Ilex Kudingcha Research Articles

Supplementation with a phenolic-rich fraction from Ilex kudingcha improves inflammatory stress, gastrocnemius weights, and foreleg muscle grip strength in murine squamous cell carcinoma (SCC7)-bearing mice

Ethanol supernatant of Ilex kudingcha methanol extract (ESIKME) was identified to be rich in phenolic compounds and inhibited murine squamous cell carcinoma (SCC)-7 growth through slightly restoring adaptive immunity and Th1-inclination immune balance in the SCC7-bearing mice. To further evaluate the inhibitory effects and mechanisms of ESIKME against SCC7-induced inflammation status, the effects of ESIKME on inflammatory stress and related cachexia induced by SCC7 cells were investigated in vitro and in vivo. Chemical components of ESIKME were measured using an advanced LC-MS/MS analysis. SCC7 cells were treated with mouse splenocyte (SCM) and macrophage conditioned media (MCM) cultured without/with ESIKME in vitro. SCC7-bearing mice were orally administered with ESIKME for 26 days in vivo. Cachexia-related biomarkers in the SCC7-bearing mice were analyzed. Most of the detected compounds in ESIKME were polymeric or oxidized phenolic compounds. Either SCM or MCM without ESIKME significantly inhibited SCC7 cell growth. The high-dose ESIKME-administered group (400 mg/kg b.w./day) had significantly higher body weights, feed efficiency, and energy efficiency than the dietary control (DC) group, suggesting non-adverse toxic effects for ESIKME supplementation in the SCC7-bearing mice. The DC group had a higher TNF-α and TNF-α/IL-10 secretion ratio but lower anti-inflammatory IL-10 cytokine secretions by macrophages than the vehicle control group. ESIKME administration dose-dependently and significantly reversed these adverse statuses. Medium dose ESIKME (100 mg/kg b.w./day) decreased tumor sizes but increased gastrocnemius weights and foreleg muscle grip strength. Our results suggest that ESIKME alleviated inflammatory stress and related cachexia in vitro and in vivo.

Anti-diabetic effect of dicaffeoylquinic acids is associated with the modulation of gut microbiota and bile acid metabolism

IntroductionThe human gut microbiome plays a pivotal role in health and disease, notably through its interaction with bile acids (BAs). BAs, synthesized in the liver, undergo transformation by the gut microbiota upon excretion into the intestine, thus influencing host metabolism. However, the potential mechanisms of dicaffeoylquinic acids (DiCQAs) from Ilex kudingcha how to modulate lipid metabolism and inflammation via gut microbiota remain unclear. Objectives and methodsThe objectives of the present study were to investigate the regulating effects of DiCQAs on diabetes and the potential mechanisms of action. Two mice models were utilized to investigate the anti-diabetic effects of DiCQAs. Additionally, analysis of gut microbiota structure and functions was conducted concurrently with the examination of DiCQAs’ impact on gut microbiota carrying the bile salt hydrolase (BSH) gene, as well as on the enterohepatic circulation of BAs and related signaling pathways. ResultsOur findings demonstrated that DiCQAs alleviated diabetic symptoms by modulating gut microbiota carrying the BSH gene. This modulation enhanced intestinal barrier integrity, increased enterohepatic circulation of conjugated BAs, and inhibited the farnesoid X receptor-fibroblast growth factor 15 (FGF15) signaling axis in the ileum. Consequently, the protein expression of hepatic FGFR4 fibroblast growth factor receptor 4 (FGFR4) decreased, accompanied by heightened BA synthesis, reduced hepatic BA stasis, and lowered levels of hepatic and plasma cholesterol. Furthermore, DiCQAs upregulated glucolipid metabolism-related proteins in the liver and muscle, including v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3-beta (GSK3β) and AMP-activated protein kinase (AMPK), thereby ameliorating hyperglycemia and mitigating inflammation through the down-regulation of the MAPK signaling pathway in the diabetic group. ConclusionOur study elucidated the anti-diabetic effects and mechanism of DiCQAs from I. kudingcha, highlighting the potential of targeting gut microbiota, particularly Acetatifactor sp011959105 and Acetatifactor muris carrying the BSH gene, as a therapeutic strategy to attenuate FXR-FGF15 signaling and ameliorate diabetes.

