Purified anthocyanins from Zea mays L. cob ameliorates chronic liver injury in mice via modulating of oxidative stress and apoptosis.

BACKGROUND: Purple corn (Zea mays L.) is one of the main economic crops in China and has been used in the treatment of cystitis, urinary infections and obesity. However, purple corncobs, the by-product remaining after processing and having an intense purple-black color, are normally disposed of as waste or used as animal feed. Therefore, to further expand the medicinal value of purple corncob, its content was analyzed and, after purification, the effect and mechanism of purified purple corncob anthocyanins (PPCCA) on CCl4 -induced chronic liver injury in mice were investigated. RESULTS: It was observed that the total anthocyanin content (TAC) from PPCCA (317.51 ± 9.30 mg cyanidin 3-O-glucoside (C-3-G) g-1 dry weight) was significantly higher than that from the purified purple corn seed anthocyanin (266.73 ± 3.67 mg C-3-G g-1 dry weight), of which C-3-G accounted for 90.6% and 90.4% of the TAC, respectively. Furthermore, compared with the CCl4 group, PPCCA treatment significantly reduced liver index, serum total bilirubin, alanine transaminase, aspartate transaminase and liver malondialdehyde levels, but increased liver superoxide dismutase activity. The pathological changes were also improved, such as more regular arrangement of hepatocytes, less swelling, and fewer vacuoles and apoptotic cells. Additionally, mechanistic studies showed that PPCCA downregulated the expression of Caspase-3, Bax and cytochrome P450 2E1 proteins in the liver and upregulated the expression of Bcl-2. CONCLUSION: These results demonstrated that PPCCA could ameliorate CCl4 -induced chronic liver injury by regulating oxidative stress and hepatocyte apoptosis pathways. © 2021 Society of Chemical Industry.

A Purified Anthraquinone-Glycoside Preparation From Rhubarb Ameliorates Type 2 Diabetes Mellitus by Modulating the Gut Microbiota and Reducing Inflammation.

Rheum palmatum L. is widely used in traditional Chinese medicine for the treatment of constipation. Here, the therapeutic effects and underlying mechanisms of purified anthraquinone-glycoside preparation from rhubarb (RAGP) on the type 2 diabetes mellitus (T2DM) rats were investigated. After 6 weeks of metformin and RAGP treatment, the weight returned to normal. Fasting blood glucose (FBG), glycated serum protein (GSP), insulin concentration and HOMA-IR index had significantly decreased, and glucagon-like peptide-1 (GLP-1) concentrations had increased. Histological abnormalities in the pancreas and ileum had improved. These effects were associated with enhanced intestinal integrity, thereby reducing the absorption of lipopolysaccharide (LPS) and inflammation. To investigate whether RAGP ameliorated insulin resistance via effects on the gut microbiota, we performed 16s rDNA sequencing of ileal gut contents. This showed an amelioration of gut dysbiosis, with greater abundance of probiotic Lactobacillus and short-chain fatty acid-producing bacteria, and lower abundance of the Lachnospiraceae NK4A136 group and LPS-producing Desulfovibrio. The mechanism of the hypoglycemic effect of RAGP involves regulation of the gut microbiota, activation of the GLP-1/cAMP pathway to ameliorate insulin resistance. Thus, this study provides a theoretical basis for the use of RAGP to treat T2DM, and it may be a novel approach to restore the gut microbiota.

Ameliorative Effect and Mechanism of the Purified Anthraquinone-Glycoside Preparation from Rheum Palmatum L. on Type 2 Diabetes Mellitus.

Rheum palmatum L. is a traditional Chinese medicine with various pharmacological properties, including anti-inflammatory, antibacterial, and detoxification effects. In this study, the mechanism of the hypoglycemic effect of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) in streptozotocin (STZ) and high-fat diet induced type 2 diabetes mellitus (T2DM) in rats was investigated. The rats were randomly divided into normal (NC), T2DM, metformin (Met), low, middle (Mid), and high (Hig) does of PAGR groups. After six weeks of continuous administration of PAGR, the serum indices and tissue protein expression were determined, and the pathological changes in liver, kidney, and pancreas tissues were observed. The results showed that compared with the type 2 diabetes mellitus group, the fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) levels in the serum of rats in the PAGR treatment groups were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels were noticeably increased. The expression of Fas ligand (FasL), cytochrome C (Cyt-c), and caspase-3 in pancreatic tissue was obviously decreased, and the pathological damage to the liver, kidney, and pancreas was improved. These indicate that PAGR can reduce oxidative stress in rats with diabetes mellitus by improving blood lipid metabolism and enhancing their antioxidant capacity, thereby regulating the mitochondrial apoptotic pathway to inhibitß-cell apoptosis and improve ß-cell function. Furthermore, it can regulate Fas/FasL-mediated apoptosis signaling pathway to inhibit ß-cell apoptosis, thereby lowering blood glucose levels and improving T2DM.

