A versatile economic strategy by HPLC-CAD for quantification of structurally diverse markers in quality control of Shengmai Formula from raw materials to preparations.

BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

Borneol acts as an adjuvant agent to enhance the oral absorption of Panax notoginseng saponins in rats: Effect of optical configuration and compatibility ratios.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng, shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards. AIM OF THE STUDY: This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios. MATERIALS AND METHODS: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios. RESULTS: The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d-borneol (DB), l-borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine. CONCLUSIONS: This study shed new light on the compatible use of PNS and BO from the perspective of "configuration-dose-influence" of BO. The results provide important basis for the clinical application and selection of BO.

Uncovering the secrets of agarwood aroma according to regions and grades using a comprehensive analytical strategy.

Agarwood holds significant importance as a valuable resource for aromatic purposes, however, key components responsible for aroma and the differences between regions and grades remain to be deeply elucidated. Thus, the odors of agarwood sourced from typical zones, as well as the renowned Kynam agarwood, were analyzed by HS-SPME Arrow GC-MS in SCAN and MRM modes. The integrated strategy proposed herein exploits the respective advantages of non-targeted and targeted analysis. In addition to a total of 55 volatile components identified from the NIST database, 114 odor components were matched according to the Smart Aroma Database, and a series of differential compounds was also unearthed and quantified.

Rare ginsenosides: A unique perspective of ginseng research.

BACKGROUND: Rare ginsenosides (Rg3, Rh2, C-K, etc.) refer to a group of dammarane triterpenoids that exist in low natural abundance, mostly produced by deglycosylation or side chain modification via physicochemical processing or metabolic transformation in gut, and last but not least, exhibited potent biological activity comparing to the primary ginsenosides, which lead to a high concern in both the research and development of ginseng and ginsenoside-related nutraceutical and natural products. Nevertheless, a comprehensive review on these promising compounds is not available yet. AIM OF REVIEW: In this review, recent advances of Rare ginsenosides (RGs) were summarized dealing with the structurally diverse characteristics, traditional usage, drug discovery situation, clinical application, pharmacological effects and the underlying mechanisms, structure-activity relationship, toxicity, the stereochemistry properties, and production strategies. KEY SCIENTIFIC CONCEPTS OF REVIEW: A total of 144 RGs with diverse skeletons and bioactivities were isolated from Panax species. RGs acted as natural ligands on some specific receptors, such as bile acid receptors, steroid hormone receptors, and adenosine diphosphate (ADP) receptors. The RGs showed promising bioactivities including immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes, and interaction with gut microbiota. Clinical trials indicated the potential of RGs, while high quality data remains inadequate, and no obvious side effects was found. The stereochemistry properties induced by deglycosylation at C (20) were also addressed including pharmacodynamics behaviors, together with the state-of-art analytical strategies for the identification of saponin stereoisomers. Finally, the batch preparation of targeted RGs by designated strategies including heating or acid/ alkaline-assisted processes, and enzymatic biotransformation and biosynthesis were discussed. Hopefully, the present review can provide more clues for the extensive understanding and future in-depth research and development of RGs, originated from the worldwide well recognized ginseng plants.

Study on herb-herb interaction between active components of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma based on transporters using UHPLC-MS/MS.

