On the Famous Traditional Chinese Medicine “Fu Zi”: Discovery, Research, and Development of Cardioactive Constituent Mesaconine

Wang, Feng‐Peng; Ruo-bing, Chao

doi:10.1007/s13659-020-00266-w

Cited by 12 publications

(4 citation statements)

References 8 publications

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“…Mesaconine, a natural diterpenoid alkaloid compound isolated from the lateral roots of Aconitum carmichaelii , is the main cardiotonic component in “Fuzi” ( Jian et al, 2012 ). It has been reported that the single maximum tolerated dose of mesaconine in rats reached 1200 mg/kg, leading to no appreciable toxicity or adverse reactions, which implies its safety as a novel anti-heart failure medicine ( Wang and Chao, 2021 ). However, the precise molecular mechanism and target of mesaconine remain elusive.…”

Section: Discussionmentioning

confidence: 99%

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

et al. 2023

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Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.

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Section: Discussionmentioning

confidence: 99%

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

et al. 2023

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“…The alkaloids in both 'Fuzi' and 'Chuanwu' have been reported to be the main contributors to the cardiovascular modulatory effects, as well as exhibiting anti-inflammatory, analgesic, anti-tumor, and immunomodulatory effects. 1,6,7 However, these alkaloids also cause toxicity or side effects on ion channels, neuron systems, and other organs, 8 and variation in the content and types of alkaloids in 'Fuzi' and 'Chuanwu' might be a reason for their different clinical applications 9,10 and toxicity. 11 Polysaccharides, as another promising bioactive constituent present in both 'Fuzi' and 'Chuanwu', have been shown to exhibit immunomodulatory, cardiovascular protective and anti-tumor activity.…”

Section: Introductionmentioning

confidence: 99%

Bioactive polysaccharides in different plant parts of Aconitum carmichaelii

Fu,

Li,

Zou

et al. 2023

J Sci Food Agric

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BackgroundAconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in Traditional Chinese Medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non‐toxic polysaccharides in this plant were less concerned than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were systematically isolated from different plant parts of A. carmichaelii, and their structural features and bioactivities were studied and compared.ResultsThe neutral fraction isolated from the rootlets was different from those isolated from the lateral and mother roots, consisting of less starch and more possible mannans, galactans, and/or xyloglucans, which was similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type‐I rhamnogalacturonan (RG‐I) were present in all plant parts of A. carmichaelii. However, more arabinogalactan (AG)‐II side chains in the RG‐I backbone were present in the aerial parts, while more arabinans followed by AG‐I/II were found in the roots. Various immunomodulatory effects determined by complement fixation activity and anti‐inflammatory effects on intestinal epithelial cells IPEC‐J2 of all polysaccharide fractions were observed.ConclusionThis study highlighted the diversity of polysaccharides present in A. carmichaelii, especially in the unutilized plant parts, and showed their potential medicinal values.This article is protected by copyright. All rights reserved.

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“…Gratifyingly, the above sequence secured a biomimetic synthesis of ajaconine alkaloids from the atisines. Next, we investigated the conversion of 7 into the denudatine alkaloid gymnandine (8). Treating 7 with Cp 2 Zr(H)Cl effected removal of the N-benzoyl group and concomitant transformation of the resulting hemiaminal into hydroxyl imine; further oxidation of the secondary alcohol (structure not shown) afforded ketone 33.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Molecules belonging to this unique family of natural products exhibit a wide spectrum of biological activities. In particular, several compounds such as guan-fu base A ( 1 , antiarrhythmic; Figure ), lappaconitine ( 2 , analgesic), and mesaconine ( 3 , cardiotonic) have been developed as clinical drugs or potential drug candidates. In addition to their biological significance, the diterpenoid alkaloids feature three-dimensionally complex and congested structures.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Three-Dimensionally Fascinating Diterpenoid Alkaloids and Related Diterpenes

2020

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Conspectus Three-dimensional cage-like natural products represent astounding and long-term challenges in the research endeavors of total synthesis. A central issue that synthetic chemists need to address lies in how to efficiently construct the polycyclic frameworks as well as to install the requisite substituent groups. The diterpenoid alkaloids that biogenetically originate from amination of diterpenes and diversify through late-stage skeletal reorganization belong to such a natural product category. As the characteristic components of the Aconitum and Delphinium species, these molecules display a rich array of biological activities, some of which are used as clinical drugs. More strikingly, their intricate and beautiful architectures have rendered the diterpenoid alkaloids elusive targets in the synthetic community. The successful preparation of these intriguing compounds relies on the development of innovative synthetic strategies. Our laboratory has explored the total synthesis of a variety of diterpenoid alkaloids and their biogenetically related diterpenes over the past decade. In doing so, we have accessed 6 different types of skeletons (atisine-, denudatine-, arcutane-, arcutine-, napelline-, and hetidine-type) and achieved the total synthesis of 6 natural products (isoazitine, dihydroajaconine, gymnandine, atropurpuran, arcutinine, and liangshanone). Strategically, an oxidative dearomatization/Diels–Alder (OD/DA) cycloaddition sequence was widely employed in our synthesis to form the ubiquitous [2.2.2]-bicyclic ring unit and its related ring-distorted derivatives in these complex target molecules. This protocol, in combination with additional bond-forming key steps, allowed us to prepare the corresponding polycyclic alkaloids and a biogenetically associated diterpene. For example, bioinspired C–H activation, aza-pinacol, and aza-Prins cyclizations were used toward a unified approach to the atisine-, denudatine-, and hetidine-type alkaloids via ajaconine intermediates in our first work. To pursue the synthesis of atropurpuran and related arcutine alkaloids, we harnessed a ketyl-olefin radical cyclization to assemble the carbocycle and an aza-Wacker cyclization to construct the unusual pyrrolidine ring. Furthermore, a one-pot alkene cleavage/Mannich cyclization tactic, sequential Robinson annulation, and intramolecular aldol addition were developed, which facilitated the formation of the napelline alkaloid scaffold and the first total synthesis of liangshanone. Finally, the utility of the Mannich cyclization and enyne cycloisomerization reactions allowed for access to the highly functionalized A/E and C/D ring fragments of aconitine (regarded as the “Holy Grail” of diterpenoid alkaloids). This Account provides insight into our synthetic designs and approaches used toward the synthesis of diterpenoid alkaloids and relevant diterpenes. These endeavors lay a foundation for uncovering the biological profiles of associated molecules and also serve as a reference for preparing other three-dimensionally fascinat...

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On the Famous Traditional Chinese Medicine “Fu Zi”: Discovery, Research, and Development of Cardioactive Constituent Mesaconine

Cited by 12 publications

References 8 publications

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

Bioactive polysaccharides in different plant parts of Aconitum carmichaelii

Synthesis of Three-Dimensionally Fascinating Diterpenoid Alkaloids and Related Diterpenes

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