Hyperuricemic Nephropathy in Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Hyperuricemic nephropathy （HN）， a secondary renal damage common in clinical practice， is characterized by early concealing and continuous progression. The understanding of HN in traditional Chinese medicine （TCM） is from a macroscopic perspective. According to the TCM theory， HN is caused by the combination of external pathogens and internal injuries， with the main pathogenesis being root deficiency combined with superficial excess and deficiency-excess in complexity. In western medicine， the understanding of HN is from the microscopic perspective， which holds that the occurrence of HN is the result of inflammation， oxidative stress， renin-angiotensin-aldosterone system （RAAS） activation， and metabolic abnormalities. The TCM syndromes of HN include internal dampness and heat， obstruction in dampness and turbidity， deficiency of spleen and kidney， and deficiency of kidney yin. Accordingly， the prescriptions should clear heat and dampness， remove dampness and turbidity， tonify spleen and kidney， and nourish kidney yin， respectively. In addition to TCM prescriptions， single herbal medicines and their extracts， Chinese patent medicines， and external applications of Chinese medicines have played a significant role in the treatment of HN， promoting the application of TCM in the treatment of HN. Moreover， the integrated traditional Chinese and western medicine has also played a role in the treatment of HN， enriching the treatment schemes of HN. Different from common kidney diseases such as acute and chronic glomerulonephritis and nephrotic syndrome， HN with particularity should be carefully differentiated in clinical practice. This article systematically summarizes the research progress in the treatment of traditional Chinese medicine and integrated traditional Chinese and western medicine on hyperuricemic nephropathy with TCM and integrated traditional Chinese and western medicine， aiming to enrich the system and theory of HN treatment and further guide the clinical practice.

Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS / 中国中药杂志

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels / 中国中药杂志

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics / 中国中药杂志

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Comparison of alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata based on UHPLC-Q-Exactive Orbitrap MS/MS / 中国中药杂志

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.

Fitting Degrees of Cathartic Colon Animal Models with Disease Characteristics of Western Medicine and Syndrome Characteristics of Traditional Chinese Medicine / 中国实验方剂学杂志

Cathartic colon （CC） is a common and refractory digestive system disease， with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore， establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine （TCM） is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals， drugs and their dosage forms， doses， administration methods， and modeling period of CC varied in different studies， and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing， which， however， may cause water electrolyte disorders， decreased immunity， and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose， while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools， and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles， approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition， the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes： liver depression and spleen deficiency， both Qi and Yin deficiency， Qi stagnation and blood stasis， and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM， so as to facilitate the research on CC mechanism and drug development.

Effect of Ramie on the Production Performance of Laying Hens, and the Quality, Nutrient Composition, Antioxidation of the Eggs.

Ramie (Boehmeria nivea), which is rich in protein, fatty acid, vitamins and minerals, has become a potential alternative feed resource for poultry, and has attracted more and more attentions in nutrition research. The objective of this study is to evaluate the effect of dietary ramie at different concentrations on the production performance of the hens, and the quality, nutrient composition, and antioxidation of the eggs. A total of 432 34-week-old Lohmann commercial laying hens were divided into four groups, that were fed with corn-soybean meal-based control diet, control mixed with ramie at concentrations of 3, 6, or 9% separately for 8 weeks. Results showed that dietary ramie did not affect production performance. And egg yolk color gradually deepened as the inclusion levels of ramie increased. Ramie at tested concentration could significantly reduce the content of malondialdehyde (MDA) (p = 0.002) and 3% ramie supplementation significantly increased total antioxidative capacity (T-AOC) concentrations in egg yolk compared to the control group (p = 0.033). In addition, dietary supplementation with 6% ramie significantly reduced total cholesterol (T-CHO) content (p < 0.05) compared with controls. For egg nutrient composition, compared with the control group, the addition of 6% ramie significantly increased (p < 0.05) total omega-3 polyunsaturated fatty acids (n-3PUFA) and phenylalanine (Phe) in yolk. In conclusion, dietary inclusion of 6% ramie was most effective in improving the color, antioxidative capability, and reducing T-CHO contents of the egg yolks without any negative impacts on the production performance of the hens.

