Antitumor effect of a polysaccharide from Pseudostellaria heterophylla through reversing tumor-associated macrophages phenotype.

Tumor-associated macrophages (TAMs), which are predominant tumor-infiltrating immune cells in the tumor microenvironment, participate in promoting the occurrence and metastasis of tumor cells. Reprogramming TAMs has become a promising immunotherapeutic approach for novel cancer treatments. In this study, a homogeneous polysaccharide (PHP-1) was obtained from Pseudostellaria heterophylla, and its antitumor and immunological activities, as well as the underlying molecular mechanisms were explored. These findings suggested that PHP-1 can switch M2 macrophages to the M1 type, thereby promoting tumor cell apoptosis in vitro. In addition, PHP-1 can modulate the TAMs phenotype, maintain the CD4+/CD8+ lymphocyte balance, and exert antitumor effects in H22 tumor-bearing mice. Mechanistically, PHP-1 is recognized by the TLR4 receptor, promotes Ca2+ release, and activates the NF-κB and MAPK signaling pathways to reset the M2-type macrophages. These findings indicate that PHP-1 from P. heterophylla can function as a tumor immunotherapeutic modulator.

Green synthesized gold nanoparticles from Pseudobulbus Cremastrae seu Pleiones show efficacy against hepatic carcinoma potentially through immunoregulation.

Nanobiotechnology, the interface between biology and nanotechnology, has recently emerged in full bloom in the medical field due to its minimal side-effects and high efficiency. To broaden the application of nanobiotechnology, we composed gold nanoparticles from the extract of Pseudobulbus Cremastrae seu Pleiones (PCSP) using an efficient and green procedure. The biosynthesized Au nanoparticles containing PCSP (PCSP-AuNPs) were characterized by UV-vis spectroscopic, transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and Energy Dispersive X-ray (EDAX). After verifying the stability of PCSP-AuNPs, we detected its biosafety and immune-modulatory effects on RAW264.7 in vitro using NO assay, ELISA (TNF-α, IL-12p70, and IL-1ß), and CCK-8 test. Furthermore, we examined the direct in vitro effects of PCSP-AuNPs on hepatocellular carcinomas (HCCs). Finally, we evaluated the immune regulation of PCSP-AuNPs using a mouse model with H22-tumor by testing the index of immune organs, splenic lymphocyte proliferation, cytokines levels (TNF-α and IL-10), and the CD4+/CD8+ cell ratio in the peripheral blood. Immunohistochemical analyses including H&E and PCNA staining were performed to investigate the anti-cancer efficacy and biocompatibility of PCSP-AuNPs. We found that PCSP-AuNPs not just possessed low toxicity, but also improved the immune-mediated antitumor response as compared to PCSP alone, suggesting its potential as a novel and efficient drug for liver cancer therapy.

Study on the physicochemical properties and immunomodulatory anti-tumor effect of the Pholiota adiposa polysaccharide.

In this study, the extraction, purification, physical and chemical properties, and biological activity of the Pholiota adiposa (PAP) polysaccharide were investigated. One fraction (PAP-1a) of Pholiota adiposa polysaccharides was isolated using DEAE Sepharose™ Fast Flow and Sephacryl™ S-300 High-Resolution columns. The HPLGPC results revealed that the molecular weight of PAP-1a was 16.453 kDa. PAP-1a was composed of mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, arabinose, and fucose and their molar % was 33.41, 0.53, 1.33, 0.07, 0.27, 5.28, 38.31, 0.83, 18.04 and 2.23, respectively. PAP-1a could activate macrophages to secrete NO and cytokines such as TNF-a, IL-6, and IL-12p70. When hepatocellular carcinoma cells (HCCs) and macrophages were co-cultured, it was observed that PAP-1a inhibited the growth of Hep-G2, Hep-3B, and Huh7 via immunoregulation. It triggered cell apoptosis by blocking the cell cycle in the G0/G1 stage. Furthermore, PAP-1a had no direct cytotoxicity against the hepatocyte cell line L02 and macrophages RAW264.7.

Green synthesis and characterization of gold nanoparticles from Pholiota adiposa and their anticancer effects on hepatic carcinoma.

Gold nanoparticles (AuNPs) were successfully fabricated by Pholiota adiposa polysaccharide (PAP-1a) without employing any other chemicals. The physical and chemical properties of PAP-AuNPs were determined using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDXR), Fourier-transform infrared spectroscopy (FT-IR), and atomic force microscopy (AFM). In an attempt to analyze the immune regulation, antitumor effect, and biological safety, the production of NO and TNF-α, IL-12p70, and IL-1ß from RAW264.7 as well as the proliferation of RAW264.7 were detected in vitro. Flow cytometry was conducted to determine the ratio of the CD4+/CD8+ cell in peripheral blood and immunohistochemical analysis involving hematoxylin and eosin (H&E) and proliferating cell nuclear antigen (PCNA) staining were conducted in vivo. The results of this study showed that PAP-AuNPs had a significantly improved immune regulation and anti-tumor effect in comparison to PAP-1a alone. PAP-AuNPs showed no toxicity both in vivo and in vitro. This study demonstrates a useful application of PAP-AuNPs as a novel nanomedicine for hepatic carcinoma.