Footnote 9

Research article summary (published 29 Jun 2006):

Effects of volatile constituents of rosemary extract on lung inflammation induced by diesel exhaust particles.

Epidemiological and experimental studies have implicated that diesel exhaust particles are involved in increases in morbidity and mortality from lung diseases.

Recently, we have demonstrated that rosmarinic acid, a polyphenolic liquid component in perilla, inhibits lung inflammation induced by diesel exhaust particles in vivo, partly through its antioxidative property. We have also shown the antioxidative activities of volatile constituents of rosemary extract, the gaseous component in perilla, in vitro.

The purpose this study evaluate effects on induced icr mice were treated administration volatile before intratracheal to twenty-four hr later exposure elicited characterized infiltration neutrophils eosinophils which was confirmed by cellular profile bronchoalveolar lavage fluid histological examination particles enhanced protein expressions interleukin-1beta in pretreatment with significantly inhibited particles-induced inflammation rosemary extract treatment also suppressed the diesel exhaust particles-enhanced lung expression of inflammatory protein-1alpha macrophage protein-1 and keratinocyte chemoattractant.

These results suggest that intratracheal administration of rosemary extract can prevent lung inflammation induced by diesel exhaust particles.

The preventive effect is mediated, at least partly, through the inhibition of the enhanced lung expressions of macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractants.

Author information

Inoue, Ken-ichiro (K); Takano, Hirohisa (H); Shiga, Akira (A); Fujita, Yoji (Y); Makino, Hiroaki (H); Yanagisawa, Rie (R); Kato, Yoji (Y); Yoshikawa, Toshikazu (T); Affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan. inoue.kenichirou(-atsign-)nies.go.jp

Journal and publication information

Publication Type: Journal Article

Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol), published in Denmark. (Language: eng)

Reference: 2006-Jul; vol 99 (issue 1) : pp 52-7

Dates: Created 2006/07/26; Completed 2006/12/08;

PMID: 16867171, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 10

Effects of Perilla Seed Oil Supplementation on Leukotriene Generation by Leucocytes in Patients with Asthma Associated with Lipometabolism.


Background: Dietary sources of a-linolenic acid, such as perilla seed oil, may have the capacity to inhibit the generation of leukotrienes (LTs) by leucocytes in patients with asthma, as has been reported with the consumption of other long-chain n-3fatty acids. Methods: The factors affecting the supression of leukotriene(LT) C4 generation by leucocytes were examined by comparing the clinical features of patients with asthma who had been given dietary perilla seed oil (n-3 fatty acids). Group A consisted of patients in whom the leucocyte generation of LTC4 was supressed by dietary perilla seed oil. Group B consisted of those in whom LTC4 generation was not supressed. Results: LTC4 generation by leucocytes decreased significantly in group A after 2(p<0.05) and 4 weeks(p<0.05); conversely, it increased significantly in group B after 4 weeks(p0.05). The two study groups differed significantly in terms of LTC4 generation by leucocytes after 4 weeks of dietary supplementation(p<0.05).

Ventilatory parameters such as peak expiratory flow (PEF), forced vital capacity (FVC) and forced expirtory volume in 1 s(FEV1) increased significantly after 4 weeks of dietary supplementation in group A(p<0.05). Values of PEF, FVC, FEV1 and maximum expiratory flow at 25% of the forced vital capacity(v25) differed significantly between groups A and B prior to dietary supplementation. Serum levels of total cholesterol, low-density lipoprotein(LDL) cholesterol and phospholipid were significantly decreased by dietary supplementation in group A after 4 weeks. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL cholesterol and phospholipid differed significantly between the two study groups prior to dietary supplementation. Serum levels of triglyceride and LDL cholesterol differed significantly between the two study groups after 4 weeks of dietary supplementation.

Conclusion: Dietary supplementation with perilla seed oil in selected patients with asthmasuppresses the generation of LTC4 and is associated with clinical features such as respiratory function and lipometabolism.

Authors: Makoto Okamoto, Fumihiro Mitsunobu, Kozo Ashida, Takash Mifune, Yasuhiro Hosaki, Hirofumi Tsugeno, Seishi Harada, Yoshiro Tanizaki, Mkikio Kataoka, Kenji Niiya, Mine Harada. Affiliation: Department of Medicine, Misasa Medical Branch, Okayama University Medical School, 827, Yamada, Misasa, Tottori 682-0192 (Japan)

Published: International Archives of Allergy and Immunology. Vol. 122, No.2, 2000 Research article summary (published 30 Dec 2006): Copyright ©2000 S. Karger AG,Basel

Footnote 11

Research article summary (published 30 Dec 2006):
Anti-asthmatic effects of Perilla seed oil in the guinea pig in vitro and in vivo.

Full Abstract

The aim of this study was to investigate the anti-asthmatic effects of Perilla seed oil in vitro and in vivo in sensitized guinea pigs. Aerosolized antigen caused an immediate bronchoconstriction. Perilla seed oil per os inhibited the increase in lung resistance and the decrease in dynamic lung compliance in a dose-dependent manner with an ED50 (95 % confidence interval, CI) of 1.10 (0.98 - 1.24) g/kg and 1.07 (0.94 - 1.22) g/kg, respectively. Infiltration of leukocytes, mononuclear cells, eosinophils and neutrophils induced by inhaling antigen was also inhibited by Perilla seed oil in a dose-dependent manner with an ED50 (95 % CI) of 1.00 (0.86 - 1.15), 1.24 (1.10 - 1.38), 0.63 (0.51 - 0.77) and 0.61 (0.38 - 0.98) g/kg, respectively. Perilla seed oil (5 - 500 microg/mL) inhibited the slow reaction substance of anaphylaxis (SRS-A) release induced by antigen challenge in lung tissue of sensitized guinea pigs. It also inhibited calcium ionophore (A(23187))-induced leukotriene (LT) D4 release from the lung tissue of non-sensitized guinea pigs in a concentration-dependent manner with an IC50 (95 % CI) of 50 (36 - 69) microg/mL. These results indicate that Perilla seed oil may improve lung function in asthma by controlling eicosanoid production and suppressing LT generation.

