Protective Effects Of Compounds Research Articles

6‐Gingerdione Reduces Apoptotic Conditions in HepG2 Cells and Inhibits Inflammatory Cytokine Gene Expression in Alcoholic Liver Injured Zebrafish Larvae

Antioxidant natural products and their analogs especially phenolic compounds, exhibit diverse biological properties, including anti-inflammatory, antioxidant, and anticancer activities. Ginger which is widely used worldwide for various beneficial effects also contains several phenolic antioxidants, and 6-gingerol is one of the natural products studied extensively. However, the molecular mechanism of synthetically synthesized 6-gingerdione (compound 1) from 6-gingerol was not known. In this study, compound 1 and methylated 6-gingerdione (compound 2) were obtained semi synthetically from 6-gingerol. Compound 1 and 2 are subjected to SwissADME prediction. Then the protective effect of compound 1 was analyzed in 2 % EtOH induced HepG2 cells and zebrafish larvae. Hydroxyl and nitric oxide scavenging assays reveal that compound 1 showed more antioxidant activity than compound 2 at 50 μM. Moreover, compound 1 exhibited good anti-inflammatory activity via lipoxygenase inhibition and proteinase inhibition. Apoptosis and oxidative stress in HepG2 cells were induced by 2 % EtOH and treated with compound 1. Compound 1 significantly inhibited the EtOH induced nitric oxide production, apoptosis, and ROS generation in HepG2 cells. Encouraged by the in-vitro antioxidant and anti-inflammatory activities, compound 1 was then investigated for its protective effect in 2 % EtOH induced ALD zebrafish larva. Compound 1 protected the zebrafish larvae from liver injury by suppressing inflammatory (COX-2, TNF-α, and IL-1β) and lipogenic genes (C/EBP-α, SREBP1, and IL-1β) while upregulating the antioxidant gene. Our findings indicate that compound 1 synthesized from 6-gingerol ameliorated liver injury that likely, contributes to its potential antioxidant and anti-inflammatory properties.

The Zebrafish Embryo as a Model to Test Protective Effects of Food Antioxidant Compounds.

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, β-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except β-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, β-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.

Renoprotective activity of a new amide and a new hydroxycinnamic acid derivative from the fresh roots of Rehmannia glutinosa

A new amide, named rehmagluamide (1), and a new hydroxycinnamic acid derivative, named nepetoidin F (2), together with six known compounds, 2′-O-methyluridine (3), puroglutamic acid (4), biliverdic acid (5), peterolactam (6), nicotinic acid (7), nicotinamide (8), were isolated from the fresh roots of Rehmannia glutinosa. All the structures of compounds were identified by the interpretation of their spectroscopic data and comparison with those reported in the literatures. The protective effects of compounds 1–7 on normal rat kidney tubule epithelioid (NRK-52e) cells injury induced by LPS were investigated. The results indicated that compounds 1, 2, and 7 exhibited protective effects against LPS-induced NRK 52e cells injury.

Alkaloids of Delphinium grandiflorum and their implication to H2O2-induced cardiomyocytes injury

Three new diterpenoid alkaloids (1–3), and eight known alkaloids (4–11) were isolated from the aerial parts of Delphinium grandiflorum. Grandifline A (1) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7NC17 hemiaminal moiety and a lactone fragment through the linkage of C-17OC19 unit. And we named this newly-discovered class of rearranged C19-diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2) is the first naturally-occurring 7,17-secolycoctonine diterpenoid alkaloid with a C-7OC17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and single-crystal X-ray diffraction analysis. The protective effects of compounds 1–11 on H2O2-induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC50 values of 1.881 ± 0.680 μM and 1.904 ± 0.750 μM, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in H2O2-induced H9C2 cells.

Two mixed-ligand Cu(II) coordination polymers: protective effect on sepsis by reducing an excessive inflammatory response

By the reaction of a rigid π-conjugated H4L linker (5,5'-(1,3,6,8-tetraoxobenzo[lmn][3],[8]phenanthroline-2—7-diyl)bis-1,3-benzenedicarboxylic acid), Cu(NO3)2, and N-donor auxiliary linkers, two new Cu-based coordination polymers (CPs), namely {[Cu(L)0.5(1,4-bib)(H2O)2]·0.5H2O}n (1) and {[Cu(H2L)(4,4'-bibp)(H2O)2]}n (2) {1,4-bib = 1,4-bis(1-imidazolyl)benzene, 4,4'-bibp = 4,4'-bis(imidazolyl)biphenyl} are synthesized under solvothermal conditions and characte­rized. Furthermore, the protective effect of compounds 1 and 2 on the sepsis mice model is evaluated and the related mechanism is explored. Firstly, the CFU counting assay is performed to detect the bactericidal effect of compounds 1 and 2 in vivo. Then, the ELISA assay is conducted to measure the release of interleukin-1β (IL-1β) and interleukin-6 (IL-6) into the plasma after treatment with the compounds.

