Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years / 中国中药杂志

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage / 中国中药杂志

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

Systematic review and Meta-analysis of efficacy and safety of acupuncture therapy on hypertensive intracerebral hemorrhage / 中国中药杂志

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.

Arvensic acids A-D, novel heptasaccharide glycosidic acids as the alkaline hydrolysis products of crude resin glycosides from Convolvulus arvensis.

In this study, a resin glycoside fraction with cytotoxic activity was isolated from the alcoholic extract of C. arvensis whole plants. To describe the chemical feature of the resin glycosides, the fraction was alkaline hydrolyzed and four novel glycosidic acids, named arvensic acids A-D (1-4), were isolated. Their structures were thoroughly elucidated on the basis of spectroscopic data and chemical evidences. They all possess a same heptasacharride core, consisting of one D-fucose, two L-rhamnose and four d-glucose units. The difference among these glycosidic acids was placed on the aglycone, which is 12S-hydroxypentadecanoic acid for 1, 12S-hydroxyhexadecanoic acid for 2, 3S,12S-dihydroxypentadecanoic acid for 3, and 3S,12S- dihydroxyhexadecanoic acid for 4. These aglycones are rarely found in the structures of resin glycosides and are firstly identified in the genus Convolvulus.

Medicinal uses, pharmacology, and phytochemistry of Convolvulaceae plants with central nervous system efficacies: A systematic review.

Central nervous system (CNS) disorders play a major impact on individual lives and place a severe strain on health care resources. Convolvulaceae is a family comprising approximately 1,600-1,700 species grouped in 55-60 genera, and many species are reported to have an effect on CNS functions. A systematic review of the literature studies was carried out to summarize available evidences on Convolvulaceae plants with CNS efficacies. This review is based on various data sources such as Google Scholar, Web of Science, Scopus, PubMed, and Wanfang Data. A total of 200 related articles were included in this review. According to the research result, 54 Convolvulaceae species are suggested to display CNS efficacies historically, and 46 species have been evaluated for their CNS efficacies. In addition, 67 compounds from 16 Convolvulaceae species are recognized to possess CNS efficacies. Despite great progress made through pharmacology and phytochemistry studies on CNS active Convolvulaceae species, more exploratory research is needed to gain a better understanding of the CNS efficacies of this plant family.

(R)-panaxadiol by whole cells of filamentous fungus Absidia coerulea AS 3.3382.

The microbial transformation of 20(R)-panaxadiol (PD) by the fungus Absidia coerulea AS 3.3382 afforded three new and three known metabolites. The structures of the metabolites were characterized as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7ß- hydroxyl-20(R)-panaxadiol (2), 3-oxo-22ß-hydroxyl-20(R)-panaxadiol (3), 3-oxo- 7ß,22ß-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-7ß,24ß-dihydroxyl-20(R)-panaxadiol (5), and 3-oxo-7ß,24α-dihydroxyl-20(R)-panaxadiol (6). Among them, 2-4 were new compounds. In addition, compounds 3 and 4 exhibited significant anti-hepatic fibrosis activity.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside exerted protective effects on diabetic nephropathy in mice with hyperglycemia induced by streptozotocin.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside (TSG), an active component from the functional and medicinal herb Polygonum multiflorum Thunb, has the capacity of blocking angiotensin II (ANG II) signaling, a pathway within the renin-angiotensin system (RAS) which plays a critical role in the development of diabetic nephropathy (DN), and blockade of the RAS is currently used for the treatment of DN. Here we investigated the beneficial effect of TSG therapy on renal damage in the streptozotocin (STZ)-induced diabetes model. The STZ-treated C57BL/6J diabetic mice developed progressive albuminuria and renal tubular interstitial fibrosis within 10 weeks, accompanied by increased production of ANG II, fibronection, TGF-ß, CTGF, TNF-α, RANTES and MCP-1 and decreased expression of slit diaphragm proteins in the kidney. The treatment of the diabetic mice with a TSG ameliorated kidney mass increase prevented albuminuria, and reduced tubular interstitial fibrosis. The TSG treatment suppressed the induction of fibronection, CTGF, TGF-ß, and MCP-1 and reversed the decline of slit diaphragm proteins Neph-1, ZO-1, and FAT-1. These were accompanied by blockade of renal renin and ANG II accumulation induced by hyperglycemia. These data demonstrated that the inhibition of the RAS with TSG effectively prevented renal injury in diabetic nephropathy.

