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Background: Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo. Method: Polysaccharides (GSRBPs) were extracted from Ganoderma sinense – full-fat rice bran (GS-FRB) and Ganoderma sinense – defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice. Result: All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 μg/mL), GS-FRB-9 (43.82 μg/mL), GS-DRB-7 (48.08 μg/mL), RBS (49.56 μg/mL), GS-DRB-9 (49.91 μg/mL), GS-DRB-13 (51.89 μg/mL), GS-FRB-11 (53.75 μg/mL), GS-FRB-7 (56.84 μg/mL), GS-DRB-13 (60.63 μg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1. Conclusion: GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Liver cancer is a common malignant tumor worldwide, traditional Chinese medicine is one of the treatment measures for liver cancer because of its good anti-tumor effects and fewer toxic side effects. Ginsenoside CK (CK) is an active component of ginseng. This study explored the mechanism by which CK induced ferroptosis in liver cancer cells. We found that CK inhibited the proliferation of HepG2 and SK-Hep-1 cells, induced ferroptosis of cells. Ferrostatin-1, an ferroptosis inhibitor, was used to verify the role of CK in inducing ferroptosis of liver cancer cells. Network pharmacological analysis identified the FOXO pathway as a potential mechanism of CK, and western blot showed that CK inhibited p-FOXO1. In cells treated with the FOXO1 inhibitor AS1842856, further verify the involvement of the FOXO pathway in regulating CK-induced ferroptosis in HepG2 and SK-Hep-1 cells. A HepG2 cell–transplanted tumor model was established in nude mice, and CK inhibited the growth of transplanted tumors in nude mice, p-FOXO1 was decreased in tumor tissues, and SLC7A11 and GPX4 expressions were also down-regulated after CK treatment. These findings suggested that CK induces ferroptosis in liver cancer cells by inhibiting FOXO1 phosphorylation and activating the FOXO signaling pathway, thus playing an antitumor role. [ABSTRACT FROM AUTHOR]

Background: In mouse, it was discovered that resveratrol (Res) enhanced osteoporosis (OP) by boosting osteogenesis. Besides, Res can also have an impact on MC3T3-E1 cells, which are crucial for the control of osteogenesis and thus increase osteogenesis. Although some articles have discovered that Res enhanced autophagy to promote the value-added differentiation of MC3T3, it is unclear exactly how this affects the process of osteogenesis in mouse. Therefore, we will show that Res encourages MC3T3-E1 proliferation and differentiation in mouse pre-osteoblasts and further investigate the autophagy-related mechanism for this impact. Methods: (1) MC3T3-E1 cells were separated into blank control group and various concentrations (0.01, 0.1, 1, 10, 100µmol/L) of group in order to determine the ideal Res concentration. In the Res group, Cell Counting Kit-8 (CCK-8) was used to measure the proliferation activity of pre-osteoblasts in mice in each group after resveratrol intervention. Alkaline Phosphatase (ALP) and alizarin red staining were used to gauge the degree of osteogenic differentiation, and RT-qPCR was used to measure the expression levels of Runx2 and OCN in the osteogenic differentiation ability of the cells. (2) In the experiment, four groups were set up: the control group, 3MA group, Res group, and Res + 3MA group. To examine cell mineralization, ALP and alizarin red staining were utilized. RT-qPCR and Western blot detection of cell autophagy activity levels and osteogenic differentiation capacity in each group following intervention. Results: (1) Resveratrol might increase the number of mice pre-osteoblast, with the impact being most pronounced at 10µmol/L (P < 0.05). The nodules developed substantially more often than in the blank control group, and Runx2 and OCN expressions significantly increased (P < 0.05). (2) In contrast to the Res group, after 3MA purine blocked autophagy, the Res + 3MA group's alkaline phosphatase staining and the development of mineralized nodules were reduced. Runx2, OCN, LC3II / LC3I expression decreased, p62 expression increased (P < 0.05). Conclusion: The present study partially or indirectly demonstrated that Res may, through increased autophagy, induce osteogenic differentiation of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

