Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities

Abstract

Ethnopharmacological relevance: Piper wallichii (Miq.) Hand.-Mazz. is a medicinal plant used widely for the treatment of rheumatoid arthritis, inflammatory diseases, cerebral infarction and angina in China. Previous study showed that lignans and neolignans from Piper spp. had potential inhibitory activities on platelet aggregation. In the present study, we investigated the chemical constituents of Piper wallichii and their antithrombotic activities, to support its traditional uses.

Materials and methods: The methanolic extract of the air-dried stems of Piper wallichii was separated and purified using various chromatographic methods, including semi-preparative HPLC. The chemical structures of the isolates were determined by detailed spectroscopic analysis, and acidic hydrolysis in case of the new glycoside 2. Determination of absolute configurations of the new compound 1 was facilitated by calculated electronic circular dichroism using time-dependent density-functional theory. All compounds were tested for their inhibitory effects on platelet aggregation induced by platelet activating factor (PAF) in rabbits׳ blood model, from which the active ones were further evaluated the in vivo antithrombotic activity in zebrafish model.

Results: A new neolignan, piperwalliol A (1), and four new aromatic glycosides, piperwalliosides A-D (2-5) were isolated from the stems of Piper wallichii, along with 25 known compounds, including 13 lignans, six aromatic glycosides, two phenylpropyl aldehydes, and four biphenyls. Five known compounds (6-10) showed in vitro antiplatelet aggregation activities. Among them, (-)-syringaresinol (6) was the most active compound with an IC50 value of 0.52 mM. It is noted that in zebrafish model, the known lignan 6 showed good in vivo antithrombotic effect with a value of 37% at a concentration of 30 μM, compared with the positive control aspirin with the inhibitory value of 74% at a concentration of 125μM.

Conclusion: This study demonstrated that lignans, phenylpropanoid and biphenyl found in Piper wallichii may be responsible for antithrombotic effect of the titled plant.

Keywords: (+)-Epipinoresinol (PubChem CID: 637584); (+)-Medioresinol (PubChem CID: 181681); (+)-Pinoresinol (PubChem CID: 73399); (–)-Olivil (PubChem CID: 586733); (–)-Syringaresinol (PubChem CID: 332426); Antithrombotic effect; Aromatic glycosides; Aucuparin (PubChem CID: 442508); Coniferyl aldehyde (PubChem CID: 5280536); Isolariciresinol (PubChem CID: 160521); Lignans; Piper wallichii (Miq.) Hand.-Mazz.; Prunasin (PubChem CID: 120639); Sinapyl aldehyde (PubChem CID: 5280802); Zebrafish model.