Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration / 中西医结合学报

OBJECTIVE@#Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC).@*METHODS@#An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method.@*RESULTS@#We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38.@*CONCLUSION@#Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.

Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty: a randomized controlled trial / 中国针灸

OBJECTIVE@#To investigate the clinical effect of aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty and the influence on hypercoagulation.@*METHODS@#Seventy-three patients of knee osteoarthritis with lower extremity venous thrombosis after total knee arthroplasty (KOA) were randomly divided into an observation group (37 cases, 2 cases dropped off) and a control group (36 cases, 1 case dropped off). The patients in the control group took orally rivaroxaban tablets, 10 mg a time, once a day. On the basis of the treatment as the control group, the aconite-isolated moxibustion was applied to Yongquan (KI 1) for the patients of the observation group, once daily and 3 moxa cones were used in each treatment. The duration of treatment was 14 days in both groups. Before treatment and 14 days into treatment, the ultrasonic B test was adopted to determine the conditions of lower extremity venous thrombosis in the two groups. Before treatment, 7 and 14 days into treatment, the coagulation indexes (platelet [PLT], prothrombin time [PT], activated partial prothrombin time [APTT], fibrinogen [Fib] and D-dimer[D-D]), the blood flow velocity of the deep femoral vein and the circumference of the affected side were compared between the two groups separately, and the clinical effect was evaluated.@*RESULTS@#Fourteen days into treatment, the venous thrombosis of the lower extremity was relieved in both groups (P<0.05), and that of the observation group was better than the control group (P<0.05). Seven days into treatment, the blood flow velocity of the deep femoral vein was increased compared with that before treatment in the observation group (P<0.05), and the blood flow rate in the observation group was higher than that in the control group (P<0.05). Fourteen days into treatment, PT, APTT and the blood flow velocity of the deep femoral vein were increased in the two groups compared with those before treatment (P<0.05); and PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all reduced in the two groups (P<0.05). Compared with the control group 14 days into treatment, the blood flow velocity of the deep femoral vein was higher (P<0.05), PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all lower in the observation group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 85.7% (30/35) in the control group (P<0.05).@*CONCLUSION@#Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban can effectively treat lower extremity venous thrombosis after total knee arthroplasty, relieve hypercoagulation, accelerate the blood flow velocity and alleviate swelling of the lower extremity in the patients with knee osteoarthritis.

Traditional Chinese herbal medicine Astragalus Radix and its effects on intestinal absorption of aconite alkaloids in rats / 中草药·英文版

Objective: Astragalus Radix (AR, Huangqi in Chinese) has been widely used as a qi (energy) restoring herb that is thought to act through reinvigorating the spleen and lung. Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times, but it is limited by its strong neuro and cardiotoxicity. Since the Song Dynasty (1227), the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion, from the “Wei's Family Prescription”. However, many ancient texts also record that they are not compatible using together, suggesting they can have negative outcomes when mixed. This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite. Methods: Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption. Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and immunofluorescence microscopy, respectively. Results: The results showed that aconite alkaloids absorption could be inhibited, and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment. Conclusion: These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters (ABC transporters) and tight junction proteins. It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.

Comparative Study on the Salt-processed Excipients for Aconite Based on “Efficacy Enhancing and Toxicity Re- ducing” / 中国药房

