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1.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 363-371, 2019.
Article in English | WPRIM | ID: wpr-776875

ABSTRACT

Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1β, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.

2.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 330-340, 2017.
Article in English | WPRIM | ID: wpr-812108

ABSTRACT

The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD), regulated renal mRNA and protein levels of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), OCT2, organic cation/carnitine transporter 1 (OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), and Caspase-1, resulting in the reduction of interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α (TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.


Subject(s)
Animals , Humans , Male , Mice , Anti-Inflammatory Agents , Dipterocarpaceae , Chemistry , Hyperuricemia , Blood , Drug Therapy , Allergy and Immunology , Interleukin-18 , Genetics , Allergy and Immunology , Interleukin-1beta , Genetics , Allergy and Immunology , Interleukin-6 , Genetics , Allergy and Immunology , Kidney , Allergy and Immunology , Organic Anion Transport Protein 1 , Genetics , Allergy and Immunology , Plant Extracts , Stilbenes , Tumor Necrosis Factor-alpha , Genetics , Allergy and Immunology , Uric Acid , Blood
3.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 499-507, 2016.
Article in English | WPRIM | ID: wpr-812597

ABSTRACT

The aim of the study was to investigate the effects of Siwu decoction on hyperuricemia, kidney inflammation, and dysfunction in hyperuricemic mice. Siwu decoction at 363.8, 727.5, and 1 455 mg·kg(-1) was orally administered to potassium oxonate-induced hyperuricemic mice for 7 days. Serum urate, creatinine, and blood urea nitrogen levels and hepatic xanthine oxidase (XOD) activity were measured. The protein levels of hepatic XOD and renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), ATP-binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), OCT2, organic cation/carnitine transporter 1 (OCTN1), OCNT2, Nod-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Caspase-1, and interleukin-1β (IL-1β) were determined by Western blotting. Renal histopathology change was obtained following hematoxylin-eosin staining. Our results indicated that Siwu decoction significantly reduced serum urate, creatinine and blood urea nitrogen levels and increased fractional excretion of uric acid in hyperuricemic mice. It effectively reduced hepatic XOD activity and protein levels in this animal model. Furthermore, Siwu decoction down-regulated URAT1 and GLUT9 protein levels, and up-regulated the protein levels of OAT1, ABCG2, OCT1, OCT2, OCTN1, and OCTN2 in the kidney of the hyperuricemic mice. Additionally, Siwu decoction remarkably reduced renal protein levels of NLRP3, ASC, Caspase-1, and IL-1β in the hyperuricemic mice. These results suggested that Siwu decoction exhibited anti-hyperuricemic and anti-inflammatory effects by inhibiting hepatic XOD activity, regulating renal organic ion transporter expression, and suppressing renal NLRP3 inflammasome activation, providing the evidence for its use in the treatment of hyperuricemia and associated kidney inflammation.


Subject(s)
Animals , Humans , Male , Mice , Blood Urea Nitrogen , Creatinine , Urine , Drugs, Chinese Herbal , Hyperuricemia , Drug Therapy , Allergy and Immunology , Urine , Interleukin-1beta , Genetics , Allergy and Immunology , Kidney , Allergy and Immunology , Liver , Organic Anion Transport Protein 1 , Genetics , Allergy and Immunology , Sulfuric Acids , Uric Acid , Urine
4.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 214-221, 2013.
Article in English | WPRIM | ID: wpr-812702

ABSTRACT

AIM@#The present study was undertaken to characterize the effects of Wuling San on urate excretion and renal function, and explore its possible mechanisms of action in hyperuricemic mice.@*METHODS@#Mice were administered with 250 mg·kg(-1) potassium oxonate by gavage once daily (10 animals/group) for seven consecutive days to develop a hyperuricemia model. Different doses of Wuling powder were orally initiated on the day 1 h after oxonate was given, separately. Allopurinol was used as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were measured in hyperuricemic mice treated with Wuling San and allopurinol. Simultaneously, renal mRNA and protein levels of urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1), as well as organic cation/carnitine transporters mOCT1, mOCT2 and mOCTN2, were assayed by semi-quantitative RT-PCR and Western blot methods, respectively.@*RESULTS AND CONCLUSION@#Compared to the hyperuricemia control group, Wuling San significantly reduced serum uric acid and creatinine levels, increased 24 h urate and creatinine excretion, and FEUA in hyperuricemic mice, exhibiting its ability to enhance urate excretion and improve kidney function. Wuling San was found to down-regulate mRNA and protein levels of mURAT1 and mGLUT9, as well as up-regulate mOAT1 in the kidney of hyperuricemic mice. Moreover, Wuling San up-regulated renal mRNA and protein levels of mOCT1, mOCT2 and mOCTN2, leading to kidney protection in this model.


