Intake of flavonoids from Astragalus membranaceus ameliorated brain impairment in diabetic mice via modulating brain-gut axis.

BACKGROUND: Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown. METHODS: Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC-MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. RESULTS: We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. CONCLUSION: Our findings demonstrated that flavonoids from Astragalus membranaceus ameliorated brain impairment, and its modulation on gut-brain axis plays a pivotal role. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.

Pivotal Role of the Interaction Between Herbal Medicines and Gut Microbiota on Disease Treatment.

With the recognition of the important role of gut microbiota in both health and disease progression, attempts to modulate its composition, as well as its co-metabolism with the organism, have attracted special attention. Abundant studies have demonstrated that dysfunction or imbalance of gut microbiota is closely related to disease progression, including endocrine diseases, neurodegenerative diseases, tumors, cardiovascular diseases, etc. Herbal medicines have been applied to prevent and treat diseases worldwide for hundreds of years. Although the underlying mechanism seems to be complex, one of the important ones is through modulating gut microbiota. In this review, co-metabolism between herbal medicines and microbiota, as well as the potential pathways are summarized from most recent published papers.

Sodium Butyrate Improves Liver Glycogen Metabolism in Type 2 Diabetes Mellitus.

Liver plays a central role in modulating blood glucose level. Our most recent findings suggested that supplementation with microbiota metabolite sodium butyrate (NaB) could ameliorate progression of type 2 diabetes mellitus (T2DM) and decrease blood HbA1c in db/db mice. To further investigate the role of butyrate in homeostasis of blood glucose and glycogen metabolism, we carried out the present study. In db/db mice, we found significant hypertrophy and steatosis in hepatic lobules accompanied by reduced glycogen storage, and expression of GPR43 was significantly decreased by 59.38 ± 3.33%; NaB administration significantly increased NaB receptor G-protein coupled receptor 43 (GPR43) level and increased glycogen storage in both mice and HepG2 cells. Glucose transporter 2 (GLUT2) and sodium-glucose cotransporter 1 (SGLT1) on cell membrane were upregulated by NaB. The activation of intracellular signaling Protein kinase B (PKB), also known as AKT, was inhibited while glycogen synthase kinase 3 (GSK3) was activated by NaB in both in vivo and in vitro studies. The present study demonstrated that microbiota metabolite NaB possessed beneficial effects on preserving blood glucose homeostasis by promoting glycogen metabolism in liver cells, and the GPR43-AKT-GSK3 signaling pathway should contribute to this effect.

Laboratory Screening of 26 Essential Oils Against Cacopsylla chinensis (Hemiptera: Psyllidae) and Field Confirmation of the Top Performer, Perilla frutescens (Lamiales: Lamiaceae).

Similar to other pear psylla species in Europe and America, Cacopsylla chinensis (Yang and Li) is one of the most important pests that causes yield loss in commercial pear orchards in China. To investigate effective essential oils as alternatives to conventional pesticides against C. chinensis, 26 essential oils derived from commonly used Chinese spices and medicinal herbs were screened for insecticidal activity. Among these, the essential oil from Perilla frutescens (L.) Britton leaves was the top performer; it exhibited strong and acute toxicity against pear psylla, with an LD50 value of 0.63 µg per adult. Then, we tested the constituents of the essential oil and its toxicity in the field. Field trials showed a 72% corrected reduction in the first-second-instar population 7 d after spraying P. frutescens leaf oil solution at a concentration of 1 mg/ml and a 47% corrected reduction at days 3 and 14. This report is the first to document the application of essential oil from P. frutescens leaves to control C. chinensis under field conditions. Our results suggest that P. frutescens oil can be considered a novel potential pesticide for C. chinensis control in pear orchards.

Total Synthesis and Structure Revision of Palmarumycin B6.

Palmarumycin B6 and its regioisomer were synthesized via 7- and 13-step routes using 2-chlorophenol and 4-chlorophenyl methyl ether as the starting materials in overall yields of 2.7% and 12%, respectively. Their structures were characterized by 1H and 13C NMR, HRESIMS, and X-ray diffraction data. The structure of palmarumycin B6 was revised as 6-chloropalmarumycin CP17. The bioassay results showed that the larvicidal activity of palmarumycin B6 with an LC50 value of 32.7 µM was significantly higher than that of its 8-chloro isomer, with an LC50 value of 227.3 µM.

Insecticidal Potential of Clove Essential Oil and Its Constituents on Cacopsylla chinensis (Hemiptera: Psyllidae) in Laboratory and Field.

Cacopsylla chinensis (Yang and Li) (Hemiptera: Psyllidae) is an important pest of pear in China. As an alternative to conventional chemical pesticides, botanicals including essential oils and their constituents could provide an eco-friendly and nonhazardous control method. In this study, the essential oil of clove buds (Syzygium aromaticum) was obtained by hydrodistillation. Five constituents, accounting for 99.89% of the oil, were identified by gas chromatography-mass spectrometry, and the major constituents were eugenol (88.61%) and eugenol acetate (8.89%), followed by ß-caryophyllene (1.89%). In a laboratory bioassay, clove essential oil, commercial eugenol (99.00%) and ß-caryophyllene (98.00%) exhibited strong contact toxicity against the summerform adults of C. chinensis with LD50 values of 0.730, 0.673, and 0.708 µg/adult, and against the nymphs with LD50 values of 1.795, 1.668, and 1.770 µg/nymph, respectively. In contrast, commercial eugenol acetate (98%) had LD50 values of 9.266 µg/adult and 9.942 µg/nymph. In a field trial, clove essential oil caused significant population reductions of 73.01% (4.80 mg/ml), 66.18% (2.40 mg/ml) and 46.56% (1.20 mg/ml), respectively. Our results demonstrated that clove essential oil and its constituents have potential as a source of natural insecticides.

