Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain

Wang, Shifeng; Zhai, Chenxi; Zhang, Yanling; Yu, Yangyang; Zhang, Yuxin; Ma, Lianghui; Li, Shiyou; Qiao, Yanjiang

doi:10.3390/molecules21091145

Cited by 20 publications

(15 citation statements)

References 47 publications

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“…Antidepressants, anticonvulsants and other drugs active on the central nervous system can be used for chronic, neuropathic pain or even in the stages of terminal illnesses, being the first-line treatments for some conditions with the purpose of reducing pain and related incapacities [52]. The nociceptive drugs that act at the level of the central nervous system in the first phase are the main agents that act in the neurogenic phase of nociception and present an action mechanism characterized by the direct activation of the sensory C fibers through the cationic potential channel of the transient receptor, subfamily A, member 1 (TRPA1) [53,54,55].…”

Section: Resultsmentioning

confidence: 99%

Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model

et al. 2019

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To obtain usnic acid potassium salt (PS-UA), the usnic acid (UA) was extracted and purified from the lichen Cladonia substellata, and modified to produce PS-UA. The structure was determined by 1H-NMR, IR and elemental analysis, ratified through computational models, as well as identification the site of K+ insertion in the molecule. Antinociceptive activity was detected through contortions in mice induced by acetic acid and formalin (phases I and II) after treatments with 10 and 20 mg/kg of PS-UA, indicating interference in both non-inflammatory and inflammatory pain. After oral administration at doses of 500, 1000 and 2000 mg/kg, no deaths of mice with treatments below 2000 mg/kg were observed. Except for body weight gain, food and water consumption decreased with treatments of 1000 and 2000 mg/kg, and the number of segmented leukocytes was higher for both treatments. Regarding serum levels, cholesterol and triglycerides decreased, however, there was an increase in hepatic transaminases with both treatments. Liver and kidney histological changes were detected in treatments of 2000 mg/kg, while the spleen was preserved. The PS-UA demonstrated antinociceptive activity while the acute toxicity at the concentration of 2000 mg/kg was the only dose that presented morphological changes in the liver and kidney.

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Section: Resultsmentioning

confidence: 99%

Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model

et al. 2019

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“…The perception of pain involves various pathways which transmit the pain impulses from the site of injury to the peripheral nervous system then central nervous system. A previous study showed that cardamonin exhibited antinociceptive action by interrupting the opioidergic pathway and TRPA1 activation [ 24 , 32 ]. Cardamonin was reported to inhibit nociception through action on TRPV1 channel and glutamate receptors [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models

et al. 2020

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The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9–4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.

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“…Alpinia katsumadai hayata is a traditional Chinese herbal medicine. It induces a warming of the stomach and is used for relieving gastric discomfort and a distended abdomen (19). Cardamonin is extracted from the seed of cardamom spices and it is an active ingredient of Alpinia katsumadai hayata, which has antinociceptive effects (15,20).…”

Section: Discussionmentioning

confidence: 99%

Cardamonin as a potential treatment for melanoma induces human melanoma cell apoptosis

Yue

Liu

et al. 2019

Oncol Lett

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2',4'-dihydroxy-6'-methoxychalcone (cardamonin) is a natural compound with anti-proliferative effects on several cancer types including nasopharyngeal carcinoma. The effects of cardamonin on melanoma cells are unknown. The present study investigated the anti-proliferative effect of cardamonin on human melanoma cell lines (M14 and A375), and the underlying apoptosis inducing mechanisms. MTS assay showed that cardamonin inhibited M14 cells viability, and a reduction of the M14 cell density was also observed. Flow cytometry showed that cardamonin induced M14 cells apoptosis in a dose-dependent manner. Western blot analysis showed protein expression in M14 and A375; the pro-apoptotic protein BAX was upregulated, while the anti-apoptotic protein B-cell lymphoma-2 was downregulated. The protein expression of cleaved caspase-8, -9 and cleaved poly (ADP-ribose) polymerase was increased, whereas P65 was decreased. Furthermore, cardamonin inhibited M14 cell migration. These findings suggest that cardamonin may be a novel anticancer treatment for human melanoma.

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Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain

Cited by 20 publications

References 47 publications

Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model

Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model

Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models

Cardamonin as a potential treatment for melanoma induces human melanoma cell apoptosis

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