Optimering af behandlingsteknologi til Tiebangchui med Zanba baseret på CRITIC kombineret med Box-Behnken responsoverflademetode
Summary
Denne protokol beskriver en effektiv og standard afgiftningsbehandlingsmetode for Zanba-stir-fried Tiebangchui ved hjælp af CRITIC kombineret med Box-Behnken-responsoverflademetoden.
Abstract
Den tørrede rod af Aconitum pendul Busch., kaldet Tiebangchui (TBC) på kinesisk, er en af de mest berømte tibetanske lægemidler. Det er en meget udbredt urt i det nordvestlige Kina. Imidlertid er der opstået mange tilfælde af forgiftning på grund af TBC’s intense toksicitet, og fordi dets terapeutiske og toksiske doser er ens. Derfor er det en presserende opgave at finde en sikker og effektiv metode til at reducere dens toksicitet. En søgning gennem de tibetanske medicinklassikere viser, at behandlingsmetoden for TBC omrørt med Zanba blev registreret i “Behandlingsspecifikation for tibetansk medicin i Qinghai-provinsen (2010)”. De specifikke behandlingsparametre er dog endnu ikke klare. Denne undersøgelse sigter således mod at optimere og standardisere behandlingsteknologien for Zanba-omrørt stegt TBC.
For det første blev der udført et enkeltfaktoreksperiment på fire faktorer: skivetykkelsen af TBC, mængden af Zanba, behandlingstemperatur og tid. Med monoester og diester alkaloid indhold i Zanba-stir-fried TBC som indeks, blev CRITIC kombineret med Box-Behnken responsoverflademetoden brugt til at optimere behandlingsteknologien af Zanba-stir-fried TBC. De optimerede forarbejdningsbetingelser for Zanba-omrørt TBC var en TBC-skivetykkelse på 2 cm, tre gange mere Zanba end TBC, en behandlingstemperatur på 125 °C og 60 minutters omrøring. Denne undersøgelse fastslog de optimerede og standardbehandlingsbetingelser for brugen af Zanba-stir-fried TBC, hvilket gav et eksperimentelt grundlag for sikker klinisk brug og industriel produktion af Zanba-stir-fried TBC.
Introduction
Den tørrede rod af Aconitum pendul Busch og A. flavum Hand.-Mazz., en af de mest berømte tibetanske lægemidler, kaldes Tiebangchui (TBC) på kinesisk 1,2. De tørrede rødder af TBC er nyttige til at fjerne kulde og vind, reducere smerte og beroligende chok. Det blev optaget i det første bind af “Drug Standards (Tibetan Medicine) fra Sundhedsministeriet i Folkerepublikken Kina”, hvori det hedder, at de tørrede rødder af TBC almindeligvis anvendes til behandling af reumatoid arthritis, blå mærker og andre kolde sygdomme3. Den kliniske terapeutiske dosis af TBC svarer imidlertid til dens toksiske dosis, og tilfælde af forgiftning eller død er ofte blevet rapporteret på grund af forkert brug4. Derfor er reduktion af toksiciteten og bevarelse af effektiviteten af TBC blevet et forskningsmæssigt hotspot gennem årene.
I tibetansk medicin er forarbejdning en af de mest effektive metoder til at dæmpe toksiciteten af TBC. Ifølge “Processing specification of Tibetan medicine of Qinghai Province (2010)” skal de originale urter (TBC) placeres i en jerngryde og omrøres med Zanba, indtil Zanba bliver gul, hvorefter Zanba fjernes, og urterne tørres i luft 5,6. Der er dog ikke dokumenteret specifikke procesparametre, hvilket gør det vanskeligt at kontrollere forarbejdningsteknologien og kvaliteten af Zanba-stir-fried TBC. CRITIC-metoden er en objektiv vægtmetode, der kan undgå fuzzificering og subjektivitet og forbedre objektiviteten ved at veje7. Box-Behnken-responsoverflademetoden kan direkte afspejle samspillet mellem hver faktor gennem polynomisk tilpasning8. Kombinationen af Box-Behnken-responsfladen og CRITIC-metoden bruges almindeligvis til at optimere behandlingsteknologien for at erhverve den optimerede behandlingsprotokol 9,10. I dette papir blev en monoester-diterpenoid alkaloid (MDA) (benzoylaconitin) og to diester-diterpenoid alkaloider (DDA’er) (aconitin, 3-deoxyaconitin) anvendt som evalueringsindekser. CRITIC kombineret med Box-Behnken-responsoverflademetoden blev anvendt til at optimere behandlingsteknologien for Zanba-stir-fried TBC og etablere en standardbehandlingsmetode til klinisk sikker brug.
Protocol
Representative Results
Discussion
TBC er en vigtig tibetansk medicin med virkningerne af at fjerne kulde og lindre smerter. Det har været mest brugt til behandling af traumatisk skade og reumatisk artralgi i Kina i tusinder af år24,25,26. Diterpenoid alkaloider er både aktive og giftige ingredienser i TBC27,28,29. De vigtigste toksiske virkninger af aconitumalkaloide…
Disclosures
The authors have nothing to disclose.
