Holothuria scabra extracts possess anti-oxidant activity and promote stress resistance and lifespan extension in Caenorhabditis elegans.

Holothuria scabra is a sea cucumber that is mostly found in the Indo-Pacific region including Thailand. Extracts from many sea cucumbers possess pharmacological activities proposed to benefit human health. In this study, we investigated the anti-oxidant and anti-ageing activities of extracts from H. scabra by using Caenorhabditis elegans as a model organism. Parts of H. scabra were solvent-extracted and divided into nine fractions including whole body-hexane (WBHE), whole body-ethyl acetate (WBEA), whole body-butanol (WBBU), body wall-hexane (BWHE), body wall-ethyl acetate (BWEA), body wall-butanol (BWBU), viscera-hexane (VIHE), viscera-ethyl acetate (VIEA), and viscera-butanol (VIBU). All fractions of the extracts were tested for anti-oxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and for anti-ageing effects by lifespan assays using C. elegans as a model. The results showed anti-oxidant properties in all fractions with the highest activity shown by the DPPH assay in WBBU (EC50 = 3.12 ± 0.09 mg/ml), and by the ABTS assay in WBHE (EC50 = 0.31 ± 0.10 mg/ml). In lifespan assays the highest anti-ageing effect was detected in WBBU- and BWEA-treated C. elegans with increased mean lifespans of 8.12% and 4.77%, respectively. Furthermore, WBBU and BWEA-treated C. elegans exhibited significantly higher resistance against heat shock and paraquat-induced oxidative stresses than controls. By using LC-MS/MS, both extracts were characterized to contain triterpene glycosides as the main bioactive components. To explore mechanisms of H. scabra extracts on longevity and stress resistance, worms with genetic mutations in anti-ageing pathways were analyzed and showed that WBBU and BWEA did not prolong the lifespan of daf-16, age-1, sir-2.1, jnk-1, sek-1, and osr-1 mutants, suggesting that these genetic pathways are involved in mediating the anti-ageing effects of the H. scabra extracts. Moreover, WBBU and BWEA enhanced the nuclear translocation of the FoxO/DAF-16 transcription factor, and increased mRNA expression of this gene and its downstream targets sod-3, hsp12.3, and hsp16.2. In conclusion, this study strongly demonstrates anti-oxidant and anti-ageing properties of H. scabra extracts containing triterpene glycosides, which, in the C. elegans model, may be mediated via the insulin/IGF-1 signaling (IIS)-DAF-16 pathway.

Jattujan P ，Chalorak P ，Siangcham T ，Sangpairoj K ，Nobsathian S ，Poomtong T ，Sobhon P ，Meemon K ... -  《-》

Holothuria scabra extracts exhibit anti-Parkinson potential in C. elegans: A model for anti-Parkinson testing.

Chalorak P ，Jattujan P ，Nobsathian S ，Poomtong T ，Sobhon P ，Meemon K ... -  《-》

2-Butoxytetrahydrofuran and Palmitic Acid from Holothuria scabra Enhance C. elegans Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways.

Jattujan P ，Srisirirung S ，Watcharaporn W ，Chumphoochai K ，Kraokaew P ，Sanguanphun T ，Prasertsuksri P ，Thongdechsri S ，Sobhon P ，Meemon K ... -  《Pharmaceuticals》

Saponin-rich extracts from Holothuria leucospilota mediate lifespan extension and stress resistance in Caenorhabditis elegans via daf-16.

Saponins are secondary metabolite compounds that can be found in sea cucumbers (Holothuroidea spp.). However, little is known about how saponin-rich extracts from Holothuria leucospilota can delay and prolong the lifespan of the whole organism. In this study, anti-aging effects of H. leucospilota extracts were studied on Caenorhabditis elegans. NMR analysis revealed that body wall n-butanol-extract of H. leucospilota (BW-BU) is saponin-rich. BW-BU extracts exhibited antioxidant activities by 2,2'-diphenyl-2-picrylhydrazyl assay (EC50  = 10.23 ± 0.12 mg/ml) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid assay (EC50  = 3.91 ± 0.04 mg/ml). BW-BU extracts increased lifespan of L4 and L1 C. elegans (5.92% and 15.76%, respectively), which also increased worm growth, stress resistance, and reduced biomarkers for aging. BW-BU extracts activated DAF-16 nuclear localization and upregulated daf-16 and DAF-16 target genes expression. Taken together, this study revealed the evidences on anti-aging activities of saponin-rich extracts from H. leucospilota, which can extend lifespan of C. elegans via daf-16. PRACTICAL APPLICATIONS: In recent years, age-associated chronic diseases have had a significant impact on quality of life. Many natural compounds exhibit anti-aging activities, especially in sea cucumber, H. leucospilota. Our results indicated that H. leucospilota is good for health. Extracts from H. leucospilota contain a bioactive compound that can be potentially used to promote longevity and disease prevention in aging.

Kitisin T ，Suphamungmee W ，Meemon K 《-》

Holothuria scabra extracts confer neuroprotective effect in C. elegans model of Alzheimer's disease by attenuating amyloid-β aggregation and toxicity.

Alzheimer's disease (AD) is the most common aged-related neurodegenerative disorder that is associated with the toxic amyloid-β (Aβ) aggregation in the brain. While the efficacies of available drugs against AD are still limited, natural products have been shown to possess neuroprotective potential for prevention and therapy of AD. This study aimed to investigate the neuroprotective effects of H. scabra extracts against Aβ aggregation and proteotoxicity in C. elegans model of Alzheimer's diseases. Whole bodies (WB) and body wall (BW) of H. scabra were extracted and fractionated into ethyl acetate (WBEA, BWEA), butanol (WBBU, BWBU), and ethanol (BWET). Then C. elegans AD models were treated with these fractions and investigated for Aβ aggregation and polymerization, biochemical and behavioral changes, and level of oxidative stress, as well as lifespan extension. C. elegans AD model treated with H. scabra extracts, especially triterpene glycoside-rich ethyl acetate and butanol fractions, exhibited significant reduction of Aβ deposition. These H. scabra extracts also attenuated the paralysis behavior and improved the neurological defects in chemotaxis caused by Aβ aggregation. Immunoblot analysis revealed decreased level of Aβ oligomeric forms and the increased level of Aβ monomers after treatments with H. scabra extracts. In addition, H. scabra extracts reduced reactive oxygen species and increased the mean lifespan of the treated AD worms. In conclusion, this study demonstrated strong evidence of anti-Alzheimer effects by H. scabra extracts, implying that these extracts can potentially be applied as natural preventive and therapeutic agents for AD. Alzheimer's disease, Neurodegenerative disorder, Traditional medicine, Experimental model systems, Molecular biology.

Kleawyothatis W ，Jattujan P ，Chumphoochai K ，Chalorak P ，Sobhon P ，Meemon K ... -  《-》