OBJECTIVE：To compare the c ontents of 6 kinds of ester alkaloids in raw aconite and 5 kinds of salt-processed products，and to provide reference for the optimization of salt-processing technology. METHODS ：Processed with bittern ， magnesium chloride ，sodium chloride ，calcium chloride and potassium chloride as excipients ，and HPLC method were adopted to determine the contents of 6 kinds of ester alkaloids in raw aconite and 5 kinds of salt-processed products. The effect/toxicity ratio and toxicity component index were used to evaluate the effect and toxicity of raw aconite and 5 kinds of salt-processed products. RESULTS： The linear range of benzoylneoaconitine ， benzoylhypoconitine， benzoylaconitine， neoaconitine， aconitine and hypoconitine were 2.440-24.40，2.240-22.40，2.020-20.20，2.780-27.80，2.240-22.40，2.240-22.40 μg/mL（r≥0.999 0）. RSDs of precision，stability and repeatability tests were all less than 2％. The recovery rates were 102.13％-104.87％（RSD＝0.98％，n＝ 6），100.00％-105.00％（RSD＝2.02％，n＝6），95.00％-99.29％（RSD＝1.77％，n＝6），100.41％-104.58％（RSD＝1.78％，n＝ 6），98.87％-99.90％（RSD＝0.41％，n＝6），100.20％-104.00％（RSD＝1.55，n＝6），respectively. The contents of total alkaloids in order from the largest to the smallest was as follows ：raw aconite ＞processed products of sodium chloride ＞processed products of bittern ＞processed products of potassium chloride ＞processed products of calcium chloride ＞processed products of magnesium chloride. The order of effect/toxicity ratio was processed products of potassium chloride ＞processed products of magnesium chloride＞processed products of sodium chloride ＞processed products of calcium chloride ＞processed products of bittern ＞raw aconite. The order of toxicity component index was raw aconite ＞processed products of sodium chloride ＞processed products of bittern＞processed products of calcium chloride ＞processed products of potassium chloride ＞processed products of magnesium chloride. CONCLUSIONS ：Using 5 kinds of salt as excipients ，the proce ssing technology has different degrees of “efficacy enhancing and toxicity reducing ”effect. Among them ，magne- sium chloride ，potassium chloride and calcium chloride are better for processing and can be used for processing aconite.

Effectiveness of Makyoyokukanto Combined with Powdered Cinnamon bark and Processed Aconite Root for Chronic Sciatica / 日本東洋医学雑誌

Chronic sciatica is one of the neuropathic pains which assumed to be effective for pregabalin. However, a recent double-blind placebo-controlled trial reported that pregabalin was no more effective than placebo in patients with acute or chronic sciatica. We retrospectively investigated the effect of Kampo medicine including makyoyokukanto extracts combined with powdered cinnamon bark and processed aconite root (makyoyokukanto plus) which were administered to 14 cases with chronic sciatica in the past year. The efficacy of Kampo medicine for lower leg pain relief was assessed using NRS (numerical rating scale). It was effective in 11 of 14 cases (79%, 6 males and 5 females, the mean age : 69), and not effective in 3 of 14 cases (21%, 2 males and 1 female, the mean age : 77). In 7 of 9 cases, who were given pregabalin before prescribing makyoyokukanto plus, makyoyokukanto plus was more effective than pregabalin. Furthermore, we have continued to observe 10 cases for over a year. Two of 10 cases were completely cured even if makyoyokukanto plus was discontinued. In 5 cases we switched from makyoyokukanto plus to yokuininto extracts combined with powdered cinnamon bark and processed aconite root, which was comparable to makyoyokukanto plus in its effect. Makyoyokukanto or yokuininto extracts combined with powdered cinnamon bark and processed aconite root were effective for chronic sciatica.

Study on Anti-synovial Angiogenesis Mechanism of Licorice and Aconite Decoction in the Treatment of Adjuvant Arthritis Model Mice / 中国药房