Subject(s)
Animals , Humans , Male , Mice , Drugs, Chinese Herbal , Glucose Transport Proteins, Facilitative , Genetics , Metabolism , Hyperuricemia , Drug Therapy , Genetics , Metabolism , Kidney , Metabolism , Organic Anion Transport Protein 1 , Genetics , Metabolism , Organic Anion Transporters , Genetics , Metabolism , Up-Regulation , Uric Acid , Metabolism
5.
Acta Pharmaceutica Sinica ; (12): 1239-1246, 2010.
Article in Chinese | WPRIM | ID: wpr-354521

ABSTRACT

The effects of mangiferin on uric acid excretion, kidney function and related renal transporters were investigated in hyperuricemic mice induced by potassium oxonate. Mice were divided into normal control group, and 5 hyperuricemic groups with model control, 50, 100, and 200 mg x kg(-1) mangiferin, and 5 mg x kg(-1) allopurinol. Mice were administered by gavage once daily with 250 mg x kg(-1) potassium oxonate for seven consecutive days to create the model. And 3 doses of mangiferin were orally initiated on the day 1 h after potassium oxonate was given, separately. Serum uric acid, creatinine and urea nitrogon levels, as well as urinary uric acid creatinine levels were measured. Mouse uromodulin (mUMOD) levels in serum, urine and kidney were determined by ELISA method. The mRNA and protein levels of related renal transporters were assayed by RT-PCR and Western blotting methods, respectively. Compared to model group, mangiferin significantly reduced serum uric acid, creatinine and urea nitrogon levels, increased 24 h uric acid and creatinine excretion, and fractional excretion of uric acid in hyperuricemic mice, exhibiting uric acid excretion enhancement and kidney function improvement. Mangiferin was found to down-regulate mRNA and protein levels of urate transporter 1 (mURAT1) and glucose transporter 9 (mGLUT9), as well as up-regulate organic anion transporter 1 (mOAT1) in the kidney of hyperuricemic mice. These findings suggested that mangiferin might enhance uric acid excretion and in turn reduce serum uric acid level through the decrease of uric acid reabsorption and the increase of uric acid secretion in hyperuricemic mice. Moreover, mangiferin remarkably up-regulated expression levels of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2), increased urine mUMOD levels, as well as decreased serum and kidney mUMOD levels in hyperuricemic mice, which might be involved in mangiferin-mediated renal protective action.


Subject(s)
Animals , Male , Mice , Blood Urea Nitrogen , Carrier Proteins , Genetics , Metabolism , Creatinine , Blood , Glucose Transport Proteins, Facilitative , Genetics , Metabolism , Hyperuricemia , Blood , Urine , Kidney , Metabolism , Membrane Proteins , Genetics , Metabolism , Octamer Transcription Factor-1 , Genetics , Metabolism , Organic Anion Transport Protein 1 , Genetics , Metabolism , Organic Anion Transporters , Genetics , Metabolism , Organic Cation Transport Proteins , Genetics , Metabolism , Organic Cation Transporter 2 , Oxonic Acid , Protective Agents , Pharmacology , RNA, Messenger , Metabolism , Random Allocation , Solute Carrier Family 22 Member 5 , Uric Acid , Blood , Urine , Uromodulin , Blood , Urine , Xanthones , Pharmacology
6.
China Journal of Chinese Materia Medica ; (24): 2808-2812, 2008.
Article in Chinese | WPRIM | ID: wpr-324799

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of gamma linolenic acid (GLA) on atherogenesis in rats.</p><p><b>METHOD</b>Sixty healthy male rats were randomly divided into 6 groups: normal contro 1, fed by normal feed; atherogenesis mode 1, fed by high lipid diet; positive control group 0.9 mg x kg(-1) x d(-1) of lovastatin and group IV 250 mg x kg(-1) x d(-1) duoxikang; high dose of 375 mg x kg(-1) x d(-1) GLA; low dose of 187.5 mg x kg(-1) x d(-1) GLA. After the model group received atherogenic diet for six weeks, serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were detected by enzyme method to confirm the formation of atherogenic. After fed for another five weeks, morphologic atherosclerosis of aorta in rats was observed by HE staining methods. The blood samples were collected and serum TC, TG, HDL-C, LDL-C, T-AOC, HL, LPL, NO, NOS, MDA and GSH were determined.</p><p><b>RESULT</b>GLA attenuated the formation of atherosclerotic plaques, inhibited the level of serum TC, TG, MDA, OX-LDL, NO, NOS, HL, LPL and LDL-C and increased the level of T-AOC.</p><p><b>CONCLUSION</b>GLA might significantly attenuate the development of atherosclerosis in rats fed with high lipid diet through improving the antioxidation capacity of the body.</p>


