Volume 11,Issue 3,2019 Table of Contents

1 Building a bridge between ecology and Chinese herbal medicined

Fang Rui

2019, 11(3). DOI: 10.1016/j.chmed.2019.07.002

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2 An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s

Zi-jun?Wua , Li-li?Wang?a , b , Xue?Gaoa , Yue?Hai?a , Wen-li?Liua , Le-mei?Dua , Lei?Zhanga , Ai-hong?Yang?a , b , Nan-nan?Huanga

2019, 11(3). DOI: 10.1016/j.chmed.2019.07.001

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Reactive metabolites (RMs) generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI). Like many synthetic drugs undergoing metabolic activation to form RMs which are often associated with drug toxicity, it is recognized that some herbal components may be also converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYP450s). This review focuses on the metabolic activation of herbal components and its liver toxicological implications. By summarizing references, we found that hepatotoxic herbal components via producing RMs have some certain structural dependence. There is a correlation between the generation of RMs and the structures, which provides a good chance for the early discovery of toxic ingredients in Traditional Chinese medicines (TCMs): i) A potential hepatotoxic component information database based on active functional groups can be built, which might provide an early information for the basic research of hepatotoxic substances in TCMs; ii) RMs can combine with CYP450s to form a complete antigen, which eventually leads to an antigen-specific immune response. RMs-CYP450 protein complete antigen can be set up, and the potential idiosyncratic liver toxicity might be predicted by testing RMs-CYP450 protein antibody in plasma.

3 Towards a scientific rationale for traditional properties of Chinese medicinal plants: a€?naturesa€? and a€?flavorsa€?

Li-ping?Li?a , b , Ben-gang?Zhangb , c , ? , Zhao?Zhangb , Xiao-jin?Lic , Guo-ping?Wang?c , Hai-long?Songc , Cong-zhao?Fanc , Yang-ming?Jianga , Tuo?Wanga , Hui-hui?Zhaoa , Jiang-shan?Lai?d , Xiu-lian?Chi?e , Xue-ping?Wei?b , Chong-ming?Wub , Yao-dong?Qi?b , Hai-tao?Liu?b , Pei-gen?Xiaob , Eimear Nic Lughadhaf , Christine J. Leong

2019, 11(3). DOI: 10.1016/j.chmed.2019.05.002

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Objective According to theory of Chinese medicine property, the ecological environment shapes properties (natures and flavors) of Chinese materia medica (CMM) and there are close relationships between certain natures and flavors. However, to date these observations have not been validated scientifically in the context of the whole flora of a region. The present study aims to address this gap. Methods We collected geographical distributions of 3637 vascular plant species native to the Xinjiang region of northwest China, of which around 812 are medicinal plants. The CMM property characters of these medicinal plants were also collected. All medicinal plants were then analyzed in the occurrence of their natures (cold, cool, neutral, warm, and hot) and flavors (sweet, bitter, sour, salty, and pungent). Possible correlations between these properties and environmental factors, notably climate, as well as correlations with plant species richness of the wider native flora of Xinjiang were then investigated using permutation test and regression. Results Cold species (38.5%) were more numerous than warm (21.0%) and neutral (22.3%), while bitter species (43.3%) were more numerous than pungent (25.6%), sweet (22.4%) and sour (6.7%) ones. Species with bitter flavor were most commonly also cold (48.6%) in nature, sour flavor usually coincided with cold (44.2%) or cool nature (26.0%), whereas pungent or sweet species tended to be warm (34.4%, 28.4%) or neutral (27.8%, 28.4%). The percentages of species of cold/cool nature, bitter flavor were higher in mountainous regions, and the percentages of warm/neutral and pungent/sweet/sour were higher in basins. The percentages of species of bitter, cold/cool, bitter were positively correlated with actual evapotranspiration (AET), plant species richness andbut had a bell-shaped relationship with potential evapotranspiration (PET), whereas the inverse situation was shown for warm/neutral and pungent/sweet/sour species. Conclusion Analysis of the data in Xinjiang region of China supports the qualitative observations concerning natures and flavors in traditional theory of Chinese medicine property. Specifically, (i) certain natures and flavors co-occur more frequently than if randomly distributed; (ii) correlations between proportions of natures and flavors and climatic variables suggest a role for the environment in shaping the properties of CMM.

