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.

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.

Bone Protective Effects of Danggui Buxue Tang Alone and in Combination With Tamoxifen or Raloxifene in vivo and in vitro.

Danggui Buxue Tang (DBT), a traditional Chinese Medicine decoction containing Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), is commonly prescribed for women in China as a remedy for menopausal symptoms. Previous study indicated that DBT stimulated cell growth and differentiation of human osteosarcoma MG-63 cells and exhibited estrogenic properties via estrogen receptors (ERs). The present study aimed to study the bone protective effects of DBT and its potential interactions with selective estrogen receptor modulators (SERMs, tamoxifen and raloxifene) in both in vivo and in vitro models as they act via similar ERs. Six-month-old Sprague-Dawley rats were randomly assigned to the following treatments for 12 weeks: (1) sham-operated control group with vehicle (sham), (2) ovariectomized group with vehicle (OVX), (3) OVX with 17ß-estradiol (E2, 2.0 mg/kg day), (4) OVX with tamoxifen (Tamo, 1.0 mg/kg day), (5) OVX with raloxifene (Ralo, 3.0 mg/kg day), (6) OVX with DBT (DBT, 3.0 g/kg day), (7) OVX with DBT+Tamoxifen (DBT+Tamo), and (8) OVX with DBT+Raloxifene (DBT+Ralo). Effects of DBT and potential interactions between DBT and SERMs were also evaluated in MG-63 cells. DBT, tamoxifen, raloxifene, and their combinations significantly increased bone mineral density (BMD) and improved trabecular bone properties, including bone surface (BS), trabecular bone number (Tb.N), and trabecular bone separation (Tb.Sp), as well as restored changes in bone turnover biomarkers and mRNA expression of genes involved in bone metabolism in OVX rats. Furthermore, DBT, SERMs, and their combinations significantly increased serum estradiol and suppressed follicle stimulating hormone and luteinizing hormone in OVX rats, suggesting the possible involvement of the hypothalamus-pituitary-gonadal axis in mediating their bone protective effects. However, SERMs, but not DBT, significantly increased uterus index in OVX rats. DBT significantly induced ALP activity and estrogen response element-dependent transcription in MG-63 cells. Our study demonstrated that DBT alone and in combinations with SERMs could exert bone protective effects in vitro and in vivo.

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.

Metabonomic analysis of water extracts from Chinese and American ginsengs by 1H nuclear magnetic resonance: identification of chemical profile for quality control.

BACKGROUND: With the gaining popularity of commercially prepared decoctions of herbal medicines on the market, an objective and efficient way to reveal the authenticity of such products is urgently needed. Previous attempts to use chromatographic or spectroscopic methods to identify ginseng samples made use of components derived from methanol extracts of the herb. It was not established that these herbs can be distinguished solely from consumable components, which are responsible for the clinical efficacy of the herb.In this study, metabonomics, or metabolic profiling, based on the application of 1H-Nuclear Magnetic Resonance (NMR), is applied to distinguish the water extracts of three closely related ginseng species: P. ginseng (from two different cultivated regions in China), P. notoginseng and P. quinquefolius. METHODS: A water extraction protocol that mimics how ginseng decoctions are made for consumption was used to prepare triplicate samples from each herb for analysis. High-resolution 1H NMR spectroscopy was used to acquire metabolic profiles of the four ginseng samples. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were able to distinguish different types of ginseng. RESULTS: H NMR metabolic profiling was performed to distinguish the water extracts of P. ginseng cultivated in Hebei and Jilin of China, both of which were distinguished from extracts of P. notoginseng and P. quinquefolius, by unsupervised principle component analysis based on the entire 1H NMR spectral fingerprint Statistically significant differences were found for several discriminating features traced to common metabolites and the ginsenosides Rg1 and Rd, in the 1H NMR spectra. CONCLUSION: This study demonstrated that 1H NMR metabonomics can simultaneously distinguish different ginseng species and multiple samples of the same species that were cultivated in different regions. This technique is applicable to the authentication and quality control of ginseng products.