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1.
J Ethnopharmacol ; 289: 114518, 2022 May 10.
Article in English | MEDLINE | ID: mdl-34637968

ABSTRACT

AIM OF THE STUDY: The aim of this study was to test the anti-rheumatic effects of A. jaluense tubers in acute and chronic arthritis rats, and to assign its ingredients through UHPLC-TOF/MS. MATERIALS AND METHODS: Subcutaneous injection of carrageenan for acute arthritis and complete Freund's adjuvant (CFA) for chronic arthritis was carried out in the hind paw of SD rats. The paw volume was measured by a plethysmometer thermal hyperalgesia was tested using a thermal plantar tester, and mechanical hyperalgesia was evaluated by ankle flexion evoked vocalizations. The expression of c-Fos in the brain hippocampus was measured with the avidin-biotin-peroxidase technique. The ingredients were assigned by UHPLC-TOF/MS, chromatography was performed by UHPLC system with DAD detector and BEH C18 column, and spectroscopy was conducted by ESI-MS system. RESULTS AND DISCUSSION: The 80% ethanoic extract of A. jaluense tubers showed an acute anti-inflammatory effect by suppressing the edema volume in the hind paw of carrageenan-stimulated rats. In addition, A. jaluense tubers exerted an anti-rheumatic activity by reducing the secondary swelling volume from an immunological reaction in the left hind paw of CFA-induced chronic arthritis rats. Additionally, oral treatment with the 80% ethanoic extract -showed potent analgesic effects in the arthritis rats by recovering the paw withdrawal latency stimulated by the thermal hyperalgesia and by reducing the vocalization scores evoked by ankle flexion on both hind paws. Moreover, its treatment also indicated an anti-psychiatric effect by controlling the c-Fos protein expression of the brain hippocampus in CFA-stimulated arthritis rats. These results suggested that these therapeutic effects were exhibited by less toxic mono-esterified diterpenoid alkaloids (MDAs), and nontoxic non-esterified diterpenoid alkaloids (NDAs). CONCLUSION: A. jaluense tubers may act as viable therapeutic or preventive candidates for acute and chronic arthritis, particularly, for immune-inflammatory rheumatoid arthritis to suppress the pain and psychiatric condition.


Subject(s)
Aconitum/chemistry , Analgesics/pharmacology , Antirheumatic Agents/pharmacology , Plant Extracts/pharmacology , Analgesics/isolation & purification , Animals , Antirheumatic Agents/isolation & purification , Arthritis, Experimental/drug therapy , Disease Models, Animal , Freund's Adjuvant , Hyperalgesia/drug therapy , Male , Plant Roots , Rats , Rats, Sprague-Dawley
2.
Neurochem Res ; 43(2): 351-362, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29164430

ABSTRACT

Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3ß (GSK-3ß), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 µM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3ß signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.


Subject(s)
Cholinergic Antagonists/pharmacology , Cholinesterase Inhibitors/pharmacology , Cognitive Dysfunction/metabolism , Saponins/metabolism , Scopolamine/pharmacology , Animals , Avoidance Learning/drug effects , Cognition/drug effects , Cognitive Dysfunction/drug therapy , Disease Models, Animal , Glycogen Synthase Kinase 3 beta/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Long-Term Potentiation/drug effects , Male , Memory/drug effects , Memory Disorders/chemically induced , Mice
3.
J Ginseng Res ; 41(3): 233-239, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28701862

ABSTRACT

BACKGROUND: Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. METHODS: An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed Panax ginseng). Cytotoxicity was induced by treatment of 20µM cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination. RESULTS: The in vitro assay demonstrated that KG-KH (50 µg/mL) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, per os) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold). CONCLUSION: Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses.