OBJECTIVE： To investigate the therapeutic effect of Licorice and aconite decoction in the treatment of adjuvant arthritis （AA） model mice through anti-synovial angiogenesis pathway. METHODS： Totally 48 male Balb/c mice were randomly divided into normal group， model group， Licorice and aconite decoction group and tripterygium glycosides group （positive drug group）， with 12 mice in each group. Except for normal group， AA model was established by intradermal injection of Freund’s complete adjuvant into the left hind toe of mice. 12 d after modeling， normal group and model group were given same volume of water intragastrically； Licorice and aconite decoction group （7.8 g/kg，by total amount of crude drug） and tripterygium glycosides group （0.01 g/kg） were given relevant medicine 20 mL/kg intragastrically， once a day， for consecutive 18 d. The joint lesions of mice were observed and recorded， and the foot swelling degree of mice was measured by water volume method. HE staining was used to observe the pathological change of ankle joint in mice. The protein levels of platelet endothelial cell adhesion molecule-1 （CD31） and vascular endothelial growth factor （VEGF） were determined by immunofluorescence assay. The protein expressions of nuclear factor κB（NF-κB） and zinc finger transcription factor GATA4 （GATA4） were detected by Western blotting assay. RESULTS： Compared with normal group， ankle joint of model group mice was markedly reddened and swollen， and foot swelling degree increased significantly （P＜0.05）. Synovial tissue of ankle joint proliferated， pannus increased significantly， and a large number of inflammatory cells and joint erosion were observed. The protein expression of CD31， VEGF， NF-κB and GATA4 in synovial tissue of mice were increased significantly （P＜0.05）. Compared with model group， the redness and swelling of ankle joint in mice were alleviated， and the foot swelling degree was significantly reduced in Licorice and aconite decoction group （P＜0.05）. Pannus in synovial tissue decreased and other pathological symptoms were improved. The protein expression of CD31， VEGF， NF-κB and GATA4 were decreased significantly in synovial tissue （P＜0.05）. CONCLUSIONS： Licorice and aconite decoction can decrease the protein expression of VEGF，NF-κB and GATA4 in synovial tissue， reduce the generation of pannus in synovial tissue and effectively inhibit the angiogenesis in synovial tissue so as to prevent bone destruction and protect joint of AA model mice.

Comparative analysis of aconitine alkaloids in aconite tube using direct ionization and wooden tip spray mass spectrometry / 药学学报

In this manuscript, a rapid and simple analysis method for aconitine alkaloids was established. The method was based on the use of direct ionization and wooden tip spray ionization technology to detect the aconite. The aconite tuber slices were wrapped with wet filter paper overnight, cut into triangles, and extracted with a few solvents for direct ionization and wooden tip spray mass spectrometry. The results showed that alkaloids in aconite tuber can be rapid detected by two mass spectrometric methods without tedious sample pretreatment. Both methods are superior to that of traditional capillary electrospray ionization mass spectrometry (ESI-MS). The direct ionization MS is better than the wooden tip spray MS for analysis of aconite except under the condition of methylene chloride as extract or spray solvent. Different types of alkaloids in aconite tuber can be selectively detected when different solvents are used. The experiments provide a rapid and no pretreatment MS spectrometric method for analysis of alkaloids in aconite. These sample methods are important for research on aspects of plant varieties, storage, prescription compatibility, and quality control of aconite.

Compound Compatibility Law of Rhubarb and Aconite Decoction Based on CYP450 Enzymes / 中国药学杂志

OBJECTIVE: To study the law of compatibility and detoxification of rhubarb and aconite decoction based on the CYP450 enzyme-mediated metabolic interaction. METHODS: The activities of CYP1A2 and CYP3A4 enzymes were determined by incubating the "Cocktail" probe drugs in vitro. The total content of CYP450 enzyme in liver microsomes was determined by carbon monoxide differential method. And the expression of CYP1A2 and CYP3A4 mRNA was detected by RT-PCR method. RESULTS: Rhubarb group, aconite root combined with rhubarb group and rhubarb combined with asarum group showed significant induction effects on CYP1A2 enzyme activity. CYP1A2 enzyme activity was significantly inhibited in the aconite root combined with asarum group. CYP3A4 enzyme activity was significantly inhibited in the asarum group and the aconite root combined with asarum group. Rhubarb group, rhubarb combined with asarum group and rhubarb and aconite decoction had significant induction effects on CYP3A4 enzyme activity. Rhubarb group significantly induced the total content of CYP450 enzyme, asarum group and aconitum root combined with asarum group inhibited the total content of CYP450 enzyme, rhubarb and aconite decoction had slight induction effects on the total content of CYP450, but there was no significant difference. Rhubarb group, rhubarb combined with asarum group and rhubarb and aconite decoction group could up-regulate the mRNA expression of CYP1A2. In addition, rhubarb and aconite decoction and rhubarb group could up-regulate the mRNA expression of CYP3A4. And asarum group and aconite combined with asarum group could down-regulate the mRNA expression of CYP3A4. CONCLUSION: The drug combination weakened the strong induction of CYP1A2 and CYP3A4 enzymes by rhubarb alone, reflecting the holism concept of compound traditional Chinese medicine. The effects of rhubarb and aconite decoction on CYP3A4 enzyme activity are likely to be regulated by the mRNA levels of CYP3A4 enzyme. Whether there is correlation between the cold-heat compatibility based on the pharmacological theory and the induction or inhibition of CYP450 enzyme needs further study.

