Publications by authors named "Peigen Xiao"

121 Publications

A Bibliometrics Analysis of Metformin Development From 1980 to 2019.

Front Pharmacol 2021 28;12:645810. Epub 2021 Apr 28.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Metformin, the first-line oral blood glucose-lowering agent to manage type 2 diabetes, has gained growing popularity on both clinical application and basic research since early 1980s. A thorough and systematic knowledge map of metformin is pertinent to evaluate the research frontier and determine knowledge gaps. To this end, 20, 526 publications were analyzed by bibliometrics and data visualization to demonstrate the current global research status, potential hotspots, and perspectives on future research directions. In addition, the metformin development along the historical line was illustrated over the last 40 years. In sum, this study provides a comprehensive analysis that delineates the evolution of the historical milestones of metformin development, and we discuss the future research directions based on objective data analysis from a wide spectrum of metformin research areas.
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http://dx.doi.org/10.3389/fphar.2021.645810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113770PMC
April 2021

What's the choice for goji: Lycium barbarum L. or L. chinense Mill.?

J Ethnopharmacol 2021 Aug 6;276:114185. Epub 2021 May 6.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: For over one millennium, goji berries have been used traditionally as food and medicine in eastern Asia. In recent decades, it has become increasingly popular globally. However, the biocultural development of goji is poorly known. The botanical origin of goji is controversial: in many but not all modern regional or international quality standards, L. barbarum is accepted exclusively as the botanical origin of goji.

Aim Of The Study: Focusing on historical, biogeographical, botanical, phytochemical and pharmacological data, the overarching aim is to understand the biological origin of goji's historical uses, as well as whether the two species can be used interchangeably.

Materials And Methods: The taxonomic literature on L. barbarum and L. chinense were analysed, followed by a study of botanical specimens and fieldwork. Historical herbals and gazetteers were employed to define the historical producing areas and medical properties of goji. An identification of the species used in history was carried out. In a final step the phytochemical and pharmacological literature on the species was compared.

Results And Discussion: Due to their morphological similarity and different accessibility, fruits of both L. barbarum and L. chinense have been used interchangeably as food and medicine at least since 682 CE. While the fruit of L. barbarum was recognized to be superior in quality, the fruit of L. chinense was commonly used as an equivalent because of its easier accessibility. Cultivation of L. barbarum in China since 1960s improved its availability, which likely lead to its exclusive use as source of goji in China. The long-term safe use with no reported major safety concerns supports that these two species both are useful sources for medicinal Lycium.

Conclusions: Medicinal plants had been used traditionally long before they were named in scientific nomenclature system. Therefore, the understanding of traditional herbal knowledge and the adequate use of those traditional medicines require a reliable identification based on archival records. This study developed an approach for the identification of species used historically, with an integrated analysis of specimens, historical herbals, and national gazetteers. Additionally, their different chemical profiles and pharmacological activities indicate that they should not be used interchangeably. Further scientific evidence is required for their safe and effective use.
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http://dx.doi.org/10.1016/j.jep.2021.114185DOI Listing
August 2021

Correction: The chemopreventive effects of Huangqin-tea against AOM-induced preneoplastic colonic aberrant crypt foci in rats and omics analysis.

Food Funct 2021 Mar;12(5):2336-2337

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100193, China. and Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.

Correction for 'The chemopreventive effects of Huangqin-tea against AOM-induced preneoplastic colonic aberrant crypt foci in rats and omics analysis' by Jie Shen et al., Food Funct., 2020, 11, 9634-9650, DOI: 10.1039/D0FO01731K.
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http://dx.doi.org/10.1039/d1fo90005fDOI Listing
March 2021

Stilbenoids isolated from the roots of Rheum lhasaense under the guidance of the acetylcholinesterase inhibition activity.

J Nat Med 2021 Mar 7;75(2):372-380. Epub 2021 Jan 7.

Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China.

Four unknown stilbenoids, including one dimer, namely 4'-methoxy-scirpusin A (5) and three monomeric stilbene glycosides, namely piceatannol-3'-O-[2''-(3,5-dihydroxy-4-methoxybenzoyl)]-β-D-glucopyranoside (13), piceatannol-3'-O-(2''-galloyl)-β-D-glucopyranoside (14) and piceatannol-3'-O-(6″-p-coumaroyl)-β-D-glucopyranoside (16) together with 15 described compounds, were isolated from the ethyl acetate fraction of the ethanol extract of roots of Rheum lhasaense based on the guidance of the inhibitory effect on acetylcholinesterase. The structures of the unknown compounds were established by combined spectroscopic analysis and comparing their spectral data with compounds with similar structures. Some selected components were also investigated for their inhibitory abilities on acetylcholinesterase (AChE), indicating that compound 13 may be responsible for higher inhibitory activity of the ethyl acetate fraction on AChE.
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http://dx.doi.org/10.1007/s11418-020-01478-7DOI Listing
March 2021

Genus Paeonia: A comprehensive review on traditional uses, phytochemistry, pharmacological activities, clinical application, and toxicology.

J Ethnopharmacol 2021 Apr 24;269:113708. Epub 2020 Dec 24.

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: Paeonia, which comprises approximately 52 shrubs or herbaceous perennials around the world, is the only genus of the Paeoniaceae and is pervasively distributed in Asia, southern Europe, and North America. Many species of the genus Paeonia have been used for centuries in ethnomedical medical systems.

Aim Of The Review: The present study aims to summarize the traditional uses, clinical applications, and toxicology of the genus Paeonia, to critically evaluate the state-of-the-art phytochemical and pharmacological studies of this genus published between 2011 and 2020, and to suggest directions for further in-depth research on Paeonia medicinal resources.

Materials And Methods: Popular and widely used databases such as PubMed, Scopus, Science Direct, and Google Scholar were searched using the various search strings; from these searches, a number of citations related to the traditional uses, phytochemistry, biological activities, clinical application, and toxicology of the genus Paeonia were retrieved.

Results: The use of 21 species, 2 subspecies, and 7 varieties of the genus Paeonia as traditional herbal remedies has been reported, and many ethnomedicinal uses, such as the treatment of hematemesis, blood stasis, dysmenorrhea, amenorrhea, epilepsy, spasms, and gastritis, have been recorded. The roots and root bark are the most frequently reported parts of the plants used in medicinal applications. In phytochemical investigations, 451 compounds have been isolated from Paeonia plants to date, which contains monoterpenoid glucosides, flavonoids, tannins, stilbenes, triterpenoids and steroids, and phenols. Studies of their pharmacological activities have revealed the antioxidant, anti-inflammatory, antitumour, antibacterial, antiviral, cardiovascular protective, and neuroprotective properties of the genus Paeonia. In particular, some bioactive extracts and compounds (total glucosides of peony (TGP), paeonol, and paeoniflorin) have been used as therapeutic drugs or tested in clinical trials. In addition to the "incompatibility" of the combined use of "shaoyao" and Veratrum nigrum L. roots in traditional Chinese medicine theory, Paeonia was considered to have no obvious toxicity based on the available toxicological tests.