Co(II) and Cu(II) coordination polymers: Crystal structures and treatment effect on acute lung injury treatment by inhibiting inflammatory response

Two coordination polymers named [Co(tib)(H2O)3]· ipa·2H2O (1, H2ipa = iso-phthalic acid) and [Cu3(tib)2(BTB)2]·DMF·2H2O (2, H3BTB = 4,4′,4′′-gbenzene-1,3,5-triyl-tribenzoic acid, DMF = N,N-dimethylformamide) were constructed using a solvothermal method by reaction of metal salts with the 1,3,5-tris(1-imidazolyl)benzene (tib) ligands and different carboxylate linkers as the co-ligands. The two complexes have been characterized by X-ray diffraction as well as the elemental analyses. Subsequently, the protective effect of compounds 1 and 2 on the acute lung injury and its related mechanism was explored. Firstly, the enzyme linked immunosorbent assay (ELISA) was performed to detect the release of the inflammatory cytokines. Then, the partial pressure of oxygen (PaO2) and the partial pressure of carbon dioxide (PaCO2) was measured with blood gas analysis.

RETRACTED ARTICLE: TWO Cu(II)-BASED COORDINATION POLYMERS: STRUCTURAL DIVERSITY AND TREATMENT ACTIVITY AGAINST NEONATAL SEPSIS BY ENHANCING THE ANTIBACTERIAL RESPONSE OF THE IMMUNE SYSTEM

In this work, two Cu(II)-based coordination polymers with the chemical formulae of [Cu(333cptpy)2]n·2nH2O (1, H333cptpy = 4′-(3-carboxyphenyl)-3,2′:6′,3″-terpyridine) and [Cu(233cptpy)2(H2O)2]n (2, H233cptpy = 4′-(2-carboxyphenyl)-3,2′:6′,3″-terpyridine) are hydrothermally synthesized using two positionally isomeric pyridyl-carboxylate ligands. The two as-prepared complexes are studied via X-ray single crystal diffraction along with the elemental analysis. Furthermore, the protective effect of compounds 1 and 2 against neonatal sepsis is evaluated. Firstly, ELISA is performed to detect the content of the C-reactive protein (CRP) in the serum of newborns after treatment with compounds 1 and 2. Next, the inflammatory level in the body is detected by the RT-PCR measurement of nf-κb and tnf-α.

Quercitrin, the Main Compound in Wikstroemia indica, Mitigates Skin Lesions in a Mouse Model of 2,4-Dinitrochlorobenzene-Induced Contact Hypersensitivity

Hapten-induced contact hypersensitivity (CHS) is widely utilized to induce immune activation in animal models of allergic contact dermatitis. Our previous findings suggested that the 95% EtOH extract of Wikstroemia indica (L.) C. A. Mey. has antiallergic and anti-inflammatory effects in DNCB-treated CHS SKH-1 hairless mice. The aim of this study was to evaluate the protective effects of compounds isolated from the EtOAc fraction of W. indica in RBL-2H3 cells and 2,4-dinitrochlorobenzene- (DNCB-) induced CHS mice. Of eight compounds in W. indica, that is, umbelliferone, daphnoretin, wikstrocoumarin, (+)-syringaresinol, tricin, (+)-lariciresinol, erythro-guaiacylglycerol-β-coniferyl ether, and quercitrin, quercitrin exhibited the most antiallergic activity against antigen-induced β-hexosaminidase release and IL-4 mRNA expression, which are markers of degranulation in RBL-2H3 cells. After a 7-sensitizing period, 14 days of DNCB treatment with or without topical pimecrolimus (1%) or quercitrin (0.5%) treatment, quercitrin was found to suppress DNCB-induced increases in serum IL-4 and IgE concentrations and transepidermal water loss. These results indicate that quercitrin has therapeutic potential for treatment of allergies and allergy-related contact dermatitis.

