Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p

Abstract

Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs.

Overview of Research Trends in Precious Chinese Medicines

“…Pharmacologically, Polygonati Rhizoma has diverse therapeutic actions, including anti-oxidant, anti-diabetic, anti-osteoporosis, anti-cancer, anti-microbial, anti-hyperlipidemic, cardiomyocyte protection, immunomodulatory function, effects against infertility, and enhancement of sleep and memory. [17192021]…”

“…Pharmacologically, Polygonati Rhizoma has diverse therapeutic actions, including anti-oxidant, anti-diabetic, anti-osteoporosis, anti-cancer, anti-microbial, anti-hyperlipidemic, cardiomyocyte protection, immunomodulatory function, effects against infertility, and enhancement of sleep and memory. [17,[19][20][21] Astragalus membranaceus (A. membranaceus) is a major tonic used in TCM practice. The medicinal use of this herb was first recorded in the Shen Nong Ben Cao Jing (《神农本 草经》Shennong's Classic of Materia Medica), which was written approximately 2000 years ago.…”

Combination of PolygonatumRhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON3‐induced mitochondrial damage and endoplasmic reticulum stress in A549 cells

“…At the same time, it treats osteoporosis, diabetes, and lung disease. [3][4][5] Scutellaria baicalensis (SB) is a traditional Chinese medicine (TCM) widely used in clinical practice. According to "Shennong's Classic of Materia Medica," it is an herb of the genus Scutellaria and is used as a medicine by its roots.…”

“…Polygonatum Rhizoma (PR) is a perennial herb of the genus, first published in the ancient Chinese book “The Book of Famous Doctors.” 2 It is mainly for lung‐dryness with nonproductive cough and body deficiency. At the same time, it treats osteoporosis, diabetes, and lung disease 3–5 . Scutellaria baicalensis (SB) is a traditional Chinese medicine (TCM) widely used in clinical practice.…”

Editorial: Cancer therapy: The challenge of handling a double-edged sword

“…Current drugs promoting the recovery of BMHSC functions, such as erythropoietin and thrombopoietin, are expensive, while a recombinant colony-stimulating factor can potentially stimulate tumor cell proliferation. Gu et al, (2021) tested the anti-myelosuppressive efficacy of the main bioactive components of traditional Chinese medicine Shuanghuang Shengbai granule in a mouse model of cyclophosphamide (CTX)-treated lung adenocarcinoma. The study demonstrated that these bioactive components improve the hematopoietic function of BMHSCs via upregulation of high mobility group box 1 protein through inhibition of miR-142-3p, which alleviates CTX-induced cell injury and myelosuppression in this model.…”