Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function

Zhang, Huijie; Qin, Jiawei; Lan, Xin-Qiang; Zeng, Weirong; Zhou, Jing; Huang, Tian-E; Xiao, Wan-Li; Wang, Qiquan; Sun, Sujiao; Su, Wencheng; Nie, Wei; Yang, Shan; Yang, Ji Hye; Gao, Qian; Xiang, Yang

doi:10.1007/s10522-022-09950-5

Cited by 13 publications

(21 citation statements)

References 60 publications

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“…C. elegans is a traditional and powerful model for aging and longevity studies that have helped elucidate the molecular mechanism 35 and discover novel therapeutics for aging 25 . In our present study, we found that neither knockdown nor overexpression of LIN‐24 extended the C. elegans lifespan, suggesting that its physiological role is tightly regulated.…”

Section: Discussionmentioning

confidence: 46%

Caenorhabditis elegansLIN‐24, a homolog of bacterial pore‐forming toxin, protects the host from microbial infection

Zhang,

Zeng,

Zhao

et al. 2023

The FASEB Journal

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Aerolysin‐like pore‐forming protein (af‐PFP) superfamily members are double‐edge swords that assist the bacterial infection but shied bacteria from the host by various mechanisms in some species including the toad Bombina maxima and zebrafish. While members of this family are widely expressed in all kingdoms, especially non‐bacteria species, it remains unclear whether their anti‐bacterial function is conserved. LIN‐24 is an af‐PFP that is constitutively expressed throughout the Caenorhabditis elegans lifespan. Here, we observed that LIN‐24 knockdown reduced the maximum lifespan of worms. RNA‐seq analysis identified 323 differentially expressed genes (DEGs) post‐LIN‐24 knockdown that were enriched in “immune response” and “lysosome pathway,” suggesting a possible role for LIN‐24 in resisting microbial infection. In line with this, we found that Pseudomonas aeruginosa 14 (PA14) infection induced LIN‐24 expression, and that survival after PA14 infection was significantly reduced by LIN‐24 knockdown. In contrast, LIN‐24 overexpression (LIN‐24‐OE) conferred protection against PA14 infection, with worms showing longer survival time and reduced bacterial load. Weighted gene co‐expression network analysis of LIN‐24‐OE worms showed that the highest correlation module was enriched in factors related to immunity and the defense response. Finally, by predicting transcription factors from RNA‐seq data and knocking down candidate transcription factors in LIN‐24‐OE worms, we revealed that LIN‐24 may protect worms against bacterial infection by stimulating DAF‐16‐mediated immune responses. These findings agree with our previous studies showing an anti‐microbial role for the amphibian‐derived af‐PFP complex βγ‐CAT, suggesting that af‐PFPs may play a conserved role in combatting microbial infections. Further research is needed to determine the roles this protein family plays in other physio‐pathological processes, such as metabolism, longevity, and aging.

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Section: Discussionmentioning

confidence: 46%

Caenorhabditis elegansLIN‐24, a homolog of bacterial pore‐forming toxin, protects the host from microbial infection

Zhang,

Zeng,

Zhao

et al. 2023

The FASEB Journal

Self Cite

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“…Handelin was isolated from the Chinese herb chrysanthemum and is a guaianolide dimer. This compound suppresses inflammatory responses and is considered the key anti-inflammatory component of wild chrysanthemum in Chinese medicine [27, 28]. This study provides the first demonstration, to our knowledge, that handelin has antiviral effects against FCV.…”

Section: Introductionmentioning

confidence: 93%

Drug screening identified that handelin inhibits feline calicivirus infection by inhibiting HSP70 expression in vitro