Conclusion: A large number of phytochemical and pharmacological reports have indicated that Paeonia is an important medicinal herb resource, and some of its traditional uses including the treatment of inflammation and cardiovascular diseases and its use as a neuroprotective agent, have been partially confirmed through modern pharmacological studies. Monoterpenoid glucosides are the main active constituents. Although many compounds have been isolated from Paeonia plants, the biological activities of only a few of these compounds (paeoniflorin, paeonol, and TGP) have been extensively investigated. Some paeoniflorin structural analogues and resveratrol oligomers have been preliminarily studied. With the exception of several species (P. suffruticosa, P. ostii, P. lactiflora, and P. emodi) that are commonly used in folk medicine, many medicinal species within the genus do not receive adequate attention. Conducting phytochemical and pharmacological experiments on these species can provide new clues that may lead to the discovery of medicinal resources. It is necessary to identify the effective phytoconstituents of crude extracts of Paeonia that displayed pharmacological activities by bioactivity-guided isolation. In addition, comprehensive plant quality control, and toxicology and pharmacokinetic studies are needed in the future studies.
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http://dx.doi.org/10.1016/j.jep.2020.113708DOI Listing
April 2021

Traditional uses, phytochemistry, pharmacology, and toxicology of Coreopsis tinctoria Nutt.: A review.

J Ethnopharmacol 2021 Apr 11;269:113690. Epub 2020 Dec 11.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: Coreopsis tinctoria Nutt. (family Asteraceae) is an important traditional medicine in North America, Europe, and Asia for quite a long historical period, which has received great attention due to its health-benefiting activities, including disinfection, treatment sexual infection, diarrhoea, acute and chronic dysentery, red-eye swelling as well as pain, heat, thirst, hypertension, palpitation, gastrointestinal discomfort, and loss of appetite.

Aim Of The Review: The purpose of this review is to give an overview of the current phytochemistry and pharmacological activities of C. tinctoria, and reveals the correlation among its traditional uses, phytochemistry, pharmacological profile, and potential toxicity.

Materials And Methods: This review is based on published studies and books from electronic sources and library, including the online ethnobotanical database, ethnobotanical monographs, Scopus, SciFinder, Baidu Scholar, CNKI, and PubMed. These reports are related to the traditional uses, phytochemistry, pharmacology, and toxicology of C. tinctoria.

Results: Coreopsis tinctoria is traditionally used in diarrhoea, infection, and chronic metabolic diseases. From 1954 to now, more than 120 chemical constituents have been identified from C. tinctoria, such as flavonoids, polyacetylenes, polysaccharides, phenylpropanoids, and volatile oils. Flavonoids are the major bioactive components in C. tinctoria. Current research has shown that its extracts and compounds possess diverse biological and pharmacological activities such as antidiabetes, anti-cardiovascular diseases, antioxidant, anti-inflammatory, protective effects on organs, neuroprotective effects, antimicrobial, and antineoplastic. Studies in animal models, including acute toxicity, long-term toxicity, and genotoxicity have demonstrated that Snow Chrysanthemum is a non-toxic herb, especially for its water-soluble parts.

Conclusions: Recent findings regarding the main phytochemical and pharmacological properties of C. tinctorial have confirmed its traditional uses in anti-infection and treatment of chronic metabolic disease and, more importantly, have revealed the plant as a valuable medicinal plant resource for the treatment of a wide range of diseases. The available reports indicated that most of the bioactivities in C. tinctorial could be attributed to flavonoids. However, higher quality studies on animals and humans studies are required to explore the efficacy and mechanism of action of C. tinctoria in future.
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http://dx.doi.org/10.1016/j.jep.2020.113690DOI Listing
April 2021

The chemopreventive effects of Huangqin-tea against AOM-induced preneoplastic colonic aberrant crypt foci in rats and omics analysis.

Food Funct 2020 Nov;11(11):9634-9650

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100193, China.

Despite that colorectal cancer (CRC) is a severe global health problem, effective chemopreventive strategies against CRC are still lacking. Huang-qin tea (HQT), a healthy herbal tea, is prepared from the aerial parts of Scutellaria baicalensis Georgi and has been consumed in China for thousands of years. HQT contains abundant flavonoids, which display potent anticancer effects, but no research studies have investigated the cancer-preventive effects of HQT on CRC in vivo. Here, we found that HQT inhibits azoxymethane-induced aberrant crypt foci (ACF) formation in a preneoplastic colonic ACF rat model. The essential role of the gut microbiota in the chemopreventive effect of HQT on CRC in a pseudo-germ-free rat model was confirmed. Besides, HQT modulates inflammatory cytokine expression by significantly decreasing IL-1β, IL-6, IL-10, and TNF-α expression, and elevating IFN-γ production. 16S rDNA sequencing analysis indicated that HQT regulated the gut microbiota by increasing the abundance of beneficial bacteria (Lachnoclostridium, Alistipes, Roseburia, and Lactococcus) and reducing the levels of Bacteroides, Parasutterella, and unidentified_Clostridiales. Fecal metabolomics showed that HQT modulated the AOM-induced metabolomic disorder, and these altered metabolites were almost involved in the lipid metabolic pathways. The Spearman correlation analysis revealed a correlation between the gut microbiota and fecal metabolites. Collectively, these results suggested that HQT exerted beneficial effects on host health by inhibiting inflammation, and by regulating the gut microbiota profile and certain metabolic pathways. In conclusion, HQT inhibits AOM-induced ACF formation by modulating the gut microbiota composition and improving metabolomic disorders, indicating the potential of HQT as a functional beverage candidate for the prevention and treatment of CRC.
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http://dx.doi.org/10.1039/d0fo01731kDOI Listing
November 2020

Target RNA modification for epigenetic drug repositioning in neuroblastoma: computational omics proximity between repurposing drug and disease.

Aging (Albany NY) 2020 Oct 12;12(19):19022-19044. Epub 2020 Oct 12.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.

