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[The influence of common perilla (Perilla frutescens (L.) Britton) on non-specific cell-mediated immunity--phagocytosis activity].

OBJECTIVE: To examine the effect of plant preparations, obtained from Perilla frutescens (L.) Britton introduced in Lithuania, on non-specific cell-mediated immunity. MATERIALS AND METHODS: Non-specific cellular immunity was estimated by phagocytosis activity. The study of phagocytosis activity in peripheral rabbits blood (ability of leukocytes to phagocyte polystyrene latex parts of 0.8 microm diameter) was performed before (control) and after the experiments (injecting or administering per os perilla leaves extracts for one week and four weeks, respectively). The extracts were prepared from the leaves of perilla using repercolation method. For the studies in vitro the extract containing 1 mg/ml of perilla was used. In the studies in vitro two preparations of Perilla frutescens were used: 1) 32% sterile aqueous solution derivable from extract of perilla leaves and 2) 38% ethanol extract of perilla leaves. RESULTS. The phagocytosis activity studies in vitro showed that after 30 minutes of incubation with Perilla frutescens (L.) Britton extract phagocytosis activity was stimulated from 39+/-1.2 to 61+/-2.2% (p<0.001). Phagocytosis index increased from 1.26 to 1.79. The experiments in vivo showed that injected perilla leaves preparation to rabbits (1.2 mg/kg) increased phagocytic activity compared to the control (32.17+/-2.13%). The largest increase of phagocytosis activity was detected after seven days - 40.67+/-4.68%. Phagocytic activity of neutrophils in peripheral blood of rabbits increased after oral administration of perilla leaves extracts already after one week, but the largest increase of phagocytic activity was detected after four weeks (62.00+/-2.76%). CONCLUSIONS: Perilla frutescens (L.) Britton contains natural substances that increase the activity of phagocytes in vivo and in vitro and stimulate phagocytosis.

Administration, Oral↗

Identification of rosmarinic acid as a novel antidepressive substance in the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba).

The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are found in some traditional oriental herbal medicines that are primarily used to treat affective disorders such as depression and anxiety. The aim of the present study was to identify the bioactive component in Perillae Herba that possesses antidepressive activity. The effects of a water extract of Perillae Herba and six fractions therefrom were evaluated in mice by use of the forced-swimming test. An oral administration of a water extract of Perillae Herba significantly reduced the duration of immobility. Moreover, 50% methanol extract of the water extract of Perillae Herba and its 30% methanol extract also reduced the duration of immobility. Three-dimensional high-performance liquid chromatography and FAB-MS and NMR spectral analysis clearly showed that the extracts with anti-immobility effects contained abundant rosmarinic acid. The oral and intraperitoneal administration of rosmarinic acid significantly reduced the duration of immobility. In contrast, a water extract from another species of Perillae Herba, which contains only low levels of rosmarinic acid, had no anti-immobility effect. These results suggest that rosmarinic acid may be the main component involved in the antidepressive effect of Perillae Herba in the forced-swimming test. Thus it may be a novel antidepressive substance.

Animals↗

[Common perilla (Perilla frutescens (L.) Britton.) as a perspective immunomodulator].

Common perilla (Perilla frutescens (L.) Britton) is a new perspective annual medicinal dead-nettle family (Lamiaceae Lindl.) plant in Lithuania. Its medicinal raw material and preparations produced of it are characterised by the variety of pharmacological effects: desensitizing, antimicrobial, anti tumorous, and antioxidative. This species was introduced from the East Asia and cultivated in many European, Asian, and North American countries. The common perilla has been cultivated in Lithuania as a decorative plant in parks and squares since 1990. This plant has been introduced in the collection and exposition of medicinal plants in Kaunas Botanical Garden of Vytautas Magnus University since 1998 with the purpose to analyze biological and pharmacological properties of plants and to assess the quality and quantity of the raw herb. It would be reasonable to carry out experimental research on biological qualities and raw material of the common perilla in Lithuania in accordance with the contemporary technologies and requirements of the European Union standards.

Adjuvants, Immunologic↗

Perilla ketone: a potent lung toxin from the mint plant, Perilla frutescens Britton.

Perilla ketone, from the essential oil of Perilla frutescens, is a potent pulmonary edemagenic agent for laboratory animals and livestock. This finding would account for reported effects of the plant on grazing cattle. The use of perilla in oriental foods and medicinal preparations suggests possible hazards to human health as well.

Animals↗

Monoterpene biosynthesis: specificity of the hydroxylations of (-)-limonene by enzyme preparations from peppermint (Mentha piperita), spearmint (Mentha spicata), and perilla (Perilla frutescens) leaves.

