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Coptis,Pinellia,and scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection

World Journal of Clinical Cases 2022年第34期10卷 12500-12514页

作者： Zhang Yu Wu-Dong Sheng Xu Yin Yu Bin Department of Internal Medicine The First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina Department of Surgery The First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina

BACKGROUND Helicobacter pylori(H.pylori)is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.AIM To identify efficient therapeutic agents or strategies that can treat H.pylori infection.METHODS We performed literature analysis,experimental validation,and network pharmacology.First,traditional Chinese medicine(TCM)prescriptions for the treatment of H.pylori infection were obtained from the China National Knowledge Infrastructure,China Biology Medicine,China Science and Technology Journal Database,and WanFang databases.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://***).Next,we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions.Then,an H.pylori-associated chronic mouse model of gastritis was established.The antibacterial properties and antiinflammatory potential of the core drug combination were evaluated by the rapid urease test,modified Warthin-Starry silver staining,histopathological analysis,and enzyme linked immunosorbent assay.Finally,the active compounds,hub targets,and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology.RESULTS The TCM treatment of H.pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing,bitter descending,cold and warm drugs.The combination of Coptis,Pinellia,and scutellaria(CPS)was identified as the core drug combination from 207 prescriptions and 168 herbs.This drug combination eradicated H.pylori,alleviated the gastric pathology induced by H.pylori infection,and reduced the expression levels of tumor necrosis factor-α(P=0.024)and interleukin-1β(P=0.001).Moreover,a total of 35 compounds and 2807 targets of CPS were identified using online databases.Nine key compounds(tenaxin I,neobaicalein,norwogonin,skullcapflavone II,baicalein,5,8,2'-trihydroxy-7-methoxyflavone,acacetin,pan

关键词： Coptis Pinellia scutellaria Anti-Helicobacter pylori Drug combination Traditional Chinese medicine

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Three new lignan glucosides from the roots of scutellaria baicalensis

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Acta Pharmaceutica Sinica B 2016年第3期6卷 229-233页

作者： Hailin Long Haijing Zhang Anjun Deng Lin Ma Lianqiu Wu Zhihong Li Zhihui Zhang Wenjie Wang Jiandong Jiang Hailin Qin State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

Three new lignan glucosides, baicalensinosides A–C(1–3), were isolated from the roots of scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofurantype lignan glycoside with a mono-hydroxyl substitution at the 70-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin(OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 μmol/L, compounds 1–3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively.

关键词： scutellaria baicalensis Roots Labiatae Lignan glucoside Baicalensinosides A–C 3 4-Dibenzyltetrahydrofuran Osteoprotegerin-activating activity Anti-osteoporotic activity

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Comparative Genome Analysis of scutellaria baicalensis and scutellaria barbata Reveals the Evolution of Active Flavonoid Biosynthesis

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Genomics, Proteomics & Bioinformatics 2020年第3期18卷 230-240页

作者： Zhichao Xu Ranran Gao Xiangdong Pu Rong Xu Jiyong Wang Sihao Zheng Yan Zeng Jun Chen Chunnian He Jingyuan Song Key Lab of Chinese Medicine Resources Conservation State Administration of Traditional Chinese Medicine of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China Engineering Research Center of Chinese Medicine Resource Ministry of EducationBeijing 100193China China National Traditional Chinese Medicine Co. LtdBeijing 102600China

scutellaria baicalensis(S.baicalensis)and scutellaria barbata(S.barbata)are common medicinal plants of the Lamiaceae family.Both produce specific flavonoid compounds,including baicalein,scutellarein,norwogonin,and wogonin,as well as their glycosides,which exhibit antioxidant and antitumor activities.Here,we report chromosome-level genome assemblies of S.baicalensis and S.barbata with quantitative chromosomal variation(2 n=18 and 2 n=26,respectively).The divergence of S.baicalensis and S.barbata occurred far earlier than previously reported,and a whole-genome duplication(WGD)event was identified.The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement.Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes,such as the S.baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase,and the S.barbata-specific duplication of genes encoding 4-Co A ligase.In addition,the paralogous duplication,colinearity,and expression diversity of CYP82 D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S.baicalensis and S.barbata.Analyzing these scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes.Thus,these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.

