INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 19
·9510
·
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.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·Vol. 74
·期 31
·24277-24291
·
IF 6.7
Wu Yuwei,Zhao Meiqi,Zhang Peng,Ho Chi-Tang
Asiaticoside,
a triterpenoid saponin abundant in Centella asiatica , exhibits notable anti-inflammatory
activity but suffers from poor oral bioavailability. Here, we reveal
a gut microbiota-dependent mechanism underlying its therapeutic efficacy
against chronic intestinal inflammation. Using a DSS-induced mouse
model and antibiotic-mediated microbiota depletion, we demonstrate
that asiaticoside requires microbial metabolism to alleviate epithelial
injury, oxidative stress, and inflammatory cytokine production. HPLC
analysis showed that asiaticoside is hydrolyzed by gut microbes into
asiatic acid, which accumulates in colonic tissues and suppresses
IL-17 signaling, NF-κB, and JAK2/STAT3 activation while restoring
Nrf2-mediated antioxidant responses. The released glycosides are further
fermented into butyrate and other short-chain fatty acids, supporting
colonocyte metabolism and intestinal barrier function. Antibiotic
treatment abolishes asiaticoside conversion, SCFA production, and
therapeutic efficacy. These findings establish microbial biotransformation
as a critical determinant of asiaticoside activity and a key mechanism
governing natural glycoside pharmacology.
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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.
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AVIAN DISEASES
·
2024
·
IF 1.3
Pang Xiaoyue,Qiu Wenyue,Zhang Xinting,Huang Jianjia,Zhou Shuilian,Wang Rongmei,Tang Zhaoxin,Su Rongsheng
Acute myocardial injury (AMI) induced by lipopolysaccharide (LPS) can cause cardiovascular dysfunction and lead to death in poultry. Traditional antibiotic therapy has been found to have many limitations and negative effects. Asiatic acid (AA) is a naturally occurring pentacyclic triterpenoid that is extracted from Centella asiatica and has anti-inflammatory, antioxidant, and anticancer pharmacological properties. Previously, we studied the effect of AA on LPS-induced liver and kidney injury; however, the impact of AA on LPS-induced AMI remained unclear. Sixty 1-day-old broilers were randomly divided into control group, LPS group, LPS + AA 15 mg/kg group, LPS + AA 30 mg/kg group, LPS + AA 60 mg/kg group, and control + AA 60 mg/kg group. The histopathology of cardiac tissues was detected by hematoxylin and eosin (H&E) staining. The mRNA and protein expressions related to mitochondrial dynamics and mitophagy were detected by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemistry. Disorganized myocardial cells and fractured myocardial fibers were found in the LPS group, and obvious red-blood-cell filling can be seen in the gaps between the myocardial fibers in the low-dose AA group. Nevertheless, the medium and high dose of AA obviously attenuated these changes. Our results showed that AA significantly restored the mRNA and protein expressions related to mitochondrial dynamic through further promoting mitophagy. This study revealed the effect of AA on LPS-induced AMI in broilers. Mechanically, AA regulated mitochondrial dynamic homeostasis and further promoted mitophagy. These novel findings indicate that AA may be a potential drug for LPS-induced AMI in broilers.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Han-jun Qin,Si-ying He,Shu-bi Zhao,Ting-hui Xiao,Feng-ting Cui,Ling-Yu Zhang,Gao-yang Chen,Jing-yu Chen,Da-mao Dai,Xue-yan Liu,Xin-jia Hu
Infectious bone defects (IBD), characterized by persistent bacterial infection and impaired bone regeneration, remain a major clinical challenge. Although numerous biomaterials have been developed, most fail to simultaneously achieve antibacterial efficacy and osteogenic promotion. Here, we innovatively designed a strontium ion (Sr²⁺)-coordinated asiatic acid/silk fibroin (AA-Sr/SF) composite hydrogel that synergistically integrates a natural bioactive compound, inorganic ions, and a protein matrix. This unique strategy endows the hydrogel with dual antibacterial and osteoinductive functions. Systematic characterization demonstrated its excellent mechanical stability, controlled degradability, and sustained release behavior. Functional assays revealed that AA-Sr/SF effectively inhibited Staphylococcus aureus while significantly enhancing osteoblast differentiation. In vivo, the hydrogel reduced bacterial burden in infected defects, facilitated new bone formation, and restored bone mass. Transcriptomic analysis further suggested that AA-Sr/SF promotes osteogenesis via activation of the BMP4–ID2/ID3 axis and calcium signaling pathway. Collectively, this study introduces a multifunctional hydrogel integrating antibacterial, osteogenic, and translational advantages, offering a promising material-based strategy for the precise treatment of infectious bone defects.
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CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 13.2
Jianqing Peng,Yuanhu Mao,Lei Huang,Qin Wang,Yun Zhao,Yi Chen,Lei Tang,Zipeng Gong
Inhalable liposomes modified with polyethylene glycol (PEG) serve as effective carriers for pulmonary drug delivery. However, the significantly lower protein concentration in the pulmonary microenvironment compared to plasma disrupts the exchange between protein and PEG-lipid, resulting in high retention of PEG which impedes cellular uptake. Furthermore, accelerated blood clearance mediated by anti-PEG IgM antibodies diminishes therapeutic outcomes and increases adverse reactions. To address these issues, we developed a novel strategy to construct inhalable dePEGylated liposomes using amino acid lipids (ALs) that were composed of anionic head groups, L-aspartic acid or L-glutamic acid linker and double alkyl chains. The dePEGylated liposomes are utilized to facilitate pulmonary delivery of asiatic acid (AA) for the treatment of idiopathic pulmonary fibrosis (IPF). Compared to PEGylated liposomes, dePEGylated liposomes exhibited promoted cellular uptake and transcellular transport by lung epithelial cells, effectively evaded clearance by alveolar macrophages, and enhanced pulmonary drug exposure, leading to improved therapeutic efficacy against IPF in mice. Our findings highlight the novel ALs-incorporated dePEGylated liposomes as a promising strategy to enhance treatment efficacy for IPF and overcome the limitations of PEGylated liposomes, which offers an efficient pulmonary drug delivery strategy for the other pulmonary diseases as well.