Microsomal preparations from the epidermal oil glands of Mentha piperita, Mentha spicata, and Perilla frutescens leaves catalyze the NADPH- and O2-dependent allylic hydroxylation of the monoterpene olefin (-)-limonene at C-3, C-6, and C-7, respectively, to produce the corresponding alcohols, (-)-trans-isopiperitenol, (-)-trans-carveol, and (-)-perillyl alcohol. These transformations are the key steps in the biosynthesis of oxygenated monoterpenes in the respective species, and the responsible enzyme systems meet most of the established criteria for cytochrome P450-dependent mixed function oxygenases. The reactions catalyzed are completely regiospecific and, while exhibiting only a modest degree of enantioselectivity, are highly specific for limonene as substrate. Of numerous monoterpene olefins tested, including several positional isomers of limonene, only the 8,9-dihydro analog served as an alternate substrate for ring (C-3 and C-6) hydroxylation, but not side chain (C-7) hydroxylation. In addition to the regiospecificity of the allylic hydroxylation, these enzymes are also readily distinguishable based on differential inhibition by substituted imidazoles.

Cyclohexenes↗

[Effects of extracts from different parts of Folium perillae (L.) Britt. on Hemorrheological parameters in rats].

In order to provide experimental data for the development and application of drug in clinic, we determined the effects of extracts from different parts of folium perillae (L. ) Britt. on hemorheological parameters, extracted from leaves (folium perillae), seeds (fructus perillae) and peduncles (caulis perillae). The results showed that all extracts from different parts of folium perillae (L. ) Britt. can significantly reduce the whole blood viscosity at low shear rate (10 s(-1)), erythrocyte aggregation index, erythrocyte electrophoresis index (P<0.05), and the whole blood reductive viscosity at low shear rate (10 s(-1)) (P<0.01). Extracts from folium perillae and caulis perillae can significantly decrease erythrocyte deformation index (P<0.05), whereas extracts from fructus perillae can not. Extracts from fructus perillae and caulis perillae can significantly decrease plasma viscosity at low shear rate(10 s(-1)), but extracts of folium perillae can not. Aspirin can only decrease the whole blood reductive viscosity at low shear rate and plasma viscosity (P<0.05). All extracts from different parts of folium perillae (L. ) Britt. had no significant effects on hematocrit, erythrocyte rigidity index, fibrinogen concentration , the whole blood viscosity and the whole blood reductive viscosity at middle and high shear rate (60 s(-1),120 s(-1)).

Animals↗

Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats.

We have investigated the modulatory effect of dietary perilla oil which is rich in the n-3 polyunsaturated fatty acid, alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats. Animals were given three weekly subcutaneous injections of AOM (15 mg/kg body weight) to induce ACE. The rats were fed a basal diet containing either 12% olive oil, 12% safflower oil, 12% perilla oil, 6% perilla oil plus 6% olive oil, or 3% perilla oil plus 9% olive oil for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection. The amount of food consumed and body weight gain were identical among every dietary group. The frequency of ACF was significantly lower in the rats fed 12% perilla oil than in those fed 12% olive oil or 12% safflower oil (P < 0.01 and P < 0.05, respectively). The suppressive effect of perilla oil was dose-dependent, as the number of ACF was 20.7, 40.7 and 47.4% of those of the 12% olive oil-fed controls in rats fed 12% perilla oil, 6% perilla oil plus 6% olive oil and 3% perilla oil plus 9% olive oil, respectively. Perilla oil significantly reduced ras expression as well as the AgNORs count (cell proliferation biomarkers) in the colonic mucosa, as compared with olive oil or safflower oil (P < 0.01, respectively). Marked increases in n-3 polyunsaturated fatty acids in membrane phospholipid fractions and decreased PGE2 levels were observed in colonic mucosa of perilla oil-fed rats. These results suggest that perilla oil, even in small amounts, suppresses the development of aberrant crypt foci, and is therefore a possible preventive agent in the early stage of colon carcinogenesis.

Animals↗

Comparative effects of perilla and fish oils on the activity and gene expression of fatty acid oxidation enzymes in rat liver.

