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Dracocephalum palmatum Stephan extract induces apoptosis in human prostate cancer cells via the caspase-8-mediated extrinsic pathway.

Se-Eun LEE ; Zhanna OKHLOPKOVA ; Chiyeon LIM ; Suin CHO

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):793-800. doi:10.1016/S1875-5364(20)60019-X

Dracocephalum palmatum Stephan is a medicinal plant traditionally used by nomadic people in Eastern Russia; however, research on this plant is currently limited. Recently, although studies have been conducted on the constituents of this plant and their antioxidant effects, data on its various pharmacological activities are still lacking. Thus, this study examined the anticancer potential of the dried leaves of D. palmatum S. (DpL) using human prostate cancer PC-3 cells. The antioxidant potential of DpL was evaluated by estimating the total flavonoid and total phenolic content (TFC and TPC, respectively). Additionally, we investigated the effects of the DpL ethyl acetate fraction (DpLE) on cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis, and cell cycle arrest in this cell line. The expression levels of superoxide dismutase (SOD)-1, SOD-2, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) ratio, phospho-protein kinase B (p-AKT), cleaved caspase-8, poly adenosine diphosphate (ADP) ribose polymerase (PARP), and cleaved-PARP were evaluated by western blotting. The results indicated that DpLE causes apoptosis and exerts intracellular ROS-independent anticancer effects on prostate cancer cells, associated with increased SOD-2, cleaved caspase-8, and cleaved-PARP expression and inhibited p-AKT signaling. Thus, DpLE may be a potential resource for the development of promising chemotherapeutic agents for prostate cancer.

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Protective effect of Yi-Qi-Huo-Xue Decoction against ischemic heart disease by regulating cardiac lipid metabolism.

Fang-He LI ; Xiao-Lou HUANG ; Hui WANG ; Shu-Wen GUO ; Ping LI

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):779-792. doi:10.1016/S1875-5364(20)60018-8

Yi-Qi-Huo-Xue Decoction (YQHX) is the recombination of Dang-Gui-Bu-Xue Decoction (DBD), which is one of the well-known traditional Chinese Medicine (TCM) prescription, and has long been shown to have significant protective effects against myocardial ischemic injury. In previous studies, we found that YQHX could regulate lipid and glucose metabolism, promote angiogenesis, attenuate inflammatory response, and ameliorate left ventricular function in myocardial ischemia rat models. However, the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far. In this study, the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9c2 cell injury model. YQHX (8.2 g·kg) and positive-control drug trimetazidine (10 mg·kg) were administered daily on the second day after left anterior descending (LAD) operation. At 7 days and 28 days after surgery, changes of cardiac morphology, structure, and function were evaluated by H&E staining and echocardiography, respectively. The plasma lipid levels and mitochondrial ATP content were also evaluated. Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK, PGC-1α, CPT-1α, and PPARα. YQHX improved cardiac function and ameliorated lipid metabolism disorders. Furthermore, YQHX increased the expression of p-AMPK, PGC-1α, and CPT-1α without changing PPARα in ischemic rat myocardium. In vitro, YQHX activated the protein and mRNA expression of PGC-1α, CPT-1α, and PPARα in hypoxia-induced H9c2 cells injury, whereas AMPK inhibitor Compound c blocked the effects of YQHX. Taken together, the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.

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Novel SNP markers on ginsenosides biosynthesis functional gene for authentication of ginseng herbs and commercial products.

Wen-Ru WU ; Chun-Song CHENG ; Qi-Qing CHENG ; Chi-Chou LAO ; Hao CUI ; Zi-Yu TANG ; Yue OUYANG ; Liang LIU ; Hua ZHOU

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):770-778. doi:10.1016/S1875-5364(20)60017-6

Panax ginseng and Panax quinquefolius have similar bioactive components and morphological characteristics, but they are known to have different medicinal values, high-sensitive and accurate method is expected to identify the sources of ginseng products and evaluate the quality, but with a huge challenge. Our established UHPLC-TOF/MS method coupled with orthogonal partial least squares discriminant analysis (OPLS-DA) model based on 18 ginsenosides was applied to discriminate the sources of raw medicinal materials in ginseng products, and nested PCR strategy was used to discover 6 novel single nucleotide polymorphism (SNP) sites in functional dammarenediol synthase (DS) gene for genetic authentication of P. ginseng and P. quinquefolius for the first time. OPLS-DA model could identify the sources of raw ginseng materials are real or not. SNP markers were applied to identify ginseng fresh samples as well as commercial products, and proved to be successful. This established molecular method can tell exact source information of adulterants, and it was highly sensitive and specific even when total DNA amount was only 0.1 ng and the adulteration was as low as 1%. Therefore, this study made an attempt at the exploration of new type SNP marker for variety authentication and function regulation at the same time, and the combination of chemical and molecular discrimination methods provided the comprehensive evaluation and authentication for the sources of ginseng herbs and products.

