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Danggui Buxue Tang (DBT) is a well-known Chinese herbal recipe often prescribed in clinical treatment for menopausal and cardiovascular symptoms. 5-Fluorouracil (5-FU) is a chemotherapy drug that treats several cancers; however, it causes severe adverse effects and multidrug resistance. Combining natural medications can reduce the side effects of 5-FU use. Hence, we aimed to determine the role of DBT in strengthening the anticancer capabilities of 5-FU in a cultured colorectal adenocarcinoma cell line (HT-29 cell) and xenograft nude mice. HT-29 cells cultured with DBT did not exhibit cytotoxicity. However, co-administration of DBT with 5-FU significantly increased apoptosis and the expression of apoptotic markers. The inhibition of proliferation induced by DBT and 5-FU was shown to be mediated by c-Jun N-terminal kinase signaling. In addition, the potentiation effect of 5-FU and DBT was demonstrated in reducing tumor size, expressions of Ki67 and CD34 in HT-29 xenograft mice. This finding suggests that DBT can work with 5-FU as a novel chemotherapeutic strategy for treating colon cancer.

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.

Ethnopharmacological relevance: In traditional Chinese medicine (TCM) theory, “Qi” is classified as energetic essence supporting the life activities in human. “Blood” is categorized as nourishing essence and circulating in the body. “Blood” and “Qi” have an intimate relationship. Astragali Radix (AR; root of Astragalus membranaceus (Fisch.) Bge. Var. mongholicus (Bge.) Hsiao) has a broad spectrum of application for “Qi-Blood” enrichment. Astragaloside IV, a major saponin in AR, has therapeutic functions in erythropoietic, cardiovascular and immune systems. However, the efficacy of astragaloside IV in erythrophagocytosis has not been elucidated. Aim of the study: The possible functions of astragaloside IV in heme iron recycling during erythrophagocytosis in cultured macrophage were elucidated. Methods: The translational and transcriptional expressions of heme recycling enzymes were determined after incubating of astragaloside IV for 24 h in cultured macrophage. Results: In astragaloside IV-treated macrophage, the expressions, both RNA and protein levels, of regulators of heme recycling, e.g. heme oxygenase-1 (HO-1), ferroportin (FPN), biliverdin reductase A and B (BVRA, BVRB), were markedly induced in dose-dependent manners. In parallel, the transcriptional activity of antioxidant response element, cloned within an expression vector as pARE-Luc and transfected in cultured macrophages, was markedly induced after a challenge with astragaloside IV in a dose-dependent manner. Moreover, the translocation of Nrf2, a transcriptional factor in regulating expression of heme recycling protein, was induced by astragaloside IV, leading to an enrichment at nucleus fraction. Conclusion: Astragaloside IV shed lights in enhancing the expression of heme recycle proteins via Nrf2/ARE signaling pathway. © 2020 Elsevier B.V.

Background. Guizhi Fuling capsule (GFC), a well-known formula composed of five medicinal herbs, is commonly prescribed to treat primary dysmenorrhea, as well as to achieve good clinical efficacy in China. However, the active components of GFC have not been identified. Here, the anti-inflammatory functions of GFC, as well as its major ingredients, were evaluated in human umbilical vein endothelial cells (HUVECs). Methods. Lipopolysaccharide (LPS) was used in HUVECs to imitate the cellular inflammation. Then, GFC-triggered mRNA expressions of cyclooxygenase-1 (COX-1) and COX-2 were determined by real-time PCR, while the expression of COX-2 protein was revealed by western blotting. Besides, nine components of GFC were evaluated for their contribution value in the anti-dysmenorrhea effects Results. The application of GFC downregulated the mRNA expressions of COX-1 and COX-2 mRNAs. Nine major components of GFC were tested in the inflammatory system, and three compounds, including paeoniflorin, benzoylpaeoniflorin, and amygdalin, exhibited robust activation in HUVECs. The combination of paeoniflorin, benzoylpaeoniflorin, and amygdalin showed over 80% of the anti-inflammatory activation. Conclusion. Our study supports that GFC plays a promising role in anti-dysmenorrhea function by decreasing COXs’ expression. Besides, paeoniflorin, benzoylpaeoniflorin, and amygdalin could be considered as major regulators for the anti-dysmenorrhea effects of GFC.

