scholarly journals Tanshinones from Salvia miltiorrhiza inhibit Mycobacterium tuberculosis via disruption of the cell envelope surface and oxidative stress

2021 ◽  
pp. 112405
Author(s):  
Elwira Sieniawska ◽  
Rafal Sawicki ◽  
Andrey S. Marchev ◽  
Wieslaw Truszkiewicz ◽  
Milen I. Georgiev
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Cell Envelope ◽  
Salvia Miltiorrhiza ◽  
Envelope Surface ◽  
And Oxidative Stress

scholarly journals Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Ting Wu ◽  
Ling-Peng Xie ◽  
Yue Hua ◽  
Hong-Lin Xu ◽  
Guang-Hong Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Knockout Mice ◽  
Salvia Miltiorrhiza ◽  
Mapk Signaling ◽  
Related Factor ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Tanshinone I ◽  
Nrf2 Knockout ◽  
And Oxidative Stress

Cardiovascular disease, a disease caused by many pathogenic factors, is one of the most common causes of death worldwide, and oxidative stress plays a major role in its pathophysiology. Tanshinone I (Tan I), a natural compound with cardiovascular protective effects, is one of the main active compounds extracted from Salvia miltiorrhiza. Here, we investigated whether Tan I could attenuate oxidative stress and oxidative stress–induced cardiomyocyte apoptosis through Nrf2/MAPK signaling in vivo and in vitro. We found that Tan I treatment protected cardiomyocytes against oxidative stress and oxidative stress–induced apoptosis, based on the detection of relevant oxidation indexes such as reactive oxygen species, superoxide dismutase, malondialdehyde, and apoptosis, including cell viability and apoptosis-related protein expression. We further examined the mechanisms underlying these effects, determining that Tan I activated nuclear factor erythroid 2 (NFE2)–related factor 2 (Nrf2) transcription into the nucleus and dose-dependently promoted the expression of Nrf2, while inhibiting MAPK signaling activation, including P38 MAPK, SAPK/JNK, and ERK1/2. Nrf2 inhibitors in H9C2 cells and Nrf2 knockout mice demonstrated aggravated oxidative stress and oxidative stress–induced cardiomyocyte injury; Tan I treatment suppressed these effects in H9C2 cells; however, its protective effect was inhibited in Nrf2 knockout mice. Additionally, the analysis of surface plasmon resonance demonstrated that Tan I could directly target Nrf2 and act as a potential Nrf2 agonist. Collectively, these data strongly indicated that Tan I might inhibit oxidative stress and oxidative stress–induced cardiomyocyte injury through modulation of Nrf2 signaling, thus supporting the potential therapeutic application of Tan I for oxidative stress–induced CVDs.

scholarly journals Deletionof Mycobacterium tuberculosis Sigma Factor E Results inDelayed Time to Death with Bacterial Persistence in the Lungsof Aerosol-InfectedMice

2003 ◽  
Vol 71 (12) ◽  
pp. 7170-7172 ◽  
Author(s):  
Masaru Ando ◽  
Tetsuyuki Yoshimatsu ◽  
Chiew Ko ◽  
Paul J. Converse ◽  
William R. Bishai
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Heat Shock ◽  
Sodium Dodecyl Sulfate ◽  
Sigma Factor ◽  
Sodium Dodecyl ◽  
Bacterial Persistence ◽  
Time To Death ◽  
And Oxidative Stress ◽  
Sigma Factor E

ABSTRACT The stress-induced extracytoplasmic sigma factor E (SigE) of Mycobacterium tuberculosis shows increased expression after heat shock, sodium dodecyl sulfate treatment, and oxidative stress, as well as after phagocytosis in macrophages. We report that deletion of sigE results in delayed lethality in mice without a significant reduction of bacterial numbers in lungs.

scholarly journals Salvia miltiorrhiza hydroalcoholic extract inhibits postoperative peritoneal adhesions in rats

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Abbas Raisi ◽  
Omid Dezfoulian ◽  
Farshid Davoodi ◽  
Shayan Taheri ◽  
Soroush Afshar Ghahremani
Keyword(s):  
Oxidative Stress ◽  
Salvia Miltiorrhiza ◽  
Control Group ◽  
Distilled Water ◽  
Oxidative Stress Biomarkers ◽  
Peritoneal Adhesions ◽  
Hydroalcoholic Extract ◽  
Treatment Groups ◽  
Stress Biomarkers ◽  
And Oxidative Stress

