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Essential oil from leaves of Cinnamomum osmophloeum acts as a xanthine oxidase inhibitor and reduces the serum uric acid levels in oxonate-induced mice

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The xanthine oxidase (XOD) inhibitory activity and anti-hyperuricemia effect in mice of Cinnamomum osmophloeum, which is an endemic tree in Taiwan, were evaluated in this study. The results demonstrated that the essential oil of C. osmophloeum leaves presented the strongest XOD inhibition activity (IC(50)=16.3μg/ml); however, no significant XOD inhibition activities were found in ethanolic and hot water extracts. Furthermore, among the main compounds of essential oil, the cinnamaldehyde exhibited the potent XOD inhibition activity with an IC(50)=8.4μg/ml. Besides, the reducing serum uric acid levels in oxonate-induced mice by cinnamaldehyde were further investigated. The hyperuricemic mice were oral administrated cinnamaldehyde at a dosage of 150mg/kg, the uric acid value in serum was reduced from 5.25±0.63 to 2.10±0.04mg/dl, the levels of serum uric acid in mice was lowered down by 84.48% as compared to the hyperuricemic control group. Based on the results obtained in this study, cinnamaldehyde may be a potential lead compound for developing the pharmaceutic for anti-hyperuricemia agent.

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... Cinnamomum osmophloeum, commonly known as indigenous cinnamon or pseudocinnamon, is endemic to Taiwan's natural hardwood forests [1]. Major components of the essential oils extracted from C. osmophloeum leaves explored by high-performance liquid chromatography (HPLC) are as follows: α-pinene, camphene, benzaldehyde, β-pinene, 3-pheayl pionaldehyde, cis-cinnamaldehyde, trans-cinnamaldehyde, isobornylacetate, eugenol, and cinnamil acetate [2]. The essential oils extracted from C. osmophloeum leaves comprise 101 volatile compounds, as identified by GC/MS analysis, including monoterpenoids, sesquiterpenoids, alcohols, phenols, aldehydes, ketones, esters, acids, and other miscellaneous compounds. ...
... Specific studies (2 to 4) discussed the beneficial biological activities [3,[18][19][20][21][22] and suggested more than one chemical compound as the active content. Some beneficial biological activities have been summarized in Table 1 and consist of anti-inflammatory activities [20,[22][23][24][25][26][27][28][29][30], wound repair activities [20], antibacterial activities [31,32], antifungal activities [33,34], antioxidant activities [18,20,[35][36][37], anti-hyperglycemic activities [3,18,21], antidyslipidemia activities [38,39], anti-cancer and anti-tumor activities [22], renal disease therapy, and anti-hyperuricemia activities [2,4]. In addition, studies on the leaves, twigs, barks, heartwoods, and roots of C. osmophloeum were also reported. ...
... The inhibitory activity of α-glucosidase and α-amylase It was conveyed that C. osmophloeum comprised six chemotypes; cinnamaldehyde, cinnamaldehyde/cinnamyl acetate, cinnamyl acetate, linalool, camphor, and mixed types ( Table 2). The chemical structures of cinnamaldehyde, cinnamyl acetate, linalool, and camphor are given in Figure 2. Most of the studies showed that the dominant chemical contents of the cinnamaldehyde type were cinammaldehyde/trans-cinnamaldehyde [2,29,[31][32][33][34]36,37,47,48], benzaldehyde [32,33,37,48], benzenepropanal [37,[47][48][49], and cinnamyl acetate/trans-cinnamyl acetate [2,29,36]. ...
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The aim of this review was to provide an updated overview of studies on the medical-biological activities of Cinnamomum osmophloeum (C. osmophloeum) in vitro and in vivo and the potential therapeutic use of natural agents prepared from this plant for the alleviation of oral mucositis (OM). Reported articles were collected using web search engine tools. The systematic review was organized according to the preferred reporting items for reviews and meta-analyses (PRISMA) statement. Additional sources were identified through cross-referencing to identify the potential use of C. osmophloeum in the alleviation of OM. The results disclosed that C. osmophloeum is comprised of bioactive ingredients that could act diversely as a reagent in anti-inflammation, antibacterial, antioxidant, anti-hyperglycemic, antidyslipidemia, anti-cancer, renal disease therapy and anti-hyperuricemia capacities. Recent studies revealed that the overall effects on anti-inflammation, wound repair, and the antibacterial and antioxidant activities of its constituents would act as a potential remedy for oral mucositis. Up-to-date in vitro and in vivo studies on the medical-biological activities of C. osmophloeum suggested that C. osmophloeum and its constituents could be promising remedies as adjuvants in OM therapy and warrant further investigation.
... C. cassia bark has been used to treat immune-related diseases, gastritis, diarrhea, and cancer in traditional medicine and has been shown to have anticancer and antidiabetic effects [16,17]. In addition, C. indicum flower and C. cassia bark inhibited XOD activity in vitro, and decreased serum uric acid levels in animal models of potassium oxonate (PO)-induced hyperuricemia [14,[18][19][20]. Interestingly, in our previous study, we demonstrated the antihyperuricemic effect of C. indicum flower and C. cassia bark as well as the synergistic antihyperuricemic effect of their mixture [21]. ...
... Based on our previous research, we further study the understanding of the mechanism underlying the antihyperuricemic effects. In this study, we found that DKB114 significantly decreased serum uric acid levels in normal rats and rats with PO-induced hyperuricemia, consistent with that of our previous study and other studies [18][19][20][21]. Furthermore, DKB114 increased uric acid levels in urine, indicating that DKB114 has the ability to increase uric acid excretion and that it might be a potent uricosuric agent, which may explain its antihyperuricemic effects. ...
... Thus, inhibition of XOD activity should be a target to control hyperuricemia. In our study, DKB114 inhibited the in vitro XOD and hepatic XOD activity in rats with PO-induced hyperuricemia, which supports the findings of previous studies [18][19][20][21]. Furthermore, DKB114 decreased liver uric levels in hyperuricemic models, indicating that inhibition of XOD activity by DKB114 might be attributable to the reduction in uric acid production. ...
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Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Presl bark (CB) extracts have been used as the main ingredients in several prescriptions to treat the hyperuricemia and gout in traditional medicine. In the present study, we investigated the antihyperuricemic effects of DKB114, a CF, and CB mixture, and the underlying mechanisms in vitro and in vivo. DKB114 markedly reduced serum uric acid levels in normal rats and rats with PO-induced hyperuricemia, while increasing renal uric acid excretion. Furthermore, it inhibited the activity of xanthine oxidase (XOD) in vitro and in the liver in addition to reducing hepatic uric acid production. DKB114 decreased cellular uric acid uptake in oocytes and HEK293 cells expressing human urate transporter (hURAT)1 and decreased the protein expression levels of urate transporters, URAT1, and glucose transporter, GLUT9, associated with the reabsorption of uric acid in the kidney. DKB114 exerts antihyperuricemic effects and uricosuric effects, which are accompanied, partially, by a reduction in the production of uric acid and promotion of uric acid excretion via the inhibition of XOD activity and reabsorption of uric acid. Therefore, it may have potential as a treatment for hyperuricemia and gout.
... [42] Urate lowering is important for the treatment of GA. Many scholars hold the view that the level of uric acid, in vitro or in vivo, could be reduced by the ethanolic extract of ramulus cinmomi, [43] cinnamaldehyde, [44] and total glucosides of paeony. [45,46] According to Ying and Huang, [47] the level of serum uric acid could be reduced by ephedrine in hyperuricemia model rats by regulating urine pH. ...
... Because XOD is a crucial enzyme in purine catabolism that catalyzes hypoxanthine and xanthine to uric acid in human metabolism. [48] Studies have shown that XOD activity could be inhibited by ramulus cinmomi oil, [49] cinnamaldehyde, [43,44] and total glucosides of paeony. [46] One study by Cao et al [50] suggested that licoflavonol may decrease the level of uric acid in adenosine-induced renal tubular epithelial cell NRK-52E, possibly via XOD. ...
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Background Guizhi-Shaoyao-Zhimu decoction (GSZD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of gouty arthritis patients could be improved by GSZD. However, no previous study has evaluated and analyzed its efficacy, safety, underlying mechanisms, and the relationship between related ingredients of herbs and targets of gouty arthritis. Methods Randomized controlled trials of GSZD for gouty arthritis were retrieved from various databases. Meta-analysis was performed by Stata 17 software. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger test and funnel plot. The related ingredients of herbs and the targets of herbs and gouty arthritis were obtained from several databases, such as TCMSP, HERB, and DrugBank. The protein-protein interaction network was conducted by the STRING platform. DAVID database was used to perform GO and KEGG analysis. Molecular docking and visualization of docking results were carried out by AutoDock and PyMOL software. Results Twenty studies with 1633 patients were included. Meta-analysis indicated that GSZD could better improve the clinical efficiency and visual analogue scale score, and reduce the level of blood uric acid and inflammatory biomarkers (including C-reactive protein, erythrocyte sedimentation rate, interleukin 6, interleukin 8, and tumor necrosis factor-α) than conventional treatment. In addition, we retrieved 157 active compounds, 517 herb target genes, 3082 disease targets, and 295 intersection targets of herb and disease. The results of network pharmacology analysis showed that the core related ingredients included quercetin, kaempferol, sitosterol, luteolin, catechin, etc. The core intersection targets contained AKT1, TNF-α, TP53, IL6, etc. And the critical signaling pathways included IL-17, HIF-1, TNF, PI3K-Akt, etc. Among the 56 molecular docking results, only 8 results had binding energy values greater than −5.0 kcal/mol. Conclusion GSZD could be a satisfactory complementary and alternative therapy for treating gouty arthritis. However, it should be verified by further studies. Future research on gouty arthritis could be conducted from the active components including beta-sitosterol and sitosterol, the targets including TNF-1, IL1B, and ESR1, and the signaling pathways including IL-17 and HIF-1.
... In contrast, the whole oil was observed to exert stronger antioxidant, anti-inflammatory, anti-proliferative and antiviral activities than 1,8 cineole by other studies [21,22]. Similarly, purified cinnamaldehyde, while exerted equal effects with cinnamon oils in anti-cancer activities [23], was observed to be less effective in several anti-inflammatory parameters [24], but showed stronger activities in the anti-tyrosinase, anti-melanogenic and xanthine oxidase inhibitory effects [25,26]. Our study is the first one that aimed to examine the effects of CC and EG essential oils along with purified major ingredients on a set of bacteria to generally compare their antibacterial properties. ...
... Superior effects observed with whole extracts over the isolated compounds in both vapor-and liquid-phase suggest the important involvement of minor ingredients in the plants' total effects. Our results, together with previous researches about other pharmacological functions of CC and EG essential oils [20][21][22][23][24][25][26], confirm that while higher contents of major active constituents, including (E)-cinnamaldehyde and 1,8 cineole, are generally considered to represent higher therapeutic qualities of plant materials [1,8,9], they might not be able to exert equal effects with the whole extracts if applied as isolated drugs. On the other hand, our study also observed that while CC oil were more potent than (E)-cinnamaldehyde against B. sub, S. aureus and 2 E. coli strains, it only exerted similar activities against P. aeruginosa and S. typhimurium, suggesting that the comparison results were also dependent on bacteria. ...
