Li Zhi He
StarLitchi chinensis Sonn.
Traditionally used for
- Digestion
- Menstrual & women's health
- Pain & joints
Cautions & contraindications
- Diabetes
☯ TCM Properties
Moves Qi and Dissipates Nodules; Dispels Cold and Alleviates Pain; Soothes the Liver and Regulates Qi; Warms the Middle Burner and Stops Pain
Traditional Chinese Uses
Li Zhi He (lychee seed) is a warming, bitter-sweet herb whose primary action is on the Liver channel, where it moves stagnant Qi to relieve pain and swelling. It is most commonly applied to testicular or inguinal hernia pain, orchitis, and lower abdominal pain from Liver Qi stagnation or cold invasion. It is also used for menstrual pain and distension associated with gynecological Qi stagnation patterns.
Western Herbalism Properties
Relationships
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Botanical Description
Litchi chinensis is a subtropical evergreen tree in the Sapindaceae family, native to southern China and now cultivated widely across tropical and subtropical regions. The tree grows 10-20 meters tall with a dense, rounded canopy and smooth grey-brown bark. The alternate, pinnately compound leaves bear two to four pairs of glossy, leathery, lanceolate leaflets, each 5-15 cm long. Small, petalless, greenish-yellow flowers are borne in terminal panicles in spring. The fruit is a distinctive ovoid drupe, 3-4 cm long, with a rough red leathery skin enclosing fragrant, translucent white aril surrounding a single shiny brown seed. In TCM, the seed (Li Zhi He) is used as a warm, bitter, sweet herb to move qi, disperse cold, and relieve pain, particularly in the lower abdomen and testes.
Active Constituents
alpha-(Methylenecyclopropyl)glycine (MCPG)
Non-proteinogenic cyclopropyl amino acidConcentration: 85.7 to 3420 micrograms per gram across commercial litchi seed samples, and 8.72 to 905 micrograms per gram in seeds collected during the Muzaffarpur outbreak investigation
This is the constituent that makes Li Zhi He a genuinely hazardous drug rather than a bland one, and it is concentrated in the seed, which is exactly the part dispensed. MCPG is metabolised to methylenecyclopropyl-formyl-CoA, which inhibits acyl-CoA dehydrogenases and so blocks fatty acid beta-oxidation and impairs gluconeogenesis. The result is hypoglycaemia that is worst in a fasted subject, because a fasted person depends on precisely the pathways MCPG blocks. Seed concentrations are one to three orders of magnitude above those in the edible aril, and MCPG accumulates as the seed matures. No published work shows that decoction, roasting or the traditional charring destroys it.
Hypoglycin A
Non-proteinogenic cyclopropyl amino acidConcentration: 2.57 to 267 micrograms per gram across litchi seed samples; the 2018 quantitation was the first reported for litchi seed
The ackee toxin, present in litchi seed alongside MCPG and acting by the same route: its CoA metabolite inhibits beta-oxidation, producing hypoglycaemia with a characteristic acylcarnitine profile. Litchi seed carries substantially more MCPG than longan or mamoncillo seed, and the commercial seed samples did not differ significantly from those collected during an outbreak investigation, meaning ordinary market material carries the toxins too.
Procyanidin A1 and A2
ProanthocyanidinConcentration: among the principal polyphenols of the seed; the seed polyphenol fraction is the part responsible for the extract's metabolic effects
A-type procyanidins dominate the litchi seed polyphenol profile and are the constituents most often credited with the antioxidant and insulin-sensitising activity seen in diabetic rodent models.
Cinnamtannin B1
ProanthocyanidinConcentration: identified among twenty-one compounds in the seed polyphenol extract used in the diabetic rat work
An A-type trimeric proanthocyanidin, part of the polyphenol fraction associated with improved glucose tolerance and reduced insulin resistance in streptozotocin and high-fat-diet rats.
Phlorizin
Dihydrochalcone glycosideConcentration: identified in the seed polyphenol extract; not separately quantified
Phlorizin is a classical inhibitor of sodium-glucose cotransporters and produces glycosuria and lowered blood glucose. Its presence in the seed is one more reason the glucose-lowering effect of this drug should be treated as real rather than nominal.
Scopoletin
CoumarinConcentration: identified in the seed polyphenol extract; not separately quantified
A simple coumarin, not an anticoagulant one. It contributes to the antioxidant and anti-inflammatory activity attributed to the seed extract.
Rutin
Flavonol glycosideConcentration: identified in the seed polyphenol extract; not separately quantified
A common flavonol glycoside, present as part of the broader phenolic fraction of the seed.
Protocatechuic acid
Phenolic acidConcentration: isolated from a 95 percent ethanol extract of the seed
One of the free phenolic acids of the seed, active in DPPH radical-scavenging and Trolox equivalent antioxidant assays.
Triterpenoid saponins
SaponinConcentration: reported as one of the three main constituent groups of the seed alongside organic acids and flavonoids; content not reliably quantified
The saponin fraction is the one most often studied in Chinese pharmacological work on this drug. Reports of quantitative content vary widely between sources and should be treated as unsettled.
⚠ Drug Interactions
Insulin and insulin secretagogues (sulfonylureas, glinides)
Two independent mechanisms converge. First, the seed's MCPG and hypoglycin A block fatty acid beta-oxidation and impair gluconeogenesis, so the patient cannot mount the normal counter-regulatory response to a falling glucose; this is the established mechanism of litchi-associated hypoglycaemic encephalopathy and it is not a theoretical concern, having produced outbreaks with 31 percent case fatality in undernourished children. Second, litchi seed polyphenol extract independently lowers glucose and improves insulin sensitivity in diabetic rats. A patient on insulin or a sulfonylurea who also takes a drug that removes the body's ability to defend against hypoglycaemia is in a materially worse position than one taking an ordinary glucose-lowering herb. The seed concentrations of MCPG, at 85.7 to 3420 micrograms per gram, are far above those in the fruit pulp that caused the outbreaks.
