Salacia spp.: recent insights on biotechnological interventions and future perspectives.

The plants of the genus Salacia L. are the storehouse of several bioactive compounds, and are involved in treating human diseases and disorders. Hitherto, a number of reports have been published on in vitro biotechnology as well as microbial involvement in the improvement of Salacia spp. The present review provides comprehensive insights into biotechnological interventions such as tissue culture for plant propagation, in vitro cultures, and endophytic microbes for up-scaling the secondary metabolites and biological potential of Salacia spp. Other biotechnological interventions such as molecular markers and bio-nanomaterials for up-grading the prospective of Salacia spp. are also considered. The in vitro biotechnology of Salacia spp. is largely focused on plant regeneration, callus culture, cell suspension culture, somatic embryogenesis, and subsequent ex vitro establishment of the in vitro-raised plantlets. The compiled information on tissue cultural strategies, involvement of endophytes, molecular markers, and nanomaterials will assist the advanced research related to in vitro manipulation, domestication, and commercial cultivation of elite clones of Salacia spp. Moreover, the genetic diversity and other molecular-marker based assessments will aid in designing conservation policies as well as support upgrading and breeding initiatives for Salacia spp. KEY POINTS: • Salacia spp. plays a multifaceted role in human health and disease management. • Critical and updated assessment of tissue culture, endophytic microbes, metabolites, molecular markers, and bio-nanomaterials of Salacia spp. • Key shortcomings and future research directions for Salacia biotechnology.

In Vitro and In Vivo Inhibitory Activities of Selected Traditional Medicinal Plants against Toxin-Induced Cyto- and Entero- Toxicities in Cholera.

Careya arborea, Punica granatum, Psidium guajava, Holarrhena antidysenterica, Aegle marmelos, and Piper longum are commonly used traditional medicines against diarrhoeal diseases in India. This study investigated the inhibitory activity of these plants against cytotoxicity and enterotoxicity induced by toxins secreted by Vibrio cholerae. Cholera toxin (CT) and non-membrane damaging cytotoxin (NMDCY) in cell free culture filtrate (CFCF) of V. cholerae were quantified using GM1 ELISA and cell-based assays, respectively. Hydro-alcoholic extracts of these plants and lyophilized juice of P. granatum were tested against CT-induced elevation of cAMP levels in CHO cell line, binding of CT to ganglioside GM1 receptor and NMDCY-induced cytotoxicity. Significant reduction of cAMP levels in CFCF treated CHO cell line was observed for all extracts except P. longum. C. arborea, P. granatum, H. antidysenterica and A. marmelos showed >50% binding inhibition of CT to GM1 receptor. C. arborea, P. granatum, and P. guajava effectively decreased cytotoxicity and morphological alterations caused by NMDCY in CHO cell line. Further, the efficacy of these three plants against CFCF-induced enterotoxicity was seen in adult mice ligated-ileal loop model as evidenced by decrease in volume of fluid accumulation, cAMP levels in ligated-ileal tissues, and histopathological changes in intestinal mucosa. Therefore, these plants can be further validated for their clinical use against cholera.

Network pharmacology and in vitro testing of Theobroma cacao extract's antioxidative activity and its effects on cancer cell survival.

Theobroma cacao L. is a commercially important food/beverage and is used as traditional medicine worldwide against a variety of ailments. In the present study, computational biology approaches were implemented to elucidate the possible role of cocoa in cancer therapy. Bioactives of cocoa were retrieved from the PubChem database and queried for targets involved in cancer pathogenesis using BindingDB (similarity index ≥0.7). Later, the protein-protein interactions network was investigated using STRING and compound-protein via Cytoscape. In addition, intermolecular interactions were investigated via molecular docking. Also, the stability of the representative complex Hirsutrin-epidermal growth factor receptor (EGFR) complex was explored using molecular dynamics simulations. Crude extract metabolite profile was carried out by LC-MS. Further, anti-oxidant and cytotoxicity studies were performed in Chinese hamster ovary (normal) and Ehrlich ascites carcinoma (cancer) cell lines. Herein, the gene set enrichment and network analysis revealed 34 bioactives in cocoa targeting 50 proteins regulating 21 pathways involved in cancer and oxidative stress in humans. EGFR scored the highest edge count amongst 50 targets modulating 21 key pathways. Hence, it was selected as a promising anticancer target in this study. Structural refinement of EGFR was performed via all-atom molecular dynamics simulations in explicit solvent. A complex EGFR-Hirsutrin showed the least binding energy (-7.2 kcal/mol) and conserved non-bonded contacts with binding pocket residues. A stable complex formation of EGFR-Hirsutrin was observed during 100 ns MD simulation. In vitro studies corroborated antioxidant activity for cocoa extract and showed a significantly higher cytotoxic effect on cancer cells compared to normal cells. Our study virtually predicts anti-cancer activity for cocoa affected by hirsutrin inhibiting EGFR. Further wet-lab studies are needed to establish cocoa extract against cancer and oxidative stress.