PMID: 

Molecules. 2017 Apr 20 ;22(4). Epub 2017 Apr 20. PMID: 28425933

Abstract Title: 

Study on the Rationality for Antiviral Activity of Flos Lonicerae Japonicae-Fructus Forsythiae Herb Chito-Oligosaccharide via Integral Pharmacokinetics.

Abstract: 

In the present study, the rationality for the antiviral effect (H1N1 virus) of(FLJ, named JinYinHua)-Fructus forsythiae (FF, named LianQiao) herb couple preparations improved by chito-oligosaccharide (COS) was investigated. We found that the improvement of antiviral activity for four preparations attributed to the enhancement of bioavailability for the FLJ-FF herb couple in vivo, and that caffeic acid derivatives are the most important type of components for antiviral activity. The anti-Influenza virus activity-half maximal inhibitory concentration (IC), not area under concentration (AUC) was considered as the weighting factor for integrating the pharmacokinetics of caffeic acid derivatives. It was found that the integral absorption, both in vitro and in vivo, especially that in Shuang-Huang-Lian, can be improved significantly by COS, an absorption enhancer based on tight junction. The results indicated that the antiviral activity in four preparations improved by COS was mainly attributed to the integral absorption enhancement of caffeic acid derivatives.

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PMID: 

Int J Biol Macromol. 2017 Sep ;102:396-404. Epub 2017 Apr 15. PMID: 28419828

Abstract Title: 

Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of Lonicera japonica in streptozotocin-induced diabetic rats.

Abstract: 

Hyperglycemia and dyslipidemia are classic features for diabetes mellitus (DM). In this study, one fraction of the crude polysaccharides extracted from Lonicera japonica flower buds (LJP) were investigated for its hypolipidaemic and hypoglycaemic activities by means of streptozotocin (STZ)-induced diabetic rats. Interestingly, after orally administrated with 800mg/kg body weight (B.W.) LJP for 42 days, the food and water intake and the levels of sugar and insulin in blood for the diabetic rats were drastically decreased, while the contents of liver and skeletal muscle glycogen and the concentrations of hepatic pyruvate kinase and hexokinase were obviously increased (p

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PMID: 

Oncol Lett. 2017 Apr ;13(4):2521-2530. Epub 2017 Feb 23. PMID: 28454429

Abstract Title: 

Polyphenolic compounds from KoreanThunb. induces apoptosis via AKT and caspase cascade activation in A549 cells.

Abstract: 

Thunb. (T.) has historically been used in Korean herbal medicine due to its anticancer and protective effects on the respiratory system. In the present study, the polyphenolic compounds inT. were investigated using high-performance liquid chromatography coupled with tandem mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a dose-dependent manner. Flow cytometry and western blot analysis demonstrated that polyphenolic compounds induce apoptosis by regulating the protein expression levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2-associated X-protein/B-cell lymphoma-extra large ratio. Furthermore, polyphenolic compounds inhibited mitochondrial membrane potential activity. Caspase-3 activity was increased in a dose-dependent manner and polyphenolic compounds inhibited the activation of protein kinase B by dephosphorylation. These results suggest that polyphenolic compounds in A549 cells indicate the anticancer activity through the induction of apoptosis.

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PMID: 

Pak J Pharm Sci. 2017 Mar ;30(2):347-353. PMID: 28649055

Abstract Title: 

Lonicera quinquelocularis: A rich source of antioxidant for protection against chronic diseases.

Abstract: 

The purpose of the research work was to examine the in vitro antioxidant activity of the different aqueous and organic fractions of Lonicera quinquelocularis Hardwicke. The methanol extract was dissolved in distilled water and fractioned with n-hexane, chloroform, ethyl acetate and n-butanol, successively. The antioxidant potential of the remaining aqueous and organic fractions was determined by using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity, total antioxidant activity, ferric reducing antioxidant power (FRAP) assay, ferric thiocyanate assay and total phenolics method. Among these fractions ethyl acetate fraction displayed the maximum antioxidant activity with IC50 of (11.13±0.12µg/ml). It also exhibited the highest total antioxidant activity (0.595±0.00), FRAP value (128.2±4.54µg/mL) and total phenolic contents (66.89±7.73µg/g) as compared to other organic fractions. Phytochemical investigation of the above mentioned fractions showed the presence of flavanoids,phenolics, terpenoids, sugars, alkaloids, tannins, saponins and cardiac glycosides in appreciable amounts, which have major contribution towards antioxidant activity.

