• Journal of Pharmacopuncture
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• v.26 no.3
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• pp.247-256
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• 2023

Objectives: Enterococcus faecalis is a gram positive diplococci, highly versatile and a normal commensal of the gut microbiome. Resistance to vancomycin is a serious issue in various health-care setting exhibited by vancomycin resistant Enterococci (VRE) due to the alteration in the peptidoglycan synthesis pathway. This study is thus aimed to detect the VRE from the patients with root caries from the clinical isolates of E. faecalis and to evaluate the in-silico interactions between vanA and the Aegles marmelos bio-compounds. Methods: E. faecalis was phenotypically characterized from 20 root caries samples and the frequency of vanA and vanB genes was detected by polymerase chain reaction (PCR). Further crude methanolic extracts from the dried leaves of A. marmelos was assessed for its antimicrobial activity. This is followed by the selection of five A. marmelos bio-compounds for the computational approach towards the drug ligand interactions. Results: 12 strains (60%) of E. faecalis was identified from the root caries samples and vanA was detected from two strains (16%). Both the stains showed the presence of vanA and none of the strains possessed vanB. Crude extract of A. marmelos showed promising antibacterial activity against the VRE strains. In-silico analysis of the A. marmelos biocompounds revealed Imperatonin as the best compound with high docking energy (-8.11) and hydrogen bonds with < 140 TPSA (Topological polar surface area) and zero violations. Conclusion: The present study records the VRE strains among the root caries with imperatorin from A. marmelos as a promising drug candidate. However the study requires further experimentation and validation.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.67.1-67.15
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• 2023

Background: Feline immunodeficiency virus (FIV) causes an acquired immunodeficiency-like syndrome in cats. FIV is latent. No effective treatment has been developed for treatment the infected cats. The first and second generations non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment, nevirapine (NVP) and efavirenz (EFV), and rilpivirine (RPV), were used to investigate the potential of NNRTIs for treatment of FIV infection. Objective: This study aims to use experimental and in silico approaches to investigate the potential of NNRTIs, NVP, EFV, and RPV, for inhibition of FIV reverse transcriptase (FIV-RT). Methods: The FIV-RT and human immunodeficiency virus reverse transcriptase (HIV-RT) were expressed and purified using chromatography approaches. The purified proteins were used to determine the IC₅₀ values with NVP, EFV, and RPV. Surface plasmon resonance (SPR) analysis was used to calculate the binding affinities of NNRTIs to HIV-RT and FIV-RT. The molecular docking and molecular dynamic simulations were used to demonstrate the mechanism of FIV-RT and HIV-RT with first and second generation NNRTI complexes. Results: The IC₅₀ values of NNRTIs NVP, EFV, and RPV against FIV-RT were in comparable ranges to HIV-RT. The SPR analysis showed that NVP, EFV, and RPV could bind to both enzymes. Computational calculation also supports that these NNRTIs can bind with both FIV-RT and HIV-RT. Conclusions: Our results suggest the first and second generation NNRTIs (NVP, EFV, and RPV) could inhibit both FIV-RT and HIV-RT.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.661-673
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• 2023

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.