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Na Li – 1st expert on this subject based on the ideXlab platform
pharmacokinetics and tissue distribution of eighteen major alkaloids of Aconitum Carmichaelii in rats by uhplc qqq msJournal of Pharmaceutical and Biomedical Analysis, 2020Co-Authors: Yida Zhang, Xingxing Zong, Jianlin Wu, Hua Zhou, Na LiAbstract:
Abstract Aconitum Carmichaelii Debeaux is a widely used herbal medicine, which has anti-inflammatory and analgesic activities. However, due to its high toxicity, poisoning incidents often occur all over the world. To systematically understand the pharmacokinetics (PK) and tissue distribution of A. Carmichaelii, 18 representative alkaloids, including 8 amine- (ADA), 4 monoester- (MDA) and 6 diester-type (DDA) diterpenoid alkaloids, were simultaneously quantified by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QQQ-MS) with dynamic multiple reaction monitoring (MRM) mode. PK results suggested that benzoylmesaconine, mesaconitine, 10-OH-aconitine and aconitine had lower bioavailability, which might relate to the substitution at C-3. In tissue distribution, alkaloids present higher concentrations in the liver, kidney, and only songorine, neoline and benzoyldeoxyaconine were detected in the brain. Moreover, the concentrations of extremely toxic DDAs in high-dose group were much higher than that of low-dose group, indicating that these DDAs might be the main reason for the toxicity of Aconitum. The results also suggested that benzoyldeoxyaconine and deoxyaconitine should be determined for the quality control of A. Carmichaelii due to their high concentrations in both herbal extract and tissues. The systematic investigation into these 18 representative alkaloids could basically illuminate the PK and distribution of A. Carmichaelii in rats, and provide some information for clinical studies.
potentially cardiotoxic diterpenoid alkaloids from the roots of Aconitum CarmichaeliiJournal of Natural Products, 2019Co-Authors: Xingxing Zong, Jianlin Wu, Hua Zhou, Na LiAbstract:
Aconitum Carmichaelii is a traditional Chinese herbal medicine used for the treatment of pain and inflammation in the joints. However, the strong cardiotoxicity hinders its use. Although diester- and monoester-type diterpenoids, e.g., aconitine, mesaconitine, and hypacaonitine, are commonly considered as the toxic components, the toxicity of A. Carmichaelii cannot be completely explained by the compounds reported. To investigate further the cardiotoxic compounds and their potential mechanism, the chemical constituents were first isolated by column chromatography and identified using mass spectrometry and NMR spectroscopy. Two new hetisine-type (1 and 2) and four new aconitine-type alkaloids (3–6) were assigned. The cardiac cytotoxicity assessed on H9c2 cells indicated that the new compound 4 as well as six known alkaloids (7 and 9–13) exhibited significant toxicities. A preliminary structure–toxicity relationship study suggested that substitution at C-8 and C-10 both have a significant influence on cardio…
qualitative and quantitative analysis of lipo alkaloids and fatty acids in Aconitum Carmichaelii using lc ms and gc msPhytochemical Analysis, 2018Co-Authors: Ying Liang, Xingxing Zong, Jianlin Wu, Hua Zhou, Na LiAbstract:
INTRODUCTION: Lipo-alkaloid (LA) is a kind of C19 -norditerpenoid alkaloid in Aconitum species, which usually contains an aconitane skeleton and one or two fatty acid residues. OBJECTIVE: To qualify and quantify the fatty acids and lipo-alkaloids in Aconitum Carmichaelii. METHODOLOGY: An ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-QQQ-MS) method was established to quantify LAs, while the free fatty acids were identified by gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS). RESULTS: Six major LAs (1-6) containing linoleic, palmitic, and oleic acid residues as side chains were quantified. Eighteen fatty acids were determined by GC-MS, and 15 were detected as the side chains of LAs. The LAs containing these 15 fatty acid residues accounted for about a third of the total identified LAs. Moreover, the contents of linoleic, palmitic, and oleic acids were highest. In addition, 12 oxygenated fatty acids were also identified by UHPLC-Q-TOF-MS for the first time. CONCLUSION: The positive correlation between free fatty acids and LAs in A. Carmichaelii indicated that the types and contents of LAs were influenced by free fatty acids.
