Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Chemical constituents from the roots of Ampelopsis delavayana and their antibacterial activities.

Two new aromatic glycosides, 2-methylphenyl O-ß-d-xylopyranosyl-(1→6)-O-ß-d-glucopyranoside (1) and 2-methylphenyl O-α-arabinofuranosyl-(1→6)-O-ß-glucopyranoside (2), together with eight known compounds were isolated from the roots of Ampelopsis delavayana. Their structures were elucidated on the basis of extensive spectroscopic analysis. Furthermore, the in vitro antibacterial activities of 1 and 2 were investigated using serial twofold dilution in three bacteria including Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.

Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels.

A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum.

[A new biflavone from Dysosma versipellis].

This study was conducted to investigate the chemical constituents in the root of Dysosma versipellis(Hance) M. Cheng. The constituents were isolated by silica gel, lichroprep RP-C(18) and pharmadex LH-20 column chromatography and the IR, MS, NMR, 2D-NMR spectroscopic analysis were employed for the structural elucidation. Ten compounds were isolated from the 95% ethanol extract of Dysosma versipellis, their structures were elucidated as dysoverine D (1), dysoverine F (2), dysoverine A (3), podoverine A (4), α-peltatin (5), rutin (6), kaempferol-3-O-ß-D-glucopyranoside (7), quercetin-3-O-ß-D-glucopyranoside (8), kaempferol (9) and quercetin (10). Compound 2 is a new compound, and compounds 1 and 3-6 were isolated from this plant for the first time.

[Risk assessment and countermeasures of BTEX contamination in soils of typical pesticide factory].

Soil samples around three representative pesticide factories were collected in Zhangjiakou City, Hebei Province, and analyzed to identify their pollution characteristics and health risk of BTEX by purge-and trap and gas chromatography/mass spectroscopy method. Total concentrations of BTEX in soils in Plant A, B and C ranged from 673.50 to 32 363.50 ng x g(-1), nd to 6 461.80 ng x g(-1) and 461.70 to 8 740.80 ng x g(-1), respectively. Concentrations of detected toluene (4 619.50-7 234.30 ng x g(-1)) and ethylbenzene (364.60-7 944.60 ng x g(-1)) had exceeded the Canadian guidelines for industrial land (370 ng x g(-1) and 82 ng x g(-1)), and concentration of xylene (19 799.40 ng x g(-1)) in dust in production area of Plant A was larger than the Dutch soil intervention value (17 000 ng x g(-1)). While concentrationsn of BTEX around Plant A (Region I ) and Plant B and C (Region II) ranged from nd to 645.81 ng x g(-1), and nd to 309.13 ng x g(-1), respectively, which were below the Canadian guidelines for agricultural land. The non-carcinogenic risk of BTEX in Plant A (2.90E-06 -1.32E-04), B (nd -4.30E-05) and C (1.29E-06 -5.64E-05) were all below 1, which suggested that no obvious health risk existed in each plant. The non-carcinogenic risks in Region I (nd -2.02E-06) and Region II (nd -1.10E-06) were below than 1, and also lower than those in factories. High risk areas were mainly concentrated in the downwind, moreover, soils around villages and towns were also with higher risk. In conclusion, soils and dusts in each factory had been polluted and the quality of agricultural land had been partly deteriorated. Finally, environmental management and occupational protection countermeasures were proposed based on the research results.

[Risk assessment and countermeasures of heavy metals pollution in Wanquan segment of Yanghe River].

In order to investigate heavy metals contamination status in Wanquan segment of Yanghe River, Zhangjiakou, 9 water and sediments samples were collected respectively for analyzing Cu, Ni, Cd, Zn, Cr, Pb, Hg and As, with water quality indicators determined at the same time. The potential ecological risk index (PERI) was then employed to evaluate potential ecological risk of heavy metals in sediments. Results indicated that the concentrations of Cu, Ni, Cd, Zn, Cr, Pb, Hg and As in water samples ranged from 1.28-24.13, 1.13-16.84, 0.08-0.11, 1.80-10.65, 1.40-19.12, 0.13-2.05, 0.06-0.99, 0.46-4.22 microg x L(-1), respectively, which are all below the national water quality standard for the demands of industrial use and agricultural irrigation. Principal component analysis (PCA) was conducted to reveal the relationship between water quality indicators and heavy metals pollution in water samples. Concentrations of Cu, Ni, Cd, Zn, Cr, Pb, Hg and As in sediments ranged from 5.90-110.11, 17.34-56.04, 0.07-0.31, 38.71-116.74, 40.39-85.77, 18.65-22.74, nd-0.047, 0.85-9.98 mg x kg(-1), respectively. The descending order of potential ecological risk intensity caused by different heavy metals was: Cd > Cu > Hg > Ni > As > Pb > Cr > Zn, and the average value of each heavy metal was low, while middle-grade risk level of Cd and Hg were also found in several sites. Among all monitoring sites, the descending order of PERI of all target heavy metals was: YH-07 > YH-03 > YH-09 > YH-02 > YH-06 > YH-04 > YH-05 > YH-01, and the average value reached slight grade, while middle-grade risk level was detected in YH-07. Sampling locations in YH-02-YH-03 and YH-07-YH-09 were found with relatively high ecological risk level because of agricultural and anthropogenic activities, respectively. Finally, three risk management regions were figured out and corresponding countermeasures for improving the environmental quality of the watershed were proposed based on the research results.

