Perilla Uses, Benefits & Dosage - Drugs.com Herbal Database

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# Perilla

Scientific Name(s): Perilla frutescens (L.) Britt.
Common Name(s): Aka-jiso (red perilla), Ao-jiso (green perilla), Beefsteak plant, Chinese basil, Dlggae, Korean perilla, Nga-Mon, Perilla, Perilla mint, Purple mint, Purple perilla, Shiso, Wild coleus, Zisu

Medically reviewed by Drugs.com. Last updated on Nov 1, 2022.

## Clinical Overview

### Use

Perilla leaves have been used to treat a variety of conditions in Chinese medicine, as a garnish in Asian cooking, and as a possible antidote to food poisoning. Leaf extracts have shown antioxidant, antiallergic, anti-inflammatory, antidepressant, GI, and dermatologic properties. However, clinical trial data are lacking to recommend use of perilla for any indication.

### Dosing

Clinical trial data are lacking to support specific dosing recommendations. Various preparations and dosing regimens have been studied in clinical trials. See specific indications in Uses and Pharmacology section.

### Contraindications

Contraindications have not been identified.

### Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

### Interactions

None well documented.

### Adverse Reactions

Perilla oil may cause dermatitis.

### Toxicology

No data.

## Scientific Family

- Lamiaceae (mint)

## Botany

Perilla is an annual herb indigenous to eastern Asia and naturalized to the southeastern United States, particularly in semishaded, damp woodlands. The plant has deep purple, square stems and reddish-purple leaves. The leaves are ovate, hairy, and petiolated, with ruffled or curly edges; some very large red leaves are reminiscent of a slice of raw beef, hence the common name "beefsteak plant." Small tubular flowers are borne on long spikes that arise from the leaf axils between July and October. The plant has a strong fragrance sometimes described as minty.(Duke 2002, USDA 2022)

## History

Perilla leaves and seeds are widely consumed in Asia. In Japan, perilla leaves (referred to as "soyo") are used as a garnish on raw fish dishes, serving as both a flavoring and an antidote to possible food poisoning. The seeds are expressed to yield edible oil that is used in commercial manufacturing processes for varnishes, dyes, and inks. Dried leaves have many applications in Chinese herbal medicine, including treatment of respiratory conditions (eg, asthma, cough, colds), as an antispasmodic, to induce sweating, to quell nausea, and to alleviate sunstroke.(Duke 2002, Ota 2021, Ueda 2002)

## Chemistry

Perilla leaves yield about 0.2% of a delicately fragrant essential oil that varies widely in composition and includes hydrocarbons, alcohols, aldehydes, ketones, and furan. The seeds have a fixed oil content of approximately 40%, with a large proportion of unsaturated fatty acids, mainly alpha-linolenic acid. The plant also contains pseudotannins and antioxidants typical of the mint family. An anthocyanin pigment, perillanin chloride, is responsible for the reddish-purple coloration of some cultivars. Several different chemotypes have been identified. In the most frequently cultivated chemotype, the main component is perillaldehyde, with smaller amounts of limonene, linalool, beta-caryophyllene, menthol, alpha-pinene, perillene, and elemicin. The oxime of perilla aldehyde (perillartin) is reported to be 2,000 times sweeter than sugar and is used as an artificial sweetener in Japan. Other compounds of possible commercial interest include citral, a pleasantly lemon-scented compound; rosefurane, used in the perfume industry; and simple phenylpropanoids of value to the pharmaceutical industry. Rosmarinic, ferulic, caffeic, and tormentic acids and luteolin, apigenin, and catechin have also been isolated from perilla, as well as long-chain policosanols of interest in platelet aggregation. A high myristin content renders certain chemotypes toxic; ketones (eg, perilla ketone, isoegomaketone) found in other chemotypes are potent pneumotoxins. High-performance liquid chromatography, gas, and thin-layer chromatography have all been used to identify chemical constituents.(Adhikari 2006, Duke 2002, Müller-Waldeck 2010, Seo 2009)