RNA modifications modulate most steps of gene expression. However, little is known about its role in neuroblastoma (NBL) and the inhibitors targeting it. We analyzed the RNA-seq (n=122) and CNV data (n=78) from NBL patients in Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The NBL sub-clusters (cluster1/2) were identified via consensus clustering for expression of RNA modification regulators (RNA-MRs). Cox regression, principle component analysis and chi-square analysis were used to compare differences of survival, transcriptome, and clinicopathology between clusters. Cluster1 showed significantly poor prognosis, of which RNA-MRs' expression and CNV alteration were closely related to pathologic stage. RNA-MRs and functional related prognostic genes were obtained using spearman correlation analysis, and queried in CMap and L1000 FWD database to obtain 88 inhibitors. The effects of 5 inhibitors on RNA-MRs were confirmed in SH-SY5Y cells. The RNA-MRs exhibited two complementary regulation functions: one conducted by TET2 and related to translation and glycolysis; another conducted by ALYREF, NSUN2 and ADARB1 and related to cell cycle and DNA repair. The perturbed proteomic profile of HDAC inhibitors was different from that of others, thus drug combination overcame drug resistance and was potential for NBL therapy with RNA-MRs as therapeutic targets.
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http://dx.doi.org/10.18632/aging.103671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732279PMC
October 2020

Traditional uses, ten-years research progress on phytochemistry and pharmacology, and clinical studies of the genus Scutellaria.

J Ethnopharmacol 2021 Jan 30;265:113198. Epub 2020 Jul 30.

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: Scutellaria (Lamiaceae), which includes approximately 360-469 accepted species, is widespread in Europe, North America, East Asia, and South America. Several species have a long history being used as traditional medicines to treat respiratory, peptic, neurological, and hepatic and gall diseases. The phytochemistry and pharmacology of the genus Scutellaria have been developed dramatically in the past ten years, and the traditional uses and clinical studies of the genus have not been systematically summarized. Therefore, it is especially valuable to review the current state of knowledge to provide a basis for further exploration of its medicinal potential.

Aim Of The Review: The review aims to provide updated information on the ethnopharmacology, the ten-year research progress of phytochemistry and pharmacology, and clinical studies of Scutellaria and to explore the potential medicinal values and further studies of Scutellaria.

Materials And Methods: This review is based on published studies and books from the library and electronic sources, including SciFinder, Scopus, PubMed, Web of Science, Baidu Scholar, CNKI, the online ethnobotanical database, and ethnobotanical monographs. This literature is related to ethnopharmacology, the ten-year research progress on the phytochemistry and pharmacology, and clinical studies of Scutellaria.

Results: A total of 50 species, 5 subspecies and 17 varieties of the genus Scutellaria are used as traditional medicine with various biological activities. In the past ten years, 208 chemical constituents have been identified from 16 species and 1 variety of the genus Scutellaria, such as neo-clerodane diterpenoids, sesterterpenoids, terpenoids, flavonoids. Pharmacological research has demonstrated that the extracts and compounds identified from this genus exhibit extensive biological activities, including anticancer, antioxidant, anti-inflammatory, antiviral and antibacterial activities, effects on cardiovascular, cerebrovascular diseases as well as hepatoprotective and neuroprotective effects. The species S. baicalensis, S. barbata, and S. lateriflora and the main compounds baicalein, baicalin and wogonin are involved in clinical trials, which point the way for us to conduct further studies, such as study on the anticancer, antihypertensive, anti-infective, anti-inflammatory, neuroprotective and other effects of Scutellaria.

Conclusions: The species included in the genus Scutellaria can be used to treat cancer, infection, hepatic disorders, cardiovascular and cerebrovascular diseases, neurodegenerative diseases, and other diseases. Some indications in traditional medicines have been confirmed by modern pharmacological studies, such as anticancer, anti-inflammatory, anti-infective activity, and hepatoprotective and neuroprotective effects. The available literature indicated that most of the bioactivities could be attributed to flavonoids and neo-clerodane diterpenoids. Although there are some uses of Scutellaria in clinical practice, the existing research on this genus is still limited. In order to expand the development of medicinal resources of Scutellaria, the already studied species in this genus are recommended for more comprehensive investigation on their active substances, pharmacological mechanisms, quality control, clinical use and new drug research. Additionally, it is necessary to study species that their chemical composition or pharmacological activity have not yet been investigated, especially those used in folk medicine.
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http://dx.doi.org/10.1016/j.jep.2020.113198DOI Listing
January 2021

Transcriptome Sequencing and Chemical Analysis Reveal the Formation Mechanism of White Florets in L.

Plants (Basel) 2020 Jul 4;9(7). Epub 2020 Jul 4.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

L. (safflower), an economic crop and herb, has been extensively studied for its diverse chemical constituents and pharmacological effects, but the mechanism of safflower pigments (SP) leading to different colors of florets has not been clarified. In the present study, we compared the contents of SP in two varieties of safflower with white and red florets, named Xinhonghua No. 7 (WXHH) and Yunhong No. 2 (RYH). The results showed the contents of SP in RYH were higher than WXHH. To investigate genes related to SP, we obtained six cDNA libraries of florets from the two varieties by transcriptome sequencing. A total of 225,008 unigenes were assembled and 40 unigenes related to safflower pigment biosynthesis were annotated, including 7 unigenes of phenylalanine ammonia-lyase (PAL), 20 unigenes of 4-coumarate-CoA ligase (4CL), 1 unigene of trans-cinnamate 4-monooxygenase (C4H), 7 unigenes of chalcone synthase (CHS), 4 unigenes of chalcone isomerase (CHI), and 1 unigene of flavanone 3-hydroxylase (F3H). Based on expression levels we selected 16 differentially expressed unigenes (DEGs) and tested them using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR), which was consistent with the sequencing results. Consequently, we speculated that in WXHH, 3 , 3 , 1 , 1 , and 1 , which were down-regulated, and 1 , which was up-regulated, may play a key role in the formation of white florets.
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http://dx.doi.org/10.3390/plants9070847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412316PMC
July 2020

Resveratrol oligomers from Paeonia suffruticosa protect mice against cognitive dysfunction by regulating cholinergic, antioxidant and anti-inflammatory pathways.

J Ethnopharmacol 2020 Oct 19;260:112983. Epub 2020 May 19.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: Paeonia suffruticosa Andr. has been widely used in traditional Chinese medicine as an anti-tumour, anti-oxidant, anti-inflammatory and neuroprotective agent. Resveratrol oligomers are the main components of the seed coat extracts of Paeonia suffruticosa (PSCE) and have DPPH free radical scavenging and β-secretase inhibitory activity. However, studies of its effect on ameliorating cognitive deficits are limited, and analyses of the underlying mechanisms are insufficient.

