bims-polyam 2022-05-22 papers

Issue of 2022–05–22
four papers selected by
Sebastian J. Hofer, University of Graz

Plant Physiol Biochem. 2022 May 13. pii: S0981-9428(22)00222-4. [Epub ahead of print]183 128-137

Developmental and phytochemical changes in pot marigold (Calendula officinalis L.) using exogenous application of polyamines.

Vahid Tavallali, Nasrin Alhavi, Hossein Gholami, Faezeh Mirazimi Abarghuei.

Polyamines (PAs) are natural active compounds having more than two amino groups that play important roles in many physiological and developmental processes in plants. The purpose of this research was to see how foliar polyamine spray affected growth and photosynthetic indices, as well as secondary metabolites and antioxidant activity of the aqueous and methanolic extracts of pot marigold (Calendula officinalis L.). The experiment lasted for three months and was arranged in a randomized complete design with four replications. Three separate concentrations (0.5, 1 and 2.5 mM) of spermine (SPM), spermidine (SPD), and putrescine (PUT) were sprayed at four/five fully expanded leaf stage and some physiochemical attributes were evaluated. The treatments caused a significant increase in morphological and photosynthetic parameters and total oil. There were also significant variations in total phenolic and flavonoid content. Compared to other polyamines, 1 mM SPD foliar spraying showed the greatest effect. Furthermore, the highest antioxidant capacity (DPPH* scavenging assay, ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and β-carotene bleaching activity) was observed in the 1 mM SPD treatment. The results showed that the calendula essential oils (EOs) were rich in sesquiterpenes hydrocarbons (55.92-95.94%), with c-Cadinene and d-Cadinene as the major sesquiterpenes in the EOs. Also, the flowers were rich sources of carotenoids (lutein, flavoxanthin and luteoxanthin) following polyamines application. Hence, it can be inferred that polyamines specially spermidine would find a wide range of application in pharmaceutical industries due to its impact on antioxidant properties of phenolic and flavonoid compounds.

Keywords: Antioxidant activity; Calendula; Essential oil; Lutein; Lycopene; Phytostimulator

DOI: https://doi.org/10.1016/j.plaphy.2022.05.011

J Agric Food Chem. 2022 May 18.

Spermidine Ameliorates Nonalcoholic Steatohepatitis through Thyroid Hormone-Responsive Protein Signaling and the Gut Microbiota-Mediated Metabolism of Bile Acids.

Yinhua Ni, Yating Hu, Xiaoyi Lou, Nianke Rong, Fang Liu, Congrong Yang, Aqian Zheng, Song Yang, Jianfeng Bao, Zhengwei Fu.

Spermidine, a natural polyamine and physiological autophagy inducer, is involved in various physiological processes. However, the impact and mechanism of spermidine on nonalcoholic steatohepatitis (NASH) remains unclarified. We found that daily spermidine intake was significantly lower in volunteers with liver dysfunction than the healthy controls, and the serum and fecal spermidine levels were negatively correlated with the NASH phenotypes. Spermidine supplementation significantly attenuated hepatic lipid accumulation, insulin resistance, hepatic inflammation, and fibrosis in NASH mice induced by a western diet. The ameliorating effect of spermidine on lipid accumulation might be partly regulated by thyroid hormone-responsive protein (THRSP) signaling and autophagy. Moreover, spermidine altered the profile of hepatic bile acids (BAs) and microbial composition and function. Furthermore, spermidine reversed the progression of hepatic steatosis, inflammation, and fibrosis in mice with preexisting NASH. Therefore, spermidine ameliorates NASH partly through the THRSP signaling and the gut microbiota-mediated metabolism of BAs, suggesting that spermidine might be a viable therapy for NASH.

Keywords: THRSP; autophagy; bile acid; microbiota; nonalcoholic steatohepatitis; spermidine

DOI: https://doi.org/10.1021/acs.jafc.2c02729

Autophagy. 2022 May 17.

Distinct designer diamines promote mitophagy, and thereby enhance healthspan in C. elegans and protect human cells against oxidative damage.

Vijigisha Srivastava, Veronica Zelmanovich, Virendra Shukla, Rachel Abergel, Irit Cohen, Shmuel A Ben-Sasson, Einav Gross.

Impaired mitophagy is a primary pathogenic event underlying diverse aging-associated diseases such as Alzheimer and Parkinson diseases and sarcopenia. Therefore, augmentation of mitophagy, the process by which defective mitochondria are removed, then replaced by new ones, is an emerging strategy for preventing the evolvement of multiple morbidities in the elderly population. Based on the scaffold of spermidine (Spd), a known mitophagy-promoting agent, we designed and tested a family of structurally related compounds. A prototypic member, 1,8-diaminooctane (VL-004), exceeds Spd in its ability to induce mitophagy and protect against oxidative stress. VL-004 activity is mediated by canonical aging genes and promotes lifespan and healthspan in C. elegans. Moreover, it enhances mitophagy and protects against oxidative injury in rodent and human cells. Initial structural characterization suggests simple rules for the design of compounds with improved bioactivity, opening the way for a new generation of agents with a potential to promote healthy aging.

Keywords: Aging; Caenorhabditis elegans; diamine; healthspan; lifespan; mitochondrial autophagy; mitophagy; oxidative stress; spermidine

DOI: https://doi.org/10.1080/15548627.2022.2078069

Biomed Pharmacother. 2022 May;pii: S0753-3322(22)00307-9. [Epub ahead of print]149 112918

Are mitophagy enhancers therapeutic targets for Alzheimer's disease?

Jangampalli Adi Pradeepkiran, Ashly Hindle, Sudhir Kshirsagar, P Hemachandra Reddy.

Healthy mitochondria are essential for functional bioenergetics, calcium signaling, and balanced redox homeostasis. Dysfunctional mitochondria are a central aspect of aging and neurodegenerative diseases such as Alzheimer's disease (AD). The formation and accumulation of amyloid beta (Aβ) and hyperphosphorylated tau (P-tau) play large roles in the cellular changes seen in AD, including mitochondrial dysfunction, synaptic damage, neuronal loss, and defective mitophagy. Mitophagy is the cellular process whereby damaged mitochondria are selectively removed, and it plays an important role in mitochondrial quality control. Dysfunctional mitochondria are associated with increased reactive oxygen species and increased levels of Aβ, P-tau and Drp1, which together trigger mitophagy and autophagy. Impaired mitophagy causes the progressive accumulation of defective organelles and damaged mitochondria, and it has been hypothesized that the restoration of mitophagy may offer therapeutic benefits to AD patients. This review highlights the challenges of pharmacologically inducing mitophagy through two different signaling cascades: 1) The PINK1/parkin-dependent pathway and 2) the PINK1/parkin-independent pathway, with an emphasis on abnormal mitochondrial interactions with Aβ and P-Tau, which alter mitophagy in an age-dependent manner. This article also summarizes recent studies on the effects of mitophagy enhancers, including urolithin A, NAD+, actinonin, and tomatidine, on mutant APP/Aβ and mutant Tau. Findings from our lab have revealed that mitophagy enhancers can suppress APP/Aβ-induced and mutant Tau-induced mitochondrial and synaptic dysfunctions in mouse and cell line models of AD. Finally, we discuss the mechanisms underlying the beneficial health effects of mitophagy enhancers like urolithin A, NAD+, resveratrol and spermidine in AD.

Keywords: Alzheimer’s disease; Aβ; Mitochondrial dysfunction; Mitophagy; Phosphorylated tau

DOI: https://doi.org/10.1016/j.biopha.2022.112918