Author information

Author/s: Deng, Yang-mei (YM); Xie, Qiang-min (QM); Zhang, Shui-juan (SJ); Yao, Hong-yi (HY); Zhang, Hui (H);

Affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration, Medical Science College of Zhejiang University, People's Republic of China.

Journal and publication information Publication Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't

Journal: Planta medica (Planta Med), published in Germany. (Language: eng)
Reference: 2007-Jan; vol 73 (issue 1) : pp 53-8
Dates: Created 2007/02/21; Completed 2007/03/13;
PMID: 17315310, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 12

Research article summary (published 30 Aug 2005):
Rosmarinic acid inhibits the formation of reactive oxygen and nitrogen species in RAW264.7 macrophages.
Full Abstract

Antioxidant action of Rosmarinic acid (Ros A), a natural phenolic ingredient in many Lamiaceae herbs such as Perilla frutescens, sage, basil and mint, was analyzed in relation to the Ikappa-B activation in RAW264.7 macrophages. Ros A inhibited nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein synthesis induced by lipopolysaccharide (LPS), and also effectively suppressed phorbol 12-myristate 13-acetate (PMA)-induced superoxide production in RAW264.7 macrophages in a dose-dependent manner. Peroxynitrite-induced formation of 3-nitrotyrosine in bovine serum albumin and RAW264.7 macrophages were also inhibited by Ros A. Moreover, Western blot analysis demonstrated that LPS-induced phosphorylation of Ikappa-Balpha was abolished by Ros A. Ros A can act as an effective protector against peroxynitrite-mediated damage, and as a potent inhibitor of superoxide and NO synthesis; the inhibition of the formation of reactive oxygen and nitrogen species are partly based on its ability to inhibit the serine phosphorylation of Ikappa-Balpha.
Author information
Author/s: Qiao, Shanlou (S); Li, Weihua (W); Tsubouchi, Ryoko (R); Haneda, Miyako (M); Murakami, Keiko (K); Takeuchi, Fumio (F); Nisimoto, Yukio (Y); Yoshino, Masataka (M);
Affiliation: Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. qiaosl (-atsign-)aichi-med-u.ac.jp

Journal and publication information

Publication Type: Journal Article
Journal: Free radical research (Free Radic Res), published in England. (Language: eng)
Reference: 2005-Sep; vol 39 (issue 9) : pp 995-1003
Dates: Created 2005/08/09; Completed 2006/09/06; Revised 2006/11/15;
PMID: 16087481, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 13

Research article summary (published 31 May 2007):

Dietary lipids impacts on healthy ageing.
Full Abstract

Healthy ageing is gaining attention in the lipid nutrition field. As in vivo biomarkers of healthy ageing, we have evaluated the survival, learning/memory performance, and physical potencies in rodents fed a diet supplemented with high-linoleic acid (LNA, omega6) safflower oil or high-alpha-linolenic acid (ALA, omega3) perilla oil for long periods. The results suggested that perilla oil with a low omega6/omega3 ratio is beneficial for healthy ageing. In order to address this issue further, we determined the survival of stroke-prone SHR (SHRSP) rats fed a conventional rodent diet supplemented with 10% fat or oil. Survival was longer with omega3-rich oils compared with omega6-rich oils. However, some kinds of vegetable oils and hydrogenated oils shortened the survival of SHRSP rats to an unusual degree (ca. 40% compared with that of omega6-rich oil) that could not be accounted for by the fatty acid and phytosterol composition of the oils. The observed decrease in platelet counts was associated with pathological changes in the kidney and other organs. Dihydro-vitamin K1 is proposed as a likely candidate as a stroke-stimulating factor in hydrogenated oils. Thus, factors other than fatty acids (omega6/omega3 balance) and phytosterols must be taken into account when fats and oils are evaluated in relation to healthy ageing.

Author information
Author/s: Okuyama, Harumi (H); Yamada, Kazuyo (K); Miyazawa, Daisuke (D); Yasui, Yuko (Y); Ohara, Naoki (N);
Affiliation: Laboratory of Preventive Nutraceutical Sciences, Kinjo Gakuin University College of Pharmacy, 2-1723 Omori, Moriyamaku, Nagoya, 463-8521, Japan. okuyamah(-atsign-)kinjo-u.ac.jp
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Review
Journal: Lipids (Lipids), published in United States. (Language: eng)
Reference: 2007-Sep; vol 42 (issue 9) : pp 821-5
Dates: Created 2007/10/22; Completed 2008/02/06;
PMID: 17546469, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 14

Research article summary (published 29 Nov 2007):

Herbal medicines for the treatment of allergic rhinitis: a systematic review.

Full Abstract

OBJECTIVE: To evaluate the efficacy of herbal medicines for the treatment of allergic rhinitis (AR). DATA SOURCES: Five electronic databases until November 8, 2005; bibliographies of located articles; manufacturers of commercially available preparations; and experts in the field. Study Selection: We only included double-blind randomized clinical trials (RCTs), which tested a herbal medicine against placebo or active comparator, in patients with AR, and evaluated clinically relevant outcomes. Study selection, data extraction, and evaluation of methodological quality were performed independently by 2 reviewers. Discrepancies were resolved by discussion and by seeking the opinion of the third reviewer. Meta-analysis was only performed if data were considered suitable for pooling. RESULTS: Sixteen eligible RCTs, testing 10 different herbal products against placebo or active comparator, were included. Six RCTs studied Petasites hybridus (butterbur) extract for AR and suggest that P hybridus is superior to placebo or similarly effective compared with nonsedative antihistamines for intermittent AR. Two RCTs studied an Indian herbal combination, Aller-7, in patients with AR and reported positive results. Single RCTs were identified for 8 other herbal products as treatments for AR, reporting positive outcomes, except for grape seed extract. The median methodological quality score was 4 of a possible maximum of 5. CONCLUSIONS: There is encouraging evidence suggesting that P hybridus may be an effective herbal treatment for seasonal (intermittent) AR. However, independent replication is required before a firm conclusion can be drawn because of the financial support from the manufacturer of P hybridus extract to the 3 large trials. There are also promising results generated for other herbal products, particularly Aller-7, Tinospora cordifolia, Perilla frutescens, and several Chinese herbal medicines. Although these results are confined to the paucity of data and the small sample size, confirmation in larger and more rigorously designed clinical trials is warranted.

