Caries prevention mechanism of the Xinjiang Mori Cortex based on network pharmacology and its effect on the main cariogenic bacteria / 口腔疾病防治

Objective@#To investigate the potential caries prevention mechanism of the Xinjiang Mori cortex and to analyze its effect on the main cariogenic bacteria.@*Methods@#The active components of the Xinjiang Mori cortex and the main targets were predicted and screened using the TCMSP database. The GeneCards, DisGENET and TTD databases were used to obtain caries-related targets. The common targets were derived, and core genes were screened. The enrichment analysis was performed using the DAVID data platform. Molecular docking was performed using AutoDock software. In in vitro antibacterial experiments, first, the 50% minimum inhibitory concentration (MIC50) and the minimum bactericidal concentration (MBC) of the Xinjiang Mori Cortex extract against Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus were determined and the growth curves were measured. The effects of the Xinjiang Mori Cortex extract on acid production, polysaccharide production and adhesion ability of Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus in the planktonic state were determined. The 50% minimum biofilm inhibition concentration (MBIC50) and 50% minimum biofilm reduction concentration (MBRC50) were determined by crystal violet staining, and biofilm morphology was visualized using scanning electron microscopy (SEM).@*Results@#The main active components of the Xinjiang Mori cortex included quercetin, kaempferol, and β-sitosterol. Tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) could be the most important targets of the Xinjiang Mori cortex for the prevention of dental caries. The enrichment analysis results showed that Mori cortex extract may have effects on the AGE-RAGE signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. The antibacterial experiment results showed that the MIC50 values of Xinjiang Mori Cortex extract against Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus were 0.5, 0.5 and 0.25 mg/mL, respectively, and the MBCs were 4.0, 2.0 and 1.0 mg/mL, respectively. The inhibitory effect of Xinjiang Mori Cortex extract on the acid production, polysaccharide production and adhesion ability of three major cariogenic bacteria in the planktonic state was stronger than that of the control group, and the differences were statistically significant (P<0.05). The MBIC50 was 1.0, 1.0, and 0.5 mg/mL, and the MBRC50 was 4.0, 4.0, and 2.0 mg/mL. SEM observation showed that the amount of biofilm formation decreased with the drug concentration compared with the control group.@*Conclusion@#Xinjiang Mori cortex extract can prevent caries through quercetin, kaempferol, and β-sitosterol active ingredients, TNF、IL-6、IL-1β key targets and multiple pathways and inhibit the growth, acid production, polysaccharide production, and adhesion ability of three major cariogenic bacteria in the planktonic state and has some inhibitory effect on corticogenic biofilm formation.

Quality Evaluation of Mori Cortex from Different Producing Areas Based on Entropy Weight-TOPSIS Method / 中国实验方剂学杂志

ObjectiveTo evaluate the quality of Mori Cortex from different producing areas by the entropy weight-technique for order preference by similarity to an ideal solution（TOPSIS）， and to provide a new evaluation method for the quality control of Mori Cortex. MethodAccording to the five key indexes of color， thickness， texture， powdery and cortex remain， a subjective scoring table was designed to evaluate the appearance of Mori Cortex. High performance liquid chromatography（HPLC） was used to determine the fingerprint and the contents of multiple components（mulberroside A， chlorogenic acid， oxyresveratrol， mulberroside C， sanggenone D， sanggenone C， morusin）， and chemometrics was used to explore the differential components of Mori Cortex from different habitats. On this basis， TOPSIS was used to comprehensively evaluate the quality of Mori Cortex from different habitats， and SPSS 22.0 software was used to carry out bivariate correlation analysis between thickness and appearance color with contents of seven components of Mori Cortex. ResultThose with lighter color， thicker root bark， tougher texture， sufficient powder and less cortex remain scored higher， and the top five were all from Anhui. The established fingerprint and determination methods were stable and reliable. Partial least squares-discriminant analysis（PLS-DA） screened three components with the variable importance in the projection（VIP） value>1（mulberroside A， sanggenone D， sanggenone C）， which made an important contribution to the difference in the origin of Mori Cortex. Correlation analysis showed that there was a significantly positive correlation between mulberroside C with lightness value（L*） and total chromaticity value（E*ab） and mulberroside A with yellow-blue value（b*）（P<0.05， P<0.01）， a significantly negative correlation between sanggenone C with b* and between morusin with L*（P<0.05， P<0.01）. And there was a significantly negative correlation between mulberroside A， chlorogenic acid， and morusin with thickness（P<0.01）， a clearly negative correlation between sanggenone D with thickness（P<0.05）， a significantly positive correlation between sanggenone C with thickness（P<0.01）. TOPSIS comprehensive scores showed that the samples from Anhui had a good score and ranked high. ConclusionThere are great differences in the quality of Mori Cortex from different habitats， and those with the close habitats show similar characteristics in appearance and component content， and lighter color and less cortex were positively correlated with the quality. Among them， the quality of Mori Cortex from Anhui is relatively good.