Aim Of Study: This study aimed to investigate the cholinesterase inhibitory activities of resveratrol oligomers from P. suffruticosa in vitro and their effects on diminishing the oxygen-glucose deprivation/reoxygenation (OGD/R) -induced cytotoxicity in PC12 cells and scopolamine-induced cognitive deficits in mice. Moreover, the underlying mechanisms were further explored.

Materials And Methods: In vitro, the inhibitory effects of PSCE and its 10 stilbenes on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated using the Ellman's assay, and its protective effects on normal and OGD/R-injured PC12 cells were evaluated using the MTT assay. For the in vivo assay, C57BL/6 mice were orally administered with PSCE at doses of 150 and 600 mg/kg for 28 days, and injected with scopolamine (1.5 mg/kg) to induce cognitive deficits. The memory behaviours were evaluated using the novel object recognition, Morris water maze and inhibitory avoidance test. Levels of various biochemical markers were also examined, including AChE, choline acetyltransferase (ChAT), acetylcholine (ACh), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) in the mouse brain and interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4) in serum.

Results: PSCE and its 10 stilbenes display good inhibition of AChE and BuChE activities and significantly increase the viability of normal and OGD/R-injured PC12 cells. PSCE improves the cognitive performance of scopolamine-treated mice in behavioural tests. Meanwhile, PSCE increases AChE, ChAT, SOD, and CAT activities and ACh, GSH, IL-4 levels, and decreases IL-1β, IL-6, TNF-α levels in the model animals.

Conclusions: Resveratrol oligomers from P. suffruticosa show neuroprotective effect in vitro and in vivo by regulating cholinergic, antioxidant and anti-inflammatory pathways, may have promising application in the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.jep.2020.112983DOI Listing
October 2020

Liver Transcriptomic Reveals Novel Pathways of Empagliflozin Associated With Type 2 Diabetic Rats.

Front Endocrinol (Lausanne) 2020 17;11:111. Epub 2020 Mar 17.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

The hypoglycaemic target of empagliflozin (EMP), as a novel inhibitor of sodium-glucose cotransporter (SGLT2), is clear. However, recent studies have shown that EMP also has an important role in lipid metabolism and cardiovascular diseases. The liver plays an important role in the development of type 2 diabetes (T2D), although whether EMP affects liver glucose metabolism is currently not reported. This study was designed to evaluate the effect of EMP on hepatic glucose metabolism in T2D and the underlying mechanism. A model of T2D was established by a high-fat and glucose diet (HFD) combined with streptozotocin (30 mg/kg) in male Wistar rats. Serum samples were collected to measure biochemical indicators, and liver samples were extracted for RNA-seq assay. Quantitative real-time PCR (qPCR) was used to further verify the gene expression levels detected by the RNA-seq assay. The EMP group showed significantly decreased blood glucose, triglyceride, cholesterol, non-esterified fatty acid and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels in serum compared with the type 2 diabetes model (MOD) group. Furthermore, EMP decreased the levels of inflammatory factors IL-1β, IL-6, and IL-8 in the serum compared to the MOD. Liver transcriptome analysis showed EMP affects a large number of upregulated and downregulated genes. Some of these genes are novel and involve in the metal ion binding pathway and the negative regulation of transcription from the RNA polymerase II promoter pathway, which are also closely related to glucolipid metabolism and insulin signaling. Our study provides new knowledge about the mechanism through which SGLT inhibitor can offer beneficial effects in T2D and especially in the hepatic metabolism. These genes found in this study also laid a solid foundation for further research on the new roles and mechanisms of EMP.
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http://dx.doi.org/10.3389/fendo.2020.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092631PMC
February 2021

Metabolomics of the Protective Effect of and Its Major Active Compound Dihydromyricetin on the Liver of High-Fat Diet Hamster.

Evid Based Complement Alternat Med 2020 28;2020:3472578. Epub 2020 Jan 28.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 151 Malianwa North Road, Beijing 100193, China.

The flavonoid dihydromyricetin (DMY) is the main component of (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MS . Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.
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http://dx.doi.org/10.1155/2020/3472578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007936PMC
January 2020

Ultra-performance convergence chromatography, a more efficient method for chemical quality evaluation of Gaoben medicinal materials compared with the ultra-performance liquid chromatography.

J Chromatogr A 2020 Apr 29;1616:460755. Epub 2019 Nov 29.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.

Ultra-performance convergence chromatography (UPC2), which combines the advantages of both reversed phase liquid chromatography (RPLC) and gas chromatograph (GC), is a novel, eco-friendly analytical method and could be a powerful supplement for RPLC and GC. Based on these characteristics, an UPC2 method was developed for the chemical analysis of Gaoben medicinal materials including six batches of Ligusticum sinense, six batches of Ligusticum jeholense and six batches of Conioselinum vaginatum and compared with the results by ultra-performance liquid chromatography (UPLC) method at the same time. Six compounds were determined by UPC2 method, and eight compounds were quantitatively analyzed by UPLC method. Hierarchical cluster analysis (HCA) and principle component analysis (PCA) methods were used to elucidate the resemblance relationship among these 18 samples. The results showed the samples from same species analyzed by UPC2 method were grouped together respectively. However, UPLC method could not distinguish these three kinds of Gaoben medicinal materials effectively. The compounds determined by UPC2 method showed the chemical taxonomic significance than those of UPLC method, and were more suitable for chemical quality evaluation of Gaoben medicinal materials from different regions. This showed good complementarity between UPC2 and UPLC methods. And the UPC2 method might provide a more efficient analytical method for the chemical quality evaluation of medicinal materials rich in volatile oils, which would be a powerful supplement to the current quality evaluation.
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http://dx.doi.org/10.1016/j.chroma.2019.460755DOI Listing
April 2020

Screening of acetylcholinesterase inhibitors and characterizing of phytochemical constituents from Dichocarpum auriculatum (Franch.) W.T. Wang & P. K. Hsiao through UPLC-MS combined with an acetylcholinesterase inhibition assay in vitro.

J Ethnopharmacol 2019 Dec 22;245:112185. Epub 2019 Aug 22.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China. Electronic address:

Ethnopharmacological Relevance: The genus Dichocarpum is endemic to East Asia, and many of them are traditionally used folk medicine in China. Dichocarpum auriculatum (Franch.) W. T. Wang et P. K. Hsiao has the effect of clearing away heat, removing toxicity, and relieving swelling in southwestern China. Intriguingly, its root and whole herb also used as remedy for the neurological disease epilepsy. However, there are not any scientific reports on the phytochemistry and pharmacological activities of D. auriculatum.