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Essential oils from Cinnamomum cassia bark and Eucalyptus globulus leaves have been traditionally applied for bacterial infections, through both of aromatherapy and oral application. (E)-cinnamaldehyde and 1,8 cineole have been identified as their major secondary metabolites, and are also generally considered as the main active ingredients responsible for their medicinal applications. However, ethnobotanical doctors still prefer to use whole essentials oils over purified compounds in bacterial infections. We therefore hypothesized that multi-compound extracts might exert better effects than isolated ingredients. In order to verify the hypothesis about advantages of whole materials, we examined antibacterial properties of the 2 plant essential oils in the comparison with their isolated major compounds, such as (E)-cinnamaldehyde and 1,8 cineole. Effects of liquid- and vapor-phase were examined on a set of 6 gram-positive and -negative bacteria, applying broth dilution, agar well diffusion and disc volatilization methods. In all 3 investigations, we observed that whole cinnamon and eucalyptus oils, with the lower concentrations of (E)-cinnamaldehyde (89.1%) and 1,8 cineole (61.2%), were able to induce better effects than the purified active compounds (≥ 99%). These results partly explain the advantages of using whole essential oils over isolated ingredients, and therefore support the application of traditional dosage forms for bacterial infections in ethnomedicine.
... XOD is an enzyme that catalyzes the oxidation reaction of hypoxanthine and xanthine to gout. Inhibition of XOD activity will inhibit the biosynthesis of gout [19]. ...
... The main components essential oils from C. verum leaves from Madagascar are eugenol (63%) and carryophyllene (5%). This essential oil can inhibit the growth of E. coli O157: H7 with MIC value of 0.1% and MCT 0.013%, S. typhimurium SL 134 with a MIC value of 0.1% and MCT 0.013%, S. aureus with a MIC value of 0.05 % and MCT 0.013%, and against L. monocytogenes with MIC values 0.2%, MCT 0.006% [19]. (Oussalah et al., 2007). ...
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Cinnamon has been widely used as a spice in food and medicine. Cinnamon grow in the Asian region. Indonesia is one of the cinnamon producing countries. The chemical composition of cinnamon plants varies according to the variety, the part of the plant, the place and the climate to grow. The main bioactive component in cinnamon bark is cynnamaldehide. Cynnamaldehide in cinnamon has good physiological effects on body health such as antioxidants, anticancer, anti-inflammatory, antidiabetic, antidyslipidemicanti-hyperuricemia, and antimicrobial properties. Research is generally still conducted in vitro, clinical trial limited. Keywords— cinnamon; antioxidant; anticancer; cynnamaldehyde.
... Terpinenes: Borneol; camphene; camphor; limonene; linalool; myrcene; p-cymene; spathulenol; viridiflorol; b-caryophyllene; b-pinene; d-cadinene; ⍺-cadinol; ⍺pinene; ⍺-terpineol [176] [166] Lborneol, a-terpineol, p-allylanisole, transcinnamaldehyde, L-bornyl acetate, eugenol, acopaene, b-caryophyllene, cinnamyl acetate, acaryophyllene, curcumene, d-cadinene, a-calacorene, elemicin, e-nerolidol, spathulenol, caryophyllene oxide, trans-b-elemenone, c-eudesmol, caryophylla-4 (14), 8(15)-dien-5.a-ol, d-cadinol, T-cadinol, cadalene, guaiol acetate [209] Kaempferol glycosides: [210] Anticancer, [130,211] antidiabetic, [212,213] antidyslipidaemic, [214] antiinflammatory, [209,215] antimicrobial [216,217] , antioxidant, [213,218] cardioprotective, [219] cytotoxicity, [220] hair growth, [221] hepatoprotective, [222] hypolipidaemic effect, [223] hypouricaemic effects, [224] immunomodulatory, [225] larvicidal, [29] pancreas-protective effect, [226] tyrosinase, [220,227] wound healing, [227] xanthine oxidase inhibitory [224] Arthritis, [228] cough and cold, [228] diabetes, [228] infection, [222] inflammation, [228] nerve pains, [228] pyrexia [228] Bark Flavonoids: (E)-Cinnamaldehyde; (Z)cinnamaldehyde. [229] Hydrocarbon: Phenol; c-muurolene [229] Flavonoids: cis-Cinnamaldehyde; transcinnamaldehyde [5,230,231] ; cinnamaldehyde. ...
... Terpinenes: Borneol; camphene; camphor; limonene; linalool; myrcene; p-cymene; spathulenol; viridiflorol; b-caryophyllene; b-pinene; d-cadinene; ⍺-cadinol; ⍺pinene; ⍺-terpineol [176] [166] Lborneol, a-terpineol, p-allylanisole, transcinnamaldehyde, L-bornyl acetate, eugenol, acopaene, b-caryophyllene, cinnamyl acetate, acaryophyllene, curcumene, d-cadinene, a-calacorene, elemicin, e-nerolidol, spathulenol, caryophyllene oxide, trans-b-elemenone, c-eudesmol, caryophylla-4 (14), 8(15)-dien-5.a-ol, d-cadinol, T-cadinol, cadalene, guaiol acetate [209] Kaempferol glycosides: [210] Anticancer, [130,211] antidiabetic, [212,213] antidyslipidaemic, [214] antiinflammatory, [209,215] antimicrobial [216,217] , antioxidant, [213,218] cardioprotective, [219] cytotoxicity, [220] hair growth, [221] hepatoprotective, [222] hypolipidaemic effect, [223] hypouricaemic effects, [224] immunomodulatory, [225] larvicidal, [29] pancreas-protective effect, [226] tyrosinase, [220,227] wound healing, [227] xanthine oxidase inhibitory [224] Arthritis, [228] cough and cold, [228] diabetes, [228] infection, [222] inflammation, [228] nerve pains, [228] pyrexia [228] Bark Flavonoids: (E)-Cinnamaldehyde; (Z)cinnamaldehyde. [229] Hydrocarbon: Phenol; c-muurolene [229] Flavonoids: cis-Cinnamaldehyde; transcinnamaldehyde [5,230,231] ; cinnamaldehyde. ...
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Objectives: Cinnamomum (Family Lauraceae) is traditionally used for flavouring food and in pharmaceutical preparations against various ailments. Detailed literature on the ethnobotanical and pharmacological properties of Cinnamomum is segregated and not present in well-documented form. In the present review, we have been trying to gather its detailed medicinal as well as pharmacological properties. The ethnobotanical and pharmacological properties of Cinnamomum were collected by searching several scientific databases, that is PubMed, Elsevier, Google Scholar, Science Direct and Scopus. Key findings: The plant extracts have been reported to possess astringent, warming stimulant, carminative, blood purifier, digestive, antiseptic, antifungal, antiviral, antibacterial, antioxidant, anti-inflammatory and immunomodulatory properties and also help to reduce cholesterol and blood sugar levels. A wide range of phytochemical compounds including aldehydes, acetate, alcohol, terpinenes, flavonoids, alkaloids, anthraquinones, coumarins, phenols, saponins, tannins, carboxylic acid, hydrocarbons, camphene, spathulenol, fatty acids, actinodaphnine, butanolides, lignans, steroids, propenoids and kaempferol glycosides are found in various parts of plant. Summary: This review provides detailed information about history, traditional uses, phytochemistry and clinical impacts of cinnamon as a spice and medicine. So we recommend further study on the clinical, medicinal, purification and identification of the most effective antibacterial activity of cinnamon to cure various infectious diseases.
... The most distinguished feature of C. osmophloeum is that the composition of leaf essential oil is similar to those of C. cassia bark essential oil. 4,5 A recent study by Yeh et al demonstrated that coumarin content in various clones of C. osmophloeum were much lower than that of Cassia cinnamons. In addition, C. osmophloeum leaf essential oils contain about 80% (w/w) of cinnamaldehyde and 0.4% to 2.7% (w/w) of eugenol 6 and the cinnamaldehyde-rich indigenous cinnamon could be a better candidate to produce essential oil with a longer storage time without decomposition compared to other commercial cinnamons. ...
... We have previously reported that C. osmophloeum leaf essential oils and cinnamaldehyde, a predominant compound, exerted xanthine oxidase inhibition and reduced serum uric acid levels in oxonate-induced mice. 5 Except for essential oils, oral administration of the hot water leaf extracts of C. osmophloeum reduced the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic hamsters induced by high-fat diet. 11 However, the biological activities of raw indigenous cinnamon leaf powder were poorly elucidated. ...
Article
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Indigenous cinnamon ( Cinnamomum osmophloeum Kaneh) is a native tree species in Taiwan and has been reported to have various bioactivities including insecticidal, larvicidal, and antimicrobial effects. The chemical finger print of C. osmophloeum is similar to that of commercial cinnamon species with lower coumarin content. The present study was aimed to investigate the antidyslipidemia effects of indigenous cinnamon ( Cinnamomum osmophloeum Kaneh) leaf powder (CoLP) on hypercholesterolemia hamsters. Hyperlipidemia was induced by high-cholesterol (HChol) diet for 4 weeks. Two percent and 5% CoLP, and gemfibrozil (positive control; 0.25%) were administered for 10 weeks following HChol diet. Control groups were fed with normal diet (ND) or ND+5% CoLP. Behavioral, physiological, and serum biochemical parameters were determined. We found that oral administration of CoLP for 10 weeks significantly reduced the HChol-induced increase of total cholesterol (TC), triglyceride, and low-density lipoprotein levels in plasma of hamsters. In addition, HChol-induced elevation of serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels was significantly reversed by CoLP in a dose-dependent manner, whereas blood urea nitrogen and creatinine levels were unaffected. Further standard diagnostic tests support that consumption of CoLP did not show any behavioral and morphological changes in hamsters. Furthermore, chemical composition analysis revealed that two new flavanol glycosides, kaempferol-3- O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinofuranosyl-7- O-α-l-rhamnopyranoside (4) and kaempferol-3- O-β -d-apiofuranosyl-(1→2)-α-l-arabinofuranoside (5) along with 4 known flavonoid glycosides were identified in leaves of C. osmophloeum. Taken together, these results concluded that CoLP possessed strong antidyslipidemic effects. Therefore, C. osmophloeum leaves could be a safe food supplement for treating hypercholesterolemia.
... XOD activity were measured by modified procedure protocol of Wang et al. (2008) [15]. ChondroT at concentrations of 100, 300, and 500 μg/mL was added to 0.1 M potassium phosphate buffer (pH 7.5) containing 0.4 U/mL XOD and then incubated for 10 min at 37°C. ...
... XOD activity were measured by modified procedure protocol of Wang et al. (2008) [15]. ChondroT at concentrations of 100, 300, and 500 μg/mL was added to 0.1 M potassium phosphate buffer (pH 7.5) containing 0.4 U/mL XOD and then incubated for 10 min at 37°C. ...
