TISSUE & CELL
·
2025
·
IF 2.5
Peiying Shi,Shuo Han,Yang Sun,Mengmeng Li,Xueling Xu
Pathological cardiac hypertrophy (CH) often progresses towards heart failure, which presents a serious threat to global public health security. Fortunately, peptides from animal venoms have emerged as potential drugs for the therapeutic care of cardiovascular diseases. This paper aims to investigate the therapeutic potentials and mechanism of bee venom (BV) using isoproterenol (ISO)-induced CH models in vivo and in vitro . Melittin was identified as the dominant component in air-dried BV using UPLC-Q/TOF-MS, and subsequently it confirmed that BV prevented electrocardiogram and echocardiography abnormalities, and attenuated morphological and histopathological alterations of hypertrophic hearts in mice. Mechanistically, through network pharmacology exploration, angiotensin-converting enzyme (ACE) and renin (REN) were predicted as the key targets of melittin against CH. This was further confirmed by the in vitro experimental results that BV significantly downregulated the protein or mRNA expression levels of CH markers (β-MHC, ANP, BNP), ACE, and IL-1β in ISO-induced hypertrophic cardiomyocytes. Furthermore, it was ascertained that BV inhibited JAK2/NF-κB signaling cascade via decreasing the protein expression ratio of p-JAK2/JAK2 and the protein expression level of NF-κB. This study showed that BV alleviated ISO-induced CH in vivo and in vitro via JAK2/NF-κB signaling cascade, providing a basis for treating CH with BV or melittin.
研究领域:
药理学
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心血管医学
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分子生物学
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毒理学
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2023
·
IF 7.4
Jianzhong Zhang,Xue Liu,Yutian Xia,Shuyu Xu,Xuan Liu,Haiqing Xiao,Xiaoyong Wang,Chao Liu,Gang Liu
Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody-melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio-synthetically fabricated, with the recombinant protein (hGC33 scFv-melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14-responsive manner at tumor sites, which reduced off-target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small-molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co-delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.
研究领域:
癌症治疗
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药物递送系统
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纳米技术
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生物医学工程
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药学
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Meng Zeng,Ping Deng,Qin Li,Qi Tang,Jixiang Li,Liangke Zhang
Psoriasis, an immune-mediated disease, commonly utilizes topical drug administration in clinical treatments, yet the thickening of skin presents a challenge to conventional topical drug delivery methods. In this study, we have successfully developed a multifunctional composite ionic liquid (CIL) that enhances the local delivery of melittin (CIL@Mel) by modifying the fluidity of the stratum corneum and the structure of keratin. In addition, CIL@Mel can transport H 2 S to the psoriatic microenvironment, effectively regulating the redox imbalance within it. The in vivo experimental results demonstrated that CIL@Mel effectively mitigates the progression of psoriasis, provides relief from oxidative stress, reduces the production of inflammatory factors, and promotes the repolarization of macrophages. Computational simulations and experimental validation revealed that CIL@Mel exerts its effects by inhibiting the expression of EGFR, STAT3, IL-6, SRC, and HSP90AA1. In conclusion, this study unveils the transdermal promotion mechanism of CIL@Mel and validates its efficacy in psoriasis.
