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
·
皮肤病学
·
生物化学
✓ 已验证
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
·
神经科学
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肿瘤学
·
生物医学
✓ 已验证
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
·
细胞生物学
✓ 已验证
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
·
生物医学工程
·
风湿病学
✓ 已验证
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
✓ 已验证
DOI
高影响因子
ACS Nano
·
2019
·
IF 13.903
Haojie Liu,Yan Hu,Yajie Sun,Chao Wan,Zhanjie Zhang,Xiaomeng Dai,Zihan Lin,Qianyuan He,Zhe Yang,Piao Huang,Yuxuan Xiong,Jinguo Cao,Xu Chen,Qi Chen,Jonathan F. Lovell,Zushun Xu,Honglin Jin,Kunyu Yang
Photodynamic therapy (PDT) is a clinical cancer treatment modality based on the induction of therapeutic reactive oxygen species (ROS), which can trigger immunogenic cell death (ICD). With the aim of simultaneously improving both PDT-mediated intracellular ROS production and ICD levels, we designed a serum albumin (SA)-coated boehmite (“B”; aluminum hydroxide oxide) organic–inorganic scaffold that could be loaded with chlorin e6 (Ce6), a photosensitizer, and a honey bee venom melittin (MLT) peptide, denoted Ce6/MLT@SAB. Ce6/MLT@SAB was anchored by a boehmite nanorod structure and exhibited particle size of approximately 180 nm. Ce6/MLT@SAB could significantly reduce hemolysis relative to that of free MLT, while providing MLT-enhanced PDT antitumor effects in vitro. Compared with Ce6@SAB, Ce6/MLT@SAB improved Ce6 penetration of cancer cells both in vitro and in vivo, thereby providing enhanced intracellular ROS generation with 660 nm light treatment. Following phototreatment, Ce6/MLT@SAB-treated cells displayed significantly improved levels of ICD and abilities to activate dendritic cells. In the absence of laser irradiation, multidose injection of Ce6/MLT@SAB could delay the growth of subcutaneous murine tumors by more than 60%, compared to controls. When combined with laser irradiation, a single injection and phototreatment with Ce6/MLT@SAB eradicated one-third of subcutaneous tumors in treated mice. The addition of an immune checkpoint blockade to Ce6/MLT@SAB phototreatment further augmented antitumor effects, generating increased numbers of CD4+ and CD8+ T cells in tumors with concomitant reduction of myeloid-derived suppressor cells.
研究领域:
肿瘤学
·
免疫学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yuhan Zheng,Qingyun Wei,Xuan Han,Xiangmin Tao,Tao Cao,Tianbao Chen,Peng Cao,Qichen Zhan
Despite exhibiting potent anticancer activity, the strong hemolytic properties of melittin (MEL) significantly restrict its delivery efficiency and clinical applications. To address this issue, we have devised a strategy wherein homologous dopamine (DA), an essential component of bee venom, is harnessed as a vehicle for the synthesis of MEL–polydopamine (PDA) nanoparticles (MP NPs). The ingenious approach lies in the fact that MEL is a basic polypeptide, and the polymerization of DA is also conducted under alkaline conditions, indicating the distinctive advantages of PDA in MEL encapsulation. Furthermore, MP NPs are modified with folic acid to fabricate tumor-targeted nanomedicine (MPF NPs). MPF NPs can ameliorate the hemolysis of MEL in drug delivery and undergo degradation triggered by high levels of reactive oxygen species (ROS) within solid tumors, thereby facilitating MEL release and subsequent restoration of anticancer activity. After cellular uptake, MPF NPs induce cell apoptosis through the PI3K/Akt-mediated p53 signaling pathway. The tumor growth inhibitory rate of MPF NPs in FA receptor-positive 4T1 and CT26 xenograft mice reached 78.04% and 81.66%, which was significantly higher compared to that in FA receptor-negative HepG2 xenograft mice (45.79%). Homologous vehicles provide a new perspective for nanomedicine design.
