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The Constituents Isolated from Peucedanum japonicum Thunb. and their Cyclooxygenase (COX) Inhibitory Activity

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Five coumarins, psoralen (1), scopoletin (2), isoimperatorin (4), (+)-marmesin (5) and xanthotoxin (6), three chromones, cimifugin (3), hamaudol (7) and sec-O-glucosylhamaudol (10), one sterol, daucosterol (8) and one aliphatic alcohol, galactitol (9) were isolated from the root of Peucedanum japonicum. Their chemical structures were identified by the physicochemical and spectroscopic data by comparing literature values. Among them, compounds 9 and 10 were isolated for the first time from this plant. The anti-inflammatory effects of isolated compounds were examined on cyclooxygenase (COX), compounds 1, 2 and 7 showed inhibitory activity on COX-1 with values of 0.88, 0.27 and 0.30 mM, respectively. In the test for COX-2 activity, only compound 7 showed significant inhibitory activity with the value of 0.57 mM. The other compounds exhibited weak inhibitory or no inhibitory activity.
... treat fever, rheumatism, neuralgia, and headache [4]. Bioactive substances derived from 'Bangpung' showed antioxidant [5] and anti-inflammatory effects [6,7]. These properties of 'Bangpung' suggested potential pharmaceutical candidates [2]. ...
... As mentioned above, 'Bangpung' was traditionally used to treat fever and pain. The anti-inflammatory and antioxidant activity of the bioactive substances derived from S. divaricata may correspond to those effects [5][6][7]. According to the phytochemical studies, Prim-O-glucosylcimifugin is the main chromone present in S. divaricata, with antipyretic, anti-inflammatory, and analgesic properties [4]. ...
... In the current study, cimifugin reduced the flinch response in both phases; however, significant antinociceptive effects were observed upon treatment with 300 μg in phase 1 (70.8% of control) and 100 μg in phase 2 (65.5% of control). However, its maximal antinociceptive effect with the 1,000 μg dose was more effective in phase 1 (phase 1: 41.0% of control vs. phase 2: 50.6% of control).These results are consistent with a previous study reporting the anti-inflammatory effects of isolated compounds from P. japonicum Thunb., which showed a relatively weak inhibitory activity of cimifugin against both COX-1 and COX-2 [7]. Therefore, it is suggested that cimifugin has an antinociceptive effect mediated via anti-inflammatory effect at low concentrations and via other non-inflammatory analgesic effects at high concentration. ...
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Background: Cimifugin is one of the components of the root of Saposhnikovia divaricata. The extract derived from S. divaricata is traditionally used as an analgesic. This study was conducted to evaluate the analgesic effect of intrathecal cimifugin in the formalin test. Methods: Male Sprague-Dawley rats (n = 20) were randomized into four groups for intrathecal administration of 70% dimethylsulfoxide and various doses of cimifugin (100 μg, 300 μg, and 1,000 μg). The typical flinch response after the injection of 5% formalin into the hind paw was assessed in two distinct phases: phase 1 until 10 min, and phase 2 from 10 min to 60 min. ED50 values were calculated via linear regression. Results: Intrathecal cimifugin significantly reduced the flinch response in both phases of the formalin test. Significant antinociceptive effects of cimifugin were found with the dose of 300 μg in phase 1 and the dose of 100 μg in phase 2. The ED50 value (95% confidence intervals) of intrathecal cimifugin was 696.1 (360.8-1,342.8) μg during phase 1 and 1,242.8 (42.0-48,292.5) μg during phase 2. Conclusions: Intrathecal cimifugin has an antinociceptive effect against formalin-induced pain. Cimifugin has an anti-inflammatory effect at low concentrations, and non-inflammatory analgesic effect at higher concentrations.
