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Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-kappa B complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs.

Y̱u P̠ing F̠eng S̠an (YPFS; Jade screen powder; 玉屏風散), a Chinese herbal decoction comprised of A̱stragali Ṟadix (AR; Huangqi), A̱tractylodis M̱acrocephalae Ṟhizoma (AMR; Baizhu) and S̱aposhnikoviae Ṟadix (SR; Fangfeng). Clinically, YPFS has been widely used to regulate immune functions; however, the action mechanism of which is not known. Here, we addressed this issue by providing detail analyses of chemical and biological properties of YPFS. In order to standardize YPFS chemically, a typical HPLC fingerprint of YPFS at absorbance of 210 nm was developed: the fingerprint was used to ensure the detection of the chosen chemical markers from the herbal extracts. More important this fingerprint served as an index for identification of YPFS. Moreover, we developed a rapid resolution liquid chromatography coupled with mass spectrometry method to simultaneously identify different chemicals from the three herbs, as a means of quality assessment for YPFS. These marker chemicals included: (i) AR-derived flavonoids: calycosin-7-O-β-D-glucoside, calycosin, ononin and formononetin; (ii) AR-derived saponins: astragaloside IV, III and II; (iii) AMR-derived sesquiterpenoids: atractylenolide I, II and III; (iv) SR-derived chromones prim-O-glucosylcimifugin and 5-O-methylvisammioside; and (v) SR-derived coumarins: scopoletin, isopsoralen and psoralen. In this case, the quantity of these chemicals might be used not only for quality control of YPFS, but also for elucidation of the compatible principle. In addition, the chemical analysis could serve a parameter for chemical standardization and repeatability of YPFS preparation. These values defined the minimal amount of chemicals for a standardized YPFS being prepared for each time, and which could be used as a quality index for the biological studies. In order to reveal the immune functions of YPFS in innate immunity, the standardized extract was applied onto cultured murine macrophages. Innate immunity includes inflammatory respons

Yu Ping Feng San (YPFS), a Chinese herbal decoction, is composed of Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu) and Saposhnikoviae Radix (SR; Fangfeng) in a weight ratio of 1:2:1. Clinically, YPFS has been widely used to regulate immune functions; however, the action mechanism of it is not known. Here, we addressed this issue by providing detail analyses of chemical and biological properties of YPFS. By using rapid resolution liquid chromatography coupled with mass spectrometry, fifteen chemicals deriving from different herbs of YPFS were determined, and which served as a control for the standardization of the herbal extract of YPFS. In general, the amounts of chosen chemical markers were higher in a preparation of YPFS as compared to that of single herb or two-herb compositions. In order to reveal the immune functions of YPFS, the standardized extract was applied onto cultured murine macrophages. The treatment of YPFS stimulated the mRNA and protein expressions of pro-inflammatory cytokines via activation of NF-kappa B by enhancing I kappa B alpha degradation. In contrast, the application of YPFS suppressed the expressions of pro-inflammatory cytokines significantly in the lipopolysaccharide (LPS)-induced chronic inflammation model. In addition, YPFS could up regulate the phagocytic activity in cultured macrophages. These results therefore supported the bi-directional immunemodulatory roles of YPFS in regulating the releases of cytokines from macrophages.

Radix Astragali (RA) is commonly used as a health food supplement to reinforce the body vital energy. Flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-d-glucoside, are considered to be the major active ingredients within RA. Here, we provided different lines of evidence that the RA flavonoids stimulated the expression of erythropoietin (EPO), the central regulator of red blood cell mass, in cultured human embryonic kidney fibroblasts (HEK293T). A plasmid containing hypoxia response element (HRE), a critical regulator for EPO transcription, was tagged upstream of a firefly luciferase gene, namely, pHRE-Luc, which was being transfected into fibroblasts. The application of RA flavonoids onto the transfected cells induced the transcriptional activity of HRE. To account for the transcriptional activation after the treatment of flavonoids, the expression of hypoxia-inducible factor-1α (HIF-1α) was markedly increased: The increase was in both mRNA and protein levels. In addition, the degradation of HIF-1α was reduced under the effect of flavonoids. The regulation of HIF-1α therefore could account for the activation of EPO expression mediated by the RA flavonoids. The current results therefore reveal the function of this herb in enhancing hematopoietic functions. © 2011 American Chemical Society.