Subject(s)
Animals , Male , Rats , Atherosclerosis , Blood , Drug Therapy , Metabolism , Cholesterol , Metabolism , Diet, Atherogenic , Lipids , Blood , Random Allocation , Rats, Sprague-Dawley , gamma-Linolenic Acid
7.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 76-79, 2006.
Article in Chinese | WPRIM | ID: wpr-234803

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of Tiaozhi Jiangtang Tablet (TJT) on insulin resistance (IR) in rats with diebetes mellitus type 2.</p><p><b>METHODS</b>The model rats of diebetes mellitus were induced by intraperitoneal injection of streptozotocin (30mg/kg) and feeding with high lipid forage. The rats in the TJT group were treated with TJT and those in the metformin group treated with metformin as positive controls. The glucose infusion rate (GIR) was detected by glucose clamp technique after treatment for 8 weeks. At the same time, fasting blood glucose ( FBG), fasting insulin ( FINS), free fatty acids ( FFA), total cholesterol ( TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were measured respectively, and insulin sensitivity index (ISI) and HDL-C/TC calculated. The changes of insulin sensitivity and lipid metabolism were evaluated.</p><p><b>RESULTS</b>TC, TG, HDL-C/TC, FINS, and FFA significantly reduced in the TJT group as compared with those in the control group, while ISI and GIR significantly increased, the effects of TJT were similar to those of metformin.</p><p><b>CONCLUSION</b>TJT is effective in increasing insulin sensitivity and improving glucose and lipid metabolisms in rats with diebetes mellitus type 2.</p>


Subject(s)
Animals , Rats , Blood Glucose , Cholesterol , Blood , Cholesterol, HDL , Blood , Diabetes Mellitus, Experimental , Blood , Drug Therapy , Diabetes Mellitus, Type 2 , Blood , Drug Therapy , Drugs, Chinese Herbal , Therapeutic Uses , Fatty Acids, Nonesterified , Blood , Hypoglycemic Agents , Therapeutic Uses , Insulin , Blood , Insulin Resistance , Tablets , Triglycerides , Blood
8.
China Journal of Chinese Materia Medica ; (24): 145-148, 2005.
Article in Chinese | WPRIM | ID: wpr-276626

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of processing Phellodendron anurene with salt on anti-gout.</p><p><b>METHOD</b>The mouse serum uric acid level and liver xanthine oxidase activity were used to evaluate anti-gout effects of raw and processing P. amurense with salt.</p><p><b>RESULT</b>Both raw and processing P. amurense with salt reduced serum uric acid levels in the in hyperuricemic mice, and inhibited activities of liver xanthine oxidase at the low and high doses respectively, thus exhibiting anti-gout effects. Moreover, they showed the tendency to decrease the uric acid levels in the normal animal only at the high dose. The latter was a little weaker than the former.</p><p><b>CONCLUSION</b>Processing with salt might not significantly change anti-gout effect of P. amurense.</p>


Subject(s)
Animals , Male , Mice , Drugs, Chinese Herbal , Pharmacology , Gout Suppressants , Pharmacology , Hot Temperature , Hyperuricemia , Blood , Liver , Phellodendron , Chemistry , Plants, Medicinal , Chemistry , Random Allocation , Sodium Chloride , Technology, Pharmaceutical , Methods , Uric Acid , Blood , Xanthine Oxidase , Metabolism
9.
China Journal of Chinese Materia Medica ; (24): 55-59, 2003.
Article in Chinese | WPRIM | ID: wpr-266818