Acknowledgements
Dette arbejde blev økonomisk støttet af National Natural Science Foundation of China (nr. 82130113), China Postdoctoral Science Foundation (nr. 2021MD703800), Science Foundation for Youths of Science & Technology Department of Sichuan-provinsen (nr. 2022NSFSC1449) og “Xinglin Scholars” Research Promotion Program fra Chengdu University of Traditional Chinese Medicine (nr. BSH2021009).
Materials
| 3-Deoxyaconitine | Chengdu Desite Biotechnology Co., Ltd. | DST221109-033 | |
| Aconitine | Chengdu Desite Biotechnology Co., Ltd. | DSTDW000602 | |
| Ammonium acetate | Tianjin Kermel Chemical Reagent Co., Ltd | Chromatographic grade | |
| Benzoylaconitine | Chengdu Desite Biotechnology Co., Ltd. | DSTDB005502 | |
| Design-Expert software | Stat-Ease, Inc., Minneapolis, MN, USA | version 13.0 | |
| Electronic analytical balance | Shanghai Liangping Instruments Co., Ltd. | FA1004 | |
| High performance liquid chromatography | SHIMADZU Co., Ltd. | LC-20A | |
| High-speed smashing machine | Beijing Zhongxing Weiye Instrument Co., Ltd. | FW-100 | |
| Millipore filter | Tianjin Jinteng Experimental Equipment Co., Ltd | φ13 0.22 Nylon66 | |
| stir-Fry machine | Changzhou Maisi Machinery Co., Ltd | Type 5 | |
| Tiebangchui | Gannan Baicao Biotechnology Development Co., Ltd | 20211012 | |
| Ultra pure water systemic | RephiLe Bioscience, Ltd. | Genie G | |
| Ultrasonic cleansing machine | Ningbo Xinyi Ultrasonic Equipment Co., Ltd | SB2200 | |
| Zanba | 27 Chuanzang Road, Ganzi County | – |
References
- Li, C. Y., et al. Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemistry, bioactivities and processing methods. Journal of Ethnopharmacology. 292, 115216 (2022).
- Wang, J., Meng, X. H., Chai, T., Yang, J. L., Shi, Y. P. Diterpenoid alkaloids and one lignan from the roots of Aconitum pendulum Busch. Natural Products and Bioprospecting. 9 (6), 419-423 (2019).
- Yu, L., et al. Traditional Tibetan medicine: therapeutic potential in rheumatoid arthritis. Frontiers In Pharmacology. 13, 938915 (2022).
- Zhao, R., et al. One case of ventricular arrhythmia caused by poisoning of traditional Chinese medicine Aconitum pendulum Busch. Journal of People’s Military Medical. 61 (4), 346-348 (2018).
- Qinghai Medical Products Administration. Processing specification of Tibetan medicine of Qinghai province. Qinghai Nationalities Publishing House. , 96-97 (2010).
- Li, J., et al. Comparison of three objective weighting methods to optimize the extraction process of Jianwei Chupi granules. Journal of Guangdong Pharmaceutical University. 38 (6), 91-97 (2022).
- Feng, Z. G., et al. Processing methods and the underlying detoxification mechanisms for toxic medicinal materials used by ethnic minorities in China: A review. Journal of Ethnopharmacology. 305, 116126 (2023).
- Hsu, Y. T., Su, C. S. Application of Box-Behnken design to investigate the effect of process parameters on the microparticle production of ethenzamide through the rapid expansion of the supercritical solutions process. Pharmaceutics. 12 (1), 42 (2020).
- Cheng, F., et al. Optimization of the baked drying technology of Cinnamomi Ramulus based on CRITIC combined with box-behnken response surface method. Journal of Chinese Medicinal Materials. 2022 (8), 1838-1842 (2022).
- Huang, X., et al. Optimization of microwave processing technology for carbonized Gardenia jasminoides by Box-Behnken response surface methodology based on CRITIC weighted evaluation. Chinese Herbal Medicines. 48 (6), 1133-1138 (2017).
- Elling, U., et al. Derivation and maintenance of mouse haploid embryonic stem cells. Nature Protocols. 14 (7), 1991-2014 (2019).
- Gu, J., Wang, Y. P., Ma, X. Simultaneous determinnation of three diester diterpenoid alkaloids in the toots of Aconiti flavi et penduli by HPLC method. Chinese Pharmaceutical Affairs. 28 (6), 618-621 (2014).
- Zhang, Y., Fu, X. UPLC simultaneous determination of six esteric alkaloids components in Aconitum Flaram Hand.Mazz. Asia-Pacific Traditional Medicine. 16 (5), 62-65 (2020).
- Rumachik, N. G., Malaker, S. A., Paulk, N. K. VectorMOD: Method for bottom-up proteomic characterization of rAAV capsid post-translational modifications and vector impurities. Frontiers In Immunology. 12, 657795 (2021).