Ilex kudingcha extract ameliorates alterations in behaviors, neurochemical markers and Purkinje cells in the sodium valproate murine model of autism spectrum disorder

Ilex kudingcha extract ameliorates alterations in behaviors, neurochemical markers and Purkinje cells in the sodium valproate murine model of autism spectrum disorder

Ilex kudingcha’s phenolic-rich fraction inhibits murine squamous cell carcinoma (SCC7) through restoring adaptive immunity and Th1-polarized immune balance in vitro and in vivo

The Ilex kudingcha methanol extract ethanol supernatent (ESIKME) was analyzed for its phenolic compounds using high-performance liquid chromatography. Murine squamous cell carcinoma (SCC)-7 was treated in vitro and in vivo. ESIKME was found abundant in 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid and modulated the immune response toward Th1-polarized immune balance through changing the splenocytes’ Th1/Th2 cytokine secretion profile in vitro. ESIKME had a significant effect against SCC7 cells in vitro. ESIKME administration by daily gavage for 26 days did not cause any apparent toxicity to SCC7-bearing mice. There were relatively lower tumor weights in the medium dose group (KM, 100 mg/kg b.w./day). KM administration slightly restored the B-cell and T-cell immunity through increasing serum non-specific antibody levels and the splenocytes’ proliferative ability in the experimental mice. KM administration tended to increase Th1-polarized immune balance through increasing (IL-2+TNF-⍺)/IL-10 (Th1/Th2) secretion ratios using splenocytes isolated from the experimental mice. Th1/Th2 cytokine secretion ratios by splenocytes were negatively correlated with tumor weights, revealing that ESIKME inhibits SCC7 through restoring adaptive immunity and Th1-polarized immune balance. Our results are the first to prove that ESIKME, which is a phenolic-rich fraction, inhibits SCC7 through partly restoring adaptive immunity and Th1-polarized immune balance in the tumor-bearing mice.

Network pharmacology- and molecular docking-based analyses of the antihypertensive mechanism of Ilex kudingcha.

Herein, network pharmacology was used to identify the active components in Ilex kudingcha and common hypertension-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, and molecular docking was performed to verify molecular dynamic simulations. Six active components in Ilex kudingcha were identified; furthermore, 123 target genes common to hypertension were identified. Topological analysis revealed the strongly associated proteins, with RELA, AKT1, JUN, TP53, TNF, and MAPK1 being the predicted targets of the studied traditional Chinese medicine. In addition, GO enrichment analysis revealed significant enrichment of biological processes such as oxidative stress, epithelial cell proliferation, cellular response to chemical stress, response to xenobiotic stimulus, and wound healing. Furthermore, KEGG enrichment analysis revealed that the genes were particularly enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, and other pathways. Molecular docking revealed that the key components in Ilex kudingcha exhibited good binding potential to the target genes RELA, AKT1, JUN, TP53, TNF, and IL-6. Our study results suggest that Ilex kudingcha plays a role in hypertension treatment by exerting hypolipidemic, anti-inflammatory, and antioxidant effects and inhibiting the transcription of atherosclerosis-related genes.

Identification of Phyto-Compounds from Ilex kudingcha as Inhibitors of Sterol-14α-Demethylase Protease: A Computational Approach Against Chagas Disease

Identification of Phyto-Compounds from Ilex kudingcha as Inhibitors of Sterol-14α-Demethylase Protease: A Computational Approach Against Chagas Disease

Ursolic acid-enriched kudingcha extract enhances the antitumor activity of bacteria-mediated cancer immunotherapy

BackgroundBacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities.MethodsWe investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.t△ppGpp in the mice colon cancer models.ResultsIn the present study, KDCE combined with S.t△ppGpp BCI improved antitumor therapeutic efficacy compared to S.t△ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.t△ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK.ConclusionsUrsolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.t△ppGpp and KDCE is a potential cancer therapeutic strategy.

Separation and Purification of Kudinoside D and Its Nanoparticle Preparation and Characterization

Objective: To improve the water solubility of Kudinoside D. Methods: Using atmospheric column chromatography, semi-preparative high performance liquid chromatography and other means to separate and purify saponins from Ilex kudingcha C.J.Tseng, the compound Kudinoside D was obtained. Using polyglutamic acid (γ-PGA) and L-phenylalanine ethyl ester (L-PAE) as raw materials, Kudinoside D nanoparticles were prepared by precipitation method and dialysis method respectively. The physical and chemical properties of nanoparticles were characterized by transmission electron microscopy and dynamic nanoparticle size analyzer, and their in vitro drug release characteristics were investigated by dialysis. Results: Compared with the precipitation method, the encapsulation efficiency and drug loading of Kudinoside D nanoparticles prepared by the dialysis method were increased by 1.5 and 4.5 times, respectively, the encapsulation rate reached 65.46%, and the drug loading reached 13.24%. Kudinoside D nanoparticles had a regular spherical shape with an average particle size of (75±25) nm and a Zeta potential of 33.7. Conclusion: In vitro drug release experiments show that Kudinoside D nanoparticles can significantly improve the water solubility of the drug and have a good sustained release effect in vitro.