Research progress on chemical constituents and pharmacological activities of Morus alba / 中国中药杂志

Morus alba, a traditional economic crop, is also a significant medicinal plant. The branches(Mori Ramulus), leaves(Mori Folium), roots and barks(Mori Cortex), and fruits(Mori Fructus) of M. alba are rich in chemical components, such as alkaloids, flavonoids, flavanols, anthocyanins, benzofurans, phenolic acids, and polysaccharides, and possess hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, anti-microbial, liver protective, immunoregulatory, and other pharmacological activities. This study analyzed the sources, classification, and functions of the main chemical components in M. alba and systematically summarized the latest research results of essential active components in M. alba and their pharmacological effects to provide references for in-depth research and further development as well as utilization of active components in M. alba.

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

Through consulting the ancient herbs， medical books and modern literature， this paper made textual research on the name， origin， producing area， quality evaluation， collection and processing of medicinal materials of Sang （Mori Folium， Mori Cortex， Mori Ramulus， Mori Fructus） in famous classical formulas， in order to provide a basis for the development of famous classical formulas containing medicinal materials of Sang. According to the research， Mori Folium and Mori Cortex were first used as medicines in Shengnong Bencaojing ， Mori Ramulus was first used as medicine in Jinxiaofang， and Mori Fructus was first used as medicine in Xinxiu Bencao. Before the Tang dynasty， there were Nyusang and Shansang. Since Tang dynasty， there were many sources of medicinal materials of Sang， including Baisang （Morus alba）， Jisang （M. australis）， Shansang （M. mongolica）， etc. According to textual research， the mainstream varieties were M. australis， M. alba and their cultivated varieties. In modern times， according to the relevant information and the Chinese Pharmacopoeia， M. alba is the original base. In ancient times， the origin of mulberry changed with the development of sericulture， mulberry has been widely planted since the Song dynasty. In the Ming and Qing dynasties， mulberry has been planted most in Jiangsu and Zhejiang. In modern times， they are mainly produced in Jiangsu， Zhejiang， Anhui， Hunan and other places. In recent years， due to the related policies and strategies such as "moving silkworms from east to west"， the center of silkworm breeding has gradually transferred to the west. As for the quality evaluation and harvesting and processing of mulberry medicinal materials， Most of the ancient and modern records of Mori Folium are the same. They are harvested after frost， and dried after removing impurities. The quality is better when the leaves are large and thick， yellowish green， holding prickly hands and undergoing frost. The harvesting period of Mori Cortex is slightly different in ancient and modern records. Ancient books record that it can be harvested all the year round， but in modern times， it is mostly harvested from late autumn to the next spring. The processing methods include removing soil and fibrous roots， scraping off yellow-brown rough skin， peeling off white skin and drying in the sun. The quality is better when they are white， thick， flexible， free of rough skin and full of powder. There are few records about the collection， processing and quality evaluation of Mori Ramulus and Mori Fructus in ancient Chinese herbal books. According to modern literature， Mori Ramulus is usually collected in late spring and early summer， with leaves removed， slightly dried， sliced while fresh， and dried in the sun. The best quality of Mori Ramulus is fine and tender with the yellow and white section. Mori Fructus is harvested from April to June when the fruit turns red， and dried in the sun， or slightly steamed and dried in the sun， and it is better to be big， dark purple， oily and thick. There are many processing methods of mulberry medicinal materials. Ancient books record stir frying， baking， burning and steaming of Mori Folium， in modern times， there is honey-roasted method， but most of them are used as raw products. In ancient materia medica， Mori Cortex has firing method， baking method， stir-frying method， honey-fried method， etc. In modern times， there are stir-fried and honey-fried methods， and most of them are used as raw products. Ancient books record that Mori Ramulus has cutting and frying methods， while modern ones have cutting， frying， wine-processed and bran-processed methods. Processing methods of Mori Fructus are consistent in ancient and modern times， and they are mostly dried after being cleaned or steamed. Based on the research results， it is suggested that M. alba should be selected as mulberry medicinal materials in the famous classical formulas， and appropriate medicinal parts and processing methods can be selected according to the indications of the famous classical formulas.