Aim Of Study: Traditional and folk medicinal knowledge would be useful for finding new pharmaceutical resources. There are many evidences over the years reported that an interaction probably exists between epilepsy and Alzheimer's disease (AD). The aim of the study was to investigate the potential AChE inhibitors and the phytochemical profiles of the specie D. auriculatum.

Materials And Methods: The AChE inhibitory activity of plant extracts of D. auriculatum and other 6 species from different regions of the genus Dichocarpum were evaluated in vitro assays and the UPLC-Q-TOF-MS technique was used to analyze the chemical constituents. Moreover, UPLC-ESI-MS/MS was used to determine the distribution of 12 standard compounds in samples.

Results: As a preferred source of potential acetylcholinesterase inhibitors of the genus Dichocarpum, D. auriculatum has been further investigated. The screening results show that the ability of root extracts from D. auriculatum (IC = 0.15 mg·mL) to inhibit AChE was better than other samples, it is consistent with traditional medicinal records. The phytochemical constituents of D. auriculatum was surveyed firstly by UPLC-Q-TOF-MS analysis, and 36 compounds, including 14 alkaloids, 16 flavonoids, 6 others, were identified tentatively. Further experiments showed that five compounds (columbamine, palmatine, dauricine, jatrorrhizine and berberine) from D. auriculatum were confirmed the potential inhibition of AChE activity in vitro (IC: 0.24-6.37 μM) and UPLC-ESI-MS/MS results showed that the content of most active compounds in roots was much higher than in aerial parts. Palmatine (IC = 0.34 μM) and columbamine (IC = 0.24 μM) showed prominent AChE inhibitory activity among the tested compounds.

Conclusions: This is the first report about the evaluation of AChE inhibitory activity and phytochemical profiles of D. auriculatum, led to the identification of 36 compounds including alkaloids and flavonoids, and five alkaloids exhibited a significant AChE inhibitory activity and had the potential as AChE inhibitors. This study provided scientific experimental basis for the traditional efficacy of neurological disease of the plant.
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http://dx.doi.org/10.1016/j.jep.2019.112185DOI Listing
December 2019

Acteoside From (Roxb.) Blume Ameliorates Lipid Metabolism and Synthesis in a HepG2 Cell Model of Lipid Accumulation.

Front Pharmacol 2019 24;10:602. Epub 2019 May 24.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of ; the leaves of , known as kudingcha (bitter tea), have long been used in China as an herbal tea for weight loss. Recently, based on previous studies, our team reached a preliminary conclusion that phenylpropanoid glycosides from most likely contribute substantially to reducing lipid levels, but the mechanism remains unclear. Here, we conducted an screen of currently known phenylethanoid glycosides from and attempted to explore the hypolipidemic mechanism of ACT, the representative component of phenylethanoid glycosides in , using RNA-seq technology, quantitative real-time PCR (qPCR) and Western blotting. First, the screening results for six compounds were docked with 15 human protein targets, and 3 of 15 protein targets were related to cardiovascular diseases. Based on previous experimental data and docking results, we selected ACT, which exerted positive effects, for further study. We generated a lipid accumulation model using HepG2 cells treated with a high concentration of oleic acid and then extracted RNA from cells treated for 24 h with 50 μmol/L ACT. Subsequently, we performed a transcriptomic analysis of the RNA-seq results, which revealed a large number of differentially expressed genes. Finally, we randomly selected some genes and proteins for further validation using qPCR and Western blotting; the results agreed with the RNA-seq data and confirmed their reliability. In conclusion, our experiments proved that ACT from alters lipid metabolism and synthesis by regulating the expression of multiple genes, including , , , , , , , and , which are involved several pathways, such as the glycolytic, AMPK, and fatty acid degradation pathways.
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http://dx.doi.org/10.3389/fphar.2019.00602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543445PMC
May 2019

Dietary Supplementation of Vine Tea Ameliorates Glucose and Lipid Metabolic Disorder via Akt Signaling Pathway in Diabetic Rats.

Molecules 2019 May 15;24(10). Epub 2019 May 15.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.

A traditional Chinese tea with many pharmacological effects, vine tea (VT) is considered a potential dietary supplement to improve type 2 diabetes (T2D). To investigate the effect and mechanism of VT on glucose and lipid metabolic disorders in T2D rats, Wistar rats fed a normal diet served as the normal control, while rats fed a high-fat diet combined with low-dose streptozotocin (STZ)-induced T2D were divided into three groups: The model group (MOD); the positive control group (MET, metformin at 200 mg/kg/d); and the VT-treated group (VT500, allowed to freely drink 500 mg/L VT). After four weeks of intervention, biochemical metrics indicated that VT significantly ameliorated hyperglycemia, hyperlipidemia and hyperinsulinemia in T2D rats. Metabolomics research indicated that VT regulated the levels of metabolites closely related to glucose and lipid metabolism and promoted glycogen synthesis. Furthermore, VT had a significant influence on the expression of key genes involved in the Akt signaling pathway, inhibited gluconeogenesis through the Akt/Foxo1/Pck2 signaling pathway, and reduced fatty acid synthesis via the SREBP1c/Fasn signaling pathways. In conclusion, VT has great potential as a dietary supplement to ameliorate glucose and lipid metabolic disorders via the Akt signaling pathway in T2D rats.
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http://dx.doi.org/10.3390/molecules24101866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571802PMC
May 2019

Comprehensive metabolic profile analysis of the root bark of different species of tree peonies (Paeonia Sect. Moutan).

Phytochemistry 2019 Jul 29;163:118-125. Epub 2019 Apr 29.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.

Tree peonies (Paeonia Sect. Moutan) are well-known for their medicinal and ornamental uses but most wild species in the Moutan section are endangered. The comprehensive metabolomics evaluation of tree peonies is essential to distinguish different species and to identify undescribed compounds, thereby elucidating the diversity of their metabolites and discovering potential active ingredients. In this study, the metabolome variations of root barks of nine species and their varieties collected from one botanical garden after years of localization were systematically investigated. A digital database of specialized metabolites was established to improve feature identification or annotation and various bio- and cheminformatics tools were employed to analyse and visualize the profiled metabolomic data. As a result, 384 compounds were identified or annotated, including various monoterpene glycosides, flavonoids, phenols, terpenoids and steroids, tannins, stilbenes and others. All samples were clearly divided into two subsections: Vaginatae and Delavayanae. The distribution and abundance of metabolites were also analysed and discussed in order to find potential biomarkers in different wild tree peonies.
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http://dx.doi.org/10.1016/j.phytochem.2019.04.005DOI Listing
July 2019

Dihydromyricetin ameliorates memory impairment induced by acute sleep deprivation.

