Polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles: Characterization, immunological effect and mechanism.

Atractylodes macrocephala Koidz (A. macrocephala) has been used both as a traditional medicine and functional food for hundreds of years in Asia. And it has a variety of biological activities, such as enhancing the ability of immunity and modulating effect on gastrointestinal motility. In this study, a water-soluble polysaccharide with molecular weight of 2.743 × 103 Da was isolated from the root of A. macrocephala. Polysaccharide from A. macrocephala (AMP) consisted of arabinose, galactose, glucose, xylose, mannose, ribose, galactose uronic acid, glucose uronic acid, with a percentage ratio of 21.86, 12.28, 34.19, 0.43, 0.92, 0.85, 28.79, and 0.67%, respectively. Zinc plays an important role in immune system. Therefore, we supposed that AMP binding with zinc oxide (ZnO) nanoparticles (AMP-ZnONPs) might be an effective immunostimulator. AMP-ZnONPs was prepared by Borch reduction, and its structural features were characterized by Scanning Electron Microscope (SEM), Transmission electron microscope (TEM), TEM-energy dispersive spectroscopy mapping (TEM-EDS mapping), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), X-ray diffraction (XRD), particle size and zeta-potential distribution analysis. Then, its immunostimulatory activity and the underlying mechanism were evaluated using RAW264.7 cells. The results showed that AMP-ZnONPs remarkably promoted cell proliferation, enhanced phagocytosis, the release of nitric oxide (NO), cytokines (IL-6 and IL-1ß) and the expression of co-stimulatory molecules (CD80, CD86 and MHCII). Moreover, AMP-ZnONPs could promote the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), TNF receptor associated factor 6 (TRAF6), phospho-IκBα (P-IκBα) and phospho-p65 (P-p65), and TLR4 inhibitor (TAK242) inhibited the expression of these proteins induced by AMP-ZnONPs. Therefore, AMP-ZnONPs activated macrophages by TLR4/MyD88/NF-κB signaling pathway, indicating that AMP-ZnONPs could act as a potential immunostimulator in medicine and functional food.

Shikonin inhibits the proliferation of cervical cancer cells via FAK/AKT/GSK3ß signalling.

Cervical cancer is one of the most lethal malignancies of the female reproductive system. Shikonin, a naphthoquinone pigment extracted from the traditional medicinal herb, Lithospermum erythrorhizon, has been demonstrated to exert significant inhibitory effects on a variety of tumours in vitro and in vivo. In the present study, the effects of shikonin on cervical cancer and the underlying mechanisms were investigated. The effects of shikonin on the viability on HeLa and SiHa cervical cancer cells was examined using cell counting kit (CCK-8) and colony formation assays. Immunofluorescence assay was performed to detect the levels of the proliferation-related protein, Ki67. Western blot analysis was utilized to measure the phosphorylated and total expression levels of proteins, including focal adhesion kinase (FAK), AKT, and glycogen synthase kinase 3ß (GSK3ß). Cell migration was determined by using wound healing assay. Metastasis-associated 1 (MTA1), TGFß1 and VEGF mRNA expression levels were determined using reverse transcription-quantitative PCR. It was demonstrated that, shikonin inhibited cervical cancer cell proliferation and migration. The data of the present study revealed that shikonin inhibited the proliferation of HeLa and SiHa cells in a concentration- and time-dependent manner. Mechanistically, shikonin blocked the proliferation of cervical cancer cells by downregulating the phosphorylation of FAK, AKT and GSK3ß induced by EGF. In addition, shikonin significantly suppressed cell migration and reduced the expression of migration-related proteins, including MTA1, TGFß1 and VEGF. On the whole, the present study demonstrates that shikonin may exert an inhibitory effect on the cervical cancer cell proliferation and migration through the FAK/AKT/GSK3ß signaling pathway. These findings suggest that shikonin may function as a potential therapeutic drug for the treatment of cervical cancer.

The Therapeutic Effects and Mechanisms of Quercetin on Metabolic Diseases: Pharmacological Data and Clinical Evidence.

Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.

The Therapeutic Effects and Mechanisms of Salidroside on Cardiovascular and Metabolic Diseases: An Updated Review.

