Astragaloside IV, a saponin from Astragalus membranaceus var. mongholicus, induces expressions of heme recycle proteins via signaling of Nrf2/ARE in cultured macrophages.

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.

Evaluation of Anti-Inflammatory Components of Guizhi Fuling Capsule, an Ancient Chinese Herbal Formula, in Human Umbilical Vein Endothelial Cells.

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.

The effect of methanol extract from Saussurea involucrata in the lipopolysaccharide-stimulated inflammation in cultured RAW 264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussureae Involucratae Herba (SIH), known as "snow lotus" in Uyghur and/or Chinese medicines, is generated from the dried aerial part of Saussurea involucrata (Kar. et Kir.) Sch.-Bip. (Asteraceae). The major pharmaceutical value of SIH has been recorded in China Pharmacopoeia, i.e. to balance the immune system, and thus SIH is commonly used for rheumatoid arthritis treatment. Nevertheless, the detailed mechanism of SIH in immune function is still unresolved. AIM OF THE STUDY: Here, we employed macrophage RAW 264.7 cell as a model to demonstrate the signaling pathways, triggered by SIH, in regulating the LPS-induced inflammation. METHODS: The application of SIH methanolic extract suppressed the expression of cytokines, a hallmark of chronic inflammation, in lipopolysaccharide (LPS)-stimulated cultures. RESULTS: The anti-inflammatory functions of SIH were shown to be triggered via NF-κB/PI3K/MAPK signaling pathways by revealing the specific biomarkers, i.e. translocation activities of NF-κB and phosphorylations of Erk1/2, JNK and Akt. CONCLUSION: The aforementioned results showed the underlying action mechanism of SIH in chronic inflammation mitigation, and which might shed light on clinical applications of SIH in traditional Chinese and/or Uyghur medicines.

Saussureae Involucratae Herba (Snow Lotus): Review of Chemical Compositions and Pharmacological Properties.

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" (Xue liánhua 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.

Polysaccharide of Danggui Buxue Tang, an Ancient Chinese Herbal Decoction, Induces Expression of Pro-inflammatory Cytokines Possibly Via Activation of NFκB Signaling in Cultured RAW 264.7 Cells.

Danggui Buxue Tang (DBT) is an ancient Chinese herbal decoction containing two herbs, Astragali Radix (AR) and Angelicae Sinensis Radix (ASR): this herbal decoction serves as dietary supplement for women during menopause. DBT has been known to modulate immune responses, and its polysaccharide is proposed to be one of the active components. However, the polysaccharide-induced signaling in immune activation is not revealed. Here, we are identifying that the immune activation, triggered by DBT, could be mediated by polysaccharide. In cultured macrophages (RAW 264.7 cells), the application of polysaccharide-enriched extract of DBT significantly increased the expressions of mRNA and protein levels of interleukin-1ß, interleukin-6 and tumor necrosis factor. The induction was much stronger than the polysaccharide extract generated singly from AR, or from ASR, or from their simple mixture. The induced cytokine release in cultured macrophage was revealed to be triggered by activation of nuclear factor-kappa B (NF-κB) signaling, including (i) degradation of IkBα; (ii) translocation of NF-κB p65 from cytosol to nuclei; and (iii) activation of NF-κB transcriptional elements. These results verified the possible role of DBT polysaccharide in modulating immune responses. Copyright © 2016 John Wiley & Sons, Ltd.