Dietary omega-3 LCPUFA intake in the prevention of neovascular age-related macular degeneration: a systematic review and meta-analysis.

Introduction: Purpose: to evaluate the protective effect of omega-3 long-chain unsaturated fatty acids on the progression of wet age-related macular degeneration (wAMD). Methods: this meta-analysis was designed, implemented, and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol and is reported following PRISMA guidelines. Results: in this study we included 5 observational trials, including 2 cross-sectional studies, 2 case-control studies, and 1 confrontation study. These tests are conducted in the U.S., Europe and Japan, and are of high quality. In general, people with high dietary long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) have a lower risk of progression to advanced age-related macular degeneration (AMD) (effect size, ES: 0.51, 95 % CI [0.34, 0.75], I2 = 70 %, p = 0.01). When assessing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake and wAMD risk a total of the three above studies were included, which also produced similar results. Conclusions: the highest DHA consumption reduced the risk of disease by 39 % (effect size: 0.61, 95 % CI [0.50, 0.74], I2 = 14 %, p = 0.31); compared with the lowest EPA consumption, the highest EPA consumption reduced the risk of wAMD by 32 % (ES: 0.68, 95 % CI [0.57, 0.82], I2 = 39 %, p = 0.20).

Introducción: Propósito: evaluar el efecto protector de los AGPICL omega-3 sobre la degeneración macular húmeda asociada a la edad (DMAE). Métodos: este metaanálisis fue diseñado, implementado y analizado de acuerdo con el protocolo de Metaanálisis de Estudios Observacionales en Epidemiología (MOOSE) y se informa siguiendo las directrices de PRISMA. Resultados: en este estudio se incluyeron 5 ensayos observacionales, entre ellos 2 estudios transversales, 2 estudios de casos y controles y 1 estudio de confrontación. Estos ensayos se realizan en Estados Unidos, Europa y Japón y son de alta calidad. En general, las personas con una dieta alta en ácidos grasos poliinsaturados de cadena larga (AGPICL omega-3) tienen un menor riesgo de progresión hacia la degeneración macular avanzada relacionada con la edad (DMAE) (tamaño del efecto, ES: 0,51, IC 95 % [0,34, 0,75], I2 = 70 %, p = 0,01). Al evaluar la ingesta de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) y el riesgo de DMAE se incluyeron en total tres de los estudios anteriores, que también arrojaron resultados similares. Conclusiones: el mayor consumo de DHA redujo el riesgo de enfermedad en un 39 % (tamaño del efecto: 0,61, IC del 95 % [0,50, 0,74], I2 = 14 %, p = 0,31); en comparación con el menor consumo de EPA, el mayor consumo de EPA redujo el riesgo de wAMD en un 32 % (ES: 0,68, IC del 95 % [0,57, 0,82], I2 = 39 %, p = 0,20).

Antinociceptive and Anti-inflammatory Effect of Corynoline in Different Nociceptive and Inflammatory Experimental Models.

Pain is growing to be a massive health issue across the globe. It is reported that one in every five adults tends to suffer from pain worldwide each year, regardless of age and gender. Inflammation caused by tissue damage, chemical stimulus, and foreign substances is commonly associated with pain. Inflammatory pain is mainly caused by the direct effect of inflammatory mediators on particular classes of nociceptive neurons. In the current investigation, the antinociceptive and anti-inflammatory effect of corynoline, a phytochemical compound isolated from Corydalis bungeana Turcz., has been evaluated in experimental mice. The experimental mice were divided into 5 groups of 6 animals each. The first control group was fed with water. The second, third, and fourth groups received different doses of corynoline and the fifth group of mice received positive controls. Nociception was induced with the help of acetic acid, formalin, glutamate, capsaicin, hot plate, and tail immersion in mice whereas carrageenan was used to induce inflammation. The peritoneal cavity leukocyte infiltration and pro-inflammatory mediator generation were also analyzed to confirm the anti-inflammatory effect and the natural locomotor activity was determined using an open field test. Corynoline treatment significantly suppressed the paw licking, writhing in the abdominal region, and displayed high nociceptive inhibitory reaction in a dose-related manner. Additionally, corynoline significantly reduced the carrageenan-triggered paw edema and also reduced the levels of pro-inflammatory cytokines. Thus, the antinociceptive and anti-inflammatory activity of corynoline has been successfully established.