The increasing incidence of metabolic and cardiovascular diseases has severely affected global human health and life safety. In recent years, some effective drugs with remarkable curative effects and few side effects found in natural compounds have attracted attention. Salidroside (SAL), a phenylpropane glycoside, is the main active ingredient of the plateau plant Rhodiola. So far, many animal experiments proved that SAL has good biological activity against some metabolic and cardiovascular diseases. However, most of these reports are scattered. This review systematically summarizes the pharmacological progress of SAL in the treatment of several metabolic (e. g., diabetes and non-alcoholic fatty liver disease) and cardiovascular (e. g., atherosclerosis) diseases in a timely manner to promote the clinical application and basic research of SAL. Accumulating evidence proves that SAL has beneficial effects on these diseases. It can improve glucose tolerance, insulin sensitivity, and ß-cell and liver functions, and inhibit adipogenesis, inflammation and oxidative stress. Overall, SAL may be a valuable and potential drug candidate for the treatment of metabolic and cardiovascular diseases. However, more studies especially clinical trials are needed to further confirm its therapeutic effects and molecular mechanisms.

Berberis kansuensis extract alleviates type 2 diabetes in rats by regulating gut microbiota composition.

BACKGROUND: The stem bark of Berberis kansuensis Schneid (BK) is a commonly used Tibetan medicine for the treatment of type 2 diabetes (T2D). However, its therapeutic mechanisms remain unclear. AIM OF THE STUDY: Our aim is to clarify the role of gut microbiota in the anti-diabetic activity of BK extract. MATERIALS AND METHODS: High fat diet combined with low-dose streptozotocin (45 mg/kg) was used to establish a T2D rat model, and the body weight of rats was measured every five days. Fasting blood glucose (FBG), glycosylated serum protein (GSP), insulin resistance index (HOMA-IR), insulin sensitivity index (ISI), lipopolysaccharide (LPS), and three inflammatory factors (TNF-α, IL-1 ß and IL-6) were measured to evaluate the anti-diabetic activity of BK. Moreover, pseudo-germ-free animals were prepared by oral administration of an antibiotic mixture (100 mg/kg neomycin, 100 mg/kg ampicillin and 50 mg/kg metronidazole) twice per day for 6 days to assess the role of gut microbiota. Gut microbiota analysis was performed through 16S rRNA high-throughput sequencing method. RESULTS: After 30 days of administration, BK extract could significantly decrease the levels of body weight, FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1ß and IL-6, and increase ISI levels in T2D rats. However, when the gut microbiota of T2D rats was disturbed by antibiotics, BK could not improve HOMA-IR and ISI levels in T2D rats. The results indicated that the anti-diabetic effect of BK might depend on the gut microbiota. Moreover, sequencing of 16S rRNA genes demonstrated that BK could significantly improve the gut microbiota disorder of T2D rats. Specifically, BK increased the abundance of phyla Bacteroidetes and genera Akkermansia and the ratio of Bacteroides/Firmicutes, while reducing the abundance of phyla Proteobacteria and genera Collinella, [Ruminococcus]_gauvreauii_Group, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella, and Prevotella_9 in T2D rats. Additionally, correlation analysis revealed that Akkermansia was positively correlated with ISI, while [Ruminococcus]_gauvreauii_Group, Collinella, Escherichia Shigella, Enterococcus, Fusobacterium, Holdemanella and Prevotella_9 were positively correlated with FBG, GSP, LPS, HOMA-IR, TNF-α, IL-1ß, and IL-6. CONCLUSION: BK extract has a good anti-diabetic effect on T2D rats. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of gut microbiota.

Qing-Luo-Yin Alleviated Experimental Arthritis in Rats by Disrupting Immune Feedback Between Inflammatory T Cells and Monocytes: Key Evidences from Its Effects on Immune Cell Phenotypes.

