Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth.

BACKGROUND: It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy. METHODS: A novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from Panax ginseng C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF. RESULTS: GDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue. CONCLUSIONS: GDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.

Isolation and pharmacological characterization of a new cytotoxic L-amino acid oxidase from Bungarus multicinctus snake venom.

ETHNOPHARMACOLOGICAL RELEVANCE: Bungarus multicinctus snake belongs to Elapidae family and is widely distributed in southern China. It is widely used in traditional Chinese medicine with the effect of dispelling wind and removing obstruction in the meridians. Moreover, it is also as a chief ingredient of many polyherbal formulations for the treatment of cancer. AIM OF THE STUDY: To evaluate the antitumor activity of Bungarus multicinctus snake venom components and isolate, characterize the most effective anti-tumor component of Bungarus multicinctus snake venom. MATERIALS AND METHODS: The in vitro antitumor activity of Bungarus multicinctus venom components was detected by cytotoxicity assay and cell apoptosis assay. A unique LAAO from Bungarus multicinctus venom named as BM-Apotxin was isolated and characterized by Sephadex G-75 gel filtration, Sephadex G-25 desalting, Q ion-exchange chromatography and subsequent amino acids sequence determination. The LAAO activity and enzyme kinetics of BM-Apotxin was detected by microplate assay. RESULTS: BM-Apotxin, a 65KDa glycoprotein, which contributed to the most anti-tumor effects of Bungarus multicinctus venom. BM-Apotxin can selectively kill tumor cells, with less cytotoxicity to the normal cells. BM-Apotxin is an L-amino acid oxidase (LAAO) with high sequence identity to other snake venom LAAOs. Its anti-tumor activity is mainly due to the hydrogen peroxide produced from LAAO oxidation. But the catalase did not reverse its anti-tumor effect completely. Like other snake venom LAAOs, BM-Apotxin can oxidize many L amino acids, not D amino acids. The optimum substrate for BM-Apotxin is L-Phe. Moreover, BM-Apotxin deglycosylation can significantly reduce the LAAO activity and anti-tumor activity of BM-Apotxin. CONCLUSION: This study will facilitate the study on anti-tumor mechanism of snake venom and drug development based on Bungarus multicinctus venom.

Bacillus as a potential diagnostic marker for yellow tongue coating.

Observation of tongue coating, a foundation for clinical diagnosis and treatment in traditional Chinese medicine (TCM), is a major indicator of the occurrence, development, and prognosis of disease. The biological basis of tongue diagnosis and relationship between the types and microorganisms of tongue coating remain elusive. Thirteen chronic erosive gastritis (CEG) patients with typical yellow tongue coating (YTC) and ten healthy volunteers with thin white tongue coating (WTC) were included in this study. Patients were provided a 2-course targeted treatment of a herbal medicine Ban Xia Xie Xin decoction, traditionally prescribed for CEG patients with YTC, to evaluate the relationship between tongue coating microbiota and diagnosis of CEG with typical YTC. The tongue coating segregation structure was determined using Illumina Miseq sequencing of the V4-V5 region of the 16S ribosomal RNA gene. Bacillus was significantly observed only in CEG patients with YTC, but not in patients who received the decoction. YTC (n = 22) and WTC (n = 29) samples were collected for bacterial culturing to illustrate the relationship between Bacillus and YTC. The Bacillus positivity rate of YTC samples was 72.7%; Bacillus was not observed in WTC samples. In conclusion, Bacillus was strongly associated with YTC.