Equivalent current dipole sources of neurofeedback training-induced alpha activity through temporal/spectral analytic techniques.

Much of the work in alpha NFT has focused on evaluating changes in alpha amplitude. However, the generation mechanism of training-induced alpha activity has not yet been clarified. The present study aimed to identify sources of training-induced alpha activity through four temporal/spectral analytic techniques, i.e., the max peak average (MPA), positive average (PA), negative average (NA) and event-related spectral perturbation average (ERSPA) methods. Thirty-five healthy participants were recruited into an alpha group receiving feedback of 8-12-Hz amplitudes, and twenty-eight healthy participants were recruited into a control group receiving feedback of random 4-Hz amplitudes from the range of 7 to 20 Hz. Twelve sessions were performed within 4 weeks (3 sessions per week). The control group had no change in the amplitude spectrum. In contrast, twenty-nine participants in the alpha group showed significant alpha amplitude increases exclusively and were identified as "responders". A whole-head EEG was recorded for the "responders" after NFT. The epochs of training-induced alpha activity from whole-head EEG were averaged by four different methods for equivalent current dipole source analysis. High agreement and Cohen's kappa coefficients on dipole source localization between each method were observed, showing that the dipole clusters of training-induced alpha activity were consistently located in the precuneus, posterior cingulate cortex (PCC) and middle temporal gyrus. The residual variance (goodness of fit) for dipole estimation of the MPA was significantly smaller than that of the others. Our findings indicate that the precuneus, PCC and middle temporal gyrus play important roles in enhancing training-induced alpha activity. The four averaging methods (especially the MPA method) were suitable for investigating sources of brainwaves. Additionally, three dipoles can be used for dipole source analysis of training-induced alpha activity in future research, especially the training sites are around the central regions.

Effect of Sinisan on NLRP3 Inflammasomes and Depression-like Behaviors in Depressed Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Sinisan on behaviors and NOD-like receptor protein 3 （NLRP3） inflammasomes of depressed rats induced by chronic unpredictable mild stress （CUMS） and further explore the anti-depressant mechanism of Sinisan. MethodFifty male rats were randomly divided into a normal group， a model group， an NLRP3 inhibitor （MCC950） group （10 mg·kg-1）， and low- （2.5 g·kg-1） and high-dose （5 g·kg-1） Sinisan groups， with 10 rats in each group. The depression model was induced by 42 d CUMS in rats except for those in the normal group. Drug intervention was performed on the 22nd day of modeling by gavage in the Sinisan groups and by intraperitoneal injection in the MCC950 group. Except for the MCC950 group， the remaining four groups received 10 mg·kg-1 physiological saline by intraperitoneal injection， while the rats in the model group， the normal group， and the MCC950 group were administered with 3 mL of physiological saline by gavage. Twenty-one days later， the sucrose preference test and open field test were performed. Western blot was used to detect the protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， ionized calcium-binding adapter molecule 1 （Iba1）， and CD68 in the hippocampus of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the hippocampus of rats. Nissl staining and TUNEL were used to assess the pathological changes and apoptosis level in the hippocampal CA1 region of rats， respectively. ResultThe sucrose preference rate and consumption volume in the sucrose preference test， the total distance， the percentage of central movement distance， and the percentage of residence time in the open field test of rats in the model group were lower than those in the normal group （P<0.01）. Compared with the model group， the Sinisan groups and the MCC950 group showed improved depression-like behaviors， apoptosis level in the hippocampal CA1 region， and neuron loss to varying degrees. Sinisan could reduce the levels of IL-1β， IL-18， Bax， Iba1， and CD68 in the hippocampus （P<0.05， P<0.01）， increase the level of Bcl-2 （P<0.05， P<0.01）， and inhibit the protein expression of NLRP3， ASC， and Caspase-1 related to NLRP3 inflammasomes （P<0.05， P<0.01）. ConclusionSinisan can improve the depression-like behaviors and pathological damage of hippocampal neurons in CUMS-induced rats， and the mechanism may be related to the inflammatory response mediated by the NLRP3 inflammasome signaling pathway.

