RSC Advances
·
2018
·Vol. 8
·期 60
·34726-34732
·
IF 2.936
Xu Zhongyu,Ren Jiangmeng,Jing Qiufang,Ren Fuzheng,Huang Mengting,Ding Wenrui,Zeng Bubing
Andrographolide (AP) is a diterpenoid separated from Andrographis paniculata with a wide spectrum of biological activities including anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. However, its poor water solubility and instability result in lower bioavailability, which seriously limit its pharmacological function. In this study, the attempt to use regenerated silk fibroin (RSF) as a drug-carrier to encapsulate AP was reported. The AP-loaded RSF nanoparticles were prepared by a facile and clean method without any toxic agents. Moreover, special attention was paid to the optimization of formulation. Finally, the sizes of the AP-loaded RSF nanoparticles ranged from 200 to 1000 nm, and the nanoparticles were spherically shaped, as seen by transmission electron microscopy. The drug loading and encapsulation efficiency were about 25.9% and 87.3%, respectively. Furthermore, the release time of AP-loaded RSF nanoparticles was about 3 days. The particle size and drug release behaviour could be adjusted by treating with glycol amine. The in vitro cytotoxicity studies demonstrated that the RSF nanoparticles showed negligible cytotoxicity to cells, and the anti-proliferative activity of AP-loaded RSF nanoparticles showed that the AP-loaded RSF nanoparticles can adhere to Hela cells and MDA-MB-231 cells easily. All these results imply that this biomacromolecule drug nanocarrier has great potential for chemotherapy in clinical applications.
研究领域:
药理学
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纳米医学
·
生物材料科学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Yi Cai,Liduan Huang,Yanhong Hou,Peiwen Pang,Ying Zhou,Xuan Zhang,Yiyin Long,Huajian Li,Halimulati Muhetaer,Man Zhang,Bo Wu
Andrographolide, a diterpene compound derived from the medicinal plant Andrographis paniculata , possesses anti-inflammatory, antioxidant, antitumor, and antiviral properties. Injectable formulations containing andrographolide, such as Potassium Sodium Dehydroandrographolide Succinate for Injection (PSDS), are widely used in clinical practice to treat various diseases, including upper respiratory tract infections. However, clinical reports have highlighted that andrographolide-based herbal injections may induce acute kidney injury and other renal adverse effects, thereby restricting its clinical application. Despite these concerns, the molecular mechanisms underlying andrographolide-induced nephrotoxicity remain poorly understood. In this study, we demonstrated that andrographolide induces inflammation and fibrosis in renal tubular epithelial cells and mouse kidneys. Notably, we identified for the first time that andrographolide promotes cellular senescence in renal tubular epithelial cells and mouse kidneys while downregulating the expression and enzymatic activity of SIRT3. Mechanistic investigations revealed that andrographolide mediates kidney injury and senescence through inhibition of the SIRT3/p53 signaling pathway. Furthermore, andrographolide was found to disrupt the interaction between SIRT3 and p53, resulting in increased acetylation of p53 and upregulation of its downstream target genes involved in inflammation, fibrosis, and senescence. These findings elucidate the molecular mechanisms of andrographolide-induced nephrotoxicity and provide a scientific basis for developing strategies to reduce its toxic effects.