4.
J Ethnopharmacol ; 190: 165-73, 2016 Aug 22.
Article in English | MEDLINE | ID: mdl-27267831

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata L. (Asteraceae) has been prescribed for whole body nourishment and nervine tonic in Asia. However, the effects of E. prostrata in learning and memory have not been fully explored. AIM OF THE STUDY: To scientifically elucidate the effects of E. prostrata on cognitive functions, we examined whether E. prostrata could ameliorate a cholinergic blockade-induced memory impairment, and we also investigated the effects of E. prostrata on the synaptic plasticity in the hippocampus. MATERIALS AND METHODS: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. The anti-amnesic effects of the ethanolic extract of Eclipta prostrata L. (EEEP) were measured in mice by the passive avoidance, Y-maze and Morris water maze tasks. To test the effects of EEEP on synaptic plasticity, we measured long-term potentiation (LTP) in the hippocampus. We also studied several signaling molecules related to learning and memory, such as phosphorylated protein kinase B (Akt) or phosphorylated glycogen synthase kinase-3ß (GSK-3ß). RESULTS: In the passive avoidance task, EEEP (50 or 100mg/kg, p.o.) significantly ameliorated the shortened step-through latency induced by scopolamine. EEEP (100mg/kg, p.o.) also showed significant increase in alternation behavior during the Y-maze task. In the Morris water maze task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by EEEP (50 or 100mg/kg, p.o.). Moreover, EEEP (100µg/ml) significantly enhanced hippocampal LTP without affecting basal synaptic transmission. The administration of EEEP (100mg/kg) increased the phosphorylation levels of Akt and GSK-3ß in the hippocampal region. CONCLUSION: These results suggest that EEEP has memory-ameliorating activity against scopolamine-induced cognitive impairment and facilitates LTP in the hippocampus. This could be, at least in part, mediated by the activation of the Akt-GSK-3ß signaling pathway.


Subject(s)
Amnesia/prevention & control , Behavior, Animal/drug effects , Cognition Disorders/prevention & control , Cognition/drug effects , Eclipta/chemistry , Ethanol/chemistry , Hippocampus/drug effects , Memory/drug effects , Nootropic Agents/pharmacology , Plant Extracts/pharmacology , Scopolamine , Solvents/chemistry , Amnesia/chemically induced , Amnesia/physiopathology , Amnesia/psychology , Animals , Cognition Disorders/chemically induced , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Disease Models, Animal , Dose-Response Relationship, Drug , Glycogen Synthase Kinase 3 beta/metabolism , Hippocampus/metabolism , Hippocampus/physiopathology , Long-Term Potentiation/drug effects , Male , Maze Learning/drug effects , Mice, Inbred ICR , Motor Activity/drug effects , Nootropic Agents/isolation & purification , Phosphorylation , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , Proto-Oncogene Proteins c-akt/metabolism , Reaction Time/drug effects , Signal Transduction/drug effects
5.
Biol Pharm Bull ; 38(9): 1415-9, 2015.
Article in English | MEDLINE | ID: mdl-26328499

ABSTRACT

Ginseng (Panax ginseng C.A. MEYER, Araliaceae), which contains protopanaxadiol-type and protopanaxatriol-type ginsenosides, has been used for inflammation, fatigue, stress, and tumor in Asian countries. Orally administered ginsenosides are metabolized to their aglycones 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) by gut microbiota. However, their anti-fatigue effects have not been studied thoroughly. Therefore, we investigated the anti-fatigue activities of PPD and PPT in mice, using the weight-loaded swimming (WLS) and the rota-rod tests. Ginseng water extract (GW), ginseng saponin fraction (GWS) and ginseng polysaccharide fraction (GWP) at concentrations of 50 and 100 mg/kg and PPD and PPT at 5 and 10 mg/kg were orally administered to mice once daily for 5 d. GW, GWS, and PPT significantly increased the WLS time, however, GWP and PPD did not cause any significant change. PPT induced the most significant increase in WLS time. PPD (10 mg/kg) and PPT (5 and 10 mg/kg) inhibited the WLS-induced increase in corticosterone, lactate, lactate dehydrogenase (LDH), and creatinine levels as well as the reduction in glucose level. PPT increased the riding time in the rota-rod test, and also inhibited corticosterone, lactate, and creatinine levels. These findings suggest that the anti-fatigue effect of ginseng may be attributable to its saponins, particularly PPT, rather than to its polysaccharides.