The combined efficacy in lowering serum lipid levels and increasing kidney protection of Plantago asiatica L. seed (Plantago) and Coptis chinensis Franch. rhizoma (Coptis) is far better than the effects of either herb alone. This finding suggests that there must be some degree of herb-herb interactions (HHI) affect potency. Here, we chose geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA) as active components in Plantago, and berberine (BBR) as the active component in Coptis, and, using transporter gene-transfected Madin-Darby canine kidney (MDCK) cells in combination with specific substrates and inhibitors, investigated Plantago- Coptis HHIs. We also established a UPLC-MS/MS analytical method to determine substrate content. Results showed that PLA in Plantago was a substrate of rOCT1/2 and rMATE1, and had inhibitory effects on rOCT2 and rMATE1. We also found that ACT is a substrate of rMATE1, but GPA was not a substrate of any transporter that we investigated. When BBR was used as the substrate, the inhibition rate of 10 µM PLA was 53.6% on rOCT2 and 31.5% on rMATE1. The inhibition rates of 30 µM ACT and 30 µM GPA on rMATE1 were 47.0% and 31.0%, respectively. Thus, our findings suggest that GPA, ACT, PLA, and BBR have competitive interactions that are driven by the rOCT2 and rMATE1 transporters. These interactions affect the transport and excretion of compounds and result in efficacy changes after co-administration.

Electroacupuncture Ameliorates Depression-Like Behaviors Comorbid to Chronic Neuropathic Pain via Tet1-Mediated Restoration of Adult Neurogenesis.

Although electroacupuncture (EA) stimulation is a widely used therapy for chronic pain and comorbid psychiatric disorders, its long-term effects on chronic neuropathic pain-induced depression and the underlying mechanisms remain elusive. In the present study, we found that EA stimulation was able to restore adult neurogenesis in the ventral dentate gyrus (DG), by both increasing neuronal differentiation and restoring the normal morphology of newborn dendrites, in mice with spared nerve injury surgery. By ablating the Nestin+ neural stem cells (NSCs) via diphtheria toxin fragment A expression, we further proved that neurogenesis in the ventral DG was crucial to the long-term, but not the immediate antidepressant effect of EA, nor was it associated with nociception. Furthermore, we found that the restoration of neurogenesis was dependent on Tet1-mediated epigenetic modification upon EA treatment. Tet1 could bind to the promoter of the Prox1 gene, thus catalyzing its demethylation and facilitating its expression, which finally contributed to the restoration of neurogenesis and amelioration of depression-like behaviors induced by chronic neuropathic pain. Thus, we conclude that EA stimulation restores inhibited Tet1 expression in hippocampal NSCs of mice with chronic neuropathic pain, and increased Tet1 expression ameliorates hypermethylation of Prox1 and restores normal adult neurogenesis in the ventral DG, which contributes to the long-term antidepressant effect of EA.

The history, stereochemistry, ethnopharmacology and quality assessment of borneol.

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol (BO) represents a global trade-driven spreading of ethnic medicine traceable to the classical age, and won its name specific to its original habitat "Borneo". BO shows broad spectral pharmacological effects, such as anti-inflammatory, analgesic, antipyretic, inducing resuscitation, and widely applied in the protection and treatment of cardiovascular and cerebrovascular diseases, used singly or mostly in compound formulae. AIM OF THE STUDY: Three stereoscopic configuration forms of BO, l-borneol (LB), d-borneol (DB), and dl-borneol (synthetic, SB), are formulated in broad spectral application, yet their diverse pharmacodynamic and pharmacokinetic properties caused by configurations, and accurate assay and quality assessment are often overlooked. A systematic review and analysis of lumped studies and applications is necessary to clarify the relationship between configuration and its original plant, analysis method, activity and side effect BO in order to guarantee the efficacy and safety during their application. MATERIALS AND METHODS: The public databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure were referenced to summarize a comprehensive research and application data of BO published up to date. RESULTS: This review includes following sections: History and current status, Stereochemistry, Ethnopharmacology, and Quality assessment. In the section of history, the changes of the plant origins of the two isomeric forms of natural BO were described respectively, and the methods for synthetic racemate SB were also included. The section of stereochemistry deals with the stereoscopic structures, physical/chemical property, optical rotation of the three forms of BO, as well as the main related substances like isoborneol, obtained in SB via chemical transformation of camphor and turpentine oil. In the section of Ethnopharmacology, pharmacological activities and pharmacokinetics of different forms of BO were discussed. BO is usually used as an "adjuvant", by enhancing the permeability of the blood-brain barrier and intervene the ADME/T pathways of the other ingredients in the same formulation. In the section of quality assessment, the analytical methods, including chromatography, especially GC, and spectroscopy were addressed on the chiral separation of the coexisting enantiomers. CONCLUSIONS: This overview systematically summarized three forms of BO in terms of history, stereochemistry, ethnopharmacology, and quality assessment, which, hopefully, can provide valuable information and strategy for more reasonable application and development of the globally reputed ethnic medicine borneol with characteristics in stereochemistry.

