JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Zhi-Ting Liu,Ying Zhang,Rui Fang,Monique Simmonds,Xiu-Juan Zhang,Tong-Tong Zhang,Tong-Tong Sun,Xiao-Qiang Chen
Ethnopharmacological relevance In the snake-infested mountainous regions of China, Saxifraga stolonifera [L.] Meeb is widely utilized as an immediate remedy for venomous snake bites. However, the scientific understanding of S. stolonifera 's efficacy in snakebite treatment remains limited and requires further investigation. Aim of the study The aim of this study was to assess the inhibitory effects of Saxifraga stolonifera phenolic extracts (SSPE) on Deinagkistrodon acutus venom (DAV) and explore the potential of S. stolonifera as a valuable candidate for antivenom development. Materials and methods We employed our previously optimized extraction conditions to obtain SSPE. In vitro experiments utilizing diverse models were conducted to assess the inhibitory effects of the extracted phenolic compounds on DAV, specifically targeting phospholipase A 2 (PLA 2 ), proteolytic, fibrinolytic , and hyaluronidase enzymes. Furthermore, in vivo investigations were conducted to evaluate the inhibitory potential of the extracted compounds against DAV-induced hemorrhagic and edematogenic activity. To elucidate the chemical composition of the phenolic extracts, Ultra Performance Liquid Chromatography-mass spectrometry (UPLC-MS) analysis was performed. Results Our in vitro inhibition study showed that S. stolonifera was able to inhibit the activities of PLA 2 enzyme, proteolytic enzyme , hyaluronidase and fibrinogenolytic. The median effective dose (ED 50 ) values of SSPE for inhibiting PLA 2 enzyme, proteolytic enzyme and hyaluronidase activities were 0.115 mg/mL, 0.026 mg/mL and 0.238 mg/mL, respectively. The DAV-induced hemorrhagic and edematogenic effects of the SSPE were also successfully inhibited in vivo , and the high SSPE concentration was able to completely inhibit the hemorrhage and edema. It is noteworthy that the mice suffered no harm from the high SSPE concentration. The composition analysis showed that the phenolic substances contained in SSPE are gallic acid , protocatechuic acid , chlorogenic acid , rutin , kaempferol-3-O-ɑ-L-rhamnoside, kaempferol-3-O-β-D-glucopyranoside, quercetin and kaempferol . Conclusions This study provides scientific validation of the inhibitory efficacy of S. stolonifera as an emergency treatment for venomous snake bites , offering a theoretical foundation for future drug development strategies targeting snakebite.
研究领域:
药理学
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毒理学
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植物化学
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ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
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2024
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IF 4.1
Junyao Wang,Xi Liu,Yuxin Song,Zhonghua Liu,Xing Tang,Huaxin Tan
Antibiotic resistance has become a critical concern in recent years, and antimicrobial peptides may function as innovative antibacterial agents to address this issue. In this work, we identified a novel antimicrobial peptide, LC-AMP-I1, derived from the venom of Lycosa coelestis, demonstrating substantial antibacterial properties and minimal hemolytic activity. LC-AMP-I1 was subjected to additional assessment for antibacterial efficacy, anti-biofilm properties, drug resistance, stability, and cytotoxicity in vitro. It exhibited comparable antibacterial efficacy to melittin against six common clinical multidrug-resistant bacteria, effectively inhibiting biofilm formation and disrupting established biofilms. Additionally, LC-AMP-I1 demonstrated minimal bacterial resistance, excellent stability, negligible mammalian cell toxicity, low hemolytic activity, and appropriate selectivity for both normal and tumor cells. When combined with traditional antibiotics, LC-AMP-I1 exhibited additive or synergistic therapeutic effects. In a neutropenic mouse thigh infection model, LC-AMP-I1 exhibited a therapeutic effect in inhibiting bacterial proliferation in vivo. The mechanistic investigation indicated that LC-AMP-I1 could influence bacterial cell membrane permeability at low concentrations and directly disrupt structure-function at high concentrations. The results of this work indicate that LC-AMP-I1 may function as a viable alternative to traditional antibiotics in addressing multidrug-resistant bacteria.