... The root of the Peucedanum japonicum Thunb., distributed throughout Japan, Philippines, China, and Korea has been traditionally used as not only a food but also as an herbal medicine for cough, cold, headaches, and neuralgic disease [8,9]. It has been recognized that substances derived from the Peucedanum species show antiplatelet aggregation [9], antioxidant activity [10], antiinflammatory activity [11], and inhibitory activity on cyclooxygenase (COX) 1 and 2 [12]. According to studies on the isolated constituents of Peucedanum japonicum Thunb., sec-O-glucosylhamaudol (SOG) shows analgesic activity [12,13]. ...
... It has been recognized that substances derived from the Peucedanum species show antiplatelet aggregation [9], antioxidant activity [10], antiinflammatory activity [11], and inhibitory activity on cyclooxygenase (COX) 1 and 2 [12]. According to studies on the isolated constituents of Peucedanum japonicum Thunb., sec-O-glucosylhamaudol (SOG) shows analgesic activity [12,13]. In particular, a recent study showed that intrathecal SOG administration has an antinociceptive effect in a formalin test on a rat model, and shows the possibility of the involvement of SOG on opioid receptors [14]. ...
... has been traditionally used as an analgesic for headaches or neuralgic disease [8,9]. Substances derived from Peucedanum species show effects such as antiplatelet aggregation, antioxidant activity, anti-inflammatory activity, and COX-1 and COX-2 inhibition [9][10][11][12] which are the same bioactivity as chromone derivatives [24]. Chromones (4H-chomen-4-ones) are a group of naturally occurring compounds ubiquitous in nature, particularly in plants [26]. ...
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Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG (10 μg, 30 μg, 100 μg, and 300 μg) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG 300 μg in order to assess the involvement of SOG with an opioid receptor. The protein levels of the δ-opioid receptor, κ-opioid receptor, and μ-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of 300 μg at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was 191.3 μg (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG (300 μg) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.
... Furanochromones, one class of the important active components, commonly found in the families of Umbelliferae [63,64] and Ranunculaceae [65,66]. Compounds (71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83) are members of furanochromone derivatives. Different from compounds (71)(72)(73)(74)(75)(76)(77), there is a dihydrofuran rather than furan attached to the chromone moiety in compounds (78)(79)(80)(81)(82)(83). ...
... Compounds (71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83) are members of furanochromone derivatives. Different from compounds (71)(72)(73)(74)(75)(76)(77), there is a dihydrofuran rather than furan attached to the chromone moiety in compounds (78)(79)(80)(81)(82)(83). Cimitriteromone B and D (82)(83) attract attention owing to the presence of triterpene group. ...
... Different from compounds (71)(72)(73)(74)(75)(76)(77), there is a dihydrofuran rather than furan attached to the chromone moiety in compounds (78)(79)(80)(81)(82)(83). Cimitriteromone B and D (82)(83) attract attention owing to the presence of triterpene group. ...
Article
Chromones are a group of compounds widely distributed in nature with wide range of biological activities, including antitumor, antimicrobial, antiviral, anti-inflammatory, antioxidant, and so on. This review mainly summarizes chromones with antitumor activity in nature and classifies them into three groups, including chromanones, simple chromones, and fused chromones. They exhibit antitumor activity through broad range of mechanisms including cytotoxicity, antimetastasis, antiangiogenesis, chemoprevention, immune regulation, etc.
... It is a perennial herb which was used for cough, colds, headaches, and neuralgic disease [2,3]. In a previous study, it was discovered that the Peucedanum species have bioactivities such as antioxidant activity [4], antiplatelet aggregation [3], anti-inflammatory activity [5] and anti-inflammatory activity on COX-1 and COX-2 [6]. ...
... The constituents isolated from Peucedanum japonicum Thunb. are known as Psoralen, Scopoletin, Cimifugin, lsoimperatorin, (+)-Marmesin, Xanthotoxin, Hamaudol, Daucosterol, Galactitol, Sec-O-glucosylhamaudol (SOG), and etc. [6]. In the previous study, SOG which was isolated from the root of Saposhnikovia divaricate (the family of Umbelliferae), showed an analgesic activity [7]. ...
