Volume 12,Issue 4,2020 Table of Contents

1 Rudolf Bauer: China anti-COVID-19 success is closely related with the role TCM played

De-an Guo , Chang-xiao Liu

2020, 12(4). DOI: 10.1016/j.chmed.2020.09.001

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2 Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases

Bo-ning Ma , Xiao-jiaoyang Li

2020, 12(4). DOI: 10.1016/j.chmed.2020.07.003

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Lung diseases and their related complications represent a critical source of morbidity and mortality globally and have become a research focus in recent years. There are plenty of hazards that threaten the health of lung by exposure to external environmental stimuli, such as dust, cigarette smoke, PM2.5, air pollution and pathogen infection. These risks lead to the impairment of lung function and subsequent lung diseases including pneumonia, chronic obstructive pulmonary disease (COPD), asthma and idiopathic pulmonary fibrosis (IPF). Compared with antibiotics and corticosteroids therapies, traditional Chinese medicine prescriptions are more effective with fewer side effects. A considerable variety of bioactive ingredients have been extracted and identified from Chinese herbal medicines and are used for the treatment of different lung diseases, including resveratrol. Increasing studies have reported promising therapeutic effects of resveratrol against lung diseases by inhibiting oxidative stress, inflammation, aging, fibrosis and cancer both in vitro and in vivo. In this review, the recent progress in the studies of lung-protective effects and underlying mechanisms of resveratrol and also highlight the potency of resveratrol and traditional Chinese prescriptions containing resveratrol as promising therapeutic options were summarized for the treatment of lung and respiratory diseases.

3 Brusatol: A potential anti-tumor quassinoid from Brucea javanica

Xiao-qi Yua , Xin-yue Shanga , Xiao-xiao Huanga , Guo-dong Yaoa , b , Shao-jiang Songa

2020, 12(4). DOI: 10.1016/j.chmed.2020.05.007

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Brusatol, a triterpene lactone compound mainly from Brucea javanica, sensitizes a broad spectrum of cancer cells. It is known as a specific inhibitor of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. In this review, we provide a comprehensive overview on the antitumor effect and molecular mechanisms of brusatol in vitro and in vivo. This review also covers pharmacokinetics studies, modification of dosages forms of brusatol. Increasing evidences have validated the value of brusatol as a chemotherapeutic agent in cancers, which may contribute to drug development and clinical application.

4 Combined application of extended depth of field imaging, image stitching, and polarized microscopy techniques in identification of Spatholobus suberectus

Ying-xian Maa , Chayanis Sutcharitchanb , Xiao-die Lia , Qian Menga , Xin Wang a , Shen Jic , Ya-jun Cuia

2020, 12(4). DOI: 10.1016/j.chmed.2020.10.001

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Objective As traditional techniques for microscopic identification of Chinese medicines currently lack objective and high-quality reference images, here we developed a systemic procedure to be used in microscopic identification of Chinese medicines, which would lead to more objective, effective and accurate identification process. Methods Spatholobi Caulis (Jixueteng in Chinese) was used as the specimen in the development of such procedure. Jixueteng samples were microscopically examined in bright- and dark-field microscopy. Microscopic images were obtained by regular, EDF, and image stitching techniques. Results The microscopic images of the characteristics in pulverized Jixueteng were captured, thanks to EDF imaging and image stitching techniques which allowed the detailed and full sighting of each characteristic to be obtained simultaneously. Different layers in anatomical transverse section, including cork, phelloderm, cortex, phloem, cambium, xylem and pith, were distinctively observed. Moreover, by comparing images of bright- and dark-field microscopy, birefringent and non- birefringent components could readily be distinguished. Conclusion With application of the developed procedure, high-definition, panoramic, microscopic images were acquired, which could be used as the reference images for microscopic identification of Chinese medicines.