Development of Green and Efficient Extraction of Bioactive Ginsenosides from Panax ginseng with Deep Eutectic Solvents.

The extraction of active constituents from natural sources in a green and efficient manner is considered an important field in the pharmaceutical industry. In recent years, deep eutectic solvents (DESs), a new type of green solvent, have attracted increasing attention. Therefore, we aimed to establish a green and high-efficiency extraction method for ginsenosides based on DESs. This study takes Panax ginseng as a model sample. Eighteen different DESs were produced to extract polar ginsenosides. Ultrasound-assisted extraction (UAE) was applied for simplicity and efficiency. A binary DES synthesized using choline chloride and urea at a proportion of 1:2 prepared by a heating stirring method is proven to be more effective than other solvents, such as the widely used 70% ethanol for the extraction of ginsenosides. Three variables that might affect the extraction, including the DES content in the extraction solvent, liquid/solid ratio, and ultrasound extraction time, were evaluated for optimization. The optimum extraction conditions for ginsenosides were determined as follows: DES water content of 20 wt%, liquid/solid ratio of 15 mL g-1, and an ultrasonic extraction time of 15 min. The extraction yield for the optimized method is found to be 31% higher than that for 70% ethanol, which achieves efficient extraction. This study shows that DESs are available to extract ginsenosides for use in traditional Chinese medicine. The discovery also contributes to further research into the green extraction of ginsenosides.

Rapid analysis of differential chemical compositions of Poria cocos using thin-layer chromatography spray ionization-mass spectrometry.

Poria cocos, with medicinal and edible properties, contains multiple chemical components that pose difficulties in its quality control. Herein, we established a simple thin-layer chromatography spray ionization-mass spectrometry (TLCSI-MS) device that allows the simultaneous separation and identification of bioactive compounds. The triterpene acids in different medicinal parts of Poria cocos were characterized, and the markers of differences were revealed. The quantitative analysis of its pharmaceutical preparation has also been performed to verify the feasibility. The study provides a new analytical perspective for the screening and identification of multiple compounds and a good option for the quality evaluation of herbal medicines and foods.

Mass spectrometry-based profiling and imaging strategy, a fit-for-purpose tool for unveiling the transformations of ginsenosides in Panax notoginseng during processing.

BACKGROUND: Panax notoginseng, a valuable medicinal plant, is traditionally used to treat trauma, body pain, and cardiovascular diseases in two clinical forms including raw (crude) and processed form. Processing-triggered compound transformation is responsible for the distinct bioactivity between raw and processed Panax notoginseng. Nevertheless, investigating the chemical diversity and dynamic transformation pattern of processed Panax notoginseng is challenging. METHODS: A new approach, which integrates multi-components characterization, processing trajectory depiction, discovery of differential markers, transformation mechanism of metabolites, in situ spatial distribution and transformation of metabolites, was established to elucidate the role of processing on the holistic chemical transformations of Panax notoginseng (PN). RESULTS: In this study, 136 ginsenosides (mainly rare ginsenosides) were identified or tentatively characterized and the temperature-dependent chemical variation trajectory was depicted via principal component analysis (PCA). Nineteen processing-associated markers were confirmed by orthogonal partial least squares-discriminant analysis (OPLS-DA). For the first time, the transformation pathway of ginsenosides during processing were elucidated by integrating the precursor ion scan (PIS) and mimic processing strategy that involves with deglycosylation, dehydration, hydration, acetylation, and isomerization. Results of mass spectrometry imaging (MSI) revealed the major ginsenosides M-Rb1, R1, Rg1, Rb1, Rd, and Re exhibited distinct spatial distribution pattern that are highly abundant in the xylem and showed a downward trend during processing. We firstly depicted the spatial distribution of processing-triggered rare ginsenosides (Rg3, Rk1, Rg5, etc.), and in situ transformation of ginsenosides was discovered in the process of steaming. Additionally, this variation trend was consistent with untargeted metabolomics results. CONCLUSION: This study comprehensively revealed chemical diversity and dynamic transformation pattern and depicted the spatial distribution of ginsenosides of PN during processing. It could provide a clue for the distinct bioactivities between raw and processed PN and elucidate the role of processing on the holistic chemical transformations of natural products, more importantly, the proposed strategy is valuable for the quality evaluation and control of the processing of natural product.

