Zi Su Zi
StarPerilla frutescens (L.) Britt.
Traditionally used for
- Cough & breathing
- Digestion
- Bowel health
Cautions & contraindications
- Toxic — professional use only
☯ TCM Properties
Descends Qi and Transforms Phlegm; Stops Cough and Calms Wheezing; Moistens the Intestines and Unblocks the Bowels
Traditional Chinese Uses
Zi Su Zi (perilla fruit) is a warm, oily herb used to redirect rebellious Lung and Stomach Qi downward, dissolve Phlegm, and relieve wheezing and cough. Its natural oil content additionally softens the intestines to relieve constipation from dryness. This combination of Phlegm-resolving, Qi-descending, and bowel-lubricating actions makes it particularly valuable in elderly patients with chronic cough, difficult breathing, and constipation occurring together.
Western Herbalism Properties
Traditional Uses
The Rappahannock used Perilla frutescens as an ingredient in a blood medicine (Speck, Hassrick and Carpenter 1942).
Relationships
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Botanical Description
Perilla frutescens (Zi Su Zi when referring to the seed; the leaf is Zi Su Ye) is an aromatic annual herb in the Lamiaceae family, typically growing 30 to 100 centimeters tall, with quadrangular, often purple-tinged stems and opposite, broadly ovate leaves 7 to 12 centimeters long, coarsely serrate with pointed tips and frequently flushed purple on one or both surfaces. The whole plant emits a pungent, characteristic aroma reminiscent of basil and anise. Small white to pinkish-purple flowers are borne in dense terminal and axillary racemes through late summer, each subtended by a persistent calyx that enlarges in fruit. The fruits are small grayish-brown to dark brown nutlets about 1 to 2 millimeters in diameter, four contained within each persistent calyx, with a reticulate surface and oily contents rich in alpha-linolenic acid. Native to East and Southeast Asia, Perilla frutescens has long been cultivated for culinary and medicinal use across China, Korea, and Japan, and has naturalized widely.
Active Constituents
alpha-Linolenic acid
Omega-3 polyunsaturated fatty acidConcentration: Perilla seed is about 40 percent fixed oil, of which more than 60 percent is alpha-linolenic acid; the seed oil is one of the richest plant sources known.
The dominant constituent of the drug by weight and the one carried into every human trial of perilla seed oil. In asthmatic patients four weeks of perilla seed oil supplementation reduced leukocyte generation of leukotriene B4 and C4 and raised peak expiratory flow, forced vital capacity and FEV1, while corn oil did the opposite. In healthy Japanese adults twelve months of the oil raised calcaneal bone density index and lowered the bone resorption marker TRACP-5b. This is the compound that makes the traditional wheeze-calming indication mechanistically plausible.
Rosmarinic acid
Caffeic acid ester (phenylpropanoid)Concentration: The principal phenolic of Perilla frutescens, quantified across leaf, stem and fruit; content varies markedly by plant part and variety.
The main antioxidant and anti-inflammatory phenolic of the plant, and the marker compound used for perilla drugs generally. It inhibits epidermal inflammatory responses in murine models. Note that most rosmarinic acid research is on the leaf drug rather than on the fruit, and the fruit carries less of it than the leaf.
Luteolin and apigenin
FlavonesConcentration: Minor flavones, isolated specifically from the fruit of Perilla frutescens rather than from the leaf.
Both were isolated from the fruit and shown to functionally activate monoamine transporters in vitro. This is one of the few pharmacological findings anchored to the fruit rather than borrowed from the leaf, though it has no bearing on the traditional respiratory indication.
Linoleic and oleic acids with the residual triacylglycerol fraction
Omega-6 and omega-9 fatty acidsConcentration: The balance of the fixed oil after alpha-linolenic acid, together with palmitic and stearic acids.
The remainder of the seed oil. It is the reason the drug moistens the intestines and unblocks the bowels, a purely physical fixed-oil effect that becomes a loose stool at higher doses, and it is why the herb is traditionally avoided in patients who already have diarrhoea.