Background: 'Taikong blue' lavender, a space-bred cultivar of Lavandula angustifolia, is one of the main lavender essential oil production crops in Xinjiang Province, China. Several cases of local usage indicated that 'Taikong blue' lavender essential oil (TLEO) had excellent anti-inflammatory and antioxidant properties for skin problems. However, to date, substantial data on these functions are lacking. In this study, we aimed to investigate the composition and bioactivities of TLEO and the potential underlying mechanisms through LPS-induced inflammatory models of HaCaT and RAW264.7 cells. Methods: The composition of TLEO was determined by GC‒MS. To study the anti-inflammatory and antioxidative properties of TLEO, we induced HaCaT and RAW264.7 cells by LPS. TLEO (0.001%-0.1%, v/v) was used to treat inflamed cells with dexamethasone (DEX, 10 μg/mL) as the standard drug. A variety of tests were carried out, including biochemical assays, ELISA, RT‒PCR, and western blotting. Docking of components was performed to predict potential ligands. Results: The GC‒MS analysis revealed that 53 compounds (> 0.01%) represented 99.76% of the TLEO, and the majority of them were esters. TLEO not only reduced the levels of oxidative stress indicators (NO, ROS, MDA, and iNOS at the mRNA and protein levels) but also protected the SOD and CAT activities. According to the RT‒PCR, ELISA, and Western blot results, TLEO decreased inflammation by inhibiting the expression of TNF-α, IL-1β, IL-6, and key proteins (IκBα, NF-кB p65, p50, JNK, and p38 MAPK) in MAPK-NF-кB signaling. Molecular docking results showed that all of the components (> 1% in TLEO) were potent candidate ligands for further research. Conclusion: The theoretical evidence for TLEO in this study supported its use in skin care as a functional ingredient for cosmetics and pharmaceutics. [ABSTRACT FROM AUTHOR]

Background: Tanshinone I (Tan-I), an ingredient of Salvia miltiorrhiza, displays protective effects in several disease models. We aim to study the effect of Tan-I on renal fibrosis and explore its underlining mechanism. Methods: Rat renal fibroblasts (NRK-49F) were used as an in vitro model to study the effect of Tan-I. Mouse renal fibrosis model was induced by unilateral ureteral obstruction (UUO) or peritoneally injection of aristolochic acid I (AAI). Results: We found that Tan-I dose-dependently inhibited the expression of pro-fibrotic markers in rat renal fibroblasts. Masson staining and Western blotting analysis showed that Tan-I treatment attenuated renal fibrosis in UUO or AAI induced fibrotic kidneys. RNA sequencing analysis identified inhibin beta-A (INHBA), a ligand of TGF-β superfamily, as a downstream target of Tan-I in fibrotic kidneys, which were further verified by qPCR. Western blotting analysis showed that INHBA is up-regulated in UUO or AAI induced fibrotic kidneys and Tan-I reduced the expression of INHBA in fibrotic kidneys. Inhibition of INHBA by Tan-I was further confirmed in rat fibroblasts. Moreover, knockdown of INHBA reduced the expression of pro-fibrotic markers and abolished the ani-fibrotic effect of Tan-I in rat renal fibroblasts. Conclusions: We conclude that Tan-I attenuates fibrosis in fibrotic kidneys through inhibition of INHBA. [ABSTRACT FROM AUTHOR]