Abstract Background One of the most prevalent postoperative complications is believed to be intra-abdominal peritoneal adhesions, which is followed by several complications. Several adhesion prevention products have been examined, yet none of them were found to be completely effective. The current research is conducted to evaluate the beneficial effects of Salvia miltiorrhiza hydroalcoholic extract in inhibiting postoperative peritoneal adhesions in rats. Methods Forty rats were randomly classified into five equal groups (n = 8): 1) the normal group did not undergo surgical operations, 2) the control group in which the adhesion was induced, and which did not receive any treatment, 3) distilled water group that received distilled water, and 4,5) treatment groups treated with 1 and 5% of Salvia miltiorrhiza hydroalcoholic extract. The rats were euthanized 14 days following the surgery and the macroscopic score, the microscopic score of granulomatous inflammation and granulation tissue formation, IHC markers (vimentin, CD31, IL-1β, COX-2, and iNOS), and oxidative stress biomarkers (MDA, GPx, CAT, and TAC) were assessed in the experimental groups of the study. Results The difference between the control group and other groups for the adhesions macroscopic score, microscopic score, IHC markers, and oxidative stress biomarkers was significant (p < 0.05). Distilled water had no protective effect on the formation of peritoneal adhesions. Salvia miltiorrhiza treatment in two different doses significantly reduced macroscopic and microscopic scores, MDA concentration, Vimentin, IL-1β, COX-2, and iNOS compared to the control group (p < 0.05). The levels of GPx, CAT, and TAC in the treatment groups increased significantly compared with the control group (p < 0.05). Our findings revealed that a higher dose of Salvia miltiorrhiza was more effective in reducing peritoneal adhesions, proinflammatory and mesenchymal cell markers, and oxidative stress. Conclusions Salvia miltiorrhiza extract, owing to its strong antioxidant and anti-inflammatory properties, could effectively reduce peritoneal adhesions. Therefore, Salvia miltiorrhiza is recommended to be used as an effective anti-peritoneal post-operative adhesive agent.

scholarly journals Mitochondrial dysfunction promotes alternative gasdermin D-mediated inflammatory cell death and susceptibility to infection

2021 ◽  
Author(s):  
Chi G Weindel ◽  
Xiao Zhao ◽  
Eduardo Martinez ◽  
Samantha L Bell ◽  
Krystal J Vail ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Cell ◽  
Inflammatory Diseases ◽  
Neutrophil Infiltration ◽  
Inflammasome Activation ◽  
Leucine Rich Repeat ◽  
Susceptibility To Infection ◽  
And Oxidative Stress

Human mutations in mitochondrial-associated genes are associated with inflammatory diseases and susceptibility to infection. However, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) promotes mitochondrial hyper-fission, depolarization, and oxidative stress in macrophages. In the presence of Lrrk2G2019S-dependent mitochondrial perturbations, AIM2 inflammasome activation promotes more cell death but not more pyroptotic IL-1β release. Instead, inflammasome activation in Lrrk2G2019S macrophages triggers gasdermin D (GSDMD)-mediated mitochondrial pores, driving up ROS-mediated RIPK1/RIPK3/MLKL dependent necroptosis. Consequently, infection of Lrrk2G2019S mice with Mycobacterium tuberculosis elicits hyperinflammation and immunopathology via enhanced neutrophil infiltration. By uncovering that GSDMD promotes non-pyroptotic cell death in Lrrk2G2019S macrophages, our findings demonstrate that altered mitochondrial function can reprogram cell death modalities to elicit distinct immune outcomes. This provides mechanistic insights into why mutations in LRRK2 are associated with susceptibility to chronic inflammatory and infectious diseases.