⚠ Drug Interactions
Zi Su Ye (perilla leaf) and Zi Su Geng (perilla stem)
Three separate drugs come from this one plant and the Pharmacopoeia treats them separately. Zi Su Zi is the fruit, dominated by fixed oil and used to descend Qi, transform phlegm and calm wheezing. Zi Su Ye is the leaf, dominated by volatile essential oil, used to release the exterior and disperse cold and to resolve fish and crab poisoning. Zi Su Geng is the stem, used to move Qi in the middle burner and calm a restless fetus. Rosmarinic acid content and the volatile profile differ substantially between the parts, so leaf research does not establish anything about the seed drug and the reverse is equally true.
Clinical note: Read the plant part on the prescription and the label. The seed is the oily, ovoid, greyish-brown fruit; if what arrives is dried purple leaf, it is a different drug with a different indication.
Perilla ketone chemotype material and whole-herb perilla preparations
Perilla ketone, a furanoketone of the Perilla frutescens essential oil, is a potent pulmonary edemagenic agent in laboratory animals and livestock, and is the cause of acute pulmonary oedema and emphysema in cattle grazing the flowering plant. In instrumented sheep it produced increased pulmonary microvascular permeability oedema with protein-rich lung lymph flow, hypoxaemia and radiographic oedema without any change in pulmonary haemodynamics. Its presence is a chemotype trait, not a species trait: of five Perilla frutescens varieties assayed, two contained perilla ketone and were judged unsuitable for consumption, and Laotian material sorted into five essential-oil chemotypes of which one was the perilla ketone type. Critically, the toxin is a volatile essential-oil constituent characterised from the aerial parts, and the fruit drug and the human trials on it concern the fixed oil, not the volatile oil. The 1977 report that identified perilla ketone nevertheless flagged the use of perilla in foods and medicinal preparations as a possible human hazard. No study quantifying perilla ketone in the fruit or in cold-pressed seed oil was found for this record, so the honest position is that the toxin has not been shown to matter in the seed and has not been assayed out of it either.
Clinical note: Do not extrapolate the cattle poisoning to the seed drug, and do not dismiss it. Prefer suppliers who identify the cultivar and, where the intended product is the oil, prefer cold-pressed fixed oil over whole-herb or steam-distilled preparations. Treat any new dyspnoea or hypoxia during perilla use as needing investigation rather than a dose increase.
Leukotriene modifiers (montelukast, zafirlukast, zileuton)
This is one of the better-characterised herb-drug overlaps in the phlegm-transforming group because the human data exist. In asthmatic patients, dietary perilla seed oil significantly reduced leukocyte generation of leukotriene B4 and C4 within two to four weeks while corn oil raised them, and in sensitised guinea pigs perilla seed oil inhibited slow-reacting substance of anaphylaxis release and calcium-ionophore-induced leukotriene D4 release from lung tissue with an IC50 of 50 micrograms per millilitre. A leukotriene modifier targets the same pathway. Nothing suggests harm, but a patient may report an effect larger than either alone.
Clinical note: No dose change is needed. Do not let the herb be a reason to reduce or stop a prescribed controller medication, and record the combination so any improvement is not misattributed.
Warfarin, direct oral anticoagulants and antiplatelet drugs
Alpha-linolenic acid is an omega-3 precursor, and high-dose long-chain omega-3 intake is the classical source of concern about platelet function. The perilla seed oil trials used modest amounts, 0.88 g of alpha-linolenic acid daily over twelve months in the cognition and bone studies, and reported no adverse findings and no bleeding events. Alpha-linolenic acid is also converted to eicosapentaenoic acid only inefficiently in humans. The theoretical concern is therefore real but small, and there is no pharmacokinetic interaction on record.
Clinical note: No routine action. Mention the herb before elective surgery, and if a patient on warfarin also takes concentrated perilla seed oil, an international normalised ratio at the next scheduled visit is enough.
Osmotic and stimulant laxatives, and any drug requiring intact intestinal transit
The drug is roughly forty percent fixed oil and its classical function of moistening the intestines and unblocking the bowels is that oil load acting physically. Combined with an osmotic or stimulant laxative the effect is additive, and accelerated transit can reduce absorption of a co-administered oral drug. Traditional practice already contraindicates the herb in patients with loose stools or diarrhoea from Spleen deficiency.
Clinical note: Avoid in patients already loose, and reduce the dose if stools soften. Separate the herb from a narrow-therapeutic-index oral drug by a couple of hours if transit accelerates.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 3–10 g | Daily | — | — | 中国药典 2020 【用法与用量】3～10g。 【性味与归经】辛，温。归肺经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Dui Yao — Herb Pairs
The classical two-herb combinations this herb appears in, each with an action neither herb has alone.