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PMID: 

Pharmacognosy Res. 2017 Apr-Jun;9(2):128-132. PMID: 28539735

Abstract Title: 

Pharmacognostic Specification, Chlorogenic Acid Content, andAntioxidant Activities ofFlowering Bud.

Abstract: 

BACKGROUND: Thunb. or Japanese Honeysuckle has been widely used in traditional medicine for antipyretic.OBJECTIVE: To establish the pharmacognostic specification offlowering bud in Thailand and to determine its chlorogenic acid content andantioxidant activities.MATERIALS AND METHODS: Driedflowering bud from 15 various herbal drugstores throughout Thailand were investigated for pharmacognostic specification. Their chlorogenic acid contents were quantitatively analyzed by thin layer chromatography (TLC) densitometry with winCATS software. The mobile phase for TLC development consisted of ethyl acetate: formic acid: acetic acid: water (10:1.1:1.1:2.6). Antioxidant activities were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric ion reducing antioxidant power assay, nitric oxide scavenging assay, andβ-carotene bleaching assays.RESULTS: Qualifiedflowering bud in Thailand was presented that the contents of loss on drying, total ash, acid-insoluble ash, and water should not be>10.11%, 6.59%, 1.14%, and 10.82% by weight, respectively. The ethanol and water soluble extractive values should not be

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PMID: 

Int J Biol Macromol. 2018 Feb ;107(Pt A):112-120. Epub 2017 Aug 31. PMID: 28863894

Abstract Title: 

Characterization of a pectin from Lonicera japonica Thunb. and its inhibition effect on Aβaggregation and promotion of neuritogenesis.

Abstract: 

Pectin is a class of complex polysaccharides and recognized for its potential bioactivities. In this study, we showed that a pectic polysaccharide, LFA03-a, was extracted from Lonicera japonica Thunb. flowers and purified with DEAE-cellulose and Sephacryl S-100HR. LFA03-a was composed of rhamnose, arabinose, galactose and galacturonic acid in the molar ratio of 18.1:25.3:36.8:19.5. Its structure was determined to possess a rhamnogalacturonan I (RG-I) backbone consisting ofα-l-1,2-Rhap and α-d-1,4-GalAp disaccharide repeating unit, substituted at O-4 of l-rhamnose. The side chain was involved with β-d-1,4-Galp, β-d-1,3-Galp, β-d-1,3,6-Galp and branched α-l-1,5-Araf. Fluorescence spectroscopic analysis with thioflavine T (ThT) and atomic force microscopy (AFM) results showed that LFA03-a inhibited Aβaggregation in a dose dependent manner and impeded Aβoligomerization and fibril formation. In addition, LFA03-a mildly induced the differentiation of PC12 cells and promoted neuritogenesis.The results suggested that pectin LFA03-a might be a potential targeted therapeutic drug for Alzheimer's disease.

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PMID: 

Biomed Pharmacother. 2017 Nov ;95:477-486. Epub 2017 Sep 12. PMID: 28865368

Abstract Title: 

Sweroside eradicated leukemia cells and attenuated pathogenic processes in mice by inducing apoptosis.

Abstract: 

Acute myeloid leukemia (AML), characterized by extremely heterogeneous molecular and biologic abnormalities, is an aggressive hematologic malignancy, hampering the research and development of effective targeted treatment modalities. Sweroside (SWE), an iridoid glycoside, is isolated from Lonicera japonIca. It has diverse biological activities, but little is known in human leukemia. Here, our study showed the potential of sweroside as an effective agent against human leukemia using in vitro and in vivo approaches. Sweroside treatment obviously reduced the cell viability in human leukemia cell lines and primary human leukemia cells. S and G2/M cell-cycle arrest were induced by sweroside, associated with the down-regulation of Cyclin D1, cyclin-dependent kinase 4 (CDK4), CDC2 and CDC25 as well as the up-regulation of p53 and p21. In addition, apoptosis was highly induced by sweroside both in vitro and in vivo through enhancement of cleaved Caspase-3 and poly (ADP-ribosyl) transferase (PARP). Consistently, anti-apoptotic molecule of B cell CLL/lymphoma 2 (Bcl-2) was impeded by sweroside, while pro-apoptotic signal of Bcl-2-associated X protein (Bax) was elevated. In vivo, HL-60-bearing tumor growth was considerably inhibited by sweroside, which was related to proliferation suppression and apoptosis induction. Our study highlighted the therapeutic potential of sweroside, and provided new insights into the molecular mechanism of sweroside chemosensitization in human leukemia.