Assessment of Patients Treated with Kampo Decoctions Containing Aconite Root Before Processing (uzu) / 日本東洋医学雑誌

We examined 57 patients treated with Kampo decoctions containing uzu for 5 years and 3 months from September 2013. Sekiganryo, which was administered to 32 patients, was the most commonly used decoction. The value of uzu dosage and duration of administration were spread widely and the medians (ranges) are 8.0 (1.0-41.0)g/day and 180 (3-1700) days, respectively. Complete recovery, partial recovery, no recovery, and deterioration in terms of the chief complaint, were observed in 36, 11, 9, and 1 patients, respectively. The number of patients exhibiting complete or partial recovery was higher than that of patients showing no recovery or deterioration when the duration of uzu administration was more than one month and the dosage was higher than 4 g/day (p < 0.05). The patients treated with uzu more than 20 g/day were all sekiganryo administrated ones. Side effects were observed in three patients. Thus, under careful observation, uzu was safely used over a long term and at high doses.uzu: aconite root before processing

The Decocting Time and the Contents of the Aconitine-type Diester Alkaloids in the Decoctions of the Formula Containing Unprocessed Aconite Root in “Songban Shanghanlun” / 日本東洋医学雑誌

We investigated the decocting time to prepare the formulas containing unprocessed aconite root, such as shigyakuto, tsumyaku shigyakuto, and kankyobushito, which had been registered in “Shanghanlun” edited in Song Dynasty, using the weights and measures in Houhan Dynasty when the original “Shanghanlun” was regarded to have been established. Also the contents of aconitine-type diester alkaloids (ADA) eluted from unprocessed aconite root in the decoction were analyzed in time-dependent manners. As regards the modified formula for the “physically strong patients” in the texts of tsumyakushigyakuto in “Shanghanlun”, adding dried ginger was found to lead the decocting time to be shorter and the sum of ADA content in the decoction of the modified formula to increase about 20%. It was also found that the compositions of diterpene alkaloids derived from aconite root in kankyobushito decoction were highly different from those in shigyakuto decoction, containing less ADA and more aconine and hypaconine, due to the high pH of the decoction, which was the consequence of lacking glycyrrhiza in kankyobushito formula. It is suggested that the doctors in the era of “Shanghanlun” establishment may have carefully adjusted the contents of ADA in the decoctions using unprocessed aconite root by choosing co-decocted crude drugs.

A Case of Sarcoidosis Complicated by Knee Pain and Fatigue Successfully Treated with Uzu / 日本東洋医学雑誌

A 48-year-old man presented with knee pain and general fatigue. He had been diagnosed with sarcoidosis 15 years previously. Prednisolone was administered, but the pain and fatigue persisted. Morphine, fentanyl, and a tramadol/acetaminophen combination were then administered, but their effects were not sufficient. Finally, the patient was treated with sekiganryo, uzuto, uzukeishito, and daiuzusen, all of which contained uzu (aconite root without processing). His pain and fatigue improved after administration of these drugs, and he became able to perform various activities of daily living. In this case, uzu alleviated knee pain and general fatigue in a patient with sarcoidosis.

