Akriti Dhyani¹ , Rajni Chopra*¹and Meenakshi Garg²

¹Department of Foods and Nutrition, Institute of Home Economics, University of Delhi, F-4 Hauz Khas Enclave, New Delhi, 110016, India.

²Department of Food Technology, Bhaskaracharya College of Applied Sciences, University of Delhi, Dwarka, New Delhi, 110075, India.

Corresponding Author E-mail: rajn145ihe@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/1685

Abstract

Perilla frutescens is an annual herb belonging to the mint family (Lamiaceae). It is majorly produced in countries like China, Japan, India, Thailand and Korea. Recently, Perilla plant is gaining more attention because of its medicinal benefits and phytochemical contents. The major phytochemical compounds reported in this species are phenolic compounds (Rosmarinic acid, caffeic acid, ferulic acid), flavonoids (luteolin, apigenin), Phytosterols, Tocopherols, Policosanols and Fatty acid. Perilla seed oil is also a rich source of essential fatty acid such as α-linolenic acid (54-64%) and linoleic acid (14%). Perilla seeds and its oils have been widely used in traditional nutritional and medicinal formulations. Biological analysis of Perilla seeds revealed that it showed anticancer, ant-diabetic, antiasthma, antimicrobial, anti-inflammatory, antioxidant and cardioprotective effect. The aim of this review is to provide an update on the nutritional composition, phytochemical profile and pharmacological research of Perilla seed.

Keywords

Antioxidant; Bioactive Compounds; Fatty Acid, Linolenic Acid; Perilla Seed

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Introduction

Perilla frutescens L. belongs to the family Lamiaceae which consists of 236 genera and more than 7000 species. P. frutescens commonly known as Perilla is an annual herb found in China, Korea, Japan and the Himalayan region of India and Nepal. Now it is also being cultivated by some western countries like U.S.A, Russia, and Europe due to its growing economic importance.¹ In Japan, it is found in Aomori, Akita, Iwate, Yamagata, Miyagi, Oshika, Fukushima, Ishikawa, Ibaraki, Gunma, and Nagano prefecture. In Korea, it is reported from Kangwan, Kyonggi, Kyongsangbuk, Kyongsangnam, Chungchongbuk, Chungchongnam, Chollabuk and Chollanam province. In China, it is distributed in southeastern and southwestern parts mainly Gansu, Shaanxi, Jiangsu, Zhejiang, Jiangxi, Hunan, Xichuan, Yunnan, and Guangxi.² In India, it founds in Uttarakhand, Kashmir, Himachal Pradesh, Sikkim, Manipur, Mizoram and Meghalaya state.³ Perilla plant contains a number of important phytochemicals such as Rosmarinic acid, Luteolin, Chrysoeriol, Quercetin, Catechin, Caffeic acid and Ferulic acid.^4,5 The presence of Phytosterols, Tocopherols, Squalene, and Polyunsaturated fatty acid has also been reported from Perilla seed.⁶ Biological analysis of Perilla plant revealed that this plant showed anti-microbial, anti-allergic, anti-cancer, anti-tumor, anti-depression, anti-viral, anti-asthmatic and antioxidant activities.^7-9 It is utilized as functional food in various parts of the world but in some parts, there is no organized cultivation of this crop and in spite of having numerous benefits and uses, it is still an underutilized crop.¹⁰

There are few review papers available on Perilla frutescens. Two review papers are available on the comprehensive information on phytochemical and pharmacological properties.^11-12  Some scientists have reviewed various aspects of Perilla plant such as its bioactive components and its use as food as well as medicine.^13-14  Another review¹⁵ focused on the health benefits of Perilla plants but there is no complete review with detailed information about the nutritional aspects of Perilla. The purpose of this review is to provide complete information on the botany, uses, Phytochemistry, nutritional and pharmacological research of Perilla with more emphasis on Perilla seed and Perilla seed oil. Moreover, this review would provide scientific gaps in current knowledge and offer a systematic basis for future research work on Perilla.

Methodology

All the available information about the botany, uses, nutritional composition, phytochemistry and pharmacological properties (84 Research papers) on Perilla up to 2018 was collected via electronic search (using PubMed, Scopus, Web of Science, Science Direct, J-Gate, Google Scholar, and other web search engines, such as Google, Yahoo) and a library search for articles published in peer-reviewed journals, unpublished materials, theses, as well as some of the government survey reports. All obtained data from previously published literature are summarized in 5 tables (Botanical description, Proximate, Phytochemicals, Minerals and Fatty acid composition) and 2 figures. Reported bioactive constituents from this plant are presented in figure 1.

Plant Description

Perilla is an annual herb that grows up to 150 cm height with shiny green or purple, downy-hair ovate to round leaves, square stem, small tubular purplish to white flowers 3-4 mm in length,  Flower-stalks length are about 1.5 mm, Calyx is about 3 mm with brown seeds. Perilla seeds are small and weigh about approximately 4g/1000 seeds. Its seeds are sown in the month of May and harvesting period is September – October, which varies and depending on geographic area. It is grown in mixed cropping; the crop requires moisture absorbent soil but not a very fertile soil. Useful parts of Perilla plant are its leaves and seeds.^1,3,16,17 The plant, seeds and seed oil are shown in Fig. 1. Botanical descriptions of Perilla plant are presented in Table 1.

Table 1: Botanical description of Perilla plant.

Kingdom –	Plantae
Subkingdom –	Tracheobionta
Division –	Spermatophyta
Superdivision –	Magnoliophyta
Class –	Magnoliopsida
Subclass –	Asteridae
Order –	Lamiales
Family –	Lamiaceae – Mint Family
Genera –	Perilla

 

Vernacular Names of Perilla

Perilla has different synonyms and vernacular names that vary from area to area. In China it is known as Zisu, Shiso in Japan,⁵ Deulkkae or Tilkae in Korea,^15,19 Silam in Nepal. In India, it has several names across the state, such as Bhanjeer or Banjiraa (Uttarakhand), Hanshi or thoiding (Manipur), chhawhchhi (Mizoram).¹⁶

