Perilla

Perilla oil refers to the fat soluble component (oil) of the seeds from the plant perilla frutescens (of the family lamiaceae), where the seeds are initially roasted and then pressed to provide the oil.^[1] This oil is frequently used as a condiment (Asian cuisine) due to its nutty taste and novel aromatic profile,^[2]

There is also an oil that can be derived from the leaves of perilla frutescens which is the medicinal component of the plant,^[3][4] and this oil may have a different composition than the seed oil (due to some volatiles also removed in the extraction process that remain in the oil)

Perilla seed oil is a dietary oil which confers a nutty taste after it is roasted and processed into an oil, and appears to be used in some asian cuisine. Perilla oil may also refer to an oil taken from the leaves which is sometimes used medicinally, and while the oil itself is similar there may be different minor components depending on which plant part it came from

It is sought after as a dietary supplement since, among vegetable sources of oil, perilla contains the highest proportion of omega-3 fatty acids relative to omega-6 fatty acids with omega-3 (as alpha-linolenic acid) being in the 54-65% range and omega-6 (as linoleic acid) being in the 14-20% range.^[5] This is the same fatty acid (alpha-linolenic acid; ALA) which comprises the omega-3 profile of other plant products such as flaxseed oil (55% ALA^[6]), salvia hispanica (Chia), borage oil, and walnuts but not animal based fish oil products.^[5]

Perilla oil (seed and leaf) is a source of plant-based omega-3 fatty acids, and appears to be one of the better sources when looking at the omega-3 content relative to omega-6 fatty acid content

Perilla frutescens (Perilla seeds; unless otherwise specified) include:

• Dietary lipids (35-45% raw seed weight^[6][2]), the leaves contain only 0.2% lipids by weight^[6]
• Rosmarinic acid in free form (average 1716.9μg/g in the seeds^[7]) and the 3-O-glucoside (average 1752.7μg/g in the seeds)^[7][8] totalling almost all phenolics (49% and 48%, respectively)^[8]
• Caffeic acid and its 3-O-glucoside (Minimally in seeds^[8] and up to 0.4% in leaves after methanolic extraction^[7])
• Luteolin and its 3-O-glucoside (Minimum in seeds^[8] and up to 7.1% in the leaves after methanolic extraction^[7])
• Apigenin and its 3-O-glucoside (Minimal in seeds^[8])
• Chrysoeriol (Minimal in seeds^[8])
• Scutellarin (Leaves at 1.9% after 50% methanolic extraction^[7]
• Perilla ketone (ie. 1-(3-furanyl)-4-methyl-1-pentanone) which is doubled to tripled in the roasting process^[2]
• Perilla aldehyde (doubled in the roasting process^[2]) thought to be unique to perilla, except for a small content in orange juice (0.1ppm or less^[9])
• Pyrazine compounds such as 2-methyl-3-propylpyrazine,^[10] tetramethylpyrazine,^[10] 2,3-diethyl-5-methylpyrazine,^[10] 2-methylpyrazine,^[1] 2,5-dimethylpyrazine,^[1] trimethylpyrazine,^[1] 2-ethyl-3,5-dimethylpyrazine,^[1]
• Furan compounds such as vinylfuran,^[1] 3-methylfuran,^[1] 5-Methylfurfuraldehyde,^[1] 2-Furanmethanol,^[1] 2-Furancarboxaldehyde^[1]
• Sulfur compounds such as Dimethyl sulfide^[1] and methanethiol^[1]

The final oil product of perilla frutescens (Perilla oil derived from seeds) contains:

• Alpha-linolenic acid (ALA in a 54-65% range^[5] with isolated studies reporting 64.19%^[1] and 59.08%^[11])
• Oleic acid (13-21% range,^[5] isolated studies at 14.20%^[1] and 16.70%^[11])
• Linoleic acid (14-21% range,^[5] isolated studies at 12.79%^[1] and 14.79%^[11])
• Palmitic acid (5.95-7.38%^[11][1])
• Stearic acid (1.85-1.93%^[11][1])
• Glycolipids in the 4-6% range^[5]
• Phospholipids in the 2-3% range^[5]
• Polyphenolis (mostly rosmarinic acid) at 80.56+/-1.79µg/g^[11]
• Vitamin E at 641.15+/-17.36µg/g which is mostly γ-tocopherol at 89% (comparable to corn oil overall, slightly more γ-tocopherol^[11])

Whereas Perilla oil derived from the leaves may contain:

• L-perillaldehyde^[3][4]
• Limonene^[3][4]
• Trans-caryophyllene^[3][4]
• Selinene^[3][4]
• Santalene^[3][4]
• Bergamotene^[3][4]

Roasting of perilla seeds is sometimes the only processing technique prior to oil extraction,^[1] and the composition of the final oil can vary depending on whether or not seeds are lightly or heavily roasted which can be determined by a heavy browning of the seeds during the roasting process.^[1]