5 Complete chloroplast genome sequence of Amomum villosum and comparative analysis with other Zingiberaceae plants

Li Yang , Chong Feng , Miao-miao Cai , Jie-hu Chen , Ping Ding

2020, 12(4). DOI: 10.1016/j.chmed.2020.05.008

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Objective Amomum villosum (AV) is an herb whose dried fruit has been extensively used in modern medicine to treat digestive system diseases such as dysentery, vomiting and abdominal pain. This paper aims to supplement chloroplast (cp) genomic resources and to be used in phylogenetic studies and identification of AV related plants. Methods High-throughput sequencing technology was used to determine the complete sequence of the AV cp genome, and the sequence was then compared with three related species. Results The genome size of AV we obtained was 163,968 bp with an obvious tetrad structure. The AV cp genome was observed to contain 125 unique genes and 81 simple sequence repeat (SSRs) had been determined and the majority of which were adenine-thymine (AT)-rich. Comparative analysis of genome sequence of four ginger plants showed that the atpF, clpP and rpl32 genes are potential markers for identifying Amomum species. Phylogenetic analysis suggested that AV was closely related to A. kravanh and A. compactum. Conclusion These results have brought useful genetic resources for further identification researches, DNA barcoding, resolving taxonomy and understanding the evolutionary mode of Zingiberaceae cp genome.

6 Enzymatic synthesis of myricetin 3-O-galactoside through a whole-cell biocatalyst

Zhen Xu , Wei-qing He , Chun-sheng Liu , Jian-qiang Kong

2020, 12(4). DOI: 10.1016/j.chmed.2020.03.009

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Objective: Myricetin 3-O-galactoside is an active compound with pharmaceutical potential. The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-O-galactoside. Thus, it is necessary to develop a biosynthetic process for myricetin 3-O-galactoside through metabolic engineering. Methods: Two genes OcSUS1 and OcUGE1 encoding sucrose synthase and UDP-glucose 4-epimerase were introduced into BL21(DE3) to reconstruct a UDP-D-galactose (UDP-Gal) biosynthetic pathway in Escherichia coli. The resultant chassis strain was able to produce UDP-Gal. Subsequently, a flavonol 3-O-galactosyltransferase DkFGT gene was transformed into the chassis strain producing UDP-Gal. An artificial pathway for myricetin 3-O-galactoside biosynthesis was thus constructed in E. coli. Results: The obtained engineered strain was demonstrated to be capable of producing myricetin 3-O-galactoside, reaching 29.7 mg/L. Conclusion: Biosynthesis of myricetin 3-O-galactoside through engineered E. coli could be achieved. This result lays the foundation for the large-scale preparation of myricetin 3-O-galactoside.

7 Total alkaloids of Sophora alopecuroides- and matrine-induced reactive oxygen species impair biofilm formation of Staphylococcus epidermidis and increase bacterial susceptibility to ciprofloxacin

Fang Jiaa , Mei-yang Sunb , Xiang-jun Zhanga , Xue-zhang Zhoua

2020, 12(4). DOI: 10.1016/j.chmed.2020.02.006

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8 Antihyperglycemic and antihyperlipidemic activities of wild musk melon (Cucumis melo var. agrestis) in streptozotocin-nicotinamide induced diabetic rats

K. Gopalasatheeskumar a , G. Ariharasivakumar b , V. K. Kalaichelvan a , T. Sengottuvel b , V. Sanish Devan b , V. Srividhya b

2020, 12(4). DOI: 10.1016/j.chmed.2020.02.005

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Objective: Wild musk melon (Cucumis melo var. agrestis, CMA) is one of the edible plants form Tamil Nadu. Traditionally, this plant was used as diabetic diet (leaves of CMA with Momordica charantia leaves), but there is no scientific report on antidiabetic action of this plant material. Hence, the current research work was designed to evaluate its evaluate the anti-hyperglycemic and antihyperlipidemic effect of hydroalcoholic extract of CMA leaves (HALEC) in streptozotocin (STZ)-nicotinamide (NIC)-induced diabetic rats. Methods: Diabetes was induced by administration of STZ (60 mg/kg, i.p.) after 15 min of NIC (120 mg/kg i.p.) administration. The diabetic rats were treated with HALEC (300 and 600 mg/kg, p.o., respectively) for 21 d. Results: After the management with HALEC, blood glucose, HbA1c levels, total cholesterol, LDL cholesterol, triglycerides levels, glycogen phosphorylase and glucose-6-phosphatase levels were significantly diminished in diabetic rats. However, haemoglobin level, HDL cholesterol, liver glycogen, total protein, hexokinase, glucose-6-phosphate dehydrogenase levels were significantly increased in HALEC treated diabetic rats. The histopathological studies of the pancreas in HALEC-treated diabetic rats showed almost normal appearance. L6 cell line study revealed the increased glucose uptake activity of HALEC. High performance thin layer chromatography (HPTLC) analysis confirms the presence of active principles such as rutin, gallic acid and quercetin in HALEC. Conclusion: The results indicated that HALEC possess significant antihyperglycemic and antihyperlipidemic activity in STZ-NIC-induced type II diabetic rats with protective effect. This research work will be useful for the isolation of active principles and development of herbal formulation in phytopharmaceuticals.