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Background ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). We previously reported that ChondroT showed significant anti-arthritis and anti-inflammatory effects. Methods This study was designed to evaluate the effect of ChondroT on hyperuricemia. First, the effect of ChondroT was evaluated on xanthine oxidase (XOD) activity in vitro. The anti-hyperuricemic effect of ChondroT was also studied in potassium oxonate (PO)-induced hyperuricemic model mice. Uric acid (UA) and XOD were evaluated in the serum, urine, and liver of the mice. In addition, we measured serum creatinine (Cr) and blood urea nitrogen (BUN) levels as well as mRNA expression of the mouse urate transporter 1 (mURAT1) to evaluate kidney function and urate excretion in hyperuricemic mice. Results ChondroT showed in vitro XOD inhibitory activity in a dose-dependent manner (P < 0.05). We demonstrated that ChondroT (37.5, 75 and 150 mg/kg) significantly reduced serum UA (P < 0.01 and P < 0.001, respectively), and upregulated urinary UA (P < 0.001, respectively) in PO-induced hyperuricemic mice. In addition, ChondroT (75 and 150 mg/kg) significantly reduced Cr (P < 0.05 and P < 0.01, respectively), BUN (P < 0.05 and P < 0.001, respectively), GOT (P < 0.05 and P < 0.01, respectively), and GPT (P > 0.05 and P < 0.05, respectively) levels in PO-induced hyperuricemic mice. ChondroT (75 and 150 mg/kg) also significantly downregulated serum (P < 0.05) and liver (P < 0.05) XOD activity. Compared to the hyperuricemic mice, the ChondroT (37.5, 75, and 150 mg/kg)-treated mice showed decreased mURAT1 protein expression level. Conclusion ChondroT displayed anti-hyperuricemic effects by regulating XOD activity and kidney mURAT1.
... Extensive research has highlighted the presence of essential oils in the inflorescences, leaves, and stems of P. benghalensis, which comprise a wide range of active constituents, such as monoterpene, sesquiterpene, and diterpene derivatives, such as β-bisabolene, α-pinene, β-ocimene, p-cymene, γ-terpinene, linalol, β-elemene, borneol, α-humulene, germacrene D, β-caryophyllene, valencene, caryophyllene oxide, phytol, viridiflorol, spathulenol, and more [26,55,56]. Numerous studies have indicated that these terpenoids possess remarkable inhibitory effects against xanthine oxidase, highlighting their potential as promising agents in this regard [57][58][59][60][61]. Therefore, it is highly recommended that a systematic evaluation employing animal models be conducted, guided by bioassays, to delve deeper into the potential therapeutic effects of P. benghalensis inflo-rescence and stem bark extracts, for managing gout. ...
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This research is focused on assessing the antibacterial properties of Pogostemon benghalensis stem bark and inflorescence extracts, as well as their inhibitory effects on xanthine oxidase, antioxidant potential, overall phenolic content, and flavonoid concentration. The cold maceration technique was used to obtain extracts using water, methanol, and ethyl acetate solvents. The disk diffusion method demonstrated the significant antibac- terial efficacy of the methanol stem bark extract against Staphylococcus epidermidis, with a zone of inhibition (ZOI) of 13 mm, and the inflorescence methanol extract against Kleb- siella pneumonia (ZOI: 12.9 mm). Moreover, the methanol stem bark extract exhibited the minimum bactericidal concentration (MBC) at 1.56 mg/mL and the minimum inhibitory concentration (MIC) at 0.78 mg/mL against S. epidermidis. The ethyl acetate inflorescence extract displayed noteworthy xanthine oxidase inhibition (IC50: 29.1 μg/mL) comparable to allopurinol (IC50: 12.7 μg/mL). Furthermore, the methanol stem bark extract exhibited a remarkable DPPH free radical inhibitory effect, showing an IC50 value of 42.5 μg/mL. The total polyphenol content ranged from 29.9 μg to 161.3 μg GAE per mg of dried extract weight in the methanol inflorescence extract, while the total flavonoid content ranged from 38.4 μg to 96.8 μg QE per mg of dried extract weight within the water-derived extract. Overall, these findings demonstrate the potent antibacterial properties, xanthine oxidase inhibition, and antioxidant activity of P. benghalensis extracts..
... Kali oxonat một chất ức chế enzym uricase, enzym thoái hoá acid uric, dẫn dến tăng acid uric máu và thường được sử dụng trong nhiều nghiên cứu trên chuột [10,11]. Bằng cách tiêm cách ngày trong suốt 2 tuần, đề tài đã mô phỏng được tình trạng tăng acid uric máu dài hạn, trong vòng 15 ngày trên chuột nhắt như đã thực hiện trong các nghiên cứu trước đây [9,12]. Lô đối chiếu cho uống allopurinol đã cho thấy tác dụng làm hạ acid uric máu trên chuột bị tăng acid uric cấp và mạn tính. ...
Article
Đặt vấn đề: Tình trạng tăng acid uric máu kéo dài dẫn đến lắng đọng tinh thể urat ở các khớp, gây viêm khớp và có thể gây biến dạng khớp. Nghiên cứu nhằm xây dựng mô hình viêm khớp do tăng acid uric trên chuột thực nghiệm và áp dụng để khảo sát hiệu quả của cao ethyl acetat từ lá Tía tô (cao EA). Đối tượng và phương pháp nghiên cứu: Chuột nhắt đực Swiss albino do Viện Pasteur TP. Hồ Chí Minh cung cấp. Chuột được gây tăng acid uric máu kéo dài bằng cách tiêm cách ngày kali oxonat với liều giảm dần (từ 300 mg/kg xuống 150 mg/kg) trong vòng 2 tuần, kết hợp tiêm tinh thể urat vào khớp cổ chân chuột ở ngày thứ 8 để gây sưng phù. Allopurinol và diclofenac được dùng làm thuốc đối chiếu để đánh giá đáp ứng của mô hình. Cao EA được chiết bằng cách lắc phân bố với ethyl acetat từ cao toàn phần lá Tía tô. Kết quả: Tiêm lặp lại kali oxonat làm tăng acid uric ổn định trong suốt thử nghiệm nhưng không làm lắng đọng acid uric tại khớp. Do đó, cần tiêm tinh thể urat vào khớp cổ chân vào ngày 8 để gây sưng phù khớp cổ chân chuột và mô phỏng tình trạng viêm khớp do gout. Allopurinol làm giảm rõ acid uric máu ở ngày 1 và ngày 7, thấp hơn cả lô sinh lý ở ngày 15. Diclofenac làm giảm mức độ sưng phù khớp cổ chân của lô chuột đối chiếu và không khác biệt so với lô sinh lý vào cuối thử nghiệm. Cao EA chưa thể hiện rõ tác động làm hạ acid uric cũng như tác động giảm viêm trên mô hình chuột viêm khớp do gout. Kết luận: Mô hình có thể áp dụng để khảo sát đồng thời tác động hạ acid uric và kháng viêm của các dược liệu tiềm năng trong điều trị bệnh gout. Từ khoá: acid uric, cao ethyl acetat, gout, lá Tía tô
... CA exhibits multiple beneficial effects. It not only inhibits xanthine oxidase activity in vitro and reduces the hyperuric acid caused by oxonate in a mouse model [17], but also inhibits the lipopolysaccharide (LPS)-induced inflammatory response in macrophages [18]. Furthermore, CA reduces the expression of vascular cell adhesion protein 1 and intercellular adhesion molecule-1 in tumour necrosis factor (TNF)-stimulated endothelial cells and inhibits the expression levels of cyclooxygenase-2 and prostaglandin E2 in IL-1β-stimulated endothelial cells [19,20]. ...
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Background Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. Methods Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. Results CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1β and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. Conclusion CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.
... The essential oils extracted from CO leaves have been shown to possess bioactivity against various organisms, including bacteria [19], termites [20], mildew [21], and fungi [22]. Additionally, we have investigated the potential use of CO leaves in food supplements and found that the essential oils and their dominant compound, trans-cinnamaldehyde, exhibit potent xanthine oxidase inhibitory activity and have an anti-hyperuricemia effect in mice [23]. Apart from essential oils, oral administration of CO hot water extracts or leaves to hyperlipidemic hamsters has been found to reduce total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels [24,25]. ...
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Cinnamomum osmophloeum Kanehira (CO) is an endemic species of Taiwan. This study elucidated the composition of CO hydrosol, revealing trans-cinnamaldehyde (65.03%), trans-cinnamyl acetate (7.57%), and coumarin (4.31%) as the main volatile compounds. Seven compounds were identified in the water fraction of hydrosol, including a novel compound, 2-(2-hydroxyphenyl)oxetan-3-ol. This marks the first investigation into high-polarity compounds in hydrosol, extending beyond the volatile components. Notably, two compounds, trans-phenyloxetan-3-ol and cis-phenyloxetan-3-ol, demonstrated significant inhibition activity against phosphodiesterase type five (PDE5), with IC50 values of 4.37 µM and 3.40 µM, respectively, indicating their potential as novel PDE5 inhibitors. Furthermore, CO hydrosol was evaluated against enzymes associated with erectile dysfunction, namely acetylcholinesterase (AChE), angiotensin-I converting enzyme (ACE), and arginase type 2 (ARG2). These findings underscore the potential of CO hydrosol to modulate erectile function through diverse physiological pathways, hinting at its prospects for future development in a beverage or additive with enhanced effects on erectile function.
... It belongs to the family Lauraceae. The essential oils extracted from Cinnamomum osmophloeum leaves, identified through HPLC, include -pinene, camphene, benzaldehyde, -pinene, 3-pheayl pionaldehyde, cis-cinnamaldehyde, trans-cinnamaldehyde, isobornylacetate, eugenol, and cinnamil acetate (Wang et al., 2008). The study found that leaf essential oil from eight indigenous cinnamon sources, including cinnamaldehyde, exhibited excellent antiviral effects against Aedes aegypti, with cinnamaldehyde showing the most effective activity (Cheng et al., 2004). ...
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Dengue fever is an illness instigated by Aedes mosquitoes (genus Flavivirus) belonging to the Flaviviridae family. It is predominant in most tropical and subtropical areas, primarily it is affecting Asia and Africa. Dengue virus spread with four different prevalent serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). WHO classified dengue fever as nonspecific fever, and dengue haemorrhagic fever (DHF). DHF extends from mild bruising on the skin to a clinical symptom of shock. In Ayurveda, Dandaka jwara can be correlated with dengue fever because they showed similar symptoms of dengue fever. Increased temperature, severe breaking pain in the joints, swelling and tenderness in joints, and flu-like symptoms are the common symptoms of dengue fever. Ayurveda has a variety of drugs that can act in viral conditions like Andrographis paniculata, Acorus calamus, Azadirachta indica, etc. They can help in dengue fever by improving immunity and controlling the hyperthermia. This study aimed to evaluate a deep understanding of dengue fever and admit a new approach for the management of its complications with an Ayurvedic perspective.
... In the literature reports many studies have shown that cinnamon tree barks and leaves were effective in improving chronic diseases such as neurodegeneration, diabetes and cancer, which can be attributed to the presence of phytochemicals such as cinnamaldehyde, eugenol, trans-cinnamic acid, flavonoids and phenolic acids (3,32). As cinnamaldehyde is the dominant bioactive compound accounting for >90% in cinnamon leaves, its protective role in the prevention of various chronic diseases has been extensively studied. ...
