Building a bridge between ecology and Chinese herbal medicines Publication date: Available online 9 July 2019 Source: Chinese Herbal Medicines Author(s): Rui Fang, George He

An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s Publication date: Available online 9 July 2019 Source: Chinese Herbal Medicines Author(s): Xin He, Zi-jun Wu, Li-li Wang, Xue Gao, Yue Hai, Wen-li Liu, Le-mei Du, Lei Zhang, Ai-hong Yang, Nan-nan Huang Abstract 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.

Comparative pharmacokinetics of naringin and neohesperidin after oral administration of flavonoid glycosides from Aurantii Fructus Immaturusin normal and gastrointestinal motility disorders mice Publication date: Available online 20 June 2019 Source: Chinese Herbal Medicines Author(s): Zhi-ru Xu, Chun-hong Jiang, Si-yang Fan, Ren-jie Yan, Ning Xie, Chun-zhen Wu Abstract 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.

Synergistic activity of lawsone methyl ether in combination with some antibiotics and artocarpin against methicillin-resistant Staphylococcus aureus, Candida albicans, and Trychophyton rubrum Publication date: Available online 18 June 2019 Source: Chinese Herbal Medicines Author(s): Pharkphoom Panichayupakaranant, Abdi Wira Septama, Akarawat Sinviratpong Abstract Objective One appealing strategy to overcome and prevent resistant problem is the use of combined two or more antibacterial substances. Lawsone methyl ether (LME) is the naphthoquinone found in the leaves of Impatiens balsamina. The objective of this study is to determine the interaction of LME with some antibiotics (ampicillin, tetracycline, norfloxacin, and clotrimazole) and a natural compound, artocarpin against methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans, and Trychophyton rubrum. Methods A broth microdilution method was used to determine the minimum inhibition concentration (MIC). Synergistic effects were evaluated at their own MIC using the checkerboard method and time-kill assay. Results LME showed moderate antibacterial activity against MRSA with MIC value of 15.6 µg/mL, and exhibited strong antifungal activities against T. rubrum and C. albicans with MIC values of 7.8 and 3.9 µg/mL, respectively. The interaction of LME with the natural compound artocarpin against MRSA produced a synergy with fractional inhibitory concentration index (FICI) value of 0.31, while the combination of LME and clotrimazole exhibited synergy against C. albicans and T. rubrum with FICI values of 0.38 and 0.24, respectively. The time-kill assays confirmed that the compounds in combination enhanced their antimicrobial activities against the resistant microorganisms with different degrees. Conclusion LME in combination with clotrimazole exhibited synergy effect against C. albicans and T. rubrum. In combination with artocarpin, it showed synergy effect against MRSA.

In vivo antiplasmodial potential of three herbal methanolic extracts in mice infected with Plasmodium berghei NK65 Publication date: Available online 18 June 2019 Source: Chinese Herbal Medicines Author(s): Pachiyappan Rajiv Gandhi, Chinnaperumal Kamaraj, Elangovan Vimalkumar, Selvaraj Mohana Roopan Abstract 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 four days suppressive test at different doses of 150, 300 and 600 mg/kg per day. 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 ± 4.02)%, (72.0 ± 8.44)% and (52.7 ± 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.

Quinoline alkaloids isolated from Scolopendra subspinipes mutilans Publication date: Available online 6 June 2019 Source: Chinese Herbal Medicines Author(s): Yan-fang Li, Wu-zhan Liu, Jian-wei Fan, Chuan-liang Huang, Li-hua Deng, Hui-fang Zhuang, Yong-xia Guan Abstract 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.

Parasitic relationship of Cistanche deserticola and host-plant Haloxylon ammodendron based on genetic variation of host Publication date: Available online 6 June 2019 Source: Chinese Herbal Medicines Author(s): Liang Shen, Rong Xu, Sai Liu, Chang-qing Xu, Fang Peng, Xiao-jin Li, Guo-qiang Zhu, Cai-xiang Xie, Jun Zhu, Tong-ning Liu, Jun Chen Abstract 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.

Formulation optimization, in situ intestinal absorption and permeability of psoralen and isopsoralen Publication date: Available online 30 May 2019 Source: Chinese Herbal Medicines Author(s): Wan-Jin Sun, Peng Zhang, Xiang-Wei Qu, Li-Min Xu, Chun-Bao Yang, Shi-Ping Gu Abstract 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.

Mechanisms of Chinese medical formula Fangji Huangqi Decoction as an effective treatment of nephrotic syndrome based on systems pharmacology Publication date: Available online 30 May 2019 Source: Chinese Herbal Medicines Author(s): Wang-ning Zhang, Liu Yang, Sheng-sheng He, Ai-ping Li, Xue-mei Qin Abstract Objective With the development of the society, the number of people who catch the nephrotic syndrome (NS) is going up roughly. As we all know, traditional Chinese medicine (TCM), especially Fangji Huangqi Decoction (FHD), has a long history with good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated. Methods In this study, TCMSP platform was employed to screen active compounds of each herb of Fangji Huangqi Decoction combined with literatures. Furthermore, PharmMapper and SEA were used to predict and screen the active targets of FHD, and the HOME-NCBI-GENE, GeneCards and OMIM database were used to screen the active targets of NS. The GO and KEGG pathways involved in the targets were analyzed by ClueGO. Finally, contribution index was used to screen the active ingredients of FHD in the treatment of NS. Results After drug-likeness (DL) and bioavailability (OB) filtering, 43 compounds were selected from FHD, interacting with 85 NS-related targets. Systematic analysis of the constructed networks revealed that it was mainly involved in PI3K-Akt signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway and TNF signaling pathway. The contribution index of every active ingredient also indicated five compounds, including astragaloside IV, quercetin, glycyrrhizic acid, glycyrrhizin and fangchinoline. Conclusions These results have successfully predicted the pharmacodynamic material basis and the mechanism efficiency of FHD in the treatment of NS.

Antiobesity and antihyperlipidemic effect of Ixora coccinea on Triton X-100 induced hyperlipidemia in rats: An approach to evaluate asymmetrical temperature distribution analysis using thermography Publication date: Available online 30 May 2019 Source: Chinese Herbal Medicines Author(s): Sidhra Syed Zameer Ahmed, Syed Zameer Ahmed Khader, Krishnaveni Radhakrishnan, Vanmathi Marimuthu, Muniraj Chinnusamy, Venkatesan Thangavel, Karamchand Ravi, Manimaran Vetrivel Abstract 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.