Author information
Author/s: Guo, Ruoling (R); Pittler, Max H (MH); Ernst, Edzard (E);
Affiliation: Department of Complementary Medicine, Peninsula Medical School, University of Exeter, England. ruoling.guo(- atsign-)pms.ac.uk
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't;
Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol), published in United States. (Language: eng)
Reference: 2007-Dec; vol 99 (issue 6) : pp 483-95
Dates: Created 2008/01/28; Completed 2008/02/19;
PMID: 18219828, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine

Footnote 15

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. Exp Biol Med (Maywood). 2004 Mar;229(3):247-54. Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical,suppresses allergic immunoglobulin responses and inflammation caused by polymorphonuclear leukocytes (PMNL) in mice. However, few placebo-controlled clinical trials have examined the efficacy and safety of polyphenolic phytochemicals for treatment of allergic inflammatory diseases in humans. The present study determined whether oral supplementation with rosmarinic acid is an effective intervention for patients with seasonal allergic rhinoconjunctivitis (SAR). In this 21-day, randomized, double-blind, age-matched, placebo-controlled parallel group study, patients with mild SAR were treated daily with extract of Perilla frutescens enriched for rosmarinic acid (200 mg [n=10] or 50 mg [n=9]) or placebo (n=10). Patients recorded symptoms daily in a diary. Profiles of infiltrating cells and concentrations of eotaxin, IL-1beta, IL-8, and histamine were measured in nasal lavage fluid. Serum IgE concentrations and routine blood tests were also examined. As compared with placebo supplementation, supplementation with extract of Perilla frutescens enriched for rosmarinic acid resulted in a significant increase in responder rates for itchy nose, watery eyes, itchy eyes, and total symptoms (P<0.05). Active treatment significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid (P<0.05 vs. placebo). Patients reported no adverse events, and no significant abnormalities were detected in routine blood tests. In conclusion, extract of Perilla frutescens enriched for rosmarinic acid can be an effective intervention for mild SAR at least partly through inhibition of PMNL infiltration into the nostrils. Use of this alternative treatment for SAR might reduce treatment costs for allergic diseases.

Footnote 16

1: Planta Med. 2005 May;71(5):406-11.
Mechanisms of relaxant action of luteolin in isolated guinea pig trachea.
Ko WC, Shih CM, Leu IJ, Chen TT, Chang JP.
Graduate Institute of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC. wc_ko@tmu.edu.tw

We have investigated the mechanisms of action of luteolin, a flavone found in Perilla frutescens, a Chinese herbal medicine for treating asthma. In fact, luteolin occurs mostly as a glycoside in many plant species. The tension changes of tracheal segments were isometrically recorded on a polygraph. Luteolin concentration-dependently relaxed histamine (30 microM)-, carbachol (0.2 microM)- and KCl (30 mM)-induced precontractions, and inhibited cumulative histamine- and carbachol- induced contractions in a non-competitive manner. Luteolin also concentration-dependently and non-competitively inhibited cumulative Ca2+-induced contractions in depolarized (K+, 60 mM) guinea-pig trachealis. The nifedipine (10 microM)- remaining tension of histamine (30 microM)-induced precontractions was further relaxed by luteolin, suggesting that no matter whether VDCCs were blocked or not, luteolin may have other mechanisms of relaxant action. The relaxant effect of luteolin was unaffected by the removal of epithelium or by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM), glibenclamide (10 microM), Nomega-nitro-L-arginine (20 microM), or alpha- chymotrypsin (1 U/mL). However, luteolin (10-20 microM) produced parallel and leftward shifts of the concentration-response curve of forskolin or nitroprusside. Luteolin or IBMX at various concentrations (10-300 microM) concentration-dependently and significantly inhibited cAMP- and cGMP-PDE activities of the trachealis. The IC50 values of luteolin were estimated to be 32.4 and 34.6 microM, respectively. IBMX at various concentrations (10-300 microM) selectively inhibited neither cAMP-, nor cGMP-PDE activity. In contrast to IBMX, luteolin at 100 and 300 microM more potently (P < 0.05) inhibited cGMP-, than cAMP-PDE activity. The above results indicate that the mechanisms of relaxant action of luteolin may be due to its inhibitory effects on both PDE activities and its reduction on [Ca2+]i of the trachealis.

Footnote 17

1: Immunopharmacol Immunotoxicol. 2000 Aug;22(3):489-500. Links
Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Perilla frutescens.
Shin TY, Kim SH, Kim SH, Kim YK, Park HJ, Chae BS, Jung HJ, Kim HM.
College of Pharmacy, Woosuk University, Chonju, Chonbuk, South Korea.

We investigated the effect of aqueous extract of Perilla frutescens (Labiatae) (PFAE) on the mast cell-mediated immediate- type allergic reactions. PFAE (0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in rats. PFAE (0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. When pfae was pretreated at same concentrations with systemic allergic reaction test the plasma histamine levels were reduced in a dose-dependent manner PFAE (10(-3) to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When PFAE (1 mg/ml) was added, transiently and significantly increased about 4-fold compared with that of basal cells. Moreover, PFAE (0.001 and 0.01 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results indicate that PFAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Footnote 18

1: Medicina (Kaunas). 2008;44(9):699-705.(pdf) Links
Effect of Perilla frutescens aqueous extract on free radical production by human neutrophil leukocytes.
Zekonis G, Zekonis J, Sadzeviciene R, Simoniene G, Kevelaitis E.
Department of Dental and Maxillofacial Orthopedics, Kaunas University of Medicine, Kaunas, Lithuania. zekonisg@hotmail.com

OBJECTIVE: The present study was intended to evaluate the antioxidant properties of aqueous extract of the Perilla frutescens (L.) Britton. MATERIAL AND METHODS: The antioxidant properties of Perilla frutescens were analyzed employing neutrophil leukocytes stimulated by the nonopsonized Escherichia coli. The neutrophil leukocytes were affected by adding an aqueous extract of Perilla. The generation of the reactive oxygen species by neutrophil leukocytes was investigated using assessment of luminol- and lucigenin-dependent chemiluminescence. RESULTS: We found out that the treatment of neutrophil leukocytes with the Perilla aqueous extract inhibited the release of reactive oxygen species, measured as luminol- and lucigenin-dependent chemiluminescence, by about 30% and more than 90%, respectively. CONCLUSION: The results of this study show that the aqueous extract of the Perilla frutescens inhibits significantly free radical production by neutrophil leukocytes, which was especially obvious when the lucigenin-dependent chemiluminescence assessment method was applied.


