Antinociceptive, anti‐inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide

Alonso-Castro, Ángel Josabad; Guzmán-Gutiérrez, Silvia Laura; Betancourt, Clara Alba; Gasca‐Martínez, Deisy; Álvarez-Martínez, Karla Lorena; Pérez-Nicolás, Miriam; Espitia-Pinzón, Clara; Reyes‐Chilpa, Ricardo

doi:10.1002/ddr.21471

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…We have demonstrated that the mice that received the topical application of (DMC) 2 @β-CD (FL) demonstrated a qualitative reduction of granulation tissue in relation to the saline group (Figure 6), probably due to the anti-inflammatory action of the coumarins as already demonstrated in other studies. 27 In wound repairs, it has been shown that less inflammatory activity leads to better healing, more similar to the regeneration process. [9][10][11]68 One of the cells that helps decrease the area of granulation tissue 7 days after the injury is mast cells, which are decreased in the groups that received a topical application of coumarins.…”

Section: In Vivo Wound Healing Studiesmentioning

confidence: 99%

“…The anti-inflammatory activity of coumarins in repairing skin wounds has not yet been demonstrated. However, it has been shown to reduce edema in rabbit ears and mouse paws. , Therefore, the insolubility of some compounds in water restricts the application of drugs in some biological studies. In addition, poorly soluble drugs have bioavailability problems, with dissolution being the limiting factor for their absorption in the body.…”

Section: Introductionmentioning

confidence: 99%

“…The anti-inflammatory activity of coumarins in repairing skin wounds has not yet been demonstrated. However, it has been shown to reduce edema in rabbit ears 27 and mouse paws. 28 , 29 Therefore, the insolubility of some compounds in water restricts the application of drugs in some biological studies.…”

Section: Introductionmentioning

confidence: 99%

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Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing

Dutra,

Francisco,

Carneiro Pires

et al. 2024

ACS Appl. Mater. Interfaces

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Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2Hchromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2one (MMC)/β-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/β-CD, and hydrogen bonds along with π−π stacking interactions are responsible for the better stability, especially for (MMC) 2 @β-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC) 2 @β-CD (FL) and (MMC) 2 @β-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC) 2 @β-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.

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Section: In Vivo Wound Healing Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing

Dutra,

Francisco,

Carneiro Pires

et al. 2024

ACS Appl. Mater. Interfaces

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“…Neuropathic pain (NP) is caused by primary nervous system injury and dysfunction, which seriously affects the quality of patients' life (Barragan-Iglesias et al, 2014;Alonso-Castro et al, 2018). At present, treatment options for NP include nerve block with anesthetics, opioid receptor antagonism, nerve damage, etc.…”

Section: Introductionmentioning

confidence: 99%

Integrated 16S rRNA Gene Sequencing and Metabolomics Analysis to Investigate the Important Role of Osthole on Gut Microbiota and Serum Metabolites in Neuropathic Pain Mice

Wang

Dang

et al. 2022

Front. Physiol.

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Accumulating evidence suggests that neuropathic pain (NP) is closely connected to the metabolic disorder of gut microbiota, and natural products could relieve NP by regulating gut microbiota. The purpose of this study is to investigate the important regulatory effects of osthole on gut microbiota and serum metabolites in mice with chronic constriction injury (CCI). Mice’s intestinal contents and serum metabolites were collected from the sham group, CCI group, and osthole treatment CCI group. The 16S rRNA gene sequencing was analyzed, based on Illumina NovaSeq platform, and ANOVA analysis were used to analyze the composition variety and screen differential expression of intestinal bacteria in the three groups. Ultra-high-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry (UHPLC-Q-TOF-MS) was used for analyzing the data obtained from serum specimens, and KEGG enrichment analysis was used to identify pathways of differential metabolites in the treatment of neuralgia mice. Furthermore, the Pearson method and Cytoscape soft were used to analyze the correlation network of differential metabolites, gut microbiota, and disease genes. The analysis results of 16S rRNA gene sequencing displayed that Bacteroidetes, Firmicutes, and Verrucomicrobia were highly correlated with NP after osthole treatment at the phylum level. Akkermansia, Lachnospiraceae_unclassified, Lachnospiraceae_NK4A136_group, Bacteroides, Lactobacillus, and Clostridiales_unclassified exhibited higher relative abundance and were considered important microbial members at genus level in neuralgia mice. Serum metabolomics results showed that 131 metabolites were considered to be significantly different in the CCI group compared to the sham group, and 44 metabolites were significantly expressed between the osthole treatment group and the CCI group. At the same time, we found that 29 differential metabolites in the two comparison groups were overlapping. Integrated analysis results showed that many intestinal microorganisms and metabolites have a strong positive correlation. The correlation network diagram displays that 10 genes were involved in the process of osthole alleviating NP through a metabolic pathway and gut microbiota, including IGF2, GDAP1, MYLK, IL18, CD55, MIR331, FHIT, F3, ERBB4, and ITGB3. Our findings have preliminarily confirmed that NP is closely related to metabolism and intestinal microbial imbalance, and osthole can improve the metabolic disorder of NP by acting on gut microbiota.

