Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake

Oxidative stress plays a relevant role in the progression of chronic conditions, including cardiometabolic diseases. Several Cameroonian plants, including spices, are traditionally used as herbal medicines for the treatment of diseases where oxidative stress contributes to insulin resistance, like type 2 diabetes mellitus. This study evaluated the antioxidant capacity and the effects on oxidative-stress-induced impairment of glucose uptake of 11 Cameroonian spice extracts. H2O2-induced reactive oxygen species (ROS) production by human HepG2 cells was significantly reduced by 8/11 extracts. The most effective extracts, Xylopia parviflora, Echinops giganteus, and Dichrostachys glomerata, showed a concentration-dependent ROS-scavenging activity, which involved Nrf2 translocation into the nucleus. Xylopia parviflora, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum extracts showed the highest antioxidant capacity, according to oxygen radical absorbance capacity (ORAC) (2.52–88 μM Trolox Eq/g of extract), ferric-reducing antioxidant power (FRAP) (40.23–233.84 mg gallic acid Eq/g of extract), and total phenol (8.96–32.96% mg gallic acid Eq/g of extract) assays. In HepG2 cells, glucose uptake was stimulated by 4/11 extracts, similarly to insulin and metformin. H2O2-induced oxidative stress reduced glucose uptake, which was rescued by pretreatment with Xylopia aethiopica, Xylopia parviflora, Scorodophloeus zenkeri, Monodora myristica, and Dichrostachys glomerata extracts. The ROS-scavenging ability of the spice extracts may reside in some secondary metabolites observed by phytochemical profiling (reverse-phase high-performance liquid chromatography coupled to a diode array detector (HPLC-UV-DAD)). Further studies are needed to better clarify their biological activities and potential use to control oxidative stress and promote insulin sensitivity.

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Physicochemical and Bioactive Characteristics of Wild Grown Bilberry (Vaccinium myrtillus L.) Genotypes from Northeastern Turkey

Notulae Botanicae Horti Agrobotanici Cluj-Napoca ◽

10.15835/nbha46110842 ◽

2018 ◽

Vol 46 (1) ◽

pp. 128-133 ◽

Cited By ~ 4

Author(s):

Ferit CELIK ◽

Mehmet Ramazan BOZHUYUK ◽

Sezai ERCISLI ◽

Muttalip GUNDOGDU

Keyword(s):

Vitamin C ◽

Antioxidant Capacity ◽

Gallic Acid ◽

Antioxidant Properties ◽

Fruit Weight ◽

Total Phenolic ◽

Soluble Solid Content ◽

Anthocyanin Content ◽

Total Anthocyanin ◽

Antioxidant Power

In present study, fruit weight, fruit firmness, external fruit color, soluble solid content, pH, titratable acidity, vitamin C, total phenolics, total anthocyanins, and antioxidant capacity of eight wild bilberry grown in Coruh valley in northeastern Turkey were determined. The blueberry cv. ‘Bluecrop’ is also included study to make comparison with bilberry genotypes. Antioxidant activity of bilberry and blueberry fruits were comparatively assessed by FRAP (Ferric reducing antioxidant power) assay. Significantly higher content of phenolics and anthocyanins was found in bilberry fruits than in blueberry fruits. However blueberry cv. ‘Bluecrop’ exhibited higher fruit weight and vitamin C content than bilberry fruits. Total phenolic and total anthocyanin content was 327 mg gallic acid equivalent and 142 mg of cyanidin-3-glucoside equivalent in 100 g fresh fruit in cv. ‘Bluecrop’ while it was between 492-563 mg gallic acid equaivalent and 307-342 mg of cyanidin-3-glucoside equivalent in 100 g fresh fruits of bilberry accessions. Moreover, wild accessions approximately had 2-3 folds higher antioxidant capacity than cv. ‘Bluecrop’. Results suggest the possibility of improving the bioactive and antioxidant properties of bilberry cultivars based food products by using wild ones in cross breeding. It was also concluded that genotypes significantly affect their bioactive content and consequently the possibility of using wild bilberry fruits as a potential source of natural antioxidants in food industry.

