optimization-processing-tiebangchui-with-highland-barley-wine-based

Optimization of Processing of Tiebangchui with Highland Barley Wine Based on the Box-Behnken Design Combined with the Entropy Method

The processing of toxic ethnomedicines is of great significance for their safe clinical application. Thus, the limitations of traditional processing ...

Chengdu University of Traditional Chinese Medicine

Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy.

Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemistry, bioactivities and processing methods.

Tibetan medicine is an important part of traditional Chinese medicine and a significant representative of ethnic medicine in China. Tibetan medicine is gradually recognized by the world for its unique curative effects. Wuwei Shexiang pills (WPW) has been widely used to treat "Zhenbu" disease (Also known as rheumatoid arthritis) in Tibetan medicine, however, its potential bioactive ingredients and mechanism for RA treatment remain unclear. In this study, we used a combination of gas chromatography-mass spectrometry (GC-MS), ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS), network analysis and experimental validation to elucidate the potential pharmacodynamic substances and mechanisms of WPW in the treatment of rheumatoid arthritis (RA). The results showed that songoramine, cheilanthifoline, saussureanine C, acoric acid, arjunolic acid, peraksine, ellagic acid, arjungenin and other 11 components may be the main activities of WPW in the treatment of RA. PIK3CA, AKT, MAPK, IL-6, TNF, MMP1, MMP3, and CDK1 are considered as core targets. PI3K-AKT, MAPK, apoptosis, cell cycle, and other signaling pathways may be the key pathways for WPW to play a role in the treatment of RA. Furthermore, we validated the underlying molecular mechanism of WPW predicted by network analysis and demonstrated its possible mechanism through  animal experiments. It was found that WPW could significantly improve the degree of paw swelling, and reduce ankle joint diameter and arthritis index. Further histomorphological analysis showed that WPW could reduce the degree of synovial tissue inflammation and ankle joint cartilage damage. Meanwhile, WPW could down-regulate the levels of IL-6, IL-1β, and IL-17, and increase the levels of IL-10 and IL-4 in the serum of AA rats. TUNEL staining confirmed that WPW could significantly promote the apoptosis of synovial cells. Moreover, the immunohistochemical results showed that WPW decreased the expression of PI3K, AKT, MAPK, MMP1, MMP3, CDK1, and Bcl-2, as well as increased the expression of Bax protein. In conclusion, we successfully combined GC-MS, UPLC-Q-TOF/MS, network analysis, and experimental validation strategies to elucidate the inhibition of inflammation by WPW in AA model rats  PI3K/AKT, MAPK, cell cycle and apoptotic pathways process. This not only provides new evidence for the study of potential pharmacodynamic substances and the mechanism of WPW in the treatment of RA, but also provides ideas for the study of other Tibetan medicine compound preparations.

Network analysis combined with pharmacological evaluation strategy to reveal the mechanism of Tibetan medicine Wuwei Shexiang pills in treating rheumatoid arthritis.

Various toxic medicinal materials have been used by different ethnic minorities in China for thousands of years because of their extraordinary pharmacological activities. However, the improper use and complex toxicity-efficacy relationship could cause poisoning and even death. Therefore, the study of toxicity-attenuating methods and mechanisms is necessary.

Processing methods and the underlying detoxification mechanisms for toxic medicinal materials used by ethnic minorities in China: A review.

Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking.

Radix Aconiti, also known as Tie-bang-chui (TBC), Pang-a-na-bao, and Bang-na, is a typical aconitum Tibetan medicine and a perennial herb of the genus  Busch. and  Hand. -Mazz. dry roots. It has high toxicity and remarkable efficacy; as such, it is a typical "highly toxic and effective" drug that needs be processed and used. Processing methods of this Tibetan medicine include non-heating of highland barley wine (HBW) and fructus chebulae soup (FCS). This work aimed to understand differences in chemical composition between non-heat processed products and raw TBC. In this study, high-performance thin-layer chromatography (HPTLC) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) were used to analyze the chemical composition of TBC processed by FCS (F-TBC) and HBW (H-TBC). The MRM mode of HPLC-QqQ-MS/MS was selected to determine the changes of several representative alkaloids to comparison with the former results. A total of 52 chemical constituents were identified in raw and processed products, and the chemical composition of F-TBC and H-TBC changed slightly compared with that of raw TBC. The processing mechanism of H-TBC was also different from that of F-TBC, which might be related to the large amount of acidic tannins in FCS. It was found that the content of all six alkaloids decreased after processing by FCS, and all five alkaloids decreased except aconitine increased after processing by HBW. The combination of HPTLC and DESI-MSI could be an effective method for rapid identification of chemical components and changing rules in ethnic medicine. The wide application of this technology provides not only an alternative method for the traditional separation and identification of secondary metabolism but also a reference for research on the processing mechanism and quality control of ethnic medicine.

Rapid visual characterization of alkaloid changes in traditional processing of Tibetan medicine  by high-performance thin-layer chromatography coupled with desorption electrospray ionization mass spectrometry imaging.

Article	Year
Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemistry, bioactivities and processing methods. Journal of ethnopharmacology\| PubMed ID: 35331875	2022
Network analysis combined with pharmacological evaluation strategy to reveal the mechanism of Tibetan medicine Wuwei Shexiang pills in treating rheumatoid arthritis. Frontiers in pharmacology\| PubMed ID: 35924046	2022
Processing methods and the underlying detoxification mechanisms for toxic medicinal materials used by ethnic minorities in China: A review. Journal of ethnopharmacology\| PubMed ID: 36610672	2023
Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking. Medicine\| PubMed ID: 36626523	2022
Rapid visual characterization of alkaloid changes in traditional processing of Tibetan medicine by high-performance thin-layer chromatography coupled with desorption electrospray ionization... Frontiers in pharmacology\| PubMed ID: 37153806	2023

Xiaoyan Tan

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