9 In vitro and in silico anti-oxidant, cytotoxicity and biological activities of Ficus benghalensis and Duranta repens

Pukar Khanal , Basanagouda M. Patil

2020, 12(4). DOI: 10.1016/j.chmed.2020.02.004

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Objective: To report in vitro anti-oxidant activity and cytotoxicity of hydroalcoholic extract of Ficus benghalensis (bark) and Duranta repens(whole plant), and present the probable biological spectrum of major anti-oxidants from both plants. Methods: The coarse powder of both plants was first extracted with 70% ethanol (maceration) and followed by 99% ethanol (Soxhlet-extraction). Anti-oxidant activity of the extracts was evaluated by using DPPH, H2O2, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), NO scavenging assay, total antioxidant capacity, cupric reducing antioxidant capacity (CUPRAC), and metal chelating assay. Cytotoxicity of both extracts was evaluated by using MTT assay in both tumor and normal cell lines i.e. Chinese hamster ovary cells (CHO) and A549 cells. Biological activity of individual anti-oxidant compounds was identified by using prediction of activity spectra for substances and a docking study was performed by using autodock4.0. Results: Hydroalcoholic extract of F. benghalensis and D. repens showed the highest free radical scavenging capacity (ABTS) and chelating capacity respectively. Both extracts showed minimum cytotoxicity in normal cell lines compared to tumor cell lines. Computer imitation hits reflected the multiple biological activities agreeing with the folk use and some scientific reports. Further, we found the potent binding affinity of predicted anti-oxidant compounds with multiple protein molecules involved in oxidative stress. Conclusion: The present study reports the probable anti-oxidant mechanism for two folk agents and also presents probable pharmacological activities via computer simulations.

10 Long-term consumption of virgin coconut (Cocos nucifera) oil diet impairs learning and memory in CD1 mice

Sunday A. Bisonga , Clement O. Nkua , Olushola A. Sanyaa , Sunday O. Itab , Victor A. Fischerc , Favour E. Abuod

2020, 12(4). DOI: 10.1016/j.chmed.2020.03.008

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Objective: Virgin coconut oil (VCO) has been used in the management of dementia in Alzheimer’s disease (AD). Therefore, this research investigated the effect of long-term consumption of VCO diet on learning and memory in CD1 mice. Methods: Thirty male CD1 mice (divided into three groups, n = 10) were fed with standard rodent chow (control), 5% and 20% VCO diets (respectively) for 28 d. The Morris Water Maze (MWM) test was used to test the effect of VCO on visuo-spatial learning and memory, while the Novel Object Recognition Test (NORT) was used to measure short- and long-term recognition memory. Results: Learning performance of mice did not differ in the MWM. During the probe trial, duration in the retention quadrant and annulus crossings were lower (P < 0.05) in the 5% and 20% VCO diet groups compared to the control diet group, showing that VCO impaired visuo-spatial memory. During the NORT, mice showed more total approaches in the 20% VCO diet group (P < 0.05) compared to control and the 5% VCO diet groups during the short-term memory test. During the long-term memory retention test, the total approaches were also higher in the 20% VCO group compared to control and 5% VCO group (P > 0.05). The discrimination index was also lower in the 20% VCO group compared to control and 5% VCO diet groups indicating impaired long-term cognitive memory in mice given 20% VCO diet. Histological examination of brains showed damage within the CA1 pyramidal cell layer of the hippocampus in the 20% VCO diet group, in line with the behavioural observations. Conclusion: Long-term consumption of virgin coconut oil diet impairs memory in mice.

