FITOTERAPIA
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2025
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IF 2.6
Weijian Qu,Yi Lan,Zhuoqing Cheng,Han Yuan,Honghong Zhan,Xiaozhong Lan,Zhihua Liao,Guowei Wang,Min Chen
Diabetic kidney disease (DKD) is a common complication in patients with diabetes, and glycolipid metabolism disorders are an important cause of DKD. The root of Oxybaphus himalaicus (Edgew.) Heimerl is a traditional Tibetan medicine commonly used to treat kidney-related diseases. Nevertheless, contemporary pharmacological investigations into O. himalaicus , especially those associated with the treatment of renal disorders, remain scarce. The objective of this research was to explore the pharmaceutical impacts and mechanisms of action of O. himalaicus in the treatment of DKD. The active fraction and potential pharmacological effects of O. himalaicus were determined through network pharmacology. Then, in vivo and in vitro efficacy and mechanism studies were conducted through streptozotocin-induced DKD mice and high glucose-induced HK-2 cells. Network pharmacology research speculated the ethyl acetate (EA) fraction as the main active component of O. himalaicus for treating DKD. In vivo and in vitro experiments showed that EA reduces renal lipotoxicity by upregulating PPARα pathway proteins, enhancing fatty acid oxidation (FAO), and downregulating inflammatory factors such as TNF-α and IL-6. Molecular docking studies revealed that the active components of EA with a high affinity for PPARα are mainly rotenoid compounds. EA mitigates DKD through the activation of PPARα, which serves to augment FAO, abate lipid accumulation, and impede the expression of inflammatory factors. Among these, rotenoids may be the main active components that exert pharmacological effects.
研究领域:
药理学
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内分泌学
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肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
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IF 4
Hanju Fan,Meng Yan,Yongshuai Jing,Ziyan Li,Yaqian He,Zhiwei Li,Junna Song,Lanfang Wu
Crataegus pinnatifida is the dried fruit of Crataegus pinnatifida . Crataegus pinnatifida polysaccharides (CPPs) eluted with water as the mobile phase (CPPs-H-1) is one of the important active components. CPPs-H-1 has anti-oxidation and blood lipid regulation activities in vitro. Therefore, we investigated the effects of CPPs-H-1 on nonalcoholic fatty liver disease (NAFLD) in C57/BL6J mice. As a result, CPPs-H-1 inhibited the rapid growth of body weight and alleviated the liver injury caused by high-fat diets, significantly reducing the liver index and blood lipid levels in the model group, inhibiting the production of inflammation and cytokines, and inhibiting oxidative stress. CPPs-H-1 also enhanced intestinal barrier function. At the phylum level, CPPs-H-1 reduced the ratio of Firmicutes to Bacteroides (F/B) and regulated the content of short-chain fatty acids (SCFAs). The CPPs-H-1 may regulate intestinal flora composition, and improve intestinal barrier function, ultimately delaying the progression of NAFLD in mice. Also, CPPs-H-1 improved NAFLD progression by enhancing the Amp-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα) signaling pathway to enhance fatty acid oxidation. All these results confirm that CPPs-H-1 plays a multi-pathway and multi-target role in the improvement of NAFLD.
研究领域:
营养学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2025
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IF 4
Hao Wu,Tong Xu,Naixi Yang,Shiwen Xu
Microplastics (MPs) and Emamectin Benzoate (EMB) were identified as hazardous environmental pollutants, frequently coexisting in aquatic ecosystems, posing potential risk in the immune system of human and animal. However, the hazards of concurrent exposed to MPs and EMB on the carp spleen, and the specific mechanisms remain unclear. Here, we employed MPs and EMB-exposed carp models, and cultured splenocytes in vitro, to demonstrate that PPARα signals suppression underlay MPs and EMB-induced carp spleen injury, based on transcriptomics and lipomics analysis. This suppression exacerbated the buildup of polyunsaturated fatty acid (PUFA), and promoted ACSL4 expression, resulting in increased lipid peroxidation. Further studies found that the accumulation of lipid peroxides predominantly occurred in the mitochondria, which evoked mitochondrial homeostasis imbalance and compromised mitochondrial function, thereby initiating ferroptosis. Additionally, enhancing PPARα signaling, inhibiting ACSL4, or scavenging mitochondrial ROS was favor of mitigating accumulation of lipid peroxides, reducing mitochondrial damage and inhibiting ferroptosis. Notably, MPs and EMB co-exposure caused more severe damage than single exposure. These findings uncovered a potential mechanism, involving PPARα signaling inhibition by MPs and EMB co-exposure, which evoked lipid remodeling and increased ACSL4, to drive ferroptosis and carp splenic injury. This study highlighted the potential hazards to the aquaculture environments where co-exposure of MPs and EMB and provided reference for environmental toxicology research and the sustainable development of the aquaculture industry.