Prescriptions with Mori Cortex in Treatment of Respiratory Diseases： A Review / 中国实验方剂学杂志

Mori Cortex is sweet and pungent in taste， cold in nature， and has the tropism to the lung meridian. It has the functions of purging the lung and relieving asthma and can treat oliguria and edema， being one of the commonly used herbal medicines in clinical practice. The prescriptions with Mori Cortex， such as Sangbaipi Tang， Qingjin Huatanfang， and Qingfei Huatantang， are widely used in clinical practice. The main active components in Mori Cortex are the material basis for its efficacy. Owing to the mature methods for the identification of pharmacodynamic substances in Chinese herbal medicines， the research on the chemical components of Mori Cortex has been in-depth and systematic. This article reviews the recent studies about the chemical components and pharmacological effects of Mori Cortex， as well as the treatment of respiratory diseases by the prescriptions with Mori Cortex. On this basis， the effect and mechanism of Mori Cortex and related prescriptions in the treatment of respiratory diseases are summarized. Furthermore， this article analyzes the formulation compatibility and commonly used dosages of Mori Cortex-related prescriptions in clinical practice. It provides reference for the clinical application of Mori Cortex and related prescriptions in the treatment of respiratory diseases.

Prescriptions with Mori Cortex in Treatment of Respiratory Diseases： A Review / 中国实验方剂学杂志

Mori Cortex is sweet and pungent in taste， cold in nature， and has the tropism to the lung meridian. It has the functions of purging the lung and relieving asthma and can treat oliguria and edema， being one of the commonly used herbal medicines in clinical practice. The prescriptions with Mori Cortex， such as Sangbaipi Tang， Qingjin Huatanfang， and Qingfei Huatantang， are widely used in clinical practice. The main active components in Mori Cortex are the material basis for its efficacy. Owing to the mature methods for the identification of pharmacodynamic substances in Chinese herbal medicines， the research on the chemical components of Mori Cortex has been in-depth and systematic. This article reviews the recent studies about the chemical components and pharmacological effects of Mori Cortex， as well as the treatment of respiratory diseases by the prescriptions with Mori Cortex. On this basis， the effect and mechanism of Mori Cortex and related prescriptions in the treatment of respiratory diseases are summarized. Furthermore， this article analyzes the formulation compatibility and commonly used dosages of Mori Cortex-related prescriptions in clinical practice. It provides reference for the clinical application of Mori Cortex and related prescriptions in the treatment of respiratory diseases.

Systematic analysis on chemical constituents of Mori Cortex, mulberry root bark and its phellem layer based on HPLC-ESI-MS / 中国中药杂志

In this study, HPLC-ESI-MS and HPLC methods were established to explore the differences in the main chemical components and content of Mori Cortex with(mulberry root bark) and without(Mori Cortex) the phellem layer from both qualitative and quantitative aspects. The HPLC-ESI-MS method was used for quality analysis in positive and negative ion modes, and 33 compounds were identified in mulberry root bark, 22 compounds in Mori Cortex, and 26 compounds in phellem layer; mulberry root bark and Mori Cortex shared 22 components, and mulberry root bark has 11 unique compounds; Mori Cortex and its phellem layer shared 15 components, while Mori Cortex has 7 unique compounds. HPLC method was used to simultaneously determine 7 major constituents, including mulberroside A, chlorogenic acid, dihydromorin, oxyresveratrol, moracin O, kuwanon G, and kuwanon H, and the developed method showed good linearity(r>0.998 9) within the concentration range and the recoveries varied from 99.88% to 103.0%, and the RSD was 1.7%-2.9%. The HPLC results showed that the contents of the 7 compounds have great differences in 13 batches samples, compared with mulberry root bark, the contents of mulberroside A, chlorogenic acid, dihydromorin and moracin O of Mori Cortex were increased, while the contents of oxyresveratrol, kuwanon G and kuwanon H were decreased after peeling process. These results can provide a basis for the rationality and quality control of Mori Cortex required to remove the phellem layer.