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PSXV-27 Late-Breaking: Evaluation of antioxidant capacity in receiving beef calves challenged with lipopolysaccharide (LPS)

Journal of Animal Science ◽

10.1093/jas/skab235.699 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 381-382

Author(s):

Samantha N Barker ◽

Treylr Jackson ◽

John Richeson ◽

Jeff A Carroll ◽

Nicole C Burdick-Sanchez ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Repeated Measures ◽

Colorimetric Assay ◽

Post Challenge ◽

Antioxidant Power ◽

Blood Samples ◽

Endotoxin Challenge ◽

Beef Calves ◽

Lps Challenge

Abstract The objective of this study was to evaluate antioxidant capacity in plasma of beef calves challenged with LPS. Following an initial feeding period of 40 d, steers (n = 32; 379 kg ± 30.7) were transported to the Livestock Issues Research Unit’s Bovine Immunology Research and Development Complex and challenged intravenously with LPS (0.25 µg/kg BW) on d 41. Blood samples were collected via jugular catheter at -2, 0, 2, 4, 6, 8, 10, 12, 18, 24, 36 and 48 h relative to the LPS challenge at 0 h. Blood samples were processed to isolate plasma for indicators of oxidative stress with a colorimetric assay to determine ferric reducing antioxidant power (FRAP) values via concentration of ferrous iron (µM). Data were analyzed as repeated measures using the GLIMMIX procedure of SAS. Antioxidant values did vary with time (P < 0.001) being greater (P < 0.05) at -2, 0, 2, 36, and 48 h. Antioxidant capacity was reduced at 6 and 8 h (P < 0.05), with the least FRAP value observed at 8 h post-challenge. Antioxidant capacity increased (P < 0.05) again at 10 h, showing similar (P > 0.05) concentrations to those observed at 4 h. By 24 h post-challenge, plasma FRAP values increased (P < 0.05) similar to initial values at -2, 0, and 2 h. It can be inferred that oxidative stress contributes to reduced antioxidant capacity, ultimately interfering with animal growth and productivity. While these values reflect the oxidative stress response to an acute endotoxin challenge, and a subsequent recovery returning to homeostasis within 24 to 48 h, they may also correlate with other physiological and immunological indicators associated with an acute endotoxin challenge.

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Anti-Diabetic Activity of 2,3,6-Tribromo-4,5-Dihydroxybenzyl Derivatives from Symphyocladia latiuscula through PTP1B Downregulation and α-Glucosidase Inhibition

Marine Drugs ◽

10.3390/md17030166 ◽

2019 ◽

Vol 17 (3) ◽

pp. 166 ◽

Cited By ~ 9

Author(s):

Pradeep Paudel ◽

Su Seong ◽

Hye Park ◽

Hyun Jung ◽

Jae Choi

Keyword(s):

Glucose Uptake ◽

Methyl Ether ◽

In Silico ◽

Hepg2 Cells ◽

Halogen Bond ◽

Biological Activities ◽

Tyrosine Phosphatase ◽

Docking Simulations ◽

Insulin Resistant ◽

Ring Number

The marine alga, Symphyocladia latiuscula (Harvey) Yamada, is a good source of bromophenols with numerous biological activities. This study aims to characterize the anti-diabetic potential of 2,3,6-tribromo-4,5-dihydroxybenzyl derivatives isolated from S. latiuscula via their inhibition of tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Additionally, this study uses in silico modeling and glucose uptake potential analysis in insulin-resistant (IR) HepG2 cells to reveal the mechanism of anti-diabetic activity. This bioassay-guided isolation led to the discovery of three potent bromophenols that act against PTP1B and α-glucosidase: 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). All compounds inhibited the target enzymes by 50% at concentrations below 10 μM. The activity of 1 and 2 was comparable to ursolic acid (IC50; 8.66 ± 0.82 μM); however, 3 was more potent (IC50; 5.29 ± 0.08 μM) against PTP1B. Interestingly, the activity of 1–3 against α-glucosidase was 30–110 times higher than acarbose (IC50; 212.66 ± 0.35 μM). Again, 3 was the most potent α-glucosidase inhibitor (IC50; 1.92 ± 0.02 μM). Similarly, 1–3 showed concentration-dependent glucose uptake in insulin-resistant HepG2 cells and downregulated PTP1B expression. Enzyme kinetics revealed different modes of inhibition. In silico molecular docking simulations demonstrated the importance of the 7–OH group for H-bond formation and bromine/phenyl ring number for halogen-bond interactions. These results suggest that bromophenols from S. latiuscula, especially highly brominated 3, are inhibitors of PTP1B and α-glucosidase, enhance insulin sensitivity and glucose uptake, and may represent a novel class of anti-diabetic drugs.