Herbal Textual Research on Myrrha in Famous Classical Formulas / 中国实验方剂学杂志

In order to provide the basis for the development of famous classical formulas containing Myrrha， the name， origin， quality evaluation， harvest and processing of Myrrha were systematically researched by consulting the ancient herbal and medical books， combining with the modern related literature. According to textual research， the results showed that Commiphora myrrha was the main base in ancient times， which was produced in Somalia， Ethiopia and northern Kenya. In addition， raw and fried products of Myrrha were the commonly used specifications in ancient herbal medicine， which are still used today. Nowadays， Myrrha， fried Myrrha and vinegar-processed Myrrha were the commonly used specifications. Among the three specifications， Myrrha is the raw products after cleaning， fried Myrrha is a kind of processed products， which has relevant records in ancient materia medica and is still used today. Vinegar-processed Myrrha is a new processing specification in modern times. Based on the research results， it is suggested that Myrrha in Shentong Zhuyutang should be the purified raw Myrrha in accordance with the 2020 edition of Chinese Pharmacopoeia.

Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing" / 中国中药杂志

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model / 中西医结合学报

OBJECTIVE@#In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish.@*METHODS@#The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 μmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio.@*RESULTS@#According to the Chinese Pharmacopoeia (2015), β-ecdysone (β-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of β-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 μmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 μmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and β-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1.@*CONCLUSION@#RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Columbamine-Mediated PTEN/AKT Signal Pathway Regulates the Progression of Glioma.

PURPOSE: At present, comprehensive therapy has been widely used in the treatment of glioma, but the curative effect is not good, and the survival rate of patients is low. Therefore, it is crucial to explore further the regulatory mechanism of the occurrence and development of glioma and find potential therapeutic targets. We aimed to investigate the columbamine (a tetrahydroisoquinoline alkaloid derived from the rhizome of Chinese herbal medicine Rhizoma Coptidis) on glioma progression. METHODS: MTT, clone formation assay, wound healing assay, and transwell assay were performed to detect the cell viability, proliferation, migration, and invasion ability. Flow cytometry, TUNEL, and Western blot were used to identify the apoptosis level in glioma cells. PTEN inhibitor (SF1670) and AKT activator (SC79) were used to explore the mechanism of columbamine on glioma cell progression. RESULTS: Columbamine inhibits proliferation, migration, invasion, and induces apoptosis in glioma cell lines (SHG44 and U251). Columbamine prevents phosphorylation of AKT and promotes the expression of PTEN. Blocking PTEN level or inducing phosphorylation of AKT attenuates columbamine function on SHG44 cells proliferation, metastasis, and apoptosis. CONCLUSION: In this research, we find that columbamine could inhibit proliferation and metastasis of glioma cell lines, and promote apoptosis of glioma cell lines via regulating PTEN/AKT signal pathway. It provides a new theoretical basis for the development of anti-glioma drugs.

