Dehydrocostus lactone induces prominent apoptosis in kidney distal tubular epithelial cells and interstitial fibroblasts along with cell cycle arrest in ovarian epithelial cells

Singireesu, Soma Shiva Nageswara Rao; Mondal, Sujan Kumar; Misra, Sunil; Yarlagadda, Suresh; K, Suresh Babu

doi:10.1016/j.biopha.2018.01.099

Cited by 11 publications

(8 citation statements)

References 54 publications

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“…In this study, negligible level of PLSCR was detected in control group cells, whereas this protein was significantly increased in the CaOx group, indicating overexpression of PLSCR. These results are consistent with the findings of Singireesu et al regarding the potential toxic effects of DHCL on kidney cells [ 33 ]. When cells in the CaOx group were treated with anti-TGF-β1 antibody, the level of PLSCR was significantly lowered, indicating that the activation of PLSCR was mediated by TGF-β1.…”

Section: Discussionsupporting

confidence: 93%

Phosphatidylserine eversion regulated by phospholipid scramblase activated by TGF-β1/Smad signaling in the early stage of kidney stone formation

Gan

Wang

2021

Urolithiasis

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The mechanism underlying phosphatidylserine eversion in renal tubule cells following calcium oxalate-mediated damage remains unclear; therefore, we investigated the effects of TGF-β1/Smad signaling on phosphatidylserine eversion in the renal tubule cell membrane during the early stage of kidney stone development. In a rat model of early stage of calcium oxalate stone formation, phosphatidylserine eversion on the renal tubular cell membrane was detected by flow cytometry, and the expression of TGF-β1 (transforming growth factor-β1), Smad7, and phospholipid scramblase in the renal tubular cell membrane was measured by western blotting. We observed that the TGF-β1/Smad signaling pathway increased phosphatidylserine eversion at the organism level. The results of in vitro studies demonstrated that oxalate exposure to renal tubule cells induced TGF-β1 expression, increasing phospholipid scramblase activity and phosphatidylserine eversion in the renal tubule cell membrane. These results indicate that TGF-β1 stimulates phosphatidylserine eversion by increasing the phospholipid scramblase activity in the renal tubule cell membrane during the early stage of kidney stone development. The results of this study form a basis for further detailed research on the development of therapeutic agents that specifically treat urolithiasis and exert fewer adverse effects.

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Section: Discussionsupporting

confidence: 93%

Phosphatidylserine eversion regulated by phospholipid scramblase activated by TGF-β1/Smad signaling in the early stage of kidney stone formation

Gan

Wang

2021

Urolithiasis

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“…Dehydrocostus lactone (DHL) is a natural sesquiterpene lactone derived from various medicinal plants such as Inula helenium L. and Saussurea lappa [20]. Numerous studies have found that DHL has anti-tumor properties, as well as hepatoprotective and immunomodulatory effects, and that some of these effects are associated with the downregulated activity of NF-κB mediated by P38/MK2 and Akt signaling pathway [21,22,23]. However, whether DHL has a beneficial effect on macrophage-mediated ALI has yet to be fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt

et al. 2019

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Acute lung injury (ALI) is a severe clinical disease marked by dysregulated inflammation response and has a high rate of morbidity and mortality. Macrophages, which play diverse roles in the inflammatory response, are becoming therapeutic targets in ALI. In this study we investigated the effects of dehydrocostus lactone (DHL), a natural sesquiterpene, on macrophage activation and LPS-induced ALI. The macrophage cell line RAW264.7 and primary lung macrophages were incubated with DHL (0, 3, 5, 10 and 30 μmol/L) for 0.5 h and then challenged with LPS (100 ng/mL) for up to 8 hours. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI) and then treated with a range of DHL doses intraperitoneally (5 to 20 mg/kg). The results showed that DHL inhibited LPS-induced production of proinflammatory mediators such as iNOS, NO, and cytokines including TNF-α, IL-6, IL-1β, and IL-12 p35 by suppressing the activity of NF-κB via p38 MAPK/MK2 and Akt signaling pathway in macrophages. The in vivo results revealed that DHL significantly attenuated LPS-induced pathological injury and reduced cytokines expression in the lung. NF-κB, p38 MAPK/MK2 and Akt signaling molecules were also involved in the anti-inflammatory effect. Collectively, our findings suggested that DHL is a promising agent for alleviating LPS-induced ALI.

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“…Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone ( Figure 1 ) isolated from medicinal plants (such as Inula helenium L. of the Asteraceae family and Saussurea lappa Clarke of the Compositae family) that has anti-oxidant, anti-inflammatory, anti-tumor, anti-ulcer, hepatoprotective and immunomodulatory properties [ 51 , 124 , 125 , 126 , 127 ]. Its biological activities are mainly exerted through the modulation of NF-κB, MAPK and PI3K/Akt signaling pathways [ 125 , 126 , 127 , 128 , 129 ].…”

Section: Plant-derived Compounds With a Reported Senotherapeutic Acti...mentioning

confidence: 99%

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Mavrogonatou,

Kletsas

2024

Metabolites

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Chronic low back pain, a major cause of disability with a great global socioeconomic impact, has been inextricably associated with intervertebral disc degeneration. On the other hand, an enhanced number of senescent cells has been identified in aged and degenerated intervertebral discs and their senescence-associated secretory phenotype (SASP) has been connected with qualitative/quantitative alterations in the extracellular matrix and ultimately with the disturbance of tissue homeostasis. Given that selective elimination of senescent cells (by the so-called senolytics) or amendment of their secretome towards a less catabolic/inflammatory phenotype (by molecules known as senomorphics) has been reported to alleviate symptoms of several age-associated diseases and to improve tissue quality during aging, here we will review the emerging role of senolytic and senomorphic agents derived from plants and natural products against intervertebral disc degeneration. The mode of action of these senotherapeutics, as well as the challenges in their practical application, will also be explicitly discussed in an attempt to direct their more targeted and effective use in exclusive or combinatorial therapeutic schemes for the prevention and/or treatment of disc degenerative disorders.

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Dehydrocostus lactone induces prominent apoptosis in kidney distal tubular epithelial cells and interstitial fibroblasts along with cell cycle arrest in ovarian epithelial cells

Cited by 11 publications

References 54 publications

Phosphatidylserine eversion regulated by phospholipid scramblase activated by TGF-β1/Smad signaling in the early stage of kidney stone formation

Phosphatidylserine eversion regulated by phospholipid scramblase activated by TGF-β1/Smad signaling in the early stage of kidney stone formation

Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

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