关键词： scutellaria Whole-genome duplication Flavonoid biosynthesis Tandem duplication Species-specific evolution

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Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix scutellaria extract in rats

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Chinese Journal of Natural Medicines 2018年第6期16卷 418-427页

作者： ZHANG Xue-Ju LIU Shu XING Jun-Peng LIU Zhi-Qiang SONG Feng-Rui National Center of Mass Spectrometry in Changchun Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass SpectrometryChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Chinese Academy of Sciences Beijing 100039China

Radix scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher Cmax and AUC values(P scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix scutellaria.

关键词： Radix scutellaria Diabetes mellitus Flavonoid Pharmacokinetics Tissue distribution

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Flavonoids from scutellaria barbata inhibit activation of tumor-associated macrophages by blocking the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB signaling pathway

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Journal of Traditional Chinese Medicine 2019年第2期39卷 160-165页

作者： Bao Xiaoxia Li Liuye Xue Xiaoou Department of Gynecology Dongzhimen Hospital Beijing University of Chinese Medicine

OBJECTIVE: To determine the efficacy of scutellaria barbata flavonoids and polysaccharides on Ishikawa endometrial carcinoma cells co-cultured with U937 macrophages.METHODS: The presence of CD163 and CD206 was determined by flow cytometry. Thiazolyl Blue Tetrazolium Bromide assays were used to assess the proliferation effect of tumor-associated macrophages(TAMs) on Ishikawa cells. The secretion of interleukin(IL)-10 in the co-culture conditioned media was examined using an enzyme-linked immunosorbent assay. The protein expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88) and nuclear factor(NF)-κB p65 were detected by Western blot. The mRNA expression levels of TLR4 and MyD88 were analyzed by real-time polymerase chain reaction(PCR). The expression levels of IL-12, IL-1β and tumor necrosis factor-α(TNF-α) were evaluated with real-time PCR.RESULTS: Compared with the U937 control group,the expression levels of CD163 and CD206 in the TAM group were higher(P scutellaria barbata flavonoids group(P scutellaria barbata flavonoids group(P scutellaria barbata flavonoids may inhibit TAM activation by blocking the TLR4/MyD88/NF-κB signaling pathway.

关键词： Endometrial neoplasms scutellaria baicalensis Flavonoids Toll-like receptor 4 Myeloid differentiation factor 88 Macrophages

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Essential oil composition of two scutellaria species from Iran

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Journal of Traditional Chinese Medical Sciences 2019年第3期6卷 244-253页

作者： Gharari Zahra Bagheri Khadijeh Danafar Hossein Sharafi Ali Department of Plant Production and Genetics Faculty of AgricultureUniversity of ZanjanZanjanIran School of Pharmacy Zanjan University of Medical SciencesZanjanIran Zanjan Applied Pharmacology Research Center School of PharmacyZanjan University of Medical SciencesZanjanIran Zanjan Pharmaceutical Biotechnology Research Center Zanjan University of Medical SciencesZanjanIran

Objective:Medicinal plants scutellaria multicaulis and scutellaria bornmuelleri belong to the scutellaria genus and Lamiaceae family,and are widely used in traditional Iranian medicine.This study aims to characterize promising bioactive phytochemicals found in the aerial parts of S.multicaulis and S.bornmuelleri.Methods:Accordingly,volatile oils were obtained by hydrodistillation of S.multicaulis and S.bornmuelleri leaves and stems,and then analyzed by gas chromatographyemass spectrometry(GC/MS).Results:A total of 88 components,representing 92.4%of the oil(oil yield determined to be 0.53%,v/w),were identified in the essential oils of S.multicaulis.The main group was sesquiterpene hydrocarbons(24%),with a-himachalene(7.2%),a-longipinene(6.8%),and a-copaene(3.2%)as the main components.A total of 89 chemicals,representing 83.2%of the essential oil(oil yield determined to be 0.31%,v/w),were detected in the essential oil of S.bornmuelleri.The main components were steroids,such as 14-b-H-pregna(32.9%),hydrocarbons(22.5%),sesquiterpenes(11.4%),and monoterpenes(4.6%),which were considered minor constituents.The contents of sesquiterpene and monoterpene hydrocarbons present in S.multicaulis and S.bornmuelleri were 24%and 7.1%,respectively.However,the contribution of oxygenated monoterpenes(4%)and sesquiterpenes(4.3%)in both species was less than 5%.Conclusion:As the first report on the chemical composition of S.multicaulis and S.bornmuelleri,this study showed that the major compounds were steroids and sesquiterpenes.