## Uses and Pharmacology

### Anti-inflammatory and antiallergic effects

#### Animal and in vitro data

In vitro modeling has been used to describe anti-inflammatory properties of perilla. A marked influx of neutrophils and formation of leukotriene B4, along with changes in thromboxane B2 levels, was demonstrated in 1 experiment. In another, large increases in prostaglandin levels were observed. In a contact dermatitis model, perilla inhibited hypersensitivity mediated by leukotrienes, prostaglandins, histamine, inflammatory cytokines, and immunoglobulin E (IgE).(Ueda 2001) Extracts of perilla have also been shown to suppress the overproduction of tumor necrosis factor alpha, a cytokine important in immunologic and inflammatory reactions. Several anti-inflammatory components of perilla leaf have been identified, including luteolin and tormentic acid.(Banno 2004, Ueda 2002) In vitro and in vivo immunoenhancing effects have been described for a crude polysaccharide extract isolated from the leaves of perilla.(Jin 2010, Kwon 2002)

Topically applied triterpene acids isolated from dried perilla leaves produced a marked reduction in induced ear inflammation in mice.(Takano 2004) Greatest improvement was observed with the application of tormentic acid, an ursane triterpene. Inhibition of inflammation with this agent was similar to that produced by hydrocortisone and indomethacin. In another study, orally administered perilla leaf extract inhibited acute inflammation in 3 different models, including one of contact dermatitis(Ueda 2001) and another of arthritis in which redness, swelling, synovial hyperplasia, and inflammatory cell infiltration were significantly reduced.(Jin 2019)

#### Clinical data

Improvement in the symptoms of seasonal allergic rhinoconjunctivitis was reported in a small study (N=30) evaluating perilla extract enriched with rosmarinic acid (200 mg or 50 mg). Although objective symptom scores were not affected, patient evaluation of symptoms showed improvement scores of 30%, 55.6%, and 70% for patients receiving placebo, P. frutescens plus rosmarinic acid 50 mg, and P. frutescens plus rosmarinic acid 200 mg, respectively (P=0.05 for placebo vs P. frutescens plus rosmarinic acid 200 mg). Numbers of inflammatory cells in nasal lavage fluid were significantly lower at 3 days in patients receiving P. frutescens plus rosmarinic acid. However, this effect was no longer apparent at 21 days.(Guo 2007, Takano 2004)

### Antimicrobial and antiviral effects

#### In vitro data

Luteolin extracted from perilla seed oil showed marked antimicrobial activity against bacteria commonly associated with dental caries.(Yamamoto 2002) Activity of perilla oil against toxins produced by Staphylococcus aureus has been demonstrated,(Qiu 2011) while the essential oil of P. frutescens exhibited dose-dependent activity against Enterococcus faecalis, with a minimum inhibitory concentration of 0.5 mcL/mL.(Zhou 2020)

In a study identifying novel anti–SARS-CoV-2 agents from traditional Chinese medicine, perilla leaf extract demonstrated broad-spectrum inhibitory activity against SARS-CoV-2 as well as other RNA viruses (ie, enterovirus A71, influenza virus) in a highly specific manner. No activity was observed against the human coronavirus HCoV-229E that causes the common cold. The extract inhibited SARS-CoV-2 viral entry into human lung alveolar cells, thereby preventing the initial step of viral replication and viral protein synthesis. As a result, virus titers (P<0.005), viral spike protein, and the ratio of infected cells (P<0.01) were significantly reduced with perilla leaf extract. This virucidal activity was synergistic in the presence of remdesivir. The several-fold increase in the production of proinflammatory cytokines/chemokines (ie, CXC motif chemokine ligand 10, interleukin 6 [IL-6], tumor necrosis factor alpha, interferon gamma, monocyte chemoattractant protein 1) induced by SARS-CoV-2 infection was also significantly inhibited by the extract in a manner similar to remdesivir.(Tang 2021) Potent activity of perilla extract against Ebola virus has also been demonstrated. The extract prevented viral attachment and postattachment fusion (P<0.001) to the host cell and inactivated free viral particles (P<0.0001), with better neutralizing activity than the positive control.(Kuo 2021)