Antioxidant and Tyrosinase Inhibitory Activities of Seed Oils from Torreya grandis Fort. ex Lindl.

Torreya grandis Fort. ex Lindl. is a plant belonging to the Taxaceae family and Torreya grandis cv. Merrillii is the only grafted and thoroughbred species belonging to this species. In this study, we extracted five different seed oils, including T. grandis seed oil (TGSO), T. grandis "Xiangyafei" seed oil (XYSO), T. grandis "Zhimafei" seed oil (ZMSO), T. grandis "Majus"seed oil (TGMSO), and T. grandis "cunguangfei" seed oil (CGSO) using physical pressure. The resulting extracts were analyzed to determine their fatty acid composition, antioxidant activity, and inhibitory activity towards tyrosinase. The results of the antioxidant activity assays revealed that XYSO and ZMSO exhibited much greater DPPH radical scavenging activity and ferric reducing power than TGSO. Notably, all five of the seed oils showed dose-dependent inhibitory activity towards tyrosinase. XYSO and TGSO gave the highest activities of all of the seed oils tested in the current study against monophenolase and diphenolase, with IC50 values of 227.0 and 817.5µg/mL, respectively. The results of this study show that wild TGSOs exhibit strong antioxidant and tyrosinase inhibition activities. These results therefore suggest that wild TGSOs could be used as a potential source of natural antioxidant agents and tyrosinase inhibitors.

The Protective Effect of the Total Flavonoids of Abelmoschus esculentus L. Flowers on Transient Cerebral Ischemia-Reperfusion Injury Is due to Activation of the Nrf2-ARE Pathway.

Abelmoschus esculentus L. has favorable nutritional/medicinal features. We found the content of total flavonoids in flower extract to be the highest (788.56 mg/g) of all the different parts of A. esculentus; according to high-performance liquid chromatography, the quercetin-3-O-[ß-D-glu-(1 → 6)]-ß-D-glucopyranoside content was 122.13 mg/g. Protective effects of an extract of the total flavonoids of A. esculentus flowers (AFF) on transient cerebral ischemia-reperfusion injury (TCI-RI) were investigated. Compared with the model group, mice treated with AFF (300 mg/kg) for 7 days showed significantly reduced neurologic deficits, infarct area, and histologic changes in brain tissue, accompanied by increased contents of superoxide dismutase, whereas contents of nitric oxide and malondialdehyde decreased. AFF upregulated the expression of Nrf2, HO-1, and NQO1. These data suggest that AFF protects against TCI-RI by scavenging free radicals and activating the Nrf2-ARE pathway.

Protection of Anthocyanin from Myrica rubra against Cerebral Ischemia-Reperfusion Injury via Modulation of the TLR4/NF-κB and NLRP3 Pathways.

Myrica rubra (MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3-O-glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi¹ MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.

Preparation and Evaluation of Antidiabetic Agents of Berberine Organic Acid Salts for Enhancing the Bioavailability.

Berberine has many pharmacological effects, such as antidiabetic, antimicrobial, anti-inflammatory, and antioxidant, but the question remains on how its low oral bioavailability has greatly limited its clinical application. As a safer hypoglycemic agent, we must evaluate the bioavailability of berberine organic acid salts (BOAs) to ensure that the bioavailability of berberine is not negatively affected. It has been proven that the bioavailability of BOAs is higher than that of BH (berberine hydrochloride); especially BF (berberine fumarate) and BS (berberine succinate), which are improved by 1.278-fold and 1.313-fold, respectively. After 1 h of oral administration, berberine mainly acted on the stomach of mice, it also influenced the liver, kidney, lungs, and intestines after 4 h. The accumulation of BF in the lung is more evident than BH. Our analysis shows that these results are closely related to the regulation of organic acids and berberine in the intestinal tract, they also indicate the influence of intestinal flora on berberine metabolism.

Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress.

Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.

Antitumor Effects of Ethanol Extracts from Hyptis Rhomboidea in H22 Tumor-bearing Mice.