Ying Xu – 2nd expert on this subject based on the ideXlab platform
mother root of Aconitum Carmichaelii debeaux exerts antinociceptive effect in complet freund s adjuvant induced mice roles of dynorpin kappa opioid system and transient receptor potential vanilloid type 1 ion channelJournal of Translational Medicine, 2015Co-Authors: Chao Wang, Hui Wang, Xiang-hong Jing, Shuping Chen, Tengfei Xu, Ying XuAbstract:
Processed Chuanwu (PCW), the mother root of Aconitum Carmichaelii Debeaux, has been widely used as a classic Traditional Chinese Medicine for pain relieve for over two millennia clinically. However, its action on chronic inflammatory pain has not been clarified. Here, we investigated the antinociceptive effect of PCW in complete freund’s adjuvant (CFA)-induced mice and its possible mechanisms associated with opioid system and TRPV1 ion channel. Male ICR mice were intraplantarly injected with CFA. PCW (0.34, 0.68 and 1.35 g/kg) was orally given to mice once a day for 7 days. Von frey hairs and plantar test were assessed to evaluate the antinociceptive effect of PCW. To investigate the participation of dynorphin/opioid system in PCW antinociception, subtype-specific opioid receptor antagonists or anti-dynorphin A antiserum were used. To eliminate other central mechanisms
that contribute to PCW antinociception, hot plate (50 °C) test were performed. Further, involvements of TRPV1 in PCW antinociception were evaluated in CFA-induced TRPV1−/− and TRPV1+/+ C57BL/6 male mice, and in capsaicin-induced nociception ICR naive mice pretreated with nor-binaltorphimine (nor-BNI). Meanwhile, calcium imaging was performed in HEK293T-TRPV1 cells. Finally, rotarod, open-field tests and body temperature measurement were carried out to assess side effects of PCW. PCW dose-dependently attenuated mechanical and heat hypersensitivities with no tolerance, which could be partially attenuated by coadministration of κ-opioid receptor antagonist nor-BNI or anti-dynorphin A (1–13) antiserum. And PCW antinociception was totally erased by pretreatment with nor-BNI in the hot plate test. In addition, PCW antinociception was decreased in TRPV1−/− mice compared to TRPV1+/+ group. And PCW still manifested inhibitory effects in capsaicin-induced nociception with nor-BNI pretreatment. PCW significantly inhibited capsaicin-induced calcium influx in HEK293T-TRPV1 cells. Finally, no detectable side effects were found in naive mice treated with PCW. This study shows PCW’s potent antinociceptive effect in inflammatory conditions without obvious side effects. This effect may result from the activation of κ-opioid receptor via dynorphin release and the inhibition of TRPV1. These findings indicate that PCW might be a potential agent for the management of chronic inflammatory pain.
coadministration of pinellia ternata can significantly reduce Aconitum Carmichaelii to inhibit cyp3a activity in ratsEvidence-based Complementary and Alternative Medicine, 2014Co-Authors: Jinjun Wu, Zaixing Cheng, Linlin Lu, Guiyu Zhang, Ying Wang, Ying XuAbstract:
Chuanwu (CW), the mother root of Aconitum Carmichaelii Debx., is a traditional Chinese medicine (TCM) for treating traumatic injuries, rheumatoid arthritis, and tumors. CW coadministered with banxia (BX), the root of Pinellia ternata, is also widely prescribed in clinical practice. However, the mechanism of this combination is yet deciphered. Current study aimed to investigate the effects of CW, including raw chuanwu (RCW) and processed chuanwu (PCW) alone, as well as CW coadministered with BX on CYP3A activity. Buspirone (BP) and testosterone (Tes) were used as specific probe substrates in vivo and ex vivo, respectively. CYP3A activity was determined by the metabolites formation ratios from the substrates. Compared with those in the control group, the metabolites formation ratios significantly decreased in the RCW and PCW alone groups, accompanied by a marked decrease in CYP3A protein and mRNA levels. However, there was a significant increase in those ratios in the RCW-BX and PCW-BX groups compared to the RCW and PCW alone groups. The results indicated that both RCW and PCW can inhibit CYP3A activity in rats because of downregulation of CYP3A protein and mRNA levels. Decreases in CYP3A activity can be reversed by coadministration with BX.
