Metabolite fingerprinting of phytoconstituents from Fritillaria cirrhosa D. Don and molecular docking analysis of bioactive peonidin with microbial drug target proteins

Abstract

Fritillaria cirrhosa D. Don (Liliaceae), a valuable and critically endangered medicinal herb of northwest India, including Jammu and Kashmir, grows in temperate to alpine regions of the Himalaya. It is known as the traditional herb for cardiovascular diseases, respiratory diseases, and metabolic disorders. The plant bulbs are precious and are used to cure many other health complications. The current study analysed the phytoconstituents by liquid chromatography-mass spectrometry (LC–MS) of different crude extracts (methanolic, petroleum ether, and ethyl acetate) of F. cirrhosa. The LC–MS analysis from the bulbs of F. cirrhosa yielded 88 bioactive compounds, with the vast majority having therapeutic applications. Further, determination of minimum inhibitory concentrations (MICs) by broth microdilution method of F. cirrhosa against tested bacterial and fungal pathogens showed remarkable results with MICs ranging between 6.25–200 µg/mL and 50–400 µg/mL, respectively. Subsequently, these 88 identified phytocompounds were tested for their bioactivity through ADMET prediction by SwissADME and in silico molecular docking studies. Results revealed that Peonidin might have maximum antibacterial and antifungal activity against various microbial protein drug targets among the phytochemical compounds identified. Furthermore, the highest binding affinity complex was subjected to molecular dynamic simulation (MDS) analysis using Desmond Schrodinger v3.8. The root-mean-square deviation (RMSD) graphs obtained through the molecular dynamic simulations indicated the true bonding interactions, further validated using the root-mean-square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. To our best knowledge, this is the first description of the phytochemical constituents of the bulbs of F.cirrhosa analyzed through LC–MS, which show pharmacological significance. The in silico molecular docking and molecular dynamics study of peonidin was also performed to confirm its broad-spectrum activities based on the binding interactions with the antibacterial and antifungal target proteins. The present study results will create a way for the invention of herbal medicines for several ailments by using F. cirrhosa plants, which may lead to the development of novel drugs.

Integrons in the development of antimicrobial resistance: critical review and perspectives

“…We believe rising novel resistance genes in diverse microbial habitats through integrons would further hinder our efforts to devise treatment strategies, such as targeting integrons by antibiotics with adjuvants to inhibit SOS response. Development of new synthetic as well nature-based antimicrobials to combat the AMR ( Chakravorty et al, 2020 ; Terreni et al, 2021 ; Bhat et al, 2022a , b ; Mir et al, 2022a , b ; Ashraf et al, 2023 ). At the end of 2020, there were 43 antibiotics in clinical development, of which, 15 were Phase I, 13 in Phase II, and 13 in Phase III to combat AMR.…”

Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma

“…Medicinal plants are regarded as a renewable source of bioactive compounds that can be exploited in the treatment of various ailments including cancer ( Tariq et al, 2021 ; Mir et al, 2022a ; Mir et al, 2022b ). Phytochemicals play an important role in the initiation, development, and advancement of carcinogenesis, as well as in suppressing or reversing the early stages of cancer or the invading potential of premalignant cells and also regulate cell proliferation and apoptosis signalling pathways in transformed cells ( George et al, 2021 ; Bhat et al, 2022a ; Bhat et al, 2022b ).…”

Integrated study of HR-LC/MS and network pharmacology to identify breast cancer-related molecular targets of Fritillaria cirrhosa D. Don active constituents in combination with molecular dynamic simulation and experimental evaluation

“…Fritillaria (fritillaries) is a genus of perennial herbaceous bulbous lily family (Liliaceae) plants that bloom in the spring. Fritillaria species have been used in traditional Chinese medicine for over two thousand years, and they are today one of the most widely used treatments [20][21][22] . It has been estimated that the production of natural medicines from F. cirrhosa is worth US$400 million per annum.…”

“…It is a part of the Astavarga group, a collection of eight herbs utilized in traditional Indian and Himalayan medicine 24 . The alkaloids present in the bulbs of the F. cirrhosa displayed unique biological activity especially anti-in ammatory and antitumor 22,25 .…”