Food Science & Nutrition
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2023
·
IF 3.9
Baozhang Shi,Jinqiang Qian,Hongyue Miao,Shuo Zhang,Yue Hu,Puqing Liu,Liping Xu
Liver fibrosis is caused by a variety of pathogenic factors. It is mainly characterized by chronic liver damage mediated by the imbalance between extracellular matrix synthesis and degradation. If the injury factor cannot be removed for a long time, fibrosis will progress to cirrhosis or even cancer. The development of liver fibrosis is a very complex process which is related to the activation of hepatic stellate cells (HSCs), oxidative stress, and cytokines produced by immune cells. At present, screening of substances with anti-inflammatory activity from natural plant extracts has become a new research focus in the prevention and treatment of liver fibrosis. Mulberry twig is a commonly used traditional Chinese medicine. Pharmacological studies have shown that mulberry twig has anti-inflammatory and antioxidant activities. Thus, it is likely that Mulberry twig contains active substances with liver protection functions. The present study aimed to explore the effect of Mulberroside A (MulA), the main active ingredient from Mulberry twig, on acute liver injury induced by CCl 4 in mice. MulA treatment could significantly alleviate the CCl 4 -induced liver injury, as evidenced by histological analysis and Masson staining. However, we observed that MulA inhibited the expressions of collagen I and α-SMA in livers of CCl 4 -treated mice but did not directly inhibit the proliferation and activation of HSCs. Finally, we analyzed the anti-inflammatory effect of MulA and demonstrated that it could markedly inhibit the pro-inflammatory cytokines release in liver tissues and in cultured macrophages, thereby alleviating liver fibrosis. Our findings suggest MulA as a potential therapeutic candidate for liver injury and inflammatory diseases.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
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高影响因子
Biology-Basel
·
2025
·Vol. 14
·期 9
·1114
·
IF 3.5
Jin Li,Jiawen Wang,Yaodong Li,Jingyi Guo,Ziliang Jin,Shourong Qiao,Yunxia Zhang,Guoyin Li,Huazhen Liu,Changjing Wu
Simple SummaryAlzheimer’s disease is a severe, gradually worsening brain disorder leading to memory loss and dementia, with no effective treatments currently available. In this study, we investigated a natural compound called mulberroside A, derived from the mulberry plant, to determine its potential protective effects against Alzheimer’s disease. Utilizing a mouse model and human brain cells, we discovered that mulberroside A enhanced memory and decreased brain cell damage. Additionally, it increased the levels of crucial brain chemicals, facilitating better communication between nerve cells. Moreover, it alleviated harmful stress in the brain and reduced the formation of two hallmark pathologies: toxic tau protein tangles and amyloid plaques. The compound significantly decreased phosphorylated tau—a key driver of neuronal degeneration—while simultaneously inhibiting amyloid plaque formation. Mulberroside A operated by activating specific neuroprotective pathways that promote brain health, including those that encourage nerve growth. These findings indicate it could serve as a promising new treatment to slow or prevent Alzheimer’s disease by targeting multiple disease mechanisms.Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)—a bioactive glycoside fromMorus albaL.—present promising alternatives. This study investigated MsA’s neuroprotective potential using scopolamine-induced AD-like mice and N2a/APP695swe cells. In vivo, MsA significantly ameliorated cognitive deficits and neuronal loss, concurrently enhancing cholinergic neurotransmission through increased acetylcholine levels and inhibited acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) activities. MsA also upregulated neurotrophic factors (BDNF, CREB) in critical brain regions. In vitro, MsA restored cholinergic function, mitigated oxidative stress, and crucially reduced amyloid-β (Aβ) production by dual regulation of APP processing: promoting the non-amyloidogenic pathway via ADAM10 upregulation and inhibiting the amyloidogenic pathway via suppression of BACE1 and γ-secretase components. Mechanistically, these multi-target benefits were mediated by MsA’s activation of the PI3K/AKT pathway, which triggered downstream inhibitory phosphorylation of GSK3β—directly reduced tau hyperphosphorylation—and activation of CREB/BDNF signaling. Collectively, our findings demonstrate that MsA confers comprehensive neuroprotection against AD pathology by simultaneously targeting cholinergic dysfunction, oxidative stress, Aβ accumulation, tau phosphorylation, and impaired neurotrophic signaling, highlighting its strong therapeutic candidacy.