Saussureae Involucratae Herba is the dried ground part of Saussurea involucrata (Kar. et Kir.) Sch.-Bip, which is also named as “Snow lotus” and being used in traditional Uyghur and/or Chinese medicine. This rare herb can be found at 4,000 m elevation in western part of Tianshan Mountain, Xinjiang China. According to China Pharmacopoeia (2015), the major pharmaceutical values of “Snow lotus” (Xuě liánhuā in Chinese) are alleviating rheumatoid arthritis, accelerating blood circulation and mitigating other “cold” syndromes. Traditionally, the clinical application of “Snow lotus” includes the treatments in inflammation-associated disorder, blood circulation acceleration and heat and dampness elimination. Recent studies suggested that “Snow lotus” possessed therapeutic effects associating with anti-cancer, anti-oxidation, adipogenesis suppression and neuroprotection activities, which were proposed to be related with its bioactive constitutes, i.e. acacetin, hispidulin, and rutin. In the present review, we aim to summarize pharmacological effects and underlying cell signaling pathways of “Snow lotus” in treating various medical problems. Copyright © 2020 Gong, Huang, Yang, Qi, Han, Zheng, He, Chan, Tsim and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Background. Abnormal storage of white adipocyte tissue (WAT) is the major factor causing obesity. The promising strategies for obesity treatment are building up the brown adipocyte tissue (BAT) and/or expedite fatty acid catabolism. Traditional Chinese Medicine (TCM) sheds light on preventing obesity. Ginger is one of the most effective herbs for antiobesity by accelerating browning WAT. To fortify the antiobesity effect of ginger, an ancient Chinese herbal decoction composed of four herbs, Angelicae Sinensis Radix (ASR), Astragali Radix (AR), Jujuba Fructus (JF), and Zingiberis Rhizoma Recens (ZRR; ginger), was tested here: This herbal formula was written in AD 1155, named as Danggui Buxue Tang (DBT1155). Therefore, the antiobesity function of this ancient herbal decoction was revealed in vitro by cultured 3T3-L1 cells. Materials and Method. The lipid accumulation was detected by Oil Red O staining. Furthermore, the underlying working mechanisms of antiobesity functions of DBT1155 were confirmed in 3T3-L1 cells by confocal microscopy, western blot, and RT-PCR. Results. DBT1155 was able to actuate brown fat-specific gene activations, which included (i) expression of PPARγ, UCP1, and PCG1α and (ii) fatty acid oxidation genes, i.e., CPT1A and HSL. The increase of browning WAT, triggered by DBT1155, was possibly mediated by a Ca2+-AMPK signaling pathway, because the application of Ca2+ chelator, BAMPTA-AM, reversed the effect. Conclusion. These findings suggested that the herbal mixture DBT1155 could potentiate the antiobesity functions of ginger, which might have potential therapeutic implications. © 2019 Guowei Gong et al.