RETRACTED: Two transition metal coordination polymers: Photocatalytic properties and treatment effect on lipopolysaccharide (LPS) induced kidney injury by regulating pink 1 gene expression and reducing inflammatory response

Abstract Two novel mixed ligand coordination polymers (CPs) {[Co(bdc)(bidp)]·H2O}n (1, bidp = 1,3-bis(5,6-dimethylbenzimidazol-1-yl)propane, H2bdc = 1,4- terephthalic acid) and {[Cd(bdc)(bibh)1.5]·H2O}n (2, bibh = 1,6-bis(benzimidazol-1-yl)hexane) and were prepared and then characterized via powder X-ray diffraction (PXRD) and IR spectra, the analysis of element and the analysis of single crystal X-ray diffraction. In addition, these two complexes have good photocatalytic activities for the degradation of methyl orange (MO) and methylene blue (MB) under the irradiation of ultraviolet light. In the study of biological functions, the protective effect of compounds 1 and 2 were assessed, and their detail mechanisms were discussed. First of all, the relative expression level of the pink 1 gene was determined by reverse transcription-polymerase chain reaction (RT-PCR). After that, the IL-1β and TNF-α content was detected by the enzyme linked immunosorbent assay (ELISA) detection kit.

Oleanane- and Ursane-Type Triterpene Saponins from Centella asiatica Exhibit Neuroprotective Effects.

Six new pentacyclic triterpenoid saponins, centelloside F (1), centelloside G (2), 11-oxo-asiaticoside B (3), 11-oxo-madecassoside (4), 11(β)-methoxy asiaticoside B (5), and 11(β)-methoxy madecassoside (6), along with seven known ones, asiaticoside (7), asiaticoside B (8), madecassoside (9), centellasaponin A (10), isoasiaticoside (11), scheffoleoside A (12), and centelloside E (13), were separated from the 80% MeOH extract of the whole plant of Centella asiatica, which has been used as a medicinal plant and is now commercially available as a diatery supplement in many countries. Compounds 1 and 2, 3 and 4, and 5 and 6 are three pairs of isomers with oleanane- or ursane-type triterpenes as aglycones. The chemical structures of the new triterpene saponins were fully characterized by extensive analysis of their nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The protective effects of compounds 1-13 on PC12 cells induced by 6-OHDA were screened, and compound 3 displayed the best neuroprotective effect, with 91.75% cell viability at the concentration of 100 μM. Moreover, compound 3 also attenuated cell apoptosis and increased the mRNA expression of antioxidant enzymes, including superoxide dismutase and catalase. Additionally, compound 3 activated the phosphatidylinositol 3-kinase/Akt pathway, including PDK1, Akt, and GSK-3β. These findings suggested that triterpene saponins from C. asiatica were worthy of further biological research to develop new neuroprotective agents.

RETRACTED ARTICLE: A fluorescent Zn(II)-containing coordination polymer for antibiotic sensing and treatment activity on periodontal tissue inflammation after orthodontics by inhibiting the growth of Porphyromonas gingivalis

A novel fluorescent zinc(II)-containing coordination polymer {[Zn(DIPT)](NO3)(H2O)3} (1) having the channel-type framework was generated via using rigid three-terminal nitrogenous hetero-ligand 5-(3,5-di(1H-imidazol-1-yl)phenyl)-2H-tetrazole (HDIPT) in solvent thermal reaction. Benefitting from its excellent fluorescent emission along with high water stability, complex 1 shows selective luminescence sensing for sulfonamide antibiotics with high sensitivity in water. In addition, the anti-bacterial activity of compound 1 against Porphuromonas gingivalis (P. gingivalis ATCC 33277) in vitro and in vivo was evaluated. Firstly, the growth curves of P. gingivalis ATCC 33277 was measured after compound 1 treatment for the in vitro activity evaluation. Then, the in vivo protective effect of compound 1 was further explored, the IL-8 and TNF-α level in gingival fluid revealed the excellent inhibitory effect of compound 1 on the inflammatory response. The results acquired via pose scoring software as well as molecular docking indicated that the compound 1 might bind and inhibit the NF-κB protein function, this might provide a latent regulatory mechanism for compound 1.

Protective Effects of Compounds from Cimicifuga dahurica against Amyloid Beta Production in Vitro and Scopolamine-Induced Memory Impairment in Vivo.

