Aquilaria crassna Leaf Extract Ameliorates Glucose-Induced Neurotoxicity In Vitro and Improves Lifespan in Caenorhabditis elegans

Pattarachotanant, Nattaporn; Sornkaew, N; Warayanon, Watis; Rangsinth, Panthakarn; Sillapachaiyaporn, Chanin; Vongthip, Wudtipong; Chuchawankul, Siriporn; Prasansuklab, Anchalee; Tencomnao, Tewin

doi:10.3390/nu14173668

Cited by 12 publications

(9 citation statements)

References 58 publications

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“…But these effects were observed in a low frequency in Madhugrit treated groups. Similar attenuation of high glucose-induced reduction in brood size is reported after treatment of worms with leaves of Aquilaria crassna (agarwood) ( 78 ). Secondly, we observed that high levels of glucose accumulation in the nematode promoted lipogenesis and enhanced triglyceride formation which was visually inspected by Nile red staining.…”

Section: Discussionsupporting

confidence: 71%

Anti-hyperglycemic contours of Madhugrit are robustly translated in the Caenorhabditis elegans model of lipid accumulation by regulating oxidative stress and inflammatory response

et al. 2022

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BackgroundThe prevalence of diabetes has considerably increased in recent years. In the long run, use of dual therapy of anti-diabetic agents becomes mandatory to attain euglycemia. Also, the incidences of diabetes-related co-morbidities have warranted the search for new therapeutic approaches for the management of the disease. Traditional herbo-mineral, anti-diabetic agents like Madhugrit are often prescribed to mitigate diabetes and related complications. The present study aimed to thoroughly characterize the pharmacological applications of Madhugrit.MethodsPhytometabolite characterization of Madhugrit was performed by ultra-high performance liquid chromatography. Evaluation of cell viability, α-amylase inhibition, glucose uptake, inflammation, and wound healing was performed by in vitro model systems using AR42J, L6, THP1, HaCaT cells, and reporter cell lines namely NF-κB, TNF-α, and IL-1β. The formation of advanced glycation end products was determined by cell-free assay. In addition, the therapeutic potential of Madhugrit was also analyzed in the in vivo Caenorhabditis elegans model system. Parameters like brood size, % curling, glucose and triglyceride accumulation, lipid deposition, ROS generation, and lipid peroxidation were determined under hyperglycemic conditions induced by the addition of supraphysiological glucose levels.ResultsMadhugrit treatment significantly reduced the α-amylase release, enhanced glucose uptake, decreased AGEs formation, reduced differentiation of monocyte to macrophage, lowered the pro-inflammatory cytokine release, and enhanced wound healing in the in vitro hyperglycemic (glucose; 25 mM) conditions. In C. elegans stimulated with 100 mM glucose, Madhugrit (30 µg/ml) treatment normalized brood size, reduced curling behavior, decreased accumulation of glucose, triglycerides, and lowered oxidative stress.ConclusionsMadhugrit showed multimodal approaches in combating hyperglycemia and related complications due to the presence of anti-diabetic, anti-inflammatory, anti-oxidant, wound healing, and lipid-lowering phytoconstituents in its arsenal. The study warrants the translational use of Madhugrit as an effective medicine for diabetes and associated co-morbidities.

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Section: Discussionsupporting

confidence: 71%

Anti-hyperglycemic contours of Madhugrit are robustly translated in the Caenorhabditis elegans model of lipid accumulation by regulating oxidative stress and inflammatory response

et al. 2022

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“…33 A. crassna leaf extracts have been demonstrated to ameliorate glucose-Induced neurotoxicity in vitro. 34 Our unpublished experimental data also indicate that both leaf and agarwood extracts of A. crassna can exert protective effects against D-galactose induced neurotoxicity in mouse hippocampal HT-22 cell line.…”

Section: Introductionmentioning

confidence: 68%

“…35 Limited number of in vitro experiments have shown that the leaves, stem, and agarwood of Aquilaria plants, among other plant parts, exhibit neuroprotective properties. 27,28,30,32,33,46 Scientific investigation into the phytochemical components of agarwood is still quite limited because of the high industrial demand and loss of its natural resources. Therefore, it is crucial to carry out additional research investigations to develop premium goods and medications using agarwood's beneficial phytochemical components.…”