Subject(s)
Fatigue/drug therapy , Sapogenins/therapeutic use , Animals , Corticosterone/blood , Creatinine/blood , Fatigue/blood , Fatty Acids, Nonesterified/blood , Lactic Acid/blood , Male , Mice , Mice, Inbred ICR , Rotarod Performance Test , Sapogenins/pharmacology , Swimming
6.
Biol Pharm Bull ; 38(2): 331-5, 2015.
Article in English | MEDLINE | ID: mdl-25747994

ABSTRACT

Panax ginseng C.A. MEYER (Araliaceae), which contains ginsenosides as its main components, has been shown to have various biological effects, including anti-inflammatory, anxiolytic, anti-stress, and anti-tumor effects. Orally administered ginsenoside Rb1 and Re are metabolized to 20(S)-protopanaxadiol (PPD) and compound K via ginsenoside Rd and 20(S)-protopanaxatriol (PPT) and ginsenoside Rh1 via ginsenoside Rg1 by gut microbiota, respectively. Therefore, we investigated the anti-stress effects of these metabolites, PPD and PPT, by measuring their anxiolytic and anti-inflammatory effects in immobilized mice. Treatment with PPD and PPT prior to immobilization stress increased the time spent in open arms and open arm entries in the elevated plus-maze (EPM) test. The anxiolytic effects of PPD (10 mg/kg) and PPT (10 mg/kg) were comparable to that of buspirone (1 mg/kg). This observed anxiolytic effect of PPD was significantly blocked by flumazenil or bicuculline, and the effect of PPT was blocked by WAY-100635. Treatment with PPD also potently suppressed immobilization stress-induced serum levels of corticosterone and interleukin (IL)-6 by the enzyme-linked immunosorbent assay. However, PPT treatment did not suppress them. Based on these findings, PPD and PPT may exhibit the anxiolytic effect via γ-aminobutyrateA (GABAA) receptor(s) and serotonergic receptor(s), respectively, and PPD may have an anti-inflammatory effect that is more potent than that of PPT.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Sapogenins/therapeutic use , Stress, Psychological/drug therapy , Animals , Anti-Anxiety Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Bicuculline/pharmacology , Corticosterone/blood , Flumazenil/pharmacology , GABA Modulators/pharmacology , GABA-A Receptor Antagonists/pharmacology , Interleukin-6/blood , Male , Mice, Inbred ICR , Piperazines/pharmacology , Pyridines/pharmacology , Receptors, GABA-A/metabolism , Receptors, Serotonin/metabolism , Restraint, Physical , Sapogenins/pharmacology , Serotonin Antagonists/pharmacology , Stress, Psychological/blood
7.
J Ethnopharmacol ; 153(3): 928-32, 2014 May 14.
Article in English | MEDLINE | ID: mdl-24709311

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV, a major component extracted from the roots of Astragalus membranaceus (AM), possesses anti-inflammatory, anti-oxidative, anti-fibrotic, anti-infarction and immunoregulatory effects. To clarify anti-stress effect of AM, anxiolytic and anti-inflammatory effects of 80% ethanol extract of AM and astragaloside IV were investigated in immobilization stress model. MATERIALS AND METHODS: The mice were orally administered with AM (50, 200, and 500 mg/kg), astragaloside IV (5, 10, and 20 mg/kg) and buspirone, a positive drug, 1h before immobilization treated for 2h. For anxiolytic activity assay, EPM test was performed in mice. For anti-inflammatory activity assay, serum levels of corticosterone, IL-6 and TNF-α were measured using ELISA kits. RESULTS: AM extract and astragaloside IV increased dose-dependently time spent on open arms and open arm entries in the EPM test. Anxiolytic effects of AM extract (500 mg/kg) and astragaloside IV (20 mg/kg) were comparable to those of buspirone (1 mg/kg). Their anxiolytic effects were blocked by WAY-100635 (0.5 mg/kg, i.p.), a 5-HT1A receptor antagonist (p<0.01), but not by flumazenil (3 mg/kg, i.p.) and bicuculline (0.5 mg/kg, i.p.), GABAA receptor antagonists. AM extract and astragaloside IV also reduced serum levels of corticosterone, IL-6 and TNF-α dose-dependently. CONCLUSIONS: AM, particularly astragaloside IV, may ameliorate immobilized stress-induced anxiety and inflammation.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Phytotherapy , Saponins/therapeutic use , Stress, Psychological/drug therapy , Triterpenes/therapeutic use , Animals , Anti-Anxiety Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Behavior, Animal/drug effects , Corticosterone/blood , Interleukin-6/blood , Male , Mice, Inbred ICR , Restraint, Physical , Saponins/pharmacology , Stress, Psychological/blood , Triterpenes/pharmacology , Tumor Necrosis Factor-alpha/blood
8.
Int J Mol Med ; 32(1): 241-50, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23652775

