Aconiti Lateralis Preparata Research Articles

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Sini decoction against renal fibrosis.

To investigate the mechanism by which Sini decoction (, SND) improves renal fibrosis (Rf) in rats based on transforming growth factor β1/Smad (TGF-β1/Smad) signaling pathway. Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf. The targets of SND drug components and the targets of Rf were obtained by searching databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP) and GeenCard. The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram. Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway. The Rf rat model was established by unilateral ureteral occlusion (UUO). The expression levels of transforming growth factor, matrix metalloproteinase-9 (MMP-9), matrix metal protease-2 (MMP-2), connective tissue growth factor (CTGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by Masson staining of rat renal tissue, and immunohistochemical methods. The expression levels of Smad3, Smad2, and Smad7 in renal tissue were determined by Western blotting (WB). The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway. A total of 12 drug components of Fuzi (Radix Aconiti Lateralis Preparata), 5 drug components of Ganjiang (Rhizoma Zingiber), and 9 drug components of Gancao (Radix Glycy et Rhizoma) were obtained from the database search, and 207 shared targets were found. A total of 1063 Rf targets were found in the database search. According to the Venn diagram, in total, 96 intersection targets were found in two database searches. The metabolic pathways involved included TGF-β signaling pathway, phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling (PI3K/Akt) pathway, and hypoxia-inducible factor-1 (HIF-1) signaling pathway. Masson staining analysis showed that compared with the model group, the renal interstitial collagen deposition levels in the SSN and SND groups were significantly lower (P < 0.05). Immunohistochemical analysis, compared with the control group, the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the model group were significantly decreased (P < 0.05, P < 0.01), and the positive cell area expression levels of CTGF and TGF-β1 were significantly increased (P < 0.01). Compared with the model group, the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the SSN and SND groups were significantly increased (P < 0.05, P < 0.01), and the positive cell area expression levels of CTGF and TGF-β1 in the kidney tissue were significantly decreased (P < 0.05, P < 0.01). WB results showed that the SSN group and the SND group could reduce the expression of Smad2 and Smad3 (P < 0.05) and increase the expression of Smad7 (P < 0.05).

Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.

Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1β, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis.

Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial

Ethnopharmacological relevanceAmyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by progressive paralysis of voluntary muscles. Mecasin, the extract of modified jakyakgamchobuja-tang—a herbal preparation comprising of Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Gastrodiae, Radix Polygalae, Curcuma Root, Fructus Chaenomelis, and Rhizoma Atractylodis Japonicae—shows neuroprotective and anti-neuroinflammatory effects and alleviates the symptoms in patients with ALS. Aim of the studyThis trial aimed to evaluate the efficacy and safety of mecasin in these patients. Material and methodsPatients were randomized to receive mecasin 1.6 g daily, mecasin 2.4 g daily, or placebo for 12 weeks. The primary endpoint was the Korean version of ALS Functional Rating Scale-Revised (K-ALSFRS-R) score. The secondary endpoints were muscular atrophy measurements, pulmonary function test results, creatine kinase levels, body weight, safety, and scores of the Medical Research Council (MRC) scale for muscle strength; Visual Analog Scale for pain (VAS pain); Hamilton Rating Scale for Depression; and Fatigue Severity Scale. ResultsAmong the 30 patients randomized, 24 completed the follow-up. Significant between-group differences were detected in the primary endpoint using the omnibus F-test. The changes in the K-ALSFRS-R score between 12 weeks and baseline were −0·25, −1·32, and −2·78 in the mecasin 1.6 g, mecasin 2.4 g, and placebo groups, respectively. The difference in the K-ALSFRS-R score between the mecasin 1.6 g and placebo groups was 2·53 points (95% confidence interval [CI]: 0·61–4·45), and that between the 2.4 g and placebo groups was 1·46 points (95% CI: 0·48–3·40). However, no significant differences were detected in the secondary endpoints (MRC: dyspnea, p = 0·139; VAS pain, p = 0·916; forced vital capacity, p = 0·373). The incidence of adverse events was similar and low in all groups. ConclusionsMecasin may retard symptomatic progression without major adverse effects. A phase IIb study to evaluate its long-term effects in ALS is ongoing.

