Search Results (16)

Trigeminal neuralgia is a chronic pain disorder due to neuronal damage. The present study was designed to investigate the effect of 7,8-dimethoxy coumarin (DMC) in a rat model of trigeminal neuralgia. The neuropathic pain was induced by the single endoneural injection of tumor necrosis factor-alpha (TNF-α; 0.1 μL: stock 10 pg/mL) in the rat trigeminal nerve. The DMC (100 and 200 mg/kg) and carbamazepine (100 mg/kg) were administered orally for 10 consecutive days from the 5th day of TNF-α injection. The battery of behavioral tests, i.e., acetone drop and Von Frey filament test, was performed to assess the degree of thermal and mechanical allodynia on 0, 1st, 7th, and 14th days. In addition, the biochemical tests, i.e., total protein, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and TNF-α, were also performed in trigeminal nerve tissue. Furthermore, TNF-α-induced neuronal histopathological changes were also evaluated by the eosin and hematoxylin staining method. The administration of DMC was shown to demonstrate the significant (p < 0.05) reversal of TNF-α-induced percentage reduction of thermal and mechanical sensitivity, along with a rise in TBARS and TNF-α and a decrease in GSH levels. Further, DMC also attenuates the histopathological changes. It may be concluded that DMC may be a potential therapeutic agent for the management of trigeminal neuralgia disorders. Full article

Invasive bacteria have caused tremendous losses to global ecosystems and agricultural production, yet effective control measures remain elusive. Plant specialized metabolites are being investigated as an important source of antimicrobial active substances. And Ailanthus altissima is an abundant tree widespread throughout Northeast China. In this study, we identified 21 compounds from A. altissima leaves, including steroids, terpenes, phenolics, and coumarins. Two new steroidal compounds, ailanstigol A (1) and ailanstigol B (2), and one new coumarin (2′R,3′R)-7-(2′,3′,6′-trihydroxy-3′-methylhexyloxy)-6,8-dimethoxycoumarin (3) were isolated. Antibacterial screening revealed that compounds 1 and 2 exhibited inhibitory activity against two invasive bacteria, Xanthomonas oryzae pv. oryzae PXO 71A and PXO 86A and Pseudomonas syringae pv. maculicola ES4326. Further mechanistic screening unveiled that the steroidal compounds 1 and 2 may inhibit bacterial growth and reproduction by reducing cell viability, disrupting the cell membrane and increasing protein leakage, and inhibiting biofilm formation. In summary, our results enriched the known chemical diversity of A. altissima and provided a foundation for investigating the mechanisms by which steroidal compounds inhibit invasive bacterial growth. Full article

Dengue fever is currently a major global issue, especially in tropical and subtropical countries. The absence of specific antiviral medications supports alternative dengue treatment strategies. South Asian countries have been using Carica papaya leaves as a traditional remedy for dengue for many years. Carica papaya possesses several biological features, including anti-inflammatory, antiviral, cancer-fighting, anti-diabetic, and antioxidant qualities. Additionally, numerous studies have demonstrated that bioactive compounds found in papaya leaf extracts, including carpaine, dehydrocarpaine I and II, chymopapain, and papain, significantly influence platelet counts, while phenolic compounds, such as chlorogenic acid, kaemferol, protocatechuic acid, quercetin, and 5,7-dimethoxycoumarin significantly inhibit viral replication in dengue patients, with negligible side effects. Carica papaya may be considered a viable pharmacological candidate with several targets for treating dengue. It has been shown to prevent infections, reduce oxidative stress, control cytokine storms and the immune system, lessen thrombocytopenia, and increase the body’s protein and hemoglobin levels. This literature review highlights the pathophysiological mechanism of dengue, as well as the pharmacological action of Carica papaya, both of which combat this debilitating disease. Despite these findings, additional investigation, including clinical studies, is necessary to confirm the effectiveness and safety of papaya-based treatments. It is necessary to address issues like standardizing papaya extracts, figuring out the best dosages, and assessing any drug interactions. Full article