BACKGROUND: Research the antitumor effects of ethanol extracts from Hyptis rhomboidea in H22 tumor-bearing mice. At the fist-stage of the experiments, the research team took MTT method to measure the antitumor activity in vitro, then selected the most inhibitory tumor cell strain as the test object of antitumor activity in vivo, established three models of a solid tumor H22 liver cancer, ascites tumor, and immunodeficiency in male mice. From inflammatory factor, liver toxicity, in vivo antioxidant index to observe antitumor activity of ethanol extracts from H. rhomboidea. MATERIALS AND METHODS: Hundred and twenty ICR male mice were used to establish three models of a solid tumor H22 liver cancer, ascites tumor, and immunodeficiency in male mice and models group of a solid tumor H22 liver cancer randomly divided into six groupshe normal control group, the model control group, the positive group (cyclophosphamide), the sample treated group (high - 1.300 g/kg, medium - 0.750 g/kg, low - 0.373 g/kg). The animals were sacrificed 15d after oral administration and tumors were taken out for the tumor weights and antitumor rates. Blood in eyeball was collected for the determination of aspartate transaminase, alanine transaminase, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-2, and tumor necrosis factor (TNF)-α in serum. Sections of tumor issue were prepared, and morphological changes in tumor tissue cells were observed using hematoxylin and eosin staining technique. RESULTS: The results showed that ethanol extracts from H. rhomboidea have a certain inhibitory effect on the digestive tumor cells. In solid tumor model, the inhibitory rate is up to 68.84% of the high dose of treated group from H. rhomboidea, and H. rhomboidea could improve the immune organ index, decrease the concentration of TNF-α and IL-2 in serum. In ascites tumor model, H. rhomboidea could slow down weight gain in mice and prolong the survival time; in immunodeficiency model, H. rhomboidea could improve the serum TNF-α and, IL-2 levels, increase SOD activity, and reduce MDA content, so as to achieve antitumor effect. CONCLUSIONS: Ethanol extracts from H. rhomboidea have obvious antitumor activity in vivo and can improve a tumor-burdened mice inflammation factors, improve the survival quality of H22 tumor mice, and enhance immunity and antitumor activity. SUMMARY: Ethanol extracts from Hyptis rhomboidea have obvious antitumor activity without obviously liver damageThe experiment results prompt that the antitumor activity probably caused by decreasing the inflammatory factors, improve the survival quality, enhance the abnormal cytokines and scavenging free radicals, and raising autoimmune function in H22 tumor bearing mice. Abbreviations used: H. rhomboidea: Hyptis rhomboidea; AST: Aspartate transaminase; ALT: Alanine transaminase; MDA: Malondialdehyde; SOD: Superoxide dismutase; IL-2: Interleukin 2; TNF-α: Tumor Necrosis Factor-α; CTX: Cyclophosphamide.

[R-value comprehensive evaluation of effect of three methods for lung-kidney comprehensive evaluation study on R value of three methods for regulating and invigorating lung and kidney in regulating lung inflammation signaling pathways in COPD rats].

Previous studies showed that three methods for regulating and invigorating lung and kidney (lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, and Qi supplementing and kidney nourishing) could regulate inflammatory signaling pathways of chronic obstructive pulmonary disease (COPD) in rats, so as to alleviate inflammation. In the present study, R-value comprehensive evaluation method was used to evaluate the comprehensive effect of three methods for regulating and invigorating lung and kidney on inflammatory signaling pathways. Rats were randomly divided into control, model, lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline groups. The COPD rat models were established by cigarette smoking combined with bacterial infection, and orally administered with drugs between the 9th and 20th week. Afterwards, efforts were made to observe the long-term effects between the drug withdrawal and the 32rd week and detect indicators in two batches in the 20th week and 32th week. Specifically, (1) Linking JAK/STAT signaling pathway: JAK2 mRNA, and protein expressions of STAT-1, STAT-3, STAT-5, JAK-2; (2) NF-kappaB signaling pathway: Smad2 mRNA and protein expressions of I-kappaB, NF-kappaB, TGF-beta1; (3) PPARgamma and antioxidant signaling pathway: SOD, PGE mRNA, PPARgamma protein. According to the results, 5 indicators in JAK/STAT pathway, 4 indicators in NF-kappaB pathway, and 3 indicators in PPARgamma pathway were significantly rectified by three methods for regulating and invigorating lung and kidney in between the 20th week and 32nd week. Between the 20th and 32nd week, the recipes for rectifying JAK/STAT pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, Qi supplementing and kidney nourishing, lung invigorating and kidney tonifying, aminophylline, particularly those for lung invigorating and spleen strengthening; The recipes for rectifying NF-kappaB pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline, particularly the first three types of drugs. The recipes for rectifying PPARgamma and antioxidant signaling pathway with intensity from high to low were recipes for lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing, lung invigorating and spleen strengthening and aminophylline. Therefore, three methods for regulating and invigorating lung and kidney showed better long-term effects in regulating COPD lung inflammation signaling pathways. Specifically, recipe for lung invigorating and spleen strengthening showed a better effect in JAK/STAT and NF-kappaB pathways, while recipe for lung invigorating and kidney tonifying and Qi supplementing and kidney nourishing showed better effects in PPARgamma and antioxidant signaling pathways. In conclusion, R-value comprehensive evaluation method can evaluate the comprehensive effect of medicines and define the ranking of multiple drugs and their main targets.