ABSTRACT

In this study, Chrysanthemum zawadskii extract (CZE) was investigated to determine its effects on 2-deoxy-D-ribose (dRib)-induced oxidative damage and cellular dysfunction in the MC3T3-E1 mouse osteoblastic cell line. Osteoblastic cells were treated with the highly reducing sugar, dRib, in the presence or absence of CZE. Cell viability, apoptosis and reactive oxygen species (ROS) production were subsequently examined. It was observed that dRib reduced cell survival, while it markedly increased the intracellular levels of ROS and apoptosis. However, pre-treatment of the cells with CZE attenuated all the dRib-induced effects. The antioxidant, N-acetyl-L-cysteine (NAC), also prevented dRib-induced oxidative cell damage. In addition, treatment with CZE resulted in a significant increase in alkaline phosphatase (ALP) activity and collagen content, as well as in the expression of genes associated with osteoblast differentiation [ALP, collagen, osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OC) and bone morphogenetic protein (BMP)2, BMP4 and BMP7]. In mechanistic studies of the antioxidative potential of CZE, we found that CZE reversed the dRib-induced decrease in the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT)1 and AKT2 genes, which are master regulators of survival-related signaling pathways. CZE also upregulated the gene expression of the antioxidant enzymes, superoxide dismutase (SOD)2, SOD3 and glutathione peroxidase 4 (GPx4), which was inhibited by dRib. Taken together, these results suggest that CZE attenuates dRib-induced cell damage in osteoblastic cells and may be useful for the treatment of diabetes-associated bone disease.


Subject(s)
Antioxidants/pharmacology , Chrysanthemum/chemistry , Deoxyribose/toxicity , Osteoblasts/drug effects , Osteoblasts/metabolism , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Animals , Antioxidants/chemistry , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Survival/drug effects , Collagen/biosynthesis , Gene Expression Regulation/drug effects , Mice , Osteoblasts/cytology , Oxidation-Reduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism
9.
J Ginseng Res ; 37(1): 87-93, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23717161

ABSTRACT

To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin reduced serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase activities increased by adenine. Based on these findings, the ameliorating effect of SG on chronic renal failure may result from its saponin.

10.
J Ethnopharmacol ; 146(1): 294-9, 2013 Mar 07.
Article in English | MEDLINE | ID: mdl-23313392

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (family Araliaceae) is traditionally used as a remedy for cancer, inflammation, stress and aging. AIM OF STUDY: To explore whether ginsenosides Rg5 and Rh3, the main constituents of heat-processed ginseng (the root of Panax ginseng), could protect memory deficit. MATERIALS AND METHODS: We isolated ginsenosides Rh3 and Rg5 from heated-processed ginseng treated with and without human feces, respectively. Then we investigated their protective effects on memory impairment using the passive avoidance, Y-maze and Morris water maze tasks in mice. Memory deficit was induced in mice by the intraperitoneal injection of scopolamine. RESULTS: Ginsenosides Rg5 or Rh3 increased the latency time reduced by scopolamine in passive avoidance test. Treatment with ginsenoside Rg5 or Rh3 significantly reversed the lowered spontaneous alteration induced by scopolamine in Y-maze task. Ginsenoisde Rg5 or Rh3 (10 mg/kg) significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of training trial sessions in Morris water maze task. Furthermore, ginsenosides Rg5 and Rh3 inhibited acetylcholinesterase activity in a dose-dependent manner, with IC50 values of 18.4 and 10.2 µM, respectively. The inhibitory potency of ginsenoside Rh3 is comparable with that of donepezil (IC50=9.9 µM). These ginsenosides also reversed hippocampal brain-derived neurotrophic factor (BDNF) expression and cAMP response element-binding protein (CREB) phosphorylation reduced by scopolamine. Of them, ginsenoside Rh3 more potently protected memory deficit. CONCLUSIONS: Ginsenoside Rg5 and its metabolite ginsenoside Rh3 may protect memory deficit by inhibiting AChE activity and increasing BDNF expression and CREB activation.


