JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yicong Zhang,Yujia Wang,Hanming Zhang,Shiqi Huang,Yuai Li,Jiaying Long,Yikun Han,Qing Lin,Tao Gong,Xun Sun,Zhirong Zhang,Ling Zhang
Cholesterol is an indispensable component of most liposomes , heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo . On the other hand, as an active ingredient, AA can decrease TGF-β secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Omega
·
2026
·
IF 5.2
Yuhan Yang,Yanlin Zhu,Hongyan Yuan,Zun Yang,Jie Zhou
Emerging evidence highlights a bidirectional relationship between diabetes and periodontitis, with both conditions sharing common pathogenic mechanisms. Biomaterials capable of modulating macrophage polarization hold significant therapeutic potential for promoting tissue repair in diabetic periodontitis. Asiatic acid (AA), a clinically proven compound with potent antioxidant and antiinflammatory properties, presents an attractive therapeutic candidate. In this study, we developed a multifunctional hybrid hydrogel, AA@GO (AA@GO/SA/CCS, abbreviated as AA@GO), composed of sodium alginate (SA), carboxymethyl chitosan (CCS), and graphene oxide (GO) for effective AA delivery. The AA@GO hydrogel demonstrated remarkable mitophagy-enhancing capabilities, effectively reducing intracellular ROS levels and restoring mitochondrial function in macrophages. Notably, this material significantly increased the M2/M1 polarization ratio by facilitating macrophage phenotype switching from M1 to M2, thereby attenuating inflammatory responses. Our findings elucidate the unique mechanism of AA@GO hydrogel action and propose a promising novel strategy for diabetic periodontitis treatment through macrophage polarization regulation.
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PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 4.9
Mingming Li,Suhong Fu,Jiaxin Chen,Xinxing Sun,Yang Chen,Lei Yang
High-quality wound healing is a primary clinical goal, yet it remains difficult to achieve reliably with current treatments. For this purpose, this study developed an ion-paired asiatic acid (AA) hydrogel specially for wound healing and systematically evaluated its pharmacodynamic efficacy both in vitro and in vivo. The formulation strategy involved screening organic amines as counter-ions using an ex vivo stratum corneum-removed skin model. Triethanolamine was identified as the optimal counterion, maximizing AA penetration into local tissue while minimizing systemic permeation via the formation of an ion-pair as confirmed by Nuclear Magnetic Resonance. The resulting hydrogel exhibited ideal properties for wound application, as characterized by its water vapor transmission rate, swelling ratio, degradability ratio, and water retention. In vitro , the hydrogel accelerated wound closure by stimulating cellular proliferation and migration, promoting vascular differentiation, and exhibiting selective antibacterial efficacy against S. aureus . In a rat full-thickness skin defect model, the hydrogel effectively facilitated scarless healing, which was mechanistically linked to collagen remodeling (indicated by a higher proportion of type III relative to type I collagen), suppression of TNF-α-mediated inflammation, and downregulation of TGF-β-driven fibrosis. Collectively, this work establishes a strategically designed ion-pair hydrogel system that coordinates key healing processes, offering a promising strategy for achieving reliable, high-quality wound regeneration.
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高影响因子
Biomedicines
·
2025
·Vol. 13
·期 7
·1544
·
IF 3.9
Lei Guo,Peili Wu,Qijian Feng,Xiaochun Lin,Yuan Wang,Minghai Wu,Feifei Cai,Jin Zhang,Chuyi Yang,Xuelin Li,Churan Wen,Yingbei Lin,Nannan Liu,Yuxuan Hu,Huiyun Wang,Xinzhao Fan,Meiping Guan
Background/Objectives:The role of glycogen metabolism in diabetic kidney disease (DKD) remains unclear. This study investigated the therapeutic potential of asiatic acid (AA) on glycogen metabolism in DKD and its underlying mechanisms.Methods:A DKD mouse model was established using a high-fat diet and streptozotocin, followed by AA treatment for 8 weeks. Network pharmacology and molecular docking identified STBD1 as a potential target of AA, and its overexpression in mice was performed.Results:AA reduced blood glucose levels and the urinary albumin-to-creatinine ratio (UACR) and downregulated TGFβ-1, KIM-1, and PDK4. Additionally, AA treatment reversed abnormal glycogen accumulation and restored STBD1 expression. Network pharmacology and molecular docking identified STBD1 as a potential target of AA, and its overexpression in mice demonstrated similar beneficial effects. Gene enrichment analysis revealed that STBD1 is involved in key metabolic pathways related to DKD.Conclusions:These findings suggest that AA alleviates renal damage in DKD, possibly through modulation of STBD1, highlighting its therapeutic potential and the critical role of STBD1 in renal glycophagy.