The activity and mRNA level of hepatic enzymes in fatty acid oxidation and synthesis were compared in rats fed diets containing either 15% saturated fat (palm oil), safflower oil rich in linoleic acid, perilla oil rich in alpha-linolenic acid or fish oil rich in eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) for 15 days. The mitochondrial fatty acid oxidation rate was 50% higher in rats fed perilla and fish oils than in the other groups. Perilla and fish oils compared to palm and safflower oils approximately doubled and more than tripled, respectively, peroxisomal fatty acid oxidation rate. Compared to palm and safflower oil, both perilla and fish oils caused a 50% increase in carnitine palmitoyltransferase I activity. Dietary fats rich in n-3 fatty acids also increased the activity of other fatty acid oxidation enzymes except for 3-hydroxyacyl-CoA dehydrogenase. The extent of the increase was greater with fish oil than with perilla oil. Interestingly, both perilla and fish oils decreased the activity of 3-hydroxyacyl-CoA dehydrogenase measured using short- and medium-chain substrates. Compared to palm and safflower oils, perilla and fish oils increased the mRNA level of many mitochondrial and peroxisomal enzymes. Increases were generally greater with fish oil than with perilla oil. Fatty acid synthase, glucose-6-phosphate dehydrogenase, and pyruvate kinase activity and mRNA level were higher in rats fed palm oil than in the other groups. Among rats fed polyunsaturated fats, activities and mRNA levels of these enzymes were lower in rats fed fish oil than in the animals fed perilla and safflower oils. The values were comparable between the latter two groups. Safflower and fish oils but not perilla oil, compared to palm oil, also decreased malic enzyme activity and mRNA level. Examination of the fatty acid composition of hepatic phospholipid indicated that dietary alpha-linolenic acid is effectively desaturated and elongated to form EPA and DHA. Dietary perilla oil and fish oil therefore exert similar physiological activity in modulating hepatic fatty acid oxidation, but these dietary fats considerably differ in affecting fatty acid synthesis.

3-Hydroxyacyl CoA Dehydrogenases↗

Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of beta-carotene and perilla oil in rats.

The modulating effect of the combined dietary feeding of beta-carotene and perilla oil, which is rich in alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Rats received oral administration of beta-carotene (0, 50 or 200 mg/kg body weight/day) and fed a basal diet containing either 12% olive oil, 3% perilla oil plus 9% olive oil, or 12% perilla oil. A dose-dependent suppressive effect of perilla oil was found. The numbers of ACF were 42.0 and 18.4% of those of the 12% olive oil-fed controls in the rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. The development of ACF was also reduced significantly by the addition of dietary beta-carotene in each of the oil-fed groups (P < 0.05, respectively). The suppression by the combination of beta-carotene and perilla oil was synergistic, as the numbers of ACF were 12.9 and 8.9% of those of the 12% olive oil-fed controls in beta-carotene-treated rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. beta-carotene plus perilla oil also suppressed the numbers of silver-stained nucleolar organizer regions and the expression of ras mRNA in the colonic mucosa (cell proliferation biomarkers). Following administration of beta-carotene, a significant increase in the concentration of intact beta-carotene molecules was found in the colonic mucosa, livers, and sera. However, no accumulation of retinoids was observed in the colonic mucosa, suggesting that the inhibitory effect may not be related to the provitamin A activity. These results suggest that the combination of beta-carotene and perilla oil may be useful in the prevention of colon cancer.

Administration, Oral↗

Suppressive effects of Perilla frutescens on spontaneous IgA nephropathy in ddY mice.

Perilla frutescens (perilla) is a common herb used in Japan for garnishing raw seafood to protect the alimentary tract from inflammatory diseases. The present study was performed to investigate whether or not perilla prevents the development of lesions of IgA nephropathy in ddY mice which spontaneously develop this disease. After orally administering perilla extract to ddY mice from 8 to 42 weeks of age, the changes in urine, serum, and kidneys were evaluated. Perilla extract significantly suppressed proteinuria and glomerular IgA deposition (p < 0.01 and p < 0.05, respectively). The decreased serum IgA concentration in perilla-treated mice showed a significant correlation with glomerular IgA deposition. Such findings suggest that perilla reduced glomerular IgA deposition via suppression of IgA production in the serum. On the other hand, the nitric oxide concentration in the serum of perilla-treated mice was significantly higher than that observed in the controls. The addition of the sera of perilla-treated mice to quiescent cultured murine mesangial cells resulted in a cell proliferation which was less than in controls, suggesting that perilla might either directly prevent mesangial cell proliferation or prevent proliferation by regulating circulating cytokines. Such results indicate that perilla should prevent IgA nephropathy, thus representing a promising herbal medicine for glomerulonephritis.

Administration, Oral↗

Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice.

