Evaluation of analgesic and anti-inflammatory actions of indolealkylamines from toad venom in mice using lipidomics and molecular docking

Xu, Dihui; Wang, Jiaojiao; Chen, Wuyue; Yang, Xinyi; Zhou, Jing; Ma, Hongyue; Di, Liuqing; Duan, Jin‐Ao

doi:10.1016/j.jep.2020.113677

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…Limited studies have demonstrated the presence of the B. chinensis -like isoflavonoids (irisflorentin, tectorigenin and tectoridin) in plants, which exert anti-inflammatory effects by suppressing prostaglandin E 2 , COX-2, NO, tumor necrosis factor α, and interleukin-6 production in vitro. 7 , 36 Moreover, the anti-inflammatory activity of irisflorentin may be attributed to the inhibition of NO, TNF-α, IL-1β, and IL-6 mediated by the inactivation of ERK1/2- and p38-mediated activator protein-1 pathways. 37 , 38 Lim et al 25 reported that tectorigenin exerts anti-inflammatory effects through downregulation of the inflammatory mediators iNOS, COX-2, TNF-α, and IL-6 by suppressing NF-kB/ERK/JNK-related signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Anti-Nociceptive and Anti-Inflammatory Activities of the Ethyl Acetate Extract of Belamcanda chinensis (L.) Redouté in Raw 264.7 Cells in vitro and Mouse Model in vivo

He¹,

Yan²,

Yuan³

et al. 2022

JPR

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Purpose Inflammation and accompanying pain is a common global health problem that seriously affects human quality of life worldwide. Here, we aimed to investigate the anti-nociceptive and anti-inflammatory activities of the ethyl acetate extract of B. chinensis (EAEBc) along with the underlying mechanisms of action. Methods The in vitro anti-inflammatory activity of EAEBc was explored using an LPS-induced RAW264.7 cell inflammatory model. Nitric oxide (NO) production, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were evaluated. In vivo anti-nociceptive and anti-inflammatory activities of EAEBc were assessed with the aid of classical experimental mouse models. In addition, LPS-induced biomarker contents (TNF-α, IL-1β, IL-6, NO, iNOS, and PGE2) and formalin-induced serum inflammatory factors (NO, PGE2, 5-HT, β-EP, substance P, and NE) were determined in mice. Results In vitro, EAEBc significantly reduced LPS-induced NO generation and suppressed the production of TNF-α, IL-1β, and IL-6 in RAW264.7 cells in a concentration-dependent manner. In vivo, EAEBc downregulated serum TNF-α, IL-1β, IL-6, NO, iNOS, and PGE2 contents in mice with LPS-induced inflammation in a dose-dependent manner. EAEBc displayed anti-inflammatory activity in carrageenan-induced paw edema and xylene ear edema tests. Intragastric administration of EAEBc at test doses of 100 and 200 mg/kg led to inhibition of nociception and capillary permeability induced by acetic acid to varying degrees. Similarly, EAEBc exerted analgesic effects in the formalin and hot plate tests. In particular, the administration of EAEBc reversed the changes in the levels of inflammatory indicators NO, PGE2, 5-HT, β-EP, substance P, and NE in a mouse model of formalin-induced pain. Conclusion Our findings provide considerable evidence to support the extensive application of B. chinensis in traditional medicine and demonstrate the utility of this plant species as an effective candidate for prevention or treatment of various pain and inflammation-related conditions.

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Section: Discussionmentioning

confidence: 99%

Anti-Nociceptive and Anti-Inflammatory Activities of the Ethyl Acetate Extract of Belamcanda chinensis (L.) Redouté in Raw 264.7 Cells in vitro and Mouse Model in vivo

He¹,

Yan²,

Yuan³

et al. 2022

JPR

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“…Toad venom, also named as Chan-Su, is a traditional Chinese medicine that has shown therapeutic efficacies in clinic (mainly in China) and has been widely used for the treatment of cancer, cardiovascular diseases, pain, and inflammation/inflammatory diseases as shown in Figure 1 ( Gao et al, 2017 ; Li et al, 2021a ; Xu et al, 2021 ; Zheng et al, 2022 ). Originally derived from the skin and auricular glands of Chinese toad, toad venom is used to repel toad’s natural enemies primarily, working as a protective agent.…”

Section: Introductionmentioning

confidence: 99%

Toad venom-derived bufadienolides and their therapeutic application in prostate cancers: Current status and future directions

Zhou

Han

et al. 2023

Front. Chem.