Eur J Pharmacol 2019 Jun 12;853:220-228. Epub 2019 Mar 12.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 151 Malianwa North Road, Beijing 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, 151 Malianwa North Road, Beijing 100193, China. Electronic address:

Dihydromyricetin (DHM), the major bioactive flavonoid ingredient extracted from the leaves of Ampelopsis grossedentata (Hand.-Mazz) W.T. Wang displays multiple pharmacological activities, including oxidation resistance, anti-tumour properties and free radical scavenging capacities. However, the role of DHM in sleep deprivation (SD)-induced memory impairments and its underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DHM on oxidative stress and its role in ameliorating memory impairment induced by acute SD. DHM (100, 50, 25 mg/kg) and melatonin (10 mg/kg) were administered to mice via oral gavage. The open field test was used to evaluate motor function. Spatial learning and memory were assessed using the Morris water maze task. Malondialdehyde, glutathione, and glutathione disulfide levels, as well as superoxide dismutase enzyme activity, were assessed to determine the level of oxidative stress. In addition, we employed quantitative real-time PCR assays to examine the gene expression of 29 key proteins, including protein kinase A (PKA), cAMP response element binding protein (CREB), and adcy1. The levels of proteins including those of GABAR, GABARα5, GluR1, BDNF and PSD95, were detected by western blotting. The results showed that DHM significantly attenuated SD-induced spatial learning and memory impairments (P < 0.01). The possible underlying mechanisms of DHM may be attributed to its ability to reduce oxidative stress and restore synaptic plasticity.
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http://dx.doi.org/10.1016/j.ejphar.2019.03.014DOI Listing
June 2019

Exploring on the bioactive markers of Codonopsis Radix by correlation analysis between chemical constituents and pharmacological effects.

J Ethnopharmacol 2019 May 16;236:31-41. Epub 2019 Feb 16.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine (Peking Union Medical College), Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: Codonopsis Radix is a commonly used traditional Chinese medicine, and has the effect of strengthening spleen and tonifying lung, nourishing blood and engendering liquid. In addition, it is also used as important food materials.

Aim Of The Study: The aim of the study was to explain the underlying correlations between chemical constituents and pharmacological effects and explore the bioactive markers of Codonopsis Radix.

Materials And Methods: Codonopsis Radix samples from Min county, Gansu province processed with different methods were taken as the materials, UPLC-ESI-Q-TOF-MS/MS analysis was conducted to identify the compounds and establish UPLC fingerprint. Meanwhile, hematopoietic and immunologic functions of Codonopsis Radix were investigated to obtain relevant pharmacological index. Then, the correlation analysis between chemical constituents in UPLC fingerprints and pharmacological effects was carried out. The plant name was confirmed to the database "The Plant List" (www.theplantlist.org).

Results: According to the results of canonical correlation analysis, tryptophan, syringin, tangshenoside I, codonopyrrolidium A, lobetyolin and two unknown compounds might be the potential bioactive markers related to the hematopoietic and immunologic functions of Codonopsis Radix, which could be recommended as the index compounds.

Conclusion: This study illustrated the underlying correlations between chemical constituents and pharmacological effects, explored the pharmacological material basis, and could lay a foundation for the improvement of quality standard of Codonopsis Radix.
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http://dx.doi.org/10.1016/j.jep.2019.02.032DOI Listing
May 2019

A Comprehensive Comparative Study for the Authentication of the Crude Drug.

Front Pharmacol 2018 22;9:1576. Epub 2019 Jan 22.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

The stems and roots of species have been used as the folk medicine in Traditional Chinese medicine (TCM) and have good traditional efficacy and medicinal application with a long history. Among these species, , and are the most widely distributed species in the regions of south and southwest China. Owing to their similar appearance, the crude drugs are often confusedly used by some folk doctors, even some pharmaceutical factories. To discriminate the crude drugs, haplotype analysis based on cpDNA markers and ITS was firstly employed in this study. Generic delimitation, interspecific interrelationships, and the identification of medicinal materials between and remained unresolved by the existing molecular fragments. The original plant could be identified through the morphological character of flower, fruit and leaf. However, in most situation collectors have no chance to find out these characters due to lack of reproductive organs, and have no experience with the minor difference and transitional variation of leaf morphology. The chemical characterization show that the chemometric of chemical composition owned higher resolution to discriminate three herbs of species. In conclusion, this integrative approach involving molecular phylogeny, morphology and chemical characterization could be applied for authentication of the . Our study suggests the use of this comprehensive approach for accurate characterization of this closely related taxa as well as identifying the source plant and confused herbs of TCM.
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http://dx.doi.org/10.3389/fphar.2018.01576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357937PMC
January 2019

Transcriptome analysis reveals the mechanism of the effect of flower tea Coreopsis tinctoria on hepatic insulin resistance.

Food Funct 2018 Nov;9(11):5607-5620

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.

Non-Camellia tea and herbal medicine help prevent the development of diabetes and other metabolic diseases. Previous studies revealed that Coreopsis tinctoria (CT) flower tea increases insulin sensitivity and, in some high-fat diet (HFD)-fed rats, even prevents hepatic metabolic disorders. However, the molecular mechanisms by which CT improves insulin resistance are not known. In this study, six-week-old rats were fed a normal diet (ND), an HFD or an HFD supplemented with CT for 8 weeks. Serum samples were collected, and the livers were extracted for RNA-seq gene expression analysis. Real-time PCR and western blotting further verified the RNA-seq results. In our results, dietary CT ameliorated HFD-induced hepatosteatosis, glucose intolerance, and insulin resistance. In the HFD group, 1667 differentially expressed genes (DEGs) were identified compared with the ND group. In the CT group, 327 DEGs were identified compared with the HFD group. Some of these DEGs were related to insulin signalling, hepatic lipogenesis and glucose homeostasis. This study suggested that insulin resistance with hyperinsulinaemia, and not insulin insufficiency, is an early problem in HFD-fed rats, and CT downregulates insulin secretion genes (e.g., Rasd1, Stxbp1 and Sfxn1). Hepatic gene and protein expression analyses indicated that the regulatory effects of CT on glucose and lipid homeostasis are likely mediated via the Akt/FoxO1 signalling pathway and are regulated by the transcription factors hairy and enhancer of split 1 (HES1) and small heterodimer partner (SHP). Our study provides transcriptomic evidence of the complex pathogenic mechanism involved in hepatic insulin resistance and proves that supplementation with CT improves insulin resistance at a global scale.
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http://dx.doi.org/10.1039/c8fo00965aDOI Listing
November 2018

In Investigation of the Pharmacological Mechanisms of Beneficial Effects of L. on Alzheimer's Disease.