The extract of Ilex kudingcha inhibits atherosclerosis in apoE-deficient mice by suppressing cholesterol accumulation in macrophages.

It was previously reported that oleanolic acid and ursolic acid, triterpenoid compounds occurring in Ilex kudingcha, ameliorate hyperlipidemia and atherosclerosis in apoE-deficient mice. In the present study, we investigated whether I. kudingcha extract exerts similar inhibitory effects on cholesterol accumulation in human monocyte-derived macrophages (HMDMs) and atherogenesis in apoE-deficient mice. I. kudingcha extract significantly inhibited cholesterol ester (CE) accumulation induced by acetylated LDL (acetyl-LDL) in HMDMs; however, it generated no effect on cell viability in HMDMs. I. kudingcha extract also suppressed CE accumulation in acyl-CoA:cholesterol acyl-transferase (ACAT)-overexpressing Chinese hamster ovary (CHO) cells, thereby indicating that it inhibits ACAT activity. Furthermore, the oral administration of I. kudingcha extract to apoE-deficient mice significantly decreased the levels of serum cholesterol, triglyceride, sLOX-1, as well as the regions of atherosclerotic lesions in the mice. Our study reveals crucial new-found evidence that I. kudingcha extract significantly inhibits ACAT activity and suppresses atherogenesis.

Ilex kudingcha C.J. Tseng Mitigates Phenotypic Characteristics of Human Autism Spectrum Disorders in a Drosophila Melanogaster Rugose Mutant.

Autism spectrum disorders (ASD) have heterogeneous etiologies involving dysfunction of central nervous systems, for which no effective pan-specific treatments are available. Ilex kudingcha (IK) C.J. Tseng is a nootropic botanical used in Asia for neuroprotection and improvement of cognition. This study establishes that a chemically characterized extract from IK (IKE) mitigates behavioral traits in the Drosophila melanogaster rugose mutant, whose traits resemble human ASD, and examines possible mechanisms. IKE treatment significantly ameliorated deficits in social interaction, short-term memory, and locomotor activity in Drosophila rugose, and significantly increased synaptic bouton number of size more than 2 μm2 in the neuromuscular junctions (NMJs) of Drosophila rugose. To clarify mechanism(s) of IKE action, methylphenidate (MPH), a dopamine transporter inhibitor, was included as a reference drug in the behavioral assays: MPH significantly improved social interaction and short-term memory deficit in Drosophila rugose; administration of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist sulpiride reversed the ameliorative effects of both MPH and IKE on the social interaction deficits of Drosophila rugose. To extend analysis of IKE treatment to the vertebrate central nervous system, ASD-associated gene expression in mouse hippocampus was studied by RNA-seq: IKE treatment altered the expression of genes coding phosphoinositide 3-kinases/protein kinase B (PI3K-Akt), proteins in glutamatergic, dopaminergic, serotonergic, and GABAergic synapses, cAMP response element-binding protein (CREB), and RNA transporter proteins. These results provide a foundation for further analysis of IKE as a candidate for treatment of some forms of ASD.

Determination of Polyphenols in Ilex kudingcha and Insect Tea (Leaves Altered by Animals) by Ultra-high-performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry (UHPLC-QqQ-MS) and Comparison of Their Anti-Aging Effects.