UPLC-Q-TOF/MS-based screening and identification of two major bioactive components and their metabolites in normal and CKD rat plasma, urine and feces after oral administration of Rehmannia glutinosa Libosch extract.

Rehmannia glutinosa is a widely used traditional Chinese medicine (TCM) in clinical practice to tackle chronic kidney disease for thousands of years. However, the in vivo metabolism of its two major bioactive components (catalpol and acteoside) remains unknown. In this paper, a highly sensitive, rapid and robust ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with MetaboLynx™ software combined with mass defect filtering (MDF) method was established. This validated analysis method was successfully applied to investigate the in vivo metabolic profiles of R. glutinosa extract in normal and chronic kidney disease (CKD) rats. The results showed that a total of 17 metabolites of two parent compounds in normal rats in vivo were tentatively detected and identified according to the characteristics of their protonated ions and relevant literature. While 11 of the metabolites were observed in the CKD rat samples. These metabolites suggested that catalpol was firstly deglycosylated to its aglycone and subsequently to two main metabolites (M1 and M4) by conjugation and hydrogenation respectively and acteoside was mainly metabolized by O-glucuronide conjugation and O-sulphate conjugation. In conclusion, this study showed an insight into the metabolism of R. glutinosa extract in vivo and the proposed metabolic pathways of bioactive components might play a key role in further pharmacokinetic experiments evaluations.

Characterization of pumpkin polysaccharides and protective effects on streptozotocin-damaged islet cells.

The polysaccharides from pumpkin fruit (PP) were obtained and purified by hot-water extraction, anion-exchange chromatography, and gel column chromatography. The physicochemical properties of PP were determined by gel filtration chromatography, gas chromatography, fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Results indicated that the molecular weight of PP was about 23 kDa and PP was composed of D-Arabinose, D-Mannose, D-Glucose, and D-Galactose with a molar ratio of 1 : 7.79 : 70.32 : 7.05. FTIR and NMR spectra indicated that PP was the polysaccharide containing pyranose ring. Additionally, PP protected islets cells from streptozotocin (STZ) injury in vitro via increasing the levels of super-oxide dismutase (SOD) and malondialdehyde (MDA) and reducing the production of NO. The experiment of reverse transcriptase-polymerase chain reaction further proved that PP inhibited apoptosis via modulating the expression of Bax/Bcl-2 in STZ-damaged islet cells. In conclusion, PP could be explored as a novel agent for the treatment of diabetes mellitus.

A simple method for the isolation and purification of resveratrol from Polygonum cuspidatum.

Resveratrol, a polyphenol compound with strong biological activity, has been widely used in medicine, health products and cosmetic industries. It is also the main active component of Polygonum cuspidatum, a well-known traditional Chinese medicine. We developed a simple and effective method for the preparation of resveratrol from P. cuspidatum. The whole preparative process consisted of reflux extraction, filtering, hydrolyzing, liquid-liquid extraction and eluting. Filtering is to remove non polar or less polar compounds and debris fragments from the extract. Hydrolyzing is to transform polydatin to resveratrol to improve the yield of resveratrol. Eluting is to remove impurities including strong acidic and water-soluble compounds. By acid hydrolysis of glycoside (polydatin), the yield of resveratrol increased about 4-fold. The extraction recovery in different stages was high, and the content of resveratrol in the final product was over 73.8%. Compared with other methods reported, this technology is eco-friendly, easier to perform, and also has a lower cost.