Nutrients 2018 May 10;10(5). Epub 2018 May 10.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 151 Malianwa North Road, Beijing 100193, China.

Based on compelling experimental and clinical evidence, L. exerts a beneficial effect in ameliorating mild to moderate dementia in patients with Alzheimer’s disease (AD) and other neurological disorders, although the pharmacological mechanisms remain unknown. In the present study, compounds, their putative target proteins identified using an inverse docking approach, and clinically tested AD-related target proteins were systematically integrated together with applicable bioinformatics methods in . The results suggested that the beneficial effects of on AD may be contributed by the regulation of hormone sensitivity, improvements in endocrine homeostasis, maintenance of endothelial microvascular integrity, and proteolysis of tau proteins, particularly prior to amyloid β-protein (Aβ) plaque formation. Moreover, we identified six putative protein targets that are significantly related to AD, but have not been researched or have had only preliminary studies conducted on the anti-AD effects of . These mechanisms and protein targets are very significant for future scientific research. In addition, the existing mechanisms were also verified, such as the reduction of oxidative stress, anti-apoptotic effects, and protective effects against amyloidogenesis and Aβ aggregation. The discoveries summarized here may provide a macroscopic perspective that will improve our understanding of the molecular mechanism of medicinal plants or dietary supplements, as well as new clues for the future development of therapeutic strategies for AD.
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http://dx.doi.org/10.3390/nu10050589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986469PMC
May 2018

Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet.

Front Pharmacol 2018 6;9:333. Epub 2018 Apr 6.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Maca ( Walpers) has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM) on high-fat, high-fructose diet (HFD)-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects. For 20 weeks, 6-week-old male golden hamsters were fed the following respective diets: (1) a standard diet, (2) HFD, (3) HFD supplemented with metformin, or (4) HFD supplemented with three doses of AEM (300, 600, or 1,200 mg/kg). After 20 weeks, the golden hamsters that received daily AEM supplementation presented with the beneficial effects of improved hyperlipidemia, hyperinsulinemia, insulin resistance, and hepatic steatosis . Based on the hepatic metabolomic analysis results, alterations in metabolites associated with pathological changes were examined. A total of 194 identified metabolites were mapped to 46 relative metabolic pathways, including those of energy metabolism. In addition, via profiling for secondary maca metabolites by a joint pharmacophore- and structure-based approach, a compound-target-disease network was established. The results revealed that 32 bioactive compounds in maca targeted 16 proteins involved in metabolism disorder. Considering the combined metabolomics and virtual screening results, we employed quantitative real-time PCR assays to verify the gene expression of key enzymes in the relevant pathways. AEM promoted glycolysis and inhibited gluconeogenesis via regulating the expression of key genes such as and . Moreover, AEM upregulated tricarboxylic acid (TCA) cycle flux by changing the concentrations of intermediates and increasing the mRNA levels of , , and . In addition, the lipid-lowering effects of AEM in boththe serum and liver may be partly related to PPARα signaling activation, including enhanced fatty acid β-oxidation and lipogenesis pathway inhibition. Together, our data demonstrated that AEM intervention significantly improved lipid and glucose metabolism disorder by regulating the glycolysis/gluconeogenesis-TCA cycle and by modulating gene expression levels involved in the PPARα signaling pathway.
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http://dx.doi.org/10.3389/fphar.2018.00333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897445PMC
April 2018

The genus Polygonatum: A review of ethnopharmacology, phytochemistry and pharmacology.

J Ethnopharmacol 2018 Mar 12;214:274-291. Epub 2017 Dec 12.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Ethnopharmacological Relevance: The genus Polygonatum (Asparagaceae) comprises 71 species distributed throughout the temperate Northern Hemisphere. The medicinal plants of Polygonatum have been traditionally used as tonics in China, India, Pakistan, Iran and Japan, and have been demonstrated to be highly effective in clinical practice for treating age-related diseases, diabetes, lung diseases, fatigue, feebleness and indigestion.

Aim Of The Review: This paper aims to provide the links among traditional uses, chemical constituents, pharmacological effects and toxicity to support their therapeutic potential and uncover opportunities for future research.

Materials And Methods: The relevant information on the genus Polygonatum was gathered from scientific databases (Google Scholar, Web of Science, SciFinder, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, CNKI). Information was also obtained from online databases, books, Ph.D. dissertations and M.Sc. theses. The literature cited in this review dates from 1917 to June 2017.

Results: At least 37 species and 1 variety of Polygonatum plants have been used as traditional medicine and functional food. The major chemical constituents of Polygonatum plants are steroidal saponins, triterpenoid saponins, homoisoflavanones, polysaccharides and lectins. A putative biosynthetic pathway of steroidal saponins and triterpenoid saponins has been established based on the compounds isolated from Polygonatum plants. The crude extracts and certain pure compounds from Polygonatum plants have shown a wide range of pharmacological effects such as anti-aging, anti-diabetic, anti-fatigue, and anticancer effects. The rhizomes of Polygonatum plants have a low degree of toxicity after processing.

Conclusions: Based on this review, some traditional uses of Polygonatum species have been confirmed by pharmacological studies, such as its anti-osteoporosis, neuroprotective, immunomodulatory, anti-diabetic and anti-fatigue effects. Most of the pharmacological effects of this genus can be attributed to its polysaccharides, saponins and lectins. However, to clarify the chemical differences that lead to the different traditional uses between "Huangjing" (derived from P. sibiricum, P. kingianum, P. cyrtonema) and "Yuzhu" (derived from P. odoratum), a systematic comparison of the small molecule compositions and polysaccharides of these four species is needed. In addition to these four species, other locally used medicinal Polygonatum species should be the subject of research, and the chemical and pharmacological relationships of these species should be investigated to expand the medicinal resources and standardize the use of Polygonatum species.
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http://dx.doi.org/10.1016/j.jep.2017.12.006DOI Listing
March 2018

Update on Phytochemistry and Pharmacology of Naturally Occurring Resveratrol Oligomers.