11 Shenqi Xingnao Granules ameliorates cognitive impairments and Alzheimer’s disease-like pathologies in APP/PS1 mouse model

Cui-cui Yanga , Xiao-yu Jiaa , Li Zhanga , Ya-li Li , Zhan-jun Zhangb , c , Lin Lia , Lan Zhanga

2020, 12(4). DOI: 10.1016/j.chmed.2020.04.005

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Objective: Alzheimer's disease?(AD) is along with cognitive decline due to amyloid-β (Aβ) plaques, tau hyperphosphorylation, and neuron loss.?Shenqi Xingnao Granules (SQXN), a traditional Chinese medicine, significantly ameliorated the cognitive function and daily living abilities of patients with AD. However, till date, no study has investigated the mechanism of action of SQXN on AD. The present study aimed to verify the effects of SQXN treatment on cognitive impairments and AD-like pathologies in APP/PS1 mice. Methods: Four-month-old?APP/PS1?transgenic (Tg) mice were randomly divided into a model group and SQXN-treated (3.5, 7, 14 g/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition test. All mice were sacrificed and the brain samples were collected after 75 d. The soluble Aβ contents were detected by Elisa kit; The levels of expression of NeuN, APP, phosphorylated tau and related protein were measured by Western blotting; The inflammation factors were detected by the proinflammatory panel kit. Results: Four-month-old?APP/PS1?mice were administered SQXN by oral gavage for 2.5 months. Using the Morris water maze tests and Novel object recognition, we found that SQXN restored behavioral deficits in the experimental group of Tg mice when compared with the controls. SQXN also inhibited neuronal loss?(NeuN?marker). SQXN treatment decreased soluble Aβ42 through inhibiting the expression of sAPPβ and BACE-1 without regulating full-length amyloid precursor protein (FL APP). Insulin degrading enzyme (IDE), the Aβ degrading enzyme, were increased by SQXN. In addition, SQXN reduced hyperphosphorylated tau protein levels and prevented excessive activation of p-GSK-3β in the brain of APP/PS1 mice. Compared with APP/PS1 transgenic negative mice, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-12p70, KC/GRO and TNF-α were not obviously changed in the brain of 6.5-month-old APP/PS1?transgenic (Tg) mice. However, SQXN could inhibited the expression of IL-2. Conclusion: These results demonstrate that SQXN ameliorates the cognitive impairments in APP/PS1 mice. The possible mechanisms involve its inhibition of neuronal loss, soluble Aβ deposition, tau hyperphosphorylation and inflammation.

12 Quantitative determination of multi-class bioactive constituents for quality assessment of ten Anoectochilus, four Goodyera and one Ludisia species in China

Yan-bin Wu a , Meng-chao Peng a , Chao Zhang a , Jian-guo Wu a , Bing-zhu Ye b , Jun Yi c , Jin-zhong Wu a , Cheng-jian Zheng b

2020, 12(4). DOI: 10.1016/j.chmed.2020.07.002

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Objective: To establish multi-class bioactive constituents’ determination of ten Anoectochilus, four Goodyera and one Ludisia species, and provide reference for the improvement of their quality control. Methods: HPLC-ELSD and phenol-sulphuric acid methods were used for the quantitative determination of lactone glycosides (kinsenoside and its diastereoisomer, gooderoside A) and polysaccharides, respectively, while an efficient iHPLC–MS/MS method was established for rapid determination of other minor constituents in ten Anoectochilus species and five related species. Results: The contents of kinsenoside, goodyeroside A, polysaccharides and flavonoids varied notably almost in all tested samples, including both wild plants and tissue cultures. In particular, kinsenoside was the major lactone glycoside in A. roxburghii, A. formosanus, A. xingrenensis, A. nandanensis, A. brevilabris and A. burmannicus, whereas goodyeroside A was the predominant constituent in A. lylei, A. longilobus, A. elatus, A. zhejiangensis, G. schlechtendaliana, G. biflora, G. yangmeishanensi, G. repens and Ludisia discolor. Conclusion: Our present study suggested that A. lylei, A. longilobus, A. elatus, A. zhejiangensis, Ludisia discolor and Goodyera species cannot be used as alternatives for A. roxburghii, and goodyeroside A may be reasonably used as a diagnostic marker for distinguishing A. roxburghii from A. lylei, A. longilobus, A. elatus and A. zhejiangensis, Goodyera and Ludisia species. The established method thus could be potentially used for the quality evaluation and control of Anoectochilus and some related species.