Chemical composition and insecticidal activity against Sitophilus zeamais of the essential oils derived from Artemisia giraldii and Artemisia subdigitata.

The aim of this research was to determine the chemical composition and insecticidal activity of the essential oils derived from flowering aerial parts of Artemisia giraldii Pamp. and A. subdigitata Mattf. (Family: Asteraceae) against the maize weevil (Sitophilus zeamais Motsch.). Essential oils of aerial parts of A. giraldii and A. subdigitata were obtained from hydrodistillation and investigated by GC and GC-MS. A total of 48 and 33 components of the essential oils of A. giraldii and A. subdigitata were identified, respectively. The principal compounds in A. giraldii essential oil were ß-pinene (13.18%), iso-elemicin (10.08%), germacrene D (5.68%), 4-terpineol (5.43%) and (Z)-ß-ocimene (5.06%). 1,8-Cineole (12.26%) and α-curcumene (10.77%) were the two main components of the essential oil of A. subdigitata, followed by ß-pinene (7.38%), borneol (6.23%) and eugenol (5.87%). The essential oils of A. giraldii and A. subdigitata possessed fumigant toxicity against the maize weevils with LC50 values of 6.29 and 17.01 mg/L air, respectively. The two essential oils of A. giraldii and A. subdigitata also exhibited contact toxicity against S. zeamais adults with LD50 values of 40.51 and 76.34 µg/adult, respectively. The results indicated that the two essential oils show potential in terms of fumigant and contact toxicity against grain storage insects.

Chemical analysis and biological activity of the essential oils of two valerianaceous species from China: Nardostachys chinensis and Valeriana officinalis.

In order to investigate essential oils with biological activity from local wild plants, two valerianaceous species, Nardostachys chinensis and Valeriana officinalis, were screened for their antimicrobial and antioxidant activity. The essential oils were obtained from the roots and rhizomes of the two plants by hydro-distillation, and were analyzed for their chemical composition by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Calarene (25.31%), aristolone (13.35%), α-selinene (7.32%) and ß-maaliene (6.70%) were the major compounds of the 23 identified components which accounted for 92.76% of the total oil of N. chinensis. Patchoulol (16.75%), α-pinene (14.81%), and ß-humulene (8.19%) were the major compounds among the 20 identified components, which accounted for 88.11% of the total oil of V. officinalis. Both oils were rich in sesquiterpene hydrocarbons as well as their oxygenated derivatives. Essential oils were shown to have broad spectrum antibacterial activity with MIC values that ranged from 62.5 µg/mL to 400 µg/mL, and IC(50) values from 36.93 µg/mL to 374.72 µg/mL. The oils were also shown to have moderate antifungal activity to Candida albicans growth as well as inhibition of spore germination of Magnaporthe oryzae. Two essential oils were assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, ß-carotene bleaching and ferrozine-ferrous ions assays, respectively, to show moderate antioxidant activity. Results suggest that the isolated essential oils could be used for future development of antimicrobial and antioxidant agents.

Aging-related changes of microglia and astrocytes in hypothalamus after intraperitoneal injection of hypertonic saline in rats.

To examine the aging-related changes of microglia and astrocytes in hypothalamus of rats after intraperitoneal injection of hypertonic saline in rats, old- and young-aged rats were injected with hypertonic saline solution into peritoneal cavity. Lectin histochemical techniques using Ricinus communis agglutinin-1 (RCA-1) and immunocytochemical method employing antibody against glial fibrillary acidic protein (GFAP) were used to demonstrate microglia and astrocytes in the hypothalamus of the rats, and the positively-stained cells were analyzed by computer-assisted image analysis system. Our results showed that the numbers of microglia and astrocytes were significantly increased in the hypothalamus of old-aged rats. After intraperitoneal injection of hypertonic saline, the number of microglia was significantly decreased in the hypothalamus of both young- and old-aged groups. After introperitoneal injection of hypertonic saline, the number of GFAP positive cells was significantly increased in the hypothalamus of young rats, but the number of GFAP positive cells did not show significant change in the hypothalamus of old rats. It is concluded that in the hypothalamus of old-aged rats, the increase of microglia may be related with the aging or degeneration of neurons, and the increase of astrocytes may provide more nourishment required by the aged neurons. The microglia and astrocytes in the hypothalamus of the two group rats may be affected by hypertonic saline, and the response of these cells to the stimuli is characterized by some aging-related changes.

[Effect of dahuang zhechong pill on transforming growth factor-beta 1 in hepatic stellate cells in rats].

OBJECTIVE: To explore the effect of Dahuang Zhechong Pill (DHZCP) on transforming growth factor-beta 1 (TGF-beta 1) in rats hepatic stellate cells. METHODS: Liver fibrosis model rats were induced by CCl4 compound factor, and treated with DHZCP in three different dosages (ordinary, double and triple) separately. TGF-beta 1 and alpha-smooth muscle actin (alpha-SMA) synthesis expression, and grades of fibrosis were observed. RESULTS: TGF-beta 1 and alpha-SMA expression in the group treated with ordinary dose of DHZCP was insignificantly different from those in the control group (P > 0.05), but the expression attenuated significantly after treatment with double or triple dose of DHZCP in the portal area and discontinuous fibrous septum (P < 0.05, P < 0.01). CONCLUSION: DHZCP of larger dosage could inhibit the hepatic stellate cells proliferation and secretion of TGF-beta 1, and reduce the genesis of collagen, so as to weaken the auto-secretion amplifying response of the cells, which might be one of the chief mechanisms of DHZCP in antagonizing liver fibrosis.