BACKGROUND: Qing-Luo-Yin (QLY) is an anti-rheumatic herbal formula. Despite the well-investigated therapeutic efficacy of QLY, its immune regulatory properties are largely unknown. CD4+ T cells and monocytes are two key parameters in rheumatoid arthritis (RA). This study investigated the changes in these cells in QLY-treated RA animal models. MATERIALS AND METHODS: RA models were induced in male SD rats and were orally treated with QLY. Dynamic metabolic changes in collagen-induced arthritis (CIA) rats were monitored by 1H NMR approach. The immunity profiles of CIA and adjuvant-induced arthritis (AIA) rats were evaluated using immunohistochemical, PCR, ELISA, cytokine chip, flow cytometry, and immunofluorescence experiments. The bioactive components in QLY were identified by bioinformatic-guided LC-MS analyses. The compounds with high abundance in QLY decoction and easily absorbed were taken as key anti-rheumatic components and used to treat blood-derived immune cells using in vitro experiments. RESULTS: The results indicated that QLY decreased Th17 cells frequency and T cells-released IL-6, IL-17 and GM-CSF in CIA rats, which was attributed to the impaired lymphocyte maturation and altered differentiation. QLY inhibited lactic acid production and inflammatory polarization in the monocytes during the peak period of AIA and CIA. AIA monocytes elicited significant increase in Th17 cells counts, IL-6 and IL-1ß secretion in co-cultured splenocytes, which was abrogated by QLY. QLY-containing serum suppressed the phosphorylation of JNK and p65 in AIA lymphocyte-stimulated normal monocytes and consequently inhibited iNOS and IL-1ß expression as well as IL-6 and IL-1ß production. Matrine, sinomenine and sophocarpine were identified as major bioactive compounds in QLY. These identified compounds effectively inhibited the development of inflammatory T cells using concentrations detected in QLY-treated rats. At higher concentrations (20-fold increase), the chemical stimuli significantly suppressed the production of IL-1ß in AIA monocytes by inhibiting JNK and p65 pathways. CONCLUSION: By targeting inflammatory T cells and monocytes as well as disrupting their interplay, QLY improved immune environment in RA models especially during the active stages of disease.

Traditional Tibetan Medicine in Cancer Therapy by Targeting Apoptosis Pathways.

Cancer is a leading cause of death around the world. Apoptosis, one of the pathways of programmed cell death, is a promising target for cancer therapy. Traditional Tibetan medicine (TTM) has been used by Tibetan people for thousands of years, and many TTMs have been proven to be effective in the treatment of cancer. This paper summarized the medicinal plants with anticancer activity in the Tibetan traditional system of medicine by searching for Tibetan medicine monographs and drug standards and reviewing modern research literatures. Forty species were found to be effective in treating cancer. More importantly, some TTMs (e.g., Ophiocordyceps sinensis, Phyllanthus emblica L. and Rhodiola kirilowii (Regel) Maxim.) and their active ingredients (e.g., cordycepin, salidroside, and gallic acid) have been reported to possess anticancer activity by targeting some apoptosis pathways in cancer, such as Bcl-2/Bax, caspases, PI3K/Akt, JAK2/STAT3, MAPK, and AMPK. These herbs and natural compounds would be potential drug candidates for the treatment of cancer.

Highly efficient decomposition of toluene using a high-temperature plasma-catalysis reactor.

Plasma-catalysis technologies (PCTs) have the potential to control the emissions of volatile organic compounds, although their low-energy efficiency is a bottleneck for their practical applications. A plasma-catalyst reactor filled with a CeO2/γ-Al2O3 catalyst was developed to decompose toluene with a high-energy efficiency enhanced by the elevating reaction temperature. When the reaction temperature was raised from 50 °C to 250 °C, toluene conversion dramatically increased from 45.3% to 95.5% and the energy efficiency increased from 53.5 g/kWh to 113.0 g/kWh. Conversely, the toluene conversion using a thermal catalysis technology (TCT) exhibited a maximum of 16.7%. The activation energy of toluene decomposition using PCTs is 14.0 kJ/mol, which is far lower than those of toluene decomposition using TCTs, which implies that toluene decomposition using PCT differs from that using TCT. The experimental results revealed that the Ce3+/Ce4+ ratio decreased and Oads/Olatt ratio increased after the 40-h evaluation experiment, suggesting that CeO2 promoted the formation of the reactive oxygen species that is beneficial for toluene decomposition.