Aconite cake-separated moxibustion for knee osteoarthritis with kidney-marrow deficiency / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects among aconite cake-separated moxibustion, moxibustion and acupuncture for knee osteoarthritis (KOA) with kidney-marrow deficiency and to explore the feasibility of cake-separated moxibustion as a home remedy solution.</p><p><b>METHODS</b>Ninety patients were randomized into an aconite cake-separated moxibustion group, a moxibustion group and an acupuncture group, 30 cases in each one. The acupoints in the three groups were Neixiyan (EX-LE 4), Dubi (ST 35) in the affected side, and bilateral Xuehai (SP 10), Liangqiu (ST 34), Heding (EX-LE 2), Shenshu (BL 23) and Zusanli (ST 36). All the treatment was given for 3 sessions, 10 days as a session with 2 to 3 days between 2 sessions, and once a day. The first 2 courses of aconite cake-separated moxibustion was applied in the hospital and the other 1 session was used at home guided by officer physician. Symptoms and physical signs classification score and life quality scores were recorded before and after treatment and 6 months after treatment, including walking pain, knee pain in stoop and squat, knee discomfort in stair activity and daily discomfort. The effects were evaluated.</p><p><b>RESULTS</b>The symptoms and physical signs classification scores in the three groups after treatment and at follow-up were lower than those before treatment (<0.01,<0.05), and the scores in the aconite cake-separated moxibustion group were better than those in the moxibustion group and acupuncture group (all<0.01). The scores of walking pain, knee pain in stoop and squat, knee discomfort in stair activity and daily discomfort were lower in the three groups after treatment and 6 months after treatment (<0.01,<0.05), and the scores of walking pain and daily discomfort in the aconite cake-separated moxibustion group were lower than those in the moxibustion group and acupuncture group (<0.01,<0.05). After treatments, the cured and markedly effective rate in the aconite cake-separated moxibustion group was 63.3% (19/30); that in the moxibustion group was 50.0% (15/30) and one in the acupuncture group was 43.3% (13/30). The cured and markedly effective rate of aconite cake-separated moxibustion group was more promising than those in the other two groups (both<0.05). At follow-up, the cured and markedly effective rate in the aconite cake-separated moxibustion group was 56.7% (17/30), which was better than 36.7% (11/30) in the moxibustion group and 40.0% (12/30) in the acupuncture group (both<0.05).</p><p><b>CONCLUSION</b>Aconite cake-separated moxibustion can be used for KOA patients with kidney-marrow deficiency, which can improve patients' life quality and is better than moxibustion and acupuncture. The method is feasible as a home remedy solution.</p>

Influence of Water Properties on the Contents of Aconitine-Type Diester Alkaloids in the Decoctions of Unprocessed Aconite Root / 日本東洋医学雑誌

The decoctions of unprocessed aconite root (uzu) were prepared with the tap water samples collected in Tianjin and Shanghai in China, and the contents of alkaloids in the decoctions were compared to those prepared with purified water or with tap water collected in Niigata, Japan. The contents of aconitine-type diester alkaloids (ADA) in the decoctions prepared with tap water collected in China were significantly lower than those with purified water or tap water in Niigata. It was speculated that this difference appeared by buffering effect of bicarbonic anion in tap water in China to decline pH of the decoction. When uzu was decocted with glycyrrhiza, ginger, or jujube, the contents of ADA in the decoctions exhibited the tendency to have higher levels than those prepared using unprocessed aconite root singly, and also this tendency was observed more remarkably when the decoctions were prepared with tap water collected in China. It was suggested that even the decocting period was fixed, unexpected change of the contents of ADAs might be induced by the differences in the properties of water used for decoction or the crude drugs decocted with aconite root. The physicians in the era when “Songban Shanghanlun” had established may have adjusted the contents of ADA in the decoction by carefully choosing the crude drugs combined to aconite root.

Molecular Mechanism of Aconite-Ginger Muscle against Myocardial lschemia lnjury Based on Network Pharmacology / 中国药理学与毒理学杂志

OBJECTIVE To use network pharmacology to predict and analyze the mechanism of Aconite-Ginger against myocardial ischemia. METHODS TCMSP was used to collect the active compounds of Aconite-Ginger and predict the targets of active compounds. At the same time, target sites of anti-myocardial ischemic injury drugs were collected using DisGeNET and CTD database,and then active compounds and target sites were compared.Analyze and screen out the targets of Aconite-Ginger anti-cardiac machine ischemia. GO, KEGG analysis and Aconite-Ginger drug molecule-target were performed on selected targets using MAS 3.0 and Cytoscape 3.3.0 software.RESULTS 27 common targets of Aconite-Ginger anti-ischemia ischemia and 63 signal pathways were predicted. CONCLUSION Aconite-Ginger mainly regulates calcium signal transduction, apoptosis and MAPK signaling pathway, which can also regulate through toll-like receptors, Fc epsilon RI and other signal pathways, so it is speculated that it may participate in regulation Apoptosis, inflammatory response, enhancement of myocardial function, etc., thereby exerting an anti-ischemic effect. It laid a good foundation for further revealing its mechanism of action.