Ilex kudingcha C.J. Tseng tea and insect tea, as traditional Chinese teas, are favored for their original craftsmanship, unique flavor, and biological functionality. In this study, ultra high-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS) was used to analyze the bioactive components of the extracts of Ilex kudingcha and insect tea, and D-galactose-induced aging mice were used to compare the in vivo anti-aging effects of Ilex kudingcha and insect tea extracts. The results were remarkable, UHPLC-QqQ-MS analysis showed that ITP contains 29 ingredients, while IKDCP contains 26 ingredients. However, due to the large differences in the content of the main chemical components in IKDCP and ITP, the effects are equally different. At the same time, the in vivo research results suggesting that the anti-aging effects of IKDCP and ITP (500 mg/kg) include the regulation of viscera indices of major organs; improvement in liver, skin, and spleen tissue morphology; decreased production of inflammatory cytokines; up regulation of SOD, CAT, GSH, GSH-PX, and T-AOC and down regulation of NO and MDA levels in serum and liver tissue; reductions in the concentration of pro-inflammatory factors, and increases in the concentration of anti-inflammatory factor. RT-qPCR and western blot assay also showed that IKDCP and ITP affect anti-aging by regulating the gene and protein expression of GSH-PX, GSH1, SOD1, SOD2, and CAT. The overall results indicate that ITP is more effective in treating oxidative damage in aging mice induced by D-galactose. Thus, ITP appears to be an effective functional drink owing to its rich nutritional components and anti-aging activities.

Behavioral Improvements and its Molecular Mechanism of Ilex kudingcha C.J. Tseng on Animal Model of Alzheimer’s Disease

Alzheimer's disease (AD) is a common chronic neurodegenerative disease with well-defined pathophysiological mechanisms. Ilex kudingcha (IK) C.J. Tseng is commonly known as bitter tea or “Khom” tea in Vietnam. The present study was conducted to investigate the anti-dementia effect of IK using olfactory bulbectomized (OBX) mice. OBX mice were daily treated with IK extract (540 mg/kg) or reference drug, tacrine (2.5 mg/kg) 1 week before and continuously for 3 days after the OBX surgery. The object recognition test, modified Y maze test and fear conditioning test were employed to analyze non-spatial short-term, spatial short-term and long-term memories of the mice respectively. Administration of IK extract and tacrine attenuated these OBX-induced cognitive deficits in mice. The effects of IK and tacrine on spatial short-term memory impairment were reversed by scopolamine, a muscarinic receptor antagonist. The amyloid-beta (Aβ) production in adult transgenic Drosophila brain flies was also investigated by using Western blotting with APP-HA antibody. These results indicated that IK extract improves short-term and long-term memory disturbances in OBX mice and that muscarinic receptor may play a role on these actions. In addition, our result also showed that IK extract reduces the expression of amyloid precursor protein (APP) in brain of AD model using Drosophila melanogaster.

Chemical Composition, Bioactivity and Safety Aspects of Kuding Tea-From Beverage to Herbal Extract.

Kuding tea (KT) is a bitter-tasting herbal tea that has been commonly used in traditional Chinese medicine (TCM). The large-leaved Ku-Ding-Cha (Aquifoliaceae) is composed of its representative species Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng. Because of its potential lipid-lowering, body weight-reducing and blood-glucose-lowering properties, KT has increasingly been recognised for its importance over the past several decades. KT is no longer used only as a beverage, and various extraction methods have been applied to obtain aqueous and ethanolic KT extracts (KTE) or their fractions, which could potentially be used as dietary supplements. The major bioactive components of KT are triterpene saponins and polyphenols, but the composition of KT differs substantially between and among the different KT species. This in turn might affect the physiological effects of KT. KT exhibits antiobesity properties, possibly partly by affecting the intestinal microbiota. In addition, KT may mediate putative antioxidative, anti-inflammatory and anticancer activities. However, there is evidence that high KTE supplementation can adversely affect liver metabolism. The physiological relevance of KT in humans remains rather unclear since the potential health benefits of KT and its constituents reviewed here are mainly derived on the basis of in vitro and animal studies.

Chlorogenic acid-enriched extract of Ilex kudingcha C.J. Tseng tea inhibits neutrophil recruitment in injured zebrafish by promoting reverse migration via the focal adhesion pathway.