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“…Neuropathic pain inducing by a primary lesion or disease affecting the somatosensory system is a devastating disease which mainly manifested as hyperalgesia, allodynia and spontaneous pain, and comorbidities such as anxiety, depression and sleep disorder, which seriously affects patients' quality of life and bring extreme financial burden to the country [1][2][3]. The theory and practice of pain treatment have long focused on neurons and designed therapeutic plan on these grounds.…”

Section: Introductionmentioning

confidence: 99%

Osthole alleviates neuropathic pain in mice by inhibiting the P2Y1-receptor-dependent JNK signaling pathway

Dang²,

Zhao

et al. 2020

Aging

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There are many reports about natural products relieving neuralgia. Osthole is the main component of Angelica biserrata Yuan et Shan, a natural product that treats rheumatism through the elimination of inflammation and the alleviation of pain that has a long history in the clinic. The analgesic mechanism of osthole is complicated and confusing. Astrocytes have attracted increasing attention from pain researchers. Inhibitors targeting astrocytes are thought to be promising treatments for neuropathic pain. Whether osthole can alleviate neuropathic pain through astrocytes has not been elucidated in detail. In this study, CCI surgery was used to establish the neuropathic pain model in mice. The CCI mice were treated with osthole (5, 10, or 20 mg/kg/day) for 14 days in vivo. Mechanical allodynia and heat hyperalgesia were measured to evaluate the therapeutic effect of osthole. In mechanism research, the activation of astrocytes; the protein expression of P2Y1R and p-JNK in astrocytes; the release of inflammatory factors; the variations in mEPSPs and eEPSPs; and the levels of GluA1, GluN2B, pERK , p-CREB and c-Fos in neurons were observed. The P2Y1R inhibitor MRS2179 and the p-JNK inhibitor SP600125 were used to demonstrate how osthole works in neuropathic pain. In addition, astrocytes and neurons were used to estimate the direct effect of osthole on astrocyte-neuron interactions and signal transmission in vitro. Our findings suggest that osthole treatment obviously relieved mechanical allodynia and heat hyperalgesia in CCI mice. P2Y1R is involved in CCI-induced pain hypersensitivity, and P2Y1R is required for osthole-induced p-JNK downregulation in the spinal cord. Osthole inhibited astrocyte activation and reduced inflammatory factor expression. After osthole treatment, mEPSP frequency and eEPSP amplitude were decreased in spinal lamina I-II neurons. Downstream signaling molecules such as pGluA1, pGluN2B, pERK , p-CREB and c-Fos were also reduced very quickly in osthole-treated neuralgic mice. Our conclusion is that osthole alleviates neuropathic pain in mice via the P2Y1-receptor-dependent JNK signaling pathway in spinal astrocytes, and osthole could be considered a potential pharmacotherapy to alleviate neuropathic pain.

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Antinociceptive, anti‐inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide

Cited by 8 publications

References 23 publications

Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing

Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing

Integrated 16S rRNA Gene Sequencing and Metabolomics Analysis to Investigate the Important Role of Osthole on Gut Microbiota and Serum Metabolites in Neuropathic Pain Mice

Osthole alleviates neuropathic pain in mice by inhibiting the P2Y1-receptor-dependent JNK signaling pathway

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