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Melatonin synthesis enzymes interact with ascorbate peroxidase to protect against oxidative stress in cassava

Journal of Experimental Botany ◽

10.1093/jxb/eraa267 ◽

2020 ◽

Vol 71 (18) ◽

pp. 5645-5655 ◽

Cited By ~ 1

Author(s):

Yujing Bai ◽

Jingru Guo ◽

Russel J Reiter ◽

Yunxie Wei ◽

Haitao Shi

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Stress Tolerance ◽

Ascorbate Peroxidase ◽

Stress Responses ◽

Direct Interaction ◽

Ros Scavenging ◽

Melatonin Synthesis

Abstract Melatonin is an important indole amine hormone in animals and plants. The enzymes that catalyse melatonin synthesis positively regulate plant stress responses through modulation of the accumulation of reactive oxygen species (ROS). However, the relationship between melatonin biosynthetic enzymes and ROS-scavenging enzymes has not been characterized. In this study, we demonstrate that two enzymes of the melatonin synthesis pathway in Manihot esculenta (MeTDC2 and MeASMT2) directly interact with ascorbate peroxidase (MeAPX2) in both in vitro and in vivo experiments. Notably, in the presence of MeTDC2 and MeASMT2, MeAPX2 showed significantly higher activity and antioxidant capacity than the purified MeAPX2 protein alone. These findings indicate that MeTDC2–MeAPX2 and MeASMT2–MeAPX2 interactions both activate APX activity and increase antioxidant capacity. In addition, the combination of MeTDC2, MeASMT2, and MeAPX2 conferred improved resistance to hydrogen peroxide in Escherichia coli. Moreover, this combination also positively regulates oxidative stress tolerance in cassava. Taken together, these findings not only reveal a direct interaction between MeTDC2, MeASMT2, and MeAPX2, but also highlight the importance of this interaction in regulating redox homoeostasis and stress tolerance in cassava.

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Evaluation of Salivary and Serum Total Antioxidant Capacity and Lipid Peroxidation in Postmenopausal Women

International Journal of Dentistry ◽

10.1155/2020/8860467 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Fatemeh Zovari ◽

Hadi Parsian ◽

Ali Bijani ◽

Ameneh Moslemnezhad ◽

Atena Shirzad

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Antioxidant Capacity ◽

Postmenopausal Women ◽

Total Antioxidant Capacity ◽

Premenopausal Women ◽

Control Group ◽

Antioxidant Power ◽

Whole Saliva ◽

Total Antioxidant

Objective. In menopause, reduction of estrogen hormone affects oxidative stress process in serum. Oxidative stress in saliva plays a significant role in the pathogenesis of oral diseases. The aim of this study was to investigate the total antioxidant capacity and lipid peroxidation in the serum and saliva of premenopausal and postmenopausal women. Methods. In this case control study, 50 postmenopausal women (case group) and 48 premenopausal women (control group) were selected. The unstimulated whole saliva and serum of the postmenopausal and premenopausal women were collected. The total antioxidant capacity (TAC) of the saliva and serum was measured by ferric reducing antioxidant power (FRAP). Also, malondialdehyde (MDA) was measured by thiobarbituric acid reactive substance (TBARS) method for serum and saliva. Then, the obtained data were analyzed by SPSS 17, whereby Mann–Whitney test and Spearman’s correlation test were used. P < 0.05 was considered statistically significant. Results. The postmenopausal group had significantly lower mean serum TAC and higher mean serum MDA than the control group ( P < 0 < 001 and P < 0.01 , respectively). The mean salivary TAC and MDA, however, did not differ significantly between the case and control group ( P = 0.64 and P = 0.08 , respectively). Conclusion. In postmenopausal women, with elevation of serum MDA and reduction of serum TAC, the extent of serum oxidative stress grows, but MDA and TAC levels of saliva do not change.