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PubMed
高影响因子
BURNS
·
2025
·
IF 2.9
Jiaqi Wu,Guizhen Xu,Xinlu Zhou,Jun Wan,Huaiwei Liao,Cong Li,Yan Shi,Huicai Wen
Background This study investigated the pharmacological effects of asiatic acid (AA) on keloid fibroblasts (KFs) and elucidated its therapeutic mechanisms in keloid pathogenesis. Methods Primary human KFs were isolated and expanded for experimental analysis. Cell migration capacity was evaluated through cell scratch assay and Boyden chamber assay. Immunofluorescence staining was performed to quantify α-smooth muscle actin (α-SMA) expression in AA-treated KFs, while Western blot assessed collagen type I (Col-I), α-SMA, STAT3, and phosphorylated STAT3 (p-STAT3) protein levels. STAT3 activation was pharmacologically induced in KFs using Colivelin TFA (a STAT3 agonist), with subsequent evaluation of migratory behavior and protein expression profiles using parallel methodologies. Results AA treatment significantly inhibited the viability and migratory capacity of KFs, accompanied by downregulation of Col-I, α-SMA, and p-STAT3 expression. Pharmacological activation of STAT3 via Colivelin TFA partially rescued AA-induced suppression of KF migration and Col-I expression. Conclusions AA significantly modulates the migratory capacity and extracellular matrix (ECM)-related protein expression in KFs, with the STAT3 signaling pathway implicated in this regulatory mechanism. These findings indicate that the anti-fibrotic effects of AA are mediated through STAT3 signaling.
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PubMed
高影响因子
MOLECULES
·
2015
·Vol. 20
·期 4
·7309-7324
·
IF 2.416
Yue Jing,Gang Wang,Ying Ge,Minjie Xu,Zhunan Gong
Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluatedin vitrousing different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluatedin vivousing a larval zebrafish model. Among the derivatives, compounds4–10showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds11–17had significantly less effects. The new derivative10was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative10had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.Keywords:asiatic acid;amino acid derivatives;anti-tumor activity;anti-angiogenic effect;stability;HPLC analysis
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
Smart Medicine
·
2026
·Vol. 5
·期 3
·e70047
·
IF 12.8
Zhiqiang Luo,Lingbao Zeng,Xinyu Zhu,Yuanjin Zhao
Synergy therapy of Chinese herbs is an effective strategy for wound repair and its further development focuses on the chronological release of specific herbs with healing proceeding. Herein, we report a novel asiatic acid/baicalein nanocarrier integrated microcapsule with spatiotemporal release feature from microfluidic electrospray for wound healing. Benefiting from advantages of both nanocarrier formulation and integration capacity of microfluidic electrospray, synthesized baicalein-tannic acid nanoparticles are integrated into the shell of microcapsule while fabricated asiatic acid liposomes are located at the core region. This design enables chronological release: baicalein is first released to kill bacteria, followed by releasing asiatic acid liposomes to enhance cell migration and granulation tissue formation. In vitro tests confirm the excellent biocompatibility, antibacterial and pro-migration property of microcapsules. The results from in vivo wound healing studies showed the outcomes of reduced inflammation and accelerated wound closure in microcapsules-treated wounds. Therefore, it is believed that this herbal microcapsule with spatiotemporal and hierarchical release of baicalein and asiatic acid is an effective therapeutic platform for clinical wound treatment. Highlights AA liposomes were derived from concentrated extrusion of AA and phospholipid molecule. Baicalein-tannic acid nanoparticles (BTANPs) were synthesized by solvent exchange. AA liposomes and BTANPs were integrated into ABNM by microfluidic electrospray. ABNM could chronologically release BTANPs and AA liposomes with their biodegradation. ABNM were highly curative to the healing of wounds.