Background: Danggui Buxue Tang (DBT) is a historical Chinese herbal decoction, and which has more than 800 years of applications. This herbal decoction solely contains two materials: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) at a weight ratio of 5:1. Clinically, DBT aims to improve anemia syndrome. In complementary and alternative medicine theory, the cause of neurodegenerative disease is proposed to be related with anemia. In line to this notion, low levels of hemoglobin and red blood cell have been reported in patients suffering from Alzheimer's disease (AD), a chronic neurodegenerative disease caused by β-amyloid peptide (Aβ) accumulation. Therefore, we would like to probe the neuroprotective functions of this ancient herbal formula in vitro. Method: The neuroprotective effects of DBT in the Aβ-induced cell death were detected in cultured cortical neurons by multiple techniques, i.e. confocal and western blot. Results: In the cultures, application of DBT reduced Aβ-induced apoptosis rate in a dose-dependent manner. In Aβ-treated cortical neurons, the expression ratio of Bcl2 to Bax was altered by DBT. In parallel, application of DBT markedly suppressed the Aβ-induced expressions of apoptotic markers, i.e. cleaved-caspase 3/9 and PARP. Conclusion: Taken these results, DBT shows promising protective effects against Aβ-induced stress or insult in cultured neurons. © 2019 The Author(s).

Danggui Buxue Tang (DBT; 當歸補血湯), a herbal decoction that is composed of Astragali Radix (AR; Huangqi, 黃芪) and Angelica Sinensis Radix (ASR; Danggui, 當歸), has been used for treating menopausal irregularity in women for more than 800 years in China. Among thousands of traditional Chinese medicine (TCM) herbal formulae, most of them consist of multiple herbs, while DBT is considered to be the simplest decoction. Here, we chose DBT as an example to explain the TCM theory by using chemical and biological assessment. According to the traditional record of DBT preparation, ASR had to be processed by yellow wine before usage, which markedly increased the efficacy of ASR, as well as enhanced the bioactivities of DBT. However, the underlying mechanism of the wine-processing is unknown. Here, the level of ligustilide, a volatile oil, could be reduced by wine-processing, while the level of ferulic acid could be increased by wine-processing. The evidence suggested that ligustilide and ferulic acid could be the critical regulators of DBT. After chemical and biological evaluations, ligustilide and ferulic acid had been demonstrated to be a negative regulator and a positive regulator of DBT, respectively. The current results strongly supported the traditional practice of preparing DBT by using the wine-processed ASR. To reveal the mechanism of DBT-induced erythropoietin (EPO) expression, the upstream regulator of this gene was revealed in cultured human embryonic kidney fibroblasts (HEK293T). The plasmid containing hypoxia response element (HRE), when being transfected into fibroblasts, was highly responsive to the challenge of DBT. To account for the transcriptional activation of HRE, DBT treatment was shown to increase the expression of mRNA and protein of hypoxia-inducible factor-1 (HIF-1α), as well as the blockage of the degradation pathway of HIF-1α protein. In addition, the activation of a mitogen-activated protein kinase (MAPK)-dependent signaling by DBT could also enhance t

OBJECTIVE: To establish the HPLC fingerprints for assessing the quality of Fructus Aurantii from different habitats, and to determine the contents of naringin, neohesperidin and synephrine. METHODS: HPLC fingerprinting and content determination methods were applied to evaluate 10 batches of Fructus Aurantii from different habitats. The samples were separated by Alltima C 18·column(4.6 mmx250 mm, 5 μm) using acetonitrile-0.1% phosphoric acid and 0.1% SDS water solution as mobile phase with gradient elution. The flow rate was 1.0 mL·min-1. The detection wavelengths were 224 nm for fingerprinting, 283 nm for content determination of naringin and neohesperidin, and 224 nm for content determination of synephrine, respectively. RESULTS: HPLC fingerprint of Fructus Aurantii was established with good separation and repeatability, which could be used for quality assessment of Fructus Aurantii. Six common peaks were defined in characteristic fingerprints, and similarity evaluation system was applied to evaluate the fingerprints of the 10 batches of Fructus Aurantii. The contents of naringin, neohesperidin and synephrine in Fructus Aurantii from different habitats were obviously different from each other. CONCLUSION: The method is sensitive, repeatable and accurate, which can be used for the quality control of Fructus Aurantii. The contents of naringin, neohesperidin and synephrine vary significantly in Fructus Aurantii from different habitats, which suggests that more attention should be paid to the clinical use of Fructus Aurantii.