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GC-MS analysis and Mitochondrial Functionality Potential of the Fruits ofTetrapleura tetraptera By Cupric Reducing Antioxidant Capacity Assay

Journal of Phytomedicine and Therapeutics ◽

10.4314/jopat.v19i1.2 ◽

2020 ◽

Vol 19 (1) ◽

pp. 338-347

Author(s):

Chinwe S. Alaribe ◽

Akolade R. Oladipupo ◽

Osamede Ojo-Nosakhare ◽

Omotayo Kehinde ◽

Adeniyi S. Ogunlaja

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Antioxidant Capacity ◽

Vaccenic Acid ◽

Octadecenoic Acid ◽

Ethanol Extract ◽

Gas Chromatography Mass Spectrometry ◽

Ms Analysis ◽

Degenerative Disorders ◽

Tetrapleura Tetraptera

The use of antioxidants has emerged as a promising therapeutic strategy for the management of mitochondrial dysfunction and other oxidative stress-related degenerative pathologies. Tetrapleura tetraptera is a well-known tree and its fruit is applied traditionally as spice and in the preparation of remedies for different ailments. In this study, the gas chromatography-mass spectrometry (GC-MS) analysis and mitochondrial functionality potential of T. tetraptera fruits were investigated. GC-MS was used to detect compounds in then-hexane and ethanol extracts of T. tetraptera fruits. Cupric reducing antioxidant capacity (CUPRAC) assay was used to evaluate the mitochondrial functionality potential of the ethanol extract. GC-MS analysis revealed the presence of six compounds in then-hexane extract of T. tetraptera fruits. These compounds were detected in trace quantities, the most abundant being 2,3-dimethyl-3-buten-2-ol (0.04%). The compounds: cis-vaccenic acid (35.37%), n-hexadecanoic acid (28.09%), 6-octadecenoic acid (25.21%), and octadecanoic acid (11.33%) were identified in the ethanol extract of the fruits. Consequently, the ethanol extract was subjected to CUPRAC assay. The ethanol extract exhibited a concentration-dependent high cupric reducing capacity, returning CUPRAC values in the range of 0.090 to 0.403 at the concentration of 10 – 80 μg/ml. This activity was comparable to that of the positive control, naringenin, which showed CUPRAC values of 0.059 – 0.378 at the same concentrations. These results indicate that T. tetraptera fruits possess good antioxidant property as evaluated by other related antioxidant assays. This could be attributed to a synergistic effect of the phytochemical constituents. Hence consumption of T. tetraptera fruits could be beneficial for the prevention of mitochondrial dysfunction and other oxidative stress-related degenerative disorders. Keywords: Tetrapleura tetraptera, mitochondrial dysfunction, degenerative disorders, CUPRAC, GC-MS, Nigeria

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Salivary antioxidant status and oral health in children and adolescents

New Medicine ◽

10.25121/newmed.2019.23.4.145 ◽

2019 ◽

Vol 23 (4) ◽

Author(s):

Paula Piekoszewska-Ziętek ◽

Emilia Raćkowska ◽

Natalia Korytowska ◽

Dorota Olczak-Kowalczyk

Keyword(s):

Oxidative Stress ◽

Oral Health ◽

Antioxidant Capacity ◽

Children And Adolescents ◽

Oral Hygiene ◽

Protective Factor ◽

Salivary Flow ◽

White Spot ◽

White Spot Lesions ◽

Antioxidant Power

Introduction. The pathogenesis of oral diseases may be associated with oxidative stress. Salivary antioxidant system constitutes one of the key salivary defence mechanisms against pathogens and a protective factor for oral cavity. Aim. To investigate the relationship between oral health (hygiene level, gingival and dental health), age and gender and antioxidant capacity parameters in children and adolescents with permanent dentition. Material and methods. A total of 87 patients were examined. DMFT/DMFS and white spot lesions (WSL), oral hygiene level and gingival health were assessed. Salivary samples were collected from all participants. Unstimulated salivary flow was calculated and salivary samples were assayed for total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP). Results. Antioxidant capacity parameters were lower in patients with caries, active caries, white spot lesions, poor oral hygiene and gingivitis, but the differences were not statistically significant. Oxidative stress parameters were significantly higher in low unstimulated salivary flow. Spearman’s rank correlation analysis revealed no relationship between TAC or FRAP values and patients’ gender, but there was a positive correlation between TAC/FRAP and patients’ age. Conclusions. Salivary antioxidant capacity parameters differ in certain oral conditions. There is a correlation between salivary antioxidant capacity parameters and patients’ age.