Identifying potential ligands specifically binding to beta1-adrenoceptor from Radix Aconiti Lateralis Praeparata extract by affinity chromatographic method

As expressed predominantly in cardiac tissue, beta1-adrenoceptor (β1-AR) is broadly accepted as one of the main targets for drugs against cardiovascular ailments. However, the discovery of β1-AR ligand is gravely challenged due to the lack of efficient screening method. This work developed a general strategy for pursuing β1-AR ligands from the herbal extract by immobilizing haloalkane dehalogenase (Halo)-tagged β1-AR onto microspheres coated with 6-chlorohexanoic acid, and applying the immobilized β1-AR in the analysis of ligand-receptor interaction. The morphology was characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The chromatographic specificity of the immobilized receptor column was evaluated by determining the association constants of atenolol, esmolol and metoprolol using stepwise frontal analysis plus injection amount-dependent method. The potential ligands binding to β1-AR was screened by collecting the peak with retention time longer than the void time, and identified the collection by reverse phase liquid chromatography coupled with tandem mass spectrometry. The association constants of the three drugs to β1-AR were (3.33 ± 0.29)× 106 M−1, (2.33 ± 0.23)× 106 M−1 and (2.06 ± 0.03)× 106 M−1, indicating a desired specificity of the immobilized receptor for recognizing its ligands. Molecular docking showed that van der Waals, hydrogen bonds, and hydrophobic interactions were the principal interaction forces for the receptor-drug complexes. Benzoylmesaconine was screened as the potential ligand of β1-AR in Radix Aconiti Lateralis Praeparata extract. The association constant of the ligand was (1.06 ± 0.02)× 105 M−1, hinting structural modification may be required before clinical application. The immobilized β1-AR is possible to provide a rapid method for screening potential ligands in herbal extract.

The Ameliorative Effect of Mahuang Fuzi and Shenzhuo Decoction on Membranous Nephropathy of Rodent Model is Associated With Autophagy and Wnt/β-Catenin Pathway.

The increased incidence of membranous nephropathy (MN) has made it the most common pathological type of primary nephrotic syndrome in adults in China. According to the theory of Traditional Chinese Medicine (TCM), Mahuang Fuzi (Chinese ephedra and Radix Aconiti Lateralis Preparata) and Shenzhuo Decoction (MFSD) could be used to treat such diseases. We treated patients of MN with MFSD, and observed comparable efficacy to glucocorticoid and/or immunosuppressants. In this study, we observed the therapeutic effect of MFSD on the rat model of passive Heymann nephritis (PHN), a classical MN model. Our results showed that MFSD treatment significantly reduced urinary protein level and podocyte injury in PHN rats, and correspondingly improved renal pathology, with the improvement effect on MN comparable to that of Cyclosporine A (CsA) alone. To explore the potential therapeutical mechanism of MFSD, the main chemical components of MFSD were determined by High-performance liquid chromatography-mass spectrometry (HPLC-MS). There were about 30 active components of MFSD. Next, based on network pharmacology methods, we screened related targets of MSFD on MN, which provided a preliminary understanding of the MFSD bioactive compounds. The clustering analysis showed that its active site might be in the autophagy-related protein and Wnt/β-catenin pathway, which was related to podocyte injury. Finally, we observed an improvement in renal autophagy and a down-regulation of the Wnt/β-catenin pathway after MSFD treatment in a PHN rat model. According to this study, autophagy and Wnt/β-catenin pathway may be potential targets for MFSD in the treatment of MN.

Risk compounds, potential mechanisms and biomarkers of traditional Chinese medicine-induced reproductive toxicity.