Traditional Application of Perilla

 Useful parts of Perilla plant are its leaves and seeds. Perilla leaves are used as vegetable and spice as well to impart color and flavor in many dishes. In Japan, Perilla oil is marketed as vegetable edible oil²⁰ and its leaves are mainly used in garnishing, tempura dish and to color plum pickles known as Umeboshi, its color is the result of the reaction of citric acid with anthocyanin present in Perilla.^21,22 In Korea, Perilla seeds and leaves are added in various dishes to add flavor. Its seeds are available in two forms, powder, and oil, for salad dressings and seasonings. Oil of roasted Perilla seed is used as a condiment oil.¹⁶ Perilla seed powder is added to soup to add thickness and flavor. In Korea and Japan, Rice porridge prepared using Perilla seed and ‘rayu’ (Pepper oil sauce), a traditional condiment prepared using Perilla seed oil.^23,24 Perilla leaves herbal tea is also available in some Korean shops for cold and cough. Perilla rice porridge is also consumed in Vietnam in case of cold.^1,3In India, it is mainly cultivated in Uttarakhand, Uttar Pradesh, Himachal Pradesh and Kashmir states for its flavoring essential oil. Perilla seeds are roasted with onion and tomato to form chutney (sauce) and also used in the curry material.¹⁰ In Northeast Asia, it is mainly used by tribal groups for its edible seeds as it is a less expensive source of fat and protein. Grounded roasted seeds are consumed in a salad called ‘Singju’ in Manipur. Its leaves can be used as a vegetable and can be preserved by drying. Its flower buds are edible raw and young shoots are used in soup preparation.^25,26

It has been conventionally used as a therapeutic food in many countries, mainly China and Japan. According to the Chinese ministry of health, it is recognized as food as well as medicine used to treat different infections.²⁷ Leaves of Perilla are a major constituent of traditional Chinese herbal medicine ‘Banxia Houpu Decoction’ and SYJN which is used to treat depression.^7,28 In Japan, dried leaves and stems of Perilla are used in the preparation of herbal medicine ‘saiboku-to’, which is used in the treatment of asthma and morning sickness.^29,30 Also, its fresh leaves are cooked with seafood to prevent food poisoning. Perilla is also used in skin creams, soaps, and medicinal preparations because of its antioxidant and anti-allergic properties.³¹ Perilla is also a major constituent of herb Houttuynia cordata Thunb (HC), which is used in the treatment of alopecia.³² As a medicinal plant, Perilla is used as a treatment for cold, cough, vomiting, abdominal pain and constipation. Volatile oil from Perilla leaves used to prepare microcapsules, and these capsules are used as a food preservative agent.³³ Perilla leaves are also used in the preparation of herbal tea for cold and fever.²⁵ Juice from Perilla leaves applied to wounds and cuts because of its anti-bacterial properties.³⁴ A chewable tablet is prepared by³⁵ using Perilla leaf powder and extract, a good source of vitamin and minerals especially calcium. It can also be used as a treatment for cold, cough, vomiting, abdominal pain and constipation.³

Composition and Functional Properties of Perilla Seed and Perilla Seed Oil

The entire plant of Perilla is very useful and nutritious as it contains fat, protein, vitamins, minerals and phytochemicals. The crude protein, crude fat and moisture content of Perilla leaf extract is 5.47%, 7.61% and 7.68% respectively.³⁶ Similar to spinach leaves, Perilla leaves are also a rich source of carotenoids.³⁷ The seed contain a nutty flavor, yellowish oil (40%), protein, amino acids (Valine, Leucine, Isoleucine, Lysine, Tryptophan, Threonine, Tyrosine, Phenylalanine, Cysteine, Methionine, Histidine, Aspartate, Serine, Glutamate, Proline), polyphenols  The protein content of Perilla seed improved with hulling and roasting, as protein content of whole Perilla seed and Perilla kernel are 17.2% and 20.1% respectively [38]. Proximate content of Perilla seed is summarized in table 2. Perilla seed also have been found to contain some essential mineral (Calcium, iron, zinc, magnesium and phosphorous). Mineral composition of Perilla seeds are summarized in table 3.

Table 2: Proximate composition of Perilla seeds.

Components	Perilla seed (%)
Moisture	6.02 ± 0.12
Ash	3.33  ± 0.02
Total lipids	42.27  ± 1.69
Crude protein	25.38  ± 0.10
Carbohydrate	23.00  ± 1.54

 

Values reported as means ± SD of three replicate analyses (n = 3).

Source- Sargi et al., 2013.³⁹

Table 3: mineral composition of Perilla seeds (per 100g).

Minerals	Perilla seed
Calcium (mg)	249.9
Magnesium (mg)	261.7
Phosphorous (mg)	677.2
Iron(mg)	9.54
Manganese(mg)	4.93
Zinc (mg)	4.22
Chromium (µg)	17.6
Copper (mg)	0.20

 

Source – Longvah & Deosthale (1991).²⁶

In a study Perilla seed oil was extracted with a mixture of chloroform and methanol solvent (2:1, v/v) and total lipid content was found to be 40%. Major fatty acids reported in Perilla oil were
linolenic acid, linoleic acid, palmitic acid, oleic acid and stearic acid (Table 4). Neutral lipids accounted for about 91.2- 93.9% followed by glycolipids (3.9-5.8%) and phospholipids (2-3%) respectively. The neutral lipids contain triacylglycerol (88.1-90%), sterol ester (4.1-6.2%) and hydrocarbon (1.9-2.7 %) and some amount of free fatty acid. The glycolipid fraction separated into four fractions by thin layer chromatography, the major GL were esterified steryl glycoside (48.9-53.2%) and sterylglycoside (22.1-25.4%). Monogalactosyldiacylglycerol and digalactosyldiacylglycerol were present in small quantities. Among the phospholipids, phosphatidylethanolamine (50.4-57.1%), phosphatidylcholine (17.6-20.6%) and phosphatidic acid (13.6-19.9%) were the most abundant.  Lysophosphatidylcholine, phosphatidylserine and phosphatidylinositol were present in small quantities [40]. In an another study compressed fluids (CO2 and LPG) were used under different condition of pressure and temperature to extract Perilla seed oil and it was found that Perilla seed oil extracted with compressed LPG showed higher yield (42.20 %) and  antioxidant activity.⁴¹

Table 4: Analysis of fatty acid (as a percentage of total oil).