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OncoTargets and Therapy
·
2022
·
IF 4.345
Yue Jing,Gang Wang,Ying Ge,Minjie Xu,Shuainan Tang,Zhunan Gong
Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.
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PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Xian Zheng,Yuanyue Jiang,Wenbo Wang,Kekang Sun,Libin Zhou,Yanru Zhang,Jie Cui,Haiyan Yu,Wenbin Dong,Baofei Yan
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica , has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.
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OncoTargets and Therapy
·
2023
·
IF 4
Gang Wang,Yue Jing,Lingsen Cao,Changchang Gong,Zhunan Gong,Xiangrong Cao
Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP)-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer.
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FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Asiatic acid (AA), a triterpenoid compound isolated from Centella asiatica , has anti-inflammatory, antioxidant and anticancer biological characteristics . To explore the effect of AA on LPS-induced acute kidney injury (AKI) in broilers, a total of 60 one-day-old broilers were randomly divided into 6 groups, including the normal group, AKI model group, AKI + AA 15 mg/kg group, AKI + AA 30 mg/kg group, AKI + AA 60 mg/kg group and normal + AA 60 mg/kg group. Hematoxylin-eosin staining was used to observe the histopathology in kidney tissue, and the mRNA and protein expressions related to oxidative stress and ferroptosis were tested by qPCR and western blotting respectively. AA mitigated vacuolar degeneration and enlarged glomerular space caused by LPS in kidney tissue. Additionally, AA significantly increased the mRNA levels of Nrf2, HO-1, NQO1, GCLC, GCLM , GPX4 , SLC7A11 and FTH1 , and decreased the mRNA levels of Keap1 and PTGS2 in LPS-induced AKI. Likewise, AA significantly upregulated the protein expressions of Nrf2, HO-1, NQO1, GPX4, SLC7A11 and FTH1, and downregulated the protein expressions of Keap1 and PTGS2 in LPS-induced AKI. These results suggested that AA alleviated LPS-induced AKI by inhibiting oxidative stress and ferroptosis through targeting regulation of the Nrf2 pathway in broilers.
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JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
·
2024
·
IF 2.2
Wenyue Qiu,Wenxin Jiang,Yiman Su,Hui Huang,Jiali Ye,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Lipopolysaccharides (LPS) is the major compoent of Gram-negative bacteria and an important factor in inducing inflammation, which usually leads to multiple organ failure in broilers, seriously affecting the growth performance of broilers and hindering the development of poultry farming. Under the policy of prohibiting antibiotics in feed, it has become more urgent to find natural drugs to prevent liver damage caused by LPS in broilers. Asiatic acid (AA) is a pentacyclic triterpene that has been proven to have anti-inflammatory and antioxidant effects. However, the protective effects of AA in LPS-induced liver damage in broilers still need to be clarified. This study aims to explore the complete mechanism of AA against LPS-induced acute liver injury (ALI) in broilers. A total of 60 broilers (1 day old) were randomly divided into the control group, LPS group, LPS+AA (15, 30 and 60 mg/kg) group and control+AA (60 mg/kg) group. At 16, 18 and 20 days of age, the broilers were attacked with LPS (0.5 mg/kg) to construct liver injury model. H&E staining assessed liver pathological changes. The mRNA and protein expression levels related to the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis in the liver tissue were detected. Our results founded that intraperitoneal injection of LPS in broilers increased the activities of AST and ALT, as well as raising the related gene and protein expression of the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis. Interestingly, AA improved LPS-induced liver damage and decreased the activities of AST and ALT in broilers. Additionally, AA mitigated LPS-induced ALI by reducing the mRNA levels and protein expressions of the HMGB1/TLR4/NF-κB pathway, pyroptosis and ERS-mediated apoptosis. In conclusion, the present study investigated that AA mitigated LPS-induced ALI in broilers by reducing pyroptosis and ERS-mediated apoptosis via inhibition of the HMGB1/TLR4/NF-κB pathway. Therefore, AA may serve as a potential feed additive for the prevention of LPS-induced ALI in broilers.
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Pharmaceutics
·
2022
·Vol. 14
·期 11
·2532
·
IF 6.525
Mingming Li,Qiuyue Wang,Naiying Chen,Sicheng Yao,Xinxing Sun,Peng Quan,Yang Chen
Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation for AA and improve its skin penetration by various penetration enhancement methods. Four kinds of hydrogel bases were selected to prepare the AA hydrogel, in which different organic amines and chemical enhancers were incorporated in combination with microneedle pretreatment. The results showed that AA had good release profiles in the presence of hyaluronic acid as the hydrogel base and organic amines as the counter-ions. Diethylamine and Span 80 could promote drug penetration into the skin, and pretreatment with microneedles could further increase the drug permeability. In conclusion, the optimized hyaluronic acid hydrogel has great potential for use in the topical delivery of AA, and its penetration via the skin can be further improved by different pharmaceutical approaches.Keywords:asiatic acid;hydrogel;counterion;chemical enhancer;microneedle
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