PMID: 

Free Radic Biol Med. 2018 12 ;129:310-322. Epub 2018 Sep 25. PMID: 30266681

Abstract Title: 

Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans.

Abstract: 

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 μg/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 μg/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp-16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-Esignificantly delayed amyloid β-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 μg/mL chlorogenic acid, 15 μg/mL 1,5-dicaffeoylquinic acid and 7.5 μg/mL 1,3-dicaffeoylquinic acid) of 500 μg/mL LJ-E could significantly delay paralysis in CL4176 worms caused by Aβ toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.

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PMID: 

PLoS One. 2018 ;13(10):e0204152. Epub 2018 Oct 8. PMID: 30296293

Abstract Title: 

Immunomodulatory activity of a novel polysaccharide from Lonicera japonica in immunosuppressed mice induced by cyclophosphamide.

Abstract: 

Lonicera japonica is a typical Chinese herbal medicine. We previously reported a method to isolate polysaccharides from Lonicera japonica (LJP). In this study, we first performed a qualitative analysis of LJP using the Fourier Transform Infrared Spectrometer (FT-IR) and explored the monosaccharide composition of LJP using the pre-column derivatization high performance liquid chromatography (HPLC) method. We then investigated the immunomodulatory function of LJP in cyclophosphamide (CTX)-induced immunosuppressed mouse models. The results showed that LJP had the characteristic absorption of typical polysaccharides consisting of 6 types of monosaccharides. In addition, LJP can increase significantly the organ index, splenic lymphocyte proliferation, macrophage phagocytosis, and natural killer (NK) cell activity in CTX-treated mice. LJP could also restore the levels of serum cytokines interleukin (IL-2), tumor necrosis factor (TNF-α) and Interferon-γ (IFN-γ) in the CTX-treated mice. Finally, the results on measuring the T-lymphocytes subsets of spleen also confirmed LJP-induced immunomodulatory activity in immunosuppressed mice from another perspective. Therefore, LJP could be used as a potential immunomodulatory agent.

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PMID: 

Int J Biol Macromol. 2019 Feb 15 ;123:801-809. Epub 2018 Nov 13. PMID: 30445085

Abstract Title: 

Anti-hyperuricemic and anti-gouty arthritis activities of polysaccharide purified from Lonicera japonica in model rats.

Abstract: 

In this present study, we investigated the anti-hyperuricemic and anti-gouty arthritis effect of a puried water-soluble polysaccharide (LJP-1) obtained from Lonicera japonica. A series of characterization of the purified polysaccharide were carried out in this paper. Monosaccharide analysis showed that LJP-1 composed of glucuronic acid, glucose, galactose, arabinose, and xylose at the ratio of 2.43:1:2.09:1.95:1.96, respectively. The estimated molecular weight of LJP-1 was 17.5 kDa. LJP-1 belonged to pyranose and possessed α- and β -glycosidic configurations. Congo red test showed that LJP-1 had a spatial triple helix structure. In pharmacodynamic experiments, the anti-hyperuricemic activity of LJP-1 was studied using hyperuricemic SD rat model induced via potassium oxonate and hypoxanthine. The result showed that LJP-1 could obviously decrease the serum uric acid level and suppress xanthine oxidase (XOD) activity. Moreover, in the gouty arthritis model established by sodium urate crystals, the degree of swelling of the ankle joint, IL-1β, IL-6, TNF-α and COX-2-related inflammatory factors levels in murine serum all declined. Taken together, these results demonstrated that LJP-1 has anti-gouty arthritis effect. Therefore, LJP-1 could serve as a promising candidate for developing novel natural anti-gouty agent.

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PMID: 

Curr Mol Pharmacol. 2019 Jul 16. Epub 2019 Jul 16. PMID: 31333144

Abstract Title: 

Therapeutic promises of Chlorogenic acid with special emphasis on its anti-obesity property.

Abstract: 

BACKGROUND: Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid. It is an ester formed between caffeic acid and the 3-hydroxyl of L-quinic acid. This polyphenol is naturally present in substantial amount in the green coffee beans. Minor quantities of CGA are also reported in apples, eggplant, blueberries, tomatoes, strawberries and potatoes. CGA is reported to be beneficial in hypertension, hyperglycemia, antimicrobial, antitumor, memory enhancer, weight management etc. Further, it is also reported to have anticancer, antioxidant and anti-inflammatory activities. Since last decade, CGA drew public attention for its widely recommended use as medicine or natural food additive supplement for the management of obesity.OBJECTIVE: The current review explores the medicinal promises of CGA and emphasizes on its anti-obese property as reported by various scientific reports and publication.CONCLUSION: CGA shows promises as an antioxidant, glycemic control agent, anti-hypertensive, anti-inflammatory, antimicrobial, neuro-protective and anti-obesity agent. It primarily activates the AMP-activated protein kinase, inhibits 3-hydroxy 3-methylglutaryl coenzyme-A reductase and strengthens the activity of carnitine palmitoyltransferase to control the obesity.