Compound	Perilla Seed Oil
C16:0 Palmitic	5.94 ± 0.12
C18:0 Stearic	2.20 ± 0.14
C20:0 Arachidic	0.20 ± 0.01
C22:0 Behenic	0.03 ± 0.01
C24:0 Lignoceric	0.01 ± 0.00
C16:1 Palmitolic	0.12 ± 0.02
C18:1 oleic acid	16.21  0.07
C18:2 linoleic acid	14.72 ± 0.08
C18:3 linolenic acid	60.93 ± 0.10
C20:1	0.17 ± 0.02
C20:2	0.05 ± 0.01
SFA	7.58 ± 0.05
MUFA	16.57 ± 0.11
PUFA	75.85 ± 0.17
Ration of n-6/n-3	0.22
Lipid %	40.0 ± 1.6

 

Source – Ciftci et al., 2012.⁶

Phytochemicals Profile

Perilla plant has undergone various phytochemical studies and a range of different compounds has been isolated. Phytochemical estimation of Perilla seed showed the presence of phenols and flavonoids. Rosmarinic acid, Rosmarinic acid-3-O- glucoside, caffeic acid, ferulic acid and caffeic acid-3-O- glucoside were major phenolic compounds identified in Perilla seed whereas apigenin, luteolin and catechin were major flavonoids present in Perilla seed [4]. Polyunsaturated fatty acid, policasonal, sterols and tocopherols were also identified in Perilla seed.^5,36 The total phenolic content (TPC) and total flavonoid content (TFC) of Perilla seed oil is 18.07 mg GAE/g oil extract and 0.15 mg RE/g oil extract respectively [20]. Major Phytochemical of Perilla seed are given in figure 1.

Figure 1: Main active polyphenols in Perilla seed. Click here to view figure

 

Table 5: Tocopherols content, Sterol and Policosanols composition of Perilla oils.

No.	Compounds	Perilla seed oil (mg/kg oil)
1	Tocopherols
	α-tocopherol	43.81 ± 0.38
	β-tocopherol	–
	γ –tocopherol	344.56 ± 0.05
	δ-tocopherol	23.10 ± 1.48
2	Sterols
	Campesterol	321.16 ± 5.16
	Stigmasterol	177.50 ± 2.65
	β-sitosterol	2773.85 ± 12.04
3	Policosanols
	C21-OH	4.51 ± 0.12
	C22-OH	–
	C23-OH	7.75 ± 0.14
	C24-OH	4.08 ± 0.11
	C25-OH	24.64 ± 0.72
	C26-OH	5.19 ± 0.09
	C27-OH	48.51 ± 0.87
	C28-OH	11.28 ± 0.25
	C29-OH	148.53 ± 0.04
	C30-OH	15.13 ± 0.88
	C31-OH	32.78 ± 4.14
	C32-OH	–

 

Values reported as means ± SD of three replicate analyses (n = 3).

Source- Jung et al., 2012.⁴²

Pharmacological Effects

Anti-Asthmatic

In China Perilla is a major constituent in various folk medicines used for the treatment of Asthma, because of the flavone luteolin present in Perilla, which gives relaxant action to the smooth muscles of the trachea.⁴³ Dietary treatment plays a key role in decreasing the Asthmatic allergies, serum OVA-specific immunoglobulin1 level, and total immunoglobulin A antibodies, hence a diet with Perilla oil supplementation helps in treating Asthma.⁴³ A clinical study on asthma patients showed that Perilla seed oil improves pulmonary function and also suppresses the leukotriene LB4 and LC4 release from leucocytes which are responsible for asthma. The effect of Perilla seed oil and Corn oil on Asthma patients was compared, and the results revealed that Perilla seed oil rich in α- linolenic acid (omega-3) inhibits the generation of leukotriene LB4 and LC4 more efficiently than corn oil rich in linoleic acid (omega-6).^44,45 In  another study, the anti-asthmatic effect of Perilla seed oil was investigated both in- vivo and in – vitro in guinea pig induced by antigen and  it was concluded that Perilla seed oil inhibited airway constriction and also improved lung function by decreasing lung resistance and increasing dynamic lung compliance.⁴⁶

Anti-Diabetic

A study carried out on the anti-diabetic effect of Perilla seed sprouts in type 2 diabetes mice model. The supplementation of Perilla seed (100, 300, and 1,000 mg/kg of body weight)  sprouts decreased body weight and serum triacylglyceride level; improved hyperglycemia, glucose tolerance and insulin resistance; induced AMP-activated protein kinase (AMPK) activation and regulated gluconeogenesis.⁴⁷ In another study, chlorogenic acid and rosmarinic acid are identified as Aldose reductase enzyme inhibitor in an ethyl acetate soluble fraction of methanol extract of Perilla, which reduces the diabetic complications.⁴⁸ Additionally the effect of Perilla oil supplementation on gut microbiota was studied in diabetic KKAy mice for 12 weeks. It was found that Perilla oil supplementation significantly reduced the microfora blautia, which is a gram positive anaerobe bacterium and responsible for glucose metabolism disturbances and increased the microfora Lactobacillus, which considered to be a beneficial bacteria as it converts sugars to lactic acid.⁴⁹

Anti-Depressant

Perilla is an important constituent of anti- depression medicines such as Hange-kouboku-to, Saiboku-to, SYJN and Banxia Houpu.^7,28,29 In literature, some researchers reported that the bioactive constituent of Perilla fructescence such as rosmarinic acid and apigenin has an anti-depression effect. The intraperitoneal administration of Rosmarinic acid (2 mg/kg.) and caffeic acid (4 mg/kg) each significantly reduced the duration of immobility in the forced swimming test in mice.^50,51 Similarly, intraperitoneal doses of Apigenin at 12.5 and 25 mg/kg significantly lessened the duration of immobility in the forced swimming test in mice.⁵²

Anti-Cancer

Perilla leaves and its seed oil showed anti-cancerous properties. In an experiment it was reported that a treatment of 12% fat diet with Perilla and safflower oil in the proportion of 1:3, 1:1 and Perilla oil alone, showed protection against MNU- induced colon tumors as compared with safflower oil alone in female f3344 rats.⁵³ further synergistic effect of  Perilla oil with β- carotene in the prevention of colon cancer was also proved, the supplementation of Perilla oil with olive oil and b carotene  reduced colonic aberrant crypt foci induced by azoxymethane  in F344 male rates.⁵⁴ The Perilla seed main active polyphenol rosmarinic acid, is reported to inhibited apoptosis in H9C2 cardiac muscle cells induced by Adriamycin (ADR) by inhibiting reactive oxygen species and the activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase.⁵⁵