Footnote 19

Immune modulatory effects of Prunella vulgaris L.
Int J Mol Med. 2005 Mar;15(3):491-6.

Prunella vulgaris has a wide array of biological effects exhibiting numerous therapeutic potentials. Its anti-microbial effects including anti-viral and anti-bacterial effects are, presently, receiving increasing attention. While its anti-viral effects are attributed mainly to the inhibition of virus replication, the biological mechanisms of its anti-bacterial effects or actions remain unknown. In view of the fact that polysaccharides isolated from medicinal herbs often function as biological response modifier of body immunity, we hypothesized that the anti-microbial effect of polysaccharides isolated from Prunella vulgaris is probably also mediated via immune modulation. We have isolated four polysaccharides containing fractions from Prunella vulgaris, one of the fractions, PV2, could markedly stimulate the production of superoxide and nitrite representing nitric oxide from murine macrophage RAW264.7 and brain macrophage BV2 cells. The amount of nitrite and superoxide produced after PV2 stimulation was as high as that seen in stimulation using bacterial endotoxin lipopolysaccharide (LPS), and this stimulatory response is dose- dependent. In addition to monocyte/macrophage, PV2 also stimulated the proliferation of splenocytes. In this study, we have shown that the polysaccharides isolated from Prunella vulgaris have marked immune stimulatory effects, which may bring about the anti-microbial effects of Prunella vulgaris.

Footnote 20

Biological activities of Prunella vulgaris extract.

Phytother Res. 2003 Nov;17(9):1082-7.

The organic fraction (OF; 25.7% w/w of rosmarinic acid) of Prunella vulgaris (total extract) was found to exhibit the following: scavenging activity on diphenylpicrylhydrazyl radical (DPPH), inhibition of in vitro human LDL Cu(II)-mediated oxidation, protection of rat mitochondria and rat hepatocytes exposed to either tert-butyl hydroperoxide, or to Cu(II) and Fe(III) ions. OF also showed a potential to inhibit rat erythrocyte haemolysis and it reduced the production of LTB(4) in bovine PMNL generated by the 5-lipoxygenase pathway. Other observations included antiproliferative effects against HaCaT cells and mouse epidermal fibroblasts and a moderate OF antimicrobial activity on gram-positive bacteria. Rosmarinic, caffeic and 3- (3,4-dihydroxyphenyl)lactic acids exhibited less potent activity than the plant extract in all bioassays. The antioxidative, antimicrobial, together with antiviral effects offer good prospects for the medicinal applications of Prunella vulgaris. Inhibition of immediate-type allergic reactions by Prunella vulgaris in a murine model.

Footnote 21

Shin TY, Kim YK, Kim HM
College of Pharmacy, Woosuk Univ., Chonju, Chonbuk, S. Korea
Immunopharmacol Immunotoxicol. 2001 Aug;23(3):423-35.

We studied the effect of aqueous extract of Prunella vulgaris (Labiatae) on immediate-type allergic reactions. Prunella vulgaris (0.005 to 1 g/kg) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/ 80 in rats. When Prunella vulgaris was given as pretreatment, at concentrations ranging from 0.005 to 1 g/kg, the serum histamine levels induced by compound 48/ 80 were reduced in a dose-dependent manner. Prunella vulgaris (0.001 to 1 g/kg) inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. Prunella vulgaris also inhibited the histamine release induced by compound 48/80 or anti-DNP IgE from the rat peritoneal mast cells (RPMC). The level of cyclic AMP in RPMC, when Prunella vulgaris was added, significantly increased, compared with that of normal control. Moreover, Prunella vulgaris (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-alpha production from RPMC. These results indicate that Prunella vulgaris inhibits immediate-type allergic reactions in rats.

Footnote 22

Prunella vulgaris extract and rosmarinic acid suppress lipopolysaccharide-induced alteration in human gingival fibroblasts.

Full Abstract

Periodontitis is a chronic disease associated with inflammation of the tooth-supporting tissues. The inflammation is initiated by a group of gram-negative anaerobic bacteria. These express a number of irritating factors including a lipopolysaccharide (LPS), which plays a key role in periodontal disease development. Plant extracts with anti-inflammatory and anti-microbial properties have been shown to inhibit bacterial plaque formation and thus prevent chronic gingivitis. In this study we tested effects of Prunella vulgaris L. extract (PVE; 5, 10, 25microg/ml) and its component rosmarinic acid (RA; 1microg/ml) on LPS- induced oxidative damage and inflammation in human gingival fibroblasts. PVE and RA reduced reactive oxygen species (ROS) production, intracellular glutathione (GSH) depletion as well as lipid peroxidation in LPS-treated cells. Treatment with PVE and RA also inhibited LPS-induced up-regulation of interleukin 1beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and suppressed expression of inducible nitric oxide synthase (iNOS). The results indicate that PVE and RA are able to suppress LPS-induced biological changes in gingival fibroblasts. The effects of PVE and RA are presumably linked to their anti-inflammatory activities and thus use of PVE and RA may be relevant in modulating the inflammation process, including periodontal disease.
Author information
Author/s: Zdarilová, A (A); Svobodová, A (A); Simánek, V (V); Ulrichová, J (J);
Affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Hnevotínská 3, Palacký University, 775 15 Olomouc, Czech Republic.

Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro), published in England. (Language: eng)
Reference: 2009-Apr; vol 23 (issue 3) : pp 386-92
Dates: Created 2009/03/02; Completed 2009/06/11;
PMID: 19159670, status: MEDLINE (last retrieval date: 6/11/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 23

Immunostimulatory activity of aqueous extract isolated from Prunella vulgaris.

Full Abstract

Prunella vulgaris (P. vulgaris) has been used as a traditional medicine in the clinical treatment of herpetic keratitis and for its antioxidative and antimicrobial activities. In this study, we examined the immunostimulatory and antitumor activity of P. vulgaris in murine macrophage RAW 264.7 cells. Thus, we investigated the effects of an aqueous extract of P. vulgaris (PVAE) on macrophage function. We found that PVAE stimulated macrophage phagocytic activity, nitric oxide (NO) production and cytostatic activity. In addition, PVAE induced gene expression and production of macrophage-related cytokines such as TNF -alpha, IL-1beta and IL-6. Transient transfection revealed that NF-kappaB mediated the PVAE-induced increases in macrophage-related cytokine expression levels. Mitogen-activated protein kinases (MAP Kinase) were also significantly activated by the PVAE-induced NF-kappaB activation. Pretreatment with NF-kappaB inhibitor and MAP Kinase inhibitors inhibited the NO production and the phagocytic activity induced by PVAE. This demonstrates that PVAE stimulates macrophage activation via NF-kappaB transactivation and MAP kinase activation.

Author information

Author/s: Han, Eun Hee (EH); Choi, Jae Ho (JH); Hwang, Yong Pil (YP); Park, Hye Jin (HJ); Choi, Chul Yung (CY); Chung, Young Chul (YC); Seo, Jong Kwon (JK); Jeong, Hye Gwang (HG);

Affiliation: BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol), published in England. (Language: eng)

Reference: 2009-Jan; vol 47 (issue 1) : pp 62-9

Dates: Created 2009/01/12; Completed 2009/03/16;

PMID: 18983886, status: MEDLINE (last retrieval date: 3/16/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 24

Inhibition of lentivirus replication by aqueous extracts of Prunella vulgaris.

Full Abstract

BACKGROUND: Various members of the mint family have been used historically in Chinese and Native American medicine. Many of these same family members, including Prunella vulgaris, have been reported to have anti-viral activities. To further characterize the anti-lentiviral activities of P. vulgaris, water and ethanol extractions were tested for their ability to inhibit equine infectious anemia virus (EIAV) replication. RESULTS: Aqueous extracts contained more anti-viral activity than did ethanol extracts, displaying potent anti-lentiviral activity against virus in cell lines as well as in primary cell cultures with little to no cellular cytotoxicity. Time-of-addition studies demonstrated that the extracts were effective when added during the first four h of the viral life cycle, suggesting that the botanical constituents were targeting the virion itself or early entry events. Further analysis revealed that the extracts did not destroy EIAV virion integrity, but prevented viral particles from binding to the surface of permissive cells. Modest levels of anti-EIAV activity were also detected when the cells were treated with the extracts prior to infection, indicating that anti-EIAV botanical constituents could interact with both viral particles and permissive cells to interfere with infectivity. Size fractionation of the extract demonstrated that eight of the nine fractions generated from aqueous extracts displayed anti-viral activity. Separation of ethanol soluble and insoluble compounds in the eight active fractions revealed that ethanol-soluble constituents were responsible for the anti-viral activity in one fraction whereas ethanol-insoluble constituents were important for the anti-viral activity in two of the other fractions. In three of the five fractions that lost activity upon sub- fractionation, anti-viral activity was restored upon reconstitution of the fractions, indicating that synergistic anti-viral activity is present in several of the fractions. CONCLUSION: Our findings indicate that multiple Prunella constituents have profound anti-viral activity against EIAV, providing additional evidence of the broad anti-viral abilities of these extracts. The ability of the aqueous extracts to prevent entry of viral particles into permissive cells suggests that these extracts may function as promising microbicides against lentiviruses.

Author information

Author/s: Brindley, Melinda A (MA); Widrlechner, Mark P (MP); McCoy, Joe-Ann (JA); Murphy, Patricia (P); Hauck, Cathy (C); Rizshsky, Ludmila (L); Nikolau, Basil (B); Maury, Wendy (W);

Affiliation: Dept Microbiology, University of Iowa, Iowa City, IA 52242, USA. melinda.brindley(-atsign-)gmail.com

Grants: 9P50AT004155-06 (Agency:NCCAM NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Virology journal (Virol J), published in England. (Language: eng)

Reference: 2009-; vol 6 (issue ) : pp 8

Dates: Created 2009/02/20; Completed 2009/03/10;

PMID: 19154592, status: MEDLINE (last retrieval date: 3/10/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 25

Experimental Biology and Medicine 232:921-926 (2007)

© 2007 Society for Experimental Biology and Medicine


Effects of Prunella vulgaris on Mast Cell–Mediated Allergic Reaction and Inflammatory Cytokine Production

Sang-Yong Kim*, Sang-Hyun Kim,1, Hye-Young Shin, Jong-Pil Lim, Byeong-Suk Chae, Jeong-Suk Park, Seong-Gyun Hong, Myung-Soo Kim*, Dong-Gwang Jo*, Won-Hwan Park|| and Tae-Yong Shin,1

* Division of Specimen and Genetic Resources, Korea National Arboretum, Pocheon, Gyeonggi 487-821, South Korea; BK21, Department of Pharmacology, Kyungpook National University Medical School, Daegu 700-422, South Korea; College of Pharmacy, Woosuk University, Jeonju, Jeonbuk 565-701, South Korea; Department of Oriental Alternative Medicine, Nambu University, Gwangju, 506-824, South Korea; and || Cardiovascular Medical Research Center and Department of AM -Pointology & Diagnostics, Dongguk University, Kyung-Ju, Kyungpook 780-140, South Korea