... According to the previous studies, the traditional analgesic effect of Peucedanum japonicum Thunb. could be related to its bioactivities such as antioxidant activity (3-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, and cnidioside) [4], anti-inflammatory activity (p-chloro-benzylamide and N-methyl-piperazide) [5], and actions on COX-1 and COX-2 (psoralen, scopoletin, and hamaudol) [6]. Especially, p-chloro-benzylamide and Nmethyl-piperazide suppressed the carrageenan-induced inflammation in mice [5]. ...
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Background The root of Peucedanum japonicum Thunb., a perennial herb found in Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was performed to examine the antinociceptive effect of intrathecal SOG in the formalin test. Methods Male Sprague-Dawley rats were implanted with an intrathecal catheter. Rats were randomly treated with a vehicle and SOG (10 µg, 30 µg, 60 µg, and 100 µg) before formalin injection. Five percent formalin was injected into the hind-paw, and a biphasic reaction followed, consisting of flinching and licking behaviors (phase 1, 0–10 min; phase 2, 10–60 min). Naloxone was injected 10 min before administration of SOG 100 µg to evaluate the involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values were calculated. Results Intrathecal SOG showed a significant reduction of the flinching responses at both phases in a dose-dependent manner. Significant effects were showed from the dose of 30 µg and maximum effects were achieved at a dose of 100 µg in both phases. The ED50 value (95% confidence intervals) of intrathecal SOG was 30.3 (25.8–35.5) µg during phase 1, and 48.0 (41.4–55.7) during phase 2. The antinociceptive effects of SOG (100 µg) were significantly reverted at both phases of the formalin test by naloxone. Conclusions These results demonstrate that intrathecal SOG has a very strong antinociceptive effect in the formalin test and it seems the effect is related to an opioid receptor.
... Additionally, caryophyllene has been reported to exhibit cyclooxygenase-2 (COX-2) inhibition activity in THP-1 (human monocytic) cells [18]. Psoralen, spathulenol, syringaldehyde, and taraxerol acetate have been found to exhibit cyclooxygenase-2 (COX-2) inhibition activity [19][20][21][22][23]. All the above findings were in agreement with our results on cyclooxygenase 2 (COX 2) inhibition activity. ...
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The Mikania genus has been known to possess numerous pharmacological activities. In the present study, we aimed to evaluate the interaction of 26 selected constituents of Mikania species with (i) cyclooxygenase 2 (COX 2), (ii) human neutrophil elastase (HNE), (iii) lipoxygenase (LOX), matrix metalloproteinase ((iv) MMP 2 and (v) MMP 9), and (vi) microsomal prostaglandin E synthase 2 (mPGES 2) inhibitors using an in silico approach. The 26 selected constituents of Mikania species, namely mikamicranolide, kaurenoic acid, stigmasterol, grandifloric acid, kaurenol, spathulenol, caryophyllene oxide, syringaldehyde, dihydrocoumarin, o-coumaric acid, taraxerol, melilotoside, patuletin, methyl-3,5-di-O-caffeoyl quinate, 3,3′,5-trihydroxy-4′,6,7-trimethoxyflavone, psoralen, curcumene, herniarin, 2,6-dimethoxy quinone, bicyclogermacrene, α-bisabolol, γ-elemene, provincialin, dehydrocostus lactone, mikanin-3-O-sulfate, and nepetin, were assessed based on the docking action with COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 using Discovery Studio (in the case of LOX, the Autodock method was utilized). Moreover, STITCH (Search Tool for Interacting Chemicals), physicochemical, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses were conducted utilizing the STITCH web server, the Mol-inspiration web server, and Discovery Studio, respectively. In the present study, STITCH analysis revealed only six ligands (dihydrocoumarin, patuletin, kaurenol, psoralen, curcumene, and nepetin) that showed interactions with human proteins. Physicochemical analysis showed that seventeen ligands complied well with Lipinski’s rule. ADMET analysis showed eleven ligands to possess hepatotoxic effects. Significantly, the binding free energy estimation displayed that the ligand methyl-3, 5-di-O-caffeoyl quinate revealed the highest binding energy for all the target enzymes, excluding LOX, suggesting that this may have efficacy as a non-steroidal anti-inflammatory drug (NSAID). The current study presents a better understanding of how Mikania is used as a traditional medicinal plant. Specifically, the 26 ligands of the Mikania plant are potential inhibitor against COX 2, HNE, LOX, MMP 2, MMP 9, and mPGES 2 for treatments for acute and/or chronic inflammatory diseases.