Antimicrobial

In a study it was found that the ethyl acetate extract of Perilla seeds and polyphenols isolated form ethyl acetate extract (luteolin) was effective against oral pathogenic bacteria (Oral Streptococci and strains of Porphyromonas gingivalis).⁵⁶ Similarly, Perilla seed oil in combination with Nisin acts as bactericidal against L. monocytogenes and S. aureus.⁵⁷

Anti-Oxidant

The antioxidant properties of Perilla seed, leaf and stalk extract investigated by DPPH, superoxide radical scavenging activity, reducing power and metal chelating ability and reported that 50% of methanol leaf extract could be used as a new functional food.⁵⁸ Perilla seeds reported to have the higher antioxidant activity than chia seeds and flax seeds, measured using ABTS, DPPH and FRAP assays, shown in Figure 2.³⁹ The average tocopherol content in Perilla seed (152.1 mg/kg) is higher than that in various other seed oil crops, such as linseed (83.0 mg/kg), mustard (69.0 mg/kg) and sesame (100.0 mg/kg).⁵⁹ Four antioxidant compounds isolated from Perilla extract and identified as rosmarinic acid, luteolin, apigenin and chrysoeriol.⁶⁰  Due to the antioxidant activity of rosmarinic acid, it protects MES23.5 cells from 6 hydroxydopamine induce neurotoxicity.⁶¹ Also Luteolin isolated from methanol extract of Perilla seed reduced the hydrogen peroxide induced cytotoxicity in primary neurons from newborn rat cortex.⁶² In a more recent study, two antioxidant peptides were isolated from enzymes hydrolysates of defatted Perilla seed protein and identified as Tyyr-Leu (YL) and Phe- Tyr (FY). It was found that these peptides inhibited the lipid peroxidation in the rat liver and protect against hydrogen peroxide induced damage in HepG-2 cells.⁶³

Figure 2: Comparison of antioxidant activity of Perilla seeds with flax and chia seeds by FRAP, DPPH and ABTS assay. Click here to view figure

 

Cardioprotective

Recently, the effect of Perilla seeds oil or palm oil were studied on serum cholesterol, hepatic lipid accumulation and hepatic expression of proteins regulating lipid metabolism in high fat diet  (HFD) fed mice for 90 days. Additionally, Perilla oil treatment produced a significantly reduction in serum cholesterol and hepatic triglyceride levels compared with palm oil treatment in HFD-fed mice, also Perilla seed oil treatment decreased lipid accumulation in the thoracic aorta and liver compared with palm oil treatment.⁶⁴ Another study was designed to compare the effect of feeding Safflower and Perilla oil on lipid metabolism in young and adult rats and concluded that α- linolenic acid present in Perilla oil regulates serum cholesterol, as α-linolenic acid reduces the expression of mRNA for HMG-CoA reductase, an enzyme essential for cholesterol biosynthesis.⁶⁵ Perilla seed oil when fed to the mice for the period of eight weeks showed cardioprotective effect, as it increases the plasma concentration of docosapentaenoic acid and eicosapentaenoic acid.⁶⁶ Furthermore, Replacement of Soybean with Perilla oil in cooking for 10 months resulted in increased serum level of n-3 fatty acid in elderly subjects, which showed cardioprotective activity without causing any side effect.⁶⁷ In an another investigation, Apigenin isolated from Perilla seed shows the anti-obesity effect by increasing pro-opiomelanocortin (POMC) and “cocaine and amphetamine-related transcript (CART) anorexigenic neuropeptides in neuronal cells which further reduced food intake in mice.^68,69 The effect of Perilla oil on platelet aggregation and thrombosis were studied in vitro in rabbits and in vivo in rats respectively. Perilla oil incubated rabbit platelet showed reduction in aggregation induced by collagen (2.5µg/ml) and thrombin (0.1U/ml), also Perilla oil treatment (0.5,1 or 2ml/kg) delayed the arterial occlusion induced by 35% FeCl3 solution in rats.⁷⁰ 10% Perilla seed oil supplementation in wister rats diet for 18 months significantly reduced the serum cholesterol and triglyceride level.⁷¹ Additionally, the use of Perilla seed oil in emulsified form in the preparation of rice porridge showed significant reduction in plasma triglycerides in human as well as in animal subject and also showed high score in sensory evaluation.⁷²

Effect on Gastrointestinal System

Gastrointestinal discomfort is caused because of ileum contraction and its risk factors are daily stress, food sensitivity and allergies, infections and genetic preposition. The effect of Perilla seed oil on gastrointestinal motility was investigated and it was found that Perilla seed oil supplementation (5ml/kg, 7.5ml/kg and 10ml/kg) increased the motility and produced a laxative effect in constipated  albino rats, constipation in rats was induced by loperamide.⁷³ Similarly, the intraperitoneal administration of Perilla seed oil (1,2 and 3ml/kg) in wister strain albino rats provide significant protection against reflux esophagitis by inhibiting esophagitis index, reducing the volume of gastric juice and increasing gastric pH.⁷⁴

Neuroprotective

The active component of Perilla seed containing certain fatty acid (α- linolenic acid) showed anti-apoptosis and anti-inflammatory effect in the brain cells of mice during atherogenic diet, thus showed neuroprotective effect.⁷⁵ Perilla seed oil rich source of α- linolenic acid, could offer a novel substitute to fish oil for neuroprotective and mitochondrial functions in the brain.⁷⁶ More recently the safety and feasibility of Perilla seed oil as an antioxidative therapy has been proved in patients with mild to moderate dementia.⁷⁷ Cold pressed seed oil of Perilla showed protective effect against beta-amyloid induced neurotoxicity in PC12 rat pheochromocytoma cells  and could be used as a functional food in Alzheimer disease.⁷⁸ In a six month randomized, placebo-controlled trial, supplementation of Perilla seed oil with brain training in elderly with mild cognitive impairment, improved plasma and erythrocyte plasma membrane α-linolenic acid levels; enhanced cognitive function measured by Frontal Assessment Battery (FAB) score.⁷⁹ Luteolin and apigenin isolated from ethanolic extract of Perilla seed possess monoamine transporter activator action in monoamine- transporter transgenic Chinese hamster ovary cell or wild dopaminergic cell lines for improvement of hypermonoaminergic neuropsychological disorders.⁸⁰ Further, long term administration of luteolin in rats improved spatial cognition deficits and neuronal damage induced by chronic cerebral hypoperfusion.⁸¹