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Introduction Cinnamomum osmophloeum Kanehira (C. osmophloeum), a broad-leaved tree species of Taiwan, contains phenolic acids, flavonoids, and phenylpropanoids such as cinnamaldehyde and cinnamic acid in leaves. Many reports have shown that the cinnamon leaf extract possesses anti-inflammatory, hypoglycemic, hypolipidemic and neuroprotective functions. This study aims to analyze bioactive compounds in C. osmophloeum (cinnamon leaves) by UPLC-MS/MS and prepare hydrosol, cinnamon leaf extract and cinnamon leaf nanoemulsion for comparison in improving Parkinson’s disease (PD) in rats. Methods After extraction and determination of total phenolic and total flavonoid contents, cinnamaldehyde and the other bioactive compounds were analyzed in cinnamon leaves and hydrosol by UPLC-MS/MS. Cinnamon leaf nanoemulsion was prepared by mixing a suitable proportion of cinnamon leaf extract, soybean oil, lecithin, Tween 80 and deionized water, followed by characterization of particle size and polydispersity index by dynamic light scattering analyzer, particle size and shape by transmission electron microscope, encapsulation efficiency, as well as storage and heating stability. Fifty-six male Sprague-Dawley rats aged 8 weeks were divided into seven groups with group 1 as control (sunflower oil) and group 2 as induction (2 mg/kg bw rotenone in sunflower oil plus 10 mL/kg bw saline), while the other groups including rotenone injection (2 mg/kg bw) followed by high-dose of 60 mg/kg bw (group 3) or low-dose of 20 mg/kg bw (group 4) for tube feeding of cinnamon leaf extract or cinnamon leaf nanoemulsion at the same doses (groups 5 and 6) every day for 5 weeks as well as group 7 with rotenone plus hydrosol containing 0.5 g cinnamon leaf powder at a dose of 10 mL/kg bw. Biochemical analysis of brain tissue (striatum and midbrain) was done to determine dopamine, α-synuclein, tyrosine hydroxylase, superoxide dismutase, catalase, glutathione peroxidase and malondialdehyde contents by using commercial kits, while catalepsy performed by bar test. Results and discussion An extraction solvent of 80% ethanol was found to be the most optimal with a high yield of 15 bioactive compounds being obtained following UPLC analysis. A triple quadrupole tandem mass spectrometer with electrospray ionization mode was used for identification and quantitation, with cinnamaldehyde present at the highest amount (17985.2 µg/g). The cinnamon leaf nanoemulsion was successfully prepared with the mean particle size, zeta potential, polydispersity index and encapsulation efficiency being 30.1 nm, -43.1 mV, 0.149 and 91.6%, respectively. A high stability of cinnamon leaf nanoemulsion was shown over a 90-day storage period at 4 and heating at 100 for 2 h. Animal experiments revealed that the treatments of cinnamon leaf extract, nanoemulsion and hydrosol increased the dopamine contents from 17.08% to 49.39% and tyrosine hydroxylase levels from 17.07% to 25.59%, while reduced the α-synuclein levels from 17.56% to 15.95% in the striatum of rats. Additionally, in the midbrain of rats, an elevation of activities of superoxide dismutase (6.69-16.82%), catalase (8.56-16.94%), and glutathione peroxidase (2.09-16.94%) was shown, while the malondialdehyde content declined by 15.47-22.47%. Comparatively, the high-dose nanoemulsion exerted the most pronounced effect in improving PD in rats and may be a promising candidate for the development of health food or botanic drug.
... leaf essential oil demonstrates plenty of biological activities, such as anti-inflammatory activities. A study in Taiwan [15] found that the C. osmophloeum leaves' essential oil exhibited the most potent inhibitory effects on XOD compared to ethanolic and hot water extracts. No marked XOD inhibitory effects were observed in these two extracts. ...
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In the last few decades, hyperuricemia has drawn increasing attention owing to its global prevalence. Observational surveys have manifested that there is a relation between hyperuricemia and increased risks of hypertension, chronic kidney disease, cardiovascular events, metabolic disorders, end stage renal disease, and mortality. As alternatives, Traditional Chinese medicinal herbs have demonstrated concrete effects in mitigating hyperuricemia in different experiments. Researchers have made efforts to investigate the role of herbal medicine in attenuating hyperuricemia. This review focuses on traditional Chinese herbal medicines that have been reported to ameliorate hyperuricemia in experimental studies.
... Hyperuricemia is a causative precursor in the establishment of gout. 3 Xanthine oxidase (XO) inhibitors can reduce the production of UA in the purine metabolism, thus reducing the serum UA level. 4 Allopurinol is a drug for long-term prophylaxis, which reduces the serum urate by blocking XO, and plays a key role in the conversion of hypoxanthine and xanthine into uric acid. However, currently used hypouricemic medicines have various side effects, which limit their use in patients. ...
... Hyperuricemia is a causative precursor in the establishment of gout. 3 Xanthine oxidase (XO) inhibitors can reduce the production of UA in the purine metabolism, thus reducing the serum UA level. 4 Allopurinol is a drug for long-term prophylaxis, which reduces the serum urate by blocking XO, and plays a key role in the conversion of hypoxanthine and xanthine into uric acid. However, currently used hypouricemic medicines have various side effects, which limit their use in patients. ...
Article
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Hyperuricemia is a metabolic disorder with characteristic elevated serum uric acid. Recently, several plant-based medicines are being used for the treatment of hyperuricemia. The study aimed to find the hypouricemic potential of Berberis vulgaris in in-vitro and in-vivo study models. In i n-vitro studies, xanthine oxidase inhibition assay was performed to evaluate IC 50 value and capsule absorbance of the drug, respectively. For in-vivo experiment, the study comprised 15 groups of rats. In-vitro results revealed that significant xanthine oxidase inhibition was shown by Berberis vulgaris with an IC 50 value of 272.73±.3 μg/mL. Similarly, oral administration of Berberis vulgaris with dosages of 250 and 500 mg/kg decreased serum and liver uric acid levels significantly in a dose- and time-dependent manner in oxonate-induced hyperuricemic rats. Furthermore, 3-day and 7-day administration of Berberis vulgaris showed more potential compared to 1-day administrations. The present study indicated marked hypouricemic effects of Berberis vulgaris in rats. Due to caveat of the small sample size, a firm assumption of the hypouricemic effect of Berberis vulgaris cannot be made. However, extensive study is needed to find out the exact molecular mechanism involved and to translate its effects into clinical trials for the further validation of the results.
... cinnamyl acetate (2.97-16.10%), cinnamyl alcohol, and trans-Cinnamic acid [35] C. burmanni bark extract trans-Cinnamaldehyde [36] C. burmanni bark extract trans-Cinnamaldehyde, coumarin, and brazilin [37] C. camphora leaf -Isoborneol-type, camphora-type, cineole-type, linalool-type, and borneol-type [38] C. tamala leaf -Eugenol [39] C. osmophloeum α-Pinene, camphene, benzaldehyde, β-Pinene, 3-pheayl pionaldehyde, cis-Cinnamaldehyde, trans-Cinnamaldehyde, isobornylacetate, eugenol, and cinnamyl acetate [40] C. osmophloeum leaf EO Linalool, trans-Cinnamyl acetate, camphor, cinnamaldehyde [41] Cinnamomum altissimum bark EO Linalool (36.0%), methyl eugenol (12.8%), limonene (8.3%), α-Terpineol (7.8%), and terpinen-4-ol (6.4%) [42] (E)-Cinnamaldehyde (62.96%), coumarin (11.36%), α-Copaene (3.78%), 3-methoxy-1,2-propanediol (3.26%), and α-Cuaiene (3.19%) [43] C. loureiroi bark extract (E)-Cinnamaldehyde (51.69%), α-Copaene (16.14%), cinnamaldehyde dimethyl acetal (5.66%), β-Cadinene (3.19%), and α-Muurolene (4.78%). ...
Article
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Dental medicine is one of the fields of medicine where the most common pathologies are of bacterial and fungal origins. This review is mainly focused on the antimicrobial effects of cinnamon essential oil (EO), cinnamon extracts, and pure compounds against different oral pathogens and the oral biofilm and the possible effects on soft mouth tissue. Basic information is provided about cinnamon, as is a review of its antimicrobial properties against the most common microorganisms causing dental caries, endodontic and periodontal lesions, and candidiasis. Cinnamon EO, cinnamon extracts, and pure compounds show significant antimicrobial activities against oral pathogens and could be beneficial in caries and periodontal disease prevention, endodontics, and candidiasis treatment.
... Before the experiments, ICR mice (25-28 g) were acclimated for at least 1 week. The method used to evaluate the effects of TF1 on animal hyperuricemic model was followed by the previous reported method with some adjustments [25]. There were five groups with six mice per group (n = 6) totally. ...
Article
Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Excessive production of uric acid leads to hyperuricaemia. Due to the serious side effects of allopurinol, it is an urgent need to explore new XO inhibitors. Herein, the effects of theaflavin (TF1) on XO and anti-hyperuricaemia effect in hyperuricemic mice were investigated. Kinetic analysis indicate that TF1 is a reversible competitive inhibitor and has a significant inhibitory effect on XO with an IC50 value of 63.17 ± 0.13 μmol/L. Analysis of fluorescence spectra suggests that TF1 causes the obvious fluorescence quenching of XO, which is mainly driven by hydrophobic interactions and hydrogen bonds. Docking studies demonstrate that TF1 interacts with dozens of amino acid residues surrounded in the active cavity of XO, including Glu-879, Pro-1012, Thr-1010, Val-1011, Lys-771, Glu-802, Pro-1076, Leu-873, Leu-1014, Asn-768, Leu-648 and Phe-649. The inhibitory mechanism may be the insertion of TF1 into the active site of XO, which hinders the substrate xanthine to enter into the site. Furthermore, the results from animal experiments demonstrate that TF1 is effective in reducing serum uric acid in mice. These findings suggest that TF1 may be a potential drug candidate for the treatment of hyperuricaemia.
... Pharmacological studies have reported that Co has antifungal, anti-inflammatory, antitermitic, antibacterial, and antioxidative effects and reduced serum uric acid levels. [1][2][3][4][5] Research investigating the plant's phytochemical constituents has also shown that cinnamaldehyde makes 76% of essential oil in Co, which is higher than in other Cinnamomum species. [4] Therefore, Co essential oil may have high value added for the production of cosmetics or other related healthy products. ...
... In addition to anti-microorganism studies, the potential application of CO leaves in food supplements is an interesting subject. It was found that CO leaf essential oils and its major compound, cinnamaldehyde possessed xanthine oxidase inhibitory and anti-hyperuricemia activities in mice [16]. In addition to essential oils, oral administration of aqueous leaf extracts of CO reduced total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in hyperlipidemic hamsters [17]. ...
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The number of people with metabolic syndrome (MetS) is increasing year by year, and MetS is associated with gut microbiota dysbiosis. The demand for health supplements to treat or prevent MetS is also growing. Cinnamomum osmophloeum Kaneh (CO) and Taiwanofungus camphoratus (TC) are endemic to Taiwan. Both have been shown to improve the symptoms of MetS, such as dyslipidemia and hyperglycemia. Herein, we investigated the effect of CO, TC and their formulations on diet-induced obese mice. Male C57BL/6J mice were fed with a high-fat diet (HFD) for 10 weeks to induce MetS. After that, the mice were fed with HFD supplemented with CO, TC, and various CO/TC formulations, respectively, for 14 weeks. The changes in physiological parameters and the composition of the gut microbiome were investigated. The results indicated that CO, TC, and their formulations effectively reduced hyperglycemia, and tended to alleviate MetS in obese mice. Moreover, we also observed that CO, TC, and their formulations improved gut microbiota dysbiosis by decreasing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of Akkermansia spp. Our results revealed that CO and TC might have potential for use as a prebiotic dietary supplement to ameliorate obesity-related metabolic disorders and gut dysbiosis.
... Used as an effective medicine for this disease, which causes serious side effects. We could not discuss our results with other researches in literature because there is no research similar to ours, only the nearest one was done by a group of Taiwan researchers when attempting to inhibit the XO by the essential oil of C. osmophloeum leaves and presented the strongest XO inhibition activity with an IC50 of 16.3 mg/ml (Wang et al., 2008). ...