With the increasing application of traditional Chinese medicine (TCM), TCM-induced reproductive toxicity has gradually aroused people's concern. Various TCM, such as Tripterygium wilfordii Hook. f., Radix Aconiti lateralis Preparata and Rhizoma Pinelliae, are currently reported to cause reproductive toxicity in humans and animals. However, a summary of the material bases, mechanisms and biological markers of TCM-induced reproductive toxicity is still lacking. This review filled the gap by searching and summarising relevant studies and articles published on PubMed, CNKI and Web of Science databases from January 2000 to November 2021. The risk ingredients involved in TCM-induced reproductive toxicity were divided into glycosides, alkaloids, phenols, terpenoids, anthraquinones, lactones, plant toxin proteins, animal toxins and so forth. Potential mechanisms underlying TCM-induced reproductive toxicity, including steroidogenic toxicity, lipids metabolism abnormity, energy insufficiency, oxidative stress and apoptosis, were illustrated. We also outlined possible biomarkers, especially biomarkers of effect involved in TCM-induced reproductive toxicity, including anti-oxidant enzymes, signalling pathways, genes and growth factors.

Pharmacokinetics and tissue distribution of trans-ferulic acid-4-β-glucoside in rats using UPLC-MS/MS.

Trans-ferulic acid-4-β-glucoside (FAG) is a monomer extracted from Radix Aconiti Lateralis Preparata, which is a potential candidate for the prevention and treatment of cold injury. To determine the concentration of FAG in rats, it is essential to develop an ultra-performance liquid chromatography coupled with MS/MS method. Chromatographic separation was achieved by an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7μm). A Xevo triple quadrupole tandem mass spectrometer was used to quantitatively determine FAG in the negative-ion mode. The standard calibration curve was linear over the concentration range of 0.1-100 μg/mL and 0.0626-31.28 μg/g for rat plasma and liver tissue homogenate samples, respectively. The inter- and intra-batch precision (% relative standard deviation) of the assay was ≤8.29%, and accuracy (% relative error) ranged from -7.41 to 10.99%. The matrix effect was between 92.99 and 102.39%. The oral absolute bioavailability of FAG was obtained as 1.80%. The results of tissue distribution suggested that FAG spread rarely in the liver and brown adipose, which was not propitious to exert its ability to treat cold injury. In general, these studies were significant to provide necessary information for further study.

Efficacy of Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rat.

To elucidate the protective effects of Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction (MI) through regulating myocardial autophagy. Thirty-one male Sprague-Dawley rats were randomized into five groups (n = 6 or 7 for each). After treatment for 3 weeks, electrocardiogram ( ECG ) and cardiac function were recorded. Hematoxylin and eosin (HE) staining was used to detect pathological changes in the heart. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum B-type brain natriuretic peptide (BNP), cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), and serum inflammatory cytokines. Metabolomic analysis was used to identify differential biomarkers of MI in rats. Immunohistochemistry and western blotting were used to detect BNP, cTnT, TNF-α, LC3B, Beclin-1, p62, and adenosine monophosphate activated protein kinase (AMPK) expression in cardiac tissue. Fuzi (Radix Aconiti Lateralis Preparata) alone or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) markedly ameliorated cardiac dysfunction and abnormal ECGs, demonstrated by decreases in the heart weight/body weight ratio, BNP, and cTnT. Pro-inflammation cytokine interleukin (IL)-1α significantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen (Radix Ginseng) single or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) groups compared with the control group. HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen (Radix Ginseng) or Fuzi (Radix Aconiti Lateralis Preparata) alone. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) reversed these changes to different degrees in MI rats. Furthermore, Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) down-regulated LC3B, Beclin-1, and AMPK expression in cardiac tissue and upregulated p62 expression. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) may have a greater effect on heart injury induced by MI in rats than Fuzi (Radix Aconiti Lateralis Preparata) treatment alone, and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects. These results provide fresh insight into the mechanism of co-treatment with Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) for MI.

Assessment of the anti-rheumatoid arthritis activity of Gastrodia elata (tian-ma) and Radix aconitic lateralis preparata (fu-zi) via network pharmacology and untargeted metabolomics analyses.