研究领域:
药理学
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分子生物学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Fenghe Yang,Hao Zhao,Guangcai Wang,Hao Li,Yulong Ren,Chang Ren,Mengjun Zhang,Junli Zhao,Yu Zhang,Guang Han
Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive destruction of cartilage, ultimately leading to joint dysfunction. Although various nanoparticle-based drug delivery systems have been designed for OA treatment, current systems still face significant challenges, particularly in achieving prolonged joint retention and efficient cartilage penetration. Herein, a cartilage-targeting nanoparticle platform composed of poly(lactic-co-glycolic acid) (PLGA), poly(allylamine) (PAA), targeting peptide, and andrographolide derivative (A100) (A100@PLGA–PAA-targeting peptide nanoparticle, i.e., A100@PLGA-P-T nanoparticle) is developed as a drug delivery system to address the above challenges. In vitro studies demonstrated that by adjustment of PAA concentrations, nanoparticles can be altered to either positively charged (A100@PLGA-P-T(+)) or neutral (A100@PLGA-P-T(n)) forms. In vitro and in vivo retention and penetration experiments showed that compared to A100@PLGA-P-T(n) nanoparticles, A100@PLGA-P-T(+) nanoparticles exhibit significantly enhanced retention time and cartilage penetration. Coculture experiments with chondrocytes revealed that A100@PLGA-P-T(+) nanoparticles significantly improved the viability of OA-like chondrocytes and increased the level of glycosaminoglycan synthesis. Furthermore, in an OA rat model, intra-articular injection of A100@PLGA-P-T(+) nanoparticles significantly reduced inflammation and promoted cartilage repair and regeneration. Collectively, the prolonged retention property, superior cartilage penetration capability, and potent anti-inflammatory and cartilage-repairing effects of the A100@PLGA-P-T(+) nanoparticle system position it as a clinically viable candidate for comprehensive OA treatment.
研究领域:
纳米医学
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药学
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生物医学工程
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骨科
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Crystals
·
2025
·Vol. 15
·期 9
·752
·
IF 2.4
Haifeng Luo,Yuchen Zheng,Shizhao Ren,Wangchuan Xiao,Rongrong Xue,Wei Han,Fenghua Chen
Andrographolide (ADG) is a typical poorly water-soluble drug, and a co-amorphous strategy was used here to improve its aqueous solubility. Co-amorphous systems of ADG and amino acids with a 1:1 molar ratio were screened via the neat ball milling method. L-lysine (Lys) and L-tryptophan (Trp) can be used as co-formers with ADG, forming a co-amorphous phase, which was confirmed by powder X-ray diffraction, IR and Raman spectroscopy. ADG-Trp showed poor solubility at 37 °C, which was close to that of raw ADG (0.08 mg·mL−1). ADG-Lys showed unexpectedly enhanced solubility, at 0.5 mg·mL−1in the media of water and PBS (pH 7.4) and 0.3 mg·mL−1in the medium of HCl buffer (pH 1.2) at 37 °C. ADG-Lys showed good storage stability for 5 months, but its thermal stability was poor and it could recrystallize at 100 °C. Compared with ADG-Trp, ADG-Lys has weaker hydrogen bonding interactions and stronger hydrophobic interactions related to ADG molecules, which might cause the unusual enhancement in solubility. To our knowledge, ADG-Lys prepared in this work shows the maximum ADG content (70 wt.%) and the highest ADG solubility among the reported ADG amorphous solid dispersions and co-amorphous systems.
研究领域:
药剂学
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材料科学
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药物递送
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物理化学
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产品关联
DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2025
·
IF 3.9
Jingya Li,Mingyang Xue,Chen Xu,Nan Jiang,Yiqun Li,Yuding Fan,Yong Zhou,Yan Meng
It is well-established that Largemouth bass ranavirus (LMBRaV) induces viral ulcerative syndrome, a highly transmissible and lethal viral disease afflicting largemouth bass aquaculture. Given the urgent need for available prevention and control methods, this study evaluated the antiviral activities of fifteen naturally occurring compounds derived from herbal medicines against LMBRaV using an in vitro cell model. Andrographolide (Andro) was one of the substances that was evaluated and showed highly effective anti-LMBRaV activity of a 99.2 % maximal inhibition rate of at 20 mg/L dosage. Mechanistic investigation revealed Andro prevented viral entry and directly inactivated the virus. Ultrastructural observations and fluorescence staining further supported Andro's protective effects on EPC cells from LMBRaV invasion. In vivo experiments demonstrated Andro's efficacy in reducing mortality rates in LMBRaV-infected largemouth bass by 61.54 % and significantly lowering the viral load. Additionally, Andro upregulated antiviral genes such as ifn-γ , irf-3 , and mx , indicating its immunomodulatory properties. Histopathological analysis revealed that Andro alleviated tissue damage of liver, spleen, and kidney in the infected fish. Andro also changed the microbiotic composition of gut by increasing the amounts of good bacteria and reducing amounts of bad bacteria. These findings collectively highlight Andro's substantial antiviral and immunomodulatory potential, suggesting its promising application as a natural compound for combating LMBRaV infections in largemouth bass aquaculture and potentially other aquatic animal diseases.