Yan,

Yang,

Jiao

et al. 2024

Journal of General Virology

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Feline calicivirus (FCV) is considered one of the major pathogens of cats worldwide and causes upper respiratory tract disease in all cats. In some cats, infection is by a highly virulent strain of FCV (vs.-FCV), which can cause severe and fatal systemic disease symptoms. At present, few antiviral drugs are approved for clinical treatment against FCV. Therefore, there is an imminent need for effective FCV antiviral agents. Here, we used observed a cytopathic effect (CPE) assay to screen 1746 traditional Chinese medicine monomer compounds and found one that can effectively inhibit FCV replication, namely, handelin, with an effective concentration (EC50) value of approximately 2.5 µM. Further study showed that handelin inhibits FCV replication via interference with heat shock protein 70 (HSP70), which is a crucial host factor and plays a positive role in regulating viral replication. Moreover, handelin and HSP70 inhibitors have broad-spectrum antiviral activity. These findings indicate that handelin is a potential candidate for the treatment of FCV infection and that HSP70 may be an important drug target.

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“…In eukaryotes, mitochondria are significant organelles that serve as the primary source of adenosine triphosphate (ATP) (Zhang et al 2022a). The mitochondrial respiratory chain is the main intracellular place for endogenous ROS production (Cadenas and Davies 2000).…”

Section: Anti-aging Molecular Mechanism By Alleviating Mitochondrial ...mentioning

confidence: 99%

“…The "homology of medicine and food" traditional Chinese medicine can now control lifespan through SKN-1, according to research. Zhang et al (Zhang et al 2022a) suggested that Chrysanthemum Indicum L. extract and Handelin could prolong the lifespan of wild-type C. elegans while reducing ROS levels, and inducing stable up-regulation of genes such as GST-5 and GST-33 involved in ROS scavenging. Both GST-5 and GST-33 were predicted to be the glutathione transferase activity of GST-4, which is a downstream target of SKN-1.…”

Section: Ins/igf-1 Signaling Pathways the Insulin /Igf-1 Signaling (I...mentioning

confidence: 99%

Molecular Mechanisms of Anti-aging Traditional Chinese Medicine with “Homology of Medicine and Food”: Under the Influence of Oxidative Stress

Bai

Han

Wang

et al. 2022

Preprint

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Background: The biological process of aging is brought on by a variety of variables and mechanisms, among which, the most comprehensive is the aging process caused by oxidative stress. The theory of the “homology of medicine and food”, originated from the thinking of traditional Chinese medicine, has gained popularity in recent years, and is believed to be utilized as a dietary therapy to ease the symptoms of aging. Purpose: We searched the recent 10-year literature on the “homology of medicine and food” traditional Chinese medicine to alleviate aging and prolong life, and summarized its anti-aging mechanism under the influence of oxidative stress. Experimental approach: Six electronic databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, Chinese Scientific Journals Database (VIP), PubMed, EMBASE, and Cochrane Library, were searched from June 2012 to June 2022 for identifying eligible studies. Key Results: The “homology of medicine and food” traditional Chinese medicine mainly scavenges free radicals, alleviates mitochondrial DNA damage, regulates telomeres and telomerase, regulates nutrient and energy sensing signaling, up-regulates sirtuins signaling pathway, and activates the Keap1-Nrf2/ARE signaling pathway mechanisms delay aging and prolong lifespan, and expect to find microcirculation mechanisms and new targets. Conclusions & Implications: The “homology of medicine and food” traditional Chinese medicine relieves the aging of the body and cells under oxidative stress through 6 pathways and is expected to find the correlation between the microcirculation formation mechanisms and identify new research targets and factors, which will provide new opportunities for life extension, prevention, and treatment of age-related diseases.

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Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function

Cited by 13 publications

References 60 publications

Caenorhabditis elegansLIN‐24, a homolog of bacterial pore‐forming toxin, protects the host from microbial infection

Caenorhabditis elegansLIN‐24, a homolog of bacterial pore‐forming toxin, protects the host from microbial infection

Drug screening identified that handelin inhibits feline calicivirus infection by inhibiting HSP70 expression in vitro

Molecular Mechanisms of Anti-aging Traditional Chinese Medicine with “Homology of Medicine and Food”: Under the Influence of Oxidative Stress

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