Other Pharmacological Activity

Hepatoprotective activity of the major phenolic components (rosmarinic acid and caffeic acid) present in cold-pressed Perilla frutescence seed flour (CP-PFSF) after oil extraction was investigated in vivo and in vitro. In vitro, treatment with RA-rich extract reduced H2O2-induced cytotoxicity and in In vivo, oral administration of RA-rich extract significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase, and hepatocyte degeneration and neutrophilic infiltration induced by tert-butyl hydroperoxide.⁸² It has proved that Perilla oil exerts same properties as fish oil in reduction of hepatic level of proinflammatory cytokines, the levels of IL-1𝛽, TNF- 𝛼, and IL-6 found significantly lower in fish oil and Perilla oil supplemented to high fat diet mice, also Perilla oil and fish oil supplementation showed reduction in Gram-negative Prevotella, which might be considered as a cause in the development of non-alcoholic fatty liver disease.⁸³ Perilla frutescense increases cytokine LIF (leukemia inhibitory factor) which regulates endometrial receptivity. Proper implantation of the embryo depends upon the enhancement of endometrial receptivity, thus Perilla can be beneficial for women suffering from faulty implantation.⁸⁴

Conclusion

The present review paper reports extensive information about the traditional uses, nutritional, phytochemistry and Pharmacological analysis Perilla seeds and its oil. It is found that leaves, seeds and its oil are used in various regions of the world like China, Japan, Korea and India in the preparations of spices, condiments, sauces, tea, leafy vegetables and herbal medicines. In Japan and China, this plant is also used as a major constituent of anti-depressant and anti-asthmatic herbs such as SYJN, Banxia Houpu, Hange-kouboku-to, and Saiboku-to. Components of this plant are potential in curing diseases like food poisoning, asthma, diabetes, cancer and heart diseases. Medicinal investigation showed that the plant has potential antiviral, antioxidant, anti-inflammatory, anti-allergic, anti-aging and anti-tumor activities. The major phytochemical compounds reported in this species are phenols, flavonoids, phytosterols, tocopherols, Policosanols and fatty acid. Perilla seed oil is also a rich source of essential fatty acids. Despite its numerous benefits and uses, this plant is still unknown to the common population.

There are very few toxicological researches on Perilla plant. Although, there are some studies that proved that its consumption is safe at a low dosage for a short period of time. Once the safe dosages of Perilla plant are established, its different parts could be used as an active constituent in the formulation of various functional foods. Hence, further researches are required to validate its use in product development by using seed and seed oil.

Acknowledgements
The authors are grateful to University Grant Commission (UGC), India for the doctorate fellowship and for the financial support.

Conflict of Interest

The authors have no conflicts of interest to report. Funding source of this study was University Grant Commission (UGC), India.