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 40
·6125-6138
·
IF 5.047
Yiming Han,Yuqi Jiang,You Li,Minna Wang,Tingting Fan,Mingyao Liu,Qinfei Ke,He Xu,Zhengfang Yi
The diabetic non-healing wound is one of the most common complications of diabetics. The long-term stimulus of oxidative stress, inflammation and infection caused by the hyperglycemic microenvironment in the wound site always leads to a delayed healing process of the diabetic wound. To address this issue, in this study, we prepared an asiatic acid (AA)-embedded aligned porous poly(L-lactic acid) (PLLA) electrospun fibrous scaffold (AA-PL) for accelerating diabetic wound healing. The results showed that the electrospun fibers with nanopores on the surfaces were aligned in a single direction, while the AA was well embedded in the fibers and can be continuously released from them. The in vitro results revealed that the AA-PL scaffolds can effectively alleviate the H2O2-induced oxidative stress damage to HaCat cells and downregulate the LPS-induced pro-inflammatory cytokine (IL-1β, TNF-α, IL6) gene expression in RAW 264.7 macrophage cells. Moreover, the growth of E. coli and S. aureus could be inhibited by the AA-PL scaffolds. The in vivo study further demonstrated that the AA-PL scaffolds can accelerate the re-epithelization, angiogenesis and extracellular matrix formation of a wound by relieving the high oxidative stress, inflammation and infection in the diabetic wound site. This study suggests that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable release of AA from the scaffolds is an efficient and innovative strategy for the treatment of diabetic non-healing wounds.
研究领域:
生物医学工程
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药剂学
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伤口愈合
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糖尿病
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DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Ya-Wen Zhang,Ling-Lan Tu,Yi Zhang,Jie-Chao Pan,Gao-Li Zheng,Li-Na Yin
Liver fibrosis is a major global health concern. Management of chronic liver disease is severely restricted in clinics due to ineffective treatment approaches. However, a lack of targeted therapy may aggravate this condition. Asiatic acid (AA), a pentacyclic triterpenoid acid, can effectively protect the liver from hepatic disorders. However, the pharmaceutical application of AA is limited by low oral bioavailability and poor targeting efficiency. This study synthesized a novel liver-targeting material from PEG-SA, chemically linked to ursodeoxycholic acid (UA), and utilized it to modify AA nanostructured lipid carriers (UP-AA-NLC) with enhanced targeting and improved efficacy. The formulation of UP-AA-NLC was optimized via the Box–Behnken Experimental Design (BBD) and characterized by size, zeta potential, TEM, DSC, and XRD. Furthermore, in vitro antifibrotic activity and proliferation of AA and NLCs were assessed in LX-2 cells. The addition of UP-AA-NLC significantly stimulated the TGF-beta1-induced expression of α-SMA, FN1, and Col I α1. In vivo near-infrared fluorescence imaging and distribution trials in rats demonstrated that UP-AA-NLC could significantly improve oral absorption and liver-targeting efficiency. Oral UP-AA-NLC greatly alleviated carbon tetrachloride-induced liver injury and fibrosis in rats in a dosage-dependent manner, as reflected by serum biochemical parameters (AST, ALT, and ALB), histopathological features (H&E and Masson staining), and antioxidant activity parameters (SOD and MDA). Also, treatment with UP-AA-NLC lowered liver hydroxyproline levels, demonstrating a reduction of collagen accumulation in the fibrotic liver. Collectively, optimized UP-AA-NLC has potential application prospects in liver-targeted therapy and holds great promise as a drug delivery system for treating liver diseases.
