Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.

Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

Ten dimeric phthalide racemates (1-10) were isolated from an aqueous extract of the Angelica sinensis root head (Guitou) by separation techniques of column chromatography over macroporous adsorbent resin, MCI resin, silica gel, and Sephadex LH-20, together with preparative thin-layer chromatography and reversed phase HPLC. The racemates were further separated into (+)-/(-)-1-(+)-/(-)-10 with chiral HPLC. Their structures including absolute configurations were elucidated by comprehensive analysis of spectroscopic data, combined with electronic circular dichroism (ECD) and NMR calculations as well as single crystal X-ray diffractions. Compounds (+)-/(-)-1-(+)-/(-)-10 are either new structure or new natural product, named (+)-/(-)-angelidipthalidic acids A-H [(+)-/(-)-1-(+)-/(-)-8] and (+)-/(-)-angelidipthalidols A and B [(+)-/(-)-9 and (+)-/(-)-10], respectively. Meanwhile, dimeric phthalide mono- and bis-lactone derivatives with 3.3′a,8.6′- and 3.6′,8.3′a-coupling patterns as well as determination of their relative configurations are discussed.

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L^-1.

Twelve compounds, including 5 new monoterpenes and 7 known derivatives, were isolated from a water decoction of Monochasma savatieri by column chromatography over macroporous adsorbent resin, MCI resin, Sephadex LH-20, and HW-40C, combined with preparative TLC, reversed phase HPLC, and flash column chromatographic techniques. Their structures were elucidated by comprehensive analysis of spectroscopic data, along with enzymatic hydrolysis as well as electronic circular dichroism (ECD) and NMR calculations, the new structures named monochaside I (1) and monochairidols A-D (2-5), respectively. The known compounds 6-12 were obtained from the Monochasma plants for the first time.

Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the Ziziphus jujuba var. spinosa seeds, by multiple column chromatographic separation methods using stationary phases of macroporous adsorption resin, MCI resin, normal phase silica gel, Sephadex LH-20, and Toyopearl HW-40C as well as preparative thin-layer chromatography and reversed-phase HPLC. Their structures were determined by spectroscopic data analysis, the new structures were trivially named jujubaceanothoside A (1), 23-epijujuboside A (2), and jujubosides J and K (3 and 4), while the known analogues were identified as jujubosides A-C (5-7) and II (8), alphitolic acid (9), and betulinic acid (10). The structure of 1 was confirmed by single crystal X-ray diffraction.

Eleven monoterpene glucosides were isolated from a water decoction of Monochasma savatieri by column chromatography over macroporous adsorbent resin, MCI resin, Sephadex LH-20, and HW-40C, combined with preparative TLC, reversed phase HPLC, and flash column chromatographic techniques. Their structures were elucidated by comprehensive analysis of spectroscopic data, along with acidic and enzymatic hydrolysis as well as electronic circular dichroism (ECD) and NMR calculations, including six new compounds (1-4, 7 and 8), named monochasides A-D, G and H, respectively. Comparing the reported data of 9-hydroxylinaloyl 3-O-β-D-glucoside (5), (6Z)-9-hydroxylinaloyl 3-O-β-D-glucoside (6), and kankanoside D₁ (9) with those obtained in this study, the absolute configurations of 6 and 9 were proved for the first time. Other two compounds were identified as 8-hydroxygeraniol 1-O-β-D-glucopyranoside (10) and 8-hydroxygeraniol 8-O-β-D-glucopyranoside (11), respectively.

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Calorimetry, Differential Scanning ; Desiccation ; Drug Compounding/methods* ; Drug Stability ; Silybin ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Technology ; X-Ray Diffraction

OBJECTIVE: To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. RESULTS: The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI ( CONCLUSIONS The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.
Cardiac Output ; Child ; Hemodynamics ; Humans ; Hypothermia ; Hypoxia-Ischemia, Brain/therapy* ; Infant ; Infant, Newborn ; Vascular Resistance

Cephalotaxus is the only genus of Cephalotaxaceae family, and its natural resources are declining due to habitat fragmentation, excessive exploitation and destruction. In many areas of China, folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison, many of which are cancer. Not only among Han people, but also among minority ethnic groups, Cephalotaxus is used to treat various diseases, e.g., cough, internal bleeding and cancer in Miao medicine, bruises, rheumatism and pain in Yao medicine, and ascariasis, hookworm disease, scrofula in She medicine, etc. Medicinal values of some Cephalotaxus species and compounds are acknowledged officially. However, there is a lack of comprehensive review summarizing the ethnomedicinal knowledge of Cephalotaxus, relevant medicinal phytometabolites and their bioactivities. The research progresses in ethnopharmacology, chemodiversity, and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here. Knowledge gaps are pinpointed and future research directions are suggested. Classic medicinal books, folk medicine books, herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus (Sanjianshan in Chinese). The relevant data about ethnobotany, phytochemistry, and pharmacology were collected as comprehensively as possible from online databases including Scopus, NCBI PubMed, Bing Scholar, and China National Knowledge Infrastructure (CNKI). "Cephalotaxus", and the respective species name were used as keywords in database search. The obtained articles of the past six decades were collated and analyzed. Four Cephalotaxus species are listed in the official medicinal book in China. They are used as ethnomedicines by many ethnic groups such as Miao, Yao, Dong, She and Han. Inspirations are obtained from traditional applications, and Cephalotaxus phytometabolites are developed into anticancer reagents. Cephalotaxine-type alkaloids, homoerythrina-type alkaloids and homoharringtonine (HHT) are abundant in Cephalotaxus, e.g., C. lanceolata, C. fortunei var. alpina, C. griffithii, and C. hainanensis, etc. New methods of alkaloid analysis and purification are continuously developed and applied. Diterpenoids, sesquiterpenoids, flavonoids, lignans, phenolics, and other components are also identified and isolated in various Cephalotaxus species. Alkaloids such as HHT, terpenoids and other compounds have anticancer activities against multiple types of human cancer. Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities, immunomodulatory activity, antimicrobial activity and nematotoxicity, antihyperglycemic effect, and bone effect, etc. Drug metabolism and pharmacokinetic studies of Cephalotaxus are increasing. We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms, so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs. Transcriptomics, genomics, metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants. We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.