研究领域:
水产养殖学
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病毒学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Qi Zhang,Qingxin Cui
The target identification of natural products is one of the most challenging issues in the standardized application of traditional Chinese medicine. It is widely recognized that magnetic nanoparticles (MNPs) could function as a tool that capture the target proteins of active molecule. However, the false positives caused by non-specific adsorption should not be ignored. Here, we reported a functionalized MNPs technique that could enrich the target proteins of andrographolide (AG) based on isomers approach. We designed and characterized MNPs and isomers of AG. The combination of the two could be used as an ideal coupling, which provides a feasible method for the target proteins enrichment of AG. In addition, the target proteins were identified by HPLC-MS/MS. Moreover, bioinformatics analysis and systematic computational dockings were performed to search for the interactions between target proteins and AG. Six inflammation-related proteins, including CD4, IKBKB, PKN1, PKN2, YWHAB and YWHAH were proved to be the anti-inflammatory targets of AG. All of the results indicated this integrated system could benefit target identification of bioactive natural products.
研究领域:
药理学
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蛋白质组学
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药物研发
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2019
·Vol. 73
·期 2
·388-396
·
IF 1.966
Wang Lei,Cao Fei,Zhu Li-li,Liu Peng,Shang Yu-ru,Liu Wen-hui,Dong Xin,Bao Hai-dong,Gong Peng,Wang Zhong-yu
To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups—(1) control ( n = 6), (2) control + 200 mg/kg andrographolide ( n = 6), (3) alpha-naphthylisothiocyanate (ANIT)-control ( n = 6), (4) ANIT + 50 mg/kg andrographolide ( n = 6), (5) ANIT + 100 mg/kg andrographolide ( n = 6), and (6) ANIT + 200 mg/kg andrographolide ( n = 6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.
研究领域:
药理学
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肝病学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Zhou Xuebin,Li Jinhua,Quan Shengli,Zhang Xinyue,Gu Lili,Hu Min,Huang Wenhai,Li Qin
The pathological and physiological studies of Alzheimer’s disease (AD) have been in-depth, and apolipoprotein E4 (ApoE4) has been proven to be highly correlated with AD, and clinical and experimental data show that ApoE4 can cause blood–brain barrier (BBB) injury, and the change of BBB permeability is an important factor affecting the development of AD. Andrographolide (Andro), as the active component of the natural plant Andrographis paniculata , has been proven to have anti-inflammatory and antioxidant effects, which have potential neuroprotective effects. To verify the protective effect of Andro on BBB in a short term, our research group used atorvastatin (Atorva)-mediated zebrafish brain injury model and the ApoE4-mediated cell co-culture model of BBB injury to explore the protective effects and mechanisms of Andro on BBB injury. Studies have shown that Andro can inhibit the activation of CypA/NF-κB/MMP-9 signaling pathway and has achieved the effect of antagonizing the inhibition of ApoE4 on intercellular tight junction proteins (occludin, claudin-5, and ZO-1). At the same time, Andro can inhibit the secretion of cell adhesion molecules (VCAM-1 and ICAM-1) in cells, thereby delaying the occurrence and progression of neuroinflammation and playing a protective role in BBB. In conclusion, Andro is a potent natural product which can protect the blood–brain barrier.