Background: Gastrodin (GAS), is a kind of phenolic compound extracted from the traditional Chinese herbal medicine Gastrodia elata Blume (GEB). This study was aimed at probing into the protective effect of GAS on peripheral nerve injury (PNI) and the underlying mechanism. Methods: A rat model with PNI was established, followed by intraperitoneal injection of GAS (20 mg/kg/day). Sciatic nerve function index (SFI) was used to analyze the function of sciatic nerve. The amplitude and latency of compound muscle action potential (CMAP) were examined by electrophysiology. Schwann cells (SCs) were isolated from fetal rats and treated with GAS 200 μg/mL, and H2O2-induced model of oxidative stress injury was established. EdU and Transwell assays were adopted to detect the viability and migration of SCs. Dual-luciferase reporter gene assays were applied to verify the binding site between miR-497 and brain-derived neurotrophic factor (BDNF) 3'UTR. MiR-497 expression was probed by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF, neurofilament-200 (NF-200) and myelin basic protein (MBP) expression levels were detected by Western blotting. Malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, glutathione content (GSH) and catalase (CAT) activity in SCs were also measured. Results: GAS treatment could significantly increase the SFI and amplitude of CMAP, shorten the refractory period, and ameliorate muscle atrophy of the rats with PNI. GAS treatment could markedly restrain miR-497 expression and increase the expression levels of BDNF, NF-200 and MBP in SCs. BDNF was confirmed as the target of miR-497 and BDNF overexpression could reverse the impacts of miR-497 overexpression on the proliferation, migration, and oxidative stress response of SCs. Conclusions: GAS promotes the recovery of PNI via modulating miR-497 / BDNF axis and inhibiting oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Patrinia scabra Bunge is a well-known herbal medicine for its favorable treatment on inflammatory diseases owing to its effective ingredients, in which iridoid glycoside plays an extremely significant role. This article aimed to improve the content of total iridoid glycosides in crude extract through a series optimization of extraction procedure. Moreover, considering that both pain and inflammation are two correlated responses triggered in response to injury, irritants or pathogen, the article investigated the anti-inflammatory and analgesic activities of P. scabra to screen out the active fraction. Method: P. scabra was extracted by ultrasonic-microwave synergistic extraction (UMSE) to obtain total iridoid glycosides (PSI), during which a series of conditions were investigated based on single-factor experiments. The extraction process was further optimized by a reliable statistical method of response surface methodology (RSM). The elution fractions of P. scabra extract were prepared by macroporous resin column chromatography. Through the various animal experiment including acetic acid-induced writhing test, formalin induced licking and flinching, carrageenan-induced mice paw oedema test and xylene-induced ear edema in mice, the active fractions with favorable analgesic and anti-inflammatory effect were reasonably screen out. Results: The content of PSI could reach up to 81.42 ± 0.31 mg/g under the optimum conditions as follows: ethanol concentration of 52%, material-to-liquid ratio of 1:18 g/mL, microwave power at 610 W and extraction time of 45 min. After gradient elution by the macroporous resin, the content of PSI increased significantly. Compared with other concentrations of elution liquid, the content of PSI in 30 and 50% ethanol eluate was increased to reach 497.65 and 506.90 mg/g, respectively. Owing to the pharmacology experiment, it was reasonably revealed that 30 and 50% ethanol elution fractions of P. scabra could relieve pain centrally and peripherally, exhibiting good analgesic and anti-inflammatory activities. Conclusion: Patrinia scabra possessed rich iridoids and exhibited significant analgesic and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Background: Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. Methods: After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. Results: SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. Conclusions: These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis. [ABSTRACT FROM AUTHOR]

Backgrounds: The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated. Methods: At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-β-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-β-CD inclusion compound in rats were assessed in comparison to VOC. Results: The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-β-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC. Conclusion: SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-β-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC. [ABSTRACT FROM AUTHOR]

Background: Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders. Methods: The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model. Results: Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression. Conclusion: Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment. [ABSTRACT FROM AUTHOR]

