p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models.

Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress, apoptosis, and inflammatory response. Previously, we proved that p-coumaric acid prevents ethanol induced reproductive toxicity; however, p-coumaric acid (PCA) on ethanol mediated hepatotoxicity has not been examined yet. In our work, we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs, apoptosis, oxidative stress, and Nrf2 signaling. Foremost, we found that PCA could protect ethanol induced both L-02 and HepG2 hepatic cells by inhibiting cytotoxicity, ROS production, mitochondrial depolarization, and nuclear fragmentation. Also, in vivo experiments showed that the ethanol increasing the lipid markers (TBARS, CD) and depletes the antioxidants thereby increased phosphorylation of JNK, ERK, and p38 in rat liver tissues. Interestingly, PCA treatments inhibit ethanol exposed lipid markers and depletion of antioxidants, which directs the inhibition of MAPKs activation in rat liver tissues. We also noticed that the PCA protected ethanol induced apoptosis and liver markers by inhibiting the expression of Bax, caspases; AST, ALT, ALS, and LDH in liver tissue. Overall, the ameliorative consequence of PCA on ethanol induced oxidative stress and apoptosis was achieved by suppressing the expression of CYP2E1 and overexpressing Nrf2 and its target protein HO-1 in rat liver tissue. As a result, PCA was marked to be an effective antioxidant with notable hepatoprotection by inhibiting MAPKs and apoptosis signaling via enhancing Nrf2 signaling.

Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation.

In the present study, the authors have attempted to fabricate Polydatin encapsulated Poly [lactic-co-glycolic acid] (POL-PLGA-NPs) to counteract 7,12-dimethyl benzyl anthracene (DMBA) promoted buccal pouch carcinogenesis in experimental animals. The bio-formulated POL-PLGA-NPs were characterized by dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD) pattern analysis, and transmission electron microscope (TEM). In addition, the nano-chemopreventive potential of POL-PLGA-NPs was assessed by scrutinizing the neoplastic incidence and analyzing the status of lipid peroxidation, antioxidants, phase I, phase II detoxification status, and histopathological changes and in DMBA-treated animals. In golden Syrian hamsters, oral squamous cell carcinoma (OSCC) was generated by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. After 100% tumor formation was observed, high tumor volume, tumor burden, and altered levels of biochemical status were observed in the DMBA-painted hamsters. Intra-gastric administration of varying concentration of POL-PLGA-NPs (7.5, 15, and 30 mg/kg b.wt) to DMBA-treated hamsters assumedly prevents oncological incidences and restores the status of the biochemical markers. It also significantly enhances the apoptotic associated and inhibits the cancer cell proliferative markers expression (p53, Bax, Bcl-2, cleaved caspase 3, cyclin-D1). The present study reveals that POL-PLGA-NPs is a penitential candidate for nano-chemopreventive, anti-lipid peroxidative, and antioxidant potential, and also has a modulating effect on the phase I and Phase II detoxification system, which is associated with reduced cell proliferation and induced apoptosis in experimental oral carcinogenesis.

Green synthesis, characterization and antibacterial activity of silver nanoparticles by Malus domestica and its cytotoxic effect on (MCF-7) cell line.

This article reports the utilization of Malus domestica for the synthesis of silver nanoparticles (AgNPs) with cytotoxic activity against the Michigan Cancer Foundation-7 (MCF-7) cell line as well as their antibacterial and radical scavenging potential. The biosynthesized AgNPs were confirmed using various analytical characterization techniques. The cytotoxic effect of Malus domestica-AgNPs (M.d-AgNPs) was studied by MTT assay and scavenging efficacy was assessed by DPPH, nitric oxide radical and phosphomolybdate assays. Furthermore, green synthesized nanoparticles were evaluated for their antibacterial activity against multidrug resistant-clinical isolates. M.d-AgNPs were observed to be almost spherical in shape with an average diameter from 50 to 107.3 nm as assessed by TEM and DLS. M.d-AgNPs revealed the dose-dependent antioxidant activity and antimicrobial activity against multidrug-resistant bacterial strain viz. Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Also, in vitro studies revealed dose-dependent cytotoxic effects of M.d-AgNPs treated MCF-7 cell line. The data strongly suggest that M.d-AgNPs had a potential antioxidant, antimicrobial and cytotoxicity activity.