研究领域:
环境毒理学
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水产养殖学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Yan Xie,Yimin Jin,Jianhui Wen,Guiping Li,Xue Huai,Yueyang Duan,Fuyong Ni,Juan Fu,Ming Li,Liang Li,Ming Yan,Liang Cao,Wei Xiao,Hao Yang,Zhen-zhong Wang
Non-alcoholic fatty liver disease (NAFLD), particularly advanced non-alcoholic steatohepatitis (NASH), leads to irreversible liver damage. This study investigated the therapeutic effects and potential mechanism of a novel extract from traditional Chinese medicine Alisma orientale (Sam.) Juzep (AE) on free fatty acid (FFA)-induced HepG2 cell model and high-fat diet (HFD) + carbon tetrachloride (CCl 4 )-induced mouse model of NASH. C57BL/6 J mice were fed a HFD for 10 weeks. Subsequently, the mice were injected with CCl 4 to induce NASH and simultaneously treated with AE at daily doses of 50, 100, and 200 mg/kg for 4 weeks. At the end of the treatment, animals were fasted for 12 h and then sacrificed. Blood samples and liver tissues were collected for analysis. Lipid profiles, oxidative stress, and histopathology were examined. Additionally, a polymerase chain reaction (PCR) array was used to predict the molecular targets and potential mechanisms involved, which were further validated in vivo and in vitro . The results demonstrated that AE reversed liver damage (plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte ballooning, hepatic steatosis, and NAS score), the accumulation of hepatic lipids (TG and TC), and oxidative stress (MDA and GSH). PCR array analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that AE protects against NASH by regulating the adipocytokine signaling pathway and influencing nuclear receptors such as PPARα. Furthermore, AE increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1α) and reversed the decreased expression of PPARα in NASH mice. Moreover, in HepG2 cells, AE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. Overall, our findings suggest that AE may serve as a potential therapeutic approach for NASH by inhibiting lipid accumulation and reducing oxidative stress specifically through the PPARα pathway.
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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传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
·
IF 8.3
Yingya Zhou,Meng Feng,Hongyan Hai,Xinmeng Teng,Xinxin Zhou,Yong Gao,Yanhua Zhong,Changhui Liu
Background : Due to the absence of disease-modifying treatments and mysterious molecular causes, metabolic dysfunction-associated steatotic liver disease (MASLD) poses an urgent and unmet clinical need. The active ingredient in Fructus gardenia , geniposidic acid (GPA), has anti-inflammatory, antioxidant, and hepato-protective properties. However, its effects on MASLD are still unknown. Purpose : This study aimed to determine how diet-induced hepatic steatosis in mice is affected by GPA. Methods : Dietary induction developed the mouse model of hepatic steatosis. The influence of GPA on hepatic steatosis, inflammation, and fibrosis were examined using the mouse primary hepatocyte lipid overload model. The mechanism of GPA in preventing and treating MASLD was explored through RNA-seq, and the activation of the SIRT6 signal by GPA was verified by molecular docking, pull-down, etc. Hepatocyte-specific Sirt6 -deletion mice were established, and cellular and animal studies were performed to assess SIRT6 functions in inhibiting and treating MASLD by GPA. Results : GPA therapy significantly enhanced hepatic fat accumulation, oxidative stress, inflammatory infiltration, and fibrosis in mice subjected to high fat diet (HFD) and methionine choline deficient (MCD) diets. In the meantime, GPA can reduce oxidative stress in hepatocyte metabolic stress and fat buildup brought on by oleic acid (OA) and palmitic acid (PA). RNA sequencing revealed that GPA exerts its protective effects against MASLD primarily by stimulating SIRT6 and triggering the downstream PPARα signaling cascade. Furthermore, GPA was found to interact directly with SIRT6 through specific binding sites. This interaction enables SIRT6 activation under both normal and disease conditions. However, without SIRT6, the liver-protective benefits of GPA under metabolic stress are lost. Conclusion : It was found that GPA binds directly to SIRT6 and enhances its activity, thereby inhibiting the progression of diet-induced MASLD. The findings suggest the potential of GPA as a therapeutic target for treating MASLD.
研究领域:
药理学
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分子生物学
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肝病学
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营养学
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药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
·
IF 8.2
Jing Song,Fengyun Huang,Kun Ma,Rui Ding,Kai Tan,Dan Lv,Kiyoshi Soyano,Kai Zhao
Bifenthrin (BF) is a broad-spectrum insecticide that has gained widespread use due to its high effectiveness. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. This study aimed to investigate the 50 % lethal concentration (LC 50 ) and safety concentration of Chinese giant salamanders (CGS) exposed to BF (at 0, 6.25,12.5,25 and 50 μg/L BF) for 96 h. Subsequently, CGS were exposed to BF (at 0, 0.04, and 4 μg/L BF) for one week to investigate its toxic effects. Clinical poisoning symptoms, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results indicate that exposure to BF at 4 μg/L significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) contents in the brain, liver, and kidney of CGS. Additionally, the study found that the malondialdehyde (MDA), reactive oxygen species (ROS), and 8-hydroxydeoxyguanosine (8-OHdG) contents were increased. The liver tissue exhibited significant inflammatory reactions and structural malformations. RNA-seq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS. This affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior, and detoxification, which were significantly upregulated, resulting in the differential genes significantly enriched in the calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. The results suggest that BF induces the abnormal production of free radicals, which overwhelms the body's self-defense system, leading to varying degrees of oxidative stress. This can result in oxidative damage, DNA damage, abnormal lipid metabolism, autoimmune diseases, clinical poisoning symptoms, and tissue inflammation. This work provides a theoretical basis for the rational application of bifenthrin and environmental risk assessment, as well as scientific guidance for the conservation of amphibian populations.
研究领域:
环境毒理学
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两栖生物学
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分子生物学
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生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）