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Malus baccata var. gracilis and Malus toringoides Bark Polyphenol Studies and Antioxidant, Antimicrobial and Anticancer Activities

Processes ◽

10.3390/pr8030283 ◽

2020 ◽

Vol 8 (3) ◽

pp. 283 ◽

Cited By ~ 5

Author(s):

Hosam O. Elansary ◽

Agnieszka Szopa ◽

Paweł Kubica ◽

Diaa O. El-Ansary ◽

Halina Ekiert ◽

...

Keyword(s):

High Performance ◽

Protocatechuic Acid ◽

Antioxidant Activities ◽

Biological Activities ◽

Dry Weight ◽

Jurkat Cells ◽

Aspergillus Ochraceus ◽

Array Detector ◽

Anticancer Activities ◽

Antioxidant Power

Exploring new sources of polyphenols with biological activities that work against human diseases is the target of natural product studies. This study determined the polyphenol composition of the bark of Malus species M. baccata var. gracilis (Rehder) T.C.Ku and M. toringoides (Rehder) Hughes, using high-performance liquid chromatography with a diode-array detector (HPLC-DAD) analysis. The antiproliferative, cytotoxic, antioxidant and antimicrobial applications of these extracts, as well as the identified phenol, were studied. The HPLC-DAD analysis confirmed three polyphenols in the extracts out of the 21 screened compounds: protocatechuic acid, gallic acid, and catechin. The major constituents in M. baccata and M. toringoides were protocatechuic acid, at 3.16 and 7.15 mg 100 g−1 dry weight (DW), respectively, and catechin, at 5.55 and 6.80 mg 100 g−1 DW, respectively. M. baccata and M. toringoides bark extracts showed antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), β-carotene bleaching, and ferric-reducing antioxidant power (FRAP) assays, which were attributed to the dominance of protocatechuic acid. The highest antiproliferative and cytotoxic effects were against Jurkat cells. Against MCF-7 and Hela cells, there was necrotic cell accumulation in the early apoptotic as well as the late apoptotic phase. The bark extracts showed noticeable antibacterial effects against Listeria monocytogenes, Bacillus cereus, and Escherichia coli. Protocatechuic acid showed comparable results to bark extracts. There were antifungal effects against Aspergillus ochraceus, A. niger, and Candida albicans, and the activities were higher than the commercial reagent. M. baccata and M. toringoides could be considered as a new source of phenolic acids, including protocatechuic acid with anticancer, antibacterial antifungal, and antioxidant-promising effects.

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An Investigation of Potential Sources of Nutraceuticals from the Niger Delta Areas, Nigeria for Attenuating Oxidative Stress

Medicines ◽

10.3390/medicines6010015 ◽

2019 ◽

Vol 6 (1) ◽

pp. 15 ◽

Cited By ~ 5

Author(s):

Lucky Nwidu ◽

Philip Alikwe ◽

Ekramy Elmorsy ◽

Wayne Carter

Keyword(s):