Descends qi and calms wheezing while warming the lungs and expelling thin cold phlegm.
Core pair of a classical formula — San Zi Yang Qin Tang, Han Shi Yi Tong (Han Mao)
Descends lung qi and transforms phlegm while moving qi and calming wheezing, addressing excess above with phlegm-qi counterflow.
Core pair of a classical formula — Su Zi Jiang Qi Tang, Tai Ping Hui Min He Ji Ju Fang
Descends lung qi and transforms phlegm while reducing food stagnation, so that phlegm arising from stagnant food is cleared at its source.
Cough and wheezing with copious phlegm, chest oppression and poor appetite, especially in the elderly.
Core pair of a classical formula — San Zi Yang Qin Tang, Han Shi Yi Tong (Han Mao)
Evidence Tier
Strong evidence · 7 studiesRecorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.
Systematic review / meta-analysis
0
Randomized controlled trial
4
4 verified · 0 unverified
Show 4 studies
- Effects of Dietary Supplementation with n-3 Fatty Acids Compared with n-6 Fatty Acids on Bronchial Asthma.
- Perilla seed oil improves bone health by inhibiting bone resorption in healthy Japanese adults: A 12-month, randomized, double-blind, placebo-controlled trial
- Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly
- Perilla frutescens seed oil combined with Anredera cordifolia leaf powder attenuates age-related cognitive decline by reducing serum triglyceride and glucose levels in healthy elderly Japanese individuals: a possible supplement for brain health
Other clinical trial
1
1 verified · 0 unverified
Observational / case report
0
In vitro / animal
2
2 verified · 0 unverified
Other / unclassified
0
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
Effects of Dietary Supplementation with n-3 Fatty Acids Compared with n-6 Fatty Acids on Bronchial Asthma.
Fourteen asthmatic subjects were randomly divided into a perilla seed oil group and a corn oil group for four weeks. Leukotriene B4 and C4 generation by leucocytes fell in the perilla group and tended to rise in the corn oil group, with significant between-group differences at two weeks, and the perilla group showed significant increases in peak expiratory flow, forced vital capacity, FEV1 and V25 at four weeks. This is the only randomised human comparison directly relevant to the drug's traditional wheeze-calming indication; the trial is small and short and used the pressed seed oil rather than the decocted fruit.
Effects of Perilla Seed Oil Supplementation on Leukotriene Generation by Leucocytes in Patients with Asthma Associated with Lipometabolism
A companion analysis of asthmatic patients given dietary perilla seed oil, splitting them into responders whose leukocyte leukotriene C4 generation was suppressed and non-responders in whom it was not. Leukotriene C4 fell significantly in responders at two and four weeks and rose in non-responders at four weeks, and ventilatory parameters improved only in the responders. It shows that the leukotriene effect is not universal and tracks lipid metabolism, which is a caution against promising the effect to every patient.
Perilla seed oil improves bone health by inhibiting bone resorption in healthy Japanese adults: A 12-month, randomized, double-blind, placebo-controlled trial
Fifty-two Japanese adults of mean age 54.2 years were randomised to 7.0 mL daily of perilla seed oil or olive oil for twelve months. Compared with control, the perilla group showed a rise in the calcaneal percentage of Young Adult Mean by quantitative ultrasound and a fall in the bone resorption marker TRACP-5b, alongside changes in erythrocyte membrane polyunsaturated fatty acids and serum antioxidant potential. It is the longest controlled human exposure to the seed oil on record and reported no safety problems, though the endpoint has nothing to do with the traditional indication.
Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly
A twelve-month randomised, double-blind, parallel-arm study in 49 healthy elderly Japanese people comparing 1.47 mL of perilla seed oil daily, supplying 0.88 g of alpha-linolenic acid, against the same oil plus nobiletin-rich ponkan powder. The combination arm scored higher on cognitive indices with rises in erythrocyte membrane alpha-linolenic and docosahexaenoic acid and in serum brain-derived neurotrophic factor. Note there was no placebo arm, so the trial cannot show that perilla seed oil alone does anything; it establishes tolerability of a twelve-month exposure.