Background: Non-healing wounds have been a severe issue in the global healthcare system. Regrettably, royal jelly, a traditional remedy for various skin injuries, has not been widely applied in cutaneous wounds in clinical practice nowadays, which may be due to the confusion and the lack of knowledge about the efficacies of different types of royal jelly, the bioactive constituents, and the precise mechanisms underlying the wound repairing activity. Since the compositions and bioactivities of royal jelly are predominantly influenced by nectar plants, this study aims to explore the differences in the wound-healing properties of royal jelly produced by Apis mellifera L. during the blossom seasons of different floral sources, to provide guidelines for the future rational application of royal jelly in cutaneous wounds, and to promote the further discovery of wound repair-promoting substances. Methods: Royal jelly samples were harvested during flowering seasons of Castanea mollissima Bl. (chestnut) and Brassica napus L. (rapeseed) in South China, from which hydrophilic and lipophilic fractions were extracted. The in vivo wound-healing potential was preliminarily assessed in Wistar rats' excisional full-thickness wounds, followed by investigating the mechanisms of action through in vitro assays with human epidermal keratinocytes and LPS-stimulated inflammation in macrophages. Results: The results indicated that different royal jelly samples exhibited distinct wound-healing potential, in which Castanea mollissima Bl. royal jelly was more potent. It sped up wound closure between day 2 and day 4 to 0.25 cm2/day (p < 0.05), and could accelerate wound repair by enhancing the proliferative and migratory capabilities of keratinocytes by 50.9% (p < 0.001) and 14.9% (p < 0.001), modulating inflammation through inhibiting nitric oxide production by 46.2% (p < 0.001), and promoting cell growth through increasing the secretion of transforming growth factor-β by 44.7% (p < 0.001). In contrast, Brassica napus L. royal jelly could regulate inflammation by reducing the amount of tumour necrosis factor-α by 21.3% (p < 0.001). Conclusions: The present study improves the application of royal jelly for curing difficult-to-heal wounds, in which the hydrosoluble extract of Castanea mollissima Bl. royal jelly promises the greatest potential. It also provides clues which may lead towards the identification of substances derived from royal jelly to treat wounds. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) play vital roles in acute inflammatory and antiviral responses during influenza A virus (IAV) infection. The Xijiao Dihuang decoction combined with Yinqiao powder (XDY) is applied to remedy viral pneumonia in China and its therapeutic efficacy in pneumonic mice challenged with IAV was demonstrated; however, the underlying mechanisms remain elusive. Thus, this study aimed to explore the miRNA-mRNA profiles in the lungs of IAV-infected mice and investigate the therapeutic mechanisms of XDY involving miRNAs and associated pathways. Methods: We detected the cellular miRNA contents in the lungs of mice treated with XDY (23 g/kg/d) for A/FM/1/47 (H1N1) (FM1) infection at 4 days postinoculation (dpi) and 7 dpi. MiRNA and mRNA high-throughput sequencing analyses, and miRNA and mRNA qRT-PCR analyses were used to detect and verify the relevant miRNAs and mRNAs. Conjoint analysis, GO enrichment analysis, and KEGG database analysis were applied to identify the miRNA-mRNA regulatory relationships. Results: The quantities of differentially expressed miRNAs and mRNAs were upregulated over time. The data showed that 104 miRNAs and 3485 mRNAs were differentially expressed after challenge with FM1 on day 4, while 191 miRNAs and 6126 mRNAs were differentially expressed on day 7. The GO enrichment analysis and KEGG database data showed that the differentially expressed miRNAs and mRNAs were mainly enriched in JNK activity, MAPK phosphatase activity, and the TLR, Jak-STAT and TNF signalling pathways after treatment of FM1 infection with XDY. Generally, the expression trends of differentially expressed miRNAs and mRNAs based on the qRT-PCR results exhibited good consistency with the results of the high-throughput sequencing analysis. Conclusions: MiRNAs and mRNAs were differentially expressed during FM1 infection. The therapeutic mechanisms of XDY in FM1-infected mice, might be related to regulating antiviral immunity and ameliorating excessive inflammatory responses by modulating the expression of dysregulated miRNAs and mRNAs involved in the ERK/JNK-AP-1, and IFN-β/STAT signalling pathways. [ABSTRACT FROM AUTHOR]