Protective effect of Juglans regia L., against ultraviolet-B induced photoaging in human epidermal keratinocytes.

Solar ultraviolet-B radiation (UVB) has severe adverse effects on the structure and functions of the skin. Although, UVB (290-320 nm) represents only 5-10% of UV light reaching earth's surface, its contribution towards photoaging is tremendous. In this present study was investigate the photoprotective effect of methanolic extract of the male flower of J. regia L. (MEJR) against UVB induced photoaging in human epidermal keratinocytes (HaCaT). Cells were exposed to UVB-irradiation at a dose of 20 mJ/cm2, induces the activation of several signaling pathways which are associated with oxidative stress and photoaging. A single dose of UVB irradiation increased the protein and mRNA expression of MAPKs, AP-1, MMPs, Smad7 and decreased expression of TIMP-1/2, TGF-ß1, Smad3, procollagen type-1 in HaCaT cells. In contrast, pretreatment of MEJR (80 µg/ml) prior to UVB-irradiation significantly prevented the overexpression of MAPKs, AP-1, MMPs, Smad7 and decreased expression of TIMP-1/2, TGF-ß1, Smad3 and procollagen type-1 in HaCaT cells. Moreover, pretreatment of MEJR (80 µg/ml) prior to UVB-irradiation significantly prevents apoptosis in sub Go-phase. Thus, MEJR protects UVB-mediated photoaging in human skin cells, by modulating the expression of photoaging markers. The protection might be because of the presence of the good amount of bioactive compounds in MEJR.

Alpha-pinene attenuates UVA-induced photoaging through inhibition of matrix metalloproteinases expression in mouse skin.

AIM: The present study was designed to examine the role of alpha-pinene (AP) against skin photoaging in UVA-irradiated mice. MATERIALS AND METHODS: Swiss albino mice were subjected to UVA-irradiation at the rate of 10 J/cm2 per day for ten days, totally mouse received 100 J/cm2. One hour prior to each UVA-exposure, the mouse skin was topically treated with AP (100 mg kg/b·wt). Biochemical methods were employed to study the status of antioxidant enzymes and lipid peroxidation. Histopathological observations were performed using hematoxylin and eosin (H & E) and Verhoeff van Gieson (VVG) staining in the mouse skin. The inflammatory and apoptotic protein expression was studied by immunohistochemical and Western blot methods. The mRNA expression of matrix metalloproteinases was determined by qRT-PCR and Western blot analysis. KEY FINDINGS: We found that AP pretreatment substantially ameliorated UVA-induced depletion of antioxidant enzymes and prevented UVA-induced lipid peroxidation in the mouse skin. Further, AP effectively inhibited UVA-induced activation of pro-angiogenic (iNOS and VEGF), inflammatory proteins (TNF-α, IL-6, and COX-2) expression and prevented the activation of NF-κB p65 in the mouse skin. Additionally, AP inhibited UVA-mediated apoptotic mediators (Bax, Bcl-2, caspase-3 and caspase 9) expression in the mouse skin. Moreover, AP inhibited mRNA expression of matrix metalloproteinases (MMP-13 and MMP-9) and tissue type IV collagenase (MMP-2) expression in the mouse skin. Histological studies showed that AP remarkably prevented the dermal tissue damage in UVA-irradiated mice. CONCLUSION: Thus, AP treatment effectively prevented UVA-induced photoaging probably through its antioxidant property.

p-Coumaric acid ameliorates ethanol-induced kidney injury by inhibiting inflammatory cytokine production and NF-κB signaling in rats

