Cowslip (Primula veris) and Respiratory support: evidence and sources

Reducing inappropriate antibiotic (AB) use by using effective non-antibiotic treatments is one strategy to prevent and reduce antimicrobial resistance (AMR). Andrographis paniculata (Burm. f.) Wall. ex Nees, Pelargonium sidoides DC., Echinacea species and a combination of ivy ( Hedera helix L.), primrose ( Primula veris L./ Primula elatior L.) and thyme ( Thymus vulgaris L./ Thymus zygis L.) have promising clinical effects in uncomplicated, acute upper respiratory tract infections (URTI) treatment. However, mechanistic evidence of these herbal treatments is lacking. The objective of this Pstudy is to provide an overview of mechanistic evidence for these effects. Thirty-eight databases were searched. Included studies were mechanistic studies (in vitro, animal, and human studies and reviews) on these herbs; published before June 2021. Non-mechanistic studies or studies on combinations of herbs other than ivy/primrose/thyme were excluded. Furthermore, three experts in traditional, complementary and integrative healthcare (TCIH) research and pharmacognosy were interviewed to collect additional expert knowledge. The results show that A. paniculata acts through immunomodulation and antiviral activity, possibly supplemented by antibacterial and antipyretic effects. P. sidoides acts through antiviral, indirect antibacterial, immunomodulatory and expectorant effects. Echinacea species likely act through immunomodulation. The combination of ivy/primrose/thyme combines secretolytic and spasmolytic effects from ivy with antibacterial effects from thyme. Studies on primrose were lacking. This mechanistic evidence supports the difference-making evidence from clinical studies, contributes to evidence-based recommendations for their use in URTI treatment, and guides future mechanistic studies on URTI treatments.

In this study, three new undescribed triterpene saponins named primulasaponin III-V ( 19 - 21 ) were isolated from the roots of Primula veris L. of Bulgarian origin together with the known primulasaponin I. Their structures were elucidated via 1D and 2D NMR spectroscopy and HR-ESI-MS. In addition, 17 known phenolic compounds (six flavones, three acetophenones, four bisbibenzyls, and four phenolic glycosides) were identified in the chloroform and methanol extracts. Among them, flavone, 2'-methoxyflavone, 3'-methoxyflavone, 3'-hydroxy-4',5'-dimethoxyflavone, 2',5'-dimethoxyflavone, 3'-methoxy-4',5'-methylendioxyflavone, paeonol, 2-primeverosyl-5-methoxy-acetophenone, and paeonolide were detected for the first time in the roots of P. veris. The minimum inhibitory and minimum bactericidal concentrations of the chloroform and methanol extracts of P. veris roots and the saponin-enriched fraction were determined, with MIC values ranging between 0.5 and 1 mg/mL. Additionally, the tested samples were evaluated for their ability to inhibit biofilm formation in the presence of sub-MICs. All tested samples showed better biofilm inhibition of Gram-negative strains compared to Gram-positive strains. The strongest effect was observed for the chloroform extract against the biofilm formation of Pseudomonas aeruginosa , while the saponin-enriched fraction showed the highest percentage of biofilm inhibition of Escherichia coli , Staphylococcus aureus , and Staphylococcus mutans . At the same time, chloroform extract showed lower cytotoxicity against human keranocyte cell line HaCaT, as compared with methanol extract and the saponin-enriched fraction.

Primula veris L. and Primula elatior (L.) Hill represent medicinal plants used for the production of herbal teas and preparations with antioxidant and expectorant activity. Flowers and roots of both species possess the same biological activity. In the presented study, raw materials of wild growing P. veris and P. elatior were compared in terms of the content and composition of phenolic compounds using a fast and simple HPLC-DAD method. The study showed that flowers of both species were rich in flavonoids. However, P. veris flowers were characterized with a distinctly higher content of isorhamnetin-3-O-glucoside, astragalin, and (+)-catechin, whereas P. elatior occurred to be a richer source of rutoside and isorhamnetin-3-O-rutinoside. Hyperoside was found exclusively in P. elatior flowers. Phenolic glycosides (primverin and primulaverin) were identified only in the roots. Their content was about ten times higher in P. veris in comparison with P. elatior underground organs. The obtained results clearly show that both Primula species differ distinctly in terms of the content and composition of phenolic compounds. The compounds differentiating both species to the highest degree (hyperoside, in flowers, as well as primverin and primulaverin, in the roots) may be useful chemical markers in the identification and evaluation of both species.

This paper describes the first liquid chromatographic method suitable for the simultaneous determination of bioactive compounds, saponins and phenolic glycosides, present in Primula elatior and Primula veris, including the NMR data of primulaverin and primeverin. Optimum separations were obtained with a Synergi 4mum Fusion RP 80A column, using 0.025% TFA in water and 5% acetonitrile in methanol as mobile phase. Saponins were detected by evaporative light scattering detection (ELSD), whereas the phenolic glycosides were monitored by UV at 210 nm. The method was validated for repeatability (sigma(rel) or=97.1%) and sensitivity (LOD <or=22 ng (UV) and <or=38 ng (ELSD) on-column, respectively). LC-MS experiments in negative APCI mode allowed a final peak assignment. Both Primula species could easily be differentiated by their saponin pattern. The total saponin content was highest in P. veris roots (max. 14.9%), the aerial parts or P. elatior contained significantly less amounts; primeverin (0.64-1.42%) showed to be the most dominant phenolic glycoside.