Tian Zhu Zi

A beta-adrenoceptor agonist. In isolated guinea-pig trachea, higenamine accounts for the fast, propranolol-sensitive component of the relaxation produced by Nandina domestica fruit extract, which is the most plausible pharmacological basis for the traditional use of the fruit in cough and wheezing. Higenamine has been on the WADA prohibited list as a beta-2 agonist since 2017 and Nandina domestica is named in the literature as one of the higenamine-containing plants that put athletes at risk of an adverse analytical finding.

An antagonist at 5-HT2A and alpha-1A adrenergic receptors. In isolated trachea it reproduces the slow, propranolol-resistant phase of relaxation by calcium antagonism, so the fruit extract relaxes airway smooth muscle by two independent mechanisms. Nantenine blocks the behavioural and physiological effects of MDMA in mice and has been pursued synthetically as a lead for an MDMA antagonist.

One of the characteristic aporphine markers of Nandina domestica alongside nantenine, and part of the isoquinoline series that a 2024 review identifies as the diagnostic alkaloid class for the species. Its own pharmacology in this drug is not established.

Berberine is the best-studied alkaloid of the genus and drives much of the reported antitumour and antimicrobial activity of Nandina domestica root preparations. Its presence in the fruit is reported but unquantified, and because berberine is a known inhibitor of CYP3A4 and P-glycoprotein at the doses used as an isolated supplement, the missing content figure is the reason no interaction assessment can be made for the fruit drug.

Reported among the fruit alkaloids and shown in cell work on the genus to induce apoptosis through p53 stabilisation. This is preclinical and has no bearing on the traditional antitussive use.

Enzymatic hydrolysis after ingestion liberates hydrogen cyanide. This is the toxicity that matters clinically for Tian Zhu Zi: the berries have killed cedar waxwings that gorged on them, with pulmonary, mediastinal and tracheal haemorrhage consistent with cyanide poisoning, and the drug is described in Chinese materia medica as poisonous as well as therapeutic. The published assays place the named cyanohydrins in young leaves and shoots rather than in fruit, so the exact cyanogenic compound of the berry is not securely identified, which is a gap in the evidence and not a reason to discount the hazard.

Principal volatile of the fruit essential oil, which is dominated by monoterpenoids and sesquiterpenoids. It carries the aroma of the drug and has no established role in its traditional indications.

Records that an aqueous preparation of the fruit could counteract arsenic poisoning. Modern work on the genus has revisited this claim, reporting protection against arsenic trioxide hepatotoxicity and nephrotoxicity in animals, with berberine the most active constituent, though that work used root and seed material as well as fruit.

Describes the fruit as sour and sweet in taste and explicitly as poisonous, while retaining it as a therapeutic drug. The toxicity is not a modern reinterpretation; it is carried in the source text alongside the indication.

Gives the regional indications for the fruit as clearing the liver and brightening the eyes, and treating malaria and skin ulcers, alongside the cough and wheezing indications for which it is better known.