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

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix(ACR)in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease(NAFLD)induced by a high-fat diet(HFD).The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD.Furthermore,ACR ameliorated the dysregulated lipid metabolism in NAFLD mice,as evidenced by reductions in serum triglyceride,total cholesterol,and low-density lipoprotein levels,accompanied by a concomitant increase in the high-density lipoprotein level.ACR treatment also demonstrated a profound anti-oxidative effect,effectively alleviating HFD-induced oxidative stress and promoting ATP production.These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes Ⅰ,Ⅱ,Ⅳ,and Ⅴ,in addition to the activation of the AMPK/PGC-1α pathway,suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism.Moreover,ACR administration mitigated HFD-induced endoplasmic reticulum(ER)stress and suppressed the overexpression of ubiquitin-specific protease 14(USP14)in NAFLD mice.In summary,the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress.These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of “same treatment for different diseases” in traditional Chinese medicine

Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine(TCM) theory.Codonopsis Radix(Codonopsis pilosula,Dangshen in Chinese)with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases",based on its common mechanism in the treatment of gastric diseases including gastric ulcer,gastritis and gastric cancer via network pharmacology research.Methods:Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer,gastritis and gastric cancer.The active components and their target proteins of Dangshen were integrated from TCMSP,BATMAN-TCM databases.The targets of gastric ulcer,gastritis and gastric cancer were collected through GeneCards,PubMed,TDD and DisGeNET Database.Through screening,the key components and the key targets of Dangshen in treating gastric ulcer,gastritis and gastric cancer were obtained.After KEGG pathway analysis and GO analysis,the important pathways and biological processes were analyzed.Results:Through data and literature mining,the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions.It was shown that Dangshen mainly acted on gastric ulcer,gastritis and gastric cancer through the overall regulation of the PI3K-AkT signaling pathway.With the development of the disease,it will gradually increase the control of inflammation through TNF,NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage.For tumorigenesis,it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells.In addition,Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer,gastritis and gastric cancer.Conclusion:Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer,gastritis and gastric cancer through multiple targets in multiple pathways,especially PI3K-AKT pathway and HIF-1 pathway.It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.