Perilla frutescens Britton (perilla, Labiatae) is a medicinal herb prescribed in Saiboku-to [Japanese letters: see text], which is a Kampo formula effective for allergic diseases such as bronchial asthma. The present study was conducted to evaluate the anti-allergic effect of orally administered perilla decoction and to identify the active constituents using mice ear-passive cutaneous anaphylaxis (PCA)-reaction, which is one of the animal models for type I allergy. Perilla decoction significantly suppressed PCA-reaction, and the inhibition % at the dose of 500 mg/kg was 43%. The perilla decoction contains 5.3% of luteolin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide], 1.6% of apigenin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide], 0.49% of scutellarin, and 2.5% of rosmarinic acid (weight of compound/dried weight of perilla decoction %), respectively. When these constituents were orally administered to mice at the dose equivalent to 500 mg/kg of perilla decoction, rosmarinic acid and apigenin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide] significantly suppressed PCA-reaction, and their inhibition % was 41% (p<0.01) and 32% (p<0.05), respectively. Since the inhibition % or perilla decoction and rosmarinic acid were nearly equal, the anti-allergic effect of perilla decoction depends primarily on rosmarinic acid. The standard Saiboku-to decoction contained 0.013% of rosmarinic acid, which was too low to exhibit anti-allergic activity in a daily dose of Saiboku-to in adults, suggesting that perilla would be prescribed in Saiboku-to to exhibit other pharmacological effects than its anti-allergic activity, such as a sedative.

Anti-Allergic Agents↗

Inotropic and lusitropic effects of Perilla frutescens (L.) Britton extract on the rabbit myocardium.

BACKGROUND: Common perilla (Perilla frutescens (L.) Britton) is a plant cultivated in many countries around the world. Although its immunomodulating and antioxidative properties are well known, there is a lack of data about the cardiotropic activity of the plant. The objective of this study was to determine the influence of Perilla frutescens extract on the myocardial contractility in vitro and as a food supplement in vivo. MATERIAL AND METHODS: Rabbits of the experimental group were fed with a supplement of 100 mg/kg of Perilla frutescens extract for 14 days. Rabbits of control group were fed with ordinary food. The maximal mechanical activity of isolated myocardial preparations, obtained from the rabbits of both groups, was tested during the perfusion with Ringer's solution containing 5 microM of adrenaline and 4.5 mM of CaCl2. For the assessment of the direct influence of Perilla frutescens extract on the myocardial contractility in vitro isolated heart preparations were perfused with 0.01, 0.1, and 1.0 mg/ml of Perilla frutescens extract. RESULTS: The maximum force of isometric contraction, maximum velocity of force development, and maximum velocity of relaxation were higher among the atrial and ventricular preparations from the experimental group, as compared with the control group. Perfusion of the myocardial preparations with different concentrations of Perilla frutescens extract revealed slight dose-dependent increase in the parameters of contraction and relaxation. CONCLUSIONS: The consumption of Perilla frutescens extract as a food supplement leads to an increase in the contractility of the rabbit myocardium. Perilla frutescens extract in vitro had a dose-dependent positive inotropic and lusitropic effect on the rabbit myocardium.

Animals↗

Colon cancer prevention with a small amount of dietary perilla oil high in alpha-linolenic acid in an animal model.

BACKGROUND: Epidemiologic and experimental studies suggest that dietary fish oil and vegetable oil high in omega-3 polyunsaturated fatty acids (PUFAs) suppress the risk of colon cancer. The optimal amount to prevent colon carcinogenesis with perilla oil high in omega-3 PUFA alpha-linolenic acid in a 12% medium-fat diet was investigated in female F344 rats. For comparison, safflower oil high in omega-6 PUFA linoleic acid was used. METHODS: Thirty or 25 rats at 7 weeks of age in each group received an intrarectal dose of 2 mg N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2 and were fed the diets with various levels of perilla oil and safflower oil throughout the experiment. RESULTS: The incidence of colon cancer at the termination of the experiment at week 35 was 40%, 48% and 32% in the rats fed the diets with 3% perilla oil plus 9% safflower oil, 6% perilla oil plus 6% safflower oil, and 12% perilla oil plus 0% safflower oil, respectively, whereas it was 67% in the rats fed the control diet with 0% perilla oil plus 12% safflower oil. The amount of diet consumed and the body weight gain were identical in all of the dietary groups. The ratios of omega-3 PUFA to omega-6 PUFA in the serum and the colonic mucosa at week 35 were increased in parallel to the increased intake of perilla oil. CONCLUSIONS: The results suggest that a relatively small fraction of perilla oil, 25% of total dietary fat, may provide an appreciable beneficial effect in lowering the risk of colon cancer.

Animals↗

Effect of Perilla frutescens on nitric oxide production and DNA synthesis in cultured murine vascular smooth muscle cells.