Effect Mechanism of Total Flavonoid of Mori Cortex Combined with Total Saponins of Anemarrhenar Rhizoma on Hyperlipidemia Rats with Osteoporosis / 中国实验方剂学杂志

Objective:To explore the improvement effect of total flavonoids of Mori Cortex combined with total saponins of Anemarrhena Asphodeloide on hyperlipidemia rats with osteoporosis and its possible mechanism. Method:The 40 SPF male SD rats were adaptively fed for 7 days， and then randomly divided into normal group， model group， calcitriol group （45 ng·kg^-1）， total flavonoids of Mori Cortex and total saponins of Anemarrhena Asphodeloide 1∶2 group （0.6 g·kg^-1+0.4 g·kg^-1） and 2∶1 group （1.2 g·kg^-1+0.2 g·kg^-1）. Except for the normal group， rats in the other groups were fed with high fat for 9 weeks， the normal group and the model grouotal flavonoids of total flavonoids of Mori Cortex and total saponins of Anemarrhena Asphodeloip were given normal saline by gavage， and the other groups were given corresponding drugs by gavage， after 12 weeks of administration， except for the normal group ， the other groups were given intramuscular injection of glucocorticoids at the same time. After 22 weeks of administration， the weight of rats with total flavonoids from Mori Cortex combined with total saponins of Anemarrhena Asphodeloide was measured. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， osteocalcin （BGP） and bone alkaline phosphatase （BALP） were determined by biochemical assay. Hematoxylin-eosin （HE） staining to observe the pathological changes of rat tibia. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of peroxisomal proliferators activate the receptor gamma（PPAR<italic>γ</italic>） and Runt-related transcription factor 2 （Runx2） mRNA in rat bone tissue， immunofluorescence was used to detect the expression of PPAR<italic>γ</italic> and Runx2 in rats. Result:Compared with normal group， the body mass of rats in model group was significantly increased （<italic>P</italic><0.01）， and the contents of TC， TG， and LDL-C in the serum were significantly increased （<italic>P</italic><0.01）. Compared with model group， the body weight of rats in thet total flavonoids of Mori Cortex and total saponins of Anemarrhena Asphodeloide 1∶2 group and 2∶1 group were significantly reduced （<italic>P</italic><0.01）， and the contents of TC， TG， and LDL-C in the serum were significantly reduced （<italic>P</italic><0.01）， the content of BGP and BALP increased （<italic>P</italic><0.01）. HE staining results showed that compared with the normal group， the tibia fat vacuoles of the model group increased， and the number of osteoblasts decreased， compared with the model group， the total flavonoids of the Mori Cortex and the flavonoids-total saponins of Anemarrhena Asphodeloide 1∶2 group and 2∶1 group decreased in tibia fat vacuoles and increased the number of osteoblasts， the results of immunofluorescence and Real-time PCR showed that， compared with normal group， the expression of Runx2 in the model group decreased and the expression of PPAR<italic>γ</italic> increased （<italic>P</italic><0.01）. Compared with model group， the total flavonoids of Mori Cortex-total saponins 1∶2 group and the total flavonoids of Mori Cortex-total saponins 2∶1 Group up-regulated the expression of Runx2 and down-regulated the expression of PPAR<italic>γ </italic>（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:The total flavonoids of Mori Cortex combined with the total saponins of Anemarrhena Asphodeloide up-regulated Runx2 and down-regulated the expression of PPAR<italic>γ</italic> mRNA and protein， thereby affecting the metabolism of TG and TC in the blood， achieving a therapeutic effect on osteoporosis， provides experimental basis for the clinical prevention and treatment of hyperlipidemia with osteoporosis.

Simultaneous Determination of 7 Active Components in Mori Australis Cortex and Mori Cortex from Different Sources by HPLC / 中国药房

