Homeopatia na oncologia pediátrica: é possível? Uma série de casos / Homeopathy in oncology pediatric: is it possible? case series

A Homeopatia é uma das ciências médicas complementares mais utilizadas para pacientes com Câncer, sendo também utilizada durante o tratamento de crianças com a referida moléstia, havendo relato e debate de seu uso na literatura médica. Visando construir o conhecimento e dividir experiências, relatamos seis casos de crianças e adolescentes com câncer, para os quais realizamos tratamento homeopático, em nossa experiência na cidade de São Paulo. Além da diversidade de sexos e idade, os casos apresentam diagnósticos oncológicos diferentes, bem como momentos diferentes no tratamento, sendo curativo ou paliativo, e os medicamentos homeopáticos, baseados tanto na totalidade sintomática característica quanto no modo reacional para cada indivíduo, puderam ser utilizados para todos com satisfação de famílias e pacientes, mesmo quando o desfecho letal foi a via final no estado paliativo. Assim, a Homeopatia pode também ser prescrita para os casos oncológicos infantis como terapia complementar ao tratamento convencional, sendo a pesquisa neste campo vasta e possível.

Homeopathy is one of the most used complementary medical sciences for cancer patients, and is also used duringtreatment of children with the aforementioned disease, with reports and debate of its use in medical literature. Aiming to build knowledge and sharing experiences, we report six cases of children and adolescents with cancer, for which we carry out homeopathic treatment, in our experience in the city of São Paulo. In addition to the diversity of sexes and age, the cases present different oncological diagnoses, as well as as different moments in the treatment, being curative or palliative, and homeopathic medicines, based both on symptomatic totality characteristic and in the reactional mode for each individual, could be used for everyone with the satisfaction of families and patients, even when the lethal outcome was the final route in the palliative state. Therefore, Homeopathy can also be prescribed for oncological cases children as complementary therapy to conventional treatment, research in this field is vast and possible.

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.

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.

Progress in antitumor activity of diterpenoid alkaloids in plants of Aconitum / 中国中药杂志

Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.

Comparison of alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata based on UHPLC-Q-Exactive Orbitrap MS/MS / 中国中药杂志

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.

Regularity of prescriptions for sick sinus syndrome based on latent structure combined with association rules / 中国中药杂志

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.

Research progress on structure, structure-activity relationship, and biological activity of Aconiti Lateralis Radix Praeparata polysaccharides / 中国中药杂志

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.

Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder / 中国中药杂志

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Comparative study on short and long-term intervention impacts of six Chinese herbs with cold or heat property on lipid and energy metabolism in mice / 中国中药杂志

This study selected three typical Chinese herbs with cold property(Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma) and another three with heat property(Cinnamomi Cortex, Zingiberris Rhizoma, and Aconiti Lateralis Radix Praeparata) to observe their regulatory effects on metabolism in animal organism, especially on lipid and energy metabolism in mice after a short-(7 d) and long-term(35 d) intervention. The mRNA expression levels of lipid metabolism genes in epididymal adipose tissue and liver were determined by real-time PCR. The oxygen consumption, carbon dioxide production, and energy consumption were detected by metabolic system. After the short-term intervention, the Chinese herbs with heat property significantly reduced epididymal adipose tissue index and elevated the expression levels of acetyl-CoA carboxylase(ACC), lipoprotein lipase(LPL), and carnitine-palmityl transferase 1(CPT-1) in liver and epididymal adipose tissues. However, those with cold property promoted the expression of above-mentioned genes in epididymal adipose tissue. After the long-term intervention, cold and heat Chinese herbs had no significant effect on epididymal adipose tissue index of animals, while cold Chinese herbs could increase carbon dioxide production and energy consumption and reduce activity. These findings demonstrated that the short-term intervention effects of cold and heat Chinese herbs on animal metabolism were significantly stronger than the long-term intervention effects. Specifically, the short-term intervention with cold Chinese herbs enhanced the lipid metabolism in epididymal adipose tissue, while the heat Chinese herbs promoted lipid metabolism in epididymal adipose tissue and liver. The long-term intervention with cold and heat Chinese herbs resulted in no obvious change in lipid level, but long-term intervention with cold Chinese herbs accelerated energy consumption of the body. This study preliminarily observed the effects of cold and heat Chinese herbs on normal animal physiology from lipid and energy metabolism, which would provide reference for explaining the biological basis of Chinese herbs with cold or heat property based on biological response.

Construction of a high-throughput screening model for mitochondrial function of Aconiti Lateralis Radix Praeparata by machine learning algorithm and mechanism analysis / 中国中药杂志