4 Parasitic relationship of Cistanche deserticola and host-plant Haloxylon ammodendron based on genetic variation of host

Liang Shena , b , Rong Xua , ? , Sai Liua , Chang-qing Xua , Fang Penga , Xiao-jin Lic , Guo-qiang Zhuc , Cai-xiang Xiea , Jun Zhuc , Tong-ning Liud , Jun Chena , ?

2019, 11(3). DOI: 10.1016/j.chmed.2019.04.006

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Objective Cistanche deserticola is a famous and endangered medicinal plant that is parasitic upon Haloxylon ammodendron with rather low parasitic rates. It is important to find high affinity germplasms for increasing the survival of C. deserticola. However, little is known in genetic variation and high affinity populations of H. ammodendron in China. Methods In this study, 98 accessions of H. ammodendron seeds were collected from five regions covering almost the entire natural distribution of H. ammodendron in China. Their genetic variations were analyzed using AFLP and ITS by the maximum parsimony method, and a dendrogram was constructed using the unweighted pair-group method with arithmetic average (UPGMA). The parasitic rates of C. deserticola on different accessions of H. ammodendron were calculated in the field experiment. Results Both AFLP and ITS methods consistently revealed that there was a high level of genetic diversity in the natural populations of H. ammodendron. Hierarchical population structure analysis uncovered a clear pattern that all populations were grouped into three main clusters, and eight populations from eastern region were genetically clustered together. These regions were significantly differentiated (P < 0.05), 13.10% of variation occurred among populations, and 86.90% within populations was revealed by analysis of molecular variance (AMOVA). The populations of Inner Mongolia had the highest parasitic rates followed by Ganjiahu Reserve and Yongning Plantation for the top three, which were not completely related to the genetic variation. Conclusion Genetic characteristics of H. ammodendron in China were clarified and the order of affinity of different populations was given, which were primers for discovering high affinity germplasms.

5 Identification of flower herbs in Chinese pharmacopoeia based on DNA barcoding

Xue-min Wei , Xiao-yue Wang , Zi-tong Gao , Pei Cao , Jian-ping Han

2019, 11(3). DOI: 10.1016/j.chmed.2019.05.003

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Objective Flower herbs are an important category of traditional Chinese medicinal materials, some of which are used as healthcare tea in folk. However, the increasing adulteration of medicinal herbs is threatening consumer safety. The adulteration of flower herbs and their healthcare tea products in the market were investigated. Methods A total of 33 flower herb samples from several retail pharmacies in China were randomly collected and 27 flower healthcare tea samples were purchased online. They were identified using ITS2-based Traditional Chinese Medicine Database (TCMD). Additionally, Lonicerae Japonicae Flos and the adulterants were compared in the ITS2 secondary structures. Results There were one adulterant (Inulae Flos) in flower herb materials and eight adulterants in healthcare tea samples. Inula linariifolia was an adulterate species of Inulae Flos, Robinia pseudoacacia was of Sophorae Flos, and Lonicera macranthoides was of Lonicerae Japonicae Flos. Sophorae Flos and Lonicerae Japonicae Flos were two healthcare tea products with high adulteration rates. Conclusion The TCMD is powerful tool to identify flower herbs and the adulterants that frequently occurred in the flower herb market, especially online shops.

