Biotechnology of camptothecin production in Nothapodytes nimmoniana, Ophiorrhiza sp. and Camptotheca acuminata.

Cancer is probably the deadliest human disease in recent years. In the past few years, rapid clinical progress has been made in the field of anticancer drug development. Plant secondary metabolites have been noted as extremely efficacious as promising natural source for anticancer therapy for many years. Camptothecin (CPT) is one of the popularly used anti-tumor drugs possessing clinically proven properties against a plethora of human malignancies that include ovarian and colorectal cancers. For the first time, CPT was obtained from the extracts of a Chinese medicinal tree, Camptotheca acuminata Decne. from the family Cornaceae. Subsequently, CPT was also isolated from the bark of Nothapodytes foetida (Wight) Sleumer (Icacinaceae). However, the availability of enough natural sources for obtaining CPT is a major constraint. Due to overexploitation and harvesting, loss of habitat, excessive trading, and unfavorable environmental factors, the natural source of CPT has become extinct or extremely limited and hence they are red listed under endangered species. Conventional propagation has also failed to meet the ever-expanding demand for CPT production. With this, biotechnological toolkits have constantly been used as a boon to produce sustainable source, utilization, and ex situ conservation of medicinal plants. The approaches serve as a supplement to traditional agriculture in the mass production of plant metabolites with potent bioactivities. Non-availability of enough anticancer medicine and the requirement to satisfy current demands need a sustainable source of CPT. With this background, we present a comprehensive review on CPT discovery, its occurrence in the plant kingdom, biosynthesis, phytochemistry, pharmacological properties, clinical studies, patterns of CPT accumulation, and biotechnological aspects of CPT production in three plants, viz., N. nimmoniana, Ophiorrhiza species, and C. acuminata.Key points• Biotechnological approaches on production of camptothecin from Nothapodytes nimmoniana, Ophiorrhiza species, and Camptotheca acuminata• In vitro propagation of camptothecin-producing plants• Genetic diversity and transgenic research on camptothecin-producing plants.

Anticancer and Antibacterial Activities of Silver Nanoparticles (AgNPs) Synthesized from Cucumis melo L.

The current investigation reports the structural and biological evaluation of silver nanoparticles (AgNPs) biosynthesized from the pericarp extract of Cucumis melo L. (muskmelon). The AgNPs were characterized by ultraviolet-visible (UV-Vis) spectrophotometry, XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDAX (energy-dispersive X-ray spectroscopy). The XRD analysis showed that biosynthesized AgNPs were having FCC (face centered cubic) crystalline structures. Further, the SEM and EDAX showed spherically shaped AgNPs having an average size of 25 nm. The AgNPs effectively inhibited the growth of Bacillus subtilis and Escherichia coli. Moreover, the cytotoxic assay of AgNPs revealed effective cytotoxicity against different cancer cells, such as HeLa, HCT-116, PC-3 and Jurkat in a dose reliant way. The cell viability was noticed to range from 50% to 60% with IC50 values ranging from 150 µg/mL to 224 µg/mL. The lower cell viability indicates the toxic effects of biosynthesized AgNPs against these malignant cells. Thus, the current study shows that these biosynthesized AgNPs could be utilized in various medical applications in near future.

The Antineuroinflammatory Effect of Simvastatin on Lipopolysaccharide Activated Microglial Cells.

Microglial cells, upon hyperactivation, produce proinflammatory cytokines and other oxidative stress mediators causing neuroinflammation, which is associated with the progress of many neurodegenerative diseases. Suppressing the microglial activation has hence been used as an approach for treating such diseases. In this study, the antineuroinflammatory effect of simvastatin was examined in lipopolysaccharide (LPS)-activated rat C6 glioma cells. The cell proliferation and cytotoxic effect of LPS and simvastatin on C6 glioma cells was evaluated by (MTT) assay. Neuroinflammation was induced in differentiated cell lines by treatment with 3.125 µg/mL of LPS for 12 h. Upon induction, the cell lines were treated with different concentrations (3.125, 6.25, 12.5, 25, 50, 100 µM) of simvastatin and incubated in a humidified CO2 incubator for 24 to 48 h. The optimum concentrations of LPS and simvastatin were found to be 3.125 µg/mL and 25 µM, respectively, with a cell viability of more than 90% at 24 h postincubation. Furthermore, proinflammatory marker expression was analyzed by flow cytometry and showed a decrease in interferon-γ, interleukin 6, nuclear factor-κB p65, and tumor necrosis factor-α in simvastatin-treated and LPS-induced neuroinflammatory cells, and the mean fluorescent values were found to be 21.75 ± 0.76, 20.9 ± 1.90, 19.72 ± 1.29, and 16.82 ± 0.97, respectively, as compared to the untreated cells. Thus, we show that simvastatin has the potential to regulate the anti-inflammatory response in microglial cells upon LPS challenge. Hence, simvastatin can be employed as a potent anti-inflammatory drug against neuroinflammatory diseases and neurodegenerative disorders.