Quality assessment of Fritillariae cirrhosae using portable NIR spectrometer.

This paper mainly focuses on the feasibility of rapidly identifying Fritillariae cirrhosae varieties, distinguishing its authenticity and detecting its components by using a portable near infrared (NIR) spectrometer. Five different varieties of Fritillariae cirrhosae, five common counterfeits and two main components (ethanol-soluble extractives and total alkaloids) were studied. The reference values of ethanol-soluble extractives were determined by hot dip method and the reference value of total alkaloid was determined by ultraviolet-visible spectrophotometry (UV-Vis). Linear discriminant analysis (LDA) algorithm was used to identify the sources of different varieties of Fritillariae cirrhosae and the common counterfeits of Fritillariae cirrhosae, respectively. As a result, the best models seemed to be effective, with accuracy of the two models' prediction sets reaches 83.33% and 90.91%, respectively. The partial least squares regression (PLSR) algorithm was used to relate the sample spectra with the reference values of ethanol-soluble extractives and total alkaloid content. Coefficient of determination of prediction (R2p) and root mean square errors of prediction (RMSEP) obtained were 0.8562 and 0.3911; 0.6917 and 0.0117, for ethanol-soluble extractives and total alkaloid content, respectively. The results showed that the portable NIR spectrometer could evaluate the quality of Fritillariae cirrhosae with high efficiency and practicability.

[New method for green extraction of ginsenosides based on mechanochemically-assisted extraction and deep eutectic solvents].

Ginsenosides are the main active ingredients in ginseng. Studies have shown that ginsenosides have anti-virus, anti-tumor, anti-aging, nootropic, cardiovascular diseases-protecting, and other pharmacological activities. Thus, the development and utilization of ginsenosides have persistently attracted much attention. At present, the extraction of ginsenosides is mainly based on organic solvents, and there are relatively few studies on their green extraction. In this study, different deep eutectic solvents(DESs) were synthesized by heating and stirring method, combined with an emerging technology, mechanochemically-assisted extraction(MCAE), to extract ginsenosides in a green way. Six parameters that might affect the extraction effect were optimized to determine the optimal conditions, and the method validation was conducted. The new established method was compared with a commonly used extraction method(ultrasound-assisted extraction using 70% ethanol) to evaluate its extraction efficiency. The results revealed that the optimal extraction conditions of DES-MCAE were that the volume ratio of DES3(choline chloride∶urea 1∶2) and water in the extraction solvent was 6∶4, and the liquid ratio and the linear vibration speed were 0.05 g·mL~(-1) and 4.0 m·s~(-1); the extraction was performed twice, 40 s each. With only 80 s extraction, the extraction rate of this method was 36.22% higher than that of ultrasoun-dassisted extraction using 70% ethanol. In this study, a DESs-based pretreatment method for ginsenosides was established and its rapid, green and efficient extraction was realized, which provided new ideas and methods for further research on green extraction of other active ingredients from Chinese medicine.