Objective: To examine the effects of p-coumaric acid on ethanol-induced kidney injury in Swiss Wistar rats. Methods: Ethanol (25％ v/v) was used to induce nephrotoxicity in rats. p-Coumaric acid was orally administered at 50, 100, or 200 mg/kg body weight. The levels of oxidative parameters were determined; pro-inflammatory biomarkers were analyzed by Western blotting and apoptotic protein was analyzed by immunohistochemistry. Results: Ethanol treated rats showed decreased levels of antioxidants and aberrant production of pro-inflammatory cytokines (IL-6, IL1β, TNF-α), NF-κB activation and imbalance of pro-and anti-apoptotic proteins (Bcl-2, Bax, caspase 3). Meanwhile, p-coumaric acid restored antioxidant levels and decreased the levels of inflammatory cytokines, NF-κB, and pro-apoptotic proteins and increased Bcl-2 expression. Conclusions: p-Coumaric acid ameliorates ethanol-induced kidney injury by restoring antioxidant production and suppressing cellular apoptosis and inhibiting NF-κB expression. p-Coumaric acid should be further investigated as a promising candidate for ethanol-induced kidney toxicity.

Alpha pinene modulates UVA-induced oxidative stress, DNA damage and apoptosis in human skin epidermal keratinocytes.

AIMS: This study aims to evaluate the protective effect of alpha pinene (AP), an essential oil monoterpene, against ultraviolet-A (UVA; 320-400 nm) induced cellular damages in human skin epidermal keratinocytes (HaCaT cells). MATERIALS AND METHODS: In this study, HaCaT cells were subjected to single UVA-irradiation (10 J/cm2) in the presence and absence of AP (30 µM) then different cellular end points were analyzed. The protective effect of AP against UVA-induced cytotoxicity was evaluated by MTT-based metabolic assay. Generation of reactive oxygen species (ROS), alteration of mitochondrial membrane potential (MMP), DNA single- and double strand breaks (SSBs and DSBs) and apoptotic morphological changes during different treatment conditions were measured by fluorescence microscopy and spectrofluorometry. Modulatory role of AP against UVA-mediated inflammatory markers expression, nucleotide excision repair (NER) proteins and apoptotic markers expression during AP and/or UVA treatment were studied by western blot. KEY FINDINGS: Pretreatment with AP prevented UVA-induced cytotoxicity, generation of ROS, lipid peroxidation and DNA stand breaks probably through its antioxidant property. AP also inhibited UVA-induced inflammatory mediators such as NF-κB, TNF-α and IL-6 expression in HaCaT cells. Further, AP modulates NER proteins via activation of p53 and p21 thereby subsequently prevent the formation of UVA-induced cyclobutane pyrimidine dimers (CPDs). We also noticed that AP inhibits apoptotic cell death by preventing UVA-induced loss of mitochondrial membrane potential through modulating Bax/Bcl-2 expression in HaCaT cells. SIGNIFICANCE: The present findings suggest that AP prevent UVA-induced oxidative stress, inflammation, DNA damages and apoptosis in human skin cells.

Protective effect of Juglans regia L. against ultraviolet B radiation induced inflammatory responses in human epidermal keratinocytes.

BACKGROUND: Juglans regia L. has a history of traditional medicinal use for the treatment of various maladies and have been documented with significant antioxidant and antiinflammatory properties. Although all parts of the plant are medicinally important, but male the flower of the plant has not been yet investigated against the photo-damage. PURPOSE: The present study, we sought to determine the photoprotective effect of the male flower of J. regia L. against ultraviolet-B radiation-induced inflammatory responses in human skin cells. METHODS: The profile of pharmacological active compounds present in the male flower of J. regia was analyzed by GC-MS. Then, the antioxidant property of methanolic extract of J. regia (MEJR) was analyzed by in vitro free radical scavenging assays. Further, we analyzed the sun protection factor of this extract by spectrophotometry. Moreover, we investigated the photoprotective effect of MEJR against UVB induced inflammatory signaling in human epidermal cells. Human skin epidermal keratinocytes (HaCaT) were pretreated with the MEJR (80 µg/ml), 30 min prior to UVB-irradiation at a dose of 20 mJ/cm2 and were investigated for lipid peroxidation, enzymatic antioxidants activity, apoptosis and inflammatory markers expression level. RESULTS: The GC-MS results showed the presence of good amount of pharmacologically active compounds in the MEJR. We observed that the MEJR possess significant free radical scavenging activity and it was comparable with standard antioxidants. Further, the MEJR exhibits 8.8 sun-protection-factor (SPF) value. Pretreatment with MEJR, 30 min prior to UVB-irradiation, prevented ROS generation, lipid peroxidation and restored the activity of antioxidant status in HaCaT cells. Moreover, MEJR pretreatment significantly prevented UVB activated inflammatory markers like TNF-α, IL-1, IL-6, NF-κB, COX-2 in HaCaT. CONCLUSION: The present findings suggest that MEJR exhibit photoprotective effects and hence it may be useful for the treatment of inflammation related responses. The pharmacological mechanism of MEJR partly associated with its UV absorbance, modulation of inflammatory signaling as well as due to its free radical scavenging capability.

