The toxicology and detoxification of Aconitum: traditional and modern views

Aconitum carmichaeli Debx.-derived herbal medicine has been used for anti-inflammation and anti-arrhythmia purpose for more than two thousand years. It is processed into Chuanwu (Radix Aconiti praeparata) and Fuzi (Radix Aconiti lateralis praeparata) in Traditional Chinese Medicine, which are two useful drugs but with toxic properties. There have been patients poisoned by accidental ingestion of Aconitum plants or misuse of the herbal drug, and this is of great concern to study in-depth. In this review, we provided the traditional and contemporary practice of using Aconitum herbs as medicine, from functions, processing methods to toxicity in ethnomedicine aspects to discuss the underlying connections of traditional and modern understanding on the toxicity of Aconitum plants. We summarized the functions and toxicology of the herbal drugs are analyzed from chemical and clinical aspects, with the help of traditional and modern knowledge of medicine. The medicinal doses and lethal doses determined by researches are summarized, and the usage and processing methods are updated and reviewed in the modern view. In addition, clinical management of poisoned cases using western medicine is discussed. This review provides insights and awareness of safety when using Aconitum-derived herbal medicine, and the application of modern scientific knowledge to optimize the detoxification processes. We suggest the possibility to renew the current standard processing method from the official Pharmacopoeia all over the world.

Glycyrrhiza Uralensis Promote the Metabolism of Toxic Components of Aconitum Carmichaeli by CYP3A and Alleviate the Development of Chronic Heart Failure

BackgroundCHF is a common clinical critical disease with high mortality and short survival. Aconitum, as "the first drug of choice for invigorating Yang and saving lives", has been widely used for the treatment of heart failure. However, toxic components of Aconitum can easily lead to serious arrhythmia, respiratory depression, shock and even death [1, 2]. ObjectiveTo investigate the mechanisms of Glycyrrhizae reducing the toxicity of Aconitum.Method A High Performance Liquid Chromatography (HPLC) method for the determination of aconitine (AC), mesaconitine (MA) and hypaconitine (HA) was established; The effect of Glycyrrhiza on CYP3A1 / 2 mRNA expression was detected by RT-PCR; SD rats were given Aconitum and compatibility of Glycyrrhizae and Aconitum by gavage respectively, the blood concentration of toxic components were determined by LC-MS / MS; The CHF rat model was established by intraperitoneal injection of adriamycin (2.5 mg / kg), and were randomly divided into model, Aconitum, the compatibility of Glycyrrhizae and Aconitum and Captopril group. After 4 weeks of gavage, the levels of BNP, Ang II and ALD in blood were detected by ELISA, and the contents of adenosine monophosphate (ATP, ADP and AMP) in myocardium were determined by HPLC.Result AC, MA and HA produced three, three and two metabolites respectively; Ketoconazole significantly inhibited the metabolites of AC, MA and HA; Glycyrrhiza induced CYP3A gene expression, and significantly promoted the metabolism of toxic components of Aconitum; The level of ALD in the compatibility of Glycyrrhizae and Aconitum group was significantly lower than that in Aconitum group. After intervention with the compatibility of Glycyrrhizae and Aconitum, ATP increased significantly, ADP decreased significantly.Conclusion Glycyrrhiza promoted the metabolism of toxic components of Aconitum by up regulating the expression of CYP3A, and reduced the content of BNP, Ang II and ALD, improved the energy metabolism disorder of myocardium, alleviated the development of CHF.

Study on extraction methods of polysaccharides from a processed product of Aconitum carmichaeli Debx.

By comparing the effects of extraction methods on the activity and properties of polysaccharide, a polysaccharide extraction process was screened and optimized.

Effects of Herbal Medicines on Pain Management

Pain is an unpleasant sensory and emotional experience in many diseases and is often caused by intense or damaging stimuli. Pain negatively affects the quality of life and increases high health expenditures. Drugs with analgesic properties are commonly used to relieve pain, but these Western medications could be overwhelmed by side effects including tolerance and addiction. Herbal medicines may provide alternative measures for pain management. In this review paper, after introduction of Chinese medicine theory and treatment modality, emphasis is placed on the application of Chinese herbs and herbal formulations in pain management. Three of the most commonly used herbs, i.e., Corydalis yanhusuo, Ligusticum chuanxiong, and Aconitum carmichaeli, are reviewed. Subsequently, using this ancient medical remedy, Chinese herbal formulation in treating common medical conditions associated with pain, such as headache/migraine, chest pain, abdominal pain, low back pain, neuropathic pain, osteoarthritis, and cancer pain, is presented. Chinese herbal medicines could be considered as a complementary and integrative approach in the modern armamentarium in combating pain.

New Hydroxydecanoic Acid Derivatives Produced by an Dndophytic Yeast Aureobasidium pullulans AJF1 from Flowers of Aconitum carmichaeli

Endophytes have been recognized as a source for structurally novel and biologically active secondary metabolites. Among the host plants for endophytes, some medicinal plants that produce pharmaceuticals have been reported to carry endophytes, which could also produce bioactive secondary metabolites. In this study, the medicinal plant Aconitum carmichaeli was selected as a potential source for endophytes. An endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flower of Aconitum carmichaeli, was cultured on a large scale and extracted with an organic solvent. Extensive chemical investigation of the extracts resulted in isolation of three lipid type compounds (1–3), which were identified to be (3R,5R)-3,5-dihydroxydecanoic acid (1), (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid (2), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid (3) by chemical methods in combination with spectral analysis. Compounds 2 and 3 had new structures. Absolute configurations of the isolated compounds (1–3) were established using modified Mosher’s method together with analysis of NMR data for their acetonide derivatives. All the isolates (1–3) were evaluated for antibiotic activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and their cytotoxicities against MCF-7 cancer cells. Unfortunately, they showed low antibiotic activities and cytotoxic activities.

Application of GC/MS-Based Metabonomic Profiling in Studying the Therapeutic Effects of Aconitum carmichaeli with Ampelopsis japonica Extract on Collagen-Induced Arthritis in Rats

Aconitum carmichaeli with Ampelopsis japonica (AA) is a classical traditional Chinese medicine (TCM) formula. There are a lot of examples showing that AA can be used to treat rheumatoid arthritis, but its mechanism of action is still not completely clear. In this research, collagen-induced arthritis (CIA) was chosen as a rheumatoid arthritis (RA) model. Rats of treated groups were continuously administered Aconitum carmichaeli (AC), Ampelopsis japonica (AJ) and Aconitum carmichaeli + Ampelopsis japonica (AA) orally once a day from the day after the onset of arthritis (day 7) until day 42. The results showed that AA not only significantly reduced paw swelling, but also improved the levels of TNF-α and IL-6 in serum. GC-MS-based urine metabonomics was established to analysis metabolic profiles and 21 biomarkers of RA rats were identified by the Partial Least Squares Discriminant Analysis (PLS-DA) and Support Vector Machine (SVM) methods. The prediction rate of the SVM method for the 21 biomarkers was 100%. Twenty of 21 biomarkers, including D-galactose, inositol and glycerol, gradually returned to normal levels after administration of AA. Metabolomic Pathway Analysis (MetPA) generated three related metabolic pathways—galactose metabolism, glycerolipid metabolism and inositol phosphate metabolism—which explain the mechanism of AA treatment of rheumatoid arthritis. This research provides a better understanding of the therapeutic effects and possible therapeutic mechanism of action of a complex TCM (AA) on rheumatoid arthritis.