Simultaneous quantification of eight major bioactive phenolic compounds in Chinese propolis by high-performance liquid chromatography.

A simple, sensitive and specific high-performance liquid chromatography-UV (HPLC-UV) method has been developed to simultaneously quantify the eight major bioactive phenolic compounds in Chinese propolis, namely caffeic acid, isoferulic acid, 3,4-dimethoxycinnamic acid, pinobanksin 5-methyl ether, pinocembrin, benzyl caffeate, chrysin and galangin. This HPLC assay was performed on an Agilent Zorbax Extend-C18 (250 x 4.6 mm, 5 microm) column with a gradient of methanol and 0.2% aqueous acetic acid (v/v) in 50 min, at a flow rate of 1.0 mL/min, and detected at 290 nm. All calibration curves showed good linearity (r2 > 0.999) within the test ranges. The intra- and inter-day assay precision (RSD) of eight phenolic compounds were in the range of 0.07-4.92%. The recoveries were between 98.3% and 104.8%. This assay was applied to the evaluation of nineteen samples from different origins in China. The results indicated that the developed assay could be readily utilized for the quality control of propolis.

Cytotoxic constituents of chinese propolis.

A pair of new flavanol racemates (1a and 1b) and a new flavanol racemic mixture (2) were isolated from crude propolis from Henan Province, People's Republic of China. Also obtained were nine known compounds, including two flavones, four flavonols, two flavanols, and isoferulic acid. Spectroscopic analysis was employed to assign the structures of these new compounds and the absolute configurations of 1a and 1b. Cytotoxicity of the isolated compounds against the HeLa human cervical carcinoma cancer cell line was evaluated, with only compounds 1a, 1b, 2, and rhamnetin (3) being active.

Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi.

Twelve new xanthones (1-12), a pair of new natural products (13 and 14), and 18 known related compounds were isolated from the resin of Garcinia hanburyi. The structures of 1-14 were elucidated by detailed spectroscopic analyses. A cytotoxic assay of the isolated compounds revealed that, with the exception of 2, these compounds were active against the HeLa tumor cell line.

Cytotoxic diterpenoids from Euphorbia helioscopia.

Four new jatrophane-type diterpenoids (1-4), together with 16 known related compounds, were isolated from the Chinese medicinal plant Euphorbia helioscopia. The structures of 1-4 were determined on the basis of spectroscopic and chemical methods. Cytotoxicity of the isolated compounds against HeLa and MDA-MB-231 cells was evaluated, with only helioscopinolide A (5) and euphornin (3a) being active.

Structure elucidation and NMR spectral assignments of three new lignan glycosides from Akebia trifoliata.

Three new lignan glycosides (1-3) were isolated from the stems of Akebia trifoliata. Their structures were elucidated as (7R,8R,7'R,8'R)3,3',5,5'tetramethoxy-4,4'dihydroxy-7,9':7',9-diepoxylignan-4-O-beta-D-glucopyranoside (1), (7S,8S,8'R)-4,4',9-trihydroxy-3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (2), (7R,8R,8'S)-4,4',9-trihydroxy3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (3) by spectral analyses, primarily NMR, MS and CD. The NMR assignments for the compounds were carried out using 1H, 13C, DEPT, COSY, HSQC, HMBC and ROESY NMR experiments.

[Study of chemical constituents in active parts of Mentha spicata III].

OBJECTIVE: To study the chemical constituents of Mentha spicata. METHOD: The chemical constituents were isolated by silica gel column chromatography, and identified by physical and chemical characters and spectroscopic analysis. RESULT: Compounds I - V were obtained and their structures were elucidated as protocatechuic aldehyde (I), protocatechuic acid (II), chrysoeriol (III), 5, 6-dihydroxy-7, 8, 3', 4'-tetramethoxyflavone (IV), nodifloretin (V). CONCLUSION: Compound I and II were first isolated from the genus Mentha. Compound Ill, IV and V were isolated from M. spicata for the first time.