Network Pharmacology-based Analysis on Mechanism of Aconiti Lateralis Radix Praeparata and Epimedii Folium in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Objective:To explore the mechanism of the prescription consisting Aconiti Lateralis Radix Praeparata and Epimedii Folium in the treatment of chronic heart failure （CHF） based on network pharmacology，followed by verification in H9c2 myocardial cells with hypoxia-reoxygenation injury <italic>in vitro</italic> and in zebrafish with vascular endothelial growth factor receptor （VEGFR） tyrosine kinase inhibitor Ⅱ （VRI） -induced vascular insufficiency. Method:The active ingredients in Aconiti Lateralis Radix Praeparata and Epimedii Folium were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），the corresponding target genes from the Universal Protein Resource （UniProt）， and the CHF-related targets from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Both the active ingredient-potential target network and the active ingredient-CHF-related target network were generated using Cytoscape 3.6.1， followed by the protein-protein interaction （PPI） network construction and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genome （KEGG） enrichment analysis based on MetaScape. H9c2 myocardial cells exposed to hypoxia-reoxygenation were selected for determining the proliferation-promoting effect by methyl thiazolyl tetrazolium （MTT） assay. The protein expression of B-cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein（Bax），cysteinyl aspartate-specific protease-3（Caspase-3）， protein kinase B（PKB/Akt），phosphorylated protein kinase B（p-Akt），phosphorylated extracellular signal-regulated kinases 1/2 （p-ERK1/2），extracellular signal-regulated kinase 1/2 （ERK1/2）， and poly adenosine diphosphate ribose polymerase（PARP）was detected by Western blotting. The efficacy of the prescription in promoting angiogenesis was verified in a zebrafish model of VRI-induced vascular injury. Result:There were 28 active ingredients for the prescription， 209 corresponding targets， 1 296 CHF-related targets， and 94 common gene targets shared by the prescription and CHF. PPI network clustering suggested that Aconiti Lateralis Radix Praeparata and Epimedii Folium alleviated CHF by interfering with cell differentiation and metabolism and angiogenesis. GO analysis revealed that CHF relief was achieved via the intervention in such biological processes as cell migration，vascular development， and angiogenesis. Pharmacodynamic experiments verified that Epimedii Folium （10 mg·L^-1） alone and the prescription （10 mg·L^-1）both enhanced the proliferation of H9c2 myocardial cells under the hypoxia-reoxygenation condition （<italic>P</italic><0.05），while the latter also increased the expression of Bcl-2，Bcl-2/Bax， and PARP （<italic>P</italic><0.05） and reduced the expression of Caspase-3， Akt， and ERK （<italic>P</italic><0.05）. The prescription at the concentrations of 0.3 and 0.1 g·L^-1 promoted angiogenesis （<italic>P</italic><0.05）. Conclusion:Aconiti Lateralis Radix Praeparata and Epimedii Folium exert the therapeutic effect against CHF via multiple ingredients，multiple targets， and multiple channels. Such combination promotes the proliferation of H9c2 myocardial cells under hypoxic condition and protects zebrafish from vascular injury by up-regulating the expression of Bcl-2 and PARP，increasing Bcl-2/Bax ratio，and down-regulating the expression of Caspase-3，Akt， and ERK.

Historical Evolution and Modern Clinical Application of Qingxin Lianzi Yin / 中国实验方剂学杂志

Qingxin Lianzi Yin （QXLZY）， as an ancient classical formula for clearing the heart and nourishing the Yin， was composed of nine herbs （Scutellariae Radix， Ophiopogonis Radix， Lycii Cortex， Plantaginis Semen， Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma）， coming from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It could clear away the heart-fire， promote the interaction of the heart and kidney， replenish Qi and Yin， and stop strangury-turbidity. It was used to treat gonorrhea of urination， seminal emission， restlessness， wasting-thirst and so on. At present， the usage and dosage of QXLZY and its addition and subtraction are different in clinical practice. Most of the studies just focus on its clinical efficacy， and there is few review literature reflecting its historical evolution. Based on this， this paper systematically clarified the historical evolution， composition， preparation， interpretation， function， and modern clinical application of QXLZY. This work has been explained the historical evolution of QXLZY， and found that it was wildly used in modern clinical， especially suitable for the treatment of chronic urinary system diseases. At the same time， QXLZY also had significant therapeutic effects on neurasthenia， stomatitis， diabetic nephropathy and other aspects. Through the comprehensive analysis of ancient and modern literature， this work explores the true connotation of QXLZY from the perspective of traditional Chinese medicine theory， which can point out the direction of the clinical application and positioning of this famous classical formula after it comes into the market， and also can provide reference basis for its subsequent in-depth research and development.

