Exploring Ganweikang Tablet as a Candidate Drug for NAFLD Through Network Pharmacology Analysis and Experimental Validation

Ma, Chuanrui; Wang, Xinyu; Zhang, Jing; Zhao, Yun; Hua, Yunqing; Zhang, Chao; Zheng, Guo; Yang, Guangren; Guan, Jianli; Li, Huahuan; Li, Meng; Kang, Lin; Xiang, Jiaqing; Fan, Guanwei; Yang, Shu

doi:10.3389/fphar.2022.893336

Cited by 2 publications

(1 citation statement)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, the primary pharmacological interventions for NAFLD/NASH consist of pioglitazone, metformin, and vitamin E; however, their efficacy is limited due to a low therapeutic index and notable adverse effects. For instance, pioglitazone has been associated with heart failure, osteoporosis, and weight gain [ 16 ]. The absence of a definitive treatment for NASH underscores the pressing need for the development of novel pharmaceutical agents to address and manage NAFLD/NASH [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis

Lin,

Zeng,

Ning

et al. 2024

Lipids Health Dis

View full text Add to dashboard Cite

Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg− 1), curcumin (Cur, 40 mg·kg− 1) and metformin (Met, 50 mg·kg− 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml− 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. Conclusion NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

show abstract

Section: Introductionmentioning

confidence: 99%

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis

Lin,

Zeng,

Ning

et al. 2024

Lipids Health Dis

View full text Add to dashboard Cite

show abstract

New perspectives on chemokines in hepatocellular carcinoma therapy: a critical pathway for natural products regulation of the tumor microenvironment

Ruishi,

Linyi,

Yunfan

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most common primary neoplasms of the liver and one of the most common solid tumors in the world. Its global incidence is increasing and it has become the third leading cause of cancer-related deaths. There is growing evidence that chemokines play an important role in the tumor microenvironment, regulating the migration and localization of immune cells in tissues and are critical for the function of the immune system. This review comprehensively analyses the expression and activity of chemokines in the TME of HCC and describes their interrelationship with hepatocarcinogenesis and progression. Special attention is given to the role of chemokine-chemokine receptors in the regulation of immune cell accumulation in the TME. Therapeutic strategies targeting tumor-promoting chemokines or the induction/release of beneficial chemokines are reviewed, highlighting the potential value of natural products in modulating chemokines and their receptors in the treatment of HCC. The in-depth discussion in this paper provides a theoretical basis for the treatment of HCC. It is an important reference for new drug development and clinical research.

show abstract

Exploring Ganweikang Tablet as a Candidate Drug for NAFLD Through Network Pharmacology Analysis and Experimental Validation

Cited by 2 publications

References 63 publications

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis

New perspectives on chemokines in hepatocellular carcinoma therapy: a critical pathway for natural products regulation of the tumor microenvironment

Contact Info

Product

Resources

About