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of Banxia Houpu Decoction on a chronic mild stress model of depression and investigate the antidepressive mechanism.</p><p><b>METHOD</b>With consumption of a 1% sucrose solution as an index, and by subjecting rats to a variety of mild stressors for a prolonged period of time, a chronic mild stress model was developed. The levels of the blood lipid were measured by blood lipid kits, the natural kill (NK) cell activity in the spleen was measured with the method of the enzyme lactate dehydrogenase (LDH) released, the superoxide dismutase (SOD) activity in red blood cell was assayed by the Autoxidation of Pyrogallol method, the NO synthase (NOS) activity in serum and tissue was measured by NOS kits, and the content of malondialdehyde(MDA) was measured by MDA kits.</p><p><b>RESULT</b>Banxia Houpu Decoction significantly increased the consumption of sucrose solution, increased the level of the high density lipoprotein (HDL-C), decreased the level of the Triglyceride(TG) in serum, enhanced the activity of the NK in spleen, decreased the activity of the SOD in red blood and the activity of the NOS in serum and tissue, and reduced the content of MDA in tissue by effect on lipid Peroxidation in CNS model of depression.</p><p><b>CONCLUSION</b>Banxia Houpu Decoction has antidepressant effect in different ways.</p>


Subject(s)
Animals , Male , Rats , Antidepressive Agents , Pharmacology , Depression , Allergy and Immunology , Metabolism , Drugs, Chinese Herbal , Pharmacology , Killer Cells, Natural , Allergy and Immunology , Malondialdehyde , Blood , Metabolism , Myocardium , Metabolism , Rats, Sprague-Dawley , Stress, Psychological , Sucrose , Metabolism , Superoxide Dismutase , Metabolism , Triglycerides , Blood
10.
China Journal of Chinese Materia Medica ; (24): 932-936, 2002.
Article in Chinese | WPRIM | ID: wpr-271836

ABSTRACT

<p><b>OBJECTIVE</b>To screen the antidepressant fractions of Banxia Houpu Decoction.</p><p><b>METHOD</b>Behavioral despair models in mice were used to evaluate antidepressant activities and the levels of monoamine neurotransmitters in regions of animal brains were determined with spectrophotofluoremetry method.</p><p><b>RESULT</b>The extract of Banxia Houpu Decoction (AE) and its four fractions were able to elicit time-dependent reducing of duration of immobility in the tail suspension test and the forced swimming test in mice. Among these test samples, AE, petrol fraction (AE-1) and water soluble fraction (AE-4) were more potent, but there was no significant difference between them. AE significantly increased 5-HT level in mice striatum and NE level in mice cortex, respectively, and did not affect any monoamine neurotransmitters in other regions of animal brain. AE-1 elevated 5-HT level in the striatum and the NE and DA level in the cortex, chloroform fraction (AE-2) only significantly increased DA level in cortex.</p><p><b>CONCLUSION</b>Banxia Houpu Decoction has antidepressant effect. The active parts are in AE-1 and AE-4. The antidepressant action of Banxia Houpu Decoction is probably by mediated in part through many monoamine neurotransmitter systems.</p>


Subject(s)
Animals , Male , Mice , Antidepressive Agents , Pharmacology , Behavior, Animal , Brain , Metabolism , Chloroform , Chemistry , Dopamine , Metabolism , Drugs, Chinese Herbal , Pharmacology , Ethanol , Chemistry , Magnolia , Chemistry , Mice, Inbred ICR , Pinellia , Chemistry , Plants, Medicinal , Chemistry , Serotonin , Metabolism
11.
China Journal of Chinese Materia Medica ; (24): 939-944, 2002.
Article in Chinese | WPRIM | ID: wpr-271834

ABSTRACT

<p><b>OBJECTIVE</b>To study hypouricemic effect of aqueous extract of Lysimachia christinae on hyperuricemia in mice.</p><p><b>METHOD</b>The uricase inhibitor potassium oxonate was used to induce hyperuricemia in mice, and serum uric acid level was determined with the phosphotungstic acid method.</p><p><b>RESULT</b>The aqueous extract of Lysimachia christinae, when administered orally to the oxonate-induced hyperuricemic mice at the doses of 5.2, 10.4 and 20.8 g.kg-1, was able to elicit dose-dependent hypouricemic effects. At these doses of the extract, the serum urate levels of the oxonate-pretreated mice showed no difference from the normal mice. In normal mice, however, oral administration of the extract at the same doses did not produce any observable hypouricemic effects.</p><p><b>CONCLUSION</b>The aqueous extract of Lysimachia christinae possesses potent hypuricemic effects on models of hyperuricemia in mice pretreated with oxonate.</p>


Subject(s)
Animals , Female , Mice , Drugs, Chinese Herbal , Pharmacology , Hyperuricemia , Blood , Plants, Medicinal , Chemistry , Primulaceae , Chemistry , Uric Acid , Blood
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