关键词： 14-b-H-Pregna GC/MS a-himachalene a-Longipinene scutellaria

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Ethanol extracts of scutellaria baicalensis protect against lipopolysaccharide-induced acute liver injury in mice

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Asian Pacific Journal of Tropical Biomedicine 2015年第9期5卷 733-738页

作者： Hai Nguyen Thanh Hue Pham Thi Minh Tuan Anh Le Huong Duong Thi Ly Tung Nguyen Huu Loi Vu Duc Thu Dang Kim Tung Bui Thanh School of Medicine and Pharmacy Vietnam National University Hanoi University of Pharmacy

Objective: To investigated the protective potential of ethanol extracts of scutellaria baicalensis(S. baicalensis) against lipopolysaccharide(LPS)-induced liver injury. Methods: Dried roots of S. baicalensis were extracted with ethanol and concentrated to yield a dry residue. Mice were administered 200 mg/kg of the ethanol extracts orally once daily for one week. Animals were subsequently administered a single dose of LPS(5 mg/kg of body weight, intraperitoneal injection). Both protein and m RNA levels of cytokines, such as tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in liver tissues were evaluated by ELISA assay and quantitative PCR. C yclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB protein levels in liver tissues were analyzed by western blotting. Results: Liver injury induced by LPS signifi cantly increased necrosis factor alpha, interleukin-1β, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB in liver tissues. Treatment with ethanol extracts of S. baicalensis prevented all of these observed changes associated with LPS-induced injury in liver mice.Conclusions: Our study showed that S. baicalensis is potentially protective against LPS-induced liver injury in mice.

关键词： scutellaria baicalensis Lipopolysaccharide Liver injury Cytokine Nuclear factor-κB

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Behavior and metabolomics study of the anti-aging effects of scutellaria baicalensis Georgi extract on D-galactose-induced rats

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中国药理学与毒理学杂志 2015年第S1期29卷 75-76页

作者： Yu-shiZHOU Yan-fenCHANG Guan-huaDU Xue-meiQIN Modern Research Center for Traditional Chinese Medicine of Shanxi University Taiyuan 030006 China College of Chemistry and Chemical Engineering of Shanxi University Taiyuan 030006 China Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China

OBJECTIVE Behavior research and urinary metabolomics method were applied to evaluate the anti-aging effects of scutellaria baicalensis Georgi extract(SBG)in D-galactose-induced rats.METHODS Fifty rats were randomly divided into five groups(n=10in each group).Group 1served as vehicle control with injection of saline(vehicle control group),and the other groups of rats received daily subcutaneously injected with D-galactose(aged model group)at dose of 100mg·kg-1 for ten weeks,respectively.At the same time,rats in groups 3-5were intragastrically administered SBG 〔extracted twice with 60%(V/V)ethanol〕at doses of 50,100 and 200mg·kg-1 for ten weeks,and the rats of groups 1 and 2 were administrated an equal volume of the vehicle.At the tenth week,the learning and memory abilities were examined by Morris water maze.The urine was collected using metabolic cages and analyzed by high-resolution 1HNMR spectroscopy combined with multivariate statistical analyses.Principal component analysis(PCA)was utilized to classify and reveal the differences between the model group and control group.Then,the concentration of these differences was analyzed with t-test to determine whether SBG was possible to influence the metabolic pattern induced by D-galactose.RESULTS Compared with the vehicle control group,the D-galactose-treated aged model group markedly spent longer time(P<0.05)in finding the platform on days 3-5 in the spatial learning acquisition training of Morris water maze test.However,the escape latency was significantly reduced(P<0.05)by long-term administration of SBG(50,100 and 200mg·kg-1)compared with the D-galactose-treated aged model group on days 3-5.In the probe test,the D-galactose-treated aged model group made fewer(P<0.05)platform crossings and distance travelled in target quadrant(P<0.05)than the vehicle control group,and the SBG at doses of 50,100 and 200mg·kg-1 treatments groups could significantly increase(P<0.05)the number of times of crossing over the platform site.The SBG at doses of100 and 200mg·kg-1 treatment

关键词： scutellaria baicalensis Georgi anti-aging metabolo

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Inhibition of Flavonoids from scutellaria baicalensis Stems and Leaves against Abnormal Formation of PHF and Regulation of PP in OA Induced Brain Injury in Rats

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Medicinal Plant 2018年第6期9卷 76-81,88页

