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Perilla - Certainly Looks Intriguing

This article is not medical or healthcare advice. Before starting any health or medical related regimen, seek the advice of your Primary Care Physician, or an M.D.

Perilla frutescens (L.) Britt. (PF) is an annual herbal medicinal, aromatic, functional food, and ornamental plant that belongs to the mint family, Lamiaceae. The origin of perilla traces back to East Asian countries. The leaves, seeds, and stems of P. frutescens are used for various therapeutic applications in folk medicine. The stem, leaf, and seed of the herb was equally commonly used. The drug items of the herb in traditional Chinese medicine are dried “Perilla leaf”, “Perilla stalk” and “Perilla seed”. Perilla has shown various biological activities such as antioxidant, antimicrobial, anti-allergic, antidepressant, anti-inflammatory, anticancer, and neuroprotection effects.

 Perilla has traditionally been prescribed to treat depression-related disease, anxiety, asthma, chest stuffiness, vomiting, coughs, colds, flus, phlegm, tumors, allergies, intoxication, fever, headache, stuffy nose, constipation, abdominal pain, and indigestion, and acts as an analgesic, anti-abortive agent, and a sedative. Until now, 271 natural molecules have been identified in perilla organs including phenolic acids, flavonoids, essential oils, triterpenes, carotenoids, phytosterols, fatty acids, tocopherols, and policosanols. In addition to solvent extracts, these individual compounds (rosmarinic acid, perillaldehyde, luteolin, apigenin, tormentic acid, and isoegomaketone) have attracted researchers’ interest for its pharmacological properties.

Antioxidant Activity - Rosemarinic Acid, Luteolin, TXNRD-NrF2-Keap1 Induction

It has been reported that extracts from perilla seeds and leaves exhibit concentration-dependent antioxidant activity, isolated rosmarinic acid (RA) and luteolin from the fruit of P. frutescens. Similarly, among five phenolic compounds, RA and rosmarinic acid-3-O-glucoside were the dominant phenolic antioxidants with strong activity from cold-pressed perilla var. arguta seed flour studied by Zhou et al.. RA isolated by these authors from perilla leaf exhibited DPPH radical scavenging activity of 88.3 ± 0.7% at a concentration of 10 µg/mL with a drug concentration eliciting 50% of the maximum stimulation (SC50) value of 5.5 ± 0.2 µg/mL. In vivo, the protective activity of RA from P. frutescens leaf (PFL) was demonstrated on Lipopolysaccharide (LPS)-induced liver injury of d-GalN-sensitized mice owing to the scavenging or reducing activities of superoxide or peroxynitrite rather than to inhibition of tumor necrosis factor (TNF)-α production. The roles of the flavonoid luteolin from the perilla seeds seems to provide significant antioxidant activity for drugs and extracts. This compound significantly reversed hydrogen peroxide-induced cytotoxicity in primary cultured cortical neurons. Whereas, luteolin markedly attenuated the reactive oxygen species (ROS) production, and prevented the decrease in activities of mitochondria, catalase, and glutathione in ROS-insulted primary neurons, for preventing neurodegenerative diseases. In another study, luteolin inhibited the peroxidation of linoleic acid catalyzed using soybean lipoxygenase-1 with an IC50 of 5.0 M (1.43 µg/mL) noncompetitively. The monoterpene perillaldehyde was shown to be a potent thioredoxin inducer as it activates the Nrf2-Keap1 system. As part of an in vitro study in a human subjects, purple perilla leaves showed a higher antioxidant activity, and prevented the oxidation of low-density lipoprotein (LDL) than the green leaves [67]. Another study revealed that 20 ,30 -dihydroxy-40 ,60 -dimethoxychalcone (DDC) found in green perilla leaves enhanced cellular resistance to oxidative damage through activation of the Nrf2-antioxidant response element (ARE) pathway.

Modest Antibacterial and Antifungal Activity

Perilla seed extract rich in polyphenols was examined for its antibacterial activity against oral cariogenic Streptococci and periodontopathic Porphyromonas gingivalis. The ethyl acetate extracts exhibit strong antibacterial activity against oral Streptococci and various strains of P. gingivalis. This compound was also particularly active against filament fungi, with MIC values for M. mucedo and P. chrysogenum already at a 62.5 pg/mL concentration. Antibacterial activity of the leaf ethanol extracts of PF var. acuta against S. aureus and Pseudomonas aeruginosa. The antifungal activity of perilla EO distilled from aerial parts of the plant was also tested against phytopathogenic fungi and its activity was demonstrated in the cases of Aspergillus flavus, Aspergillus oryzae, Aspergillus niger, Rhizopus oryzae, and Alternaria alternate.