To whom requests for reprints should be addressed at 1 Department of Pharmacology, Kyungpook National University Medical School, Daegu 700-422, South Korea. E-mail: shkim72@knu.ac.kr and College of Pharmacy, Woosuk University, Jeonju 565-701, South Korea. E-mail: tyshin@woosuk.ac.kr

In this study, we investigated the effect of aqueous extract of Prunella vulgaris (Labiatae; PVAE) on the mast cell–mediated allergy model. We found that PVAE (0.001–0.1 g/kg) dose dependently inhibited compound 48/80–induced systemic anaphylaxis and serum histamine release in mice. PVAE decreased the IgE-mediated local allergic reaction, passive cutaneous anaphylaxis. In addition, PVAE attenuated phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-, IL-6, and IL-8 secretion in human mast cells. The inhibitory effect of PVAE on proinflammatory cytokines was nuclear factor-B (NF-B) dependent. PVAE suppressed PMA and A23187-induced NF-B/DNA binding activity and NF-B–dependent gene reporter assay. Our findings provide evidence that PVAE inhibits mast cell–derived immediate- type allergic reactions and involvement of proinflammatory cytokines and NF-B in these effects.

Key Words: Prunella vulgaris • anaphylaxis • inflammatory cytokine • nuclear factor-B • mast cells


Footnote 27

1: J Ethnopharmacol. 2007 May 30;112(1):49-54. Epub 2007 Feb 23. Links

The anti-inflammatory effects of Pyrolae herba extract through the inhibition of the expression of inducible nitric oxide synthase (iNOS) and NO production.

Lee MH, Lee JM, Jun SH, Lee SH, Kim NW, Lee JH, Ko NY, Mun SH, Kim BK, Lim BO, Choi DK, Choi WS. Life Science R&D Center, Sinil

Pharmaceutical Co., Ltd., Chungju 380-862, Republic of Korea.

The extract of Pyrolae herba (PH), which has been used as an anti-inflammatory folk remedy in Korea and China, was investigated for its anti-inflammatory action using arachidonic acid, 12-O-tetradecanoylphorbol 13-acetate or carrageenan- induced edema assays. The anti-nociceptive activity of PH was also tested in mice using the acetic acid-induced writhing model. PH showed dose-dependent and significant (P<0.05 at 100-400mg/kg) anti-inflammatory and anti-nociceptive activities in the animal assays. The mechanism of the activities of PH was examined by testing the extract to determine if it inhibits the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) from the murine macrophages, RAW 264.7 cells. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by PH in a dose-dependent manner. PH also inhibited the activating phosphorylation of p38 MAP kinase and NF-kappaB in these cells.
These results provide a scientific basis to explain the effects of PH as an anti- inflammatory folk remedy in Asian countries.

Footnote 28

1: Eksp Klin Farmakol. 1998 Nov-Dec;61(6):58-61. Links

[The chemico-pharmacological patterns in the action of plants from the family of Pyrolaceae]

[Article in Russian]Briukhanov VM, Zverev IaF, Sanarov EM, Penzina TN.Department of Pharmacology, Altai Medical University, Barnaul, Russia.

The effect of leaf decoctions of three plants of the Pyrolaceae family, namely, umbrella wintergreen, one-side ortilia, and round-leaf Pyrola was studied in rat experiments. All plants under study were found to contain approximately equal amounts of tannins and arbutin glycoside. Their concentration was comparable though rather lower than in common bearberry, a well- known plant with diuretic and antiseptic activity. When given for a long time, all Pyrolaceae increased urination and sodium excretion. Besides, their decoctions caused an antimicrobial effect. Only round-leaf Pyrola weakened the development of experimental inflammation. Its anti-inflammatory effect was probably due the presence of flavonoids the content of which in Pyrola was maximum.

Footnote 29

1: Ann Otol Rhinol Laryngol. 1995 May;104(5):374-80. Links

Effects of compound injection of Pyrola rotundifolia L and Astragalus membranaceus Bge on experimental guinea pigs' gentamicin ototoxicity.

Xuan W, Dong M, Dong M.

Department of Otolaryngology, Guangxi Traditional Chinese Medical College, Nanning, People's Republic of China.

In attempting to find drugs effective in preventing and remedying ototoxic injury caused by aminoglycoside antibiotics, we relied on the theory that the induction of ototoxic injury by aminoglycoside antibiotics is related to a decrease of cyclic adenosine monophosphate and RNA content in the cochlea or a dysfunction of the kidney. We selected Pyrola rotundifolia L and Astragalus membranaceus Bge from traditional Chinese herbal medicine, made a compound injection of them, and observed the effect on the pattern of gentamicin ototoxicity in guinea pigs. By electrocochleography and morphology by scanning electron microscopy, the experimental results indicated that the Chinese herbal compound possessed the definite effect of protecting the guinea pig cochlea. The determination of blood urea nitrogen, urinary N-acetyl-D-aminoglucosidase, and urinary protein and observation of renal morphology showed that it also protected the kidney against nephrotoxic nephritis of gentamicin. The conjecture that protection of the kidney by the Chinese herbs may be one of the important factors in preventing ototoxicity supports some explanations of ototoxic mechanisms induced by aminoglycoside antibiotics.


Footnote 30

Research article summary (published 29 Jun 2008):

Immunomodulatory effect of Schizonepeta tenuifolia water extract on mouse Th1/Th2 cytokine production in-vivo and in- vitro.

Full Abstract

Schizonepeta tenuifolia (ST) is a major herbal constituent included in treatments for the common cold with fever, ostitis media and other skin inflammations. The present study investigated the effect of ST water extract on the pattern of cytokine production from activated T cells in-vivo and in-vitro. When ST (200 mgkg(-1)) was given orally to mice for 7 days before i.v. injection of anti-CD3 antibody, it significantly decreased mRNA levels of interleukin (IL)-4, interferon (IFN)-gamma and T-bet. Our flow cytometric analysis showed that ST administration significantly increased CD69 expression but showed little effect on the subsets of T cells. When we cultured mouse CD4 T cells under Th1/Th2 differentiation in the presence of ST, the suppressive activity of ST on IFN-gamma involved T-bet, but the downregulation of IL-4 occurred independently of the Th2 transcription factors GATA binding protein 3 (GATA-3) and c-Maf. However, it increased IL-2 secretion during Th1/Th2 differentiation. Our study demonstrates that ST regulates inflammatory responses by reducing the release of Th1 and Th2 cytokines from T cells and prevents unprimed CD4 T cells from differentiating into Th1 and Th2 cells.

