Perilla: Background. Actions

2010

Common Name

Perilla

Other Names

Beefsteak plant, Chinese basil, Purple perilla, wild sesame (English common names), Ban Tulsi (Bengali), Su Zi (Mandarin), Shosi, Egoma (Japanese). Different names are used for the different parts of the perilla plant used as foods or medicines.

Botanical Name / Family

Perilla frutescens (L.) Britt.

There are several botanical variants that seem to be used interchangeably: P. frutescens var. crispa, P. frutescens var. japonica (family Lamiaceae or Labiatae [mint family]).

Plant Parts Used

Leaf, stem and the fruit (seed) are used.

Historical Note

Perilla is an annual plant native to Eastern Asia. It was introduced to Japan from China and is now cultivated extensively in Japan, India and Korea. The seed is mainly used for its high oil content, and the leaves of Perilla frutescens var. crispa are used as a vegetable and food colouring. The salty umeboshi plum is coloured by the addition of special red perilla leaves. In China perilla has been used to reduce the risk of food poisoning by cooking seafood with the leaf. In recent times, certain compounds (monoterpines) isolated from the oil are being investigated as an anticancer treatment, and the defatted seed extract is used in the treatment of allergies.

Chemical Components

As different parts of the plant are used, this section will deal with each part individually.

RAW OIL

Perilla seed contains 25-51% lipids. The raw perilla oil has been used as a drying oil in paints, varnishes, linoleum, printing ink, lacquers and for protective waterproof coatings on cloth. It has also been used for cooking and as a fuel.

REFINED OIL

The purified oil is rich in fatty acids including palmitic acid, linoleic acid, alpha-linolenic acid, stearic acid, eicosenoic acid and arachidic acid. The n-3 essential fatty acid, alpha-linolenic acid, comprises over 60% of the oil.

DEFATTED PERILLA SEED EXTRACT

Defatted perilla seed extract is a concentrated ethanolic extract rich in polyphenolic compounds including rosmarinic acid, rosmarinic acid methyl ester and the flavones apigenin, luteolin and chrysoeriol. Normally flavonoids exist as glycosides in plants; however, in perilla seed extract they occur as aglycones (free flavonoids), which have more potent activity. The defatted extract is free of perillyl ketone, perillyl aldehyde and perillyl alcohol.

LEAF

The leaf contains flavones, including apigenin and luteolin, flavone glycosides, anthocyanins, phenolic compounds including rosmarinic acid, and aldehydes including perillyl aldehyde.

ESSENTIAL OIL

The volatile oil is distilled from the dried foliage of perilla. It contains perillyl aldehyde, elsholtziaketone, perillyl ketone, citral and perillene, in addition to more than 70 other compounds. Perillyl aldehyde is used as a sweetener and flavouring agent. One of the aldehyde isomers is 2000-fold sweeter than sugar and 4-8-fold sweeter than saccharin. Perillyl alcohol, prepared from perillyl aldehyde, is used in fragrances. There are different chemotypes of perilla; one genotype lacks perillyl aldehyde but has perillyl ketone.

Perilla: Main Actions

The herb has several different actions and the part of the plant used will determine which is exhibited. As such, this review includes information about which part of the herb is responsible for the activity listed. Additionally, much research has been conducted with the rosmarinic acid and luteolin components isolated from perilla.

ANTI-INFLAMMATORY ACTION

Both the refined oil and seed extract demonstrate anti-inflammatory activity in vitro. Refined oil The pharmacological effects of the refined oil are associated with its high level of alpha-linolenic acid, which is metabolised in the body to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor of the series-3 prostaglandins, the series-5 leukotrienes and the series-3 thromboxanes, which have anti-inflammatory and anti-atherogenic properties. The effects have been shown clinically, as perilla seed oil significantly suppressed the generation of leukotrienes in asthma patients in an observational study comparing two groups of asthma patients, one of which received perilla oil for 4 weeks. Ventilatory parameters, such as PEF, FVC and FEV1, increased significantly after 4 weeks’ dietary supplementation in the treated group.

Seed extract

Perilla seed extract, as well as its constituents luteolin, rosmarinic acid and chrysoeriol, have been shown to inhibit 5-lipoxygenase in vitro, and therefore leukotriene synthesis. Leukotrienes are associated with both allergic and inflammatory disorders, including hay fever, asthma and inflammatory bowel disorders.

ANTI-ALLERGIC ACTIVITY

In both in vitro and animal models of allergy, perilla preparations have demonstrated anti-allergic effects. Luteolin and rosmarinic and caffeic acids are chiefly responsible for this activity.

Seed extract

The defatted seed extract has been shown to inhibit chemically induced type IV allergy and inflammation in vivo, with the luteolin constituent exhibiting the most potent activity.

Perilla seed extract has also been shown to inhibit histamine release from mast cells in a dose-dependent manner. The effect is more potent than for isolated flavonoids including catechin, quercetin and caffeic acid. Additionally, in a case report of perilla seed extract, 150 mg/day for 2 weeks selectively inhibited the production of serum IgE in two human subjects suffering allergic symptoms including sneezing, nasal obstruction and itchy eyes.

Leaf

Perilla leaf extract is thought to downregulate Th2-type cytokine production and prevent the Th1/Th2 balance from shifting toward Th2-type immune responses. A study on the effects of perilla leaf extract on cytokine production in allergic reaction in mice found that it suppressed IgE and IgG antibodies as well as IL-4, IL-5 and IL-10.