In regards to the fatty acid composition, roasting appears to note minor content of butyric (short chain saturated fatty acid) and palmitoleic (monounsaturated fatty acid) which are not detectable in unroasted oils;^[1] either through oxidation of fatty acids or better yield seen with roasting.^[1]

Despite heat treatment (which may oxidize the lipids in oils^[12]), roasted perilla seeds seem to have less oxidation in the oil as assessed by DPPH.^[1] Such an unorthodox phenomena (heat treatment causing oxidative stability) has been noted with sesame seed oil^[13] thought to be due to alterations in the lignan content such as sesamin; since some of the bioactives in perilla (perilla ketone and perilla aldehyde) have been noted to be more than doubled during the roasting process^[2] it is thought that freeing these molecules up (by destroying the cell walls with heat) adds to the antioxidative properties.

Roasting in general is known to alter pyrazine molecules^[14] which applies to perilla oil pyrazines, with roasting causing a relative increase in 2-methylpyrazine (relative to 2,5-dimethylpyrazine) the more it is roasted;^[10] an overall increase in pyrazine quantity (16.78-fold) is seen in dark roasted seeds relative to light roasted^[10] and their content is further increased in a linear manner when heat treated at 190°C (34.75%) relative to 150°C (3.66%).^[2]

Acute ingestion of perilla oil results in a peak in plasma alpha-linolenic acid (ALA) levels approximately five hours after ingestion returning to near baseline levels after 24 hours^[5] and this change in ALA is not met with changes in either eicosapentaenoic acid (EPA) nor docosahexaenoic acid (DHA);^[5] enteric coated capsules may provide more overall exposure following a single dose (2.2-fold increase in plasma with 6g ALA enteric coated capsules relative to a 1.56-fold increase seen with noncoasted capsules).^[5]

Oral ingestion of 3-6mg/kg of the essential oil (derived from leaves) to mice subject to chronic unpredictable manageable stress (CUMS) testing over the course of four weeks noted that the oil had anti-stress properties in the latter two weeks with the higher dose being comparbale to 20mg/kg fluoxetine.^[3] Both treatments only saw benefits in the forced swim test but not open-field test, and it appeared that the reduction in BDNF mRNA that is seen during stress was attenuated with both treatments.^[3]

The leaf oil extract has shown benefits to stress prevention in mice, but it is not sure if this applies to the seed oil component (most commonly sold form of 'perilla oil')

Perilla oil (dosage unspecified) for 12 weeks in hyperlipidemic adults appears to improve inflammatory parameters (TNF-α, CRP, PAI-1) relative to baseline and with a potency comparable to mild-moderate exercise.^[15] This is thought to be beneficial for atherosclerosis as PAI-1 (via thrombis formation^[16]) TNF-α (via promoting inflammation^[17]) and C-reactive protein (via platelets^[18] and as a biomarker for plaque^[19]) are thought to be positively associated with cardiovascualar disease and atherosclerosis.

Supplementation of perilla oil for 12 weeks (dosage unspecified), relative to baseline values due to no placebo group, showed a minor increase in HDL-C (14%) and reductions in LDL-C (18%) and total cholesterol (11%) which was comparable in potency to brisk walking four times weekly (30-60 minutes, voluntarily increasing intensity over the 12 weeks) in these hyperlipidemic patients yet not additive.^[15]

A methanolic extract from the leaves of perilla frutescens appears to have antiproliferative effects in isolated mesangial cells induced to proliferate with IgA with an IC₅₀ of 8.8μg/mL, mostly due to the rosmarinic acid content (7.3% by weight) which had an IC₅₀ of 3.6μM and in part due to the luteolin glycoside content (IC₅₀ of 17.5μM and a 7.1% content)^[7] This is thought to be a protective effect against glomerulonephritis, which is characterized by hypercellularity of mesangial cells^[20] and has been replicated with an acetone extract (but again thought to be due to the luteolin and rosmarinic acid content^[21]) and basic seed oil^[22] while a fourth study has noted that the effects were fully reproducible with pure rosmarinic acid.^[23]

In a mouse model of spontaneous nephritis characterized by high serum IgA^[24][25] from gut‐associated lymphoid tissue,^[26] perilla leaf extract (50-500mg/kg of the 9% rosmarinic acid extract) over the course of 16 weeks appeared to reduce serum IgA levels and concentrations of IgA in glomeruli of treated mice relative to control.^[23] This was thought to be due to less IgA release from lymphoid tissue (replicated in vitro with perilla leaf extract and rosmarinic acid, mostly in spleen cells).^[23]

Perilla oil appears to be associated with a reduced rate of IgA nephropathy in in vitro and rodent research which is thought to be mostly (if not fully) due to the rosmarinic acid content