Neutrophil-regulated inflammation plays crucial roles in tissue damage and repair. Dysregulation of the neutrophil response system can contribute to diseases such as cancer. Clearance of excessive neutrophils at the site of inflammation by reverse migration provides a promising strategy to mitigate the negative effects. Chlorogenic acid treatment of injured zebrafish embryos showed low-developmental toxicity. Using a transgenic zebrafish Tg (mpx: egfp) model, chlorogenic acid-enriched kudingcha extract promoted neutrophil reverse migration via phosphorylation of ERK and AKT. Using i-TRAQ analysis, differentially expressed proteins involved in focal adhesion were identified, such as: Cdc42, SRC, MLC, ITGA, and Calpain. In support of this, ERK and AKT proteins are involved in the focal adhesion pathway. Real time qPCR determined that CGA downregulates genes associated with cancer metastasis, such as: HSPA5, YWHAZ, RP17, and ITGAV. Together, these results suggest that CGA-enriched Kudingcha extract may have potential as an anticancer or anti-inflammatory therapeutic agent. PRACTICAL APPLICATIONS: Ilex kudingcha C.J Tseng, commonly referred to as the large-leaved kudingcha, is a tea variety naturally rich in chlorogenic acid. Chlorogenic acid, the ester of caffeic and quinic acids, has antioxidant, antibacterial, anticancer, and anti-inflammatory, activities. Kudingcha has several known biological functions, including: anticancer, anti-inflammatory, antidiabetic, and hypolipidemic effects. Treatment with kudingcha extract reduces the recruitment of neutrophils, potentially by inhibiting focal adhesion, and activation of cancer metastasis-related genes. Importantly, kudingcha extract could be used as an alternative nutritional supplement for anticancer or anti-inflammation via its ability to suppress neutrophil recruitment.

Purification, characterization and molecular cloning of a dicaffeoylquinic acid-hydrolyzing esterase from human-derived Lactobacillus fermentum LF-12.

Dicaffeoylquinic acids (DiCQAs), the main components of kudingcha made from the leaves of Ilex kudingcha, could be transformed by gut microbiota. However, the information about the related microorganisms and enzymes involved in the biotransformation of DiCQAs in the human gut is limited. Therefore, a strain of bacteria that could hydrolyze DiCQAs, belonging to Lactobacillus fermentum named L. fermentum LF-12, was isolated from human feces in the present study. Furthermore, an esterase for the hydrolysis of DiCQAs was purified from L. fermentum LF-12 and heterogeneously expressed in Escherichia coli. The esterase could be induced to exert superior hydrolytic activity in the presence of lactose as the carbon source. The molecular weight of the purified esterase was determined to be 31.9 kDa, and the isoelectric point, optimal pH and temperature for the esterase were 4.71, 6.5 and 45 °C, respectively. The enzyme activity was improved by Mg2+ and Ca2+, and reduced by Co2+, Cu2+, EDTA and some kinds of organic solvents. The present results provide new insights into the metabolism of DiCQAs by the human gut.

Modulation of gut microbiota by Ilex kudingcha improves dextran sulfate sodium-induced colitis.

Increasing evidence shows that the gut microbiota contributes to the occurrence and development of colitis. Kudingcha (KDC), made from the leaves of Ilex kudingcha, could mitigate inflammation, however, little is known about the relationship between modulatory effect on gut microbiota by KDC and improvement of colitis. In this study, the attenuating effects of KDC extract (KDCE) on dextran sulfate sodium (DSS)-induced colitis and gut microbiota in C57BL/6 mice were investigated. It was found that the supplementation of KDCE could alleviate typical symptoms of IBD including weight loss, colon shortening, intestinal barrier damage, and decreases in the colitis disease activity index and pro-inflammatory cytokines. Moreover, KDCE supplementation could reverse the alteration of gut microbiota in the colitic mice by increasing the abundances of potential beneficial bacteria, e.g. Odoribacter, Prevotella and Helicobacter, and decreasing the abundances of potential harmful bacteria, e.g. Parabacteroides, Bacteroides, Turicibacter, Parasutterella and Lachnospiraceae. The levels of short-chain fatty acids in feces, cecum contents and serum were also regulated by KDCE. Furthermore, the correlation analysis suggested that KDCE could attenuate DSS-induced colitis which might be related to the alteration of gut microbiota. Therefore, the modulation of gut microbiota by KDCE might be a potential strategy for improving inflammation-driven diseases.

Dicaffeoylquinic acids from Ilex kudingcha attenuate dextran sulfate sodium-induced colitis in C57BL/6 mice in association with the modulation of gut microbiota

Kudingcha (KDC), one of herb teas in China, has been demonstrated to exhibit various health-promoting functions. In this study, the effects of dicaffeoylquinic acids (DiCQAs) from Ilex kudingcha on dextran sulfate sodium (DSS)-induced colitis and gut microbiota in mice were investigated. As results, DiCQAs could alleviate colitis disease activity index, colon shortening, colonic tissue inflammation and pro-inflammatory cytokines, and increase the level of SCFAs. Moreover, DiCQAs could modulate the gut microbiota, including increases of relative abundances of Odoribacter (from 0.06 ± 0.01% to 0.26 ± 0.05%) and Prevotella (from 0.54 ± 0.03% to 1.75 ± 0.04%), and decreases of relative abundances of Bacteroides (from 32.74 ± 0.33% to 26.16 ± 0.26%), Parasutterella (from 1.92 ± 0.06% to 1.31 ± 0.07%) and Lachnospiraceae (from 1.63 ± 0.16% to 1.16 ± 0.07%). The results suggested that DiCQAs could attenuate DSS-induced colitis which might be due to the alteration of the gut microbiota.