研究领域:
药理学
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皮肤病学
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生物化学
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产品关联
DOI
高影响因子
Frontiers in Neuroscience
·
2025
·
IF 3.2
Daxian Li,Yan Wu,Lirong Chang,Yizhi Song,Xiaoqiang Du,Fenqin Xue,Yang Liu,Jie Wu,Tianlong Wang
Introduction: As a taxane-based cytostatic agent, paclitaxel holds a broad spectrum of life-saving properties. However, its use is frequently limited by painful neuropathy in the extremities, which severely hinders the ultimate prognosis of cancer survivors. While bee venom therapy has shown promise in alleviating chemotherapy-induced neuropathic pain, the analgesic potential of its primary bioactive components, such as melittin and phospholipase A2 (bvPLA2), remains uncharacterized. This study investigated the ameliorative effects of melittin against paclitaxel-induced peripheral neuropathy in rats through integrated behavioral, in vivo electrophysiological, and neuropharmacological approaches.Methods: Paclitaxel was administered intraperitoneally (i.p.) at a total dose of 8 mg/kg. Cold and mechanical allodynia and hyperalgesia were quantified using the acetone drop and von Frey filament tests. To compare the therapeutic properties of bee venom ingredients, either melittin (0.5 mg/kg) or bvPLA2 (0.12 mg/kg) was administered subcutaneously at ST36 (Zusanli acupoint). In vivo extracellular recordings of wide dynamic range (WDR) neurons were performed in the spinal dorsal horn. Noradrenaline depletion was induced by the i.p. treatment with N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg), and serotonin depletion was conducted by the i.p. administration of para-chlorophenylalanine (PCPA, 450 mg/kg).Results: ST36 treatment with melittin, but not bvPLA2, markedly impeded mechanical and cold hypersensitivity. Electrophysiological analysis revealed that paclitaxel induced spontaneous and stimulus-evoked hyperexcitation of spinal WDR neurons. Melittin selectively suppressed evoked neuronal activities (i.e., acute responses and after-discharges) without modulating the spontaneous firing of WDR neurons. Neuropharmacological investigation demonstrated that the effects of melittin were fully reversed by noradrenaline depletion, whereas serotonin depletion had no effect.Discussion: Our findings establish that melittin treatment at ST36 could ease paclitaxel-induced neuropathic pain by partially attenuating the hyperexcitable state of spinal WDR neurons. Furthermore, these ameliorative actions were mediated by the specific recruitment of the endogenous noradrenergic system. This study provides novel evidence supporting melittin as a targeted symptomatic agent for paclitaxel-induced peripheral neuropathy, which would advance the development of promising analgesic strategies in oncological care.
研究领域:
药理学
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神经科学
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肿瘤学
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生物医学
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DOI
PubMed
高影响因子
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
·
2025
·Vol. 29
·期 4
·487
·
IF 2.2
Tingting Yu,Zirui Yuan,Jiaona Yu,Lu Chen,Wei Hao,Xiaohui Xu
Melittin (MEL) is the main bioactive component of bee venom and has been reported to have various pharmacological effects. This study investigates the protective effect of MEL on MPP + -injured HT22 cells and the possible mechanisms involved. We treated the cells with 4 mM MPP + for 24 h to induce a cellular injury model. HT22 cells were pretreated with 0.1 µM MEL for 6 h and then exposed to 4 mM MPP + for 24 h. We measured cell viability, the expression of Bax, the indicators and protein levels associated with apoptosis and parthanatos, and the co-localisation of MEL and mitochondria, and mitochondrial function-related indices such as the mitochondrial membrane potential (MMP) and mito-SOX. We show that PAR protein expression was significantly increased in the MPP + -treated cell model and that the parthanatos inhibitor DPQ significantly reduced MPP + -induced cell death, suggesting that MPP + can cause PARP1-dependent cell death. MEL significantly inhibited cell death, increased cell viability as well as NAD+ and ATP levels, increased the expression of Bcl-2 and suppressed the activation of Bax, cleaved-caspase3, and cleaved-PARP1. Moreover, MEL was found to be localised on the mitochondria of HT22 cells and to improve mitochondrial functions including increased MMP and decreased mitochondrial reactive oxygen species. We speculate that MEL may protect neurons against MPP + -induced HT22 cell injury by inhibiting Bax activation, suppressing changes in mitochondrial permeability, and improving mitochondrial function, thereby preventing cell parthanatos and apoptosis.