研究领域:
神经科学
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药理学
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分子生物学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2016
·
IF 1.546
Huihui Yuan,Bo Sun,Feng Gao,Minbo Lan
Context: Paclitaxel (PTX) is widely used in chemotherapy for cancer treatment; however, it has some serious side effects. Andrographolide (Andro) is a potential cancer therapeutic agent isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae).Objective: The objective of this study is to evaluate the effects of PTX combined with Andro against A549 cells.Materials and methods: The effects of 24–48 h treatment with 0.48–60.75 nM PTX and 5.10–328.0 μM Andro on cellular proliferation, apoptosis, cell cycle and intracellular reactive oxygen species (ROS) were determined by sulphorhodamine B assay, Annexin V-FITC/PI apoptosis detection, PI staining and ROS assay, respectively. Synergy was determined using combination index. The antitumour efficacy of 20 mg/kg PTX with 100 mg/kg Andro was studied in a xenograft murine model.Results: IC50 value of the PTX combined with Andro against A549 cells was 0.5–7.4 nM, which was significantly lower than that of PTX (15.9 nM). PTX with 10 μM Andro caused (1.22–1.27)-fold apoptosis and 1.7-fold ROS accumulation compared with PTX alone. N-Acetylcysteine, a ROS scavenger, blocked this synergy in vitro. In contrast, G2/M phase cell cycle arrest resulting from PTX was not potentiated by Andro. Moreover, PTX in combination with Andro inhibited the growth of A549 transplanted tumours by 98%.Discussion and conclusion: The results indicate that the combination of PTX and Andro exert significant synergistic anticancer effect on A549 cells in vitro and in vivo. The synergy may be the result of the accumulation of ROS. The combination of Andro and PTX represents a potential strategy for the treatment of A549 cells.
研究领域:
肿瘤学
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药理学
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分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Jianlu Qu,Li Wang,Chao liang Jia,Shule Zhang,Cunhao Li,Wei Wu,Wenlong Li
Andrographolide (AG) is a diterpene lactone with significant anti-inflammatory and antitumor activities. However, the poor water solubility limits its clinical application. An andrographolide-salicylic acid (AG-SLA) nano-cocrystal delivery system was rapidly developed using hummer acoustic resonance (HAR) technology in this research. The formulation of the AG-SLA nano-cocrystal suspension and the process parameters for HAR technology were optimized in a high-throughput manner, with SDS-Tween 80 as the optimal composite stabilizer. Nano-cocrystal suspension of AG-SLA with an average particle size of 190 nm were successfully prepared, and then the optimal formulation were tenfold scaled up. Freeze-drying was adopted to solidify the nano-cocrystal and improve its stability. Various analytical techniques were used to characterize the particle size and solid state of the nano-cocrystals. The high-energy input from the HAR instrument induced partial amorphization of the nano-cocrystals, as confirmed by PXRD and DSC analyses. Saturation solubility experiments demonstrated that the solubility in pH 1.2 hydrochloric acid buffer and pH 6.8 phosphate buffer increased by 5.74 times and 6.82 times, respectively, compared to raw AG. In vitro dissolution tests indicated that the cumulative release over 120 min in pH 1.2 hydrochloric acid buffer and pH 6.8 phosphate buffer increased by 1.60 times and 1.88 times, respectively, compared to raw AG.
研究领域:
药学
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纳米技术
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药物递送系统
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF GENERAL CHEMISTRY
·
2022
·Vol. 92
·期 10
·2178-2185
·
IF 0.779
Lai Lin,Huang Xiang,Sun Wanlin,Chen Xinan,Pei Shuchen,Chai Shuiqin,Chen Jun
Abstract The increasing use of antibiotics to treat bacteria has led to the emergence of many resistant bacteria. Therefore, it is crucial to research novel antibiotics and understand how they are used to combat bacteria. In this study, a green, effective, and ecologically acceptable hydrothermal approach was used to efficiently convert andrographolide and citric acid into carbon dots with vivid blue fluorescence and an emission wavelength of 430 nm. TEM, AFM, FT-IR, and XPS were used to analyze the surface morphology, particle size distribution, and surface functional groups of carbon dots. It was discovered that carbon quantum dots had different functional groups linked to the surface and had a common particle dimension of 2.75 nm. Additionally, it was unexpectedly discovered that carbon quantum dots confirmed great antibacterial motion in opposition to both Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ), with a MIC of 1.14 mg/mL. Carbon quantum dots have a positive charge of 16 eV, which can connect to the bacterial cell wall and destroy the normal form of bacteria by generating 1 O 2 , causing antibacterial effects, according to research on the antibacterial mechanism of carbon dots.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
微生物学
·
药学
✓ 已验证
DOI
高影响因子
Expert Opinion on Drug Delivery
·
2014
·
IF 4.116
Jinming Zhang,Yingbo Li,Wei Gao,Michael A Repka,Yitao Wang,Meiwan Chen
Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo.Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat.Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 – ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension.Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）