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.

Rapid quantification of multi-components in alcohol precipitation liquid of Codonopsis Radix using near infrared spectroscopy(NIRS)

A near infrared spectroscopy（NIRS） approach was established for quality control of the alcohol precipitation liquid in the manufacture of Codonopsis Radix. By applying NIRS with multivariate analysis, it was possible to build variation into the calibration sample set, and the Plackett-Burman design, Box-Behnken design, and a concentrating-diluting method were used to obtain the sample set covered with sufficient fluctuation of process parameters and extended concentration information. NIR data were calibrated to predict the four quality indicators using partial least squares regression（PLSR）. In the four calibration models, the root mean squares errors of prediction（RMSEPs） were 1.22 μg/ml, 10.5 μg/ml, 1.43 μg/ml, and 0.433% for lobetyolin, total flavonoids, pigments, and total solid contents, respectively. The results indicated that multi-components quantification of the alcohol precipitation liquid of Codonopsis Radix could be achieved with an NIRS-based method, which offers a useful tool for real-time release testing（RTRT） of intermediates in the manufacture of Codonopsis Radix.

Inspection Methods and Quality Grading Standards for Codonopsis pilosula Seeds

[Objective] This study aimed to investigate the inspection methods and quality grading standards for Codonopsis pilosula seeds. [Method] A total of 27 shares of C. pilosula seeds were collected and surveyed from six counties in Shanxi, Gansu and Shaanxi provinces. The inspection methods of various indicators, such as purity, 1 000-grain weight, germination rate, vitality and moisture content, were investigated in accordance with Rules for Agricultural Seed Testing （GB/T 3543.1-7, 1995）, to develop the appropriate quality inspection method for C. pilosula seeds. Based on the developed inspection method and procedures, the quality of 27 shares of C. pilosula seed samples from different regions was inspected, thus es- tablishing quality grading standards for C. pilosula seeds with K-center clustering method. [Result] C. pilosula seeds are suitable to be cultivated in cool regions. The optimal germination temperature was 25 ~C; the optimal germination bed was gauze bed; the optimal staining conditions were： staining temperature 40 ~, TTC concen- tration 0.5%, staining time 4 h. On the basis of cluster analysis, the quality of C. pilosula seeds could be divided into three grades according to five indicators, includ- ing the purity, 1 000-grain weight, moisture content, vitality, and germination rate. Specifically, vitality and germination rate were important factors of grading standards due to the significant differences, followed by purity, 1 000-grain weight and mois- ture content. [Conclusion] This study provided an important basis for standardized cultivation and industrial development of C. pilosula.

Chemical and molecular characterization of Hong Dangshen,a unique medicinal material for diarrhea in Hong Kong

Aim To investigate the plant origin and the identity of the red substance on the surface of Hong Dangshen, a unique medicinal material for diarrhea in Hong Kong. Methods The HPLC fingerprints and 5S rRNA gene spacer sequences of Hong Dangshen were obtained and compared with those of genuine species of Radix Codonopsis. The X-ray diffraction spectrum of the red substance was analyzed and compared with that of Halloysitum fingerprints to the Codonopsis species and the highest similarity to Rubrum. Results Hong Dangshen showed very similar HPLC Codonopsis pilosula var. modesta in terms of 5S rRNA gene spacer sequences. The X-ray diffraction spectrum of the red substance was consistent with that of Halloysitum Rubrum. Conclusion The source plant of Hong Dangshen was suggested to be Codonopsis pilosula var. modesta, one of the genuine original plants of Radix Codonopsis （Dangshen） in the China Pharmacopoeia （2005 edition）. The red substance on the surface of Hong Dangshen was indicated to be Halloysitum Rubrum, a traditional medicinal mineral for chronic diarrhea. Our data suggest that Hong Dangshen is derived from the roots of Codonopsis pilosula var. modesta which has been processed with Halloysitum Rubrum, and the name is suggested to be Radix Codonopsis Praeparata Halloysita Rubra.