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Andrographolide as a potent and promising antiviral agent.

Reshi LATIF ; Chi-Yong WANG

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):760-769. doi:10.1016/S1875-5364(20)60016-4

Andrographolide is a labdane diterpenoid extracted and purified from the aerial parts of plants belonging to genus Andrographis (Acanthaceae). The research has shown the plant based compound is low cytotoxic, having antimicrobial, anti-cancer, antiviral and anti-parasitic effects. Andrographolide both prevent spread as well as transmission of virus to neighboring cells by interfering with different cell signaling pathways. In addition to its medicinal value, plant has been found having nutritional value. Therefore being cost effective, easy availability and having nutritional value as a natural supplement, can be used to improve the quality of life in countries having low standard of living. Due to the limited number of effective vaccines, the plant-based antiviral drugs have provided considerable hope for fighting against the viral infections. The plant-derived compound when produced in large quantities is cost effective with low cytotoxic effects. However, much deep insight research at the molecular level is needed to develop the molecules against the viral infection. This paper aims to highlight the antiviral role of Andrographolide that can made significant contributions toward the improvement of human health and will also summarize the current status and future strategies concerning the therapeutic applications of Andrographolide to combat different viral disease in humans.

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Effect of Sargassum fusiforme polysaccharide on apoptosis and its possible mechanism in human erythroleukemia cells.

Hao-Miao DING ; Xue-Jia CHEN ; Hai-Min CHEN ; Cai-Sheng WANG ; Guo-Ying QIAN

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):749-759. doi:10.1016/S1875-5364(20)60015-2

This study aimed to investigate the effects of Sargassum fusiforme polysaccharide (SFPS I, II, and III) on the apoptosis and regulation of human erythroleukemia (HEL) cells. The effect of different doses of SFPS on HEL cell growth was detected using the Cell Counting Kit-8 method, and apoptosis was detected by Hoechst staining. Cell cycle distribution and apoptosis were detected using flow cytometry. Expression of the cell cycle gene, p53, antiapoptotic genes, Bcl-xL and Bcl-2, and pro-apoptotic genes, Bax, Bad, and Caspase-3, as well as the expression of the corresponding proteins, were detected using real-time quantitative polymerase chain reaction (qPCR) and Western blot. The results showed that SFPS II and III decreased HEL cell viability and induced HEL cell apoptosis. Different concentrations of SFPS (I, II, and III) were detected that induced much less toxic effect in normal human embryonic lung (MRC-5) cells, and SFPS I increased cell proliferation, indicating its favorable selectivity towards cancer cells. The mechanism by which SFPS induced apoptosis was also found to be related to the induction of cell cycle arrest in the G/G phase and the increased expression of apoptosis-related genes and proteins. We concluded that SFPS induces HEL cell apoptosis, possibly via activation of the Caspase pathway, providing the theoretical basis for the development of SFPS-based anti-tumor drug products.

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Phytoglycoprotein isolated from Dioscorea batatas Decne promotes intestinal epithelial wound healing.

Ji-Yun KIM ; Young-Min LEE ; Jong-Pil PARK ; Kye-Taek LIM ; Sei-Jung LEE

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):738-748. doi:10.1016/S1875-5364(20)60014-0

Dioscorea batatas Decne (DBD) has been used to heal various illnesses of the kidney and intestine as an herbal medicine in Asia. As a source of therapeutic agents, many glycoproteins have been isolated from mushrooms and plants, but the functional role of glycoprotein in intestinal epithelial wound healing has not been understood yet. In the present study, we investigated the wound healing potentials of the 30 kDa glycoprotein (DBD glycoprotein) isolated from DBD in human intestinal epithelial (INT-407) cells. We found that DBD glycoprotein (100 μg·mL) significantly increased the motility of INT-407 cells for 24 h by activating protein kinase C (PKC). DBD glycoprotein stimulated the activation of p38 mitogen-activated protein kinase (MAPK), which is responsible for the phosphorylation of NF-κB inhibitor α (IκBα). DBD glycoprotein increased the level of profilin-1 (PFN1), α-actinin and F-actin expression via activation of transcription factor, nuclear factor-kappa B (NF-κB) during its promotion of cell migration. Experimental mouse colitis was induced by adding dextran sulfate sodium (DSS) to the drinking water at a concentration of 4% (W/V) for 7 days. We figured out that administration of DBD glycoprotein (10 and 20 mg·kg) lowers the levels of disease activity index and histological inflammation in DSS-treated ICR mice. In this regard, we suggest that DBD glycoprotein has ability to promote the F-actin-related migration signaling events via activation of PKC and NF-κB in intestinal epithelial cells and prevent inflammatory bowel disease.