Subject(s)
Ginsenosides/therapeutic use , Memory Disorders/drug therapy , Neuroprotective Agents/therapeutic use , Acetylcholinesterase/metabolism , Animals , Avoidance Learning/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Ginsenosides/pharmacology , Male , Maze Learning/drug effects , Memory Disorders/chemically induced , Memory Disorders/metabolism , Memory Disorders/physiopathology , Mice , Mice, Inbred ICR , Neuroprotective Agents/pharmacology , Scopolamine
11.
J Ginseng Res ; 36(3): 270-6, 2012 Jul.
Article in English | MEDLINE | ID: mdl-23717128

ABSTRACT

The effect of orally administered sun ginseng (SG), which is a ginseng processed by steaming, was examined in adenine-induced chronic renal failure rat. SG significantly decreased both blood urea nitrogen and serum creatinine levels, indicating an improvement of renal function. Also, SG significantly increased the urinary excretion of both urea and creatinine. Furthermore it lowered the blood pressure, and inhibited adenine-induced kidney hypertrophy and edema. Based on these findings, SG may ameliorate chronic renal failures.

12.
J Ginseng Res ; 35(3): 301-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-23717073

ABSTRACT

To evaluate the difference in expressing pharmacological effects of ginseng by intestinal microflora between Koreans, metabolic activities of ginseng, ginsenoside Rb1 and Rg1 by 100 fecal specimens were measured. The ß-glucosidase activity for p-nitrophenyl- ß-D-glucopyranoside was 0 to 0.42 µmol/min/mg and its average activity (mean±SD) was 0.10±0.07 µmol/min/mg. The metabolic activities of ginsenosides Rb1 and Rg1 were 0.01 to 0.42 and 0.01 to 0.38 pmol/min/mg, respectively. Their average activities were 0.25±0.08 and 0.15±0.09 pmol/min/mg, respectively. The compound K-forming activities from ginsenoside Rb1 and ginseng extract were 0 to 0.11 and 0 to 0.02 pmol/min/mg, respectively. Their average compound K-forming activities were 0.24±0.09 pmol/min/ mg and 2.14±3.66 fmol/min/mg, respectively. These activities all were not different between males and females, or between ages. Although compound K-forming activity from the aqueous extract of ginseng was low compared to that from ginenoside Rb1, their profiles were similar to those of isolated compounds. Based on these findings, we believe that the intestinal bacterial metabolic activities of ginseng components are variable in individuals and may be used as selection markers for responders to ginseng.

13.
J Ethnopharmacol ; 126(2): 258-64, 2009 Nov 12.
Article in English | MEDLINE | ID: mdl-19715749

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance (Zingiberaceae) is an annual plant. Its rhizome has long been used as an anti-inflammatory, an analgesic, a stomachic and a carminative in traditional medicine. OBJECTIVE: The aim of this study was to test the anti-inflammatory effects of Alpinia officinarum rhizomes on acute and chronic arthritis in SD rats. METHODS: Alpinia officinarum rhizomes were extracted by refluxing using 80% ethanol. The fractions were prepared by the fractionation of ethyl acetate (EtOAc), n-butanol, and water. This extract was administrated to rats by peroral injection. Acute arthritis was induced by a subcutaneous injection of carrageenan into the hind paw of SD rats. Chronic arthritis was stimulated by a subcutaneous injection of complete Freund's adjuvant (CFA) into the hind paw of SD rats. The paw volume was measured using a plethysmometer, thermal hyperalgesia was tested using a thermal plantar tester, hyperalgesia was evaluated by ankle flexion evoked vocalizations, and the expression of c-Fos in the brain hippocampus was measured with the avidin-biotin-peroxidase technique. Nitric oxide (NO) production was evaluated on nitrite by a Griess assay in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. RESULTS: An 80% ethanolic extract showed acute anti-inflammatory activity that it reduced the edema volume in carrageenan-stimulated arthritis and inhibited NO generation in LPS-induced RAW 264.7 cells. In addition, this extract showed chronic anti-rheumatic and analgesic activities by suppressing the swelling volume, by recovering the paw withdrawal latency, and by inhibiting the flexion scores in CFA-induced arthritis. Particularly, this medicine had potent meaningful effects on the second signal of the left hind paw in the form of an immunological reaction compared to its effects on the first signal in the right hind paw after the CFA treatment. This also shows an anti-psychiatric effect through control of the expression of the c-Fos protein of the brain hippocampus in CFA-stimulated arthritis. On the other hand, each fraction showed acute anti-inflammatory effects; the action of the EtOAc fraction may have resulted from the suppression of NO production. CONCLUSIONS: Alpinia officinarum rhizomes may be viable therapeutic or preventive candidates for the treatment of acute and chronic arthritis.