研究领域:
神经科学
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药理学
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生物化学
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分子生物学
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药物化学
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神经退行性疾病
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高影响因子
Biology-Basel
·
2026
·Vol. 15
·期 13
·1030
·
IF 4.3
Jin Li,Shirui Cheng,Wenqi Zhang,Shourong Qiao,Luzhi Zhang,Mengxu Yao,Yunxia Zhang,Biao Wang,Changjing Wu
Simple SummaryAlzheimer’s disease is a progressive neurodegenerative disorder that causes memory loss, cognitive decline, and great burden on patients and families. Although many studies have focused on the brain, increasing evidence suggests that changes in the gut may also contribute to disease development. In this study, we examined whether mulberroside A, a natural compound derived from mulberry, could protect against scopolamine-induced Alzheimer’s disease-like cognitive impairment in mice. Our results showed that mulberroside A improved learning and memory, reduced inflammatory damage and oxidative stress in the brain, and protected the intestinal barrier. We also found that mulberroside A changed the composition of gut microbes, especially increasing beneficial bacteria such asDubosiella, and helped restore abnormal metabolism in the brain. Importantly, fecal microbiota transplantation from treated mice reproduced the protective effects, indicating that gut microbiota changes play a key role in the action of mulberroside A. These findings suggest that mulberroside A may improve brain health by acting through the microbiota-gut–brain axis and could be a promising natural compound for the prevention and amelioration of Alzheimer’s disease-like cognitive decline.Mulberroside A (MsA) possesses neuroprotective effects, but whether it alleviates Alzheimer’s disease (AD)-like cognitive impairment through the microbiota–gut–brain axis remains unclear. Using a scopolamine-induced mouse model of acute cognitive impairment (male ICR mice,n= 10/group), we demonstrated that daily administration of MsA (10, 20, and 30 mg/kg/day) for 5 weeks significantly ameliorated cognitive performance in novel object recognition and Morris water maze tests. At the optimal dose (30 mg/kg/day), MsA suppressed hippocampal microglial activation, reduced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and attenuated oxidative stress by decreasing malondialdehyde (MDA) while restoring superoxide dismutase (SOD) and glutathione (GSH) levels. MsA also strengthened intestinal barrier integrity (ZO-1, occludin) and significantly altered the gut microbiota, notably increasing the beneficial genusDubosiella. Brain metabolomics indicated that MsA reversed scopolamine-induced metabolic disturbances, mainly restoring phospholipid balance. Correlation analysis demonstrated a strong gut–brain connection, withDubosiellaabundance positively associated with neuroprotective phospholipids and negatively with stress markers. Furthermore, fecal microbiota transplantation from MsA-treated donors successfully replicated these behavioral improvements in recipient mice, underscoring the functional involvement of the reshaped microbiome rather than a simple autonomous recovery. These results suggest that MsA alleviates AD-like cognitive impairment by reducing neuroinflammation and oxidative stress through microbiota remodeling, enhancing the intestinal barrier, and modulating theDubosiella-associated gut–metabolite–brain axis, making MsA a promising multi-target nutraceutical for ameliorating AD-like cognitive deficits.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Ya-Nan Jia,Ya-Lin Peng,Yi-Ping Zhao,Xi-Fei Cheng,You Zhou,Chun-Li Chai,Ling-Shu Zeng,Min-Hui Pan,Li Xu
The purpose of this study was to compare the hepatoprotective effects of Oxy (oxyresveratrol), Res (resveratrol), and MulA (mulberroside A) (80 mg/kg body weight/d, i.g.) on acute liver injury (ALI) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice. After 7 h of LPS (50 μg/kg body weight, i.p.) and d-GalN (500 mg/kg body weight, i.p.) exposure, the activities of serum transaminases and antioxidant enzymes were determined. The expressions of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, the nuclear factor-kappa B (NF-κB) signal pathway, and the mitogen-activated protein kinase (MAPK) signal pathway related proteins were evaluated by Western blot assays. Histopathological analysis was performed by hematoxylin-eosin (H&E) staining on the separated livers of mice. The results showed that treatment with Oxy, Res, and MulA could significantly decreases the levels of alanine transaminase (ALT) and aspartate transaminase (AST) (P < 0.01). MulA was the most effective ingredient among the three, and the ALT and AST levels were reduced at 90.3 ± 1.3% and 93.9 ± 1.1% compared with the LPS/D-GalN treated group (P < 0.01). Meanwhile, the stilbenes curbed the expression of inflammatory factors, NF-κB pathway activation, and MAPKs phosphorylation and upregulated antioxidant enzymes, Nrf2, NAD (P) H:quinone oxidoreductase (NQO1), and heme oxygenase-1 (HO-1) expression levels. Stilbenes might protect the ALI caused by LPS/d-GalN through inhibiting the negative effectiveness of oxidation stress and inflammation. The protective performance of MulA was better than those of Oxy and Res, and we hypothesize that it might be due to the mediation of the specific metabolic pathway of the MulA in vivo. All of these results implied that stilbenes in mulberry twigs might be promising as natural additives.
研究领域:
药理学
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肝病学
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分子生物学
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高影响因子
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