Low pH-Based Method to Increase the Yield of Plant-Derived Nanoparticles from Fresh Ginger Rhizomes.

Plant-derived nanoparticles (PDNPs) are naturally
occurring exosome-like nanovesicles derived from dietary plants
containing key plant bioactives. Ginger-derived PDNPs have a
therapeutic effect on alcohol-induced liver injury, inflammatory
bowel disease, and colon cancer. PDNPs are conventionally
purified by differential ultracentrifugation, a technique not
amenable for scale up. We have recently developed a polyethylene
glycol (PEG) 6000-based method for cost-effective purification of
ginger PDNPs, with comparable efficiency to differential ultracentrifugation
(Sci. Rep. 2020, 10 (1), 4456.). Herein, we report a
4−5-fold higher ginger PDNP recovery when PEG precipitation
was carried out in low pH conditions (pH 4 and 5). Low pHderived
ginger PDNPs were smaller in size without an overt change
in zeta potential. The spontaneous intracellular entry and protection against oxidative stress in A431 cells were similar between
ginger PDNPs purified under low, neutral, and alkaline pH. Low-pH purified ginger PDNPs had higher levels of total polyphenolic
content compared to PDNPs purified under neutral and alkaline pH. Recently, ginger PDNP-derived microRNAs have been shown
to exhibit cross-kingdom regulation by targeting human, gut microbiome, and viral transcripts. Using qRT-PCR, we also verified the
presence of miRNAs that were predicted to target SARS-CoV-2 in ginger PDNPs purified under low pH. Thus, we have developed a
method to purify ginger PDNPs in high yields by using low-pH conditions without affecting the major bioactive contents of PDNPs.