Astragalus polysaccharide (PG2) Ameliorates Cancer Symptom Clusters, as well as Improves Quality of Life in Patients with Metastatic Disease, through Modulation of the Inflammatory Cascade

Abstract

Background: Improving patients’ quality of life (QoL) is a principal objective of all treatment in any clinical setting, including oncology practices. Cancer-associated inflammation is implicated in disease progression and worsening of patients’ QoL. Conventional anticancer therapeutics while selectively eliminating cancerous cells, are evaded by stem cell-like cells, and associated with varying degrees of adverse effects, thus reducing patients’ QoL. This necessitates novel therapeutic approaches with enhanced efficacy, minimal or no treatment-related adverse effects, and improved QoL in patients with cancer, especially those with metastatic/advance stage disease. Methods: Sequel to our team’s previous publication, the present study explores probable effects of Astragalus polysaccharides (PG2) on cancer-related inflammatory landscape and known determinants of QoL, as well as the probable link between the two to provide mechanistic insight. In an exploratory double blind randomized controlled trial using patients with metastatic disease (n = 23), we comparatively evaluated the therapeutic efficacy of high (500 mg) or low (250 mg) dose PG2 administered intravenously (i.v.), with particular focus on its suggested anti-inflammatory function and the probable effect of same on QoL indices at baseline, then at weeks 4 and 8 post-PG2 treatment. Results: All 23 patients with metastatic disease treated with either low or high PG2 experienced reduced pain, nausea, vomiting, and fatigue, as well as better appetite and sleep, culminating in improved global QoL. This was most apparent in the high dose group, with significant co-suppression of pro-inflammatory interleukin (IL)-1β, IL-4, IL-6, IL-13, IL-17, monocytes chemotactic protein (MCP)1, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), tumor growth factor (TGF)-β1, interferon (IFN)-γ, and immune suppressors IL-10 and IL-12. Univariate and multivariate analyses revealed that IL-1β, IL-13 and GM-CSF are independent prognosticators of improved QoL. Conclusion: This proof-of-concept study provides premier evidence of functional association between PG2 anti-inflammatory effects and improved QoL in patients with advanced stage cancers, laying the groundwork for future larger cohort blinded controlled trials to establish the efficacy of PG2 as adjuvant anticancer therapy in metastatic or advanced stage clinical settings.

Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy

“…PG2, an immunomodulator, might affect the tumor microenvironment by reducing inflammation. 19 ICIs are known to enhance the host immune response to cancer by negative regulation to prevent tumor cells from avoiding immune cell-mediated death. 20 As PG2 stabilizes or decreases the NLR, alterations in the relative proportions of circulating lymphocytes might promote the antitumor immune effect mediated by immunotherapy.…”

Astragalus polysaccharides (PG2) Enhances the M1 Polarization of Macrophages, Functional Maturation of Dendritic Cells, and T Cell-Mediated Anticancer Immune Responses in Patients with Lung Cancer

“…To gain some mechanistic insight into the therapeutic activities of PG2 observed in our recent works [23,24] against the background of its documented immunomodulatory activities [21,22,26], we further investigated the effect of PG2 on the M1/M2 macrophage skewness in NSCLC cell line H441 co-cultured with MDMs. As demonstrated in our results, compared to the PMA-treated control group, the population of CD206+ M2-polarized MDMs increased from 0.044% to 66.2% after exposure to IL-4/IL-13, while the CD80+ M1 macrophages increased from 0.589% to 1.59% (Figure 2A,B).…”

“…Corroboratory to documentation of PG2 potently modulating immunity in in vivo inflammation [33] and diabetes [34] models, our recent works demonstrated that PG2 ameliorates cancer-related fatigue and other cancer symptom clusters, as well as improves the quality of life (QoL) of patients with metastatic disease through the modulation of patients’ inflammatory cascade [23,24]; however, the underlying molecular or cellular mechanisms remain relatively unclear. While PG2 is known to exhibit anti-inflammatory potentials, as demonstrated by its ability to enhance the expression of anti-inflammatory cytokines, such as interleukin (IL)-10, transforming growth factor (TGF)-β, and 5′ adenosine monophosphate- activated protein kinase (AMPK), as well as inhibit expression of pro-inflammatory cytokines, including IL-1β, inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein (MCP)-1, IL-6, and CD11c in an AMPK-dependent manner [35], it has also been suggested that PG2 can promote the inflammatory process by increasing the level of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), NF-κB, and the production of nitric oxide (NO) [36].…”

“…However, the immune-dependent anticancer activity of PG2 in lung cancer remains largely unexplored and unclear. Thus, following our recent works demonstrating that PG2 ameliorates cancer-related fatigue and other cancer symptom clusters, as well as improving the quality of life (QoL) of patients with metastatic disease through the modulation of patients’ inflammatory cascade [23,24] against the background that macrophages and other immune cells; playing critical roles in tumor initiation, dissemination, and progression; as well as suggestions that PG2 may play a role in the differentiated status of splenic DCs; increased CD11c high CD45RB low DC population; and enhanced immune function of T lymphocyte via up-regulation of the Th1/Th2 ratio while in vitro [25], the present study hypothesized and demonstrated that PG2, by preferentially up-regulating the M1/M2 macrophage ratio, skewing the pro-inflammatory/anti-inflammatory signaling balance towards an anticancer phenotype, and repressing erstwhile-acquired immune privilege by cancerous cells in patients with NSCLC.…”

Integrative medicine considerations for convalescence from mild-to-moderate COVID-19 disease

“…The root extract contains polysaccharides which have been found to increase innate and T-cell adaptive immunity, to exert anti-oxidant and anti-proliferative effects, and to modulate inflammation. 70 The anti-inflammatory effects of intravenous astragalus have been documented in a DBRCT of 23 patients with metastatic cancers of various types 71 Astragalus resulted in significant quality of life improvements (reduced pain, nausea, fatigue, improved appetite and sleep) which was attributed to reduced inflammatory cytokines, notably IL − 1β and IL-6. In another clinical trial of 82 patients with acute exacerbation of COPD, the addition of 15mg of astragalus granules twice daily for two weeks to conventional bronchodilator therapy resulted in significant reductions in TNFα, IL − 8, IL − 1β and IL-32.…”