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Novel carbohydrate-triazole derivatives as potential α-glucosidase inhibitors.

Zi-Pei ZHANG ; Wan-Ying XUE ; Jian-Xing HU ; De-Cai XIONG ; Yan-Fen WU ; Xin-Shan YE

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):729-737. doi:10.1016/S1875-5364(20)60013-9

A series of novel pyrano[2, 3-d]trizaole compounds were synthesized and their α-glucosidase inhibitory activities were evaluated by in vitro enzyme assay. The experimental data demonstrated that compound 10f showed up to 10-fold higher inhibition (IC74.0 ± 1.3 μmol·L) than acarbose. The molecular docking revealed that compound 10f could bind to α-glucosidase via the hydrophobic, π-π stacking, and hydrogen bonding interactions. The results may benefit further structural modifications to find new and potent α-glucosidase inhibitors.

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Anomeric configuration-dependence of the Lattrell-Dax epimerization from D-glucose to synthetically useful D-allose derivatives.

Yun-Zhan NING ; Chun-Jun QIN ; Wen-Bin SUN ; Jun-Jie FU ; Jing HU ; Jian YIN

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):723-728. doi:10.1016/S1875-5364(20)60012-7

D-Allose and its derivatives play important roles in the field of health care and food nutrition. Pure and well-defined D-allose derivatives can facilitate the elucidation of their structure-activity relationship as an essential step for drug design. The Lattrell-Dax epimerization, refers to the triflate inversion using nitrite reagent, is known as valuable method for the synthesis of rare D-allose derivatives. Here, the influence of protecting group patterns on the transformation efficiency of D-glucose derivatives into synthetically useful D-alloses and D-allosamines via the Lattrell-Dax epimerization was studied. For C3 epimerization of D-glucose derivatives bearing O2-acyl group, an anomeric configuration-dependent acyl migration from O2 to O3 was found. In addition, a neighbouring group participation effect-mediated S1 nucleophilic substitution of the D-glucosamine bearing C2 trichloroacetamido (TCA) group in the Lattrell-Dax epimerization was dependent upon anomeric configuration. Thus, the effect of anomeric configuration on the Lattrell-Dax epimerization of D-glucose suggests that β-D-glucosides with low steric hindrance at C2 should be better substrates for the synthesis of D-allose derivatives. Significantly, the efficient synthesis of the orthogonally protected D-allose 13 and D-allosamine 18 will serve well for further assembly of complex glycans.

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Chemical glycobiology drives the discovery of carbohydrate-based drugs.

Jian YIN

Chinese Journal of Natural Medicines (English Ed.).2020;18(10):721-722. doi:10.1016/S1875-5364(20)60011-5

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Biopharmaceutics classification evaluation for paris saponin VII.

Xin ZHANG ; Yang SUN ; Ying CHENG ; Wei-Liang YE ; Bang-Le ZHANG ; Qi-Bing MEI ; Si-Yuan ZHOU

Chinese Journal of Natural Medicines (English Ed.).2020;18(9):714-720. doi:10.1016/S1875-5364(20)60010-3

To study the biopharmaceutics characteristics of paris saponin VII (PSVII). The solubility of PSVII was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSVII was evaluated by measuring the oil/water partition coefficient (lgP) and determining the apparent permeability coefficient (PC) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSVII transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSVII was investigated in rat. In solvents of different pH, the equilibrium solubility of PSVII was quite low, and the dose number of PSVII was larger than 1. The lgP of PSVII was less than 0. The apparent permeability coefficient [PC] of PSVII in mono-layer Caco-2 cell model was less than 14.96 × 10 cm·s, and the efflux ratio of PSVII in mono-layer Caco-2 cell model was less than 1. The transport rate of PSVII in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSVII could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSVII showed low solubility and permeability, which would result in low oral bioavailability in clinic. PSVII belonged to Class IV compound in biopharmaceutics classification system.

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