References

1. M. Nitta, J.K. Lee, O. Ohnishi, Asian Perilla Crops and Their Weedy Forms : Their Cultivation , Utilization and Genetic Relationships, Econ. Bot. 57 (2003) 245–253. http://www.jstor.org/stable/4256682.
2. Nitta M, Lee JK, Kang CW, Katsuta M, Yasumoto S, Liu D, Nagamine T, Ohnishi O. The distribution of Perilla species. Genetic Resources and Crop Evolution. 52 (2005) 797-804.
3. A. Pandey, K.C. Bhatt, Diversity distribution and collection of genetic resources of cultivated and weedy type in Perilla frutescens (L.) Britton var. frutescens and their uses in Indian Himalaya, Genet. Resour. Crop Evol. 55 (2008) 883–892. doi:10.1007/s10722-007-9293-7.
4. Y. Peng, J. Ye, J. Kong, Determination of phenolic compounds in Perilla frutescens L. by capillary electrophoresis with electrochemical detection, J. Agric. Food Chem. 53 (2005) 8141–8147. doi:10.1021/jf051360e.
5. L. Meng, Y. Lozano, I. Bombarda, E.M. Gaydou, B. Li, Polyphenol extraction from eight Perilla frutescens cultivars, Comptes Rendus Chim. 12 (2009) 602–611. doi:10.1016/j.crci.2008.04.011.
6. O.N. Ciftci, R. Przybylski, M. Rudzinska, Lipid components of flax, Perilla, and chia seeds, Eur. J. Lipid Sci. Technol. 114 (2012) 794–800. doi:10.1002/ejlt.201100207.
7. L. Luo, J.N. Wang, L.D. Kong, Q.G. Jiang, R.X. Tan, Antidepressant effects of Banxia Houpu decoction, a traditional Chinese medicinal empirical formula, J. Ethnopharmacol. 73 (2000) 277–281.
8. H.K. Kim, S. Choi, H. Choi, Suppression of hepatic fatty acid synthase by feeding α-linolenic acid-rich Perilla oil lowers plasma triacylglycerol level in rats, J. Nutr. Biochem. 15 (2004) 485–492. doi:10.1016/j.jnutbio.2004.02.010.
9. H. Ueda, M. Yamazaki, Inhibition of tumor necrosis factor- α production by orally administering a Perilla leaf extract., Biosci. Biotechnol. Biochem. 61 (1997) 1292–1295. doi:10.1271/bbb.61.1292.
10. N.K. Chauhan, S. Singh, S. Zafar Haider, H. Lohani, B.L. Kushwaha, Compositional variability in volatiles from different plant organs of Perilla frutescens l. cultivated in Uttarakhand (India), J. Pharm. Res. 6 (2013) 361–363. doi:10.1016/j.jopr.2013.03.004.
11. K. Bachheti, R, A. Joshi, T. Ahmed, Review Article A Phytopharmacological Overview on Perilla frutescens, Int. J. Pharm. Sci. Rev. Res. 26 (2014) 55–61.
12. H. Yu, J. Qiu, L. Ma, Y. Hu, P. Li, J. Wan, Phytochemical and phytopharmacological review of Perilla frutescens L . ( Labiatae ), a traditional edible-medicinal herb in China, Food Chem. Toxicol. 108 (2017) 375–391. doi:10.1016/j.fct.2016.11.023.
13. M. Asif, Nutritional importance of monounsaturated and polyunsaturated fatty acids of Perilla oil, Int. J. Phytopharm. 2 (2012) 154–161.
14. M. Igarashi, Y. Miyazaki, A review on bioactivities of Perilla: Progress in research on the functions of Perilla as medicine and food, Evidence-Based Complement. Altern. Med. (2013) 1–7. doi:10.1155/2013/925342.
15. M. Asif, Biological importance and health effect of Perilla frutescens plant., Indonesia. J. Pharm. 23 (2012) 113–121.
16. G. Singh, Perilla, (n.d.). http://www.flowersofindia.net/catalog/slides/Perilla.html (accessed April 7, 2018).
17. M. Asif, Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant oils., Orient. Pharm. Exp. Med. 11 (2011) 51–59. doi:10.1007/s13596-011-0002-x.
18. S.R. Bhandari, J.K. Lee, Y. Lee, Phytonutrient Profile of Purple Perilla ( Perilla frutescens var . crispa ) Seeds, Korean J. Crop Sci. 56 (2011) 199–204.
19. N.S. Kang, J.H. Lee, Characterisation of phenolic phytochemicals and quality changes related to the harvest times from the leaves of Korean purple Perilla ( Perilla frutescens ), Food Chem. 124 (2011) 556–562. doi:10.1016/j.foodchem.2010.06.071.
20. T.D. Xuan, G. Gangqiang, T.N. Minh, T.N. Quy, T.D. Khanh, An Overview of Chemical Profiles, Antioxidant and Antimicrobial Activities of Commercial Vegetable Edible Oils Marketed in Japan, Foods. 7 (2018) 1–14. doi:10.3390/foods7020021.
21. K. Tadao, H. Tamura, K. Yoshida, T. Goto, Structure of Malonylshisonin, a Genuine Pigment in Purple Leaves of Perilla ocimoides L. var. crispa Benth, Agric. Biol. Chem. 53 (1989) 797–800. doi:10.1080/00021369.1989.10869342.
22. L. Martinetti, A. Ferrante, N. Podetta, A. Bassoli, G. Borgonovo, A. Tosca, P. Spoleto, Effect of storage on the qualitative characteristics of Perilla, a potential new minimally processed leafy vegetable, J. Food Process. Preserv. 41 (2017). doi:10.1111/jfpp.13214.
23. J. Yang, H. Kim, L. Chung, Sensory Characteristics and Consumer Acceptability of Perilla Porridges, Food Sci. Biotechnol. 21 (2012) 785–797. doi:10.1007/s10068-012-0102-5.
24. K. Hye-Ryun, K.D. Sanjeev, K. Il-Doo, P. In-Joo, Physicochemical and sensory characteristics of pepper oil sauce prepared from Perilla oil, African J. Food Sci. 10 (2016) 352–358. doi:10.5897/AJFS2016.1500.
25. S. Kumar, The economic plants of north east India., Scientific Publishers, 1999.
26. T. Longvah, Y.G. Deosthale, Chemical and nutritional studies on Hanshi (Perilla frutescens), a traditional oilseed from northeast India, J. Am. Oil Chem. Soc. 68 (1991) 781–784. doi:10.1007/BF02662172.
27. J.M.A. Van Der Valk, C.J. Leon, M. Nesbitt, Macroscopic authentication of Chinese materia medica ( CMM ) : A UK market study of seeds and fruits, 8 (2017) 40–51.
28. Z. Huang, Q.Q. Mao, X.M. Zhong, C.R. Feng, A.J. Pan, Z.Y. Li, Herbal formula SYJN protect PC12 cells from neurotoxicity induced by corticosterone, J. Ethnopharmacol. 125 (2009) 456–460. doi:10.1016/j.jep.2009.07.018.
29. Y. Ikarashi, M. Yuzurihara, I. Sakakibara, A. Takahashi, H. Ishimaru, Y. Maruyama, Effects of an oriental herbal medicine , “ Saiboku-to ”, and its constituent herbs on Compound 48 / 80-induced histamine release from peritoneal mast cells in rats, Phytomedicine. 8 (2001) 8–15.
30. T. Makino, Y. Furuta, H. Fujii, T. Nakagawa, H. Wakushima, Effect of Oral Treatment of Perilla frutescens and Its Constituents on Type-I Allergy in Mice, Biol. Pharm. Bull. 24 (2001) 1206–1209.
