RESUMEN
The polysaccharides (FP) extracted from the lateral roots of Aconitum carmichaelii Debx. (Fuzi) are natural compounds, which have effective therapy for rheumatoid arthritis (RA). Methotrexate (MTX) is the first-line drug for RA, but its application is greatly limited to the toxicity in liver and kidney and drug resistance. In this study, an attempt is made to apply oxidized FP (OFP) as a polymer carrier based on intra-articular delivery system loaded MTX. The FP could be modified and used as comprehensive gel carriers with biocompatibility and degradability for therapy of RA. Firstly, OFP-chitosan-poloxamer 407 in situ gel (OFP-CS-F407-MTX gel) was prepared by natural non-toxic cross-linking agents. Physicochemical characterization was performed by using 1H NMR and FTIR spectroscopic techniques to assess the successful functionalization of OFP. TGA, SEM and rheological experiment of OFP-CS-F407-MTX gel were investigated. Notably, we loaded MTX into OFP-CS-F407-MTX gel which had remarkable therapeutic efficacy and biosafety for RA. Therefore, OFP-CS-F407-MTX in situ gel delivery system can potentially reduce systemic toxicity and irritation of oral administration of MTX but hold a controlled release of drug for a long period of time.
Asunto(s)
Aconitum , Artritis Reumatoide , Metotrexato/química , Aconitum/química , Artritis Reumatoide/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Polisacáridos/uso terapéuticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Aconite (Fuzi, FZ), the processed root tuber of Aconitum carmichaelii Debx., is utilized as a classic medicine to treat diseases of the cardiovascular system and immune system. Resulting from the narrow margin of safety between a therapeutic dose and a toxic dose, FZ often causes cardiotoxicity including hypotension, palpitation, and bradycardia. Contributing to the detoxification effects of the other famous herbal medicine ginseng (Renshen, RS), which is the dried root and rhizome of Panax ginseng C. A. Meyer, people broadly combine FZ and RS as compatibility more than 1800 years to attenuate the toxicity of FZ. However, the systematic detoxification mechanisms of RS to FZ have not been fully revealed. AIM OF THE REVIEW: Aiming to provide a comprehensive interpretation of the attenuation processes of FZ via RS, this review summarizes the up-to-date information about regulatory mechanisms of RS to FZ to shed the light on the essence of detoxification. MATERIALS AND METHODS: Literature was searched in electronic databases, including PubMed, Web of Science ScienceDirect, Google Scholar, CNKI and WanFang Data. Relevant studies on detoxification mechanisms were included while irrelevant and duplicate studies were excluded. According to the study design, subject, intervention regime, outcome, first author and year of publication of included data, detoxification mechanisms of RS to FZ were summarized and visualized. RESULTS: A total of 144 studies were identified through databases from their inception up to Oct. 2022. Included information indicated that diester-diterpenoid alkaloids (DDAs) were the main toxic substances of FZ. The main mechanisms that RS attenuates the toxicity of FZ were transforming toxic compounds of FZ, affecting the absorption and metabolism of FZ as well as the FZ-induced cell toxicity alleviation. CONCLUSION: FZ, as a famous traditional Chinese medicine, has good prospects for utilization. The narrow margin of safety between a therapeutic dose and a toxic dose of FZ limits its clinical effect and safety while RS is always combined with FZ to alleviate its toxicity. However, mechanisms responsible for the detoxification process have not been well identified. Therefore, detoxification mechanisms of RS to FZ are reviewed to ensure the safety and effectiveness of FZ.