Klipp dagga

Three labdane diterpenoids isolated from the plant were tested on LPS signalling in macrophages. Nepetaefuran inhibited LPS-induced nitric oxide and CCL2 production more potently than leonotinin, while leonotin was inactive. Neither active compound affected IkB-alpha degradation, p65 nuclear translocation or MAP kinase activation, but both markedly inhibited NF-kB transcriptional activity, an effect that correlated with Nrf2 activation and ER stress. This is the study that identifies which constituents carry the traditional anti-inflammatory reputation, and it is entirely in vitro.

A hydroethanolic extract of the plant showed antibacterial activity attributable to perturbation of the bacterial membrane rather than to a specific enzymatic target. The work supports the traditional use of the herb for infections but establishes no systemic activity, since membrane-active antibacterial effects in vitro rarely translate to oral efficacy.

A single dose of methanol extract reduced immobility in the tail suspension test in mice, while three doses were needed to reduce immobility in the forced swimming test. Daily dosing for 28 days improved weight gain and lowered corticosterone in mice under chronic unpredictable mild stress, implicating the HPA axis. Metabolic profiling identified nepetaefolin, methoxynepetaefolin and luteolin 7-O-glucoside as the main extract products.

GC-MS analysis of hydrodistilled leaf and flower oils from Brazilian material. Leaf oil was dominated by germacrene D (31.5%) and beta-caryophyllene (19.2%); flower oil by beta-elemene (31.2%) and germacrene D (12.1%). Broth microdilution against a broad panel of bacteria and fungi gave MIC50 values of 3.93-250 µg/mL, with the strongest results against yeasts. Confirms that leaf and flower preparations differ chemically.

Leaf essential oil (44 constituents by GC-MS, predominantly germacrene D, beta-caryophyllene, alpha-humulene and phytol) at 12.5 and 50 µg/mL reduced TNF-alpha, IL-1beta, IL-6, iNOS, COX-2 and intracellular ROS in LPS-stimulated macrophages while raising SOD, GSH, GPx and CAT. It attenuated Keap1, upregulated Nrf2 and HO-1, inhibited TLR4 and MyD88 expression, and reduced NF-kB p65 nuclear localisation. The authors state explicitly that in vivo and clinical work is still needed.

Phytochemical characterisation of flower extracts paired with a zebrafish embryo toxicity assay. Relevant here mainly as one of the very few published attempts to bound the safety of this plant experimentally; there is no human toxicology and no established dose ceiling for internal use.

Cirsiliol isolated from the plant was complexed with beta-cyclodextrin, which improved its solubility and bioavailability and enhanced its antitumour activity in testing. The practical point for a monograph is that the species marker compound is poorly bioavailable in its native form, which limits what can be inferred from in vitro potency figures for crude extracts.