Subject(s)
Alpinia , Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Arthritis/drug therapy , Hippocampus/drug effects , Plant Extracts/therapeutic use , Proto-Oncogene Proteins c-fos/metabolism , Analgesics/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Arthritis/chemically induced , Carrageenan , Edema/drug therapy , Freund's Adjuvant , Hippocampus/metabolism , Macrophages/drug effects , Models, Animal , Nitric Oxide/antagonists & inhibitors , Phytotherapy , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Rhizome
14.
J Ethnopharmacol ; 125(3): 497-500, 2009 Sep 25.
Article in English | MEDLINE | ID: mdl-19505561

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia princeps Pampanini (family Asteraceae) is an herbal medicine widely used as a hepatoprotective, antioxidative, anti-inflammatory, and antibacterial agent in Korea, China, and Japan. AIM OF THE STUDY: This study aimed to elucidate the anti-inflammatory effect of the main constituents, eupatilin and jaceosidin, isolated from Artemisia princeps. MATERIALS AND METHODS: We used carrageenan-induced inflammation in an air pouch on the back of mice and carrageenan-induced hind paw edema in rats to determine the anti-inflammatory effects of eupatilin and jaceosidin. Inflammatory makers, such as expression of pro-inflammatory cytokines and cyclooxygenase (COX)-2, and activation of nuclear factor-kappa B (NF-kappaB), were measured by enzyme-linked immunosorbent assays and immunoblot analyses. RESULTS: Eupatilin and jaceosidin blocked carrageenan-induced increase in leukocyte number and protein levels in air pouch exudates. Eupatilin and jaceosidin inhibited COX-2 expression and NF-kappaB activation, and markedly reduced TNF-alpha, IL-1beta, and prostaglandin E2 (PGE(2)) levels. They also inhibited hind paw edema induced by carrageenan. Eupatilin and jaceosidin had similar activity. CONCLUSIONS: These findings suggest that eupatilin and jaceosidin may reduce inflammation by inhibiting NF-kappaB activation, and that Artemisia princeps inhibits inflammation because of these constituents.


Subject(s)
Artemisia/chemistry , Carrageenan/adverse effects , Flavonoids/pharmacology , Inflammation/drug therapy , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/genetics , Cytokines/metabolism , Flavonoids/isolation & purification , Inflammation/chemically induced , Male , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley
15.
Planta Med ; 75(8): 836-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19266429

ABSTRACT

The anxiolytic-like effects of red ginseng (RG, the steamed root of Panax ginseng, family Araliaceae), its saponin fraction, and its representative constituents, ginsenosides Rg3 and Rh2, were investigated in mice using the elevated plus-maze test. These agents significantly increased the time spent on the open arms and the number of open-arm entries. The anxiolytic-like activities of Rg3 and Rh2 were antagonized by flumazenil but not by WAY-100635. RG and its constituents, Rg3 and Rh2, may exert anxiolytic effects by antagonizing GABA/benzodiazepines.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Ginsenosides/therapeutic use , Panax/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Animals , Anti-Anxiety Agents/isolation & purification , Anti-Anxiety Agents/pharmacology , Behavior, Animal/drug effects , Buspirone/isolation & purification , Buspirone/pharmacology , Buspirone/therapeutic use , Flumazenil/pharmacology , Ginsenosides/isolation & purification , Ginsenosides/pharmacology , Male , Maze Learning/drug effects , Mice , Piperazines/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Roots , Pyridines/pharmacology , Saponins/isolation & purification , Saponins/pharmacology , Saponins/therapeutic use
16.
Biol Pharm Bull ; 32(1): 91-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19122287