Salvia Miltiorrhiza in Anti-diabetic Angiopathy

2021 ◽  
Vol 14 ◽  
Author(s):  
Zequn Yin ◽  
Xuerui Wang ◽  
Xiaoxiao Yang ◽  
Yuanli Chen ◽  
Yajun Duan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Dysfunction ◽  
Salvia Miltiorrhiza ◽  
Vascular Lesions ◽  
Diabetic Angiopathy ◽  
Bioactive Components ◽  
Cell Matrix ◽  
Accumulation Of Lipids ◽  
And Oxidative Stress ◽  
Anti Inflammation

Background:: Salvia miltiorrhiza, a traditional Chinese medicine, also named as Danshen in China, is widely used for treatment of cardiovascular disease. It demonstrates multiple biological functions, such as anti-oxidative stress, anti-inflammation and anti-thrombosis. Diabetic angiopathy is one of the diabetic complications with macro- and microangiopathy. The macroangiopathy mainly occurs to arteries, while the microangiopathy mainly includes diabetic retinopathy and nephropathy. Many factors associated with diabetes, such as metabolic abnormalities and oxidative stress, can induce vascular lesions. These factors promote the accumulation of lipids as well as inflammatory cytokines, increase production of extracellular cell matrix, and impair endothelium functions, thereby leading to vascular dysfunction. Conclusion:: This review attempts to summarize the progress of the studies of Salvia miltiorrhiza on diabetic angiopathy, including improving endothelial function, anti-oxidative stress, reducing the risk of vascular blockage, inhibiting inflammation as well as regulating lipid metabolism. We also summarize the pharmacological activity of bioactive components in Salvia miltiorrhiza and the delivery systems. We made the conclusion that Salvia miltiorrhiza can be used as a potential auxiliary drug for treatment of diabetic angiopathy.

scholarly journals The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses in Mycobacterium tuberculosis

2001 ◽  
Vol 183 (20) ◽  
pp. 6119-6125 ◽  
Author(s):  
Sahadevan Raman ◽  
Taeksun Song ◽  
Xiaoling Puyang ◽  
Stoyan Bardarov ◽  
William R. Jacobs ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Heat Stress ◽  
Heat Shock ◽  
Stress Responses ◽  
Sigma Factor ◽  
Inducible Expression ◽  
Alternative Sigma Factor ◽  
And Oxidative Stress

ABSTRACT Mycobacterium tuberculosis is a specialized intracellular pathogen that must regulate gene expression to overcome stresses produced by host defenses during infection. SigH is an alternative sigma factor that we have previously shown plays a role in the response to stress of the saprophyte Mycobacterium smegmatis. In this work we investigated the role ofsigH in the M.tuberculosis response to heat and oxidative stress. We determined that a M. tuberculosis sigHmutant is more susceptible to oxidative stresses and that the inducible expression of the thioredoxin reductase/thioredoxin genestrxB2/trxC and a gene of unknown function, Rv2466c, is regulated by sigH via expression from promoters directly recognized by SigH. We also determined that thesigH mutant is more susceptible to heat stress and that inducible expression of the heat shock genes dnaK andclpB is positively regulated by sigH. The induction of these heat shock gene promoters but not of other SigH-dependent promoters was markedly greater in response to heat versus oxidative stress, consistent with their additional regulation by a heat-labile repressor. To further understand the role ofsigH in the M.tuberculosis stress response, we investigated the regulation of the stress-responsive sigma factor genessigE and sigB. We determined that inducible expression of sigE is regulated bysigH and that basal and inducible expression ofsigB is dependent on sigE andsigH. These data indicate that sigH plays a central role in a network that regulates heat and oxidative-stress responses that are likely to be important in M.tuberculosis pathogenesis.

scholarly journals The Mycobacterium tuberculosis Sigma Factor σB Is Required for Full Response to Cell Envelope Stress and Hypoxia In Vitro, but It Is Dispensable for In Vivo Growth

2009 ◽  
Vol 191 (18) ◽  
pp. 5628-5633 ◽  
Author(s):  
P. A. Fontán ◽  
M. I. Voskuil ◽  
M. Gomez ◽  
D. Tan ◽  
M. Pardini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Sigma Factor ◽  
Cell Envelope ◽  
Hypoxic Conditions ◽  
Envelope Stress ◽  
Stress Oxidative ◽  
In Vivo Growth

ABSTRACT The numerous sigma (σ) factors present in Mycobacterium tuberculosis are indicative of the adaptability of this pathogen to different environmental conditions. In this report, we describe the M. tuberculosis σB regulon and the phenotypes of an M. tuberculosis sigB mutant strain exposed to cell envelope stress, oxidative stress, and hypoxia. The sigB mutant was especially defective in survival under hypoxic conditions in vitro, but it was not attenuated for growth in THP-1 cells or during mouse and guinea pig infection.

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