Author information

Author/s: Kang, Hee (H); Oh, Yoo-Joung (YJ); Choi, Ho-Young (HY); Ham, In-Hye (IH); Bae, Hyun-Su (HS); Kim, Sung- Hoon (SH); Ahn, Kyoo-Seok (KS);

Affiliation: Department of Pathology, College of Oriental Medicine, KyungHee University, Seoul, 130-710, South Korea. shehee(-atsign-)khu.ac.kr

Journal and publication information

Publication Type: Journal Article

Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol), published in England. (Language: eng)

Reference: 2008-Jul; vol 60 (issue 7) : pp 901-7

Dates: Created 2008/06/13; Completed 2008/10/28; Revised 2008/11/21;

PMID: 18549677, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine.

Footnote 31

1: Immunopharmacol Immunotoxicol. 1999 Nov;21(4):705-15. Links

Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats.

Shin TY, Jeong HJ, Jun SM, Chae HJ, Kim HR, Baek SH, Kim HM. College of Pharmacy, Woosuk University, Wanju, Chonbuk, South Korea.

We investigated the effect of an aqueous extract of Schizonepeta tenuifolia (STAE) on mast cell-mediated immediate-type hypersensitivity. STAE inhibited systemic allergic reaction induced by compound 48/80 in rats dose-dependently. STAE also inhibited plasma histamine levels induced by compound 48/80. STAE inhibited local allergic reaction activated by anti- dinitrophenyl (DNP) IgE. In addition, STAE does-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. However, STAE had a significant enhancing effect on anti-DNP IgE- induced tumor necrosis factor-alpha (TNF-alpha) production from RPMC. These results indicate that STAE inhibits immediate-type hypersensitivity and suggest that STAE can selectively activate the TNF-alpha production from RPMC.

Footnote 32

1: Zhongguo Zhong Yao Za Zhi. 2007 Sep;32(17):1777-9. Links

[Effects of volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root on proinflammatory cytokine expression and regulation]

[Article in Chinese]

Ge WH, Guo JY, Shen YJ, Chen ML, Shi SL, Han YH, Lin J.

Zhejiang Chinese Medical University, Hangzhou 310053, China. geweihong@sina.com

OBJECTIVE: To study the effects of volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root (OSS) on proinflammatory cytokine expression and regulation in rats. METHOD: OA and LPS were injected intravenously to rats to develop acute lung injury (ALI). The rats were treated with OSS (45.19 microL kg(-1)). The pathological sections of lung tissue were prepared and observed in acute lung injury rats. The expression of nuclear factor- kappa B p65 (NF-kappaB p65), intercellar adhesion molecule CD54, and NF-kappaB p65 mRNA were determined in lung cells. RESULT: volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root significantly inhibited the expression of CD54, the activation of NF-kappaB p65, and the transcription of NF-kappaB p65 mRNA. CONCLUSION: OSS can reduce the expression of CD54 and NF-kappaB p65 protein synthesis, which may be its anti- inflammatory molecular mechanisms.

Footnote 33

1: Am J Chin Med. 2008;36(6):1145-58. Links

Anti-inflammatory activity of Schizonepeta tenuifolia through the inhibition of MAPK phosphorylation in mouse peritoneal macrophages.

Kim SJ, Kim JS, Choi IY, Kim DH, Kim MC, An HJ, Na HJ, Kim NH, Moon PD, Myung NY, Lee JY, Jeong HJ, Um JY, Shin TY, Kim HM, Hong SH. College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 570-749,

Republic of Korea.

Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti- inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In this study, we demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. The maximal inhibition rate of TNF-alpha and IL-6 production by ST (2 mg/ml) was 48.01 +/- 2.8% and 56.45 +/- 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE(2) and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.


Footnote 34

Research article summary (published 24 May 2006):

Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla.

Full Abstract

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of hooks with stem of Uncaria rhynchophylla using the elevated plus maze (EPM) and the hole-board apparatus in rats and mice. Control rats were treated with an equal volume of saline, and positive control rats with buspirone (1 mg/kg). Single or repeated treatments of the aqueous extract of Uncaria rhynchophylla (200 mg/kg/day, p.o.) for 7 days significantly increased the time-spent and entries into open arms of the EPM, and reduced the time-spent and entries into the closed arms versus saline controls (P<0.05). However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus saline controls. In the hole-board test, repeated treatment with the aqueous extract of Uncaria rhynchophylla (100 or 200 mg/kg/day, p.o.) significantly increased the number of head-dips (P<0.05). In addition, the anxiolytic-like effects of Uncaria rhynchophylla extract as assessed using the EPM test were abolished by WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor antagonist. These results suggest that Uncaria rhynchophylla is an effective anxiolytic agent, and acts via the serotonergic nervous system.

Author information

Author/s: Jung, Ji Wook (JW); Ahn, Nam Yoon (NY); Oh, Hye Rim (HR); Lee, Bo Kyung (BK); Lee, Kang Jin (KJ); Kim, Sun Yeou (SY); Cheong, Jae Hoon (JH); Ryu, Jong Hoon (JH);

Affiliation: Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoeki-dong, Dongdeamoon-ku, Seoul 130-701, Republic of Korea.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of ethnopharmacology (J Ethnopharmacol), published in Ireland. (Language: eng)

Reference: 2006-Nov; vol 108 (issue 2) : pp 193-7

Dates: Created 2006/10/30; Completed 2007/04/24;

PMID: 16829000, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 35

Research article summary (published 30 Jul 2006):

Uncaria rhynchophylla, a Chinese medicinal herb, has potent antiaggregation effects on Alzheimer's beta-amyloid proteins.