研究领域:
微生物学
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分子生物学
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药物开发
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感染性疾病
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高影响因子
MOLECULES
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2020
·Vol. 25
·期 18
·4269
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IF 3.267
Ji-Heng Wu,Yue-Ting Cao,Hong-Ye Pan,Long-Hu Wang
(1) Background: Toad venom (Bufonis Venenum, known as ‘Chansu’ in Chinese), the secretion of the ear-side gland and skin gland of Bufo gargarizans cantor or Duttaphrynus melanostictus Schneider, has been utilized to treat several diseases in China for thousands of years. However, due to the chemical variability of the components, systematic chemical composition and the key pharmacophores in toad venom have not yet fully understood. Besides, it contains a variety of effective compounds with different physiological activity and chemotypes, mainly including alkaloids, bufogenins, bufotoxins, and so on. The recent pharmacological researches have demonstrated that several bufogenins have remarkable pharmacological effects, such as anti-inflammatory, analgesic effects, and anti-tumor effects. Aim of the study: To identify the bioactive compounds and pharmacophores originating from toad venom based on analyzing spectrum-effect relationship by chemometrics and to explore the anti-cancer mechanism primarily. (2) Materials and methods: Fingerprint of the 21 batches of samples was established using HPLC (High Performance Liquid Chromatography). The anti-tumor activity of extracts were determined by in-vitro assays. Chemometric analysis was used to establish the spectrum-effect model and screen for active ingredients. Pharmacodynamic tests for the screened active compound monomers were conducted with in-vitro assays. Further anti-tumor mechanisms were investigated using western blot and flow cytometry. (3) Results: The established spectrum-effect model has satisfactory fitting effect and predicting accuracy. The inhibitory effect of major screened compounds on lung carcinoma cells A549 were validated in vitro, demonstrating that arenobufagin, telocinobufogenin, and cinobufotalin had significant anti-tumor effects. Through further investigation of the mechanism by western blotting and flow cytometry, we elucidated that arenobufagin induces apoptosis in A549 cells with the enhanced expression of cleaved PARP (poly (ADP-ribose) polymerase). These results may provide valuable information for further structural modification of bufadienolides to treat lung cancer and a method for discovery of anti-tumor active compounds. Conclusions: Our research offers a more scientific method for screening the principal ingredients dominating the pharmacodynamic function. These screened compounds (arenobufagin, etc.) were proven to induce apoptosis by overactivation of the PARP-pathway, which may be utilized to make BRCA (breast cancer susceptibility gene) mutant cancer cells more vulnerable to DNA damaging agents and kill them.Keywords:toad venom;spectrum-effect relationship;chemometrics;apoptosis
研究领域:
药理学
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肿瘤学
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化学计量学
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分子生物学
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PEST MANAGEMENT SCIENCE
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2024
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IF 3.8
Xinyi Wang,Wenhong Li,Xiang Yang,Mingwei Yang,Yucheng Gu,Zhao Du,Jingyi Yang,Mingxia Wen,Yoonseong Park,Chunyang Huang,Yueping He
BACKGROUND Widespread resistance of insect pests to insecticides and transgenic crops in the field is a significant challenge for sustainable agriculture, and calls for the development of novel alternative strategies to control insect pests. One potential resource for the discovery of novel insecticidal molecules is natural toxins, particularly those derived from the venoms of insect predators. RESULTS In this study, we identified three insecticidal proteinaceous toxins from the venom glands (VGs) of the predatory stink bug, Arma custos (Hemiptera: Asopinae). Transcriptomic analysis of A. custos VGs revealed 151 potentially secreted VG-rich venom proteins. Three VG-rich venom proteins (designated AcVP1 ~ 3) were produced by overexpression in Escherichia coli . Injection of the recombinant proteins into tobacco cutworm ( Spodoptera litura ) larvae showed that all of the three recombinant proteins caused paralysis, liquefaction and death. Injection of recombinant proteins into rice brown planthopper ( Nilaparvata lugens ) nymphs showed higher insecticidal activities, among which a trypsin (AcVP2) caused 100% mortality postinjection at 1.27 pmol mg −1 body weight. CONCLUSION A natural toolkit for the discovery of insecticidal toxins from predatory insects has been revealed by the present study. © 2024 Society of Chemical Industry.
研究领域:
昆虫学
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分子生物学
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农业科学
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高影响因子
Science Advances
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2023
·Vol. 9
·期 25
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IF 13.6
Zhou Zhu,Jian Wang,Xibo Pei,Junyu Chen,Xinwei Wei,Yanhua Liu,Pengcheng Xia,Qianbing Wan,Zhen Gu,Yong He
Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers’ healing speed or halting early tumor progression.
研究领域:
生物医学工程
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药学
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材料科学
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仿生学
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JOURNAL OF VENOMOUS ANIMALS AND TOXINS INCLUDING TROPICAL DISEASES
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2022
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IF 2.293
Fu Ying,Zhang Yu,Ju Shuang,Ma Bokai,Huang Wenwen,Luo Sulan
Background: Conopeptides from cone snail venom have aroused great interest related to the discovery of novel bioactive candidates, due to their excellent prospects for the treatment of various health problems such as pain, addiction, psychosis and epilepsy. In order to explore novel biopeptides, we investigated the structure and function of five novel conopeptides isolated from the venom of Conus marmoreus from South China Sea. Methods: C. marmoreus crude venom was prepared, fractionated and purified by HPLC system. The primary sequences of the five novel disulfide-poor conopeptides Mr-1 to Mr-5 were identified by comprehensive analysis of de novo MALDI-TOF tandem mass spectrometry and Edman degradation data. In order to investigate their function, these five conopeptides were synthesized by Fmoc-SPPS chemistry, and their biological effects at several heterologous rat nicotinic acetylcholine receptor (nAChR) subtypes (α1β1δε, α3β2, α3β4, α4β2) were determined by electrophysiological technique. Results: Five novel disulfide-poor conopeptides were identified and named as follows: Mr-1 (DWEYHAHPKPNSFWT), Mr-2 (YPTRAYPSNKFG), Mr-3 (NVIQAPAQSVAPP NTST), Mr-4 [KENVLNKLKSK(L/I)] and Mr-5 [NAVAAAN(L/I)PG(L/I)V]. None of them contains a disulfide bond. The sequences of conopeptides Mr-2 to Mr-5 do not belong to any category of the known disulfide-poor conopeptides. No significant activity against the above nAChR subtypes were observed for the five conopeptides at 100 µM. Conclusion: We purified and structurally characterized five novel disulfide-poor conopeptides from C. marmoreus crude venom and first investigated their nAChR inhibitory effects. This work expanded our knowledge on the structure and function of disulfide-poor conopeptides from this cone snail venom.
研究领域:
药理学
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生物化学
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毒素学
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神经科学
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高影响因子
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