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PMID: 

J Med Food. 2019 Feb ;22(2):140-151. Epub 2019 Jan 24. PMID: 30676853

Abstract Title: 

BST-104, a Water Extract of Lonicera japonica, Has a Gastroprotective Effect via Antioxidant and Anti-Inflammatory Activities.

Abstract: 

The gastroprotective effects of BST-104 (a water extract of Lonicera japonica) and the mechanisms involved were investigated in murine models of gastritis and peptic ulcer. The gastroprotective effects of BST-104 and its active components were evaluated in rat models of HCl/ethanol-induced gastritis and acetic acid-induced gastric ulcer. After orally administering BST-104, chlorogenic acid, rebamipide (positive control), or vehicle to each animal model, gastric lesion sizes, gastric mucus statuses, proinflammatory cytokine levels, and oxidative stress were measured. Superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) levels and oxidized/reduced glutathione (GSH) ratios in gastric mucosal tissues were measured to evaluate oxidative stress. To clarify the action mechanism of BST-104, we investigated nuclear factor (NF)-κB pathway involvement by real-time polymerase chain reaction (PCR). In the acetic acid-induced ulcer model, oral administration of BST-104 at 50, 100, or 200 mg/kg significantly reduced gastric lesions by 38%, 43%, and 55%, respectively, compared with vehicle controls. BST-104 significantly increased gastric mucus contents and this was accompanied by higher levels of hexosamine, sialic acid, and prostaglandin Ein gastric mucus. Furthermore, BST-104 treatment increased antioxidant activities, as evidenced by higher levels of catalase, SOD, and oxidized/reduced GSH and lower MDA levels. In addition, BST-104 significantly suppressed proinflammatory cytokine (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) increases, and real-time PCR showed that BST-104 significantly downregulated NF-κB expression. In summary, BST-104 and its active component, chlorogenic acid, were found to have gastroprotective effects by virtue of their antioxidant and anti-inflammatory properties through downregulation of NF-κB expression.

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PMID: 

Phytomedicine. 2019 Apr ;57:282-291. Epub 2018 Dec 31. PMID: 30802714

Abstract Title: 

Effects of a novel biflavonoid of Lonicera japonica flower buds on modulating apoptosis under different oxidative conditions in hepatoma cells.

Abstract: 

BACKGROUND: In our previous work, we purified a novel biflavonoid named Japoflavone D (JFD) from Lonicera japonica flower buds. Biflavonoids are chemical compounds characterized by their high levels of antioxidative activity.PURPOSE: The present study aimed to investigate the function and molecular mechanism of JFD under different oxidative conditions in hepatoma cells.METHODS: MTT assay and apoptosis assay were used to evaluate the cytotoxic effect of JFD. The activities of SOD and CAT were detected to evaluate the oxidative level. Oxidative stress was induced by HOstimulation. The molecular mechanism of JFD was investigated by analyzing relative signaling pathway.RESULTS: JFD inhibited cell viability in all hepatoma cell lines we examined. Under quiescent conditions, JFD treatment of SMMC-7721 cells resulted in upregulation of AKT/mTOR signal pathway and ERK activities and downregulation of KEAP1/NRF2/ARE signaling axis, together with apoptosis. However, under oxidative stress, JFD played a quite different role. Treatment of JFD suppressed the activation of ERK and mTOR and activated the KEAP1/NRF2/ARE signaling axis, which is a predominant regulator of cytoprotective responses to oxidative stress, thereby lessening the damage caused by excess reactive oxygen species (ROS). A molecular docking analysis suggested that JFD may interrupt the interaction between KEAP1 and NRF2 by competitively anchoring to the NRF2 binding site on KEAP1.CONCLUSION: The results indicate that JFD functions as a potent antioxidant and plays dual roles in modulating apoptosis under different oxidative conditions. JFD has the potential to be developed as a protective drug for diseases related with excess ROS.

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PMID: 

J Ethnopharmacol. 2019 Jul 15 ;239:111909. Epub 2019 Apr 23. PMID: 31026553

Abstract Title: 