Gastrodia elata and Radix aconiti lateralis preparrata are respectively named as Tian-Ma and Fu-Zi (TF) in Chinese. We explored the active components against rheumatoid arthritis (RA) from an extensively used couplet of Chinese herbs, Gastrodia elata and Radix aconiti lateralis preparata (TF) via untargeted metabolomics and network pharmacological approaches. Water extracts of TF were mixed at ratios 1:1, 3:2 and 2:3 (w/w). Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was then utilized as metabolomics screening. Human Metabolome (http://www.hmdb.ca/) and Lipidmaps (http://www.lipidmaps.org/) databases were used to annotate detected compounds. Further identification of vital genes and important pathways associated with the anti-RA properties of the TF preparations was done via network pharmacology, and verified by real-time quantitative polymerase chain reaction (RT-qPCR). Four key compounds involved in unsaturated fatty acid biosynthesis and isoflavonoid biosynthesis were identified through metabolomics analyses. Three key components of TF associated with anti-RA activity were linoleic acid, daidzein, and daidzin. Results of RT-qPCR revealed that all 3 tested TF couplets (1:1, 3:2, and 2:3) markedly suppressed the transcription of PTGS2. These results were consistent with our network pharmacological predictions. The anti-RA properties of Tian-Ma and Fu-Zi are associated with the inhibition of arachidonic acid metabolism pathway.

Relationship between cardiotonic activity of Fuzi (Radix Aconiti Lateralis Preparata) and its fingerprint determined by liquid chromatography-mass spectrometry.

To investigate the relationship between the cardiotonic activity of Fuzi (Radix Aconiti Lateralis Preparata, RALP) and its fingerprint determined by liquid chromatography-mass spectrometry (LC-MS). First, the fingerprints of six processed products of RALP were established by high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) followed by analysis of the principal component of the relative peak area of its common peaks. Next, the scores of the first five principal components were used as input for an artificial neural network (ANN). Additionally, the therapeutic effect of RALP was assessed by measuring the hemodynamic indexes of heart failure model rats. Subsequently, fluorescence semi-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay kit were used to determine the effects of RALP-processed products on the serum levels of noradrenaline (NA), angiotensin-Ⅰ (Ang-Ⅰ), and the expression of β-norepinephrine receptor mRNA (β-NRm) in the rat cardiac tissues. P < 0.05 was used as the output of the ANN. Finally, a network was constructed to display the relationship between the LC-MS fingerprints and the cardiotonic activity of the RALP-processed products. Several types of RALPs can improve diastolic function, systolic function and heart rate. On the basis of the findings from the principal component analysis (PCA) of 16 common peaks of fingerprints of six RALP-processed products, it was revealed that the first five principal components may include 100% of the information of the original data. As observed from the multilayer perceptron neural network analysis, principal component 4 presented with the strongest effects on serum levels of NA and Ang-Ⅰ in rats, while principal component 1 exerted the greatest effect on β-NRm expression in cardiac tissue. The key findings obtained from this study indicated that the network constructed by the PCA-ANN may predict pharmacodynamic effects of the main ingredients of Traditional Chinese Medicine (TCM). This method may serve as a new approach to identify the relationship between LC-MS fingerprints and the pharmacodynamic effects of TCM ingredients.

Comparative HPLC-MS/MS-based pharmacokinetic studies of multiple diterpenoid alkaloids following the administration of Zhenwu Tang and Radix Aconiti Lateralis Praeparata extracts to rats

s Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with Cmax and AUC0–∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The Cmax and AUC0–∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.

Crude Radix Aconiti Lateralis Preparata (Fuzi) with Glycyrrhiza Reduces Inflammation and Ventricular Remodeling in Mice through the TLR4/NF-κB Pathway.