Oxidative Stress ◽

Gallic Acid ◽

Inhibitory Activity ◽

Niger Delta ◽

Radical Scavenging ◽

Seed Extract ◽

Total Phenolic ◽

Fruit Extract ◽

Tetrapleura Tetraptera ◽

Ache Inhibitory Activity

Background: Diets rich in fruits, vegetables, and medicinal plants possess antioxidants potentially capable of mitigating cellular oxidative stress. This study investigated the antioxidant, anti-acetylcholinesterase (AChE), and total phenolic and flavonoids contents (TPC/TFC) of dietary sources traditionally used for memory enhancing in Niger Delta, Nigeria. Methods: Dacroydes edulis methanolic seed extract (DEMSE), Cola lepidota methanolic seed extract (CLMSE), Terminalia catappa methanolic seed extract (TeCMSE), Tricosanthes cucumerina methanolic seed extract (TrCMSE), Tetrapleura tetraptera methanolic seed extract (TTMSE), and defatted Moringa oleifera methanolic seed extract (DMOMSE); Dennettia tripetala methanolic fruit extract (DTMFE), Artocarpus communis methanolic fruit extract (ACMFE), Gnetum africana methanolic leaf extract (GAMLE), Musa paradisiaca methanolic stembark extract (MPMSE), and Mangifera indica methanolic stembark extract (MIMSE) were evaluated for free radical scavenging antioxidant ability using 2,2-Diphenyl-1-picrylhydrazyl (DPPH), reducing power capacity (reduction of ferric iron to ferrous iron), AChE inhibitory potential by Ellman assay, and then TPC/TFC contents determined by estimating milli-equivalents of Gallic acid and Quercetin per gram, respectively. Results: The radical scavenging percentages were as follows: MIMSE (58%), MPMSE (50%), TrCMSE (42%), GAMLE (40%), CLMSE (40%), DMOMSE (38%), and DEMFE (37%) relative to β-tocopherol (98%). The highest iron reducing (antioxidant) capacity was by TrCMSE (52%), MIMSE (40%) and GAMLE (38%). Extracts of MIMSE, TrCMSE, DTMFE, TTMSE, and CLMSE exhibited concentration-dependent AChE inhibitory activity (p < 0.05–0.001). At a concentration of 200 µg/mL, the AChE inhibitory activity and IC50 (µg/mL) exhibited by the most potent extracts were: MIMSE (≈50%/111.9), TrCMSE (≈47%/201.2), DTMFE (≈32%/529.9), TTMSE (≈26%/495.4), and CLMSE (≈25%/438.4). The highest TPC were from MIMSE (156.2), TrCMSE (132.65), GAMLE (123.26), and CLMSE (119.63) in mg gallic acid equivalents/g, and for TFC were: MISME (87.35), GAMLE (73.26), ACMFE (69.54), CLMSE (68.35), and TCMSE2 (64.34) mg quercetin equivalents/gram. Conclusions: The results suggest that certain inedible and edible foodstuffs, most notably MIMSE, MPMSE, TrCMSE, GAMLE, and CLMSE may be beneficial to ameliorate the potentially damaging effects of redox stress.

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Derivatization of chlorin e6 with maleimide enhances its photodynamic efficacy in HepG2 cells

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424620500248 ◽

2020 ◽

Vol 24 (09) ◽

pp. 1093-1098

Author(s):

Xiuhan Guo ◽

Shisheng Wang ◽

Fan Zhang ◽

Guangzhe Li ◽

Yueqing Li ◽

...

Keyword(s):

Oxidative Stress ◽

Hepg2 Cells ◽

Redox System ◽

Chlorin E6 ◽

Ros Scavenging ◽

Cellular Redox ◽

New Strategy ◽

Maleimide Group ◽

High Level ◽

Derivatives Of

Three derivatives of chlorin e6 (1–3) were synthesized by introduction of maleimide, cysteine and glutathione at C-13 carboxyl of the chlorin scaffold. The evaluation of their PDT effects showed that compound 1, the derivative with a maleimide group, exhibited more potent photocytotoxicity against HepG2 cells (IC[Formula: see text] 3.2 [Formula: see text]M) than 2 (IC[Formula: see text] 6.7 [Formula: see text]M) and 3 (IC[Formula: see text] 10.2 [Formula: see text]M), although the cellular uptake of 1 was slightly lower than that of 2 and 3. The high PDT effect of 1 was found to be in agreement with the high level of intracellular singlet oxygen. Further investigation of the mechanism revealed that 1 can significantly lower the GSH level in HepG2 cells due to the addiction reaction of maleimide and GSH, thus resulting in the reduction of ROS scavenging and the enhancement of cellular oxidative stress. This approach to improve PDT effects of photosensitizers by means of interfering with the cellular redox system and enhancing cellular oxidative stress offers a new strategy for development of photosensitizers in cancer therapy.

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