An aqueous extract of perilla leaf was shown in vitro and in vivo to inhibit local and systemic reactions in a mast cell-mediated immediate-type allergic reaction. Plasma histamine levels and cyclic AMP were reduced in a dose-dependent manner. Perilla also inhibited IgE-induced TNF-alpha production. Oral administration of a hot water extract of perilla leaf was also shown to inhibit histamine release from mast cells and reduce scratching in an animal model of dermatitis.

Oral administration of a perilla leaf extract inhibited the inflammatory response in an induced allergic reaction in animals. Luteolin, rosmarinic and caffeic acids were isolated and identified as active constituents. Luteolin has been shown in vivo to inhibit TNF-alpha and arachidonic acid and reduce oedema. In another inflammatory model, perilla dose-dependently reduced the allergic response in mice by over 40%. Rosmarinic acid was identified as the main active constituent and has been shown to decrease the inflammatory response and increase superoxide radical scavenging in vivo. An extract of perilla leaf with high levels of rosmarinic acid decreased cytokine activity in asthma-induced rats. A perilla leaf decoction was found to suppress IgA nephropathy in genetically predisposed rats, possibly through modulation of the intestinal mucosal immune system. Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in the mice. Rosmarinic acid seems to produce this effect synergistically with other constituents.

ANTIOXIDANT ACTIVITY

A methanolic extract of roasted defatted perilla seed has been shown to exert strong antioxidant activity and, upon fractionation, luteolin was identified as one of the active antioxidant constituents. Rosmarinic acid inhibits NO and iNOS in vitro.

IMMUNOSTIMULANT

Perilla leaf extract stimulates phagocytosis in vitro and in vivo. An increase in neutrophil phagocytosis was noted after 7 days, but was strongest after 4 weeks of treatment. A polysaccharide extract from perilla leaf has also demonstrated phagocytic ability both in vitro and in vivo.

ANTIMICROBIAL ACTIVITY

Perilla may help prevent dental caries and periodontal disease. Perilla seed extract has been shown to have antimicrobial activity against oral cariogenic streptococci and periodontopathic Porphyromonas gingivalis. The luteolin constituent showed the strongest antimicrobial effect amongst the phenolic compounds tested.

HEPATOPROTECTIVE EFFECTS

Perilla extract and its constituent rosmarinic acid have both been shown to be hepatoprotective against lipopolysaccharide-induced liver damage in mice, possibly due to the antioxidant activity.

HYPOCHOLESTEROLAEMIC

Hypocholesterolaemic effects of perilla have been demonstrated in vivo. Perilla oil lowers cholesterol by suppressing hepatic HMG-CoA reductase activity. Perilla oil also lowers plasma triacylglycerol by suppressing fatty acid synthase and stimulating acyl-CoA oxidase in the liver.

Perilla oil mixed with borage and evening primrose oil has been shown to reduce cholesterol in older rats.

ANTICANCER EFFECTS

Several constituents found in perilla have demonstrated anticancer effects in vitro and in experimental cancer models. This has prompted phase I and phase II clinical testing with one key active constituent, perillyl alcohol.

Conjugated alpha-linolenic acid from perilla oil has been shown to reduce the rate of carcinogenesis in a chemically induced rat mammary cancer model. The fibrinolytic and antioxidative activities of rosmarinic acid suppress the proliferation of mesangial cells in vivo. Animal studies have demonstrated the ability of perillyl alcohol to inhibit tumorigenesis in the mammary gland (Yuri et al 2004) and skin. The precise mechanism of action is unclear. Perillyl alcohol has been shown to inhibit part of the signal transduction cascade involved in uncontrolled cell proliferation, upregulate the mannose-6-phosphate receptor and induce apoptosis. Perillyl alcohol has also demonstrated an ability to decrease the release of vascular endothelial growth factor from cancer cells and encourage the expression of angiopoietin-2 by endothelial cells. This indicates that perilla may play a role in decreasing the vascularisation of tumours and inducing regression.

Perillyl alcohol increases the sensitivity of cancer cells in vitro to radiation treatment of prostate cancer, glioma and certain neck and head cancers.

ANTIDEPRESSANT ACTIVITY

Several different constituents within perilla leaf have demonstrated effects on behaviour in vivo, most notably antidepressant effects.

Rosmarinic acid and caffeic acid have demonstrated antidepressant activity in a forced swimming test in mice. The activity is thought to be via some mechanism other than the inhibition of monoamine transporters and monoamine oxidase. Apigenin from perilla significantly reduced immobility in a forced swimming test in mice, an effect mediated by dopaminergic mechanisms.

Rosmarinic acid and caffeic acid have been shown to decrease the duration of the defensive freezing behaviour caused by fear and stress in animals.

Perilla: Other Actions

Perilla oil has been shown to reduce the excessive growth of visceral adipose tissue in rats by downregulating adipocyte differentiation in animals. This has direct relevance to obesity, as a high-fat diet not only accelerates the filling process of pre-existing pre-adipocytes but also stimulates the proliferation of adipose precursor cells. Adipocyte differentiation, from adipoblasts to adipocytes, is a key factor underlying obesity.

A glycoprotein isolated from perilla oil has been shown to inhibit an early stage of HIV-1 replication without blocking viral adsorption in vitro.

Perilla-aldehyde has demonstrated vasodilatory activity in isolated rat aorta and appears to work by blocking Ca2+ channels.The clinical significance of this is currently unknown.