Active compounds in Piper Longum Fruits demonstrate functional food and drug potential

Piper Longum’s mature or nearly mature fruits are used as spices and are rated by traditional Chinese herbal medicines for commercial and industrial applications, as well as multiple benefits such as dispelling and relieving pain.

Considering the long history of medicinal use, P. The fruits of longum present an opportunity to explore their therapeutic ingredients. However, the chemical constituents of traditional Chinese herbal medicines are often complex, making efficient discovery of novel active compounds a challenging task in natural product research.

To address this challenge, a research team led by Professor Haji Akber Aisa of the New Jiang Institute of Technology at the Chinese Academy of Sciences has isolated 12 dimeric amide alkaloid enantiomers with anti-inflammatory and antidiabetic effects from P. longum Fruits using a molecular network-based emergency strategy. This study was published in the Journal of Agricultural and Food Chemistry.

Researchers use the feature-based molecular networking (FBMN) module of the GNPS platform to P. We created a molecular network of 95% ethanol extracts of longum fruit. Different clusters were identified within the network. This included nodes with molecular weights ranging from 486.191 to 653.255 DA, but did not correspond to known chemical structures in public databases.

The specific nodes of this cluster have a molecular weight of 627.3420 DA, and P. corresponds to previously identified amide alkaloid dimers of longum. The researchers separated these 12 dimeric amide alkaloids into 12 sets of enantiomers using chiral HPLC.

The complete structure of these compounds was elucidated through comprehensive spectroscopic data, electron cyclic dichroism (ECD) calculations, and X-ray diffraction analysis. The identified dimeric amide alkaloids include eight sets of cyclobutane dimers and four sets of cyclohexene dimers, characterized by five new sets of cyclobutane dimers and one set of new sets of cyclohexene dimers.

In vitro biological activity screening revealed that three compounds showed significant anti-inflammatory effects in a 264.7 macrophage model of LPS-induced live life. Furthermore, one compound showed significant inhibitory activity against α-glucosidase, while three compounds showed promising inhibitory activity against the protein tyrosine phosphatase-1b (PTP1B).

To investigate the mechanism of interaction between these dimeric amide alkaloids and the enzymes α-glucosidase and PTP1B, we performed using two most active compounds, representative of molecular docking studies. The results showed that both compounds formed stable complexes with their respective target proteins. Further molecular dynamics simulations provided additional evidence to support the stability of the complex formed between the active compound and the corresponding protein.

This study highlights the potential applications of these amide alkaloid dimers in the development of functional foods and drugs, thereby expanding the health promotion benefits of P. longum fruits.