Full Abstract

Because the deposition of beta-amyloid protein (Abeta) is a consistent pathological hallmark of Alzheimer's disease (AD) brains, inhibition of Abeta generation, prevention of Abeta fibril formation, or destabilization of preformed Abeta fibrils would be attractive therapeutic strategies for the treatment of AD. We examined the effects of several medicinal herbs used in traditional Chinese medical formulae on the formation and destabilization of Abeta fibrils by using the thioflavin T binding assay, atomic force microscopic imaging, and electrophoresis. Our study demonstrates that several of these herbs have potent inhibitory effects on fibril formation of both Abeta(1-40) and Abeta(1-42) in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited Abeta aggregation most intensively. Significant destabilization of preformed Abeta(1-40) and Abeta(1 -42) fibrils was also induced by Uncaria rhynchophylla as well as some other herb extracts. Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective. Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.

Author information

Author/s: Fujiwara, Hironori (H); Iwasaki, Koh (K); Furukawa, Katsutoshi (K); Seki, Takashi (T); He, Mei (M); Maruyama, Masahiro (M); Tomita, Naoki (N); Kudo, Yukitsuka (Y); Higuchi, Makoto (M); Saido, Takaomi C (TC); Maeda, Sumihiro (S); Takashima, Akihiko (A); Hara, Masahiko (M); Ohizumi, Yasushi (Y); Arai, Hiroyuki (H); Affiliation: Department of Geriatric and Complementary Medicine, Center for Asian Traditional Medicine Research, Tohoku University School of Medicine, Sendai, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neuroscience research (J Neurosci Res), published in United States. (Language: eng)

Reference: 2006-Aug; vol 84 (issue 2) : pp 427-33

Dates: Created 2006/08/14; Completed 2006/09/19; Revised 2006/11/15;

PMID: 16676329, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine.

Footnote 36

1: J Pharmacol Sci. 2003 May;92(1):70-3. Links
Protective effect of methanol extract of Uncaria rhynchophylla against excitotoxicity induced by N-methyl-D-aspartate in rat hippocampus.

Lee J, Son D, Lee P, Kim DK, Shin MC, Jang MH, Kim CJ, Kim YS, Kim SY, Kim H.
Department of Herbal Pharmacology, Graduate School of East-West Medical Science, Kyung Hee University, Seoul, Korea.

Uncaria rhynchophylla is a medicinal herb used for convulsive disorders in Oriental medicine. In this study, the effect of the methanol extract of Uncaria rhynchophylla against N-methyl-D-aspartate (NMDA)-induced excitotoxicity was investigated. Pretreatment with the extract of Uncaria rhynchopylla reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. In the patch clamp study, Uncaria rhynchophylla significantly inhibited NMDA receptor- activated ion current in acutely dissociated hippocampal CA1 neurons. These results indicate that Uncaria rhynchophylla offers protection against NMDA-induced neuronal injury and inhibitory action on NMDA receptor-mediated ion current may be a mechanism behind the neuroprotective effect of Uncaria rhynchophylla.

Footnote 37

1: Acta Pharmacol Sin. 2003 Feb;24(2):97-101. Links

Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline.

Shi JS, Yu JX, Chen XP, Xu RX.

Department of Pharmacology, Zunyi Medical College, 563003, China. jsshi@zmc.gz.cn

Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophyllineextracted from Uncaria rhynchophylla Miq Jacks were reviewed. The alkaloids mainly act on cardiovascular system and central nervous system including the hypotension, brachycardia, antiarrhythmia, and protection of cerebral ischemia and sedation. The active mechanisms were related to blocking of calcium channel, opening of potassium channel, and regulating of nerve transmitters transport and metabolism, et

Footnote 38

: Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):232-8. Epub 2003 Dec 11. Links

In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel).

Zhang WB, Chen CX, Sim SM, Kwan CY. Department of Medicine, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada.

Rhynchophylline (Rhy) and isorhynchophylline (Isorhy), indole alkaloids from Uncaria hooks, reportedly exert hypotensive and vasodilatory effects, but the mechanism of action is unclear. We therefore investigated the relaxant effects of these two isomeric alkaloids in rat arteries in vitro, in particular in respect of the various functional Ca2+ pathways. Both Rhy and Isorhy relaxed aortic rings precontracted with phenylephrine (PE, 1 microM) in a dose-dependent manner (3-300 microM). Removal of endothelium and preincubation with L-NAME (300 microM) slightly inhibited but did not prevent the relaxant response. These results indicate that Rhy and Isorhy act largely in an endothelium-independent manner. Unlike nicardipine, both alkaloids not only inhibited the contraction induced by 60 mM KCl (IC50 20-30 microM), but also that induced by PE and U46619, albeit to a lesser extent (IC50 100 and 200 microM, respectively). These results suggest that Rhy and Isorhy may act via multiple Ca2+ pathways. In contrast to their inhibitory effects on KCl-induced and receptor-mediated contractions, where both isomers were comparably potent, Rhy was more potent than Isorhy at higher concentrations (>100 microM) in inhibiting both caffeine (25 mM)- and cyclopiazonic acid (CPA, 30 microM)-induced contractions. Similar results observed with caffeine in Ca2+-containing medium were also observed in Ca2+-free medium. However, 0.1-0.3 microM nicardipine (which completely inhibited KCl-induced contraction) had no significant inhibitory effect on CPA-induced contractions. Taken together, these results indicate discrimination between these two isomers with respect to Ca2+-induced Ca2+ release and non-L-type Ca2+ channel, but not for IP3-induced Ca2+ release and L-type Ca2+ channels. Similar relaxant responses to KCl- and caffeine-induced contractions were seen when these two alkaloids were tested on the smaller mesenteric and renal arteries. In conclusion, the vasodilatory effects of Rhy and Isorhy are largely endothelium independent and are mediated by L-type Ca2+ channels. At higher concentrations, they also affect other Ca2+-handling pathways, although to a lesser extent. While there is no discrimination between the two isomers with respect to the contraction induced by KCl or agonists (PE and U46619), differential effects between Rhy and Isorhy were seen on caffeine- and CPA-induced contractions.