... Those results indicate that SOG ameliorates SNL-induced neuropathic pain by regulating proinflammatory cytokines and downregulating of autophagy through the inhibition of the p38/ JNK MAPK and NF-κB signaling pathways. Previous studies have shown the analgesic effect of SOG on various pain models, which was determined to be associated with an anti-inflammatory effect, COX inhibition, or opioid receptor interactions [11][12][13]26]. Moreover, as mentioned, a recent study demonstrated the anti-inflammatory effects of SOG on inhibiting the transcription of proinflammatory cytokines via the suppression of NF-κB activation and MAPK phosphorylation [14]. ...
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Background: This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. Methods: The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague-Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 μg/day; and Group SOG192, SOG at 192 μg/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. Results: Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. Conclusions: SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.
... medicine for the treatment of coughs, colds, and headaches as well as an anodyne [5]. The representative natural products previously isolated from P. japonicumin include pyranocoumarins, phenylcoumarins, and other coumarin derivatives, which possess diverse biological effects, including inhibition of Ca 2+ channel, monoamine oxidase, and nitric oxide synthase activities; antidiabetic, anti-in ammatory, anticonvulsant, and blood-pressure-lowering effects and ameliorative effects on bronchial asthma [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
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Background: The root of Peucedanum japonicum is used in traditional medicine in Japan, the Philippines, China, and Korea, and it has been reported to have a variety of biological activities, including anticancer activity. Inducing apoptosis in tumor cells has become a major focus of antitumor drug development; therefore, we studied the apoptotic effects of the MeOH/CH2Cl2 extract of the roots of P. japonicum and its components on HL-60 cells (a human leukemia cell line). Methods: Compounds were purified using solvents with varying polarities followed by column chromatography (reverse phase), and the structures were confirmed using nuclear magnetic resonance spectroscopy. The viabilities of HL-60, A549, and MCF-7 cells were determined using the cell counting kit-8 (CCK-8) assay. Analysis of apoptosis signaling was performed only with HL-60 cells, and cell cycle progression, Annexin V/propidium iodide (PI) staining (analyzed by flow cytometry), the mitochondrial membrane potential (MMP, as analyzed by flow cytometry), and caspase-3, 8, and 9 activity (determined using the caspase-3, -8, and -9 activity kit according to the manufacturer’s protocol) were evaluated. Results: Two coumarin molecules, (-)-isosamidin (1) and 3ʹS,4ʹS disenecioylkhellactone (2), were isolated by bioactivity-guided fractionation. Only compound 2 showed cytotoxicity in HL-60 cells, which occurred due to increases in the sub-G1 population and the initiation of early and late apoptosis as determined by Annexin V/PI staining. In addition, decreases in the MMP were observed in HL-60 cells treated with compound 2. Several apoptotic features were observed, including increased cleavage of caspase-3, -8, and -9. Moreover, treatment with Z-DEVD-FMK (a caspase-3 inhibitor), Z-IETD-FMK (a caspase-8 inhibitor), or Z-LEHD-FMK (a caspase-9 inhibitor) significantly inhibited cell cytotoxicity. Conclusions: We provide evidence that compound 2 induces apoptosis in HL-60 cells.