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PMID: 

Phytother Res. 2018 Mar ;32(3):504-513. Epub 2017 Nov 29. PMID: 29193390

Abstract Title: 

Lonicera japonica Thunb. Induces caspase-dependent apoptosis through death receptors and suppression of AKT in U937 human leukemic cells.

Abstract: 

Decoctions obtained from the dried flowers of Lonicera japonica Thunb. (Indongcho) have been utilized in folk remedies against inflammatory diseases. Recently, many agents that have used for inflammatory diseases are showing anticancer effects. Here, we have isolated polyphenols extracted from lyophilized Lonicera japonica Thunb (PELJ) and investigated the anticancer effects of PELJ on U937 cells. Here, we demonstrated that PELJ induced apoptosis by upregulation of DR4 and Fas, and further it is augmented by suppression of XIAP. In addition, The PELJ-induced apoptosis is at least in part by blocking PI3K/Akt pathway. These findings suggest that PELJ may provide evidence of anticancer activities on U937 cells. Further study for detailed mechanism and the effects on animal models is warranted to determine whether PELJ provide more conclusive evidence that PELJ which may provide a beneficial effect for treating cancer.

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PMID: 

Front Microbiol. 2017 ;8:2271. Epub 2017 Nov 17. PMID: 29204141

Abstract Title: 

Combined with Metformin Ameliorates Hepatosteatosis and Glucose Intolerance in Association with Gut Microbiota Modulation.

Abstract: 

The gut microbiota is important in energy contribution, metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with chronic metabolic diseases like type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Metformin (MET) and(FL) are common treatments for metabolic diseases in Western and Oriental medicinal fields. We evaluated the effect of treatment with FL and MET in combination on hepatosteatosis, glucose tolerance, and gut microbial composition. FL and MET were administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of genetic T2D and NAFLD. The FL+MET treatment reduced liver weight, serum cholesterol, insulin resistance, and hepatic MDA level and modulated the gut microbial composition. More specifically, the genera ofandwere negatively associated with the body and liver weights, hepatic TG and TC content, and serum insulin level. However, the relative abundance of these genera decreased in response to the FL+MET treatment. Interestingly, pathway prediction data revealed that the FL+MET treatment attenuated lipopolysaccharide-related pathways, in keeping with the decrease in serum and fecal endotoxin levels. FL and MET in combination exerts a synergistic effect on the improvement of hepatosteatosis and insulin sensitivity in OLETF rats, and modulates gut microbiota in association with the effect.

PMID: 

Environ Toxicol Pharmacol. 2018 Sep ;62:1-10. Epub 2018 Jun 8. PMID: 29908432

Abstract Title: 

Neochlorogenic acid inhibits against LPS-activated inflammatory responses through up-regulation of Nrf2/HO-1 and involving AMPK pathway.

Abstract: 

Acute and chronic inflammatory diseases are associated with excessive inflammation due to the accumulation of pro-inflammatory mediators and cytokines produced by macrophages. In the present study, we investigated the anti-inflammatory properties of neochlorogenic acid (nCGA) from Lonicera japonica on lipopolysaccharide (LPS)-activated inflammation in macrophages and participation of the AMPK/Nrf2 pathway. nCGA pretreatment significantly reduced the production of nitric oxide, prostaglandin E, TNF-α, reactive oxygen species, IL-1β, and IL-6 by LPS-activated macrophages. Moreover, both transcript and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 were reduced by nCGA in LPS-activated macrophages. nCGA inhibited NF-κB activation by attenuating IKKα/β and IκBα phosphorylation in LPS-stimulated macrophages. Moreover, nCGA attenuated LPS-elevated JAK-1, STAT-1, and MAPK phosphorylation. We further evaluated the possible role of nCGA in the induction of AMPK/Nrf2 signal pathways required for the protein expression of HO-1 and NQO-1. nCGA induced AMPK activation via phosphorylation of LKB1 and CaMKII and by the inhibitory phosphorylation of GSK3β. It stimulated the overexpression of Nrf2/ARE-regulated downstream proteins, such as NQO-1 and HO-1. Furthermore, the anti-inflammatory effects of nCGA were attenuated in macrophages subjected to siRNAs specificfor HO-1, NQO-1, Nrf2, and AMPK. Accordingly, these results indicate that nCGA, as an AMPK/Nrf2 signal activator, prevents excessive macrophage-mediated responses associated with acute and chronic inflammatory disorders.

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