Protective Effects of Kuding Tea (Ilex kudingcha C. J. Tseng) Polyphenols on UVB-Induced Skin Aging in SKH1 Hairless Mice.

In this study, the protective effects of Kuding tea polyphenols (KTPs) on ultraviolet B (UVB)-induced skin injury of SKH1 hairless mice were studied. The ion precipitation method was used for extraction of polyphenols from Kuding tea. High-performance liquid chromatography showed that KTPs contains chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C. SKH1 hairless mice were induced skin aging using 2.0 mW/s intensity of 90 mJ/cm2 UV light once a day for seven weeks. The 2.5% and 5% KTPs solution was smeared on 2 cm2 of back skin of skin aging mice twice a day. Mouse experiments showed that KTP strongly increased the serum levels of total superoxide dismutase (T-SOD) and catalase (CAT) and reduced those of malondialdehyde, interleukin 6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNF-α) in mice with UVB-induced skin damage. KTP also increased the levels of type 1 collagen (Col I), hydroxyproline, and hyaluronic acid and reduced those of Col III and hydrogen peroxide in the damaged skin tissues of mice. Pathological observations of tissues stained with H & E, Masson’s trichrome, Verhoeff, and toluidine blue showed that KTPs could protect skin cells, collagen, and elastin and decrease the number of mast cells, thus inhibiting skin damage. Quantitative PCR and western blot assays showed that KTP upregulated the mRNA and protein expression of tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2, copper/zinc-SOD, manganese-SOD, CAT, and glutathione peroxidase and downregulated the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9. In addition, the same concentration of KTP had stronger protective effects than vitamin C. The results of this study demonstrate that KTPs have good skin protective effects, as they are able to inhibit UVB-induced skin damage.

Anti-inflammatory effects of dicaffeoylquinic acids from Ilex kudingcha on lipopolysaccharide-treated RAW264.7 macrophages and potential mechanisms

Increasing evidence has shown that dicaffeoylquinic acids (DiCQAs) have anti-inflammatory activity. However, the underlying molecular mechanisms of the anti-inflammatory effects of DiCQAs are still unclear. In the present study, the anti-inflammatory effects of DiCQAs from the leaves of Ilex kudingcha and the potential molecular mechanisms on LPS-induced inflammatory responses in RAW264.7 macrophage cells were investigated. The results showed that pretreatment with DiCQAs could suppress the production of NO, PGE2 and also pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and the mRNA expression of two major inflammatory mediators of COX-2 and iNOS. The phosphorylated IκBα, ERK, JNK and p38 proteins in LPS-treated cells were significantly increased, which could be reversed by pretreatment with DiCQAs in a concentration-dependent manner. Taken together, the results suggest that DiCQAs from I. kudingcha have potent anti-inflammatory effects on LPS-induced inflammatory responses by inhibiting the NF-κB and MAPKs pathways and may be a prophylactic for inflammation.

Effects of Dicaffeoylquinic Acids from Ilex kudingcha on Lipid Metabolism and Intestinal Microbiota in High-Fat-Diet-Fed Mice.

Kudingcha made from the leaves of Ilex kudingcha and chlorogenic acid have antiobesity and intestinal microbiota modulating effects. However, the effects of kudingcha dicaffeoylquinic acids (diCQAs) on obesity and intestinal microbiota are still poorly understood. In the present study, the effects of kudingcha diCQAs on adipose accumulation and intestinal microbiota were investigated in high-fat-diet-fed mice. As a result, kudingcha diCQAs decreased the liver and adipose tissue masses, concentrations of serum inflammatory factors, and hepatic expressions of lipid synthesis related genes and increased the expressions of genes involved in lipid degradation in the liver. Kudingcha diCQAs also exhibited considerable effects on intestinal microbiota. They increased the relative abundances of Bifidobacterium and Akkermansia and affected the function of the microbial community including bile acid biosynthesis. Kudingcha diCQAs had antiobesity potential, possibly acting through affecting intestinal microbiota. Furthermore, the effects of kudingcha diCQAs on fat accumulation and intestinal microbiota had a dose-dependent manner.