Section: Discussionmentioning

confidence: 99%

In silico molecular docking and molecular dynamic simulation of agarwood compounds with molecular targets of Alzheimer’s disease 

et al. 2023

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Background Alzheimer's disease (AD) is a neurological condition that primarily affects older people. Currently available AD drugs are associated with side effects and there is a need to develop natural drugs from plants. Aquilaria is as an endangered medicinal plant genus (commonly called agarwood plants) and various products of Aquilaria plant spp. including resinous heartwood, leaves, bark, and stem have been widely used in various traditional medicine systems. Research on agarwood plants is sparse and only a few previous studies demonstrated their neuroprotective properties in vitro. Owing to the presence of a plethora of secondary metabolites in agarwood plants, it is imperative not only to protect these plants but also evaluate the bioactivity of agarwood phytochemicals. Methods Computational methods such as AutoDock Vina and molecular dynamic (MD) simulations were employed for the docking of 41 selected agarwood compounds with AD-related molecular targets. Results and Conclusion According to docking data, three compounds aquilarisin, aquilarisinin, aquilarixanthone showed highest binding affinity to selected AD targets compared to their known inhibitors. MD simulation studies revealed that, selected agarwood compounds' protein-ligand complexes showed remarkable structural stability throughout 100 ns simulation. The agarwood chemicals aquilarisin, aquilarisinin, aquilarixanthone, pillion, and agarotetrol are consequently suggested as some of the found hits against AD targets, however, additional experimental validation is required to establish their effectiveness.

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“…Previous studies have demonstrated that the high concentration of glucose (50 mM) in C. elegans can reduce body size and brood size of adult worms [ 43 ]. Our transcript analysis suggests that the reproduction and development of HGI C. elegans can be improved by Nar ( Figure 2 B).…”

Section: Resultsmentioning

confidence: 99%

“…The TGF-β pathway plays a leading role in regulating C. elegans ’ body length and width [ 59 ]. Previous studies have shown that the body length and width of HGI worms are smaller than that of control worms as larvae [ 43 ]. However, the regulation of TGF-β by Nar might allow for the HGI worm to recover its body length to some extent, resulting in the body length of the Nar treatment group on day 2 being longer than that of the HGI treatment group.…”

Section: Discussionmentioning

confidence: 99%

Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans

et al. 2023

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Naringin (Nar) is a dihydroflavonoid compound, widely found in citrus fruit and used in Chinese herbal medicine. As a phytochemical, it acts as a dietary supplement that can delay aging and prevent aging-related disease, such as obesity and diabetes. However, its exact mechanism remains unclear. In this study, the high-glucose-induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar. The mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11%, respectively, by Nar treatment. Oil red O staining revealed a significant reduction in fat accumulation and dFP::LGG-labeled worms showed the promotion of autophagy. Additionally, whole transcriptome sequencing and gene set variation analysis suggested that Nar upregulated the lipid biosynthesis and metabolism pathways, as well as the TGF-β, Wnt and longevity signaling pathways. Protein–protein interaction (PPI) network analysis identified hub genes in these pathways for further analysis. Mutant worms and RNA interference were used to study mechanisms; the suppression of hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 disabled the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Collectively, our findings indicate that Nar plays an important role in alleviating HGI-aging and anti-obesity effects by reducing fat accumulation and promoting autophagy.

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Aquilaria crassna Leaf Extract Ameliorates Glucose-Induced Neurotoxicity In Vitro and Improves Lifespan in Caenorhabditis elegans

Cited by 12 publications

References 58 publications

Anti-hyperglycemic contours of Madhugrit are robustly translated in the Caenorhabditis elegans model of lipid accumulation by regulating oxidative stress and inflammatory response

Anti-hyperglycemic contours of Madhugrit are robustly translated in the Caenorhabditis elegans model of lipid accumulation by regulating oxidative stress and inflammatory response

In silico molecular docking and molecular dynamic simulation of agarwood compounds with molecular targets of Alzheimer’s disease

Naringin Alleviates Glucose-Induced Aging by Reducing Fat Accumulation and Promoting Autophagy in Caenorhabditis elegans

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