6 Mechanisms of Chinese medical formula Fangji Huangqi Decoction as an effective treatment of nephrotic syndrome based on systems pharmacology

Xue-min Wei , Xiao-yue Wang , Zi-tong Gao , Pei Cao , Jian-ping Han

2019, 11(3). DOI: 10.1016/j.chmed.2019.05.005

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Objective: Flower herbs are an important category of traditional Chinese medicinal materials, some of which are used as healthcare tea in folk. However, the increasing adulteration of medicinal herbs is threatening consumer safety. The adulteration of flower herbs and their healthcare tea products in the market were investigated. Methods: A total of 33 flower herb samples from several retail pharmacies in China were randomly collected and 27 flower healthcare tea samples were purchased online. They were identified using ITS2-based Traditional Chinese Medicine Database (TCMD). Additionally, Lonicerae Japonicae Flos and the adulterants were compared in the ITS2 secondary structures. Results: There were one adulterant (Inulae Flos) in flower herb materials and eight adulterants in healthcare tea samples. Inula linariifolia was an adulterate species of Inulae Flos, Robinia pseudoacacia was of Sophorae Flos, and Lonicera macranthoides was of Lonicerae Japonicae Flos. Sophorae Flos and Lonicerae Japonicae Flos were two healthcare tea products with high adulteration rates. Conclusion: The TCMD is powerful tool to identify flower herbs and the adulterants that frequently occurred in the flower herb market, especially online shops.

7 Berberine reverses LPS-induced repression of CYP7A1 through an anti-inflammatory effect

Bei?Caoa , Run-bin?Sunb , Yan Genga , Guang-yu?Yang?a , Ji-ye?Aa?b , ? , Juan?Lia , ?

2019, 11(3). DOI: 10.1016/j.chmed.2019.05.004

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8 In vivo antiplasmodial potential of three herbal methanolic extracts in mice infected with Plasmodium berghei NK65

Pachiyappan Rajiv Gandhia , Chinnaperumal Kamarajb , ? , Elangovan Vimalkumara , Selvaraj Mohana Roopanc , ?

2019, 11(3). DOI: 10.1016/j.chmed.2019.06.002

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Objective The present study deals with the investigation of antiplasmodial potential of leaf methanolic extract of Aegle marmelos, Aristolochia indica and Cassia auriculata against Plasmodium berghei (NK65) infected mice. Methods The chloroquine-sensitive parasites P. berghei (1?×?106) were inoculated into Swiss albino mice intraperitoneally. The methanol extracts of three herbal plants were orally administered in P. berghei infected mice which were further assessed using the 4 d suppressive test at different doses of 150, 300 and 600?mg/kg per d. Chloroquine (CQ) was used as the standard drug with of 1.25, 2.5 and 5?mg/kg concentrations and was orally administered. Results The leaves of A. marmelos, A. indica, and C. auriculata were found to suppress P. berghei parasitaemia in Swiss albino mice by (67.0 0?±?4.02) %, (72.0 0?± 8.44)% and (52.7 7?±?2.06)% at 600?mg/kg/d with ED50 values of 284.73, 233.77 and 562.48?mg/kg, respectively. These herbal plants increased the mean survival time of infected mice and prevented body weight loss. GC-MS analysis revealed the presence of hentriacontan-16-one (C31H62O) in A. indica extract. The histopathology study showed non-toxic to kidney and liver at 600?mg/kg/body weight. Conclusions Overall results revealed that herbal plants may be active in the development of novel and cheap antimalarial compounds.

9 Effects of Raphani Semen on anti-fatigue and pharmacokinetics of Panax ginseng

Jian-bo?Chen , Mei-jia?Li , Li-xue?Chen , Yin-shi?Sun

2019, 11(3). DOI: 10.1016/j.chmed.2019.05.001

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Objective To explain the phenomenon that Panax ginseng is not compatible with Raphani Semen based on pharmacodynamics and pharmacokinetics. Methods The forced swimming time and biochemical parameters such as blood lactate (BLA), serum urea nitrogen (SUN), and hepatic glycogen (GLU) were determined for anti-fatigue experiment. The UPLC-MS/MS was used to analyze the pharmacokinetics of Rg1, Re, Rb1, and Rd after orally administration of P. ginseng and P. ginseng combined with Raphani Semen to rats. Pharmacokinetic differences of four ginsenosides between single uses of P. ginseng and combined with Raphani Semen were investigated. Results The results showed that Raphani Semen tended to significantly reduce the anti-fatigue activity of P. ginseng. Co-administration of P. ginseng and Raphani Semen had significant effects on the pharmacokinetics of the four ginsenosides in rats compared to that observed with P. ginseng extract alone. The AUC0–12?h values of the four ginsenosides in PG group were higher than the corresponding values in the PR group. It can be inferred that Raphani Semen decreased the blood exposure of the four ginsenosides in rats when it combined with P. ginseng. Conclusion The anti-fatigue activity and pharmacokinetic results showed that Raphani Semen may reduce the pharmacological actions of P. ginseng.

