DHL and promoted the regeneration of damaged inner ear hair cells compared to the control group.
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高影响因子
Journal of Advanced Research
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2026
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IF 17.1
Qianyu Zhang,Ying Zhang,Chen Wang,Lirun Zhou,Tong Yang,Qianru Zhu,Zheng Chu,Junzhe Zhang,Mengyao Jiang,Jigang Wang,Huanhuan Pang,Chengchao Xu,Huan Tang
Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by chronic inflammation and fibroblast activation, with limited treatment options. The bioactive diterpenoid andrographolide (AP) exhibits anti-inflammatory and antifibrotic properties, but its direct molecular targets and precise mechanism remain unclear. Objectives This study aimed to identify the primary functional target of AP and elucidate the molecular mechanism underlying its therapeutic effects against pulmonary fibrosis. Methods We employed activity-based protein profiling (ABPP) to identify covalent targets of AP in macrophages. Functional validation was performed using siRNA knockdown, enzymatic assays, molecular docking, and biophysical analyses. The therapeutic efficacy and target dependency of AP were evaluated in bleomycin-induced pulmonary fibrosis and LPS-induced acute lung injury mouse models, utilizing lung-specific Ptges3 knockdown. Results AP covalently bound to Cys58 of prostaglandin E synthase 3 (Ptges3), an allosteric site distinct from its catalytic and Hsp90-binding regions. This binding inhibited Ptges3 enzymatic activity, reduced prostaglandin E2 (PGE 2 ) production, and disrupted the Ptges3-Hsp90 chaperone complex, leading to suppressed NF-κB signaling. Genetic knockdown of Ptges3 significantly attenuated the anti-inflammatory and antifibrotic effects of AP both in vitro and in vivo . Conclusions Our findings establish Ptges3 as a critical functional target of AP. AP attenuates pulmonary fibrosis through a dual mechanism involving covalent inhibition of Ptges3 and disruption of the Ptges3-Hsp90-NF-κB axis, highlighting AP as a promising therapeutic agent and Ptges3 as a novel druggable target for IPF.
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DOI
PubMed
高影响因子
American Journal of Translational Research
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2018
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IF 3.061
Qin Zhu,Peifen Zheng,Xinyu Chen,Feng Zhou,Qiaona He,Yuefeng Yang
Ulcerative colitis (UC) is a chronic and nonspecific intestinal inflammatory disease, which may increase the risk of colon cancer. Andrographolide is a main active component of Andrographis paniculata . The anti-inflammatory ability of andrographolide suggested its potential therapeutic effect against UC. In the present study, elevated serum concentrations of proinflammatory factors, including (TNF)-α, interleukin (IL)-1β, IL-6 and IL-23, as well as increased percentages of Th17 cells (IL-17+CD4+ cells) in CD4+ cells were detected in UC patients compared to that in healthy donors. These data suggested that Th17 immune responses may involve in the pathogenesis of UC. Experimental colitis mouse model was then established. The results of hematoxylin and eosin staining demonstrated the therapeutic effect of andrographolide on colitis. Enzyme-linked immunosorbent assay (ELISA), flow cytometry and western blotting analyses showed that andrographolide could decreased the levels of proinflammatory factors TNF-α, IL-1β, IL-6 and IL-17A in the serum and in the colon tissues, reduced the percentages of Th17 cells in CD4+ cells, and suppressed the levels of IL-23, IL-17A, ROR-γt (key transcription factor of Th17 cells) and p-STAT3 in the colon tissues. Further, peripheral blood mononuclear cells (PBMCs) were isolated from UC patients and treated with various concentrations of andrographolide (0, 10, 20 and 30 μg/ml). Andrographolide also showed inhibitory effects on the levels of proinflammatory factors, the percentages of Th17 cells and the expression of relative proteins. Similar results were obtained in lipopolysaccharide-treated normal PBMCs. These data suggested that andrographolide may inhibit Th17 immune response via STAT3 signaling. In conclusion, we demonstrated that andrographolide inhibited the activity of IL-23/IL-17 axis and down-stream pro-inflammatory factors so as to suppress inflammation response, resulting in the relieving of UC.
研究领域:
免疫学
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药理学
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炎症性肠病
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DOI
PubMed
高影响因子
Frontiers in Immunology
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2024
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IF 5.7
Yue Zhongqun,Zhu Yue,Chen Teng,Feng Tingting,Zhou Ying,Zhang Jiaojiao,Zhang Ning,Yang Jing,Luo Gang,Wang Zuhua
Background: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG).Methods: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test.Results: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1–24 h). What’s more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG.Conclusion: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.
