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Simple Summary: Osteosarcoma is the most prevalent orthotopic bone tumor. Due to its high metastatic properties, it has become the leading cause of cancer death worldwide. At this time, there is no effective treatment for osteosarcoma. Hence, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation in MG-63 and U2OS osteosarcoma cell lines through the EGFR-Erk1/2 signaling pathways. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin. These findings suggest that ononin could be a potentially effective agent against the metastasis of osteosarcoma. Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The in vitro anti-tumorigenic and anti-migratory properties of ononin were determined by MTT, colony formation, invasion, and migration in MG-63 and U2OS osteosarcoma cell lines. The results were compared with the standard chemotherapeutic drug, doxorubicin (DOX), as a positive control. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation through the EGFR-Erk1/2 signaling pathways. Additionally, ononin significantly inhibited the invasion and migration of human osteosarcoma cells. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin by inhibiting the protein expressions of EGFR-Erk1/2 and MMP2/9. According to the histological study, ononin had no adverse effect on the liver and kidney. Overall, our findings suggested that ononin could be a potentially effective agent against the development and metastasis of osteosarcoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ultra Violet (UV) radiation is the major reason for reactive oxygen species (ROS) forming, skin cell damage, melanin production, and could horribly cause skin cancer. Saussureae Involucratae Herba (SIH) is the aerial part of Saussurea involucrata Matsum. & Koidz. This Material Medica is popular with both in Uyghur and Chinese medicines filed. SIH is one of the famous species of the Asteraceae family and which prescribed for skin protection from UV-induced damage according to China Pharmacopeia (2020). However, the detailed working mechanism involved is still not elucidated. We would like to probe the potential transduction pathway of SIH against UV-induced skin cell damages in cultured B16F10 cells. Western blot, luciferase assay, laser confocal, RT-PCR and flow cytometer were employed here to verify the protective pharmaceutical value of SIH in cultured B16F10 cells after UV pre-treatment. Our result revealed that SIH attenuates ROS formation after UV-induced damage in B16F10 cells in a dose-dependent manner. Moreover, the transcriptional and translational anti-oxidative encoding genes were up-regulated under the presence of SIH. Further studies showed that SIH activated transcriptional activity of anti-oxidant response element (ARE). Moreover, we found that SIH dramatically stimulates PI3K/Akt phosphorylation in cultured B16F10 cells, this result was further verified by its specific inhibitors, LY294002 and Tocris. Our findings concluded that SIH protect melanoma cells from UV damages via activating PI3K/Akt signaling and which could provide scientific evidence for anti-UV pharmaceutical values of this herbal extract. Image 1 [ABSTRACT FROM AUTHOR]

Danggui Buxue Tang (DBT) has been used for over 800 years to enhance Qi and nourish Blood, and it is particularly beneficial for cancer patients. Recent research has shown that combining DBT with chemotherapy agents leads to superior anti-cancer effects, thereby enhancing therapeutic efficacy. The aim of this study was to evaluate the effectiveness of a combination therapy involving doxorubicin (DOX) and Danggui Buxue Tang (DBT) in the treatment of triple-negative breast cancer (TNBC) and to elucidate the underlying mechanisms of action. In vitro experiments were performed using MDA-MB-231 and 4T1 cells, while in vivo experiments were carried out using MDA-MB-231 xenograft mice. The therapeutic effects of the combination therapy were evaluated using various techniques, including MTT assay, colony formation assay, flow cytometry, transwell assay, immunofluorescence, transmission electron microscopy (TEM), histological analysis, western blotting, and bioluminescence assay. DBT was found to enhance DOX's anti-TNBC activity in vitro by promoting ferroptosis, as evidenced by the observed mitochondrial morphological changes using TEM. The combination therapy was also found to reduce the expression of Nrf2, HO-1, and GPX4, which are all targets for ferroptosis induction, while simultaneously increasing ROS production. Additionally, the combination therapy reduced nuclear accumulation and constitutive activation of Nrf2, which is a significant cause of chemotherapy resistance and promotes cancer growth. In vivo experiments using an MDA-MB-231 xenograft animal model revealed that the combination therapy significantly reduced tumor cell proliferation and accelerated TNBC deaths by modulating the Nrf2/HO-1/GPX4 axis, with no evidence of tissue abnormalities. Moreover, the combination therapy exhibited a liver protective effect, and administration of Fer-1 was able to reduce the ROS formation produced by the DBT + DOX combination therapy. This study provides evidence that the combination therapy of DOX and DBT has the potential to treat TNBC by promoting ferroptosis through the Nrf2/HO-1/GPX4 axis. [Display omitted] [ABSTRACT FROM AUTHOR]

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. The possible functions of astragaloside IV in heme iron recycling during erythrophagocytosis in cultured macrophage were elucidated. The translational and transcriptional expressions of heme recycling enzymes were determined after incubating of astragaloside IV for 24 h in cultured macrophage. 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. Astragaloside IV shed lights in enhancing the expression of heme recycle proteins via Nrf2/ARE signaling pathway. Image 1 [ABSTRACT FROM AUTHOR]

S aussureae I nvolucratae H erba (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. 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. The application of SIH methanolic extract suppressed the expression of cytokines, a hallmark of chronic inflammation, in lipopolysaccharide (LPS)-stimulated cultures. 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. 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. Image 1 • S aussureae I nvolucratae H erba (SIH) is also named as "Snow lotus" and being used in traditional Uyghur and/or Chinese medicine. • According to China Pharmacopoeia, the major pharmaceutical values of "Snow lotus" is for inflammation-associated disorder treatments, however, the pharmacological effects and its underlying cell signaling pathways were still behind veil. • Here, we would like to employ macrophage to illustrate the working mechanisms of this herbal medicine for modulating immune systems. [ABSTRACT FROM AUTHOR]

Ononin is a flavonoid compound found in several medicinal plants, including Astragalus membranaceus, Sophora flavescens , and Ononis spinosa. These plants have been traditionally used in various parts of the world for their medicinal properties, including anti-inflammatory, antioxidant, and antitumor effects. Major depression is a common, long-lasting, and recurrent psychiatric disorder with a high suicide rate. Naturally occurring flavonoids treat depression via poorly understood mechanisms. The present study aimed to determine whether ononin conferred an antidepressant-like effect in PC12 cell models and chronic mild stress (CMS)-induced depressive rat models and to explore its possible mechanisms. Depression-related behaviors were measured using sucrose preference, tail suspension and open-field tests. Furthermore, to explore these mechanisms, we employed in vitro and in vivo assay methods, including neurite outgrowth, western blotting, quantitative RT-PCR, and staining methods. Treatment with ononin or BDNF significantly increased PC12 cells' neuronal growth and differentiation. Furthermore, ononin promotes the activation of TrkB and growth factors and upregulates the PI3K/Akt and BDNF/TrkB/CREB signaling pathways. The in vitro results were consistent with CMS-induced depressive rat models, in which ononin treatment significantly decreased depression-like behaviors and activated TrkB, growth factors, and BDNF/TrkB/CREB signaling pathways in the frontal cortex and hippocampus. Depression-induced microscopic alterations in the frontal cortex and hippocampus of rats with CMS-induced depression were also mitigated following ononin treatment. Based on these findings, we suggest that ononin is a promising antidepressant candidate for treating depression. • Ononin could significantly increase PC12 cells' neuronal growth and differentiation. • Ononin promotes the activation of TrkB and growth factors by modulating BDNF/TrkB/CREB signaling pathways. • The in vitro results were consistent with CMS-induced depressive rat models. [ABSTRACT FROM AUTHOR]