Chemical and biological assessment of Jujube (Ziziphus jujuba)-containing herbal decoctions: Induction of erythropoietin expression in cultures.

Jujubae Fructus, known as jujube or Chinese date, is the fruit of Ziziphus jujuba (Mill.), which not only serves as daily food, but acts as tonic medicine and health supplement for blood nourishment and sedation. According to Chinese medicine, jujube is commonly included in herbal mixtures, as to prolong, enhance and harmonize the efficiency of herbal decoction, as well as to minimize the toxicity. Here, we aim to compare the chemical and pharmacological properties of three commonly used jujube-containing decoctions, including Guizhi Tang (GZT), Neibu Dangguijianzhong Tang (NDT) and Zao Tang (ZOT). These decoctions share common herbs, i.e. Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, Zingiberis Rhizoma Recens and Jujube, and they have the same proposed hematopoietic functions. The amount of twelve marker biomolecules deriving from different herbs in the decoctions were determined by LC-MS, and which served as parameters for chemical standardization. In general, three decoctions showed common chemical profiles but with variations in solubilities of known active ingredients. The chemical standardized decoctions were tested in cultured Hep3B cells. The herbal treatment stimulated the amount of mRNA and protein expressions of erythropoietin (EPO) via the activation of hypoxia response elements: the three herbal decoctions showed different activation. The results therefore demonstrated the hematopoietic function of decoctions and explained the enhancement of jujube function within a herbal mixture.

[1]  K. Zheng,et al.  Chemical and biological assessment of Angelica herbal decoction: comparison of different preparations during historical applications. , 2012, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[2]  M A Goldberg,et al.  The regulated expression of erythropoietin by two human hepatoma cell lines. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Erwin G. Van Meir,et al.  Generation of bidirectional hypoxia/HIF-responsive expression vectors to target gene expression to hypoxic cells , 2001, Gene Therapy.

[4]  Jian-Guo Jiang,et al.  Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube , 2007, Natural product research.

[5]  R. Choi,et al.  Fo Shou San, an Ancient Chinese Herbal Decoction, Protects Endothelial Function through Increasing Endothelial Nitric Oxide Synthase Activity , 2012, PloS one.

[6]  G. Semenza,et al.  A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation , 1992, Molecular and cellular biology.

[7]  Jiabo Wang,et al.  Yinchenhao decoction in the treatment of cholestasis: A systematic review and meta-analysis. , 2015, Journal of ethnopharmacology.

[8]  Henry H. N. Lam,et al.  Fruit of Ziziphus jujuba (Jujube) at two stages of maturity: distinction by metabolic profiling and biological assessment. , 2015, Journal of agricultural and food chemistry.

[9]  A. Maxwell,et al.  Regulation of erythropoietin gene expression depends on two different oxygen-sensing mechanisms. , 1999, Molecular genetics and metabolism.

[10]  C. Giordano,et al.  Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. , 2012, Journal of ethnopharmacology.

[11]  Borgi Wahida,et al.  Antiulcerogenic activity of Zizyphus lotus (L.) extracts. , 2007, Journal of ethnopharmacology.

[12]  T. Dong,et al.  Chemical and biological assessment of a chinese herbal decoction containing Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having optimized properties. , 2006, Journal of agricultural and food chemistry.

[13]  F. Daneshmand,et al.  Investigation of the antimicrobial activities of Snakin-Z, a new cationic peptide derived from Zizyphus jujuba fruits , 2013, Natural product research.

[14]  M. Goldberg,et al.  Erythropoietin mRNA levels are governed by both the rate of gene transcription and posttranscriptional events. , 1991, Blood.

[15]  Chao Huang,et al.  Systems pharmacology-based approach for dissecting the addition and subtraction theory of traditional Chinese medicine: An example using Xiao-Chaihu-Decoction and Da-Chaihu-Decoction , 2014, Comput. Biol. Medicine.

[16]  J. Winer,et al.  Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. , 1999, Analytical biochemistry.

[17]  J. Duan,et al.  Bioactive components in the fruits of Ziziphus jujuba Mill. against the inflammatory irritant action of Euphorbia plants. , 2012, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[18]  M. Goldberg,et al.  Erythropoietin gene regulation: from the laboratory to the bedside. , 1991, Contributions to nephrology.

[19]  Yiyu Cheng,et al.  Derivative multiple reaction monitoring and single herb calibration approach for multiple components quantification of traditional Chinese medicine analogous formulae. , 2015, Journal of chromatography. A.

[20]  R. Choi,et al.  The extract of Rhodiolae Crenulatae Radix et Rhizoma induces the accumulation of HIF-1α via blocking the degradation pathway in cultured kidney fibroblasts. , 2011, Planta medica.

[21]  G. Birgegard,et al.  Patients with anaemia can shift from kidney to liver production of erythropoietin as shown by glycoform analysis. , 2013, Journal of pharmaceutical and biomedical analysis.

[22]  Young Sup Kim,et al.  Zizyphus attenuates ischemic damage in the gerbil hippocampus via its antioxidant effect. , 2010, Journal of medicinal food.

[23]  R. Choi,et al.  Flavonoids from Radix Astragali induce the expression of erythropoietin in cultured cells: a signaling mediated via the accumulation of hypoxia-inducible factor-1α. , 2011, Journal of agricultural and food chemistry.

[24]  M. Friedman,et al.  Distribution of free amino acids, flavonoids, total phenolics, and antioxidative activities of Jujube (Ziziphus jujuba) fruits and seeds harvested from plants grown in Korea. , 2011, Journal of agricultural and food chemistry.

[25]  So young Lee,et al.  Zizyphus jujuba and its Active Component Jujuboside B Inhibit Platelet Aggregation , 2013, Phytotherapy research : PTR.

[26]  Guanwei Fan,et al.  Liquorice, a unique "guide drug" of traditional Chinese medicine: a review of its role in drug interactions. , 2013, Journal of ethnopharmacology.

[27]  H. Shibasaki,et al.  Neuroprotective effect of cyclic GMP against radical‐induced toxicity in cultured spinal motor neurons , 2000, Journal of neuroscience research.

[28]  J. Spivak The anaemia of cancer: death by a thousand cuts , 2005, Nature Reviews Cancer.

[29]  R. Choi,et al.  A Chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis induces the expression of erythropoietin in cultured Hep3B cells. , 2008, Planta medica.

[30]  L. Levitt,et al.  Augmentation of in vitro human marrow erythropoiesis under physiological oxygen tensions is mediated by monocytes and T lymphocytes. , 1987, Blood.

[31]  T. Dong,et al.  The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1α in Cultured Hep3B Cells , 2014, Planta Medica.