10 Comparative pharmacokinetics of naringin and neohesperidin after oral administration of flavonoid glycosides from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders mice

Zhi-rua Xu , Chun-hongc Jiang , Si-yangb Fan , Ren-jiea Yan , Ningc Xie , Chun-zhenb , Wu ?

2019, 11(3). DOI: 10.1016/j.chmed.2019.03.011

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Objective: To compare the pharmacokinetics of naringin and neohesperidin after oral administration of Zhishi total flavonoid glycosides (ZSTFG) extracted from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders (GMD) mice. Methods: ZSTFG was orally given to normal and GMD mice induced by atropine or dopamine. The plasma samples were incubated with β-glucuronidase/sulfatase, the total (free?+?conjugated) naringenin and hesperitin were extracted with acetonitrile. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study. Results: The results showed that, compared with the normal group, AUC0–∞, AUC0–t and Cmax for total naringenin and hesperitin were significantly higher (P < 0.01 or P < 0.05), while CLZ/F for total naringenin and hesperitin was significantly lower (P < 0.01) in the GMD group. Tmax, t1/2z, MRT0-t, and MRT0-∞ for naringenin were longer (P < 0.01) in the GMD group than those in the normal group. Conclusion: The results showed that there were significant differences in pharmacokinetic parameters of naringenin and hesperitin between normal and GMD groups. It was suggested that the absorption of naringenin and hesperitin was increased, and the elimination processes of naringenin and hesperitin were slower in the GMD group than the normal group. The data are of value for further pharmacological studies of ZSTFG and would be useful to provide a reference for improving the therapeutic regimen of ZSTFG in clinical trials.

11 Synergistic activity of lawsone methyl ether in combination with some antibiotics and artocarpin against methicillin-resistant Staphylococcus aureus, Candida albicans, and Trychophyton rubrum

Pharkphoom Panichayupakarananta , b , ? , Abdi Wira Septamac , ? , Akarawat Sinviratponga

2019, 11(3). DOI: 10.1016/j.chmed.2019.06.001

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12 Antiobesity and antihyperlipodemic effect of Ixora coccinea on Triton X-100 induced hyperlipidemia in rats: An approach to evaluate asymmetrical temperature distribution analysis using thermography

Sidhra Syed Zameer Ahmeda , Syed Zameer Ahmed Khadera , ? , Krishnaveni Radhakrishnana , Vanmathi Marimuthua , Muniraj Chinnusamyb , Venkatesan Thangavelb , Karamchand Ravia , Manimaran Vetrivela

2019, 11(3). DOI: 10.1016/j.chmed.2019.05.006

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Objective: Obesity and hyperlipidemia is the major cause of many pathological diseases with an increase side effects using allopathic drugs. The present study focuses on the effect of Ixora coccinea on Triton X-100 induced hyperlipidemia in rats and associated complications. Methodology: In vitro radical scavenging activity of I. coccinea was assessed using DPPH, FRAP and hydrogen peroxide. In vivo antiobesity and antihyperlipidimic activity of I. coccinea was tested in Triton X-100 induced hyperlipidemic rats and assessed for its biochemical parameters in blood and tissue samples. The relationship between physiological responses and regulation of body temperature was investigated by using animal surface temperature images captured with infrared camera. Results: The results of mineral analysis, antioxidant, total flavonoid and phenolic content represented high amount of mineral and had the potential to scavenge free radicals tested with DPPH, FRAP and hydrogen peroxide radicals with dose dependent activity. The highest activity was observed in aqueous extract, DPPH with 71.5% inhibition, FRAP with 56.8%, H2O2 with 33% activity at 100?μg/mL concentration. Triton X-100 induced hyperlipidemic rats when treated with I. coccinea aqueous extract showed significant activity by regulating the biochemical parameters and maintaining the lipid profile by decreasing TC, LDL-C, VLDL-C, TG and improving HDL-C levels. Similarly, the elevated levels of creatinine, urea, uric acid, AST, ALT, ALP due to induction of hyperlipidemia, were brought back to near normal levels after treatment with I. coccinea. The levels of tissue anti-oxidants enzymes like SOD and CAT were also found to be improved in treated I. coccinea groups. The whole body asymmetrical temperature distribution analysis showed that significant decreases in temperature was observed in obesity induced groups but a gradual increase in temperature (2% – –5%) was observed after treatment. Conclusion: Thus, the results indicated that I. coccinea can be a drug of choice to decrease the risk of complications associated with hyperlipidemia and obesity.

