Natural Phytocompounds from Common Indian Spices for Identification of Three Potential Inhibitors of Breast Cancer: A Molecular Modelling Approach

Breast cancer is the second most common cancer-related cause of death for women throughout the globe. In spite of some effective measures, the main concerns with traditional anti-cancer chemotherapy are its low bioavailability, physical side effects, acquired resistance of cancer cells and non-specific targeting. Now researchers have taken the initiative to establish natural product-based therapy methods and to identify viable hits for future lead optimization in the development of breast cancer medication. Our study aims to identify the potent phytocompounds from five very popular Indian spices (Zingiber officinale Roscoe, Cuminum cyminum L., Piper nigrum L., Curcuma longa L., and Allium sativum L.). From these spices, a total of 200 phytocompounds were identified and screened against three target genes, namely, cyclin-dependent kinase 8 (CDK 8), progesterone receptor (PR) and epidermal growth factor receptor (EGFR), through structure-based virtual screening using iGEMDOCK 2.1 software. Based on the binding affinity score, the top three phytocompounds against each target protein (cynaroside (−149.66 Kcal/mol), apigetrin (−139.527 Kcal/mol) and curcumin (−138.149 Kcal/mol) against CDK8; apigetrin (−123.298 Kcal/mol), cynaroside (−118.635 Kcal/mol) and xyloglucan (−113.788 Kcal/mol) against PR; cynaroside (−119.18 Kcal/mol), apigetrin (−105.185 Kcal/mol) and xyloglucan (−105.106 Kcal/mol) against EGFR) were selected. Apigetrin, cynaroside, curcumin, and xyloglucan were finally identified for further docking analysis with the respective three target proteins. Autodock 4.2 was applied to screen the optimal binding position and to assess the relative intensity of binding interactions. In addition, the ADME/T property checks and bioactivity scores analysis of were performed to understand the suitability of these four phytocompounds to be potential candidates for developing effective and non-toxic anticancer agents. Based on this in silico analysis, we believe this study could contribute to current efforts to develop new drugs for treating breast cancer

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway

Objectives: The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Materials and Methods: Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate. Results: PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. Conclusions: The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration

Phytochemical Profiling, Biological Activities, and In Silico Molecular Docking Studies of <i>Causonis trifolia</i> (L.) Mabb. & J.Wen Shoot

Causonis trifolia (L.) Mabb. & J.Wen, commonly known as “fox grape”, is an ethnomedicinally important twining herb of the Vitaceae family, and it is used by ethnic communities for its wide range of therapeutic properties. Our research aims to investigate the chemical composition; antioxidant, anti-inflammatory, and antidiabetic activities; and mechanisms of interaction between the identified selective chemical compounds and the target proteins associated with antioxidant, anti-inflammatory, and antidiabetic effects of the optimised phenolic extract of Causonis trifolia (L.) Mabb. & J.Wen, shoot (PECTS) to endorse the plant as a potential drug candidate for a future bioprospecting programme. Here, we employed the response surface methodology (RSM) with a Box–Behnken design to enrich the methanolic extract of C. trifolia shoot with phenolic ingredients by optimising three key parameters: solvent concentration (% v/v, methanol:water), extraction temperature (°C), and extraction duration (hours). From the quantitative phytochemical estimation, it was evident that the PECTS contained good amounts of phenolics, flavonoids, tannins, and alkaloids. During the HPLC analysis, we identified a total of eight phenolic and flavonoid compounds (gallic acid, catechin hydrate, chlorogenic acid, caffeic acid, p-coumaric acid, sinapic acid, coumarin, and kaempferol) and quantified their respective contents from the PECTS. The GC-MS analysis of the PECTS highlighted the presence of 19 phytochemicals. In addition, the bioactivity study of the PECTS showed remarkable potentiality as antioxidant, anti-inflammatory, and antidiabetic agents. In silico molecular docking and computational molecular modelling were employed to investigate the anti-inflammatory, antioxidant, and antidiabetic properties of the putative bioactive compounds derived from the PECTS using the GC-MS technique to understand the drug–receptor interactions, including their binding pattern. Out of the 19 phytocompounds identified by the GC-MS analysis, one compound, ergosta-5,22-dien-3-ol, acetate, (3β,22E), exhibited the best binding conformations with the target proteins involved in anti-inflammatory (e.g., Tnf-α and Cox-2), antioxidant (SOD), and antidiabetic (e.g., α-amylase and aldo reductase) activities. The nontoxic nature of this optimised extract was also evident during the in vitro cell toxicity assay against the Vero cell line and the in vivo acute toxicity study on BALB/c mice. We believe the results of the present study will pave the way for the invention of novel drugs efficacious for several ailments using the C. trifolia plant