### Antioxidant effects

#### In vitro and experimental data

Antioxidant properties of perilla leaf and seed extracts, as well as individual chemical constituents, have been extensively studied in experimental models,(Meng 2008, Müller-Waldeck 2010, Raudonis 2010, Zekonis 2008) with limited therapeutic applications evaluated.(Eckert 2010, Kim 2007, Schirrmacher 2010, Zhao 2011, Zhao 2012)

In vitro experiments demonstrated that red perilla exhibited stronger antioxidant activity than green perilla, and that perilla upregulated superoxide dismutase and catalase.(Saita 2012)

#### Clinical data

Red perilla extract (containing 1,000 mg of polyphenols) significantly reduced oxidation of low-density lipoprotein (LDL) in 8 healthy young adult female volunteers, marked by a prolongation of oxidation lag time. Additionally, antioxidant parameters (thiobarbituric acid reactive substances assay, lipid peroxide production, mobility of LDL) were all significantly reduced.(Saita 2012) In another small study, a trend toward decreased lipid peroxidation was observed among healthy volunteers who consumed 5 g of powdered perilla leaves for 10 days.(Schirrmacher 2010)

### Cancer

#### Animal and in vitro data

The inhibitory effects of topically applied tormentic acid on carcinogenesis have been investigated in mice.(Banno 2004) Inhibitory effects were observed in a study evaluating topical application of a perilla leaf extract in mice with induced skin papillomas; the active principle was thought to be luteolin. The effects of orally administered perilla leaf extract were less marked, with no significant difference in the number of tumors observed between controls and perilla-treated groups at 20 weeks.(Ueda 2003) Reduction in the incidence of mammary and colonic tumors has been associated with perilla oil dietary supplementation in laboratory animals.(Nakayama 1993, Narisawa 1991) In vitro experiments with human leukemia and hematoma cell lines have demonstrated apoptotic and cell cycle–arresting effects that were greater for perilla leaf extract than rosmarinic acid alone.(Kwak 2009, Lin 2007) Whereas, perilla seed oil and/or a rosmarinic acid-rich fraction demonstrated significant anti-oxidant and anti-inflammatory activity but had no effect on apoptosis in lung adenocarcinoma cells.(Tantipaiboonwong 2021)

#### Clinical data

The constituent perilla alcohol has been studied clinically in skin, prostate, and breast cancers, as well as for glioblastoma.(Bailey 2008, da Fonseca 2008, Liu 2003, Stratton 2010)

### Cardiovascular risk

#### Animal data

Serum cholesterol and triglyceride levels decreased in rats fed perilla oil. Beneficial changes in the levels of eicosapentaenoic acid and arachidonic acid were also observed.(Sakono 1993)

### CNS effects

#### Animal and in vitro data

In a model of age-related deficits in learning and memory, mice fed a diet enriched with perilla oil exhibited better learning performance and less hyperactive behavior than those fed an alpha-linolenate–deficient diet.(Umezawa 1999) In vitro studies suggest chemical constituents of perilla may act via the monoamine transport system to increase monoamine levels and via inhibition of beta-secretase enzymes to reduce the production of amyloid protein.(Choi 2008, Zhao 2010) In a rat model of vascular dementia, a perilla leaf extract reduced the neuronal hippocampal death, memory issues, and microglial activation observed in untreated rats, with lower levels of neuroinflammation as measured by multiple markers.(Kang 2022)

Apigenin extracted from perilla showed limited antidepressant-like effects in mice.(Nakazawa 2003) In mice with stress-induced depression, perillaldehyde reduced the duration of immobility in a forced swimming test.(Ito 2011)

An anorexigenic effect has been demonstrated in mice fed apigenin both acutely and after 30 days, with a decrease in triglycerides but no effect on blood glucose or total cholesterol.(Myoung 2010)

Dose-dependent sedative effects of inhaled P. frutescens essential oil have been demonstrated in mice.(Ota 2021)