研究领域:
神经生物学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2025
·
IF 4.6
Tong Xiong,Du Li,Juanjuan Ren,Chuncheng Chen,Shijie Li,Zhuoyue Song,Nenggui Xu,Tao Liu,Shihui Liu
Bee venom acupuncture (BVA) offers therapeutic potential for rheumatoid arthritis (RA) but faces challenges from pain and allergies linked to live bee stings. A key hurdle is melittin (Mel), bee venom's main anti-inflammatory component, which degrades rapidly when orally ingested, leading to decreased efficacy and increased toxicity. This study proposes a solution by encapsulating melittin in liposomes to enhance stability and lessen side effects, expanding its clinical applicability. Additionally, the advancement of microneedle technology, which bypasses gastrointestinal issues by targeting the stratum corneum, opens a novel pathway for RA treatment. Employing soluble microneedles loaded with melittin-encapsulated liposomes (Mel-Lip) enables effective transdermal delivery. Results from an adjuvant-induced RA animal model show that Mel-Lip microneedles improve foot health, repair cartilage, and lower inflammatory markers, highlighting microneedling with transdermal nanocarriers as a promising, patient-friendly approach for RA management.
研究领域:
药理学
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生物医学工程
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2025
·
IF 3.7
Jun Yao,Sunfang Chen,Zaihua Zhu,Jianjiang Chen,Jiajie Xia,Bin Fang,Jingjing Guo,Bing Wu,Gaoxiang Ma
Osteoarthritis has become a common degenerative joint disease, lacking clinical means to alleviate this disease. Melittin, taken from natural honeybee venom, possesses outstanding anti-inflammatory properties and has great potential to treat OA. However, its high toxicity and hemolytic properties limit its application. In this work, a biocompatible hydrogel was prepared from extracellular matrix of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of extracellular matrix hydrogel loaded with melittin can reduce the intrinsic toxicity of melittin and prolong the release behavior, simultaneously. The in vitro study demonstrated that melittin-hydrogel could effectively inhibit phosphorylation-ERK/JNK, prevent the exacerbation of TNF-α-induced apoptosis in ATDC5 cells, and reduce their inflammatory markers, effectively alleviating osteoarthritis and preventing cartilage degradation.
Subsequently, in vivo studies have demonstrated that injecting melittin-hydrogel into the joint cavity of OA mice can effectively reduce cartilage degeneration. These findings suggest that melittin-hydrogel plays a critical role in the development of osteoarthritis and may provide a therapeutic option for the treatment of OA disease.
研究领域:
生物材料学
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药理学
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骨科医学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Lili Jin,Zhenhui Wang,Cheng Peng,Miao He,Feng Wang,Hongyan He,Changsheng Liu
Rheumatoid arthritis (RA), a persistent and debilitating chronic disease characterize by joint damage and deformity, significantly impairs the life quality of patients and presents challenges for conventional drug administration due to organ damage and unsatisfactory therapeutic outcomes. To address these challenges, this study introduces an innovative hydrogel cryo-microneedle patch (CMNP)-mediated local administration system, primarily composed of chondroitin sulfate (CS), to deliver the potent anti-inflammatory drug melittin (MEL). This innovative approach not only circumvents organ impairment but also enhances patient compliance. The acute toxicity of MEL is effectively mitigated by electrostatic binding with CS molecules, forming MC complexes that induce apoptosis in fibroblast-like synoviocytes (FLS). The MC-loaded CMNPs (MC@CCMNPs) exhibit remarkable therapeutic capacity with a notably meliorated joint damage and suppressed arthritis severity in the RA rat model. Therefore, MC@CCMNPs emerge as a promising anti-inflammatory and safe therapy for RA treatment, as well as for other inflammation related chronic diseases.