OBJECTIVE：To establish a meth od for the simultaneous determination of 7 active components in Mori Australis Cortex and Mori Cortex from different sources in Chongqing area ，so as to provide reference for improving the quality control standards of Mori Australis Cortex and Mori Cortex and comparing the equivalence of their quality. METHODS ：HPLC method was used to determine the contents of neochlorogenic acid ，mulberroside A ，chlorogenic acid ，astragalin，kaempferol，morusin and isoquercetin in 58 batches of Mori Australis Cortex and Mori Cortex. The chromatographic column was Diamonsil C 18 with mobile phase consisted of 0.1％ formic acid solution-acetonitrile （gradient elution ） at the flow rate of 1.0 mL/min. The detection wavelength was 280 nm，column temperature was 30 ℃，and the injection volume was 10 μL. Using SPSS 22.0 software， independent sample t-test，principal component analysis and cluster analysis were used to analyze the content difference of the above-mentioned 7 active components in Mori Australis Cortex and Mori Cortex. RESULTS ：There was a good linear relationship between the peak area and the concentration of the above 7 active components （r≥0.999 0）. The RSDs of precision ，stability（24 h），repeatability，durability and recovery were less than 3％. The average contents of neochlorogenic acid ，mulberroside A ， chlorogenic acid ， astragalin， kaempferol， morusin and 023-58576130。E-mail：1025473978@qq.com isoquercetin in Mori Australis Cortex were 0.304，22.462， 1.730，1.308，1.593，2.842 and 0.657 mg/g，respectively. Those of Mori Cortex were 0.305，22.995，2.486，2.438， 2.916，4.158 and 1.264 mg/g，respectively. The results of independent sample t-test showed that only the content of kaempferol in the above 7 active components of Mori Australis Cortex and Mori Cortex had significant difference （P＜0.05）. The results of principal component analysis and cluster analysis showed that there was no significant difference in the contents of above 7 active components between Mori Australis Cortex and Mori Cortex. CONCLUSIONS：The established HPLC method is simple ，sensitive and accurate ，which can provide a reference for improving the quality control standard of Mori Australis Cortex and Mori Cortex. Mori Australis Cortex and Mori Cortex have certain quality equivalence in main active components ，and the Mori Australis Cortex from M. australis and M. cathayana can be used as a substitute for the Mori Cortex.

Virtual screening of small molecular inhibitors of SARS-CoV-2 3CL hydrolase based on high-throughput molecular docking and prediction of Chinese materia medica and its compound against COVID-19 / 中草药

Objective: Based on the systematic pharmacological database of traditional Chinese medicine (TCM) and the analysis platform TCMSP, the computer virtual screening technique was used to screen the small molecule inhibitors of SARS-CoV-2 3CL hydrolase from Chinese materia medica (CMM), and speculate the potential anti-COVID-19 novel coronavirus pneumonia TCMs and its compounds. Methods: SARS-CoV-2 3CL hydrolase protein was targeted in this study. Autodock Vina software and Python script were used to realize high-throughput molecular docking. Combined with “ADME-Lipinski” rules, the re-screening was carried out to optimize the active ingredients and speculate the key TCMs and compound prescriptions. Based on the perspective of network pharmacology, a component-target-pathway network was constructed to infer the mechanism of action of core drug pairs. Results: Taking the reference ligand as positive control, 66 natural micromolecule compounds with good pharmacokinetic properties were obtained. Twelve single TCMs, two Chinese medicine pairs of Glycyrrhizae Radix et Rhizoma-Mori Cortex and Lonicerae Japonicae Flos-Forsythiae Fructus, and 12 TCM prescriptions including Sangju Drink and modified Sangju Drink and Yinqiao Powder were selected as candidate schemes to fight against novel coronavirus pneumonia. Conclusion: This study is based on high-throughput molecular docking technology to virtually screen small molecule inhibitors of SARS-CoV-2 3CL hydrolase of CMM and Chinese medicines, innovatively analyze the potential molecular mechanism in combination with network pharmacology, and provide scientific guidance and theoretical basis for TCM to resist novel coronavirus pneumonia.

Effect of Sanggenone C on MC3T3-E1 Based on Molecular Docking Technology / 中国实验方剂学杂志

Objective::To observe the effect of sanggenone C (SanC) on the proliferation and differentiation of mouse MC3T3-E1 osteoblasts induced by dexamethasone (DEX), and to explore its mechanism. Method::Molecular docking was conducted between SanC and Runt-associated transcription factor 2(Runx2) protein structure obtained by homologous modeling. MC3T3-E1 cells were jointly treated by different concentrations of SanC (8, 16, and 32 μmol·L-1) and 1 μmol·L-1 DEX, and then cell counting kit-8(CCK-8) method was used to detect the effect of SanC on the proliferation of MC3T3-E1 osteoblasts. The alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts was determined by reagent kit and the formation of mineralized bone nodules were detected by alizarin red staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of Runx2, ALP and Osterix. The protein expression of Runx2 was detected by Western blot. Result::The docking score of SanC and Runx2 was -9.78.As compared with the normal group, DEX group significantly reduced the cell survival rate (P<0.01), and the greatest difference occurred on the seventh day. As compared with DEX group, SanC could significantly promote the cell proliferation of MC3T3-E1 (P<0.01), in which 32 μmol·L-1 SanC had the largest difference in proliferation rate on seventh day. As compared with the normal group, the expression of Runx2, ALP and Osterix mRNA increased to a certain extent in DEX group(P<0.01). As compared with DEX group, the expression levels of Runx2, ALP and Osterix mRNA were up-regulated in different concentration groups of SanC in a dose-dependent manner (P<0.01). As compared with the normal group, the expression of Runx2 protein in DEX group decreased significantly (P<0.05), and as compared with DEX group, the expression of Runx2 protein in cells under the intervention of SanC increased significantly (P<0.01). Conclusion::SanC can promote the proliferation, differentiation and mineralization of MC3T3-E1 osteoblasts, and the mechanism may be related to the up-regulation of Runx2 expression.