ABSTRACT

In the present study, we investigated the effects of 3-oxoolean-12-en-27-oic acid (3-OA) isolated from the underground parts of Aceriphyllum rossii (Saxifragaceae) on the viability and apoptosis of HL-60 human promyelocytic leukemia cells, and the mechanisms underlying its action. 3-OA-treated HL-60 cells and HeLa human cervix adenocarcinoma cells displayed several apoptotic features, such as, DNA fragmentation, DNA laddering by agarose gel electrophoresis, and hypodiploid DNA contents by flow cytometry, and 3-OA also caused the activations of caspase-8, -9 and -3. Pretreatment with z-VAD-fmk (a broad-caspase inhibitor) almost completely suppressed 3-OA-induced DNA ladder formation and hypodiploid DNA contents, thereby implicating the caspase cascade in the apoptotic process. In addition, z-IETD-fmk (a caspase-8 inhibitor) and z-DEVD-fmk (a caspase-3 inhibitor) also completely neutralized the apoptotic effect of 3-OA in HL-60 cells. Furthermore, 3-OA increased Fas-related protein contents and the mRNA expressions of Fas ligand (FasL), Fas, and Fas-associated death domain (FADD). Preincubation with anti-Fas or anti-FasL blocking antibodies completely prevented 3-OA-induced apoptosis. Taken together, these results suggest that 3-oxoolean-12-en-27-oic acid induces apoptosis by activating caspase-8 via FasL-stimulated death receptor signaling.


Subject(s)
Apoptosis/drug effects , Caspase 8/metabolism , HL-60 Cells/drug effects , Saxifragaceae/chemistry , Triterpenes/pharmacology , Amino Acid Chloromethyl Ketones/pharmacology , Cell Line, Transformed , Dose-Response Relationship, Drug , Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Fas-Associated Death Domain Protein/genetics , Fas-Associated Death Domain Protein/metabolism , HL-60 Cells/metabolism , Humans , Neuroprotective Agents/pharmacology , RNA, Messenger/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Tetrazolium Salts , Thiazoles , Time Factors
17.
Phytother Res ; 22(6): 772-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18446841

ABSTRACT

An herbal mixture prepared with Cinnamomi Ramulus, Anemarrhenae Rhizoma and Alpiniae Officinari Rhizoma (CAA) is used in oriental medicine for treating several ailments. The purpose of this study was to determine the mechanisms by which CAA elicits an antiinflammatory effect on nitric oxide (NO) production in the mouse macrophage cell line RAW 264.7 cells. The results indicated that lipopolysaccharide (LPS)-induced NO production was inhibited by CAA in a dose-dependent manner. Western blotting and RT-PCR analysis demonstrated that CAA decreased LPS-induced inducible nitric oxide synthase (iNOS) protein and gene expression in RAW 264.7 cells. Furthermore, CAA inhibited the LPS-induced DNA binding activity of nuclear factor-kappa B (NF-kappaB) and this effect was mediated through inhibiting the degradation of inhibitory factor-kappaBalpha (IkappaBalpha). Therefore, the results demonstrate that CAA inhibits LPS-induced production of NO and expression of iNOS by blocking NF-kappaB activation. CAA might be a potential therapeutic candidate for treating inflammatory diseases such as arthritis.


Subject(s)
Macrophages/drug effects , NF-kappa B/metabolism , Nitric Oxide/metabolism , Plant Extracts/pharmacology , Animals , Asparagaceae/chemistry , Blotting, Western , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Lauraceae/chemistry , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/metabolism , Mice , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , Protein Binding/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Zingiberaceae/chemistry
18.
J Microbiol Biotechnol ; 17(9): 1554-7, 2007 Sep.
Article in English | MEDLINE | ID: mdl-18062237

ABSTRACT

Artemisia princeps Pampanini (AP) was fermented with Bifidobacterium infantis K-525 and its antiasthmic effect investigated. AP and fermented AP (FAP) reduced the IgE level in the blood of ovalbumin-induced asthmic mice. Moreover, FAP reduced the IgE, proinflammatory cytokine IL-6, and IL-4 levels in the trachea, as well as in the lung of the experimental asthmic mice, whereas AP only reduced the IgE and IL-6 levels in the lungs. Nonetheless, AP and FAP both inhibited the mRNA expression of IL-6 and TNF-alpha in IgE-induced RBL-2H3 cells. The in vivo antiasthmic effect of FAP was more potent than that of AP. Therefore, these findings suggest that the enhanced antiasthmic effect of AP after bifidus fermentation was possibly due to the regulation of the proinflammatory cytokine biosynthesis of IL-6 and TNF-alpha.