Lonicerin, an anti-algE flavonoid against Pseudomonas aeruginosa virulence screened from Shuanghuanglian formula by molecule docking based strategy.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The Shuanghuanglian formula (SF) is a famous antimicrobial and antiviral traditional Chinese medicine that is made of Lonicera japonica Thunb., Scutellaria baicalensis Georgi, and Forsythia suspensa (Thunb.) Vahl. According to the Chinese Pharmacopoeia, the SF is commonly administered in the forms of oral liquid, tablets, and injection. It has long been used to treat acute respiratory tract infections, especially lung infection.AIM OF THE STUDY: In the light of the increasing incidence of multidrug resistance to conventional antibiotics, the aim of this study was to screen potential anti-virulence agents against Pseudomonas aeruginosa from the extract of the SF.MATERIALS AND METHODS: The SF was used for effective compounds screening via the combination of the molecule docking approach and ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Fifty-one anti-virulence-related proteins were docked, 26 identified compounds were from SF. Subsequently, the top-scoring screened compound was assessed via bioactive-related assays, including the quantification of alginate biosynthesis, anti-biofilm assays, and the A549 human lung cells infection.RESULT: A flavonoid Lonicerin was found to be bonded with the active site of the alginate secretion protein (AlgE) with the highest score in molecule docking. Furthermore, we validated that Lonicerin could significantly reduce alginate secretion (25 μg/mL) and biofilm formation (12.5 μg/mL) at a sub-MIC concentration without inhibiting the proliferation of P. aeruginosa or influencing the expression of AlgE, which suggested that Lonicerin may directly inhibit AlgE. In addition, Lonicerin was proven to inhibit the infection of P. aeruginosa in the A549 cells.CONCLUSION: This work reported on the first potential AlgE antagonist that was derived from herbal resources. Lonicerin was proven to be an effective inhibitor in-vitro of P. aeruginosa infection.

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PMID: 

Food Sci Nutr. 2019 May ;7(5):1786-1794. Epub 2019 Apr 21. PMID: 31139392

Abstract Title: 

Extraction optimization, antioxidant activity, and tyrosinase inhibitory capacity of polyphenols from.

Abstract: 

The objective of this research was twofold: first, to optimize the extraction process ofpolyphenols using a response surface methodology, and second, to study the antioxidant activity and tyrosinase inhibitory capacity of the polyphenols of different purities. High-speed shearing homogenization extraction was used to extract the polyphenols from. The antioxidant activity and the effect of polyphenols on tyrosinase activity were studied using free radical scavenging assay and the tyrosinase method, respectively. The optimal extraction conditions with an extraction yield of 6.96% for polyphenols were determined as follows: ethanol volume fraction 57%, shearing time 3.30 min, and solid-liquid ratio 1:58.polyphenols exhibited potent scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and inhibitory capacity on tyrosinase. The results suggested thatpolyphenols could be explored as a natural antioxidant and tyrosinase inhibitor.

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PMID: 

Eur J Pharmacol. 2018 Sep 15 ;835:108-114. Epub 2018 Jul 29. PMID: 30063917

Abstract Title: 

Sulforaphane improves leptin responsiveness in high-fat high-sucrose diet-fed obese mice.

Abstract: 

Diet-induced obesity (DIO) is commonly associated with hyperleptinemia and leptin resistance. Leptin acts centrally to inhibit food intake and increase energy expenditure, thereby preventing body weight gain. Resistance to the biological effects of leptin represents a major obstacle in utilizing exogenously administered leptin as a treatment option for obesity. Of importance, recent studies demonstrate that naturally occurring compounds improve leptin sensitivity in DIO mice, as revealed by anorectic and body weight-lowering effects. To date, the role of sulforaphane (SFN, an isothiocyanate derived from cruciferous vegetables) on leptin responsiveness has not been examined, in spite of its known beneficial effects toward lowering body weight gain in DIO. In the present study, we determined the extent to which SFN regulates leptin responsiveness in high-fat high-sucrose (HFHS) diet-fed obese mice. SFN treatment (0.5 mg/kg/day, s.c.) for 23 days in HFHS-fed mice improved the responsiveness to intraperitoneally-injected leptin by promoting significant decreases in cumulative food intake and body weight gain. A single leptin injection (2 mg/kg; i.p.) resulted in significant decreases in food intake at 24 hand 38 h time points. In addition, a triple leptin injection (1 mg/kg/day, 3 days; i.p.) led to significant decreases in food intake at 14 h, 24 h, 38 h, 48 h, and 62 h time points. Furthermore, single and triple leptin injections prevented body weight gain at 38 h and 62 h time points, respectively. The present findings suggest that intervention with SFN, a naturally occurring isothiocyanate, has the potential to improve leptin responsiveness in DIO.

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PMID: 

Sci Rep. 2018 Aug 23 ;8(1):12708. Epub 2018 Aug 23. PMID: 30139948

Abstract Title: 

In Vitro Modulation of Redox and Metabolism Interplay at the Brain Vascular Endothelium: Genomic and Proteomic Profiles of Sulforaphane Activity.

Abstract: 

Sulforaphane (SFN) has been shown to protect the brain vascular system and effectively reduce ischemic injuries and cognitive deficits. Given the robust cerebrovascular protection afforded by SFN, the objective of this study was to profile these effects in vitro using primary mouse brain microvascular endothelial cells and focusing on cellular redox, metabolism and detoxification functions. We used a mouse MitoChip array developed and validated at the FDA National Center for Toxicological Research (NCTR) to profile a host of genes encoded by nuclear and mt-DNA following SFN treatment (0-5 µM). Corresponding protein expression levels were assessed (ad hoc) by qRT-PCR, immunoblots and immunocytochemistry (ICC). Gene ontology clustering revealed that SFN treatment (24 h) significantly up-regulated ~50 key genes (>1.5 fold, adjusted p 

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