Perilla frutescens seed oil combined with Anredera cordifolia leaf powder attenuates age-related cognitive decline by reducing serum triglyceride and glucose levels in healthy elderly Japanese individuals: a possible supplement for brain health
The companion twelve-month randomised double-blind parallel-arm trial, comparing perilla seed oil alone against perilla seed oil plus Anredera cordifolia leaf powder in healthy elderly Japanese participants. The combination arm scored higher on cognitive indices with lower serum triglyceride, glucose and N-epsilon-carboxymethyl-lysine. As with its sibling study there is no placebo arm, so it is evidence about the combination and about tolerability rather than about perilla seed oil as such.
Anti-Asthmatic Effects of Perilla Seed Oil in the Guinea Pig in vitro and in vivo
In sensitised guinea pigs, oral perilla seed oil dose-dependently inhibited the antigen-induced rise in lung resistance and fall in dynamic compliance with ED50 values near 1.1 g/kg, and dose-dependently reduced leukocyte, mononuclear cell, eosinophil and neutrophil infiltration. In lung tissue it inhibited slow-reacting substance of anaphylaxis release and calcium-ionophore-induced leukotriene D4 release with an IC50 of 50 micrograms per millilitre. The effective doses are large, which is worth noting before reading it as support for ordinary decoction doses.
Functional activation of monoamine transporters by luteolin and apigenin isolated from the fruit of Perilla frutescens (L.) Britt
Luteolin and apigenin isolated specifically from the fruit of Perilla frutescens functionally activated monoamine transporters in vitro. Included because it is one of the few pharmacological results tied to the fruit rather than to the leaf, not because it supports any traditional use of the seed.
Historical Texts
Ming Yi Bie Lu (Miscellaneous Records of Famous Physicians), attributed to Tao Hongjing
Han to Wei period, text as compiled c. 500 CETai Ping Hui Min He Ji Ju Fang (Imperial Grace Formulary of the Great Peace and Welfare Pharmacy)
Northern Song dynasty, formulary compiled 1078 to 1107Han Shi Yi Tong (Han's Comprehensive Medicine), Han Mao
Ming dynasty, 1522Ben Cao Gang Mu, Li Shizhen
Ming dynasty, 1596References
- Wilson Benjamin J.; Garst John E.; Linnabary Robert D.; Channell Robert B.. Perilla Ketone: A Potent Lung Toxin from the Mint Plant, Perilla frutescens Britton . Science (1977) [DOI]
- Coggeshall Jack W.; Lefferts Peter L.; Butterfield Martha J.; Bernard Gordon R.; Carroll Frank E.; Pou N. Adrienne; Snapper James R.. Perilla Ketone: A Model of Increased Pulmonary Microvascular Permeability Pulmonary Edema in Sheep . American Review of Respiratory Disease (1987) [DOI]
- Muller-Waldeck Franziska; Sitzmann Judith; Schnitzler Wilfried H.; Grassmann Johanna. Determination of toxic perilla ketone, secondary plant metabolites and antioxidative capacity in five Perilla frutescens L. varieties . Food and Chemical Toxicology (2010) [DOI]
- Ito Michiho; Honda Gisho; Sydara Kongmany. Perilla frutescens var. frutescens in northern Laos . Journal of Natural Medicines (2007) [DOI]
- Liu Jing; Wan Yuklam; Zhao Zhongzhen; Chen Hubiao. Determination of the content of rosmarinic acid by HPLC and analytical comparison of volatile constituents by GC-MS in different parts of Perilla frutescens (L.) Britt . Chemistry Central Journal (2013) [DOI]
- Bondioli Paolo; Folegatti Liliana; Rovellini Pierangela. Oils rich in alpha linolenic acid: chemical composition of perilla (Perilla frutescens) seed oil . OCL (2020) [DOI]
- Lee Kyeong-Ryeol; Lee Yongjik; Kim Eun-Ha; Lee Seul-Bee; Roh Kyung Hee; Kim Jong-Bum; Kang Han-Chul; Kim Hyun Uk. Functional identification of oleate 12-desaturase and ω-3 fatty acid desaturase genes from Perilla frutescens var. frutescens . Plant Cell Reports (2016) [DOI]
- Natsume Midori; Muto Yuko; Fukuda Kumiko; Tokunaga Takahisa; Osakabe Naomi. Determination of rosmarinic acid and luteolin in Perilla frutescens Britton (Labiatae) . Journal of the Science of Food and Agriculture (2006) [DOI]
This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.
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