Conference Paper
The garlic plant has been known in many traditional medicines recipes especially for treating hyperuricemia and arthritis. The aim of this study is to find in vitro and in silico a natural treatment with no side effect by the inhibition of the milk human xanthine oxidase (HXO) enzyme extract by the garlic essential oil (GEO) using the double enzyme detection technique and Allopurinol (ALO) as a standard inhibitor. To define the interacting amino acids in the active site of HXO with the inhibitors; GOLD program for molecular docking was used. In humans, xanthine oxidase (HXO) catalyzes the oxidation of xanthine and hypoxanthine to uric acid, the imbalance nutrition leads to excessive function of HXO in the patients causing accumulation of the uric acid in joints and articulation resulting pain and paralyzing the movement, today treatment like ALO are used as competitive inhibitor to HXO. This causes secondary effects like hepatotoxicity. The results show that GEO give an important inhibition to HXO with an IC50 of 2.58 ± 0.04 µg/ml, comparing to ALO with an IC50 of 2.73 ± 1.02 µg/ml. The molecular docking results show multiple prediction poses up to ten in the active site of HXO (PDB ID: 2CKJ) the best pose chosen is based on the minimum interatomic distance value. The 2D structure of Diallyl trisulfide (DATS) which is the major component in the GEO, and ALO was used as inhibitors to HXO. The results show that GLU800 and GLN1195 are the catalytic amino acids toward DATS and ALO with minimum distance of 2.87Å, and 1.67Å respectively. According to this result, we present the garlic essential oil as an alternative and potent treatment for gout with less side effects.
... Used as an effective medicine for this disease, which causes serious side effects. We could not discuss our results with other researches in literature because there is no research similar to ours, only the nearest one was done by a group of Taiwan researchers when attempting to inhibit the XO by the essential oil of C. osmophloeum leaves and presented the strongest XO inhibition activity with an IC50 of 16.3 mg/ml (Wang et al., 2008). ...
Article
In pharmaceutical labs, the major sources of xanthine oxidase enzyme (XO) used for the gout disease experiment are animals and humans. The aim of this study is to find the lucrative source for the experiment by the evaluation in vitro and in silico of the inhibitory activity of five essential oils (EOs), against human and bovine milk xanthine oxidase (HXO and BXO), using molecular docking and an innovative analysis method based on double enzyme detection (DED), investigated in this work for the first time. The DED method proved its efficacy, sensitivity, and quickness. The results show that the five EOs give an important inhibition to BXO and HXO with an IC50 of 3.67 ± 0.17 μg/ml, 3.89 ± 0.11 μg/ml, 3.76 ± 0.18 μg/ml, 2.37 ± 0.23 μg/ml, 3.43 ± 0.56 μg/ ml for HXO, and to BXO with an IC50 of 6.26 ± 0.92 μg/ml, 5.53 ± 0.82 μg/ml, 10.59 ± 1.59 μg/ml, 1.74 ± 1 μg/ml, 5.33 ± 0.13 μg/ml, for respectively, cumin (Cuminum cyminum L.), fennel (Foeniculum vulgare Mill.), coriander (Coriandrum sativum L.), anise (Pimpinella anisum L.), and caraway (Carum carvi L.) EOs. In silico study based on molecular docking using autodock vina program was carried out to study the BXO and HXO inhibition mechanism and involved interactions for the first time. The results show that the five used EOs give an important and similar inhibition effect against XO with both enzyme sources, therefore we propose the bovine milk as a new economic enzyme source for lab experiment, which can promote a new, approach in future gout treatment.
... Cinnamomoum osmophloeum Kanehira (COK) is a Taiwanese indigenous cinnamon species with many uses as a Chinese herbal medicine. Active compounds of COK essential oils show excellent potential as pharmacological antibacterials [12]. Although previous studies of alcohol extracts of COK leaves demonstrated anti-tyrosinase activities, almost all of these studies focussed on ethanol extracts or essential oils from COK. ...
Article
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Cinnamomoum osmophloeum Kanehira (COK) is an indigenous tree species in Taiwan. Chemical compositions, antioxidant activity, mushroom tyrosinase inhibition, melanin synthesis repression, and protection against DNA damage of hydrosol from the COK leaves by steam distillation were examined. We performed 1,1-diphenyl-2-picrylhydrazyl radical scavenging, metal ion chelating, reducing power, and Trolox equivalent antioxidant capacity (TEAC) assays and determined the correlations between total phenolic contents and antioxidant activities. The findings showed that the anti-oxidative properties of COK hydrosol are closely correlated with their phenol contents. Additionally, the major constituents of hydrosol, i.e., cinnamaldehyde and benzaldehyde, had dose-dependent anti-tyrosinase effects against both monophenolase and diphenolase activities. GC-MS analysis revealed that the major bioactive components of hydrosol were trans-cinnamaldehyde (87.7%), benzaldehyde (7.0%), and cinnamyl acetate (5.3%). Moreover, we found that the hydrosol with the presence of benzaldehyde is more potent than pure cinnamaldehyde, and enhances the tyrosinase inhibitory activity of hydrosol. In kinetic analyses, Lineweaver–Burk plots and replots showed that COK hydrosol is a mixed-type inhibitor. Additionally, we found that very low doses of COK hydrosol repressed α-melanocyte-stimulating hormone-induced synthesis of microphthalmia-associated transcription factor, leading to decreased melanin synthesis in B16-F10 melanoma cells. These results demonstrated that production of hydrosol from COK leaves using steam distillation may provide a safe and efficacious source of skin-whitening agents for cosmetic and pharmaceutical applications, with antioxidant, anti-tyrosinase, anti-melanogenesis, and DNA protective activities.
... (CO) has been used widely as a substitute for C. cassia because of the similarities in the chemical compositions of the essential oils from these plants. Studies of the essential oils extracted from CO leaves have demonstrated their excellent insecticidal [4-6], antibacterial [7,8], antifungal [9,10], anti-inflammatory [11][12][13][14][15][16] and potential use as a medicinal material for decreasing high uric acid and high blood sugar [17,18]. Cinnamomum osmophloeum leaves can be collected and essential oils extracted without damaging the trees, and the annual harvest is highly profitable. ...
Article
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The plant genus Cinnamomum contains economically important evergreen aromatic trees and shrubs belonging to the laurel family, Lauraceae. Our study tree species Cinnamomum osmophloeum Kaneh. (CO) has high economic value in Taiwan. The present study attempts to identify the gene resources of Cinnamomum osmophloeum Kaneh. by analyzing the nucleotide sequences of the partial noncoding internal transcribed spacer 2 (pITS2) of the ribosomal DNA and the trnL-trnF chloroplast genome. Seventy-three geographical strains of Cinnamomum osmophloeum, preserved in the Lien Hua-Chin Research Center of the Forestry Research Institute and the Hua-Lin Forestry Center of Chinese Culture University, were collected and analyzed by PCR amplification and DNA sequencing to study the genetic diversity and nucleotide sequence polymorphisms of the tested specimens. Our results allowed us to accurately identify the lineage of Cinnamomum osmophloeum and to conclude that the strains belonging to the Lien Hua-Chin Research Center had much higher genetic diversity than those preserved in the Hua-Lin Forestry Center. Multiple sequence alignments demonstrated that the variability of the nucleotide sequence polymorphisms for the pITS2 region was higher than those of the trnL intron and trnL-trnF intergenic spacer (IGS) regions among the 73 tested specimens of Cinnamomum osmophloeum. Cluster analyses, using the neighbor-joining and maximum parsimony methods, for the 73 tested geographical strains of Cinnamomum osmophloeum and species of Cinnamomum registered in the GenBank and EMBL databases were performed to demonstrate the genus and species distribution of the samples. Here, we describe the use of pITS2 polymorphisms as a genetic classifier and report the establishment of a DNA sequence database for CO gene resource identification. The sequence database described in this study can be used to identify CO specimens at the inter- or intraspecies level using pITS2 DNA sequences, which illustrates its value in gene resource identification. Our study results can be used further for correctly identifying the true Cinnamomum osmophloeum Kaneh.
... ALP was tested at a concentration of 136 g/mL, and KAE and RUT were tested at concentrations between 0 and 1000 g/mL. activity (100-978 mg/kg) [34][35][36][37]. The daily mouse doses of 30 and 100 mg/kg can be converted into human equivalent doses of 146 and 487 mg/60 kg human/day, based on a conversion factor of 12.33 [38]. ...
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Cudrania tricuspidata Bureau (Moraceae) (CT) is a dietary and medicinal plant distributed widely in Northeast Asia. There have been no studies on the effect of CT and/or its active constituents on in vivo xanthine oxidase (XO) activity, hyperuricemia, and gout. The aim of this study was to investigate XO inhibitory and antihyperuricemic effects of the ethanol extract of CT leaf (CTLE) and its active constituents in vitro and in vivo . Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) analyses were used to determine a chemical profile of CTLE. XO inhibitory and antihyperuricemic effects of CTLE given orally (30 and 100 mg/kg per day for 1 week) were examined in potassium oxonate-induced hyperuricemic ICR mice. CTLE exhibited XO inhibitory activity in vitro with an IC 50 of 368.2 μ g/mL, significantly reduced serum uric acid levels by approximately 2-fold (7.9 nM in normal mice; 3.8 nM in 30 mg/kg CTLE; 3.9 nM in 100 mg/kg CTLE), and significantly alleviated hyperuricemia by reducing hepatic (by 39.1 and 41.8% in 30 and 100 mg/kg, respectively) and serum XO activity (by 30.7 and 50.1% in 30 and 100 mg/kg, respectively) in hyperuricemic mice. Moreover, several XO inhibitory and/or antihyperuricemic phytochemicals, such as stigmasterol, β -sitosterol, vitamin E, rutin, and kaempferol, were identified from CTLE. Compared with rutin, kaempferol showed markedly higher XO inhibitory activity in vitro . Our present results demonstrate that CTLE may offer a promising alternative to allopurinol for the treatment of hyperuricemia and gout.
... The electrochemical method performance in this study provides relatively small IC 50 values as compared with the spectrophotometric method reported by Apaya et al. [38], Azmi et al. [39]. However, others studies also reported low IC 50 values of allopurinol , namely 2.45 [30], and 0.60 ppm [40]. Inconsistency of IC 50 values may be caused by different testing conditions and sensitivity tests. ...
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Gout, characterized by elevated uric acid levels, is a common inflammatory joint disease associated with pain, joint swelling, and bone erosion. Existing treatments for gout often result in undesirable side effects, highlighting the need for new, safe, and cost-effective anti-gout drugs. Natural products, including medicinal plants and phytochemicals, have gained attention as potential sources of anti-gout compounds. In this review, we examined articles from 2000 to 2020 using PubMed and Google Scholar, focusing on the effectiveness of medicinal plants and phyto-chemicals in managing gout. Our findings identified 14 plants and nine phytochemicals with anti-gout properties. Notably, Teucrium polium, Prunus avium, Smilax riparia, Rhus coriaria, Foenic-ulum vulgare, Allium cepa, Camellia japonica, and Helianthus annuus exhibited the highest xa-thine oxidase inhibitory activity, attributed to their unique natural bioactive compounds such as phenolics, tannins, coumarins, terpenoids, and alkaloids. Herbal plants and their phytochemicals have demonstrated promising effects in reducing serum urate and inhibiting xanthine. This review aims to report recent studies on plants/phytochemicals derived from herbs beneficial in gout and their different mechanisms.