Investigation of Xiebaisan Based on Ancient Literature / 中国实验方剂学杂志

Xiebaisan, which is one of the famous classical formulas in the Catalogue of Ancient Famous Classical Formulas (The First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018, is derived from the Xiao' er Yaozheng Zhijue with definite clinical effect. By means of bibliometrics, 118 relevant ancient book data were collected, including 75 ancient books of TCM. It was found that the main symptoms of Xiebaisan had been expanded in the past dynasties. For example, the adaptive population of Xiebaisan had been extended from children to women and adults, and the scope of symptoms and signs had also been extended from pediatrics to internal medicine and gynecology. Meanwhile, the names, pathogenesis and syndromes of diseases are also described extensively, although the dosage ratio is different, the compatibility ratio of Mori Cortex, Lycii Cortex and Glycyrrhizae Radix et Rhizoma is relatively constant, and the decoction method is mostly followed by decocted power. At the same time, doctors in Ming and Qing dynasties have made a lot of general comments on explanation of this formula, but there is little controversy.

Textual Research of Mori Cortex in Classical Prescriptions / 中国实验方剂学杂志

The research and development of classical famous prescriptions is an important way to actively promote the development of traditional Chinese medicine.It is particularly important to sort out the historical evolution of the composition of traditional famous prescriptions to make clear the origin，producing areas and concocting methods of traditional Chinese medicine，which is the source of ensuring the safety and efficacy.Through literature review，it is found that at present，the research of mulberry white skin focuses on chemical composition，pharmacological mechanism and modern clinical research，and there are few ancient literature studies.Therefore，based on the ancient literature，the author conducts a comprehensive textual research on mulberry bark from its name，origin，producing areas and concocting methods and other aspects，in order to provide literature reference for the research and development of the prescription involving mulberry bark in the classic prescription.Through research，we can know that there are more than 20 aliases of mulberry bark，and the most commonly used names in modern times are "sangbaipi""sanggenbaipi""sangpi"，etc.In Tang and Song dynasties and before，mulberry bark was mainly composed of Morus alba var. alba and jisang，after Tang and Song dynasties，mulberry bark plant sources showed diversity，in modern times，Morus alba var. alba was gradually identified as the main medicinal species of mulberry bark.Therefore，it is suggested that Morus alba var. alba be selected as the plant source of mulberry bark.According to ancient books，mulberry trees are cultivated everywhere，with Jiangsu，Zhejiang and Sichuan as the best areas，and Henan and Anhui as the most popular areas in modern times.The conclusion of ancient and modern quality of mulberry bark is basically the same，the root skin is white，thick and sweet.The morden concocting methods of mulberry bark mainly include raw mulberry bark，honey mulberry bark and fried mulberry bark.According to the textual research of ancient literature，in addition to the above three kinds of medical specifications，there have been concocting methods without auxiliary materials，such as burning，baking and roasting，as well as concocting methods with auxiliary materials，such as bran roasting，rice swill soaking，honey wine roasting，etc.The concocting methods of mulberry bark used by the classical famous recipe should be selected in combination with specific drug provisions.

Research Progress in Pharmacological Effect of Mori Cortex / 中国实验方剂学杂志

Mori Cortex is the dry root bark of Moras alba L. and usually used in clinical practice. It is sweet and cold in nature, and enters the lung meridian. With effects in purging lung and relieving asthma, and inducing diuresis to reduce edema, it is mainly used to treat lung heat, asthma, cough, swelling, urine deficiency and facial skin edema. In clinic, it is mainly used for the treatment of respiratory system, urinary infection and diabetes mellitus. In recent years, great progress has been made in studies on the pharmacological effects of Mori Cortex. The literatures on the pharmacological effects of Mori Cortex in recent years were reviewed and summarized in this paper. Mori Cortex has antitussive, anti-inflammatory, hypoglycemic, cardiovascular, antiviral, anticancer, immunoregulatory, antioxidation and anti-allergy and other pharmacological effects, in addition to antitussive, expectorant, antiasthmatic and other traditional effects. Total flavones have a strong pharmacological activity. These extended studies provide valuable reference for the further development of Mori Cortex. This paper summarizes the pharmacological effects of Mori Cortex, proposes the key directions of further studies, and provides the beneficial reference for better development and utilization of Mori Cortex.

