Tu Si Zi

The principal flavonoid marker used for assaying the seed and one of the compounds with the highest systemic exposure after oral dosing of the seed extract in rats. It carries much of the antioxidant and hepatoprotective activity attributed to the drug and is one of the constituents shown to protect progesterone output under oxidative stress. Its level in the crude drug is altered by processing, which cleaves the glycoside.

A second major flavonol glycoside of the seed and, with hyperoside, one of the compounds used in comparative pharmacokinetic work on Semen Cuscutae. Its abundance is one of the sharpest chemical discriminators between the two Cuscuta species traded as Tu Si Zi: astragalin and kaempferol are markedly higher in Cuscuta australis than in Cuscuta chinensis.

Present as such and released from its glycosides by gut microbial and intestinal hydrolysis. It accounts for much of the antioxidant and anti-apoptotic activity of the total flavonoid fraction and is the compound most responsible for the flavonoid-mediated pharmacokinetic concerns attached to this herb, since quercetin is a well-known inhibitor of several cytochrome P450 enzymes and of sulfotransferases.

Together with quercetin, one of the two aglycones dominating the absorbed flavonoid pool. Kaempferol attenuates dendritic cell function and suppresses inflammatory cytokine release, which is the mechanistic basis for the theoretical concern about the herb opposing therapeutic immunosuppression.

A large class in this species: seventeen quinic acid derivatives have been characterised from the two Cuscuta species traded as Tu Si Zi, and they are distinctly more abundant in Cuscuta chinensis than in Cuscuta australis. They contribute to the antioxidant activity of the drug and, like the flavonoid glycosides, are degraded by heat during wine-processing and toasting.

One of only two constituents (with p-coumaric acid) shown to reach high systemic exposure after oral administration of Cuscuta seed extract to rats, which makes it disproportionately important relative to its modest abundance in the crude drug. Its own pharmacology is not well characterised.

Around twenty lignans have been reported from this species, and they are one of the classes present at higher levels in Cuscuta chinensis than in Cuscuta australis. Sesamin, isolated from this herb, has been studied for anti-inflammatory effects on pregnant uterine smooth muscle via inhibition of cGAS-STING signalling.

CCL-A is a triple-helical heterogeneous polysaccharide of about 354.5 kDa, composed of galactose, glucose and mannose with a galactomannan backbone. At 150 mg/kg it improved serum total bilirubin, ALT, AST, albumin, TNF-alpha and IL-6 and reduced hepatic steatosis in high-fat-diet mice, so at least part of the herb's traditional liver-directed action sits in the non-absorbed polysaccharide fraction.

A small group of Convolvulaceae-typical resin glycosides has been isolated from the ether-insoluble fraction of this species. They are chemically characteristic of the family but are not part of routine quality control and have little pharmacological data behind them.

Tu Si Zi is listed among the upper-class drugs, credited with continuing what has been severed, supplementing insufficiency, augmenting qi and strength, and making a person robust. This is the origin of the drug's continuous use as a kidney-essence tonic rather than as a symptomatic remedy.

Extends the earlier indications towards nourishing the flesh, strengthening yin and firming the sinews and bones, which is the textual root of the later pairing of this seed with sinew-and-bone herbs such as Xu Duan and Du Zhong.

Li Shizhen describes the plant's parasitic habit, that it twines on other plants and lives without roots of its own. That observation, recorded four centuries before the pharmacology, is exactly why the identity and the host of the collected material matter for this drug in a way that it does not for a rooted herb.