In this paper, liquid–liquid chromatography was introduced for the first time for the separation of fingered citron (Citrus medica L. var. sarcodactylis Swingle). The fingered citron cultivated in Jinhua is of significant industrial and medicinal value, with several major coumarin compounds detected in its extract. Therefore, further separation for higher purity was of necessity. A preparative liquid–liquid chromatographic method was developed by combining two elution modes (isocratic and step-gradient) with selection according to different polarities of the target sample. Five coumarin derivatives—5,7-dimethoxycoumarin (52.6 mg, 99.6%), phellopterin (4.9 mg, 97.1%), 5-prenyloxy-7-methoxycoumarin (6.7 mg, 98.7%), 6-hydroxy-7-methoxycoumarin (7.1 mg, 82.2%), and byakangelicol (10.5 mg, 90.1%)—with similar structures and properties were isolated on a large scale from 100 mg of petroleum ether (PE) extract and 100 mg of ethyl acetate (EA) extract in Jinhua fingered citron. The productivity was much improved. The anti-growth activity of the isolated coumarins was evaluated against three cancer cell lines (HeLa, A549, and MCF7) with an MTT assay. The coumarins demonstrated potential anti-tumor activity on the HeLa cell line, with 5,7-dimethoxycoumarin in particular exhibiting the best anti-growth activity (IC₅₀ = 10.57 ± 0.24 μM) by inhibiting proliferation. It inhibited colony formation and reduced the size of the tumor sphere in a concentration-dependent manner. The main mechanism was confirmed as inducing apoptosis. This work was informative for further studies aimed at exploring new natural-product-based antitumor agents. Full article

The objectives of this study were to investigate the melanogenetic potentials of the naturally occurring 7-hydroxy coumarin derivatives 7-hydroxy 5,6-dimethoxycoumarin (7H-5,6DM), 7-hydroxy 6,8-dimethoxycoumarin (7H-6,8DM), 7-hydroxy 6-methoxycoumarin (7H-6M), and 7-hydroxy 4-methylcoumarin (7H-4M) in the melanogenic cells model for murine B16F10 melanoma cells. The initial results indicated that melanin production and intracellular tyrosinase activity were significantly stimulated by 7H-4M but not by 7H-5,6DM, 7H-6,8DM, or 7H-6M. Therefore, our present study further investigated the melanogenic effects of 7H-4M in B16-F10 cells, as well as its mechanisms of action. In a concentration-dependent manner, 7H-4M increased intracellular tyrosinase activity, leading to the accumulation of melanin without affecting the viability of B16-F10 cells. Our study further investigated the effects of 7H-4M on melanogenesis, including its ability to promote tyrosinase activity, increase melanin content, and activate molecular signaling pathways. The results indicate that 7H-4M effectively stimulated tyrosinase activity and significantly increased the expression of melanin synthesis-associated proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and TRP2. Based on our findings, we can conclude that 7H-4M has the ability to activate the melanogenesis process through the upregulation of cAMP-dependent protein kinase (PKA) and the cAMP response element-binding protein (CREB). Additionally, our study showed that 7H-4M induced melanogenic effects by downregulating the extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades, while upregulating the JNK and p38 signaling pathways. Finally, the potential of using 7H-4M in topical applications was tested through primary human skin irritation tests. During these tests, no adverse reactions were induced by 7H-4M. In summary, our results indicate that 7H-4M regulates melanogenesis through various signaling pathways such as GSK3β/β-catenin, AKT, PKA/CREB, and MAPK. These findings suggest that 7H-4M has the potential to prevent the development of pigmentation diseases. Full article

Viscum album L., commonly known as European mistletoe, is a hemi-parasitic plant of the Santalaceae family. The in vitro and in vivo effects of V. album differ, according to its host tree. However, little is known about the host-dependent phytochemical diversity in V. album. In this study, the metabolic profiles of V. album ssp. album from Malus domestica Bork., Quercus robur L., and Ulmus carpinifolia Gled were compared. Leaves, stems, and berries were collected in Switzerland, by the same procedure, in September 2016 and 2017. The methanolic extracts were analyzed by ultra-performance liquid chromatography, coupled to electrospray quadrupole time-of-flight mass spectrometry in positive ionization mode. The data were submitted to partial-least square discriminant analysis (PLS-DA) and the results showed that the V. album ssp. album samples were clustered into three groups, according to the three distinct host trees. Seven compounds, with high VIP scores (variable importance in projection), were responsible for this differentiation. The following four compounds were detected in both the harvest years: arginine, pipecolic acid or lysine, dimethoxycoumarin, and sinapyl alcohol, suggesting their use as host specific V. album biomarkers. The present work highlights the importance of standardized harvest and analytical procedures for the reproducibility of the chemical results of herbal materials. Full article

The current global occurrence of dengue infection annually is approximately 400 million, with a case fatality rate of 2.5%. However, there are no antiviral agents. Carica papaya leaf extract is known for its medicinal value, due to the presence of organic compounds that possess antimicrobial, anti-inflammatory, and antioxidant activities. This study determined the anti-dengue effect of C. papaya leaf extract silver synthesized nanoparticles. In this study, aqueous and non-aqueous extractions were carried out, followed by the synthesis of silver nanoparticles as well as characterization through Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy. The in vitro anti-dengue effect was evaluated using a focus reduction neutralization test on kidney Vero E2 cell lines. In silico studies involved molecular docking to determine the potential interactions between the bioactive compounds in C. papaya leaf extract and the viral NS5 protein. C. papaya leaf methanol extract silver synthesized nanoparticle was the most promising with an IC₅₀ of 9.20 µg/mL. Molecular docking showed 5,7 dimethoxycoumarin as the best ligand, with binding energy of −7.75 kcal/mol, indicating high affinity for the NS5 protein. These results highlight that C. papaya leaf methanol extract silver synthesized nanoparticles could be used to inhibit dengue virus type 2 viral replication. However, we recommend further studies to determine their toxicity and the safety profiles. Full article