Protective effect of Mori Cortex on kidney in rats with hyperlipidemia and hyperuricemia based on molecular docking technique / 中草药

Objective To investigate the mechanism of total flavonoids of Mori Cortex (TFMC) in improving hyperlipidemia and hyperuricemia related nephropathy. Methods The molecular structure of URAT1 protein and structure of Mori Cortex total flavonoids extract were docked by selecting the effective components of total flavonoids extract of Mori Cortex and related genes of uric acid. Forty SD rats were randomly divided into four groups: normal group, model group, TFMC group (1.0 g/kg) and benzbromarone group (6.25 mg/kg). The hyperlipidemia and hyperuricemia model was established by feeding with high fat diet plus adenine and ethylamine butanol. After 16 weeks, the levels of blood glucose and blood lipids in serum, uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) of rats in each group were compared. The renal pathological changes were observed by hematoxylin eosin staining. The expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), uric acid anion exchange transporter 1 (URAT1) and organic anion transporter 1 (OAT1) were detected by qRT-PCR. Results The main component of moracin of total flavonoids of Mori Cortex was the high target of the genes related to uric acid, suggesting that the moracin might be the main active component in the improvement of hyperlipidemia and hyperuricemia related nephropathy. After 16 weeks of drug intervention, the serum levels of Glu, TC, TG, LDL-C, UA, CRE and BUN in the model group were significantly higher than those in the normal group, and the level of HDL-C in the model group was significantly higher than that in the normal group (P < 0.05, 0.01). Compared with the model group, the above biochemical indexes in the TFMC group and the benzbromarone group were significantly decreased and HDL-C was significantly increased (P < 0.05, 0.01). The results of HE staining showed that the epithelial cells of renal tubules in the model group were swollen and necrotized, and the protein tubules could be seen in the renal tubules. In the TFMC group, some renal tubular epithelial cells were slightly swollen, and no inflammatory cells infiltrated around them. The structures of renal cortex and medullary were clear, and no hyperplasia or atrophy in glomerular were found, no tubular type and inflammatory cell infiltration in renal interstitial tissue of rats in benzbrommarone group were observed. The results of qRT-PCR showed that, compared with the normal group, the content of IL-6, TNF-α, and URAT1 mRNA was significantly increased, the content of OAT1 mRNA was significantly decreased in the model group; The content of above indicators was decreased and OAT1 was increased after drug intervention, (P < 0.05, 0.01). Conclusion The improvement of hyperlipidemia and hyperuricemia associated nephropathy may be related to the regulation of IL-6, TNF-α, URAT1, and OAT1 mRNA. Mori Cortex has obvious influence on the key factor of hyperlipidemia and hyperuricemia with URAT1 as its potential target, and the results of molecular virtual docking and animal experiments are similar. It provides a theoretical basis for further study on the improvement of hyperlipidemia and hyperuricemia related nephropathy and provides a reference for the further molecular mechanism.

Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats / 中国天然药物

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.

Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats / 中国天然药物

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.

Metabolic study of Mori Cortex on nephrogenic edema in rats / 中成药

AIM To conduct a metabolic research for a better understanding of nephrogenic edema and to assess the integral efficacy of Mori Cortex in rat model.METHODS The serum creatinine,urea nitrogen,albumin and urinary protein levels in rats were detected.UPLC-QTOF-MS was used to detect the urine metabolites changes,Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA)were used to screen potential biomarkers,after whose quantification,Mev software was adopted for heat map draw-ing and hierarchical cluster analysis.RESULTS The model rats manifested significantly increased levels of serum creatinine,urea nitrogen and urinary protein,decreased albumin level,and an obviously excessive amino acid metabolism as well.The 41 identified biomarkers were mainly related to disturbances in phenylalanine,pyrimidine,arginine and proline,glycine,serine and threonine,tryptophan,cysteine and methionine metabolism,and biosynthesis of pantothenic acid and coenzyme A.A reversal trend in aforementioned levels of biochemical indexes and most biomarkers due to the intervention by Mori Cortex signaled an improvement in the metabolic disorder,renal dysfunction and edema.CONCLUSION The metabolic study demonstrates the pathological status of nephrogenic edema and assesses the effect of Mori Cortex from an overall perspective,highlighting a new approach for illustrating Chinese medical syndrome and the underlying mechanism in the management of traditional Chinese medicine.