[Risk assessment and countermeasure of BTEX in pesticide factory].

BTEX are important environmental pollutants, harmful to human through respiratory inhalation, digestive tract and skin contact, and also have teratogenic, mutagenic and carcinogenic effects. BTEX were detected in multi-media to identify their distributions and assess their human health risk in a pesticide factory in Hebei province. Purge and trap GC-MS, adsorption/thermal desorption GC chromatography and the health risk assessment model were applied, and corresponding management measures were proposed. The results showed that BTEX existed in soil, dust, air, groundwater and wastewater. The concentration of BTEX in dust of the production area was 7.33 mg x kg(-1), in particular the concentration of toluene was 5.64 mg x kg(-1), exceeding the Canadian industrial land standard. Building three scenarios for working more than 10 years, 20 years and 30 years, the total non-carcinogens index was 4.19 x10(-3), 8.25 x 10(-3) and 1.22 x 10(-2), respectively, all lower than 1; the carcinogens index of benzene was 1.70 x 10(-7), 3.34 x 10(-7) and 4.92 x 10(-7), respectively, all lower than 10(-6). It indicated that there was no significant non-carcinogens and carcinogens hazard to workers inside the factory, but they might be exposed to more health risks if their work experience increase. Finally, recommendations for improving the environmental quality and personnel security in the factory were proposed based on the research results.

[Pollution characteristics and health risk assessment of atmospheric volatile organic compounds (VOCs) in pesticide factory].

A method for determining volatile organic compounds (VOCs) in air by summa canister collecting and gas chromatography/ mass spectroscopy detecting was adopted. Pollution condition and characteristics of VOCs were discussed in three representative pesticide factories in Zhangjiakou City, Hebei Province. Meanwhile, an internationally recognized four-step evaluation model of health risk assessment was applied to preliminarily assess the health risk caused by atmospheric VOCs in different exposure ways, inhalation and dermal exposure. Results showed that serious total VOCs pollution existed in all factories. Concentrations of n-hexane (6161.90-6910.00 microg x m(-3)), benzene (126.00-179.30 microg x m(-3)) and 1,3-butadiene (115.00-177.30 microg x m(-3)) exceeded the Chronic Inhalation Reference Concentrations recommended by USEPA, corresponding to 700, 30 and 2 microg x m(-3), respectively. Concentration of dichloromethane (724.00 microg x m(-3)) in factory B was also higher than the reference concentration (600 microg x m(-3)). Results of health risk assessment indicated that non-carcinogenic risk indexes of VOCs ranged from 1.00E-04 to 1.00E + 00 by inhalation exposure, and 1.00E-09 to 1.00E-05 by dermal exposure. Risk indexes of n-hexane and dichloromethane by inhalation exposure in all factories exceeded 1, and risk index of benzene by inhalation in factory B was also higher than 1. Carcinogenic risk indexes exposed to VOCs ranged from 1.00E-08 to 1.00E-03 by inhalation exposure and 1. oo00E -13 to 1.00E-08 by dermal exposure. Cancer risk of 1,3-butadiene by inhalation exceeded 1.0E-04, which lead to definite risk, and those of benzene by inhalation also exceeded the maximum allowable level recommended by International Commission on Radiological Protection (5.0E-05). The risks of dermal exposure presented the same trend as inhalation exposure, but the level was much lower than that of inhalation exposure. Thus, inhalation exposure of atmospheric VOCs was the dominant way of health risk in these factories.

Three new flavonoid glycosides isolated from Elsholtzia bodinieri.

Three new flavonoid glycosides, eriodictyol 7-O-(6''-feruloyl)-beta-D-glucopyranoside (1), eriodictyol 7-O-[6''-(3'''-hydroxy-4'''-methoxy cinnamoyl)]-beta-D-glucopyranoside (2), and luteolin 7-O-[6''-(3'''-hydroxy-4'''-methoxy cinnamoyl)]-beta-D-glucopyranoside (3), and eight known flavonoids were isolated from the whole plants of Elsholtzia bodinieri. The structures of the 3 new compounds were elucidated on the basis of extensive spectroscopic analysis.