Subject(s)
Anti-Allergic Agents/pharmacology , Artemisia/chemistry , Asthma/drug therapy , Bifidobacterium/metabolism , Lung/drug effects , Animals , Anti-Allergic Agents/immunology , Anti-Allergic Agents/therapeutic use , Artemisia/metabolism , Fermentation , Hypersensitivity/prevention & control , Immunoglobulin E , Interleukin-4 , Interleukin-6 , Lung/immunology , Lung/metabolism , Mice , Mice, Inbred BALB C , Models, Animal , Ovalbumin/blood , Ovalbumin/immunology , Plant Extracts/pharmacology , Pruritus/chemically induced , Pruritus/drug therapy , RNA, Messenger/genetics , RNA, Messenger/metabolism
19.
Arch Pharm Res ; 29(9): 752-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-17024848

ABSTRACT

Artemisia princeps Pampanini, which is called Ssajuarissuk in Korean (SS-1), was fermented with lactic acid bacteria (LAB) and their passive cutaneous anaphylaxis reaction-inhibitory activity was investigated. Of these fermented agents, SS-1 extract fermented with Bifidobacterium infantis K-525 (F-SS-1) most effectively inhibited the release of P-hexosamindase from RBL-2H3 cells induced IgE. In IgE-induced RBL-2H3 cells, F-SS-1 inhibited proinflammatory cytokines IL-6 and TNF-alpha mRNA expression. Oral administration of SS-1 and F-SS-1 to mice inhibited passive cutaneous anaphylaxis (PCA) reaction induced by IgE and scratching behaviors induced by compound 48/80. The inhibitory activity of F-SS-1 against scratching behaviors was more effective than that of SS-1. These findings suggest that the fermentation of SS-1 with LAB can increase its antiallergic activity.


Subject(s)
Anti-Allergic Agents/pharmacology , Artemisia/chemistry , Bacteria/metabolism , Lactic Acid/metabolism , Animals , Cell Line , Feces/microbiology , Female , Fermentation , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred ICR , Passive Cutaneous Anaphylaxis , Plant Extracts/pharmacology , Pruritus/chemically induced , Pruritus/drug therapy , Reverse Transcriptase Polymerase Chain Reaction , beta-N-Acetylhexosaminidases/metabolism , p-Methoxy-N-methylphenethylamine/adverse effects
20.
Biol Pharm Bull ; 29(7): 1408-13, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16819179

ABSTRACT

Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Betula platyphylla var. japonica on inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP expression and activity in rabbit articular cartilage explants. Interleukin-1alpha (IL-1alpha) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Betula platyphylla var. japonica significantly inhibited GAG and collagen release in a concentration-dependent manner. Betula platyphylla var. japonica dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1alpha-treated cartilage explant culture when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Betula platyphylla var. japonica had no harmful effect on chondrocyte viability or cartilage morphology in cartilage explants. Histological analysis indicated that Betula platyphylla var. japonica reduced the degradation of the cartilage matrix compared with that of IL-1alpha-treated cartilage explants. These results indicate that Betula platyphylla var. japonica inhibits the degradation of proteoglycan and collagen through the down regulation of MMP-3 and MMP-13 expression and activities without affecting the viability or morphology of IL-1alpha-stimulated rabbit articular cartilage explants.


Subject(s)
Betula , Cartilage, Articular/metabolism , Collagen Type II/genetics , Matrix Metalloproteinases/genetics , Plant Extracts/pharmacology , Proteoglycans/metabolism , Animals , Cartilage, Articular/cytology , Cartilage, Articular/drug effects , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Kinetics , L-Lactate Dehydrogenase/analysis , Organ Culture Techniques , Rabbits , Reverse Transcriptase Polymerase Chain Reaction
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