Cimicifuga dahurica has traditionally been used as an antipyretic, analgesic, and anti-inflammatory agent and as a treatment for uterine and anal prolapse. This study has investigated the potential beneficial effects of this medicinal plant and its components on Alzheimer's disease (AD) with a focus on amyloid beta (Aβ) production and scopolamine-induced memory impairment in mice. An ethanol extract from C. dahurica roots decreased Aβ production in APP-CHO cells [Chinese hamster ovarian (CHO) cells stably expressing amyloid precursor protein (APP)], as determined by an enzyme-linked immunosorbent assay and Western blot analysis. Then, the compounds isolated from C. dahurica were tested for their antiamyloidogenic activities. Four compounds (1-4) efficiently interrupted Aβ generation by suppressing the level of β-secretase in APP-CHO cells. Moreover, the in vivo experimental results demonstrated that compound 4 improved the cognitive performances of mice with scopolamine-induced disruption on behavioral tests and the expression of memory-related proteins. Taken together, these results suggest that C. dahurica and its constituents are potential agents for preventing or alleviating the symptoms of AD.

Two new Co(II)-based coordination polymers: structural characterization and protective effect on Parkinson disease by improving the content of dopamine in the substantia nigra

·DMF}n (1, H2amipa = 5-aminoisophthalic acid, bpe = 1,2-bis(4-pyridyl)ethylene, DMF = dimethylformamide) and {[Co(5-amipa)(bpe)](DMA)}n (2, DMA = dimethylacetamide) are successfully synthesized by the solvothermal reaction of 5-aminoisophthalic acid and the N-donor 1,2-bis(4-pyridyl)ethylene) co-ligand with Co(II) salt in different solvent systems. All compounds are adequately characterized, and their structures are verified by single crystal X-ray diffraction along with the elemental analysis. Furthermore, the protective effect of compounds 1 and 2 on Parkinson disease is evaluated in the biological function section. Firstly, the ELISA detection is performed to estimate the dopamine content in the substantia nigra after treatment with the compounds. Then the open field test is finished to reflect the treatment abi­lity of the compounds on the cognitive ability of mice.

Two Cu(II)-based coordination polymers: structural diversity and treatment activity against neonatal sepsis by enhancing the anti-bacterial response of the immune system

In this work, two Cu(II)-based coordination polymers with the chemical formulae of [Cu(333cptpy)2]n·2nH2O (1, H333cptpy = 4'-(3-carboxyphenyl)-3,2':6',3''-terpyridine) and [Cu(233cptpy)2(H2O)2]n (2, H233cptpy = 4'-(2-carboxyphenyl)-3,2':6',3''-terpyridine) are hydrothermally synthesized using two positionally isomeric pyridyl-carboxylate ligands. The two as-prepared complexes are studied via X-ray single crystal diffraction along with the elemental analysis. Furthermore, the protective effect of compounds 1 and 2 against neonatal sepsis is evaluated. Firstly, ELISA is performed to detect the content of the C-reactive protein (CRP) in the serum of newborns after treatment with compounds 1 and 2. Next, the inflammatory level in the body is detected by the RT-PCR measurement of nf-κb and tnf-α.

RETRACTED ARTICLE: A Heterometallic MOF for Highly Selective Al3+ Ion Detection and Protective Effect Against Periodontitis by Reducing P. gingivalis CFU and Inflammatory Cytokines Levels

By employment of an amide-functionalized tetracarboxylic ligand 5,5′-(carbonylbis(azanediyl))-diisophthalic acid (H4cbab), a new polyhedral metal–organic framework (MOF) with the chemical formula of {[InZn2(cbda)2(H2O)2](NMF)3}n (1, NMF = N-methylformamide) has been synthesized under the solvothermal reaction condition. The structural feature was studied via the single crystal X-ray diffraction along with ultimate analysis. This as-prepared MOF shows excellent luminescence performance which can be able to detect Al3+ ions selectively. In aqueous solutions, the detection limitation for Al3+ ion is 0.56 µM, which is significantly below the highest standard of 7.41 µM for Al3+ ion in drinking water that is defined by the World Health Organization (WHO). The protective effect of compound against periodontitis was further explored. The viable cell counts (CFU) number was counted to evaluate the inhibitory effect of compound on bacterial growth. The enzyme linked immunosorbent assay (ELISA) was carried on in order to measure accurately the proportion of inflammatory cytokines in gingival fluid around the implant. The potential binding modes of the synthesized compounds as well as the targeted protein was explored by calculating docking with high accuracy as well as pose scoring process.

