Eupatorium lindleyanum

The most complete account of the human evidence for this drug, and the only one that tabulates it. It collects seven Chinese clinical reports of Yemazhui preparations: a 52-patient comparison of modified Yemazhui capsule against Keke capsule in acute or chronic bronchitis, a 72-patient chronic bronchitis comparison, a 400-child chronic bronchitis comparison against ambroxol, 17 patients with lobar pneumonia, 32 patients given Yemazhui injection for leptospirosis, and a 150-patient trial of flavonoid, alkaloid and combined tablets. The reported cure rates are high, between 86 and 97 per cent, but these are Chinese-language reports with weak or absent blinding, response defined by symptom score, and no placebo arm, so they establish traditional clinical use rather than efficacy. The review also records rodent safety data: no effect on autonomic, cardiovascular or respiratory function at 45 g of herb per kg, and an LD50 of 225.6 g of herb per kg.

The paper that settles which part of the plant carries the activity. Flowers, leaves and stems were profiled separately: 9 alkaloids, 11 flavonoids, 14 sesquiterpene lactones, 3 diterpenoids and 24 phenolic acids were identified, and eupalinolide A, eupalinolide B and chlorogenic acid were concentrated in the flowers. Flowers suppressed TNF-alpha and IL-6 release more strongly than leaves; stems were essentially inert both chemically and pharmacologically. Stem-heavy material should therefore be treated as a quality failure, not merely a weaker grade.

The only pharmacokinetic study of the drug. After oral extract in rats, eupalinolide B peaked at about 0.57 h, eupalinolide A at about 1.00 h and hyperoside at about 1.80 h, with peak concentrations of 371.25, 144.73 and 689.60 ng/mL respectively at 625 mg/kg; exposure rose with dose. It establishes that all three markers are systemically absorbed, which the traditional decoction route had only been assumed to achieve.

A total sesquiterpenoid fraction reduced alpha-smooth muscle actin, type I collagen and fibronectin in TGF-beta1-stimulated human lung fibroblasts and cut lung hydroxyproline and collagen deposition in bleomycin-treated mice. The effect ran through serum response factor rather than Smad2/3 or Erk1/2 phosphorylation. This is an extension of the traditional respiratory indication into fibrosis and remains entirely preclinical.

An extract reduced collagen deposition, collagen I and alpha-smooth muscle actin expression and hepatic inflammation in carbon tetrachloride-treated mice, and blocked hepatic stellate cell activation in LX-2 cells, with RNA sequencing pointing to suppression of PDGF/PDGFR-beta signalling. Relevant here mainly as evidence against hepatotoxicity at the doses used, since the herb belongs to a genus in which pyrrolizidine alkaloid liver injury is a live concern.