Kappa opioid receptor controls neural stem cell differentiation via a miR-7a/Pax6 dependent pathway.

Although the roles of opioid receptors in neurogenesis have been implicated in previous studies, the mechanism by which κ-opioid receptor (OPRK1) regulates adult neurogenesis remains elusive. We now demonstrate that two agonists of OPRK1, U50,488H and dynorphin A, inhibit adult neurogenesis by hindering neuronal differentiation of mouse hippocampal neural stem cells (NSCs), both in vitro and in vivo. This effect was blocked by nor-binaltorphimine (nor-BNI), a specific antagonist of OPRK1. By examining neurogenesis-related genes, we found that OPRK1 agonists were able to downregulate the expression of Pax6, Neurog2, and NeuroD1 in mouse hippocampal NSCs, in a way that Pax6 regulates the transcription of Neurog2 and Neurod1 by directly interacting with their promoters. Moreover, this effect of OPRK1 was accomplished by inducing expression of miR-7a, a miRNA that specifically targeted Pax6 by direct interaction with its 3'-UTR sequence, and thereby decreased the levels of Pax6, Neurog2, and NeuroD1, thus resulted in hindrance of neuronal differentiation of NSCs. Thus, by modulating Pax6/Neurog2/NeuroD1 activities via upregulation of miR-7a expression, OPRK1 agonists hinder the neuronal differentiation of NSCs and hence inhibit adult neurogenesis in mouse hippocampus.

S-oxiracetam Facilitates Cognitive Restoration after Ischemic Stroke by Activating α7nAChR and the PI3K-Mediated Pathway.

S-oxiracetam (S-ORC), a nootropic drug, was used to protect against ischemic stroke by lessening the blood brain barrier dysfunction and inhibiting neuronal apoptosis. However, the potential effects of S-ORC in the recovery of cognitive functions after ischemic stroke and the underlying mechanisms remains unclear. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in rats was used as the animal model. By using Y-maze test, Morris water maze, triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTp) nick end labeling (TUNEL) assay, hematoxylin and eosin, immunohistochemical staining and western blot to evaluate the protective effect of S-ORC on cognitive recovery, we were able to confirm that S-ORC ameliorated spatial learning impairment, tissue loss, and hippocampal neuronal apoptosis and injury induced by MCAO/R in rats. These cognitive effects were achieved by restoring the normal function of synaptophysin and increasing PSD95 expression in the hippocampus. Furthermore, we found that methyllycaconitine, the antagonist of α7 nicotinic acetylcholine receptor (α7nAChR), and LY294002, the inhibitor of phosphoinositide 3-kinase (PI3K), were able to block the cognitive effects of S-ORC after MCAO/R in rats. In conclusion, α7nAChR and PI3K are key molecules that mediated the signaling pathway leading to S-ORC-induced cognitive restoration after MCAO/R.

Limonoids From the Genus Melia (Meliaceae): Phytochemistry, Synthesis, Bioactivities, Pharmacokinetics, and Toxicology.

Limonoids, as the vital bioactive chemical compounds in genus Melia plants, have attracted significant attention owing to their exclusive structural characteristics and remarkable biological activity. These compounds can be usually classified into two categories, including the ring-intact group and the ring-C-seco group. Benefiting from the development of separation and analysis technology, more than 200 limonoids have been isolated and identified from this genus. There is growing evidence that limonoids from genus Melia possess diverse pharmacological activities, especially anti-cancer effects, insecticidal activities, and anti-botulism effects. Toosendanin, one of the paramount limonoids, was considered as the pivotal bioactive marker in two medicinal herbs, including Melia toosendan Sieb. et Zucc and Melia azedarach L. In particular, limonoids are found to exhibit non-negligible toxic effects, a finding which needs further research. Besides this, the lack of clinical research data seriously hinders its further development and utilization, and necessary clinical trials should be taken into consideration. In this review, we systematically summarized the phytochemical compounds and their synthesis methods, pharmacological activities, and the structure-activity relationship, pharmacokinetics, and toxicology of genus Melia-derived limonoids. We believe that this up-to-date review could provide scientific evidence for the application of limonoids as agents beneficial to health in future clinical practice.

Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms.

Epidemiological studies showed that the metabolic syndromes (MetS) and cardiovascular diseases (CVDs) are responsible for a serious threat to human health worldwide. MetS is a syndromes characterized by fat metabolism disorder, obesity, diabetes, insulin resistance and other risk factors, which increases the risk of CVDs initiation and development. Although certain drugs play a role in lowering blood sugar and lipid, some side effects also occur. Considering the multiple pathogenesis, a great deal of natural products have been attempted to treat metabolic syndromes. Ginsenosides, as the active components isolated from Panax ginseng C.A.Mey, have been reported to have therapeutic effects on MetS and CVDs, of which pharmacological mechanisms were further studied as well. This review aims to systematically summarize current pharmacological effects of ginsenosides on MetS and CVDs, potential mechanisms and clinic trials, which will greatly contribute to the development of potential agents for related disease treatment.

Efficacy and tolerability of Guizhi-Shaoyao-Zhimu decoction in gout patients: a systematic review and Meta-analysis.

CONTEXT: Guizhi-Shaoyao-Zhimu decoction (GSZD), a famous ancient oriental Chinese prescription, has been widely used for thousands of years to treat 'arthromyodynia'. OBJECTIVE: The clinical studies of GSZD for the treatment of gout were systematically reviewed to evaluate its clinical efficacy and safety. METHODS: All randomized controlled trials (RCTs) related to GSZD and gout were collected starting from the database establishment until 29 February 2020, from the Embase, PubMed, Cochrane Library, Web of Knowledge, VIP and other databases. This systematic review and meta-analysis were performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, and all analysis of the test was completed using Stata (SE12.0) and Revman (5.3). RESULTS: A total of 535 studies were searched, and 13 studies were included in our meta-analysis (n = 1056 participants). Compared with the conventional western medicine treatments, GSZD treatment yielded a significantly increase in the number of clinically effective patients (OR = 3.67, 95%CI = 2.39-5.64, p = 0.57), an improved mean reduction in the level of uric acid (MD = -54.06; 95% CI = -69.95 to -38.17). Meanwhile, the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were also significantly decreased after the GSZD treatment with no increased relative risk of side-effects. CONCLUSIONS: Our present works suggested that GSZD could be considered as an effective alternative remedy for clinical treatment of gout. In addition, it also provides a scientific basis for GSZD to be better applied in clinic in the future.

The Application of Fermentation Technology in Traditional Chinese Medicine: A Review.

In Chinese medicine, fermentation is a highly important processing technology whereby medicinal herbs are fermented under appropriate temperature, humidity, and moisture conditions by means of the action of microorganisms to enhance their original characteristics and/or produce new effects. This expands the scope of such medicines and helps them to meet the stringent demands of clinical application. Since ancient times, Chinese medicine has been made into Yaoqu to reduce its toxicity and increase its efficiency. Modern fermentation technologies have been developed on the basis of traditional fermentation techniques and modern biological technology, and they can be divided into solid fermentation, liquid fermentation, and two-way fermentation technologies according to the fermentation form employed. This review serves as an introduction to traditional fermentation technology and its related products, modern fermentation technologies, and the application of fermentation technology in the field of Chinese medicine. Several problems and challenges facing the field are also briefly discussed.