Molecules 2017 11 24;22(12). Epub 2017 Nov 24.

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100193, China

Resveratrol oligomers (REVs), a major class of stilbenoids, are biosynthesized by regioselective oxidative coupling of two to eight units of resveratrol monomer. Due to their unique structures and pleiotropic biological activities, natural product chemists are increasingly focusing on REVs in the last few decades. This study presents a detailed and thorough examination of REVs, including chemical structures, natural resources, and biological activities, during the period of 2010-2017. Ninety-two new REVs compounds, including 39 dimers, 23 trimers, 13 tetramers, six resveratrol monomers, six hexamers, four pentamers, and one octamer, have been reported from the families of Dipterocarpaceae, Paeoniaceae, Vitaceae, Leguminosae, Gnetaceae, Cyperaceae, Polygonaceae Gramineae, and Poaceae. Amongst these families, Dipterocarpaceae, with 50 REVs, accounts for the majority, and seven genera of Dipterocarpaceae are involved, including , , , , , , and . These REVs have shown a wide range of bioactivities. Pharmacological studies have mainly focused on potential efficacy on tumors, bacteria, Alzheimer's disease, cardiovascular diseases, and others. The information updated in this review might assist further research and development of novel REVs as potential therapeutic agents.
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http://dx.doi.org/10.3390/molecules22122050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149893PMC
November 2017

Chemopreventive effects of Ku-jin tea against AOM-induced precancerous colorectal lesions in rats and metabolomic analysis.

Sci Rep 2017 Nov 21;7(1):15893. Epub 2017 Nov 21.

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100193, People's Republic of China.

Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.
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http://dx.doi.org/10.1038/s41598-017-16237-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698479PMC
November 2017

DPPH Radical Scavenging and Postprandial Hyperglycemia Inhibition Activities and Flavonoid Composition Analysis of Hawk Tea by UPLC-DAD and UPLC-Q/TOF MS.

Molecules 2017 10 13;22(10). Epub 2017 Oct 13.

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Hawk tea ( Lévl. var. (Migo) Yen C. Yang & P.H. Huang), a very popular herbal tea material, has attracted more and more attention due to its high antioxidant properties and possible therapeutic effect on type II diabetes mellitus. The raw materials of Hawk tea are usually divided into three kinds: bud tea (BT), primary leaf tea (PLT) and mature leaf tea (MLT). In this study, the DPPH radical scavenging activity and the antimicrobial properties of these three kinds of Hawk tea from different regions were comparatively investigated, and a ultra-high performance liquid chromatographic coupled with a photodiode array detector (UPLC-DAD) method was employed for comparison of the three major flavonoid constituents, including hyperoside, isoquercitrin and astragalin, in different samples of Hawk tea. At the same time, the effect of methanol extract (ME) of PLT on the mouse postprandial blood glucose and the effect of ME and its different fractions (petroleum ether fraction (PE), ethyl acetate fraction (EA), -butanol fraction (-BuOH), and water fraction (WF)) on the activity of α-glucosidase were studied. The results showed that Hawk BT and Hawk PLT possessed the higher radicals scavenging activity than Hawk MLT, while the antibacterial activity against of PLT and MLT was higher than Hawk BT. The contents of the three major flavonoid constituents in samples of Hawk PLT are higher than Hawk BT and Hawk MLT. The mouse postprandial blood glucose levels of the middle dose (0.5 g/kg) group and the high dose (1 g/kg) group with oral administration of the ME of PLT were significantly lower than the control group. What's more, the inhibitory effect of ME of PLT and its EA and -BuOH fractions on α-glucosidase was significantly higher than that of acarbose. Rapid ultra-high performance liquid chromatography/quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was used to identify the flavonoids in Hawk PLT, and a total of 20 flavonoids were identified or tentatively identified by comparing their retention times and accurate mass measurements with reference compounds or literature data. The bioactive flavonoid composition and DPPH radical scavenging activities present in different Hawk tea raw materials are quite different due to the different ontogenesis of these raw materials. Further studies on PLT showed that the substances in PLT ME could reduce the level of mouse postprandial blood glucose through inhibiting the activity of α-glucosidase.
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http://dx.doi.org/10.3390/molecules22101622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151479PMC
October 2017

Metabolomics reveals that vine tea (Ampelopsis grossedentata) prevents high-fat-diet-induced metabolism disorder by improving glucose homeostasis in rats.

PLoS One 2017 16;12(8):e0182830. Epub 2017 Aug 16.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Vine tea (VT), derived from Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang, is an alternative tea that has been consumed widely in south China for hundreds of years. It has been shown that drinking VT on a daily basis improves hyperlipidemia and hyperglycemia. However, little is known about the preventive functions of VT for metabolic dysregulation and the potential pathological mechanisms involved. This paper elucidates the preventive effects of VT on the dysregulation of lipid and glucose metabolism using rats maintained on a high-fat-diet (HFD) in an attempt to explain the potential mechanisms involved.

Methods: Sprague Dawley (SD) rats were divided into five groups: a group given normal rat chow and water (control group); a group given an HFD and water (HFD group); a group given an HFD and Pioglitazone (PIO group), 5 mg /kg; and groups given an HFD and one of two doses of VT: 500 mg/L or 2000 mg/L. After 8 weeks, changes in food intake, tea consumption, body weight, serum and hepatic biochemical parameters were determined. Moreover, liver samples were isolated for pathology histology and liquid chromatography-mass spectrometry (LC-MS)-based metabolomic research.

Results: VT reduced the serum levels of glucose and total cholesterol, decreased glucose area under the curve in the insulin tolerance test and visibly impaired hepatic lipid accumulation. Metabolomics showed that VT treatment modulated the contents of metabolic intermediates linked to glucose metabolism (including gluconeogenesis and glycolysis), the TCA cycle, purine metabolism and amino acid metabolism.

Conclusion: The current results demonstrate that VT may prevent metabolic impairments induced by the consumption of an HFD. These effects may be caused by improved energy-related metabolism (including gluconeogenesis, glycolysis and TCA cycle), purine metabolism and amino acid metabolism, and reduced lipid levels in the HFD-fed rats.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182830PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558946PMC
October 2017

Complete chloroplast genome sequences of Schisandra chinensis: genome structure, comparative analysis, and phylogenetic relationship of basal angiosperms.

Sci China Life Sci 2017 11 17;60(11):1286-1290. Epub 2017 Jul 17.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.

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http://dx.doi.org/10.1007/s11427-017-9098-5DOI Listing
November 2017