Radix Aconiti Lateralis Preparata (Fuzi) is a traditional Chinese medicine. Its alkaloids are both cardiotonic and cardiotoxic; however, the underlying mechanisms are unclear. Compatibility testing and processing are the primary approaches used to reduce the toxicity of aconite preparations. The purpose of this study was to compare the effects of crude Fuzi (CFZ), CFZ combined with Glycyrrhiza (Gancao) (CFZ+GC), and prepared materials of CFZ (PFZ) on heart failure (HF) in C57BL/6J mice and explore the potential mechanisms of action of CFZ. Transverse aortic constriction (TAC) was used to generate the HF state, and CFZ (1.5 g·mL−1), PFZ (1.5 g·mL−1), or CFZ+GC (1.8 g·mL−1) was orally administered to the HF-induced mice daily. For the subsequent 8 weeks, hemodynamic indicators, ventricular pressure indices, and mass indices were evaluated, and histopathological imaging was performed. CFZ, CFZ+GC, and PFZ significantly improved left ventricular function and structure and reduced myocardial damage. CFZ+GC was more effective than CFZ and PFZ, whereas CFZ had higher toxicity than CFZ+GC and PFZ. CFZ and CFZ+GC attenuated ischemia-induced inflammatory responses and also inhibited Toll-like receptor-4 (TLR4) and nuclear factor kappa beta (NF-κB) action in the heart. Moreover, mass spectrometry analysis revealed a decrease in the levels of toxic components of CFZ+GC, whereas those of the protective components were increased. This study suggested that GC reduces the toxicity and increases the efficacy of CFZ on HF induced by TAC. Furthermore, GC+CFZ reduces the risk of HF by ameliorating the inflammation response, which might be partially related to the inhibition of the TLR4/NF-κB pathway.

P109 - Aconitum alkaloids from Radix Aconiti Lateralis Preparata induced liver injury in rats: Mechanistic consideration on bile acid perturbations

P109 - Aconitum alkaloids from Radix Aconiti Lateralis Preparata induced liver injury in rats: Mechanistic consideration on bile acid perturbations

Extraction, structural characterization, and immunoregulatory effect of a polysaccharide fraction from Radix Aconiti Lateralis Preparata (Fuzi)

A water-soluble polysaccharide fraction named FZPS-1 was obtained from Radix Aconiti Lateralis Preparata (Fuzi in Chinese). Physicochemical and instrumental analyses indicated that the purified FZPS-1 with an average molecular weight of 6.29 × 106 Da was composed of D-arabinose and d-glucose with a molar ratio of 7.5:92.5. It would contain the main chain fragments of →4)-α-D-Glc-(1 → 4)-α-D-Glc-(1→, with the side chain of terminal α-L-Ara-(1 → linked at C6 of D-Glc skeleton. FZPS-1 exhibited significant antioxidative activity and immunomodulatory activity, wherein it promotes macrophage phagocytosis and increases the secretion of macrophage-derived biological factors in RAW 264.7 cells, and a cyclophosphamide-induced immunosuppressed model in a dose-dependent manner. Oral administration of FZPS-1 ameliorated chronic diarrhea in rhubarb-induced spleen deficiency rats and was related to its immunomodulatory activity. Therefore, the obtained FZPS-1 could be potentially utilized as a natural immunomodulatory agent in functional food supplements or drugs.

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.

Radix Aconiti Lateralis Preparata (fuzi) is the processed product of Aconitum carmichaelii Debeaux tuber, and has great potential anti-myocardial infarction effects, including improving myocardial damage and energy metabolism in rats. However, the effects of Radix Aconiti Lateralis Preparata extracts in a rat model of myocardial infarction have not yet been fully illustrated. Herein, Radix Aconiti Lateral Preparata was used to prepare Radix Aconiti Lateralis Preparata extract (RAE), fuzi polysaccharides (FPS), and fuzi total alkaloid (FTA). Then, we aimed to compare the effects of RAE, FPS, and FTA in MI rats and further explore their influence on small molecules in the heart. We reported that Radix Aconiti Lateralis Preparata extract (RAE) and fuzi total alkaloid (FTA) significantly improved left ventricular function and structure, and reduced myocardial damage and infarct size in rats with myocardial infarction by the left anterior descending artery ligation. In contrast, fuzi polysaccharides (FPS) was less effective than RAE and FTA, indicating that alkaloids might play a major role in the treatment of myocardial infarction. Moreover, via matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI–MSI), we further showed that RAE and FTA containing alkaloids as the main common components regulated myocardial energy metabolism-related molecules and phospholipids levels and distribution patterns against myocardial infarction. In particular, it was FTA, not RAE, that could also regulate potassium ions and glutamine to play a cardioprotective role in myocardial infarction, which revealed that an appropriate dose of alkaloids generated more obvious cardiotonic effects. These findings together suggested that Radix Aconiti Lateralis Preparata extracts containing an appropriate dose of alkaloids as its main pharmacological active components exerted protective effects against myocardial infarction by improving myocardial energy metabolism abnormalities and changing phospholipids levels and distribution patterns to stabilize the cardiomyocyte membrane structure. Thus, RAE and FTA extracted from Radix Aconiti Lateralis Preparata are potential candidates for the treatment of myocardial infarction.