Anti-Depressant Activity

Numerous studies focusing on the extracts and/or purified compounds of P. frutescens displayed antidepressant-like effects. Phenolic-type constituents of perilla leaf, such as apigenin, at intraperitoneal doses of 12.5 and 25 mg/kg, RA (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each led to a considerable reduction of the duration of immobility in the forced swimming test. These compounds are also supposed to inhibit the emotional abnormality produced by stress, which is possibly mediated by the dopaminergic mechanisms in the mouse brain. In another study, daily consumption of perillaldehyde (20 mg/kg, oral) demonstrated significant antidepressant-like effects in mice with LPS-induced depression and the authors concluded a potential benefit in inflammation-related depression. The oil of PF seeds might have an anti-depressant activity too since a seed oil-rich diet during a forced swim test in adult male rats modulated the fatty acid profiles and brain-derived neurotrophic factor (BDNF) expression in the brain. Moreover, perilla seed oil rich in n-3 fatty acids improved Molecules 2019, 24, 102 15 of 23 cognitive function in rats by generating new hippocampal neural membrane structures as well as by inducing specific protein expression.

Anti-Inflammatory Activity - Esophagitis

Luteolin has been isolated from PFL ethanol extracts and was demonstrated to exert beneficial effects on neuro-inflammatory diseases in a dose-dependent manner (IC50 = 6.9 µM) through suppressing the expression of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells [43]. The ethanol extract of PFL was identified to display significant anti-inflammatory activity in LPS-induced Raw 264.7 mouse macrophages through the inhibition of the expression of pro-inflammatory cytokines, inhibition of mitogen-activated protein kinase (MAPK) activation, and of nuclear factor-kappa (NF-κB) nuclear translocation in response to LPS. The seed oil from PF showed a great protective effect against reflux esophagitis and this could be attributed to the antisecretory (anticholinergic, antihistaminic), antioxidant, and lipoxygenase inhibitory activities due to the presence of α-Linolenic acid (ALA) (18:3, n-3). Furthermore, RA isolated from PFL could inhibit the release of high mobility group box 1 protein (HMGB1) and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells, HMGB1-mediated hyperpermeability, and leukocyte migration in mice, as well as reduced cecal ligation and puncture (CLP)-induced HMGB1 release and sepsis-related mortality. This could be a potential remediation for various vascular inflammatory diseases, such as sepsis and septic shock, via inhibition of the HMGB1 signaling pathway. Lipophilic triterpene acids from ethanol extracts of red and green PFL were demonstrated to have remarkable anti-inflammatory activity on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice (ID50: 0.09–0.3 mg per ear), and on the Epstein–Barr virus early antigen (EBV-EA) activation (91–93% inhibition at 1 × 103 mol ratio/TPA),. A recent study in mice showed that PF extract ameliorated inflammatory bowel disease (IBD) via protection of dextran sulfate sodium-induced murine colitis, with NF-κB and signal transduction and activator of transcription 3 (STAT3) as putative targets. A perillaketone-type and alkaloid isolated from aerial parts of perilla showed the remarkable inhibitory effect on pro-inflammatory cytokines (TNF-α and/or IL-6) and inflammatory mediator (NO) in LPS-stimulated RAW264.7 cells, indicating that these compounds might be active components for inflammatory disorders.

Miscellaneous Effects

An aqueous extract of PF showed potent anti-HIV-1 activity via inhibition giant cell formation in co-culture of Molt-4 cells with and without HIV-1 infection showing inhibitory activity against HIV-1 reverse transcriptase . Deng et al. [104] described in vitro and in vivo anti-asthmatic effects of perilla seed oil in the guinea pig and concluded that the oil may ameliorate lung function in asthma by regulating eicosanoid production and suppressing leukotriene (LT) generation. The treatments significantly reduced the elevation of plasma aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, as well as anti-TNF and sphincter of Oddi dysfunction (SOD) treatment, compared with controls. In one investigation, the hepatoprotective effects of sucrose-treated perilla leaves, other than untreated leaves, exhibited the best result in vitro and in vivo.


  1. A Review of Ethnomedicinal, Phytochemical and Pharmacological Investigations of Perilla frutescens (L.) Britt. Hiwa M. Ahmed Sulaimani Polytechnic University. Molecules 2019, 24, 102; doi:10.3390/molecules24010102.

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