Psoriasis-related Signaling Pathways Regulated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

As an inflammatory skin disease with a gradually increasing prevalence，psoriasis has negatively impacted the quality of life of patients and has attracted widespread attention from the medical community. The pathogenesis of psoriasis can be affected by a variety of genetic，environmental， and immune factors，and cytokine-driven epidermal proliferation，abnormal differentiation，inflammation， and neovascularization contribute to the pathogenesis，involving the interaction between immune and skin cells. However， some pathogenesis is still a blind spot for research，which brings great challenges to clinical treatment. Therefore， the identification of effective targets for psoriasis is critical in the research on psoriasis. Signaling pathways， another hotpot in the research on psoriasis， play an important cellular transduction role in the pathological mechanism of psoriasis and serve as key transduction factors regulating the immune and inflammatory responses to psoriasis. With the in-depth research in the field of network pharmacology and molecular biology， single Chinese medicine and Chinese medicinal compound can exert a therapeutic role by regulating multiple signaling pathways related to psoriasis. In recent years，traditional Chinese medicine （TCM） has achieved good clinical efficacy in the prevention and treatment of psoriasis，such as relieving pruritus，decreasing the area of skin lesions，improving anxiety， and preventing complications， which confirms the credibility of TCM in the understanding and treatment of psoriasis. Despite the rich theoretical and clinical research on the prevention and treatment of psoriasis，studies on the regulation of psoriasis-related signaling pathways and mechanisms of action by TCM are rarely reported. Therefore，the present study reviewed the available research in recent years and introduced the following six major signaling pathways related to psoriasis which are regulated by TCM： Janus kinase（JAK）/signal transducer and activator of transcription（STAT） signaling pathway，mitogen-activated protein kinase（MAPK） signaling pathway，phosphatidylinositol-3-kinases（PI3K）/protein kinase B（Akt） signaling pathway，nuclear transcription factor-κB（NF-κB） signaling pathway，Wnt signaling pathway， and Notch signaling pathway.

Research Advance in Mechanism of Cisplatin Toxic Injury and Its Prevention and Treatment by Traditional Chinese Medicine / 中国实验方剂学杂志

Cisplatin， as one of the commonly used broad-spectrum anti-tumor drugs in clinical practice， is used to treat testicular cancer， ovarian cancer， head and neck cancer， bladder cancer， lung cancer， cervical cancer and other solid cancers. It has obvious curative effect but strong toxic and side effect， and is easy to cause great damage to the body. The toxic reaction may involve serious toxic damages to different organs， and induce nephrotoxicity， hepatotoxicity， ototoxicity， cardiotoxicity， neurotoxicity and other toxicity. Animal experiments have shown that the toxic damage induced by cisplatin is the result of many factors in a time-and dose-dependent manner. In the course of clinical use， the therapeutic dose of cisplatin is also greatly limited due to toxic damage， which seriously affects the quality of life in patients. Therefore， it is the main research direction to find a suitable treatment plan or to use drugs in combination with cisplatin to reduce toxicity and increase efficiency. With the increasing clinical participation of traditional Chinese medicine（TCM）， TCM has shown its unique advantages in treating diseases， and can effectively reduce the cisplatin chemotherapy-induced toxic reaction by improving the oxidative stress state of the body， inhibiting normal apoptosis and inflammatory injury， activating autophagy， regulating the abnormal expression of drug transporters， etc. In this paper， the mechanism of cisplatin-induced toxic damage to various organs and the mechanism of TCM in prevention and treatment of cisplatin-induced toxic damage were summarized in detail， including the dose and mechanism of cisplatin-induced toxic damage to different organs， the effective treatment dose， combined medication mode and prevention and treatment mechanism of combined application of TCM and cisplatin， in order to provide a basis for rational application and clinical medication of TCM combined with chemotherapy drugs such as cisplatin.