Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer’s disease progression based on the “brain-gut” axis through multiple integrated omics

Gu, Xinru; Zhou, Junyi; Zhou, Yanmin; Wang, Hongjie; Si, Nan; Ren, Wei; Zhao, Wei; Xiu, Fan; Gao, Wenya; Wei, Xiaolu; Yang, Jian; Bian, Baolin; Zhao, Haiyu

doi:10.1186/s13195-021-00779-7

Cited by 44 publications

(31 citation statements)

References 108 publications

(123 reference statements)

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“…24 In addition, HLJDD suppressed gut dysbiosis and the associated Aβ accumulation, controlled neuro-inflammation and reversed cognitive impairment. 2 In our previous study, 25 HLJDD-treated APP/PS1 mice showed better performance than vehicle-treated APP/PS1 mice in the Morris water maze test. Meanwhile, in the spatial exploration test, the crossing platform frequency of HLJDD mice was significantly higher than that of model mice.…”

Section: Introductionmentioning

confidence: 86%

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Involvement of Huanglian Jiedu Decoction on Microglia with Abnormal Sphingolipid Metabolism in Alzheimer’s Disease

Qi¹,

Xia²,

Yao³

et al. 2022

DDDT

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Background Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer’s disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of β-amyloid (Aβ) 25–35 -induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and Aβ as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, real-time quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in Aβ 25-35 -stimulated BV2 microglia. Results Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and Aβ 25-35 -stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in Aβ 25-35 -stimulated BV2 cells. In AD mice, more microglia were clustered in the Aβ-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in Aβ 25-35 -stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD.

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Section: Introductionmentioning

confidence: 86%

“…Most of anti-AD drugs have a single molecular target and are mainly acetylcholinesterase inhibitors, which is not an optimal choice for AD patients with multi-pathogenesis. 2 …”

Section: Introductionmentioning

confidence: 99%

Involvement of Huanglian Jiedu Decoction on Microglia with Abnormal Sphingolipid Metabolism in Alzheimer’s Disease

Qi¹,

Xia²,

Yao³

et al. 2022

DDDT

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“…Indeed, although initially hypothesized for gastrointestinal disorders [ 102 ], gut microbiome-derived biomarkers have also been considered for psychological and neurodegenerative diseases (i.e., bipolar disorder, multiple Sclerosis, and PD), reporting powerful predictivity and differential diagnosis ability [ 103 , 104 , 105 ]. Regarding AD, promising results have recently been obtained, and Table 1 summarizes the main findings [ 72 , 73 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ] ( Table 1 ). Whilst species of Prevotella and Helicobacter have been shown to be significantly different between APP/PS1 transgenic mice and controls, Actinobacteria and TM7 phylum seem to be more accurate in diagnosing AD when using the triple transgenic mouse model [ 106 , 107 , 109 ].…”

Section: Mainmentioning

confidence: 99%

“…For example, Zhang et al report how gut microbiota composition, serum miRNAs and dietary quality scores can be used together to improve reproducibility and consistency [ 112 ]. In this respect, it would be interesting to investigate whether SCFAs, in combination with other fluid biomarkers, might prove effective in disease diagnosis and clinical monitoring, as some evidence already suggested [ 108 ].…”

Section: Mainmentioning

confidence: 99%

The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

et al. 2022

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Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.

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“…Furthermore, omics technologies have already been applied in studies searching for the potential metabolic pathways and integrative biomarkers that would help to understand the link between nutrition, food patterns [ 119 , 120 ] and brain health [ 121 ]. A recent preclinical study with mice, highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorders in Alzheimer’s progression, through an integrated metabolomic approach, showing the potential of omics techniques to understand complex mechanisms [ 122 ]. Also, in relation to the gut brain axis, another study found that a 28-day intermittent fasting regimen improved cognitive deficits in diabetic mice.…”

Section: High-throughput Techniques and Biological Models To Study Om...mentioning

confidence: 99%

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging

Mora

Arola

Caimari

et al. 2022

IJMS

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Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of “omic” technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging.

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Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer’s disease progression based on the “brain-gut” axis through multiple integrated omics

Cited by 44 publications

References 108 publications

Involvement of Huanglian Jiedu Decoction on Microglia with Abnormal Sphingolipid Metabolism in Alzheimer’s Disease

Involvement of Huanglian Jiedu Decoction on Microglia with Abnormal Sphingolipid Metabolism in Alzheimer’s Disease

The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging

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