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Cancer is the second leading cause of death worldwide. Specially, the high incidence rate and prevalence of drug resistance have rendered prostate cancer (PCa) a great threat to men’s health. Novel modalities with different structures or mechanisms are in urgent need to overcome these two challenges. Traditional Chinese medicine toad venom-derived agents (TVAs) have shown to possess versatile bioactivities in treating certain diseases including PCa. In this work, we attempted to have an overview of bufadienolides, the major bioactive components in TVAs, in the treatment of PCa in the past decade, including their derivatives developed by medicinal chemists to antagonize certain drawbacks of bufadienolides such as innate toxic effect to normal cells. Generally, bufadienolides can effectively induce apoptosis and suppress PCa cells in-vitro and in-vivo, majorly mediated by regulating certain microRNAs/long non-coding RNAs, or by modulating key pro-survival and pro-metastasis players in PCa. Importantly, critical obstacles and challenges using TVAs will be discussed and possible solutions and future perspectives will also be presented in this review. Further in-depth studies are clearly needed to decipher the mechanisms, e.g., targets and pathways, toxic effects and fully reveal their application. The information collected in this work may help evoke more effects in developing bufadienolides as therapeutic agents in PCa.

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“…These 5-substituted IAAs have been recently reported to exhibit significant analgesic activities and have anti-inflammatory effects. 21 Interestingly, evidence has shown that N-di/trimethylated 5-HT is more abundant than 5-HT and N-methyl-5-HT in B. gargarizans. According to Roseghini's study, 5-HT, bufotenine, and bufotenidine in B. gargarizans are present at 10, 175, and 215 μg/g, respectively, and N-methyl-5-HT was not even detected.…”

Section: Introductionmentioning

confidence: 99%

“…They are widely distributed in microorganisms, plants, and animals. , Generally, the potent hallucinogenic agents are found in trace amounts in humans and other animals, − but studies have showed that amphibian skins, especially toad skins, are actually storehouses of IAAs. − A species of amphibian toad, Bufo gargarizan (also known as Bufo bufo gargarizan ), whose dried secretion from the posterior auricular gland is regarded as a valuable ingredient of traditional Chinese medicinal toad venom, is revealed to contain various IAAs − such as 5-HT, N -methyl-5-HT, bufotenine, and bufotenidine (Figure ). These 5-substituted IAAs have been recently reported to exhibit significant analgesic activities and have anti-inflammatory effects . Interestingly, evidence has shown that N -di/trimethylated 5-HT is more abundant than 5-HT and N -methyl-5-HT in B. gargarizans .…”

Section: Introductionmentioning

confidence: 99%

Mining and Characterization of Indolethylamine N-Methyltransferases in Amphibian Toad Bufo gargarizans

Zhang

Zhao

2023

Biochemistry

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Strong, psychedelic indolethylamines (IAAs) are typically present in trace amounts in the majority of species, but they build up significantly in the skin of amphibian toads, especially N-methylated 5-hydroxytryptamine (5-HT) analogues. However, there is no pertinent research on the investigation of indoleamine N-methyltransferase (INMT) in amphibians, nor is there any adequate information on the key amino acids that influence the activity of known INMTs from other species. Herein, we focused on Bufo toad INMT (BINMT) for the first time and preliminarily identified BINMT 1 from the transcriptomes of Bufo gargarizans active on tryptamine, 5-HT, and N-methyl-5-HT. We established the enzyme kinetic characteristics of BINMT 1 and identified the essential amino acids influencing its activity via molecular docking and site-directed mutagenesis. Subsequently, we carried out sequence alignment and phylogenetic tree analysis on 43 homologous proteins found in the genome of B. gargarizans with BINMT 1 as the probe and selected seven of them for protein expression and activity assays. It was found that only three proteins possessing the highest similarity to BINMT 1 had INMT activity. Our research unveils the binding residues of BINMT for 5-HT analogues for the first time and initiates the study of INMTs in amphibian toads, serving as a tentative reference for further study of BINMT and providing insight into the comprehension of BINMT’s catalytic mechanism and its role in the biosynthesis of 5-HT analogues in Bufo toads. It also contributes to the expansion of the INMT library to help explore and explain interspecies evolution in the future.

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Evaluation of analgesic and anti-inflammatory actions of indolealkylamines from toad venom in mice using lipidomics and molecular docking

Cited by 11 publications

References 24 publications

Anti-Nociceptive and Anti-Inflammatory Activities of the Ethyl Acetate Extract of Belamcanda chinensis (L.) Redouté in Raw 264.7 Cells in vitro and Mouse Model in vivo

Anti-Nociceptive and Anti-Inflammatory Activities of the Ethyl Acetate Extract of Belamcanda chinensis (L.) Redouté in Raw 264.7 Cells in vitro and Mouse Model in vivo

Toad venom-derived bufadienolides and their therapeutic application in prostate cancers: Current status and future directions

Mining and Characterization of Indolethylamine N-Methyltransferases in Amphibian Toad Bufo gargarizans

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