Changes in the properties of Radix Aconiti Lateralis Preparata (Fuzi, processed aconite roots) starch during processing.

Radix Aconiti Lateralis Preparata (Fuzi) is an important, toxic traditional Chinese medicine that has been widely used in clinical practice. Due to the toxicity of its raw materials, it needs to be processed before application. The changes in the physicochemical properties of Fuzi starch during processing were evaluated by scanning electron microscopy, X-ray diffraction and differential scanning calorimetry. The results showed the following: morphological properties changed from spherical to irregular and polygonal particles, while the particle size increased significantly; amylose content and solubility decreased significantly; swelling power and water-binding capacity increased significantly; the X-ray diffraction peak disappeared, and the crystallinity decreased; and the gelatinization temperature and enthalpy decreased significantly. The properties of Fuzi starch were similar to those of pregelatinized starch. These results indicated that Fuzi starch undergone repeated processes of gelatinization and aging, which destroyed the original crystal structure of the starch.

Relationships between the Toxicities of Radix Aconiti Lateralis Preparata (Fuzi) and the Toxicokinetics of Its Main Diester-Diterpenoid Alkaloids.

The processed lateral root of Aconitum carmichaelii Deb (Aconiti Radix lateralis praeparata or Fuzi) is a potent traditional herbal medicine extensively used in treatment of cardiovascular diseases, rheumatism arthritis, and bronchitis in many Asian countries. Although Fuzi has promising therapeutic effects, its toxicities are frequently observed. Three main C19-diester-diterpenoid alkaloids (DDAs) are believed to be the principal toxins of the herb. Although toxicokinetic profiles of the toxic DDAs have already been examined in several studies, they have seldom been correlated with the toxicities of Fuzi. The current article aimed to investigate the relationship between the up-to-date toxicokinetic data of the toxic DDAs and the existing evidence of the toxic effects of Fuzi. Relationships between the cardiac toxicity and the plasma and heart concentration of DDAs in mice and rats were established. Based on our findings, clinical monitoring of the plasma concentrations of DDAs of Fuzi is recommended to prevent potential cardiac toxicities. Additionally, caution with respect to potential hepatic and renal toxicity induced by Fuzi should be exercised. In addition, further analyses focusing on the preclinical tissue distribution profile of DDAs and on the long-term toxicokinetic-toxicity correlation of DDAs are warranted for a better understanding of the toxic mechanisms and safer use of Fuzi.

Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2.

Cucurbitacin B (Cu B), a tetracyclic triterpenoid derived from Trichosantheskirilowii Maxim, exhibits anticancer effects against various types of tumor. Higenamine, isolated from Radix Aconiti Lateralis Preparata, has been used as a dietary supplement for regulating metabolic function. The present study suggested that higenamine enhances Cu B-induced cytotoxicity in breast cancer cells and invivo. Network pharmacology analysis was used to identify the possible mechanism of action. CuB alone inhibited breast cancer cell growth, induced apoptosis, and arrested the cell cycle in the G2/M phase. CuB combined with higenamine potentiated the cytotoxic effect of CuB, resulting in the enhanced induction of apoptosis and G2/M arrest. The network pharmacology analysis also found that the major predicted targets of CuB in breast cancer were AKT, endoplasmic reticulum, farnesyltransferase, CAAX box, α, platelet-derived growth factor receptor α, peroxisome proliferator-activated receptor, RET proto-oncogene, and vascular endothelial growth factor A. The possible targets of higenamine involved in the synergic action were cyclin A2, cyclin-dependent kinase2 (CDK2), dihydrofolate reductase, and protein kinase CAMP‑activated catalytic subunit α. The associated pathways were summarized by Kyoto Encyclopedia of Genes and Genomes pathway analysis, and it was hypothesized that higenamine may enhance the antitumor effects of CuB in breast cancer through inhibition of the interaction of AKT and CDK2. The protein expression was assayed by western blot analysis. The combined treatment also resulted in significant inhibition of growth invivo.