研究领域:
药学
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肿瘤学
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生物材料学
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DOI
PubMed
高影响因子
Thoracic Cancer
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2020
·Vol. 11
·期 11
·3365-3374
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IF 2.61
Qi Zhang,Qingxin Cui
Background One classic traditional Chinese medicine theory is that the “lung and intestine are exterior-interiorly related”; however, this has not been confirmed experimentally. The aim of this study was to provide a biological basis for the theory by measuring the tissue distribution of andrographolide. Methods Acute pneumonia was induced in a mouse model by repeated stimulation with lipopolysaccharide. The distribution of andrographolide in mice was observed by positron emission tomography (PET) imaging with [ 18 F]-labeled andrographolide, and changes in the in vivo distribution before and after modeling were compared. Subsequently, the consistency of pathological changes in lung and intestine was confirmed by observation of pathological sections. Finally, the results were verified by cytokine detection. Results The value of organ uptake, pathological changes and inflammatory factor expression of the lung and intestine were consistent. The concentration of andrographolide in the lung and intestine increased significantly, and was confirmed by pathology and enzyme-linked immunosorbent assays (ELISA). Conclusions Micro-positron emission tomography (microPET) can be used to visually observe the distribution of medicinal ingredients in vivo, and [ 18 F]-andrographolide can be used as a tool to assess the interior-exterior relationship between the lung and intestine.
研究领域:
药理学
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医学
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影像科学
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中医药学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
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2021
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IF 3.503
Jiaqi Lu,Lili Gu,Qin Li,Ningzi Wu,Hongxing Li,Xinyue Zhang
Context Andrographolide (Andro) has a neuroprotective effect and a potential for treating Alzheimer’s disease (AD), but the mechanism has not been elucidated.Objective The efficacy of Andro on p62-mediated Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathways in the aluminium maltolate (Al(mal)3)-induced neurotoxicity in PC12 cell was explored.Materials and methods PC12 cells were induced by Al(mal)3 (700 μM) to establish a neurotoxicity model. Following Andro (1.25, 2.5, 5, 10, 20, 40 μM) co-treatment with Al(Mal)3, cell viability was detected with MTT, protein expression levels of β-amyloid precursor protein (APP), β-site APP cleaving enzyme 1 (BACE1), Tau, Nrf2, Keap1, p62 and LC3 were measured via western blotting or immunofluorescence analyses. Nrf2, Keap1, p62 and LC3 mRNA, were detected by reverse transcription-quantitative PCR.Results Compared with the 700 μM Al(mal)3 group, Andro (5, 10 μM) significantly increased Al(mal)3-induced cell viability from 67.4% to 91.9% and 91.2%, respectively, and decreased the expression of APP, BACE1 and Keap1 proteins and the ratio of P-Tau to Tau (from 2.75- fold to 1.94- and 1.70-fold, 2.12-fold to 1.77- and 1.56-fold, 0.68-fold to 0.51- and 0.55-fold, 1.45-fold to 0.82- and 0.91-fold, respectively), increased the protein expression of Nrf2, p62 and the ratio of LC3-II/LC3-I (from 0.67-fold to 0.93- and 0.94-fold, 0.64-fold to 0.88- and 0.87-fold, 0.51-fold to 0.63- and 0.79-fold, respectively), as well as the mRNA expression of Nrf2, p62 and LC3 (from 0.48-fold to 0.92-fold, 0.49-fold to 0.92-fold, 0.25-fold to 0.38-fold). Furthermore, Nrf2 and p62 nuclear translocation were increased and keap1 in the cytoplasm was decreased in the presence of Andro. Silencing p62 or Nrf2 can significantly reduce the protein and mRNA expression of Nrf2 and p62 under co-treatment with Andro and Al(mal)3.Discussion and conclusions Our results suggested that Andro could be a promising therapeutic lead against Al-induced neurotoxicity by regulating p62-mediated keap1-Nrf2 pathways.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Jinxue Cao,Yaping Xiu,Siqi Wang,Fangling Wu,Ji Li,Dongkai Wang
Andrographolide (AG) is known as a "natural antibiotic". It has been clinically developed into capsules, dropping pills, disperse tablets, etc., for the treatment of viral and bacterial upper respiratory tract infections. It has poor water solubility, obvious P-glycoprotein efflux, and low bioavailability, so its wide application in clinical practice is limited. In this work, a novel AG dry powder inhaler (AG-DPI) was developed using experimental design to optimize the prescription and spray-drying process to obtain higher local concentrations in the lungs while lowering the administered dose; avoiding hepatic first-pass effects and gastrointestinal p-glycoprotein efflux. The short-term local anti-inflammatory effects in the lungs were evaluated using a rat model of acute pneumonia compared with oral administration. The prepared AG-DPI showed that (1) it had good aerosolization properties and was suitable for pulmonary administration, with emitted doses >90%, and fine particle fractions >60%; (2) it was superior to oral administration in the assessment of local anti-inflammatory effects in the lungs by acting on acute pneumonia. This study provides some theoretical value and reference for the inhalable dry powder of AG as a potential targeted treatment modality for lung diseases and infections.