Cheng Peng – 3rd expert on this subject based on the ideXlab platform
discrimination of the geographical origin of the lateral roots of Aconitum Carmichaelii using the fingerprint multicomponent quantification and chemometric methodsMolecules, 2019Co-Authors: Lulin Miao, Cheng Peng, Qinmei Zhou, Chunwang Meng, Xiaoya Wang, Liang XiongAbstract:
Fuzi is a well-known traditional Chinese medicine developed from the lateral roots of Aconitum Carmichaelii Debx. It is rich in alkaloids that display a wide variety of bioactivities, and it has a strong cardiotoxicity and neurotoxicity. In order to discriminate the geographical origin and evaluate the quality of this medicine, a method based on high-performance liquid chromatography (HPLC) was developed for multicomponent quantification and chemical fingerprint analysis. The measured results of 32 batches of Fuzi from three different regions were evaluated by chemometric analysis, including similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), and linear discriminant analysis (LDA). The content of six representative alkaloids of Fuzi (benzoylmesaconine, benzoylhypaconine, benzoylaconine, mesaconitine, hypaconitine, and aconitine) were varied by geographical origin, and the content ratios of the benzoylmesaconine/mesaconitine and diester-type/monoester-type diterpenoid alkaloids may be potential traits for classifying the geographical origin of the medicine. In the HPLC fingerprint similarity analysis, the Fuzi from Jiangyou, Sichuan, was distinguished from the Fuzi from Butuo, Sichuan, and the Fuzi from Yunnan. Based on the HCA and PCA analyses of the content of the six representative alkaloids, all of the batches were classified into two categories, which were closely related to the plants’ geographical origins. The Fuzi samples from Jiangyou were placed into one category, while the Fuzi samples from Butuo and Yunnan were put into another category. The LDA analysis provided an efficient and satisfactory prediction model for differentiating the Fuzi samples from the above-mentioned three geographical origins. Thus, the content of the six representative alkaloids and the fingerprint similarity values were useful markers for differentiating the geographical origin of the Fuzi samples.
soil fungal biodiversity and pathogen identification of rotten disease in Aconitum Carmichaelii fuzi rootsPLOS ONE, 2018Co-Authors: Wei Wang, Dayan Zhang, Qihao Wang, Cheng PengAbstract:
Aconitum Carmichaelii, commonly known as Fuzi, is a typical traditional Chinese medicine (TCM) herb that has been grown for more than one thousand years in China. Although root rot disease has been seriously threatening this crop in recent years, few studies have investigated root rot disease in Fuzi, and no pathogens have been identified. In this study, fungal libraries from rhizosphere soils were constructed by internal transcribed spacer (ITS) sequencing using the HiSeq 2500 high-throughput platform. A total of 948,843 tags were obtained from 17 soil samples, and these corresponded to 195,583,495 nt. At 97% identity, the libraries yielded 12,266 operational taxonomic units (OTUs), of which 97.5% could be annotated. In sick soils, Athelia, Mucor and Mortierella were the dominant fungi, comprising 10.3%, 10.1% and 7.7% of the fungal community, respectively. These fungi showed 2.6-, 1.53- to 6.31- and 1.38- to 2.65-fold higher enrichment in sick soils compared with healthy soils, and their high densities reduced the fungal richness in the areas surrounding the rotted Fuzi roots. An abundance analysis suggested that A. rolfsii and Mucor racemosus, as the dominant pathogens, might play important roles in the invading Fuzi tissue, and Phoma adonidicola could be another pathogenic fungus of root rot. In contrast, Mortierella chlamydospora, Penicillium simplicissimum, Epicoccum nigrum, Cyberlindnera saturnus and Rhodotorula ingeniosa might antagonize root rot pathogens in sick soils. In addition, A. rolfsii was further verified as a main pathogen of Fuzi root rot disease through hypha purification, morphological observation, molecular identification and an infection test. These results provide theoretical guidance for the prevention and treatment of Fuzi root rot disease.
complete chloroplast genome of medicinal plant Aconitum Carmichaelii genome characterization and phylogenetic analysisMitochondrial DNA Part B, 2016Co-Authors: Dayan Zhang, Wei Wang, Cheng PengAbstract:
AbstractThe complete chloroplast genome sequence of an important medicinal plant of the family Ranunculaceae, Aconitum Carmichaelii Debx., was characterized in this study. The assembled chloroplast genome was 154,776 bp in length, which included a large single-copy (LSC), a small single-copy (SSC), and two inverted repeat (IR) regions of 86,330bp, 15,986 bp, and 26,193 bp, respectively. The GC content of the genome was 38.1%. Phylogenetic analysis with the whole nucleotide sequences of reported Aconitum chloroplast genomes indicated a close relationship of A. Carmichaelii with A. kusnezoffii.