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Background Previous studies have shown that traditional Chinese medicine decoction (TCMD) could ameliorate the clinical symptoms and laboratory indicators of gouty arthritis (GA) patients. However, few investigations have been conducted on the efficacy and safety of TCMD for GA, the underlying mechanism of TCMD for GA, and the relationship between the TCMD active ingredients and GA targets. Methods Randomized controlled trials of TCMD for GA were retrieved from Chinese and English databases. Meta-analysis was conducted by Stata 17 software. Potential sources of heterogeneity were identified through subgroup analysis, meta-regression, and heterogeneity test. Publication bias was assessed by Egger’s test and funnel plots. The ingredients and targets related to TCMD and GA were obtained from multiple databases, such as TCMSP and DrugBank. The protein-protein interaction network, GO and KEGG analysis was constructed using STRING and DAVID. Molecular docking and visualization of the results were completed by AutoDock and PyMOL software. Results Eighty-four studies were included, involving 7151 patients and 10 outcome indicators. Meta-analysis showed that, compared to routine treatment, TCMD could better reduce the incidence of adverse events and the level of laboratory indicators including blood uric acid (BUA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α). In the section of network pharmacology, we retrieved 150 active ingredients and 303 target genes from the top 10 herbs in 84 studies, as well as 3082 disease targets and 195 cross targets of the herbs and GA. The top ranked ingredients, intersection targets, and signaling pathways included quercetin, kaempferol, and wogonin; AKT1, TNF, and TP53; as well as IL-17, HIF-1, and PI3K-AKT, etc. Among the 81 molecular docking results, we visualized 10 results with low binding energy, including IL1B and beta-sitosterol, MYC and beta-sitosterol, etc. Conclusion TCMD could be a satisfactory complementary and alternative therapy for GA. However, it should be verified by further studies. Future research could be conducted from the following active ingredients, targets, and signal pathways, such as wogonin, sitosterol, and sitosterol; AKT1, TNF, IL6, and TP53; and IL-17, HIF-1, and PI3K-AKT signaling pathway.
Chapter
Gout is a complex form of arthritis characterized by sudden, severe attacks of pain, swelling, redness, and tenderness in the joints. Gout is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Natural products offer many options to reduce the progress and symptoms of diseases, including gout. Natural compound structures including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids have anti-inflammatory, antioxidant, and XO activities. In this chapter, the author presents medicinal plants and isolated compounds that are used to prevent and reduce signals of the pathogenesis of gout disease.
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Background: Hyperuricemia belongs to metabolic syndromes where increased uric acid levels are identified in the blood serum. Such a syndrome could be responsible for kidney stone formation, gout, hypertension, and chronic kidney diseases. It has been reported that cardiovascular risks have been linked with hyperuricemia. Gout is of the most frequent manifestations due to hyperuricemia; its management involves various pharmacological available options and dietary changes. Throughout the literature, various dosage forms are studied as alternative options to the present drug delivery systems. Objective: To update and summarize the current information for gout and hyperuricemia management Methods: Authors have performed a thorough literature research from 2010-2023 using keywords such as hyperuricemia, gout, diagnosis, guidelines, drug delivery and clinical trials. The databases used were PubMed, ScienceDirect. According to our inclusion criteria, all studies which include the previous terms, as well as drugs or other molecules that can be applied for gout and/or hyperuricemia management, were added. Results: In this article, authors have summarized the pathogenesis, diagnosis and updated guidelines for gout and hyperuricemia management. Moreover, the authors have reviewed and discussed current drug delivery systems found in the literature, including drugs targeting the above disorders. Finally, the available clinical trials assessing the efficacy of newer drugs or combinations of the past ones, are being discussed. Conclusion: The available drugs and dosage forms are limited, and therefore, scientific society should focus on the development of more efficient drug delivery systems for hyperuricemia and gout management.
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Background: Cinnamic acid and its derivatives have gained significant attention in recent medicinal research due to their broad spectrum of pharmacological properties. However, the effects of these compounds on xanthine oxidase (XO) have not been systematically investigated, and the inhibitory mechanism remains unclear. Objective: The objective of this study was to screen 18 compounds and identify the XO inhibitor with the strongest inhibitory effect. Furthermore, we aimed to study the inhibitory mechanism of the identified compound. Method: The effects of the inhibitors on XO were evaluated using kinetic analysis, docking simulations, and in vivo study. Among the compounds tested, 4-NA was discovered as the first XO inhibitor and exhibited the most potent inhibitory effects, with an IC50 value of 23.02 ± 0.12 μmol/L. The presence of the nitro group in 4-NA was found to be essential for enhancing XO inhibition. The kinetic study revealed that 4-NA inhibited XO in a reversible and noncompetitive manner. Moreover, fluorescence spectra analysis demonstrated that 4-NA could spontaneously form complexes with XO, referred to as 4-NA-XO complexes, with the negative values of Δ H and Δ S. research-article Results: This suggests that hydrogen bonds and van der Waals forces play crucial roles in the binding process. Molecular docking studies further supported the kinetic analysis and provided insight into the optimal binding conformation, indicating that 4-NA is located at the bottom outside the catalytic center through the formation of three hydrogen bonds. Furthermore, animal studies confirmed that the inhibitory effects of 4-NA on XO resulted in a significant reduction of serum uric acid level in hyperuricemia mice. Conclusion: This work elucidates the mechanism of 4-NA inhibiting XO, paving the way for the development of new XO inhibitors.
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p>Xanthine oxidoreductase (XOR) is a widely distributed housekeeping enzyme in mammals that catalyzes the last two steps in human purine catabolism to produce uric acid. The enzyme exists as a homodimer with independent electron transfer in each monomer. This has been studied extensively as a major constituent of the milk fat globule membrane (MFGM) which surrounds fat globules in cow's milk even though purine catabolism is the most accepted function of XOR. A huge number of literature highlights on the different catalytic forms of XOR and their importance in the generation of reactive oxygen species/reactive nitrogen species (ROS/RNS) and synthesis of uric acid which are involved in many physiological and pathological processes. However, a slight ambiguity resides in their biochemical functions. The aim of this article was to review the literature published on the structural, catalytical, physiological and pathological role of XOR and to resolve the ambiguity in biochemical processes and to firm up various natural inhibitors of XOR collectively. Uric acid, the product of purine catabolism shows antioxidant activity, and XOR-derived ROS and RNS play a role in innate immunity, milk secretion and also be involved in signaling and metabolism of xenobiotics. Furthermore, XOR is likely to be engaged in pathology because of excessive production of uric acid and ROS/RNS. This review also reports natural XOR inhibitors in plants which inhibit the enzyme to treat XOR associated pathology.</p
Chapter
Essential oils (EOs), which are secondary metabolites of plants, have volatile and natural characteristics. The biological activities of EOs have been increasing interest for many years, and the number of studies in the literature has increased in parallel with this interest. Although their antimicrobial activities are more common than other biological activities, some areas still need research. In the first stage of this chapter, the known antimicrobial activities of EOs will mainly be evaluated under the titles such as usage of EOs in combinations and encapsulation of EOs. Further, synergistic, additive, or antagonistic interactions of EO combinations will also be associated with their chemical compositions. In the second part, the review will focus on new and remarkable biological activities of EOs such as angiotensin-converting enzyme inhibitory potential, α-amylase and α-glucosidase inhibition potential, and xanthine oxidase inhibition potentials of essential oils. While the antihypertensive activity was correlated with the inhibition of the angiotensin-converting enzyme, antidiabetic activity has been associated with the inhibition of amylase and glucosidase activities. Moreover, inhibition of the xanthine oxidase enzyme prevents overproduction of uric acid and thus hyperuricemia. This situation is associated with antigout activity.
Chapter
A variety of plants are good sources of therapeutic agents, mainly due to their secondary metabolites, chemical compounds formed from the conversion of light energy. Among these metabolites are the diterpenes, a group of structurally diverse molecules widely distributed in nature. Diterpenes exhibit a broad spectrum of biological activities and have been extensively studied due to promising results in their antitumor effects. Breast cancer is one of the most common cancer types found worldwide, varying from mild and potentially curable to incurable manifestations using the treatments available. Therefore, the search for new drugs is urgent and necessary. This chapter provides a literature update and a review of the antibreast cancer effects of diterpenes from plants, based on published studies indexed in the main databases during 2015–20. The structure, mechanism of action, molecular targets, and in silico, in vitro, and in vivo effects are presented.
Chapter
Gout is a complex form of arthritis which is characterized by sudden, severe attacks of pain, swelling, redness, and tenderness in the joints. Gout is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Natural products offer many options to reduce the progress and symptoms of diseases, including gout. Natural compound structure including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids have anti-inflammatory, antioxidant, and XO activities. In this chapter, the authors present medicinal plants and isolated compounds which are used to prevent and reduce the pathogenesis of gout.
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Xanthine oxidase (XO) is an essential enzyme in catalyzing hydroxylation of hypoxanthine to xanthine and uric acid in the kidney. Excessive formation of uric acid can lead to hyperuricemia (HUA), a condition caused by excess uric acid contamination in the blood.HUA is responsible for various diseases in the body, such as gout, cardiovascular, and renal failure. It is also associated with numerous inflammatory diseases and their metabolic pathways, including tumors, chronic hypoxia, renal injury, and hypertension. XO is a superoxide producing enzyme usually confined to lungs, liver, and blood serum. Blood assay and diagnostics for XO help in a better understanding of its associated diseases in the human body. The mechanism of how XO is released in the bloodstream is a matter of debate in medical science. In the current review article, we comprehensively discussed the role of XO in human health, inhibitors, and their regulation, isolation, and extractions of inhibitors from plants, types, and their activities towards the human health perspective are concerned.
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Xanthine oxidase (EC 1.17.3.2) (XO) is one of the main enzymatic sources that create reactive oxygen species (ROS) in the living system. It is a dehydrogenase enzyme that performs electron transfer to nicotinamide adenine dinucleotide (NAD+ ), while oxidizing hypoxanthin, which is an intermediate compound in purine catabolism, first to xanthine and then to uric acid. XO turns into an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin turns into uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is crystallized, when present in high concentrations. Thus, XO inhibitors are one of the drug classes used against gout, a purine metabolism disease that causes urate crystal storage in the joint and its surroundings caused by hyperuricemia. Urate-lowering therapy include XO inhibitors that reduce uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that obstruct uric acid synthesis through XO inhibition are allopurinol, febuxostat, and uricase. However, since the side effects, safety and tolerability problems of some current gout medications still exist; intensive research is ongoing to look for new, effective, and safer XO inhibitors of natural or synthetic origins for the treatment of the disease. In the present review, we aimed to assess in detail XO inhibitory capacities of pure natural compounds along with the extracts from plants and other natural sources via screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data pointed out to the fact that natural products, particularly phenolics such as flavonoids (quercetin, apigenin, and scutellarein), tannins (agrimoniin and ellagitannin), chalcones (melanoxethin), triterpenes (ginsenoside Rd and ursolic acid), stilbenes (resveratrol and piceatannol), alkaloids (berberin and palmatin) have a great potential for new XO inhibitors capable of use against gout disease. In addition, not only plants but other biological sources such as microfungi, macrofungi, lichens, insects (silk worms, ants, etc) seem to be the promising sources of novel XO inhibitors.