#### Clinical data

A single-blind, randomized, controlled interventional study was conducted in 180 adults 55 years or older diagnosed with mild to moderate depression who consumed fish less than 3 times per week. The study aimed to examine the effects of fish with or without perilla essential oil marinade on depressive scores and general health. A significant reduction (approximately 60%) in depression risk was observed for participants of both intervention groups who were instructed to consume fish 4 times per week compared with controls who consumed fish less than once per week. Additionally, the risk was even lower for those who consumed fish marinated with perilla essential oil compared with no perilla oil for both depression scores (difference in mean scores, −1.2; 95% CI, −2.1 to −0.3; P<0.05) and health status (difference in mean scores, −0.7; 95% CI, −1.3 to −0.2; P<0.05).(Sharifan 2017)

In a double-blind, randomized, placebo-controlled trial conducted in patients with mild to moderate dementia (N=34), adjunctive use of perilla seed oil did not significantly effect cognitive scores or laboratory assessments (ie, lipids, renal or hepatic function, CBC, blood sugar, HgA1c). Perilla seed oil 500 mg capsules was administered as 2 capsules 3 times daily before meals totalling 3 g/day for 6 months, which were taken in addition to their ordinary dementia treatment, most commonly donepezil and/or memantine. Olive oil was used in the placebo capsules.(Kamalashiran 2019)

### Dermatologic effects

#### In vitro data

In mouse melanoma cells, perilla leaf extract inhibited tyrosinase and melanin synthesis , suggesting potential applications for skin lightening.(Hwang 2007)

#### Clinical data

In a study of 30 healthy volunteers (40 to 60 years of age), topical application of a leaf extract of perilla in a cream base for 8 weeks resulted in increased skin elasticity and a finer skin texture compared to the cream base alone.(Mungmai 2020)

### Diabetes

#### Animal and in vitro data

Antidiabetic effects of perilla sprouted seed extract, perilla oil, and perilla leaf extract and fractions have been demonstrated in diabetic rodent models and have included improvements in body weight (P<0.05), hyperglycemia (P<0.001 to P<0.05), glucose tolerance, insulin level (P<0.01 to P<0.05), insulin tolerance (P<0.01), and pancreatic islet cell preservation.(Kim 2018, Wang 2020, Wang 2021) A high-dose ethyl acetate perilla leaf extract fraction was found to be equivalent to or better than acarbose in reducing body weight.(Wang 2021) A decrease in gluconeogenesis(Kim 2018) as well as dose-dependent inhibition of alpha-glucosidase, acetylcholinesterase, and tyrosinase were demonstrated in vitro.(Wang 2021)

#### Clinical data

As a component of medical nutrition therapy for patients with type 1 or type 2 diabetes, the American Diabetes Association Standards of Care (2014) recommend an increase in foods containing alpha-linolenic acid to improve lipid profiles and reduce the risk of developing atherosclerotic cardiovascular disease in patients with diabetes.(ADA 2022)

### Exercise performance

#### Animal data

In mice, a protein powder derived from purple perilla seeds (P. frutescens) improved muscle strength and fat and muscle coefficients, as well as suppressed the increased blood urea nitrogen and creatinine levels associated with fatigue.(Liu 2020)

### GI effects

#### Animal data

In a colitis mouse model, supplementation with perilla leaves minimized weight loss (P<0.05), reduced symptoms (ie, stool consistency, gross bleeding), improved clinical symptomatic scores, and improved morphological parameters (ie, colon length) significantly better than untreated controls (P<0.05 for each). The dose of the perilla leaves supplement was equivalent to human intake of 50 g/day in a 2,000 kcal–based diet. Effects were related to a reduction in several proinflammatory cytokines and enzymes (ie, IL-1beta, IL-6, cyclooxygenase-2).(Lee 2019) In an nonsteroidal anti-inflammatory drug–induced gastric ulcer model, similar protection was observed with pretreatment using a rosmarinic acid–enriched fraction extracted from perilla leaves. Although both ethanolic and aqueous extracts significantly reduced the ulcer index (P<0.05) compared with untreated controls, the aqueous fraction performed better and significantly reduced gastric secretion volume (P<0.01) and acidity (P<0.05).(Kangwan 2019)