31. J.S. Bae, M. Han, H.S. Shin, M.K. Kim, C.Y. Shin, D.H. Lee, J.H. Chung, Perilla frutescens leaves extract ameliorates ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin, J. Ethnopharmacol. 195 (2017) 334–342. doi:10.1016/j.jep.2016.11.039.
32. M.S. Chung, W.J. Bae, S.W. Choi, K.W. Lee, H.C. Jeong, F. Bashraheel, S.H. Jeon, J.W. Jung, B.I. Yoon, E.B. Kwon, H.A. Oh, S.Y. Hwang, S.W. Kim, An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla frutescens Var. acuta and green tea stimulates hair growth in mice, BMC Complement. Altern. Med. 17 (2017) 515. doi:10.1186/s12906-017-2003-x.
33. N. Li, Z.-J. Zhang, X.-J. Li, H.-Z. Li, L.-X. Cui, D.-L. He, Microcapsules biologically prepared using Perilla frutescens (L.) Britt. essential oil and their use for extension of fruit shelf life, J. Sci. Food Agric. 98 (2018) 1033–1041. doi:10.1002/jsfa.8552.
34. V.. Negi, L.. Rawat, P.. Phondani, A. Chandra, Perilla frutescens in Transition : a medicinal and oil yielding plant need instant conservation , a case study from Central Himalaya , India, Environ. We Int. J. Sci. Tech. 6 (2011) 193–200.
35. J. Wu, C. Yang, Y. Rong, Z. Wang, Preparation and nutritional characterization of Perilla chewable tablet, Procedia Eng. 37 (2012) 202–207. doi:10.1016/j.proeng.2012.04.227.
36. Y. Li, J. Gong, C. Liu, Z. Wang, Y. Wu, Phytochemicals , nutritional analysis and in vitro antioxidant activities of pickled Perilla frutescens ethanolic leaf extract, European J. Med. Plants. 4 (2014) 303–314.
37. G. Schirrmacher, T. Skurk, H. Hauner, J. Graßmann, Effect of Spinacia oleraceae L. and Perilla frutescens L. on Antioxidants and Lipid Peroxidation in an Intervention Study in Healthy Individuals, Plant Foods Hum. Nutr. 65 (2010) 71–76. doi:10.1007/s11130-009-0152-x.
38. T. Longvah, Y.G. Deosthale, Effect of dehulling, cooking and roasting on the protein quality of Perilla frutescens seed, Food Chem. 63 (1998) 519–523. doi:10.1016/S0308-8146(98)00030-2.
39. S.C. Sargi, B.C. Silva, H.M.C. Santos, P.F. Montanher, J.S. Boeing, O.O. Santos Júnior, N.E. Souza, J.V. Visentainer, Antioxidant capacity and chemical composition in seeds rich in omega-3: chia, flax, and Perilla, Food Sci. Technol. 33 (2013) 541–548. doi:10.1590/S0101-20612013005000057.
40. H.S. Shin, S.W. Kim, Lipid composition of Perilla seed, J. Am. Oil Chem. Soc. 71 (1994) 619–622. doi:10.1007/BF02540589.
41. G. Scapin, E.R. Abaide, R.F. Martins, R.G. Vendruscolo, M.A. Mazutti, R. Wagner, C.S. da Rosa, Quality of Perilla oil (Perilla frutescens) extracted with compressed CO 2 and LPG, J. Supercrit. Fluids. 130 (2017) 176–182. doi:10.1016/j.supflu.2017.08.007.
42. D.M. Jung, S.H. Yoon, M.Y. Jung, Chemical Properties and Oxidative Stability of Perilla Oils Obtained From Roasted Perilla Seeds As Affected by Extraction Methods, J. Food Sci. 77 (2012) C1249–C1255. doi:10.1111/j.1750-3841.2012.02965.x.
43. W.C. Ko, C.M. Shih, I.J. Leu, T.T. Chen, J.P. Chang, Mechanisms of relaxant action of luteolin in isolated guinea pig trachea, Planta Med. 71 (2005) 406–411. doi:10.1055/s-2005-864133.
44. M. Okamoto, F. Mitsunobu, K. Ashida, T. Mifune, Y. Hosaki, H. Tsugeno, S. Harada, Y. Tanizaki, Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma., Intern. Med. 39 (2000) 107–111.
45. H.H. Chang, C.S. Chen, J.Y. Lin, Dietary Perilla oil inhibits proinflammatory cytokine production in the bronchoalveolar lavage fluid of ovalbumin-challenged mice, Lipids. 43 (2008) 499–506. doi:10.1007/s11745-008-3171-8.
46. Y.M. Deng, Q.M. Xie, S.J. Zhang, H.Y. Yao, H. Zhang, Anti-asthmatic effects of Perilla seed oil in the guinea pig in vitro and in vivo, Planta Med. 73 (2007) 53–58. doi:10.1055/s-2006-957062.
47. D. Kim, S.J. Kim, K. Yu, S. Jeong, S. Kim, Anti-hyperglycemic effects and signaling mechanism of Perilla frutescens sprout extract, Nutr. Res. Pract. 12 (2018) 20–28.
48. J.H. Paek, K.H. Shin, Y.-H. Kang, J.-Y. Lee, S.S. Lim, Rapid Identification of Aldose Reductase Inhibitory Compounds from Perilla frutescens, Biomed Res. Int. (2013).
49. Wang, F., Zhu, H., Hu, M., Wang, J., Xia, H., Yang, X., … & Sun, G. (2018). Perilla Oil Supplementation Improves Hypertriglyceridemia and Gut Dysbiosis in Diabetic KKAy Mice. Molecular Nutrition & Food Research, 62(24), 1800299.
50. H. Takeda, M. Tsuji, M. Inazu, T. Egashira, T. Matsumiya, Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice, Eur. J. Pharmacol. 449 (2002) 261–267.
51. Y.M. Deng, Q.M. Xie, S.J. Zhang, H.Y. Yao, H. Zhang, Anti-asthmatic effects of Perilla seed oil in the guinea pig in vitro and in vivo, Planta Med. 73 (2007) 53–58. doi:10.1055/s-2006-957062.
52. T. Nakazawa, T. Yasuda, J. Ueda, K. Ohsawa, Antidepressant-Like Effects of Apigenin and 2 , 4 , 5-Trimethoxycinnamic Acid from Perilla frutescens in the Forced Swimming Test, Biol. Pharm. Bull. 26 (2003) 474–480.
53. T. Narisawa, Y. Fukaura, K. Yazawa, C. Ishikawa, Y. Isoda, Y. Nishizawa, Colon cancer prevention with a small amount of dietary Perilla oil high in alpha- linolenic acid in an animal model, Cancer. 73 (1994) 2069–2075. https://doi.org/10.1002/1097-0142(19940415)73:8%3C2069::AID-CNCR2820730810%3E3.0.CO;2-1.
54. C. Komaki, N. Onogi, M. Okuno, H. Moriwaki, T. Kawamori, T. Tanaka, H. Mori, Y. Muto, Suppressing effect of Perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats, Carcinogenesis. 17 (1996) 1291–1296. doi:10.1093/carcin/17.6.1291.
55. H. Yamamoto, T. Ogawa, Antimicrobial Activity of Perilla Seed Polyphenols against Oral Pathogenic Bacteria, Biosci. Biotechnol. Biochem. 66 (2002) 921–924. doi:10.1271/bbb.66.921.
56. E.-S. Lin, C.-C. Li, H.-J. Chou, Evaluation of the antioxidant and antiradical activities of Perilla seed, leaf and stalk extracts, J. Med. Plants Res. 8 (2014) 109–115. doi:10.5897/JMPR10.215.