7-Hydroxycoumarin prevents UVB-induced activation of NF-κB and subsequent overexpression of matrix metalloproteinases and inflammatory markers in human dermal fibroblast cells.

Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage. Human dermal fibroblasts (HDFa) were subjected to single UVB-irradiation (18mJ/cm(2)) resulting in reactive oxygen species (ROS) generation, oxidative DNA damage and upregulation of nuclear factor kappa B (NF-κB) expression. Further, it has been observed that there was a significant cytokine production (TNF-α and IL-6) in UVB irradiated HDFa cells. Our results show that 7-hydroxycoumarin (7-OHC) prevents UVB-induced activation of NF-κB thereby subsequently preventing the overexpression of TNF-α and IL-6 in HDFa cells. Further, 7-OHC prevents UVB-induced activation of cyclooxygenase-2 (COX-2) expression, an inflammatory mediator in skin cells. Moreover, 7-OHC inhibited mRNA expression pattern of matrix metalloproteinases (MMP-1 and MMP-9) in UVB irradiated skin cells. Furthermore, 7-OHC restored antioxidant status, thereby scavenging the excessively generated ROS; consequently preventing the oxidative DNA damage. It has also been noticed that 7-OHC prevents UVB mediated DNA damage through activation of DNA repair enzymes such as XRCC1 and HOGG1. In this study, we treated HDFa cells with 7-OHC before and after UVB irradiation and we found that pretreatment showed better results when compared to posttreatment. Further, 7-OHC showed 9.8416 sun protection factor (SPF) value and it absorbs photons in the UVB wavelength rage. Thus, it has been concluded that sunscreen property, free radical scavenging potential and prevention of NF-κB activation play a role for photoprotective property of 7-OHC.

Caffeic Acid Inhibits Chronic UVB-Induced Cellular Proliferation Through JAK-STAT3 Signaling in Mouse Skin.

Signal transducers and activators of transcription 3 (STAT3) play a critical role in inflammation, proliferation and carcinogenesis. Inhibition of JAK-STAT3 signaling is proved to be a novel target for prevention of UVB-induced skin carcinogenesis. In this study, chronic UVB irradiation (180 mJ cm(-2) ; weekly thrice for 30 weeks) induces the expression of IL-10 and JAK1 that eventually activates the STAT3 which leads to the transcription of proliferative and antiapoptotic markers such as PCNA, Cyclin-D1, Bcl2 and Bcl-xl, respectively. Caffeic acid (CA) inhibits JAK-STAT3 signaling, thereby induces apoptotic cell death by upregulating Bax, Cytochrome-C, Caspase-9 and Caspase-3 expression in mouse skin. Furthermore, TSP-1 is an antiangiogeneic protein, which is involved in the inhibition of angiogenesis and proliferation. Chronic UVB exposure decreased the expression of TSP-1 and pretreatment with CA prevented the UVB-induced loss of TSP-1 in UVB-irradiated mouse skin. Thus, CA offers protection against UVB-induced photocarcinogenesis probably through modulating the JAK-STAT3 in the mouse skin.