The effects of perilla (Perilla frutescens, Labiatae) on murine cultured vascular smooth muscle cells (VSMC) were investigated. The water extract of perilla leaves induced nitric oxide (NO) production of VSMC and this effect was synergistically augmented when combined with interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha, while the perilla extract significantly inhibited NO production induced by IFN-gamma combined with lipopolysaccharide (LPS). Northern blot analysis revealed that these effects of the perilla extract paralleled mRNA expression of inducible nitric oxide synthase. However, the perilla extract significantly inhibited platelet derived growth factor (PDGF) or TNF-alpha-induced VSMC proliferation measured as DNA synthesis. The inhibitory effect of the perilla extract on TNF-alpha-induced VSMC proliferation was significantly suppressed by N(G)-monomethyl-L-arginine, a non-specific nitric synthase inhibitor, suggesting that this effect was partially mediated by NO production as an autocrine/paracrine factor. The present findings suggest that perilla would be useful for the prevention of vascular diseases such as arteriosclerosis.

Animals↗

Inhibitory effect of decoction of Perilla frutescens on cultured murine mesangial cell proliferation and quantitative analysis of its active constituents.

The leaves of Perilla frutescens (perilla) are a common herb used in Japan for garnishing raw seafood. Previously, we reported that a decoction of perilla leaves had suppressive effects on the progression of glomerulonephritis in an animal model of spontaneous IgA nephropathy. The objective of the present study was to isolate anti-nephritic constituents in the perilla decoction under the guidance of its in vitro anti-proliferative activity on cultured murine mesangial cells, and to measure the contents of the active constituents in decoctions prepared from various perilla chemotypes, which differ in their composition of essential oils and/or pigments. DNA synthesis of cultured mesangial cells induced by 1% fetal calf serum was significantly inhibited by the perilla decoction (IC50 values, 8.8 microg/ml). Caffeic acid, luteolin 7-O-[beta-glucuronosyl(1-->2)beta-glucuronide], apigenin 7-O-[beta-glucuronosyl(1-->2)beta-glucuronide], scutellarin, and rosmarinic acid were isolated as active constituents. The contents of these phenolic compounds were not significantly different among chemotypes of P. frutescens. Considering the relation between the contents in the perilla decoction and the activities of these compounds, rosmarinic acid represents the in vitro anti-proliferative effect of perilla decoction.

Animals↗

Effect of Perilla frutescens extract on nitric oxide production by cultured murine mesangial cells.

The effects of a water extract of perilla (Perilla frutescens Britton) leaves on nitric oxide (NO) production by cultured murine mesangial cells were investigated. Perilla extract significantly induced NO production from mesangial cells, which was enormously augmented without cytotoxity by combination with interferon (IFN)-gamma or tumor necrosis factor-alpha. On the other hand, perilla extract suppressed a large amount of NO production induced by IFN-gamma combined with lipopolysaccharide. Northern blot analysis revealed that such effects of perilla extract were dependent on inducible NO synthase mRNA expression. Perilla extract exhibited an inhibitory effect on cytokine-induced mesangial cell proliferation, and this effect was significantly decreased upon combination with N(G)-monomethyl-L-arginine (L-NMMA), a non-specific NO synthase inhibitor, suggesting that perilla extract inhibits mesangial cell proliferation partially through the induction of NO production. Such results indicate that perilla may be a promising agent for the prevention of the progression of glomerulonephritis.

Animals↗

Suppressive effects of Perilla frutescens on mesangioproliferative glomerulonephritis in rats.

Leaves of Perilla frutescens var. crispa DECNE. (perilla, Labiatae) are used as a garnishing vegetable in East Asian countries as well as an herbal medicine prescribed in Kampo medicines such as Saiboku-to. A previous in vitro study revealed that a decoction of perilla leaves inhibits the proliferation of murine-cultured mesangial cells. In the present study, we evaluated the in vivo anti-proliferative effects of a perilla decoction using rat mesangio-proliferative glomerulonephritis induced by an intravenous injection of rabbit anti-rat thymocyte serum (ATS). Leaves of perilla were boiled, and the decoction was orally administered to the rats as drinking water at doses of 100 and 500 mg/kg/d from the day of ATS-injection (day 0) to day 8, when rats were sacrificed. In the histological evaluation, the total number of glomerular cells, proliferating cell nuclear antigen (PCNA) positive cells, and macrophage/monocyte antigen-positive cells in the glomerulus, was significantly decreased in perilla-treated rats. A significantly lower level of proliferation was induced by the serum of the perilla-treated rats than by that of the controls. These results suggest that the perilla decoction suppresses the proliferation of mesangial cells in vivo by an inhibition of the glomerular infiltration of macrophage/monocytes and of the production of circulating growth factors.

Animals↗