Clinical note: If Li Zhi He is used at all alongside insulin or a sulfonylurea, insist on regular home glucose monitoring, never dose it on an empty stomach, and never dose it to a patient who is fasting, missing evening meals or undernourished. Advise the patient and household on recognising and correcting hypoglycaemia. Withhold the herb entirely from children.
Oral antidiabetic drugs generally (metformin, SGLT2 inhibitors, DPP-4 inhibitors)
Litchi seed extract improved glucose tolerance and insulin resistance and raised liver and muscle glycogen storage, muscle hexokinase activity and Akt phosphorylation in streptozotocin and high-fat-diet rats, and reduced TNF-alpha, hyperleptinaemia and hyperinsulinaemia in insulin-resistant rats. The seed also contains phlorizin, an SGLT inhibitor, which overlaps directly with the mechanism of the gliflozin class. The animal data are consistent but there is no human trial, so the size of the effect at a 5 to 10 g decoction dose is unknown.
Clinical note: Expect the herb to move glucose. Recheck HbA1c and home readings after starting or stopping it, and tell the prescribing physician it has been added rather than letting an unexplained change in control be attributed to the drug.
Valproate and other drugs impairing fatty acid beta-oxidation or depleting carnitine
MCPG and hypoglycin A act by trapping coenzyme A and inhibiting acyl-CoA dehydrogenases, which is the same pathway that valproate disturbs when it causes carnitine depletion and hyperammonaemia. No case of the combination has been reported and this is inference from shared mechanism, not observation. It is recorded here because the consequence, if it occurred, would be a metabolic crisis rather than a mild interaction, and because a patient with an underlying fatty acid oxidation disorder would be at particular risk.
Clinical note: Avoid Li Zhi He in patients on valproate, in anyone with a known or suspected fatty acid oxidation disorder, and in anyone with a history of unexplained hypoglycaemia or Reye-like illness.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | 5–10 g | Daily | — | — | 中国药典 2020 【用法与用量】5～10g。 【性味与归经】甘、微苦，温。归肝、肾经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Evidence Tier
Moderate evidence · 4 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
0
Other clinical trial
0
Observational / case report
1
0 verified · 1 unverified
In vitro / animal
3
0 verified · 3 unverified
Show 3 studies
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
Quantitative HPLC–MS/MS analysis of toxins in soapberry seeds: Methylenecyclopropylglycine and hypoglycin A
This is the study that answers whether the litchi toxins are in the part used as medicine. MCPG was found in every litchi seed tested, at 85.7 to 1190 micrograms per gram in one commercial group and 192 to 3420 micrograms per gram across others, with outbreak-investigation seeds at 8.72 to 905 micrograms per gram. Hypoglycin A ranged from 2.57 to 267 micrograms per gram, the first time it had been quantified in litchi seed. Litchi seed carried far more MCPG than longan or mamoncillo seed. Commercial seed did not differ significantly from outbreak-associated seed, so the toxins are a property of ordinary litchi seed rather than of contaminated material.
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
A hospital-based surveillance and case-control investigation of an annual outbreak of acute encephalopathy in India's largest litchi-growing district. Of 390 patients admitted between 26 May and 17 July 2014, 122 (31 percent) died, and 204 of 327 had a blood glucose of 70 mg/dL or less on admission. Illness was associated with litchi consumption and with having missed an evening meal in the preceding 24 hours. Litchi arils contained hypoglycin A at 12.4 to 152.0 micrograms per gram and MCPG at 44.9 to 220.0 micrograms per gram. This establishes the clinical syndrome the seed's toxins produce, though the exposure studied was the fruit rather than a seed decoction.
Chemical composition and hypoglycaemic effect of polyphenol extracts from Litchi chinensis seeds
Twenty-one compounds were identified in a litchi seed polyphenol extract, including 3,5-dihydroxybenzoic acid, 3,4-dihydroxybenzaldehyde, catechin, cinnamtannin B1, procyanidin A1, scopoletin, rutin, phlorizin and epicatechin oligomers. One month of treatment in streptozotocin and high-fat-diet type 2 diabetic rats improved glucose tolerance and insulin resistance and protected pancreas, liver and kidney tissue. The result cuts both ways clinically: it supports the traditional use in diabetes and simultaneously establishes that the drug will interact with glucose-lowering medication.
Chemical constituents with antioxidant activities from litchi (Litchi chinensis Sonn.) seeds
Four new and eleven known compounds were isolated from a 95 percent ethanol extract of litchi seed, including epoxy-flavans, coumaric acid, protocatechuic acid and flavanone glycosides, with antioxidant activity measured by DPPH radical scavenging and the Trolox equivalent antioxidant capacity assay.
Historical Texts
Ben Cao Yan Yi
Song dynastyBen Cao Gang Mu
Ming dynastyReferences
- Biswajit Panda, Alfiya Momin, Geetanjali Devabattula, Ravinder Doneti, Aarti Khandwaye, Chandraiah Godugu. A review on mechanistic aspects of litchi fruit induced acute encephalopathy . Toxicon (2024) [DOI]
- Jiali Yang, Xiangrong Zhu, Pei Zhang, Yinhong Wang, Yangyang Xiao, Bao Yang, Hongxia Qu, Yueming Jiang. Detection of toxic methylenecyclopropylglycine and hypoglycin A in litchi aril of three Chinese cultivars . Food Chemistry (2020) [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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