The Humble Opinion of "YuNaiCuo" / 浙江中医药大学学报

[Objective] To narrate the cause of acne from "Yang depression". [Methods] From the point of view of "Yang depression", the different syndromes of acne were analyzed, and the etiology, pathogenesis and corresponding therapeutic views were expounded, and a sample case was cited. [Results] There are three types of acne in the textbook of Chinese medicine surgery: acne with pattern of wind-heat in lung channel, acne with heat binding in the intestines and stomach and acne with syndrome of stagnation and congelation of phlegm-damp, the prescription used is mostly bitter cold, which can easily hurt the spleen and stomach, cause cold-dampness inside, lead to the pathogenesis of cold, wet and blood stasis while taking it for a long time. In view of this, the "Yang depression" can be used to explain the different syndromes leading to acne. Inspired by the Neijing, the patients with "Yang depression" can be properly treated by warming Yang and relieving depression. The patient in the case is discriminated as the type of obstruction of defensive Yang, it was satisfied to see that using the prescription of Zhongjing: the Decoction of Ephedra Aconite and Asarum. And we can also use formula variation in accordance with signs, like clearing heat and removing toxin, invigorating spleen and draining dampness, activating blood and resolving stasis, softening and resolving hard mass. [Conclusion] Depression of the Yang is an important pathogenesis of acne. We are suggested to treat the acne of "Yang depressions" with the method of "warm Yang and relieve depression", which can be used as the prescription of Zhongjing.

Establishment of one-step approach to detoxification of hypertoxic aconite based on the evaluation of alkaloids contents and quality / 中国天然药物

Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.

"Compatibility Characteristics and Clinical Applications of Aconite as""Angle Medicines""in Classical Prescriptions" / 浙江中医药大学学报

[Objective] Analyzing and summarizing the compatibility characters and the clinical applications of theAngle Medicinesof Aconite, in order to enlighten the modern applications. [Methods] According to the theories of classical prescriptions, arranging the compatibility characteristics and clinical applications of theAngle Medicinesof Aconite, there are three kinds ofAngle Medicines, including theAngles Medicineas independent prescriptions, theAngle Medicinesas the main part of prescriptions and theAngle Medicineas the combinations of prescriptions. At last, listing two cases of theAngle Medicinesof Aconite as the examples of clinical experience to demonstrate theAngle Medicines. [Results]This article sorted out 7 pairs ofAngle Medicinesof Aconite as the first kind, 8 pairsAngle Medicinesof Aconite as the second kind, and theAngle Medicinesof Aconite as combinations. In clinic, we use the Aconite, fried ginger and Licorice to treat long-term diarrhea, use Aconite, Semen Coicis and Patrinia to treat the hypogastralgia, and we gain the good effects, which can declare the clinical practicability of theAngle Medicines. [Conclusions]There are a lot of compatibility knowledge in classical prescriptions. Comprehending and grasping the compatibility characters and the clinical applications of the Angle Medicinesof Aconiteare is very unique and ingenious for modern clinic.

Chemical constituent change regulation of processed aconite during decoction and discussion on time limit of decoction based on metabolomics / 中草药

Objective: To analyze the change regulation of chemical constituent groups in processed aconite during decocting, and also to discuss the scientificity connotation of decoction of processed aconite. Methods: An ultra-high performance liquid chromatography coupled with time of flight mass spectrometry (UHPLC-Q-TOF/MS) was carried out to acquire the chemical constituents information in samples with different decoction time. High precise mass data were processed by multivariate statistical analysis techniques to discover and identify the constituents with significant difference. Furthermore, the content change, toxicity, and activity of these constituents were also discussed. Results: Fifteen chemical markers with significant difference were screened by partial least squares discriminant analysis (PLS-DA) and t test. By analyzing the change regulation of the different constituents during 4 h decocting process, we found that it mainly happened in the constituent dissolution and chemical transformation from monoester alkaloids to aconine alkaloids, which indicates the attenuation process is secondary. Conclusion: In terms of analgesic and anti-inflammatory effect, it suggests that 0.5 h of decoction would be fine, while in terms of cardiotonic effect, it needs the further systemic comparison for cardiac activity between monoester alkaloids and aconine alkaloids to be able to investigate the necessary and scientificity for long time decoction of the processed aconite.