Inhibitory effect of Sumu (Lignum Sappan) plus Fuzi (Radix Aconiti Lateralis Praeparata) on a lung carcinoma model

OBJECTIVETo investigate the inhibitory effect of Sumu (Lignum Sappan) plus Fuzi (Radix Aconiti Lateralis Praeparata) (SF) on the growth and metastasis of Lewis lung carcinoma. METHODSA lung carcinoma model was established by subcutaneously inoculating Lewis lung carcinoma cells into C57BL/6 mice. The mice were randomly divided into four groups of 13 mice (control, low-dose, moderate-dose, and high-dose), and gavaged once-daily for 21 consecutive days. The rates of tumor inhibition, metastasis, and metastasis inhibition were observed. The differential expressions of sP-selectin and vascular endothelial growth factor C (VEGFC) were compared between the treatment groups and the control group. RESULTSThe tumor weights differed significantly between the treatment groups and the control group (P < 0.05). Administration of SF in the moderate-dosage and low-dose groups significantly inhibited the expression of sP-selectin and VEGFC (both P < 0.05), suggesting anti-tumor activity. CONCLUSIONSF can inhibit the growth and metastasis of Lewis lung carcinoma.

Acupuncture–moxibustion therapy of "banking up original qi and consolidating the foundation" for prevention and treatment of seasonal allergic rhinitis: A randomized controlled trial

ObjectiveTo observe the clinical efficacy of acupuncture–moxibustion therapy of "banking up original qi and consolidating the foundation" for prevention and treatment of seasonal allergic rhinitis. MethodsSixty included patients were divided into two groups according to the random number table method with 30 patients in each group. In acupuncture group, warming-needle moxibustion was carried out at Zúsānlĭ (足三里ST 36), and cone moxibustion on Fùzĭ (附子Radix Aconiti Lateralis Praeparata) cake was conducted at Guānyuán (关元CV 4), Qìhăi (气海CV 6) and Dàzhuī (大椎GV 14). The treatment was conducted in May or June (2 months before the onset of rhinitis in this area). The treatment was carried out for once every other day and three times per week. Treatment for 24 times was considered as 1 course of treatment. No intervention treatment was conducted in control group. The score of rhinitis symptom, the visual analogue scale (VAS) score changes of total nasal symptom score (TNSS) and total non-nasal symptom score (TNNSS) of patients in 2015 and in 2016 were observed, and the clinical efficacy of the two groups was compared. Results(1) The score of rhinitis symptom, the VAS score changes of TNSS and TNNSS in acupuncture group in 2016 declined when compared with the results in 2015, which were 4.57 ± 0.82 vs 9.40 ± 1.89, 13.37 ± 4.01 vs 30.80 ± 4.77 and 15.93 ± 6.30 vs 46.13 ± 9.79 (P < 0.001), the results in acupuncture group after treatment were lower than that in control group at same time, which were 4.57 ± 0.82 vs 7.53 ± 2.06, 13.37 ± 4.01 vs 27.17 ± 6.84,15.93 ± 6.30 vs 35.53 ± 11.69(all P < 0.001). According to comparison, there was no obvious difference in the results in control group at the two time points, which were 8.60 ± 2.39 vs 7.53 ± 2.06, 29.63 ± 6.30 vs 27.17 ± 6.84 and 40.90 ± 12.31 vs 35.53 ± 11.69 (all P > 0.05). (2) The total effective rate was 96.7% (29/30) in acupuncture group and 10% (3/30) in control group, and the difference was statistically significant (P < 0.001). ConclusionAcupuncture–moxibustion therapy of "banking up original qi and consolidating the foundation" was effective on prevention and treatment of seasonal allergic rhinitis.