研究领域:
药理学
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肝病学
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药物递送系统
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PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
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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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 19
·9510
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IF 4.9
Qingying Shi,Fengzhu Li,Yingying Peng,Qiannan Sun,Hong Zhao,Fuping Lu,Huabing Zhao
Dental caries, a prevalent biofilm-mediated chronic disease, causes enamel demineralization, pulp infection, and systemic complications. Dental plaque biofilm is the initiating factor for the occurrence and development of caries.Streptococcus mutansis an opportunistic pathogen linked to the structure and ecology of dental plaque biofilms. The molecular mechanism ofS. mutansduring biofilm ontogeny in driving cariogenesis has been extensively elucidated. Here, we observed that asiatic acid is a potent biofilm disruptor that selectively dismantlesS. mutansbiofilm architectures, prompting us to investigate its mechanism. The minimum biofilm inhibition concentration (MBIC) of asiatic acid onS. mutanswas 62.5 μM, but the MBIC level did not substantially impede planktonic growth. Using the static active-attachment model, it was demonstrated that asiatic acid significantly reduced biofilm biomass (p< 0.001) and extracellular polysaccharides (EPS) content (p< 0.001), while concurrently diminishing acid production (p= 0.017) and metabolic activity (p= 0.014). Confocal and scanning electron microscopy further confirmed structural disintegration, including bacterial detachment and reduced biofilm thickness. Transcriptome analysis ofS. mutansbiofilm treated with asiatic acid revealed 454 differentially expressed genes (adjustedp< 0.05, |log2FC| ≥ 1). Notably, genes related to the CiaRH two-component system (ciaR,ciaH), a central regulatory hub for biofilm maturation and acid tolerance. This disruption initiates a downstream cascade, causing a coordinated downregulation of critical gene clusters essential for virulence and pathogenesis, including stress response (htrA,clpP,groEL,dnaK), and the glucan-binding protein gene (gbpC) essential for biofilm structural integrity. These findings provide the first mechanistic evidence linking asiatic acid to transcriptional reprogramming inS. mutansbiofilm, offering a novel ecological strategy for caries prevention by targeting key regulatory pathways.
研究领域:
微生物学
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口腔生物学
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分子医学
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感染性疾病
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药理学
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生物膜研究
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转化医学
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DOI
PubMed
高影响因子
LIFE SCIENCES
·
2021
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IF 5.037
Mengyuan Fang,Wencui Wan,Qiuming Li,Weiwei Wan,Yang Long,Hongzhuo Liu,Xin Yang
Aim This study aimed to evaluate the effects of Asiatic acid (AA), a naturally occurring compound of pentacyclic triterpenoid, on the pathological processes of diabetic retinopathy (DR). Methods SD rats were induced to develop early DR by intraperitoneal injection of STZ (60 mg/kg). Four weeks after injection, the diabetic rats were orally administrated with 37.5 mg/kg or 75 mg/kg AA every day for four weeks. The integrity of blood-retinal barrier (BRB) was measured by Evans blue staining. The polarization of microglia was determined by real-time PCR, western blot, and ELISA assays. The inner BRB (iBRB) or outer BRB (oBRB) breakdown was induced in human retinal endothelial cells or APRE19 cells through co-culture with high glucose and LPS-stimulated microglia BV2 cells. The damage to the iBRB and oBRB was measured using transendothelial/transepithelial electrical resistance (TEER/TER) and FITC-conjugated dextran cell permeability assays. Key findings Results demonstrated that AA alleviated BRB breakdown, as evidenced by decreased protein expression of occludin, claudin-5, and ZO-1. Furthermore, AA treatment suppressed inflammation and M1 polarization, while it increased M2 polarization in the retina of DR rats. In vitro , the iBRB or oBRB breakdown was alleviated by AA. LPS-induced M1-polarization of BV2 cells under high glucose condition was also repressed through AA administration. Finally, we demonstrated that AA weakened the TLR4/MyD88/NF-κB p65 signaling pathway both in vivo and in vitro . Significance AA ameliorated early DR by regulating microglia polarization via the TLR4/MyD88/NF-κB p65 pathway. These data indicate that AA is a potential candidate for DR treatment.
研究领域:
药理学
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眼科学
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免疫学
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细胞生物学
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PubMed
高影响因子
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