研究领域:
药理学
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生物医学工程
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Dongsheng Zhang,Tingting Wang,Xun Zhang,Yuting Xu,Jiang Ming,Xiaoxiao Wang,Zhenfeng Liu,Jingchao Li,Xinhui Su
The primary goal of treating malignant tumors is to efficiently eliminate the primary tumor and prevent metastasis and recurrence. Unfortunately, the immunosuppressive tumor microenvironment (TME) is a significant obstacle to effective oncotherapy. Herein, a therapeutic strategy based on melittin (MLT) encapsulated in hyaluronic acid-modified metal–organic frameworks (MOFs) is pioneered, focusing on the safe delivery and TME-responsive release of MLT to reshaping the immunosuppressive TME and simultaneously activating the immune system to eradicate cancerous cells. Iron-based MOFs respond to glutathione and pH, degrade within a moderately acidic TME, and achieve tumor-specific release of MLT. Additionally, the iron-mediated Fenton reaction produces reactive oxygen species that augment oxidative stress, ultimately leading to tumor-specific ferroptosis, whereas MLT-induced membrane disruption promotes immunogenic cell death to activate the immune system. In combination with the immune checkpoint inhibitor anti-PD-L1, this nanodrug elicits potent antitumor immune responses, facilitating the infiltration of effector T cells and enhancing systemic antitumor T cell immunity to suppress both primary and distant tumors. This study demonstrates the tremendous potential of nanoscale self-destructive MOFs for the targeted transport and controlled release of MLT and reveals the promoting effect of combined MLT and ferroptosis delivery on cancer immunotherapy.
研究领域:
肿瘤学
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纳米医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOLOGY
·
2022
·Vol. 56
·期 6
·1012-1019
·
IF 1.54
Wang R.,Shi M.-Y.,Ma B.-B.,Sheng J.
Abstract Phosphatidylserine (PS) is an important apoptotic-cell surface signal that exists in bacterial and cancer cells. The mechanism by which melittin interacts with the PS membrane remains unclear. Here, we revealed this mechanism by using a dual-channel fluorescence microscope to observe the concentration-dependent process of pore formation in giant unilamellar vesicles (GUVs) that were exposed to melittin solution. We found that unsaturated PS membranes differed significantly from saturated PS membranes in different phases. This study provides a reference for research and development of anticancer drugs.
研究领域:
生物化学
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细胞生物学
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药理学
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DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 3
·558
·
IF 4.2
Hongyan Yang,Rong Ma,Jiarou Chen,Qian Xie,Wenhui Luo,Pinghua Sun,Zheng Liu,Jialiang Guo
The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.Keywords:antimicrobial peptides;melittin;antibacterial;anti-biofilm;anti-quorum sensing
研究领域:
微生物学
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药理学
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分子生物学
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传染病学
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DOI
PubMed
高影响因子
LIFE SCIENCES
·
2020
·
IF 3.647
Li Li,Sufang Zhang,Lei Wei,Zhongfu Wang,Wei Ma,Fangying Liu,Yanhua Shen,Shanfang Zhang,Xiulian Zhang,Yu Hang,Yechang Qian
Aims To investigate the effect and underlying mechanism of melittin and tripartite motif (TRIM) family in human embryonic lung fibroblast (HELF). Materials and methods Lentiviral RNA interference vector and lentiviral overexpression vector were constructed and packaged by transfecting 293T cells; the proliferation of HELF was examined using Cell Counting Kit 8; Western blot and qRT-PCR were performed to examine protein and mRNA expression; the interaction with protein phosphatase magnesium-dependent 1A (PPM1A) was examined by Co-immunoprecipitation. Key findings Compared with the control group, the mRNA expression of the TRIM6, TRIM8 and TRIM47 in the IPF group significantly increased. Melittin inhibited the mRNA expression and protein expression levels of TRIM47, the HELF proliferation, the hydroxyproline levels, and the phosphorylation of Smad2/3; the interference of TRIM47 inhibited the protein expression of Vimentin, α-SMA, CTGF, the phosphorylation of Smad2/3 and the synthesis of hydroxyproline; TRIM47 overexpression elevated the phosphorylation of Smad2/3, induced ubiquitination of PPM1A and decreased the expression level of PPM1A, while TRIM47 RNA interference reversed this result. Significance Melittin has anti-fibrotic effect in HELF by directly reducing the phosphorylation of Smad2/3 or indirectly reducing the phosphorylation of Smad2/3 by decreasing the expression levels of TRIM47 whose overexpression induces ubiquitination of PPM1A.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
肺纤维化
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产品关联
DOI
PubMed
高影响因子
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