Background: Ganluyin (GLY) is a famous classical prescription with a long history of use as a treatment for inflammatory conditions such as chronic pharyngitis (CP) in many parts of China. However, it has not been developed as a modern pharmaceutic and its anti-inflammatory mechanisms remain unclear. The aim of this study was to assess the anti-inflammatory efficacy of GLY and potential mechanisms in a rat model of CP. Methods: The chemical profile of GLY was analyzed by HPLC-UV. We used a mouse model of ear edema and a rat model of paw edema. Specifically, xylene was used to induce edema on the surface of one ear in mice, and carrageenan was injected subcutaneously into the right hind paws of rats to induce paw edema. The paw thickness, ear weight, and ear perfusion were measured and recorded. The CP model in rats was induced by irritating the throat with 5% ammonia and was used to evaluate the therapeutic efficacy of GLY. Levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA in serum, and protein expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa-B p65 (NF-κB p65) in the throat were detected by immunohistochemistry and Western blot to evaluate the anti-inflammatory mechanism of GLY. Hematological assays were also conducted. Results: There were four flavonoids identified in GLY: naringin, neohesperidin, baicalin, and wogonoside. The oral administration of GLY showed a significant inhibitory effect on xylene-induced ear swelling and ear blood flow in mice and significantly ameliorated rat right hind paw edema at doses of 6.2 and 12.4 g/kg. Mechanistic studies found that the anti-inflammatory activity of GLY was related to the inhibition of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE2 and that GLY reduced the expression of COX-2 and NF-κB p65 proteins in the throat, attenuated throat injury, and reduced inflammatory exudates. Hematological analysis showed that treatment with GLY prevented increases in white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH) and monocyte (MONO) levels. Conclusions: These studies indicated that GLY has beneficial anti-inflammatory effects on CP and that it acts through reducing pro-inflammatory factors such as IL-1β, IL-6, TNF-α, and PGE2, as well as decreasing WBC, NEUT, LYMPH and MONO levels and decreasing the expression of COX-2 and NF-κB p65 proteins. These findings may lay the groundwork for further studies of GLY as a suitable candidate for the treatment of inflammatory diseases such as CP. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the antioxidative activity of selenium-enriched Chrysomyia Megacephala (Fabricius) (C. megacephala) larvae powder (SCML) and its impact on the diversity and structure of intestinal microflora in a mouse model of D-galactose (D-gal)-induced oxidative damage. Methods: Sixty male ICR mice were equally randomized to a normal control (NC) group, a model group, a positive group, a low-dose SCML (L-SCML) group, a mid-dose SCML (M-SCML) group, and a high-dose SCML (H-SCML) group. Animals in NC and model groups received water, animals in the positive group received 40 mg/Kg vitamin E (VE), and those in the three SCML groups received SCML which include 300, 1000 and 3000 μg/Kg selenium (Se) respectively. An oxidative damage model induced by subcutaneous injection of D-gal for 6 weeks via the neck was established. Serum oxidative stress levels and tissue appearance were evaluated. Tissues oxidative stress levels were detected by commercially available kit. Nuclear erythroid 2-related factor (Nrf2) and gut microbiota were determined by western blot and high throughput sequencing 16S rRNA gene respectively. Results: An oxidative damage model was established successfully as represented by a significant elevation of malondialdehyde (MDA) and protein carbonylation, and inhibition of the antioxidants including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and glutathione (GSH). It was found that oxidative damage and histological alterations were attenuated, the expression of Kelch-like ECH-associated protein (Keap1) was decreased, and the expression of Nrf2 and hemeoxygenase-1 (HO-1) was increased after SCML treatment. In addition, significant changes were observed in the gut microbiota, including Proteobacteria and the ratio of Bacteroidetes to Firmicutes at the phylum level, as well as Helicobacter, Clostridium and Lactobacillus at the genus level. Conclusion: SCML exerted an antioxidative effect in vivo, probably by increasing the antioxidant activity and reducing the production of oxidation products via the Nrf2 signaling pathway. SCML could also redress the intestinal flora imbalance induced by oxidative stress. All these findings suggest that SCML could serve as a functional food and natural drug additive to protect the human body against oxidative damage. [ABSTRACT FROM AUTHOR]

Background: Monoamine oxidase (MAO) A catalyzes oxidative deamination of monoamine neurotransmitters and dietary amines and regulates brain development and functions. Recently, we showed that MAO A mediates the progression and migration of glioma and MAO A inhibitors reduce glioma cell growth. Glioblastoma (GBM) is a common and most malignant brain tumor which is difficult to treat. Temozolomide (TMZ) is the current standard chemotherapy for glioma, but tumors usually become resistant and recur. So far, no effective therapy for TMZ-resistant glioma is available. Natural plant antimicrobial solution (PAMs) is a Chinese herbal medicine which has been used for decades without toxicity and has multiple medical functions including anti- inflammatory effects. Here, we report the effects of PAMs on glioblastoma growth. Methods: The growth of TMZ -sensitive (U251S),-resistant (U251R) human glioma cells, and mouse glioma cell line GL-26 were assessed by MTS colorimetric assay, colony formation, and cell migration assays. Male C57BL/6 mice were implanted subcutaneously or intracranial with luciferase-positive mouse glioma GL-26 cells and treated with vehicle; MAO A inhibitor clorgyline (10 mg/kg); TMZ (1 mg/kg); PAMs (48 mg/kg) alone or in combination with TMZ (1 mg/kg) for 14 days. At the end of the treatment, mice were sacrificed, MAO A catalytic activity in tumors was measured, and tumor sizes were determined by imaging and weight. Results: These results show that PAMs inhibits MAO A catalytic activity in all three glioma cell lines studied U251S, U251R, and GL-26. PAMs reduced glioma growth and has greater effects in combination with low dose of TMZ than PAMS or TMZ alone in all three cell lines as shown by MTS, colony formation, and cell migration assays. Using the subcutaneous or intracranial GL-26 glioma mouse model, PAMs reduced the tumor growth and MAO A activity, similar to the MAO A inhibitor clorgyline. Combining PAMs with non-toxic dose TMZ increased survival to a greater extent than those of PAMs or TMZ alone. Conclusions: This is the first study which suggests that PAMs alone or co-administration with low doses of TMZ may be a potential adjuvant to reduce the toxicity of TMZ and to abrogate drug resistance for the effective treatment of glioma. [ABSTRACT FROM AUTHOR]