57. E. Ryan, K. Galvin, T.P.O. Connor, A.R. Maguire, Phytosterol, Squalene, Tocopherol Content and Fatty Acid Profile of Selected Seeds, Grains, and Legumes, Plant Foods Hum. Nutr. 62 (2007) 85–91. doi:10.1007/s11130-007-0046-8.
58. L. Gu, T. Wu, Z. Wang, TLC bioautography-guided isolation of antioxidants from fruit of Perilla frutescens var. acuta, Food Sci. Technol. 42 (2009) 131–136. doi:10.1016/j.lwt.2008.04.006.
59. Ren, P., Jiang, H., Li, R., Wang, J., Song, N., Xu, H. M., & Xie, J. X. (2009). Rosmarinic acid inhibits 6-OHDA-induced neurotoxicity by anti-oxidation in MES23. 5 cells. Journal of molecular neuroscience, 39(1-2), 220-225.
60. Zhao, G., Yao-Yue, C., Qin, G. W., & Guo, L. H. (2012). Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons. Neurobiology of aging, 33(1), 176-186.
61. Yang, J., Hu, L., Cai, T., Chen, Q., Ma, Q., Yang, J., … & Hong, J. (2018). Purification and identification of two novel antioxidant peptides from Perilla (Perilla frutescens L. Britton) seed protein hydrolysates. PloS one, 13(7), e0200021.
62. Kim, S. R., Je, J., Jeong, K., Kim, S. J., Lee, K. Y., Choi, S. G., … & Park, S. W. (2018). Perilla Oil Decreases Aortic and Hepatic Lipid Accumulation by Modulating Lipogenesis and Lipolysis in High-Fat Diet-Fed Mice. Journal of medicinal food.
63. M. Ihara-Watanabe, H. Umekawa, T. Takahashi, Y. Furuichi, Comparative effects of safflower oil and Perilla oil on serum and hepatic lipid levels, fatty acid compositions of serum and hepatic phospholipids, and hepatic mRNA expressions of 3-hydroxy-3- methylglutaryl CoA reductase, LDL receptor, and cholesterol, Food Res. Int. 33 (2000) 893–900.
64. K.H. Chung, H.J. Hwang, K.O. Shin, W.M. Jeon, K.S. Choi, Effects of Perilla oil on plasma concentrations of cardioprotective (n-3) fatty acids and lipid profiles in mice, Nutr Res Pr. 7 (2013) 256–261. http://dx.doi.org/10.4162/nrp.2013.7.4.256
65. O. Ezaki, M. Takahashi, T. Shigematsu, K. Shimamura, J. Kimura, T. Gotoh, Long-Term Effects of Dietary a-Linolenic Acid from Perilla Oil on Serum Fatty Acids Composition and on the Risk Factors of Coronary Heart Disease in Japanese Elderly Subjects, J. Nutr. Sci Vitaminol. 45 (1999) 759–772.
66. H.-J. Myoung, G. Kim, K.-W. Nam, Apigenin Isolated from the Seeds of Perilla frutescens Britton var crispa ( Benth .) Inhibits Food Intake in C57BL / 6J Mice, Arch Pharm Res. 33 (2010) 1741–1746. doi:10.1007/s12272-010-1105-5.
67. R. Mopuri, S. Islam, Medicinal plants and phytochemicals with anti-obesogenic potentials : A review, Biomed. Pharmacother. 89 (2017) 1442–1452. doi:10.1016/j.biopha.2017.02.108.
68. Jang, J. Y., Kim, T. S., Cai, J., Kim, J., Kim, Y., Shin, K., … & Rhee, M. H. (2014). Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation. Laboratory animal research, 30(1), 21-27.
69. T. Longvah, Y.G. Deosthale, P. Uday Kumar, Nutritional and short term toxicological evaluation of Perilla seed oil, Food Chem. 70 (2000) 13–16. doi:10.1016/S0308-8146(99)00263-0.
70. Jo, H., Kim, M., Lee, J., Kim, H., & Song, Y. O. (2013). Anti-atherogenic properties of emulsified Perilla oil (EPO) in apo E KO mice and plasma lipid lowering effects of rice porridge containing EPO in healthy young adults. Food Science and Biotechnology, 22(1), 79-85.
71. M. Asif, A. Kumar, Nutritional and Functional Characterisations of Perilla Frutescens Seed Oil and Evaluation of Its Effect on Gastrointestinal Motility, J. Pharm. Sci. 8 (2010) 1–12.
72. Arya, E., Saha, S., Saraf, S. A., & Kaithwas, G. (2013). Effect of Perilla frutescens fixed oil on experimental esophagitis in albino Wistar rats. BioMed research international, 2013.
73. J. Seong, Y.O. Song, Perilla oil rich in alpha-linolenic acid inhibits neuronal apoptosis and the expression of inflammation-mediator protein in apoE KO mice, Biocatal. Agric. Biotechnol. 1 (2012) 167–173. doi:10.1016/j.bcab.2012.01.001.
74. G.P. Eckert, C. Franke, M. Nöldner, O. Rau, M. Wurglics, M. Schubert-Zsilavecz, W.E. Müller, Plant derived omega-3-fatty acids protect mitochondrial function in the brain, Pharmacol. Res. 61 (2010) 234–241. doi:10.1016/j.phrs.2010.01.005.
75. Kamalashiran, C., Pattaraarchachai, J., & Muengtaweepongsa, S. (2018). Feasibility and Safety of Perilla Seed Oil as an Additional Antioxidative Therapy in Patients with Mild to Moderate Dementia. Journal of Aging Research, 2018.
76. P. Senavong, S. Kongkham, S. Saelim, V. Suangkavathin, Neuroprotective Effect of Perilla Extracts on PC12 Cells, J Med Assoc Thai. 99 (2016) 256–264.
77. M. Hashimoto, K. Yamashita, K. Matsuzaki, S. Kato, O. Shido, Beneficial Effects of Perilla oil and brain training intervention on cognition in elderly Japanese, 2017. doi:10.1093/geroni/igx004.1665.
78. B. Xu, X.X. Li, G.R. He, J.J. Hu, X. Mu, S. Tian, G.H. Du, Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats, Eur. J. Pharmacol. 627 (2010) 99–105. doi:10.1016/j.ejphar.2009.10.038.
79. Zhao, G., Qin, G. W., Wang, J., Chu, W. J., & Guo, L. H. (2010). Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt. Neurochemistry international, 56(1), 168-176.
80. Y. Zhang, X. Mei, Q. Zhang, M. Li, X. Wu, C. Ma, Protective effect of a rosmarinic acid–rich extract from cold-pressed Perilla frutescens seed flour on oxidative hepatotoxicity in vitro and in vivo, J. Food Biochem. 42 (2018). doi:10.1111/jfbc.12492.
81. Tian, Y., Wang, H., Yuan, F., Li, N., Huang, Q., He, L., … & Liu, Z. (2016). Perilla oil has similar protective effects of fish oil on high-fat diet-induced nonalcoholic fatty liver disease and gut dysbiosis. BioMed research international, 2016.
82. E.Y. Kim, H.J. Choi, T.W. Chung, J.Y. Choi, H.S. Kim, Y.S. Jung, S.O. Lee, K.T. Ha, Water-extracted Perilla frutescens increases endometrial receptivity though leukemia inhibitory factor-dependent expression of integrins, J. Pharmacol. Sci. 131 (2016) 259–266. doi:10.1016/j.jphs.2016.07.004 .

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