Dengue virus is a serious public health issue in tropical and subtropical regions. The global incidence of dengue necessitates the potent antiviral medication for the prevention of proliferation of the virus inside the human body. The DEN2 NS2B/NS3 protease, present in the dengue virus, is an attractive drug target due to its essential role in viral replication, survival, and other cellular activities. In traditional medicine, Carica papaya leaves have been used for the treatment of dengue fever in Sri Lanka, Pakistan, and Malaysia. Therefore, phytochemicals present in Carica papaya leaves have a potential anti-viral activity, and could be used as strong drug candidates against the dengue virus. In this investigation, two phytochemical compounds in Carica papaya leaves, 5,7-dimethoxycoumarin and p-coumaric acid, were selected from the literature and then docked against the DEN2 NS2B/NS3 protease. The compounds showed strong interactions with favorable binding energies in the active site of DEN2 NS2B/NS3 protease. To validate the molecular docking results, the docked ligand–protein complexes were subjected to molecular dynamic simulation along with the apo form of the protein for 30 ns. The molecular dynamic simulation analysis comprising root mean square deviation and fluctuation, the radius of gyration, hydrogen bonding, the Dictionary of Secondary Structure of Proteins (DSSP), and MM/PBSA, revealed the stability of the apo and complex systems. Interactions formed by these compounds with residues Leu149 and Asn152 were found to be essential for the stability of the ligand–protein complex. The findings revealed that these phytochemical compounds depict the promising results against the DEN2 serotype of the dengue virus and the potential for therapeutic drugs. Further experimentation on the proposed compounds is necessary to validate the results and could lead to the development of strong inhibitors with improved activity. Full article

Triple negative human breast cancer (TNBC) is an aggressive cancer subtype with poor prognosis. Besides the better-known artemisinin, Artemisia annua L. contains numerous active compounds not well-studied yet. High-performance liquid chromatography coupled with diode-array and mass spectrometric detection (HPLC-DAD-MS) was used for the analysis of the most abundant compounds of an Artemisia annua extract exhibiting toxicity to MDA-MB-231 TNBC cells. Artemisinin, 6,7-dimethoxycoumarin, arteannuic acid were not toxic to any of the cancer cell lines tested. The flavonols chrysosplenol d and casticin selectively inhibited the viability of the TNBC cell lines, MDA-MB-231, CAL-51, CAL-148, as well as MCF7, A549, MIA PaCa-2, and PC-3. PC-3 prostate cancer cells exhibiting high basal protein kinase B (AKT) and no ERK1/2 activation were relatively resistant, whereas MDA-MB-231 cells with high basal ERK1/2 and low AKT activity were more sensitive to chrysosplenol d treatment. In vivo, chrysosplenol d and casticin inhibited MDA-MB-231 tumor growth on chick chorioallantoic membranes. Both compounds induced mitochondrial membrane potential loss and apoptosis. Chrysosplenol d activated ERK1/2, but not other kinases tested, increased cytosolic reactive oxygen species (ROS) and induced autophagy in MDA-MB-231 cells. Lysosomal aberrations and toxicity could be antagonized by ERK1/2 inhibition. The Artemisia annua flavonols chrysosplenol d and casticin merit exploration as potential anticancer therapeutics. Full article

Easel paintings are assets with an important historic and cultural value. They usually possess a multi-tiered structure, composed of different layers some of which may present protein binders, making it important to identify these materials for restoration and conservation purposes. We propose the identification of different protein binders by a new fluorescent labeling method employing a coumarin based chromophore, C392STP (sodium(E/Z)-4-(4-(2-(6,7-dimethoxycoumarin-3-yl)vinyl)benzoyl)-2,3,5,6-tetrafluorobenzenesulfo-nate). The method was optimized using commercial proteins and was further tested on proteins extracted from hen’s egg yolk, white bovine milk, and rabbit skin glue. To model more realistic conditions, paint models of easel paintings were prepared. The paint models were made with hen’s egg yolk, white bovine milk, and rabbit skin glue, mixed with different pigments and submitted to artificial aging. Then the extracted proteins from the paint models were labeled with C392 which allowed a sensitive and selective identification by polyacrylamide gel electrophoresis (PAGE) of the different protein binders used. As a final test, three 19th century easel paintings, from the Italian painter Giorgio Marini, were analyzed. The results show the potential of the proposed method for the identification of protein binders present in easel paintings. Full article