- Wang, Y. J., Tao, P., Wang, Y. Attenuated structural transformation of aconitine during sand frying process and antiarrhythmic effect of its converted products. Evidence-Based Complementary and Alternative Medicine. 2021, 7243052 (2021).
- Wang, H. P., Zhang, Y. B., Yang, X. W., Zhao, D. Q., Wang, Y. P. Rapid characterization of ginsenosides in the roots and rhizomes of Panax ginseng by UPLC-DAD-QTOF-MS/MS and simultaneous determination of 19 ginsenosides by HPLC-ESI-MS. Journal of Ginseng Research. 40 (4), 382-394 (2016).
- vander Leeuw, G., et al. Pain and cognitive function among older adults living in the community. Journals of Gerontology Series A. Biological Sciences and Medical Sciences. 71 (3), 398-405 (2016).
- Lao, D., Liu, R., Liang, J. Study on plasma metabolomics for HIV/AIDS patients treated by HAART based on LC/MS-MS. Frontiers in Pharmacology. 13, 885386 (2022).
- Li, Y., et al. Evaluation of the effectiveness of VOC-contaminated soil preparation based on AHP-CRITIC-TOPSIS model. Chemosphere. 271, 129571 (2021).
- Zhong, S., Chen, Y., Miao, Y. Using improved CRITIC method to evaluate thermal coal suppliers. Scientific Reports. 13 (1), 195 (2023).
- Lewis, N. S., et al. Magnetically levitated mesenchymal stem cell spheroids cultured with a collagen gel maintain phenotype and quiescence. Journal of Tissue Engineering. 8, (2017).
- Chinese Pharmacopoeia Committee. . Pharmacopoeia of the People’s Republic of China. 4, (2020).
- Li, G., et al. Effect of response surface methodology-optimized ultrasound-assisted pretreatment extraction on the composition of essential oil released from tribute citrus peels. Frontiers in Nutrition. 9, 840780 (2022).
- Liu, X. F., et al. Hezi inhibits Tiebangchui-induced cardiotoxicity and preserves its anti-rheumatoid arthritis effects by regulating the pharmacokinetics of aconitine and deoxyaconitine. Journal of Ethnopharmacology. 302, 115915 (2023).
- Smolen, J. S., et al. Rheumatoid arthritis. Nature Reviews.Disease Primers. 4, 18001 (2018).
- Wang, F., et al. C19-norditerpenoid alkaloids from Aconitum szechenyianum and their effects on LPS-activated NO production. Molecules. 21 (9), 1175 (2016).
- Wang, B., et al. Study on the alkaloids in Tibetan medicine Aconitum pendulum Busch by HPLC-MSn combined with column chromatography. Journal of Chromatographic Science. 54 (5), 752-758 (2016).
- Liu, S., et al. A review of traditional and current methods used to potentially reduce toxicity of Aconitum roots in Traditional Chinese Medicine. Journal of Ethnopharmacology. 207, 237-250 (2017).
- Qiu, Z. D., et al. Online discovery of the molecular mechanism for directionally detoxification of Fuzi using real-time extractive electrospray ionization mass spectrometry. Journal of Ethnopharmacology. 277, 114216 (2021).
- El-Shazly, M., et al. Use, history, and liquid chromatography/mass spectrometry chemical analysis of Aconitum. Journal of Food and Drug Analysis. 24 (1), 29-45 (2016).
- Chan, T. Y. K. Aconitum alkaloid poisoning because of contamination of herbs by aconite roots. Phytotherapy Research. 30 (1), 3-8 (2016).
- Guo, L., et al. Exploring microbial dynamics associated with flavours production during highland barley wine fermentation. Food Research International. 130, 108971 (2020).
- Guo, T. L., Horvath, C., Chen, L., Chen, J., Zheng, B. Understanding the nutrient composition and nutritional functions of highland barley (Qingke): A review. Trends in Food Science & Technology. 103, 109-117 (2020).
- Wu, H., et al. Anti-myocardial infarction effects of Radix Aconiti Lateralis Preparata extracts and their influence on small molecules in the heart using matrix-assisted laser desorption/ionization-mass spectrometry imaging. International Journal of Molecular Sciences. 20 (19), 4837 (2019).
- Huang, G., et al. Study on cardiotoxicity and mechanism of "Fuzi" extracts based on metabonomics. International Journal of Molecular Sciences. 19 (11), 3506 (2018).
- Li, S. L., et al. An insight into current advances on pharmacology, pharmacokinetics, toxicity and detoxification of aconitine. Biomedicine & Pharmacotherapy. 151, 113115 (2022).
- Xie, Y., et al. Optimization of processing technology of braised Rehmanniae Raidx based on multiple indexes and response surface technology and correlation between components and color. Journal of Chinese Traditional Medicine. 47 (18), 4927-4937 (2022).
- Yang, X. Q., Xu, W., Xiao, C. P., Sun, J., Feng, Y. Z. Study on processing technology of Atractylodes chinensis with rice water and its pharmacodynamics of anti-diarrhea. Chinese Herbal Medicines. 53 (1), 78-86 (2022).