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Benign prostatic hyperplasia (BPH) is a widespread disorder in elderly men. Cinnamaldehyde, which is a major constituent in the essential oil of cinnamon, has been previously reported to reduce xanthine oxidase activity, in addition to its anti-inflammatory, anti-oxidant, and anti-proliferative activities. Our study was designed to investigate the potential modulatory effects of cinnamaldehyde on testosterone model of BPH in rats through reduction of uric acid level, and suppression of IL-6/JAK1/STAT3 signaling pathway. Cinnamaldehyde (40 and 75 mg/kg) was orally administered to male Wistar rats for 3 weeks, and concurrently with testosterone (3 mg/kg, s.c.) from the second week. Cinnamaldehyde ameliorated the elevation in prostatic weight and index compared to rats treated with testosterone only, that was also confirmed by alleviation of histopathological changes in prostate architecture. The protective mechanisms of cinnamaldehyde were elucidated through inhibition of xanthine oxidase activity and reduced uric acid level. That was accompanied by reduction of the pro-inflammatory cytokines; interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), and the nuclear translocation of the transcription factor NF-κB p65, that could be attributed also to the enhanced anti-oxidant defense by cinnamaldehyde. The protein expression of JAK1, which is IL-6 receptor linked protein, was reduced with subsequently reduced activation of STAT3 protein. That eventually suppressed the formation of the proliferation protein cyclin D1, while elevated Bax/Bcl2 ratio. It can be concluded that reducing uric acid level through xanthine oxidase inhibition and suppression of the inflammatory signaling cascade; IL-6/JAK1/STAT3; by cinnamaldehyde could be a novel and promising therapeutic approach against BPH.
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The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes. A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period. After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%), and total cholesterol (12-26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant. The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.
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The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 μg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 μg/ml, with 13 possessing more than 50% inhibition. At 50 μg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC50, 18 μg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC50, 22 μg/ml) and the leaves of Lycopuseuropaeus (Lamiatae) (IC50, 26 μg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC50, 38 μg/ml). The IC50 value of allopurinol used as a positive control was 1.06 μg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.
Article
Chlorprothixene treatment in the rat prolonged bleeding time, inhibited collagen-induced aggregation of blood platelets and in the presence of potassium oxonate caused an elevation in serum urate levels. A red discharge which appeared around the eyes fluoresced under exposure to U.V. light and possessed an absorption spectra characteristic of porphyrins.
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An alkaline phosphotungstate procedure was developed in which the phosphotungstic acid reagent is used both as protein-precipitating and oxidizing reagent. The procedure requires only a 0.2-ml sample and fewer reagents and manipulations than similar procedures, but yields results equivalent to those obtained by Henry’s alkaline phosphotungstate procedure. Recovery, precision, and linearity were good over a wide range of uric acid concentrations. Standardization was easy with use of aqueous albumin standards or of commercial calibration reference sera.
Article
This study was designed to focus on the potential stress that xanthine oxidase could produce in copper-deficient rats fed fructose. Fructose consumption results in an excess production of uric acid due to an increased degradation of nucleotides. The enzyme xanthine oxidase catalyzes the oxidation of both hypoxanthine and xanthine. During the oxidation process free radicals are generated, which in turn, induce lipid peroxidation and premature death. Allopurinol -- a competitive inhibitor of xanthine oxidase -- could alleviate the combined effects of fructose feeding and copper deficiency. Twenty-five male rats were fed for 4 weeks from weaning a copper-deficient or adequate diet containing fructose. Twelve rats were given a daily oral dose of 5 mg allopurinol/100 g b.wt. Two copper-deficient rats that were not treated with allopurinol died prematurely during the fourth week of the study. No mortality occurred in the group of copper-deficient rats that had been treated with allopurinol. Anemia was alleviated by allopurinol, which in turn, could be responsible for improved growth rate. Allopurinol was effective in inhibiting xanthine oxidase activity in vivo as measured by the dramatic reduction of uric acid production. Lipid peroxidation, however, was not affected by allopurinol. It is concluded that the beneficial effects of allopurinol in copper deficiency do not appear to be related to prevention of oxygen radicals, but rather, to the protection against the catabolic destruction of purines, which in turn, increases nucleotide pool.
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India has an extensive area of forest enriched with plant diversity. Several of these plants have been used as folklore medicines. However, the medicinal plants have rarely been investigated for anti-human immunodeficiency virus activity. Hence, some Indian medicinal plants were screened in vitro against human immunodeficiency virus (HIV). The inhibitory effect of plant extracts on HIV replication was monitored in terms of inhibition of virus induced cytopathogenicity in MT-4 cells. The MT-4 cells were infected with HIV. The HIV infected or mock infected MT-4 cells were incubated at 37 degrees C in a CO2 incubator in the presence of the plant extracts. After five days, cell viability was measured by tetrazolium based colorimetric assay. Of the 69 plant species screened, 16 were effective against HIV-1 and 4 were against both HIV-1 and HIV-2. The most effective extracts against HIV-1 and HIV-2 are respectively Cinnamomum cassia (bark) and Cardiospermum helicacabum (shoot + fruit). The findings provide a rationale for further studies on isolation of active principles and pharmacological evaluation.
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The antibacterial activities of the essential oils from leaves of two Cinnamomum osmophloeum clones (A and B) and their chemical constituents were investigated in this study. The nine strains of bacteria, including Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Salmonella sp., and Vibrio parahemolyticus, were used in the antibacterial tests. Results from the antibacterial tests demonstrated that the indigenous cinnamon B leaf essential oils had an excellent inhibitory effect. The MICs (minimum inhibitory concentrations) of the B leaf oil were 500 microg/ml against both K. pneumoniae and Salmonella sp. and 250 microg/ml against the other seven strains of bacteria. Cinnamaldehyde possessed the strongest antibacterial activity compared to the other constituents of the essential oils. The MICs of cinnamaldehyde against the E. coli, P. aeruginosa, E. faecalis, S. aureus, S. epidermidis, MRSA, K. pneumoniae, Salmonella sp., and V. parahemolyticus were 500, 1000, 250, 250, 250, 250, 1000, 500, and 250 microg/ml, respectively. These results suggest that C. osmophloeum leaf essential oil and cinnamaldehyde are beneficial to human health, having the potential to be used for medical purposes and to be utilized as anti-bacterial additives in making paper products.
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The natural product aesculin was demonstrated to possess potent hypouricemic effects in in vivo models of hyperuricemia in both mice and rats pretreated with oxonate. Aesculin, when administered intraperitoneally to the oxonate-induced hyperuricemic rodents, was able to elicit dose-dependent hypouricemic effects. At doses of 150 mg/kg of aesculin or above, the serum urate levels of the oxonate-pretreated mice were not different from normal mice. Such an effect in mice was observed as quick as 1.5 h after aesculin administration and was persistent for at least 5 h after aesculin administration. In rats, similar hypouricemic effects of intraperitoneally administered aesculin could also be demonstrated at doses of 100 mg/kg of aesculin or above, the serum urate levels of the oxonate-pretreated rats were not different from normal rats. Again, the effect persisted for at least 5 h after aesculin administration. In both rodents, however, oral administration at the same doses did not produce any observable hypouricemic effects. In addition, aesculin, when tested in vitro on rat and mouse liver homogenates, did not elicit any measurable inhibitory actions on the xanthine oxidase/xanthine dehydrogenase activities.
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The antitermitic activities of the essential oils from the leaves of two Cinnamomum osmophloeumclones (A and B) and their chemical ingredients against Coptotermes formosanus Shiraki were investigated according to direct contact application. Results from this experiment have demonstrated that the indigenous cinnamon B leaf essential oil has a more effective antitermitic activity than indigenous cinnamon A leaf essential oil. Furthermore, when cinnamaldehyde, eugenol, and alpha-terpineol are extracted from indigenous cinnamon leaf essential oil and used at the strength of 1 mg/g, their antitermitic effectiveness is much higher than that using indigenous cinnamon leaf essential oil. Among the congeners of cinnamaldehyde examined, cinnamaldehyde has exhibited the strongest termiticidal property.
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The inhibitory effects of Cinnamomum cassia bark-derived material on nitric oxide (NO) production in RAW 264.7 cells was determined through the evaluation of NO production and expression of inducible nitric oxide and compared to the effects of three commercially available compounds, cinnamyl alcohol, cinnamic acid, and eugenol. The biologically active constituents of C. cassia extract were characterized as trans-cinnamaldehyde by spectral analysis. The inhibitory effects varied with both chemical and concentration used. Potent inhibitory effects of cinnamaldehyde against NO production were 81.5 and 71.7% at 1.0 and 0.5 microg/microL, respectively, and a 41.2% inhibitory effect was revealed at 0.1 microg/microL. However, little or no activity was observed for cinnamic acid and eugenol. Suppression effects of cinnamaldehyde on inducible nitric oxide synthase expression were revealed by Western blot analysis. As a naturally occurring therapeutic agent, trans-cinnamaldehyde could be useful for developing new types of NO inhibitors.
Article
Xanthine oxidase (XOD) is a key enzyme playing a role in hyperuricemia, catalyzing the oxidation of hypoxanthine to xanthine and then to uric acid. This study aimed to identify the XOD inhibitors from the leaves of Lagerstroemia speciosa (L.) Pers. (Lythraceae), which was traditionally used as a folk medicine in the Philippines. Using a bioassay-guided fractionation technique, two active compounds were isolated from the aqueous extracts of the Lagerstroemia speciosa leaves, namely valoneic acid dilactone (VAD) and ellagic acid (EA). The result demonstrated that the XOD-inhibitory effect of VAD was a stronger than that of allopurinol, a clinical drug used for XOD inhibitor, with a non-competitive mode for the enzyme with respect to xanthine as the substrate. These results may explain and support the dietary use of the aqueous extracts from Lagerstroemia speciosa leaves for the prevention and treatment of hyperuricemia.
Article
Chemical compositions of leaf essential oils from eight provenances of indigenous cinnamon (Cinnamomum osmophloeum Kaneh.) were compared. According to GC-MS and cluster analyses, the leaf essential oils of the eight provenances and their relative contents were classified into five chemotypes-cinnamaldehyde type, linalool type, camphor type, cinnamaldehyde/cinnamyl acetate type, and mixed type. The larvicidal activities of leaf essential oils and their constituents from the five chemotypes of indigenous cinnamon trees were evaluated by mosquito larvicidal assay. Results of larvicidal tests demonstrated that the leaf essential oils of cinnamaldehyde type and cinnamaldehyde/cinnamyl acetate type had an excellent inhibitory effect against the fourth-instar larvae of Aedes aegypti. The LC(50) values for cinnamaldehyde type and cinnamaldehyde/cinnamyl acetate type against A. aegypti larvae in 24 h were 36 ppm (LC(90) = 79 ppm) and 44 ppm (LC(90) = 85 ppm), respectively. Results of the 24-h mosquito larvicidal assays also showed that the effective constituents in leaf essential oils were cinnamaldehyde, eugenol, anethole, and cinnamyl acetate and that the LC(50) values of these constituents against A. aegypti larvae were <50 ppm. Cinnamaldehyde had the best mosquito larvicidal activity, with an LC(50) of 29 ppm (LC(90) = 48 ppm) against A. aegypti. Comparisons of mosquito larvicidal activity of cinnamaldehyde congeners revealed that cinnamaldehyde exhibited the strongest mosquito larvicidal activity.