7,8-dimethoxycoumarin (DMC, C11H10O4), a natural coumarin compound, is present in Citrus plants including Citrus decumana and grapefruit. It is known to have protective effects on the kidneys against Cisplatin and ischemia-reperfusion injury. However, the underlying mechanisms of its inhibitory effects on skin inflammation have not been investigated in vitro. Tumor necrosis factor (TNF)-α is known to be one of the main causative agents of skin inflammation. It induces pro-inflammatory cytokines and chemokines by activating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. In this study, we investigated the inhibitory effect of DMC on the expression of pro-inflammatory cytokines and chemokines in TNF-α-treated human keratinocyte HaCaT cells. Pretreatment with DMC inhibited TNF-α-treated cytokines (interleukin 6; IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1). In addition, DMC significantly inhibited TNF-α-treated NF-κB activation and phosphorylation of MAPKs, such as c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinase (ERK). These results suggest that DMC may elicit an anti-inflammatory response by suppressing TNF-α-treated activation of NF-κB and MAPK pathways in keratinocytes. Hence, it might be a useful therapeutic drug against skin inflammatory diseases. Full article

Investigation of the chemical constituents from the fruits of Citrus medica L. var. sarcodactylis Swingle has led to the characterization of a new sesquiterpene 1 along with thirty-two known compounds. The structure of 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. In addition, most of the isolated compounds were evaluated for the activity assayed by the in vitro inhibition of superoxide anion generation and elastase release by human neutrophils. The results showed that only 6,7-dimethoxycoumarin (5) exhibited significant inhibition of superoxide anion generation, with IC₅₀ value of 3.8 ± 1.4 μM. Full article

Microglia activation and the release of various inflammatory cytokines are largely related to neurological diseases, including Parkinson’s, Alzheimer’s, and other brain diseases. The suppression of microglial cells using natural bioactive compounds has become increasingly important for brain therapy owing to the expected beneficial effect of lower toxicity. Scoparone (6,7-dimethoxycoumarin), a major bioactive compound found in various plant parts, including the inner shell of chestnut (Castanea crenata), was evaluated on lipopolysaccharide (LPS)-activated BV-2 microglia cells. The results indicated that scoparone suppresses the LPS-stimulated increase of neuroinflammatory responses and inhibited the pro-inflammatory cytokine production in the BV-2 microglial cells. A mechanistic study showed that scoparone specifically inhibited the LPS-stimulated activation via a major regulation of IRF-3 and a regulation of ERK, whereby the phosphorylation in the BV-2 microglial cells is blocked. These data suggest that scoparone has anti-neuroinflammatory effects in LPS-activated BV-2 microglial cells, and could possibly be used in the development of novel drugs for the prevention and treatment of neuroinflammatory diseases. Full article

A new coumarin, edgeworic acid (1), was isolated from the flower buds of Edgeworthia chrysantha, together with the five known coumarins umbelliferone (2), 5,7-dimethoxycoumarin (3), daphnoretin (4), edgeworoside C (5), and edgeworoside A (6). Their structures were established on the basis of spectral data, particularly by the use of 1D NMR and several 2D shift-correlated NMR pulse sequences (¹H-¹H COSY, HSQC and HMBC), in combination with acetylation reactions. Full article

In this article we describe a new methodology for the total synthesis of 3,4-unsubstituted coumarins from commercially available starting materials. Six examples were prepared, including five naturally occurring coumarins—7-hydroxy-6,8-dimethoxy-coumarin (isofraxidin), 7-hydroxy-6-methoxycoumarin (scopoletin), 6,7,8-trimethoxy-coumarin, 6,7-dimethoxycoumarin (scoparone), and 7,8-dihydroxycoumarin (daphnetin) and one synthetic coumarin, 7-hydroxy-6-ethoxycoumarin. Moreover, five important o-hydroxybenzaldehyde intermediates were also obtained, namely 2,4-dihydroxy-3,5-dimethoxybenzaldehyde, 2,4-dihydroxy-5-methoxybenzaldehyde, 5-ethoxy-2,4-dihydroxy-benzaldehyde, 2-hydroxy-3,4,5-trimethoxybenzaldehyde, and 2-hydroxy-4,5-dimethoxy-benzaldehyde. The method developed herein involves just three or four steps and allows for the rapid synthesis of these important molecules in excellent yields. This is the first synthesis of 6,7,8-trimethoxycoumarin and 7-hydroxy-6-ethoxycoumarin. Full article