Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice

Fan, Cai‐lian; WANG, Guan; Chen, M. L.; Yao, Li; Tang, Xiyang; Dai, Yi

doi:10.1016/s1875-5364(23)60403-0

Cited by 7 publications

(3 citation statements)

References 52 publications

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“…The prevalence of NAFLD is predicted to increase globally in light of the present obesity pandemic [ 87 ]. A growing amount of clinical data indicates that NAFLD is a major risk factor for the emergence of liver cirrhosis, liver fibrosis, and liver cancer [ 105 ]. However, it is still unclear how NAFLD develops and how it leads to fibrosis and chronic liver disease.…”

Section: Mechanism Of Ck Against Metabolic Diseasesmentioning

confidence: 99%

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

Morshed,

Akter,

Karim

et al. 2024

CIMB

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Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

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Section: Mechanism Of Ck Against Metabolic Diseasesmentioning

confidence: 99%

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

Morshed,

Akter,

Karim

et al. 2024

CIMB

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“…Among the diseases related to the action of these active ingredients ( Table 2 ), Lobetyolin ( He et al, 2020 ; Cheng et al, 2023 ), Luteolin ( Yu et al, 2023 ; Liu et al, 2024 ), polyacetylenes ( Wang M.-C. et al, 2022 ), Isorhamnetin ( Luan et al, 2019 ) and molecule compound D6 ( Tang X. et al, 2021 ) mainly act in the treatment of cancer, saponins act in digestive diseases ( Liu X. F. et al, 2021 ; Li et al, 2023 ), lancemaside A ( Lee et al, 2019 ; Shin et al, 2019 ) and atractylodesin III( Cao M. et al, 2019 ) act in cardiovascular diseases. In addition, in a mouse model of non-alcoholic fatty liver disease (NAFLD), Alkaloids attenuate lipid deposition in NAFLD by improving energy metabolism, reducing oxidative stress and endoplasmic reticulum stress, and thus act as hepatoprotective agents ( Fan C. et al, 2023 ). Aromatic derivatives slow down carbohydrates by inhibiting alpha-glucosidase activity during digestion, management and absorption, thus helping to control blood glucose levels ( Wang R.-Y.…”

Section: Subsections Relevant For the Subjectmentioning

confidence: 99%

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

Guo,

Lou,

Hou

et al. 2024

Front. Pharmacol.

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As a traditional Chinese medicinal herb with a long history, Codonopsis pilosula (CP) has attracted much attention from the medical community in recent years. This review summarizes the research progress of CP in the medical field in the past 5 years. By searching and analyzing the literature, and combining with Cytoscape software, we comprehensively examined the role and mechanism of action of CP in individual application, combination drug application, and the role and mechanism of action of codonopsis pilosula’s active ingredients in a variety of diseases. It also analyzes the medicinal use of CP and its application value in medicine. This review found that CP mainly manifests important roles in several diseases, such as cardiovascular system, nervous system, digestive system, immune system, etc., and regulates the development of many diseases mainly through the mechanisms of inflammation regulation, oxidative stress, immunomodulation and apoptosis. Its rich pharmacological activities and diverse medicinal effects endow CP with broad prospects and application values. This review provides valuable reference and guidance for the further development of CP in traditional Chinese medicine.

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“…Hepatic peroxisome proliferators activate receptor α (PPARα) is an essential transcriptional regulator in regulating fatty acid transport and fatty acid oxidation (FAO) in nucleus [ 18 ]. The peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), a transcriptional coactivator induced by fasting [ 19 , 20 ], can bind with PPARα to form heterodimer to regulate the expression of genes involved in lipid metabolism [ 21 ]. It has been reported that hepatocyte-specific PPARα knockout mice exhibit accelerated hepatic lipid accumulation [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization

Gao,

Zhu,

Bao

et al. 2024

Chin Med

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Background Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice. Methods The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα−/−) mice were used to confirm the CP-mediated pathway. Results CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn’t affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect. Conclusion This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.

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Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice

Cited by 7 publications

References 52 publications

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization

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