作者： Jianjun CHENG Hong MIAO Shuai MA Yang GAO Yazhen SHANG Hebei Province Key Research Office of Traditional Chinese Medicine Against Dementia Hebei Province Key Laboratory of Traditional Chinese Medicine Research and DevelopmentInstitute of Traditional Chinese MedicineChengde Medical College

[Objectives] To explore the inhibitory effects of flavonoids from scutellaria baicalensis Georgi stems and leaves against abnormal formation of PHF and regulation mechanism of protein phosphatase(PP) in okadaic acid(OA) induced brain injury in rats.[Methods]Male Sprague-Dawley rats were treated with OA(200 ng/kg) in the lateral ventricle to establish a memory impairment model,and Morris water maze was used to screen the memory impairment model.Rats were intragastrically administered with 25,50 and 100 mg/kg SSF daily for 36 d.The protein expressions of PHF,PP1,PP2A-Cα,PP2A-Cβ,PP2 CA and PP2 CB in rat cortex and hippocampus were determined by Western blot.Ginkgo biloba leaf flavonoids were used as positive control drugs.[Results]Compared with the sham-operated rats,the expression of PHF protein in the cortex and hippocampus of the model group was significantly increased(P < 0.01);protein expression of PP2A-Cα and PP2A-Cβin the cortex and hippocampus,and PP2 CB in the hippocampus were significantly decreased(P < 0.05);protein expression of PP2 CA and PP2 CB in the cortex was significantly increased(P < 0.01);protein expression of PP1 in the cortex was significantly decreased(P < 0.01).Compared with the model rats,25,50 and 100 mg/kg SSF 36 d reversed the protein expression of PHF,PP2A-Cα and PP2ACβ in rat cortex and hippocampus and expression of PP1 in rat cortex induced by OA,but had no significant effect on the protein expression of PP2 CA and PP2 CB,G.biloba flavonoids also showed similar results to SSF.[Conclusions] SSF can significantly inhibit the abnormal formation of PHF in rat brain induced by OA.The inhibitory effect may be related to the regulation of PP1,PP2A-Cα and PP2A-Cβ protein expression in cerebral cortex and hippocampus by SSF,but less related to the regulation of PP2 CA and PP2 CB.

关键词： Flavonoids from scutellaria baicalensis stems and leaves(SSF) Okadaic acid(OA) Protein phosphatase(PP) Paired helical filament(PHF) Alzheimer's disease(AD)

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Acute and 26-Week Repeated Oral Dose Toxicity Study of UP446, a Combination of <i>scutellaria</i>Extract and <i>Acacia</i>Extract in Rats

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Food and Nutrition Sciences 2013年第7期4卷 14-27页

作者： Young Chul Lee Eujin Hyun Mesfin Yimam Lidia Brownell Qi Jia Unigen Inc. Cheonan South Korea Unigen Inc. Seattle USA Unigen Inc. Seattle USA.

UP446 has been used in both joint supplements and prescription medical food. The purpose of this study was to evaluate the pharmaceutical safety of UP446 via acute and 26-week repeated oral dose toxicity study in SD rats. In acute toxicity study, UP446 was administered by oral gavage to Sprague-Dawley rats (5 males and 5 females) at a dose of 5000 mg/kg. In 26-week repeated oral dose toxicity study, UP446 at doses of 500, 1000 and 2000 mg/kg/day were given orally to groups of rats (10 rats/dose/sex) for 26-week. UP446 at a dose of 5000 mg/kg produced no treatment-related acute toxicity or mortality in any of the animals tested during 14 days of the study. In 26-week repeated dose toxicity study, there was no significant difference in body weight between the control and all treatment groups. Blackish stool and soft stool was observed in one male in the 1000 mg/kg group and in some males and females of 2000 mg/kg group. However, these changes of stool were not considered to be toxic effects because neither histopathological change in gastrointestinal tracks (GIT) nor body weight change were detected. No drug induced abnormalities were found as of body weights, food consumption, ophthalmological examinations, urinalysis, hematology, clinical chemistry, organ weights and gross necropsy in any animals in the dosing groups. These results suggest that the oral lethal dose of UP446 for male and female rats is in excess of 5000 mg/kg and the no observed adverse effect level (NOAEL) of the UP446 for both male and female rats is considered to be greater than 2000 mg/kg/day.

关键词： scutellaria baicalensis Acacia catechu Acute Oral Toxicity Repeated Oral Toxicity

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