13 UGT88B2: A promiscuous O-glycosyltransferase from Carthamus tinctorius

Song-yang Suia , Rui-mingqian Guoa , Ke-bo Xieb , Lin Yanga

2020, 12(4). DOI: 10.1016/j.chmed.2020.05.010

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Objective: In order to obtain new glycosyltransferases with highly efficient catalysis, the glycosyltransferases from Carthamus tinctorius which contains diverse types of glycosides were mined. Methods: A new glycosyltransferase gene (UGT88B2) with full length was obtained by PCR and further transformed into Escherichia coli for heterologous expression. The catalytic activity of recombinant UGT88B2 was determined by HPLC-MSn. The structures of representative catalytic products were elucidated by MS and NMR. Results: UGT88B2 exhibited catalytic promiscuity and various patterns in glycosylation of flavonoids with high efficiency. Conclusion: A new glycosyltransferase named UGT88B2 was successfully mined and can be employed as enzymatic tools in glycosylation of flavonoids.

14 Comparative pharmacokinetics of baicalin and geniposide in juvenile and adult rats after oral administration of Qingkailing Granules

Ting-yu Li a , Zhong Li a , Xiao-yan Yang a , Xin-yu Zhao b , Xu Zhang a , Xin-bo Zhao a , Song Wang a , Xiao-kui Huo b , Xiao-ping Shi a

2020, 12(4). DOI: 10.1016/j.chmed.2020.05.011

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Objective: To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacokinetics of geniposide and baicalin in juvenile and adult rats. Methods: A simple and rapid LC-MS/MS method was developed and validated to simultaneously determine geniposide and baicalin in rat plasma after a simple protein precipitation. The analytes were separated on an Agilent ZORBAX Extend-C18 column. The mobile phase consisted of acetonitrile and water with 0.1% (volume percent) formic acid at a flow rate of 0.6 mL/min. The ionization was conducted using an ESI source in negative ion mode. Multiple reaction monitoring was used for quantification at transitions of m/z 445.0 → m/z 268.9 for baicalin, m/z 433.2 → m/z 225.0 for geniposide, m/z 431.0 → m/z 341.0 for vitexin (IS). Juvenile and adult rats were administrated Qingkailing Granules (3 g/kg) orally. Plasma concentrations of baicalin and geniposide were determined by LC-MS/MS. Results: The linear ranges of the analytes were 1–1000 ng/mL for baicalin and 2–2000 ng/mL for geniposide. The method was successfully applied to compare the pharmacokinetics of the analytes between juvenile and adult rats after oral administration of Qingkailing Granules. AUC was bigger in adult rats, while t1/2 was longer in juvenile rats. Conclusion: These results suggested that the absorption and elimination of baicalin and geniposide in juvenile rats was lower than that in adult rats. Additional attention should be paid to the pharmacokinetic difference when Qingkailing Granules were used in children.

15 Yanangdaengin, a dihydrochalcone glucoside galloyl ester as active antioxidative agent from leaves of Lysiphyllum strychnifolium (syn. Bauhinia strychnifolia)

Sumet Kongkiatpaiboona , Nongnaphat Duangdeea , Ngampuk Tayanaa , Johann Schinnerlb , Markus Bacherc , Savita Chewchindad

2020, 12(4). DOI: 10.1016/j.chmed.2020.05.009

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Objective: To isolate and identify the major bioactive components from the leaves of Lysiphyllum strychnifolium, an indigenous herb used in traditional Thai medicine for detoxification, longevity, and some other health related issues. Methods: Comparative HPLC analyses of the crude extracts from three provenances were carried out for an overview of characteristic compound profiles. Isolation of the major compounds was undertaken with chromatographic methods. Chemical structures were elucidated by NMR spectroscopic techniques and mass spectrometry. DPPH scavenging assay was carried out to determine the free radical scavenging activity of isolated compounds. Results: Yanangdaengin (3), a dihydrochalcone glucoside galloyl ester, has been isolated together with its corresponding dihydrochalcone glucoside trilobatin (2) as major compounds from the leaves of L. strychnifolium. Additionally, gallic acid (1) was co-chromatographically identified. Free radical scavenging activity of isolated compounds were determined. Compound 3 exhibited higher free radical scavenging activities in comparison to Trolox and quercetin. Conclusion: The isolated compounds could be used as chemical markers for quality assessment. The present work could promote the quality control and herbal medicinal product development of this plant.

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