研究领域:
纳米医学
·
癌症治疗
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药学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 21
·11686
·
IF 4.9
Kangli Wang,Lingchen Tao,Meifei Zhu,Xinyu Yu,Yuanyuan Lu,Bin Yuan,Fuliang Hu
Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin’s pro-apoptotic and anti-metastatic effects on CRC in vitro and in vivo. The results showed that melittin-induced mitochondrial ROS bursts decreased ΔΨm, inhibited Bcl-2 expression, and increased Bax expression in both cells and tumor tissues. This led to increased mitochondrial membrane permeability and the release of pro-apoptotic factors, particularly the high expression of Cytochrome C, initiating the apoptosis program. Additionally, through wound-healing and transwell assays, melittin inhibited the migration and invasion of CRC cells. In vivo, the anti-metastatic effect of melittin was also verified in a lung metastasis mouse model. Western blotting and immunohistochemistry analysis indicated that melittin suppressed the expression of MMPs and regulated the expression of crucial EMT markers and related transcription factors, thereby inhibiting EMT. Furthermore, the melittin disrupts neovascularization, ultimately inhibiting the metastasis of CRC. In conclusion, melittin exerts anti-CRC effects by promoting apoptosis and inhibiting metastasis, providing a theoretical basis for further research on melittin as a targeted therapeutic agent for CRC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
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
·
心血管医学
·
分子生物学
·
毒理学
·
生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ARTHROPLASTY
·
2024
·
IF 3.4
Junqi Niu,Fanggang Bi,Qing Tian,Ke Tian
Background Aseptic loosening around the prosthesis is a common cause of failure in total joint arthroplasty. Polyethylene wear particles trigger the release of inflammatory factors by macrophages. Key mediators involved in osteoclastogenesis include interleukin-6, tumor necrosis factor-α, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and bone protection hormone (Osteoprotegerin [OPG]). The purpose of our experiment was to see whether melittin can slow down the release of inflammatory mediators through the NF-kB pathway, regulate the RANKL/OPG ratio, reduce osteoclast formation, and delay the onset of arthritis in rats. Methods A total of 20 male Sprague-Dawley rats (10 months, Specific Pathogen Free, 350 g ± 20 g) were randomly divided into 5 groups: sham group, model group, melittin concentration 1 group (0.2 mg/kg), concentration 2 group (0.4 mg/kg), and concentration 3 group (0.6 mg/kg). All rats were implanted with TA2 high-purity titanium rods. A drill was used to create a bone canal along the long axis of the femur in the intercondylar notch. The model group and experimental groups were exposed to polyethylene particles, while the sham group did not receive any particles. Results The melittin group exhibited significantly increased serum levels of serum P, calcium-phosphorus product, OPG, PINP, PINP/CTX-I, and OPG/RANKKL ( P < .05). In the experimental group, micro computed tomography scanning results revealed a decrease in the amount of bone defect around the prosthesis. Immunofluorescence analysis demonstrated a decrease in the expression of IKKα and P65, while the expression of OPG showed an upward trend. Both Hematoxylin-Eosin and Tartrate-Resistant Acid Phosphatase staining revealed less osteoclast and inflammatory cell infiltration in bone resorption pits. Conclusions Our study demonstrates that melittin has the ability to inhibit the NF-kB pathway in a rat model, and reduce the impact of RANKL/OPG, thereby delaying osteoclast activity and alleviating periprosthetic osteolysis.
研究领域:
骨科
·
免疫学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yiqian Wang,Yuzhi Qiu,Sihan Chen,Jinzhao Huang,Xiuwen Hu,Jiawen Chen,Sheng Wang,Xiangliang Yang,Yan Zhang,Yanhong Zhu
Systemically administered drugs often lead to off-target delivery, inducing compromised therapy efficacy and significant toxicity. We hypothesize that improving the drugs’ targeting and spatiotemporally controllable releasing capabilities can enhance the anti-tumor effects and reduce the side effects. To achieve this goal, a functionalized biomimetic photoactivatable nanotherapeutics (U-ACPT@MM) is designed. The U-ACPT@MM comprises of melittin, a pore-forming protein, functionalized within the 4 T1 tumor cell membrane, camouflaged with lanthanide-doped upconversion nanoparticles (UCNPs) conjugated with 9-aminocamptothecin (ACPT), a chemotherapeutics, by photolabile linkers. The melittin-functionalized 4 T1 tumor cell membrane not only enables homologous targeting ability to 4 T1 tumors, but also increases both the concentration of melittin and ACPT within tumor. Meanwhile, upon 808 nm irradiation, the UV emissions from UCNPs cut off photolabile linker to release ACPT. The synergism of enhanced tumor targeting and combinational therapeutic effects of ACPT and melittin leads to significant inhibition of 4 T1 tumor and lung metastasis with reduced side effects in vivo . Thus, our study provides a promising functional biomimetic photoactivatable nano-therapeutical strategy for cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-14
·
IF 10.6
Shen Wenqi,Li Yecheng,Yang Ziyi,Li Wenjing,Cao Yi,Liu Yilin,Wang Zheng,Pei Renjun,Xing Chungen
The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
肿瘤微环境
·
免疫学
✓ 已验证
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）