#### Clinical data

A double-blind, randomized, placebo-controlled pilot study explored the effects of perilla extract 150 mg twice daily for 4 weeks in 50 healthy volunteers with GI discomfort and reduced bowel movements. Significant improvements were observed in bloating (P=0.003 vs placebo), gas (P=0.026), GI rumbling (P=0.0014), fullness (P=0.0152), and abdominal discomfort (P=0.004) with administration of perilla. Additionally, a higher rate of respondents was documented in the perilla group compared with placebo, especially for bloating (83% vs 57%, respectively), with women responding more often than men.(Buchwald-Werner 2014) In female athletes, both 3 g and 9 g daily of perilla oil demonstrated improvements in intestinal microbiome profile and lower constipation scores.(Kawamura 2022)

### Hair growth

#### Animal data

In an alopecia mouse model, antagonism of testosterone and dihydrotestosterone with topical application of P. frutescens extract facilitated anagen initiation, hair growth, and significant increases in hair length compared with controls (P<0.01).(Li 2018)

### Obesity

#### Animal data

Lipid accumulation and body weight gain induced in mice fed a high-fat diet (60% kcal from fat) were significantly reduced with administration of perilla leaf ethanolic extract (P<0.05). Additionally, total cholesterol was significantly lower and triglycerides were reduced by up to 72% compared with controls. Mean adipocyte size in both epididymal and mesenteric fat was significantly reduced and less visceral fat was observed in the perilla extract group.(Thomas 2018)

### Osteoporosis

#### In vitro data

In vitro experiments have demonstrated dose-dependent suppression of osteoclast formation and induction of early-stage osteoblast differentiation with a perilla leaf extract.(Phromnoi 2022)

### Renal disease

#### Animal and in vitro data

An orally administered perilla leaf decoction resulted in reductions in proteinuria and in the numbers of glomerular and proliferative cell nuclear antigen–positive cells in animals with mesangioproliferative glomerulonephritis.(Myoung 2010) Perilla extract and one of its key components, luteolin, have been shown to significantly reduce renal tubular cell injury in an adriamycin-induced chronic kidney disease in vitro model. Cell viability was significantly increased via antioxidant activity comparable to N-acetyl-l-cysteine and via antiapoptotic mechanisms that protected the kidney against multiple insults.(Yong 2021)

### Wound healing

#### In vitro data

In human keratinocytes, low doses of a compound isolated from P. frutescens (isoegomaketone) enhanced cell proliferation and cell migration, and increased keratinocyte cell cycle progression.(Kim 2021)

## Dosing

Clinical trial data are lacking to support specific dosing recommendations. Various preparations and dosing regimens have been studied in clinical trials. See specific indications in Uses and Pharmacology section.

## Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

## Interactions

None well documented.

## Adverse Reactions

Dermatitis has been reported in perilla oil workers. Patch testing suggests that 1-perillaldehyde and perilla alcohol contained in the oil are responsible for the effect.(Duke 2002, Kanzaki 1992) Two cases of anaphylaxis resulting from oral consumption of 500 mg of perilla seeds have been reported. An IgE-mediated response was documented.(Jeong 2006)

## Toxicology

Animals grazing on perilla have developed fatal pulmonary edema and respiratory distress.(Kerr 1986) Perilla ketone, chemically related to the toxic ipomeanols derived from moldy sweet potatoes, is a potent agent for the induction of pulmonary edema in laboratory animals.(Abernathy 1992) The highest levels of perilla ketone occur in the plant during the flowering and seed stages.(USDA 2022) Perilla ketone acts by increasing the permeability of endothelial cells and may not require the presence of CYP-450 to increase vascular permeability.(Waters 1993)

The toxicity of perilla ketone has been examined in several animal species. Low intraperitoneal median lethal dose values were observed for mice and hamsters (5 mg/kg and 13.7 mg/kg, respectively), with far higher lethal doses being required for dogs and pigs (106 mg/kg and 158 mg/kg, respectively). Perilla ketone–related pathology in dogs and pigs was primarily hepatic, with only minor pulmonary effects, while mice and hamsters displayed only pulmonary lesions. Enzyme bioactivation of perilla ketone may be required for toxicosis, with species unable to produce the perilla metabolite having reduced susceptibility to its poisoning. The volatile perilla oil contains the aldehyde antioxide that has been used in the tobacco industry as a sweetener; however, this compound may be toxic.(Kerr 1986)

## References

## Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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