Investigation and optimization on ability of enzymatic hydrolysis of Mori Cortex residue / 中国中药杂志

Residue of Mori Cortex was studied to optimize its enzymatic hydrolysis process, and explore its potential as a carbon source for biochemistry and biofuel production. The cellulose content of diluted acid pretreated (DAP) and non-pretreated from Mori Cortex were measured in this study, and the results showed that the cellulose content of DAP and non-pretreated from Mori Cortex were 52.5% and 47%, respectively. This higher cellulose content indicated that residue of Mori Cortex had the potential to act as a carbon source for biochemistry and biofuel production. Enzymatic hydrolysis of pretreated and non-pretreated from Mori Cortex was conducted under different enzyme loading amount. 40 FPU·(g DW）⁻¹ enzyme loading was determined as the optimal amount by comparing the yield of sugar and the rate of enzymolysis. Under this condition, the concentrations of glucose, xylose, arabinose sugar were 23.82, 4.84, 3.6 g·L⁻¹, and the corresponding enzymatic hydrolysis rate was 45.33% which was 2.3 times higher than that of non-pretreated from Morus alba residues. Fed-batch enzymatic hydrolysis was conducted finally to get higher sugar yield, and the final glucose concentration reached up to 38 g·L⁻¹ with the enzymatic hydrolysis rate of 36.19%. The results indicated that Mori Cortex residue had higher cellulose and hemicellulose contents, so it had the potential to become a carbon source to produce the bio-chemicals and biofuels. Through enzymatic hydrolysis, it can be converted into microbial available monosaccharides; and through fermentation, it can be converted into high value-added chemicals, biofuels, etc., to solve the problem of residue pollution, and achieve the sustainable development and greening of Chinese pharmaceutical production process.

Inlfuence on Substance and Energy Metabolism of Diabetic Mouse Model of Chemical Split Fractions ofMori Cortex / 世界科学技术-中医药现代化

This article was aimed to study the impact on substance and energy metabolism by chemical split fractions of Mori Cortex among hypoglycemic diabetic mouse model, in order to explain the new hypothesis of the science connotation in nature and flavor of traditional Chinese medicine (TCM). Male Kunming mice were intraperitoneally injected with a large dose of streptozotocin (STZ) (170 mg·kg-1) to establish type 1 diabetes mellitus mouse model. Medication was given consecutively for four weeks. The enzyme-linked immunesorbent assay (ELISA) was used to detect glucosekinase (GCK), glycogen phosphorylase (PYGL), pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (α-KGDHC), phosphoglycerate kinase (PGK), acetyl coenzyme A (acetyl-CoA), adenylate kinase (ADK), fumarase (FUM), cytochrome C reductase (CCR), cytochrome C oxidase (COX) and other indicators. Enzymatic detection was used to determine the content of ATP coenzyme (ATPs), the content and ratio of NAD and NADH, the content of myocardial cell Na+-K+ ATP enzyme, as well as the content of ATP and ADP. The results showed that in the model group, the expression of PYGL was increased; and the expressions of GCK and PDH were decreased. It prompted that the source of glucose increased and the expelling of glucose decreased. The glucose level was increased. The COX expression was reduced and the respiratory chain was blocked. It regulated oxidative phosphorylation and the substrate phosphorylation level. It upregulated the expression of CCR, ATPs, NAD+, PGK, α-KGDHC and ADK. However, the expression of FUM was decreased. The activity of Na+-K+ ATPase was decreased significantly. At last, the metabolic disorders appeared. Mori Cortex aqueous extracts and the chemical split fractions significantly increased the GCK and PDH level in substance metabolism among diabetic mice. The levels of PYGL, α-KGDHC, PGK and acetyl-CoA were decreased (P < 0.05, or P <0.01). Meanwhile, it increased ATP and FUM, myocardial cell Na+-K+ ATP enzyme, and COX level in the energy metabolism (P < 0.05). It decreased the level of NAD+, CCR and ATPs (P < 0.05, or P <0.01). It was concluded that both the aqueous extracts and chemical split fractions of Mori Cortex can effectively improve the substance and energy metabolism disorders of diabetic mouse model. This effect may be related to the cold nature of Mori Cortex.