Comparative studies of contents of alkaline substances from different prescription of formulations of Chinese material medica with same dose of aconite / 中草药

Objective: To compare with the contents of alkaline substances from four different prescription of formulations of traditional Chinese medicine (single aconite decoction, Jiangfu Decoction, Sini Decoction, and Shenfu Injection) with the same dose of aconite. Methods: Taken aconitine as the standard substance, the area under absorbance-wavelength curve (AUAWC) and absorption values of alkaline substances from four formulations, namely single aconite decoction, Jiangfu Decoction, Sini Decoction and Shenfu Injection (every concentration of aconite crude herb for 0.2 g/mL as the same dose), were obtained, respectively, which were determined by the method of AUAWC after the scanning for the wavelength from 200~600 nm and the method of bromocresol green colorimetric at 415 nm, and the data calculated were compared. Results: The results are accurate and reliable, and the methods of both AUAWC and bromocresol green colorimetric are feasible. The linear equations were Y = 0.145 42 X + 3.240 4, r = 0.999 3 for the AUAWC and Y = 0.008 63 X + 0.006 57, r = 0.999 5 for the bromocresol green colorimetric, respectively. The contents of alkaline substances from single aconite decoction, Jiangfu Decoction, Sini Decoction and Shenfu Injection were acquired through the method of AUAWC, which were 1 137.992, 2 907.120, 2 455.611, and 298.208 μg/mL, respectively, and the contents of aconitum alkaline substances were obtained by bromocresol green colorimetric with the concentration of 293.824, 447.767, 343.804 and 38.382 μg/mL, respectively. The content determined by the former method was much larger than that of the latter method, but the trend of the contents from two methods was the same, which was Jiangfu Decoction > Sini Decoction > single aconite decoction > Shenfu Injection. Conclusion: The contents of alkaline substances from different prescription of formulations of traditional Chinese medicine with the same dose of aconite are different, and the concentration of overall alkaline substances from AUAWC is more comprehensive than that of aconitum alkaline substances determined by bromocresol green colorimetric, which will provide more scientific theory interpretation for compatibility mechanism and dose-effect relationship as well as security research of Chinese medicine preparation of aconite.

<b>Three Cases with Intractable Pain Treated with a Dose of Daiuzusen, and an Analysis of Aconite Concentrations in Prescriptions and Patientsʼ </b><b>Serum</b> / 日本東洋医学雑誌

<p>In 2013, we prescribed daiuzusen for 3 patients with intractable pain; pain from complex regional pain syndrome, colic pain of unknown origin after an abdominal operation, and colic pain from advanced colon cancer and ileus. A dose of daiuzusen (containing uzu 0.5-2 g) quickly relieved their pain in several minutes. Another common symptom was “cold” in their bowel or extremities when they were feeling pain. Aconite levels in drugs and patients' serum after taking daiuzusen were analyzed by liquid chromatography tandem mass spectrometry. Daiuzusen per 1 g of uzu contained aconitine 1.28 μg, mesaconitine 2.31 μg, and hypaconitine 92.89 μg, while jesaconitine was not detected; this was about 5 to 35 times the level of tsumyakushigyakuto per 1 g of uzu. Serum concentrations of hypaconitine peaked in the study at 1.11 ng/mL after about an hour of taking daiuzusen (1 g of uzu). We posit that the immediate effect after taking daiuzusen was due to transmucosal absorption of uzu components. However serum hypaconitine, which we are now able to monitor, is at least one practical way of indicating the use of uzu or bushi containing prescriptions.</p>