Article
Cinnamomum osmophloeum Kaneh is one of the hardwood species indigenous to Taiwan that possesses significant antifungal activity. To examine the antifungal activity of leaf essential oils and dominant constituents from C. osmophloeum, the essential oils of leaves from three clones (A, B, and C) collected from Haw-Lin experimental forest were extracted and their components analyzed by gas chromatography. Results from the antifungal tests demonstrated that the essential oils of both B and C leaves had strong inhibitory effects. The antifungal indices of these two leaf oils at 100 ppm against five strains of white rot fungi and four strains of brown rot fungi were all 100%. Cinnamaldehyde, the major compound in C. osmophloeum leaf essential oils, possessed the strongest antifungal activities compared with the other components. Its antifungal indices against both Coriolus versicolor and Laetiporus sulphureus were 100%. The MIC (minimum inhibitory concentration) of cinnamaldehyde against C. versicolor and L. sulphureus was 50 and 75 ppm, respectively. In addition, comparisons of the antifungal indices of cinnamaldehyde's congeners proved that cinnamaldehyde exhibited the strongest antifungal activities.
Article
Four kaempferol glycosides were isolated from the leaves of Cinnamomum osmophloeum Kaneh, a Taiwan endemic tree. These compounds namely, kaempferitrin (1), kaempferol 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (2), kaempferol 3-O-beta-D-apiofuranosyl-(1-->2)-alpha-L-arabinofuranosyl-7-O-alpha-L-rhamnopyranoside (3), and kaempferol 3-O-beta-D-apiofuranosy-(1-->4)-alpha-L-rhamnopyranosyl-7-O-alpha-L-rhamnopyranoside (4). The structure of compound 2 was determined by spectroscopic analyses and acid hydrolysis. The isolates 1-4 were evaluated as inhibitors of some macrophage functions involved in the inflammatory process. These four compounds inhibited lipopolysaccharide (LPS) and interferon (IFN)-gamma-induced nitric oxide (NO), and cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-12] in a dose-dependent manner. The concentration of 50% inhibition (IC(50)) of NO by compounds 1, 3, 4 were 40, 15, 20microM, respectively. In parallel, these concentrations were approximately in a similar manner to that observed for TNF-alpha and IL-12 production. However, compound 2 inhibited NO and cytokines production by 30% at 100microM concentration. On the other hand, compounds 3 and 4 showed no inhibitory effect on the production of NO from macrophages, when inducible NO synthase was already expressed by the stimulation with LPS and IFN-gamma. Taken together, our results provide evidence that isolates of C. osmophloeum possess an anti-inflammatory potential which constitutes a previously unrecognized biological activity.
Article
The possible mechanism of the underlying nephropathy found in the rat toxicity study of FYX-051, a xanthine oxidoreductase inhibitor, was investigated. Rats received oral treatment of either 1 or 3 mg/kg of FYX-051, with and without citrate for four weeks to elucidate whether nephropathy could be caused by materials deposited in the kidney. Furthermore, analysis of the renal deposits in rats was also performed. Consequently, interstitial nephritis comprising interstitial inflammatory cell infiltration, dilatation, basophilia and epithelial necrosis of renal tubules and collecting ducts, deposits in renal tubules and collecting ducts, and so forth was seen in six of the eight rats and in all eight rats in the 1 and 3 mg/kg FYX-051 alone groups, respectively, with the intensity in the 3 mg/kg group being moderate to severe. In the simultaneous treatment with citrate group, however, no alterations were observed in the kidney, except for minimal interstitial nephritis in one instance in the 3 mg/kg FYX-051 + citrate group along with an increased urinary pH, leading to an increase in xanthine solubility. Analysis of intrarenal deposits showed that the entity would be composed of xanthine crystals. The present study, therefore, showed that nephropathy in rats occurring after the administration of FYX-051 was a secondary change caused by xanthine crystals being deposited in the kidney, and no other causes could be implicated in this kidney lesion.
Article
The leaf essential oil from indigenous cinnamon (Cinnamomum osmophloeum Kaneh.) was investigated by gas chromatography-mass spectrometry, and 21 compounds were identified. The major constituents of leaf essential oil were the monoterpenes 1,8-cineole (17.0%) and santolina triene (14.2%) and the sesquiterpenes spathulenol (15.7%) and caryophyllene oxide (11.2%). In the antiinflammatory activity assay, we demonstrated that the essential oil has a higher capacity to inhibit proIL-1beta protein expression induced by LPS-treated J774A.1 murine macrophage. At dosages of 60 microg/mL, essential oil clearly inhibited proIL-1beta protein expression. Furthermore, a dose of 60 microg/mL of essential oil was effectively inhibitory for IL-1beta and IL-6 production but not for TNF-alpha, suggesting that essential oil was bioactive in antiinflammation in vitro. This study is the first to report antiinflammatory activity of extracts obtained from the leaf essential oil of C. osmophloeum.
Article
The essential oils isolated from nine geographical provenances of indigenous cinnamon (Cinnamomum osmophloeum Kaneh.) leaves were examined by GC-MS and their chemical constituents were compared. According to GC-MS and cluster analyses the leaf essential oils of the nine provenances and their relative contents were classified into six chemotypes-cinnamaldehyde type, cinnamaldehyde/cinnamyl acetate type, cinnamyl acetate type, linalool type, camphor type and mixed type. In addition, the antifungal activities of leaf essential oils and their constituents from six chemotypes of indigenous cinnamon were investigated in this study. Results from the antifungal tests demonstrated that the leaf essential oils of cinnamaldehyde type and cinnamaldehyde/cinnamyl acetate type had an excellent inhibitory effect against white-rot fungi, Trametes versicolor and Lenzites betulina and brown-rot fungus Laetiporus sulphureus. The antifungal indices of leaf essential oils from these two chemotypes at the level of 200 micro/ml against T. versicolor, L. betulina and L. sulphureus were all 100%. Among them, the IC(50) (50% of inhibitory concentrations) value of the essential oil of cinnamaldehyde type leaf against L. sulphureus was 52-59microg/ml. Cinnamaldehyde possessed the strongest antifungal activities in comparison with other constituents of the essential oils from cinnamaldehyde type leaf, at the level of 100microg/ml its antifungal indices against T. versicolor, L. betulina and L. sulphureus were 100%. The IC50 values of cinnamaldehyde against T. versicolor, L. betulina and L. sulphureus were 73, 74 and 73microg/ml, respectively.
Article
We investigated the hypouricemic effects of cassia oil extracted from Cinnamomum cassia using hyperuricemic mice induced by potassium oxonate, and its inhibitory actions against liver xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) activities. Oral administration of cassia oil significantly reduced serum and hepatic urate levels in hyperuricemic mice in a time- and dose-dependent manner. At doses of 450 mg/kg of cassia oil or above, serum urate levels of the oxonate-pretreated mice were not different from the normal control mice. Cassia oil at 600 mg/kg was found to be as potent as allopurinol, which reduced hepatic urate levels to lower than normal. In normal mice, urate levels in liver, but not in serum, were altered with dose-dependent decrease after cassia oil treatment. Furthermore, the ratio, liver uric acid/serum uric acid, was determined after cassia oil administration with time- and dose-dependent decreases in hyperuricemic mice. The positive dose-dependent decrease ratio was also observed after cassia oil treatment in the normal animals. The decreased extent of ratio elicited by cassia oil in normal mice appeared to be greater than that in the hyperuricemic animal. In addition, cassia oil significantly exhibited marked reductions in liver XDH/XOD activities, with an apparent dose-dependence in the normal and hyperuricemic mice. The onset of inhibition in enzyme activities elicited by allopurinol was much higher than that elicited by cassia oil. These results suggested that hypouricemic effects of cassia oil could be explained, at least partly, by inhibiting liver in vivo activities of XDH/XOD.
Article
A new bioautographic assay suitable for the localization of xanthine oxidase inhibitors and superoxide radical scavengers present in a complex matrix is described. Enzyme activity is detected by reaction of superoxide radicals with nitroblue tetrazolium to form a blue formazan salt. Both activities can be differentiated using a non-enzymatic version of the autographic assay wherein superoxide is chemically generated.
Simultaneous treatment with citrate prevents nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor, in rats Some in vivo effects in the rat induced by chloprothixene and potassium oxonate
  • T Shimoto
  • N Ashizawa
  • K Matzumoto
  • T Nakazawa
  • O Nagata
Shimoto, T., Ashizawa, N., Matzumoto, K., Nakazawa, T., Nagata, O., 2005. Simultaneous treatment with citrate prevents nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor, in rats. Toxicolog. Sci. 87, 267. Stavric, B., Clayman, S., Grodd, R.E.A., Hebert, D., 1995. Some in vivo effects in the rat induced by chloprothixene and potassium oxonate. Pharmaco. Res. Commun. 7, 117–124.
Natural variation of chemical components of the leaf oil of Cinnamomum osmophloeum Kaneh
  • T W Hu
  • Y T Lin
  • C K Ho
Hu, T.W., Lin, Y.T., Ho, C.K., 1985. Natural variation of chemical components of the leaf oil of Cinnamomum osmophloeum Kaneh. Bulletin of Taiwan Forestry Research Industry New Series, p. 78.
Study on the anti-inflammatory activity of essential oil from leaves of Cinnamomum osmophloeum
  • L K Chao
  • K F Hua
  • H Y Hsu
  • S S Cheng
  • J Y Lin
  • S T Chang
Chao, L.K., Hua, K.F., Hsu, H.Y., Cheng, S.S., Lin, J.Y., Chang, S.T., 2005. Study on the anti-inflammatory activity of essential oil from leaves of Cinnamomum osmophloeum. J. Agric. Food Chem. 53, 7274-7278.
Antimite activity of essential oils and their components from Cinnamomum osmophloeum
  • P F Chen
  • S T Chang
  • H H Wu
Chen, P.F., Chang, S.T., Wu, H.H., 2002. Antimite activity of essential oils and their components from Cinnamomum osmophloeum. Q. J. Chin. For. 35, 397-404.
Chemical composition and mosquito larvicidal activity of essential oils from leaves of different Cinnamomum osmophloeum provenances
  • S S Cheng
  • J Y Lin
  • K H Tsai
  • W J Chen
  • S T Chang
Cheng, S.S., Lin, J.Y., Tsai, K.H., Chen, W.J., Chang, S.T., 2004. Chemical composition and mosquito larvicidal activity of essential oils from leaves of different Cinnamomum osmophloeum provenances. J. Agric. Food Chem. 52, 4395-4400.
Chemical polymorphism and antifungal activity of essential oils from leaves of different provenances of indigenous cinnamon (Cinnamomum osmophloeum)
  • S S Cheng
  • J Y Lin
  • Y R Hsui
  • S T Chang
Cheng, S.S., Lin, J.Y., Hsui, Y.R., Chang, S.T., 2006. Chemical polymorphism and antifungal activity of essential oils from leaves of different provenances of indigenous cinnamon (Cinnamomum osmophloeum). Bioresour. Technol. 97, 306-312.
Simultaneous treatment with citrate prevents nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor, in rats
  • T Shimoto
  • N Ashizawa
  • K Matzumoto
  • T Nakazawa
  • O Nagata
Shimoto, T., Ashizawa, N., Matzumoto, K., Nakazawa, T., Nagata, O., 2005. Simultaneous treatment with citrate prevents nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor, in rats. Toxicolog. Sci. 87, 267.
Some in vivo effects in the rat induced by chloprothixene and potassium oxonate
  • B Stavric
  • S Clayman
  • R E A Grodd
  • D Hebert
Stavric, B., Clayman, S., Grodd, R.E.A., Hebert, D., 1995. Some in vivo effects in the rat induced by chloprothixene and potassium oxonate. Pharmaco. Res. Commun. 7, 117-124.