... 정상적인 (Fan et al., 2005). 이 병은 유럽이나 미국 등 육식을 주로 하는 나라에서 흔하며, 최근에는 한국에서 도 현저히 증가되는 추세를 보이고 있다 (Chang et al., 2005). 그러나 이 병이 발생하는 원인과 발병 기전이 비교적 복잡하여 아직까지도 정확히 알려져 있지 않다 (Dong et al., 2003 6. ...
Article
In general, Reucedani Radix (Peucedanum japonicum Thunbergis: PJ) is the Korean traditional herbal medicine used to remove dampness, to relieve pain, and spasm. So, PJ folium is believed to have the same effects. The aim of this study is to investigate the alleviation of dextran sulfate sodium (DSS) induced ulcerative colitis in mice by PJ folium. 25 mice were divided into 5 groups: normal, DSS, DSS + 100 mg/kg PJ folium (PJ100), DSS + 500 mg/kg PJ folium (PJ500), and DSS + 150 mg/kg 5-amino salicylic acid (5-ASA) groups. Body weights, colon lengths, histological changes in colon tissue, and spleen weights were observed. Inflammatory cytokines such as IL-1{\beta}, IL-6, and TNF-{\alpha} level in plasma were measured by ELISA. IL-1{\beta}, IL-6, and TNF-a mRNA expression in colon tissue were detected by RT-PCR. In the results, body weight lose was inhibited in PJ100, PJ500, and 5-ASA groups, but it was not different compared with DSS group, significantly. PJ500 group showed the preventive effects of colon length shorten and histological changes in colon tissues as good as 5-ASA group. The weight of spleen was increased in DSS group but it reduced in PJ100, PJ500, and 5-ASA groups. Moreover, IL-1{\beta} and TNF-{\alpha} cytokine levels in plasma were reduced in PJ500 and 5-ASA groups. IL-1{\beta}, IL-6, and TNF-a mRNA expression in colon tissue were inhibited in PJ100, PJ500, and 5-ASA groups and it was significantly different compared with DSS group. In conclusion, PJ folium showed the alleviative effect on DSS induced ulcerative colitis in mice.
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Peucedanum japonicum (the family Umbelliferae) is a perennial herbaceous plant with various crucial traditional values for coughs, colds, headaches, and inflammatory responses. For drug developments, the current research aims to offer an overview of the previous results in the three main aspects of traditional use, phytochemistry, pharmacological values, and molecular mechanisms regarding this medicinal species. By chromatographic analysis and separation, more than 120 isolated compounds have been obtained. Khellactone-type coumarins and phenolic compounds are the primary phytochemical classes with some coumarins, such as calipteryxin, praerutorin A, and pteryxin, being the main metabolites. Pharmacological activities of P. japonicum constituents included anticancer, antioxidative, antimicrobial, antiviral, antiplatelet, and tyrosine inhibitory activities, especially anti-inflammation and anti-obesity. It is worth mentioning that the obtained constituents joined to protect the neurons, bone, and urine systems, and exerted vasorelaxant. In general, the underlying mechanism of anti-inflammatory action can be explained by mitogen-activated protein kinase/nuclear factor-kappa B (MAPK/NF-κB) signaling pathway, whereas anti-obesity activity is deduced from regulating lipid metabolism-related genes. It also noted that pteryxin is the most active compound, but the clinical studies and synthesis of new derivatives containing enhanced medicinal values have been still limited, which should be improved.
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Chromone glycosides comprise an important group of secondary metabolites. They are widely distributed in plants and, to a lesser extent, in fungi and bacteria. Significant biological activities, including antiviral, anti-inflammatory, antitumor, antimicrobial, etc., have been discovered for chromone glycosides, suggesting their potential as drug leads. This review compiles 192 naturally occurring chromone glycosides along with their sources, classification, biological activities, and spectroscopic features. Detailed biosynthetic pathways and chemotaxonomic studies are also described. Extensive spectroscopic features for this class of compounds have been thoroughly discussed, and detailed 13C-NMR data of compounds 1–192, have been added, except for those that have no reported 13C-NMR data.
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