13 A guinea pig model of Ciwujia Injection-induced anaphylaxis for allergic substance screening

Yu-fei Feng , Zhong-xu Jing , Yan-yan Zhang , Shao Lv , Qing-xia Guan , Zhi-xin Yang , Rui Wang , Yan-hong Wang

2019, 11(3). DOI: 10.1016/j.chmed.2019.03.006

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Objective: Though especially efficient for cardiovascular and cerebrovascular diseases treatment, many serious anaphylactic diseases could be induced by Ciwujia Injection (CWJI). However, study of the mechanism and detection of allergies have been investigated by the unknown sources of allergenic substances. In this study, a guinea pig model which could mimic the symptoms of anaphylactic reactions induced by Ciwujia Injection (CWJI) was modeled and used to screen the allergenic substance of CWJI. Methods: Guinea pigs were sensitized three times every other day with CWJI and excitated 14 d after the last sensitization administration. Then, the histamine, trypsin, IL-4 and IFN-γ levels, the Annexin V positive rate of peritoneal mast cells (PMC) were detected, the numbers of B lymphocyte and the pathological changes were also analyzed to verify the guinea pig allergy model, PCA test and IgE antibody levels were determined to study the mechanism. Results: The levels of total IgE, histamine, and trypsin were significantly increased after CWJI sensitization, IL-4 level was elevated, Annexin V positive of PMC cell rate, local skin reactions, and declined IFN-γ were observed after excitation. Histological examination showed that mild pathological changes in lungs were found. Conclusion: This guinea pig model may provide a powerful tool to study the mechanism in CWJI induced anaphylaxis and screen the allergic source of CWJI.

14 Formulation optimization, in situ intestinal absorption and permeability of psoralen and isopsoralen

Wan-Jin?Suna , b , Peng?Zhanga , b , Xiang-Wei?Qua , b , Li-Min?Xuc , Chun-Bao?Yangc , Shi-Ping?Gua , b

2019, 11(3). DOI: 10.1016/j.chmed.2019.03.006

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Objective To optimize a self-emulsifying drug delivery system (SEDDS) formulation for psoralen and isopsoralen (PSO and IPSO) isolated from Psoraleae Fructus. Methods A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity, equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system. Results The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be 53.6%, 35.7% and 10.7%, respectively, which means the model is available. Conclusions The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.

15 Quinoline alkaloids isolated from Scolopendra subspinipes mutilans

Yan-fang Li , Wu-zhan Liu? , Jian-wei Fan , Chuan-liang Huang , Li-hua Deng , Hui-fang Zhuang , Yong-xia Guan?

2019, 11(3). DOI: 10.1016/j.chmed.2019.03.010

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Objective To study the quinoline alkaloids from the ethanol extract of Scolopendra subspinipes mutilans (SSM). Methods The chemical constituents were isolated and purified by macroporous resin column, medium pressure preparation chromatography, and semi-preparative HPLC. Their structures were elucidated by IR, MS, and NMR experiments. Results Three quinolone alkaloids were obtained and identified as 3-hydroxy-4-methoxyquinolin-8-yl hydrogen sulfate (1), jineol-8-sulfate (2), and jineol (3), respectively. Conclusion Compound 1 is a new compound from SSM.

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