RETRACTED ARTICLE: Zn(II)-Containing Metal–Organic Framework for Fluorescence Detection of Nitrobenzene and Prevention Effect on Hypertension via Down-Regulating the Expression of Vitamin D Receptor

A novel Zn(II)-based metal–organic framework {[Zn(L)](DMF)3}n (1) was prepared by using Zn(II) ions and bifunctional imidazole carboxylate ligands (5-(1H-imidazol-1-yl)isophthalic acid, H2L). Complex 1 is a fluorescent Zn-MOF sensor with high selectivity and sensitivity for the detection of nitrobenzene. KSV can reach 2.875 × 103 M−1. The protective effect of compound 1 on the hypertension was further explored. Firstly, the RT-PCR was performed to explore the influence of compound on vdr expression in vascular endothelial cells. Then, the ELISA assay was conducted to measure the renin and angiotensin II level in vivo after compound treatment. The results obtained from molecular docking and pose scoring software exhibited a possible binding mode of the compound binding to vitamin D receptor, which might provide potential regulation mechanisms for the compound.

A trinuclear Co(II) cluster-based metal–organic framework for selective gas sorption and protective effect on acute glomerulonephritis by inhibiting NF-κb pathway

By using a nanosized tetracarboxylate ligand 2,3,5,6-tetrakis(4-carboxyphenyl)pyrazine (H4TCPP) as a building block, the synthesis of a new microporous Co-based metal–organic framework was performed by making Co(NO2)3·6H2O and the presence of bpy ligand to react under solvothermal reaction, and its chemical formula is [Co3(OH)2(H2TCPP)2(bpy)](DMF)3 (1, bpy = 4,4ʹ-bipyridine). Gas adsorption studies reveal that the mixtures of C2H2/CH4 and C2H2/CO2 could be selectively separated by the obtained activated 1a. The protective effect of compound on AGN was further evaluated in vitro. The RT-PCR was carried out to determine the relative expression of tnf-α, nf-κb in glomerular cells after bacterial infection and compound treatment. The IL-1β and IL-18 content in glomerular cells was also evaluated by ELISA after compound treatment. Finally, the results obtained through molecular docking exhibited possible regulation mechanism on regulation of binding affinity between DNA and target protein.

Stilbenes from Veratrum maackii Regel Protect against Ethanol-Induced DNA Damage in Mouse Cerebellum and Cerebral Cortex.

Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as "Lilu" and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel, and their structures were identified as cis-mulberroside A (1), resveratrol-4,3'- O-β-d-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3,5- O-β-d-diglucopyranoside (5), oxyresveratrol- 4'- O-β-d-glucopyranoside (6), oxyresveratrol-3- O-β-d-glucopyranoside (7), oxyresveratrol (8), and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1-9 were observed to decrease DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1-9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.

Congmujingnosides B-G, triterpene saponins from the stem of Aralia chinensis and their protective effects against H2O2-induced myocardial cell injury

Phytochemical investigation of the stem of Aralia chinensis yielded six new oleanane-type triterpene saponins named as congmujingnosides B-G (1–6). The new ones were elucidated on the basis of the chemical and spectroscopic analysis. Protective effects of compounds 1−6 were tested against H2O2-induced H9c2 cardiomyocyte injury, and the data showed that compounds 1 and 5 had significant cell-protective effects. No significant DPPH radical scavenging activity was observed for compounds 1−6.

Protective effects of compounds from Garcinia mangostana L. (mangosteen) against UVB damage in HaCaT cells and hairless mice.

UltravioletB (UVB) radiation causes alterations in the skin, such as epidermal thickening, wrinkle formation and inflammation. Therefore, preventing UVB-induced skin damage can promote general health among the human population. Garcinia mangostana L. (mangosteen) is a fruit that has become a popular botanical dietary supplement because of its perceived role in promoting overall health. The present study investigated the photoprotective effects of α-, β-, γ-mangostins and gartanin against UVB radiation using the HaCaT immortalized human keratinocyte cell line as an invitro model and hairless mice as an invivo model. UVB radiation increased the expression of matrix metalloproteinase(MMP)‑1 and ‑9 and decreased the mRNA expression levels of involucrin, filaggrin and loricrin in HaCaT cells; however, these changes were attenuated by pretreating the cells with α-, β-, γ-mangostins and gartanin. Among these compounds, α-mangostin exhibited the greatest effects in reducing UVB-induced skin wrinkles, inhibited epidermal thickening in hairless mice invivo. Exposure to UVB radiation increased the expression of MMPs and pro-inflammatory cytokines and activated mitogen-activated protein kinases in hairless mice, but these changes were attenuated by α-mangostin. The authors suggested that α-mangostin exerts anti-wrinkle and anti-aging properties.