A standardized extract of Asparagus officinalis stem improves HSP70-mediated redox balance and cell functions in bovine cumulus-granulosa cells

Heat shock (HS) protein 70 (HSP70), a well-known HS-induced protein, acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to confer stress resistance to cells, HS causes cell toxicity by increasing reactive oxygen species (ROS) levels. Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the byproduct of asparagus, has been shown to induce HSP70 expression without HS and regulate cellular redox balance in pheochromocytoma cells. However, the effects of EAS on reproductive cell function remain unknown. Here, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa (CG) cells. EAS significantly increased HSP70 expression; however, no effect was observed on HSP27 and HSP90 under non-HS conditions. EAS decreased ROS generation and DNA damage and increased glutathione (GSH) synthesis under both non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression and increased progesterone levels in CG cells. Treatment with an HSP70 inhibitor significantly decreased GSH level, increased ROS level, and decreased HSF1, Nrf2, and Keap1 expression in the presence of EAS. Furthermore, EAS significantly increased progesterone synthesis. Thus, EAS improves HSP70-mediated redox balance and cell function in bovine CG cells.

Effect of A Standardized Extract of Asparagus Officinalis Stem on HSP 70 Induction and Redox Balance in Bovine Cumulus-Granulosa Cells

Heat shock protein 70 (HSP70) is a well-known heat shock (HS)-induced protein that acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to acquire stress-resistant ability to cells, HS causes toxicity to cells by increasing reactive oxygen species (ROS). Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the by-product of asparagus, was found to induce HSP70 expression without HS and regulate cellular redox balance in the cells. However, the effect of EAS on the function of reproductive cells remains unknown. In the present study, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa(CG) cells. EAS significantly increased HSP70 expression, whereas no effect was observed in HSP27 and − 90 under non-heat stress condition. EAS decreased ROS generation and DNA damage, and increased glutathione (GSH) synthesis both under non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression. EAS also increased progesterone (P4) levels in CG cells. HSP70 inhibitor significantly decreased GSH and increased ROS, as well as decreased HSF1, Nrf2, and Keap1 in the presence of EAS. These results suggest that EAS regulates redox balance through HSP70 in bovine CG cells.

Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury

The 70 kDa heat shock protein (HSP70) is a stress-inducible protein that has been shown to protect the brain from various nervous system injuries. It allows cells to withstand potentially lethal insults through its chaperone functions. Its chaperone properties can assist in protein folding and prevent protein aggregation following several of these insults. Although its neuroprotective properties have been largely attributed to its chaperone functions, HSP70 may interact directly with proteins involved in cell death and inflammatory pathways following injury. Through the use of mutant animal models, gene transfer, or heat stress, a number of studies have now reported positive outcomes of HSP70 induction. However, these approaches are not practical for clinical translation. Thus, pharmaceutical compounds that can induce HSP70, mostly by inhibiting HSP90, have been investigated as potential therapies to mitigate neurological disease and lead to neuroprotection. This review summarizes the neuroprotective mechanisms of HSP70 and discusses potential ways in which this endogenous therapeutic molecule could be practically induced by pharmacological means to ultimately improve neurological outcomes in acute neurological disease.

Isolation and Structure Determination of a Heat Shock Protein Inducer, Asparagus-Derived Proline-Containing 3-Alkyldiketopiperazines (Asparaprolines), From a Standardized Extract of Asparagus officinalis Stem

ETAS® has been developed from the stems of Asparagus officinalis L. as a functional ingredient for nutraceuticals. ETAS possesses heat shock protein 70 (HSP70) induction activity and may contribute to maintenance and improvement of health. Here, 3 compounds (1, 2, 3) were isolated from ETAS. The structures of 1, 2, and 3 were deduced by HREIMS and NMR spectroscopic data, and the compounds were identified as cyclo(l-Phe-l-Pro), cyclo(l-Tyr-l-Pro), and cyclo(l-Leu-l-Pro), respectively. Each compound contained a diketopiperazine ring derived from proline with an alkyl group at C-3; thus, we termed them asparagus-derived proline-containing 3-alkyldiketopiperazines (Asparaprolines). In an HSP70 mRNA induction assay in HL-60 cells, Asparaprolines significantly enhanced the expression of HSP70 mRNA compared with a control. To our knowledge, these results demonstrate for the first time that proline-containing diketopiperazines derived from natural amino acids exhibit HSP70 mRNA induction activity.

The possible role of heat shock protein-70 induction in collagen-induced arthritis in rats

AimThis study aimed to evaluate the possible role of heat shock protein-70 (HSP70) induction by 17-allylaminodemethoxygeldanamycin (17-AAG) in collagen-induced arthritis in rats.Material and methodsMale Wistar rats were divided into five groups (n = 10/group) and were treated intraperitoneally twice a week for 4 weeks, namely normal control (saline), arthritis control (AR; saline), AR + 17-AAG, AR + methotrexate (MTX), and AR + 17-AAG + MTX. At the end of the treatments, arthritic score was determined and then the animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx), and matrix metalloproteinase-9 (MMP-9) were determined.ResultsIn the AR group, all parameters increased significantly, except for GPx, which showed a pronounced decrease. The 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-α, RF, CRP, MDA, and MMP-9 with significant increase in GPx compared to the AR group. The HSP70 level was significantly higher in the AR + 17-AAG and the AR + 17-AAG + MTX groups but significantly lower in the AR + MTX group as compared to the AR group. Also, it was significantly lower in the AR + MTX group as compared to the AR + 17-AAG group.ConclusionWe concluded that HSP70 induction by 17-AAG attenuated the inflammatory process in a rheumatoid arthritis (RA) model induced by collagen, which suggested that HSP70 inducers can be promising agents in the treatment of RA.