Traditional uses, botany, phytochemistry, pharmacology, separation and analysis technologies of Euonymus alatus (Thunb.) Siebold: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus (Thunb.) Siebold (E. alatus), a well-known medicinal plant, has been widely used thousands of years in China for the treatment of various diseases such as urticaria, dysmenorrhea, wound, dysentery, blood stasis, rheumatism and arthritis. Due to the extensive application of E. alatus in the fields of ethnopharmacological usage, the pharmaceutical researches of E. alatus keeps deepening. AIM OF THE STUDY: This paper reviewed and summarized the integrated research progress of this medicinal plant. A comprehensive summary and comparison of traditional usages, botany, phytochemistry, pharmacology, toxicology, separation and analysis technologies of the E. alatus highlight recent scientific advances, which provides new insights into the research and development of this medicinal plant and would be helpful to promote the research situation of underlying pharmacological mechanisms and further utilizations of E. alatus. MATERIAL AND METHODS: Literature survey was carried out via classic books of herbal medicine, PhD. and MSc. Dissertations. Online scientific databases including Pubmed, SciFinder, Science Direct, Scopus, the Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI) and others were searched up to February 2020 to identify eligible studies. All literatures of the research subject are analyzed and summarized in this review. RESULTS: The E. alatus has been widely used in traditional practice in China, Korea and other Asian Countries. In the study of phytochemistry, more than 230 chemical constituents have been isolated and identified from E. alatus, including sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, phenylpropanoids, lignans, steroids, alkaloids and other compounds. Among them, literature reports show that flavonoids and steroids are the most important bioactive substances found in this plant. A number of researches also have shown that extracts and compounds from E. alatus exert a wide spectrum of pharmacological effects, including antidiabetic effect, anti-tumor effects, anti-inflammatory effects, hepatoprotective effects, antioxidant effects, antibacterial effects, as well as other effects. However, most of the studies without clinical research. Research into plant's toxicological effects has also been limited. In addition, this review also summarizes and compares the separation and analysis technologies of E. alatus. CONCLUSIONS: E. alatus has potential for the treatment of many diseases, especially tumors and diabetes. But many traditional uses of E. alatus have not been validated by current investigations. Additionally, modern studies haven't gone far enough into its pharmacological effects and the corresponding chemical constituents, more efforts should be made to illuminate the underlying mechanisms of E. alatus for treatment of tumors and diabetes. Moreover, the toxicological effects of this plant can be further studied. Currently, there are limited studies on its side effects and toxicological effects, which should provide further guidance for the safety of clinical use.

A Retrospective Study on Risk Factors for Urinary Tract Infection in Patients with Intracranial Cerebral Hemorrhage.

OBJECTIVE: This study aimed to explore the risk factors of urinary tract infection (UTI) in patients with intracranial cerebral hemorrhage (ICH). DESIGN: This is a retrospective study, and a total of 77 patients with ICH consecutively admitted to the First Affiliated Hospital of USTC (Anhui Provincial Hospital, Hefei, China) during the period of August 2015 to August 2017 were included. The patients were divided into an UTI group (24 cases) and a non-UTI group (53 cases); patients with UTI were diagnosed according to clinical manifestations, recent urinary routines, and urine culture results. The following information in these two groups was recorded: age, sex, course of disease, side of paralysis, location and type of cerebral hemorrhage, disturbance of consciousness or not, the Brunnstrom stage of paralysed lower limbs, number of basic diseases, whether there were complications (tracheotomy, retention catheterization, pulmonary infection, pressure sore, deep venous thrombosis, etc.), whether rehabilitation interventions were conducted, blood routine, biochemistry index, DIC complete set, urine routine, and urine culture data. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors of UTI in patients with ICH. RESULTS: Univariate analysis showed that age, side of paralysis, disturbance of consciousness, the Brunnstrom stage of lower limbs, tracheotomies, retention catheterization, pulmonary infection, leukocyte count, neutrophil proportion, sodium, uric acid, D-dimer, and fibrinogen may be related to UTI in patients with ICH (P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), P < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424). CONCLUSIONS: Increased age and high D-dimer are independent risk factors for UTI in patients with ICH, while right-sided paralysis is a protective factor for UTI in patients with ICH.