研究领域:
药剂学
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药理学
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呼吸病学
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药物递送系统
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2026
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IF 8.7
Jieying Zhou,Wei Luo,Lingxin Zeng,Shihao Xu,Ruohan Wu,Jiaqi Lu,Ying Li,Wei Xiong
Purpose While bubble-carrier systems hold great promise for enhancing the oral bioavailability of poorly water-soluble drugs, a deeper understanding of their underlying absorption mechanisms is still required. This study aimed to address this gap by developing a bubble-driven delivery system (BDDS) using the poorly water-soluble andrographolide (AG) as a model drug, and systematically evaluating its solubilization capacity and intestinal permeability.Methods The BDDS was optimized through the screening of effervescent formulations (citric acid: Na2CO3 = 6:5) and bile salts (sodium deoxycholate, SDC). Its performance was comprehensively assessed via in vitro dissolution tests, an everted intestinal sac assay, Caco-2 cell monolayer experiments, pharmacokinetic studies, and yeast-induced fever rat models.Results The BDDS achieved 75.0%–88.7% dissolution in gastrointestinal pH media, which was markedly superior to that of commercial dripping pills (DP; 30.5–50.2%). Its apparent permeability coefficient was 7.7-fold and 3.6-fold higher than that of free AG and DP, respectively. Transport studies indicated that SDC enhanced AG permeability primarily via the apical sodium-dependent bile acid transporter (ASBT)-mediated pathway, a mechanism further confirmed by inhibition with linerixibat. The relative oral bioavailability of BDDS versus DP reached 257.1%. BDDS demonstrated enhanced efficacy by significantly inhibiting key pro-inflammatory cytokines and thermoregulatory mediators in yeast-induced fever rats.Discussion The BDDS effectively overcomes AG’s low solubility (by SDC solubilization and CO2 bubbles) and permeability (via ASBT transport), outperforming conventional formulations in terms of preparation simplicity and storage stability.Conclusion BDDS is a promising strategy to improve oral absorption and therapeutic efficacy of BCS Class IV drugs like AG, with ASBT-mediated transport as a key mechanism.
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高影响因子
PeerJ
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2024
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IF 2.3
Zhaohong Wang,Hui Chen,Xufan Cai,Heqi Bu,Shengzhang Lin
Background Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear. Methods The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy. Results Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo . The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro. Conclusion Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2022
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IF 6.819
Wan Liu,Meng Cheng,Zhiyang Lu,Haocheng Li,Yulin Feng,Yi Jin,Shilin Yang,Jianfang Feng,Liangxing Tu
Modifying nanocrystals with functional materials have been common strategy to enlarge the enhancing ability on oral absorption via nanocrystals; however, whether the functional materials have played their full enhancing ability in oral absorption is still unknown. In this study, we synthetized a novel chitosan-based copolymer (the copolymer of sodium dodecyl sulfate (SDS), chitosan (CS) and D-α-Tocopherol polyethylene glycol 1000 succinate, SDS-CS-TPGS), and modified nanocrystals with this copolymer, aiming to enhance the oral absorption of polymer andrographolide (ADR). In real-time distribution study, we found the distribution of ADR, SDS, CS and TPGS varies in gastrointestinal tract, while the distribution of ADR and SDS-CS-TPGS was similar, revealing the SDS-CS-TPGS could able to participate in the absorption process of andrographolide timely. To explore the oral absorption enhancing ability of SDS-CS-TPGS, we prepared a series of nanocrystals modified with different materials and explored their pharmacokinetic performances on SD rats. The results showed the nanocrystals modified with SDS-CS-TPGS (S-C-TANs) exhibited the highest bioavailability, which could enhance the AUC0-∞ of ADR from 1.291 mg/L*h to 5.275 mg/L*h (enhanced for about 4.09-folds). The enhanced anti- inflammatory efficacy was also found on ICR mice by employing ear swelling rate, TNF-α, IL-1β and IL-6 and pharmacodynamic index. These results indicated that modified with synthesized copolymer containing different functional stabilizers is an efficient strategy to enlarge the enhancing ability on oral absorption of nanocrystals.
研究领域:
药学
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纳米技术
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药理学
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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）