A high-throughput screening machine learning model for mitochondrial function was constructed, and compounds of Aco-niti Lateralis Radix Praeparata were predicted. Deoxyaconitine with the highest score and benzoylmesaconine with the lowest score among the compounds screened by the model were selected for mitochondrial mechanism analysis. Mitochondrial function data were collected from PubChem and Tox21 databases. Random forest and gradient boosted decision tree algorithms were separately used for mo-deling, and ECFP4(extended connectivity fingerprint, up to four bonds) and Mordred descriptors were employed for training, respectively. Cross-validation test was carried out, and balanced accuracy(BA) and overall accuracy were determined to evaluate the performance of different combinations of models and obtain the optimal algorithm and hyperparameters for modeling. The data of Aconiti Lateralis Radix Praeparata compounds in TCMSP database were collected, and after prediction and screening by the constructed high-throughput screening machine learning model, deoxyaconitine and benzoylmesaconine were selected to measure mitochondrial membrane potential, reactive oxygen species(ROS) level and protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax) and peroxisome proliferator-activated receptor-γ-coactivator 1α(PGC-1α). The results showed that the model constructed using gradient boosted decision tree+Mordred algorithm performed better, with a cross-validation BA of 0.825 and a test set accuracy of 0.811. Deoxyaconitine and benzoylmesaconine changed the ROS level(P<0.001), mitochondrial membrane potential(P<0.001), and protein expression of Bcl-2(P<0.001, P<0.01) and Bax(P<0.001), and deoxyaconitine increased the expression of PGC-1α protein(P<0.01). The high-throughput screening model for mitochondrial function constructed by gradient boosted decision tree+Mordred algorithm was more accurate than that by random forest+ECFP4 algorithm, which could be used to build an algorithm model for subsequent research. Deoxyaconitine and benzoylmesaconine affected mitochondrial function. However, deoxyaconitine with higher score also affected mitochondrial biosynthesis by regulating PGC-1α protein.

Identification, biological characteristics, and fungicide screening of pathogen of black spot in Aconitum carmichaelii / 中国中药杂志

In Hezhang county, Guizhou province, black spot tends to occur to Aconitum carmichaelii in the hot rainy summer, with the incidence up to 50%-70%, seriously impacting the yield and quality of the medicinal material. Thus, this study aims to clarify the pathogen and the occurrence characteristics. To be specific, the pathogen was isolated and identified according to Koch's postulates and the pathogenicity and biological characteristics were determined. In addition, the sensitivity of the pathogen to four microbial fungicides, four botanical fungicides, and five chemical fungicides was determined with the mycelium growth rate method for the purpose of screening out optimal fungicides. The pathogen was identified as Alternaria alternate, as evidenced by the similar colony morphology and microscopic characteristics and 99.55%-100% similarity in sequences of rDNA-ITS, LSU, 18S, and TEF of the two. The optimum growth conditions for A. alternata were 28 ℃, pH 8, and continuous darkness. Bacillus subtilis had strong inhibitory effect on the pathogen, and the inhibition rate was more than 90% when the concentration was 1 mg·L~(-1). In addition, difenoconazole and quinoline copper can also control the pathogen, with median effective concentration(EC_(50)) of 2.92 and 9.02 mg·L~(-1), respectively. This study lays a theoretical basis for the field control of black spot in A. carmichaelii.

Aconitum heterophyllum Wall. ex Royle: A critically endangered medicinal herb with rich potential for use in medicine / 中西医结合学报

Aconitum heterophyllum (Patrees) is a critically endangered medicinal herb of the northwestern Himalayas and has enormous pharmacological potential. It is the only nonpoisonous member of the genus Aconitum, and has been used as a medicinal herb since ancient times. A. heterophyllum is an important ingredient in many traditional systems of medicine. Mostly, it is harvested for its roots, and its medicinal properties are due to the presence of diverse bioactive secondary metabolites, commonly known as aconites. Our understanding of the pharmacological properties of this intriguing genus is continuously growing due to its broad chemical diversity. The therapeutic uses identified by traditional medicinal practice are receiving extensive study. Multiple in vitro experimental investigations of A. heterophyllum have reported the analgesic, anti-inflammatory, antiarrhythmic, antiparasitic and anticancer properties, as well as its effects on the central nervous system. In this review, we highlight the classification, distribution, commerce, traditional uses, phytochemistry, pharmacology and conservation measures relevant to this species. Additionally, this review includes the biosynthetic pathways of A. heterophyllum's key constituents, which could be targeted to enhance the expression levels of desired metabolites via genetic interventions. Studying the genomics, transcriptomics, proteomics and metabolomic aspects of this species would be helpful in developing highly designed genotypes and chemotypes of this species to be used in commercial production.

Herbalogical analysis of Aconiti Carmichaeli Radix / 中国中药杂志

Tianxiong has been used as a Chinese medicinal in China for thousands of years, and the earliest record can be traced back to the Shennong's Classic of Materia Medica. It is effective in dispersing wind, dissipating cold, and replenishing fire to streng-then yang. To clarify the origin of Tianxiong, the present herbalogical study reviewed the ancient and modern literature from the origin, processing, and clinical efficacy. Before the Tang Dynasty, although the description of Tianxiong was quite superficial, an apparent difference between Tianxiong and Fuzi was recognized. In the Tang and Song Dynasties, Tianxiong and Fuzi were mistakenly recognized to be prepared from a same plant since their raw materials came from artificial cultivation. Medical literature in the Ming and Qing Dynasties mostly followed the previous records, with the origin of Tianxiong remaining controversial. There were three mainstream views about the origin of Tianxiong according the ancient medical books. First, Tianxiong was a kind of Aconiti Radix(Chuanwu) without attachment of Fuzi. Second, Tianxiong was the large Fuzi. Third, Tianxiong derived from Aconiti Kusnezoffii Radix(Caowu) about 10 cm in length. By contrast, Fuzi in a large size was simply regarded as Tianxiong in modern times. The processing methods were diversified in the ancient times, and the fire-processing was continuously applied. With the deepening of the research on the efficacy and detoxification mechanism, more methods were discovered, such as processing with ginger juice, child's urine and alcohol. As for modern times, the processing of Tianxiong has not been nearly passed down. The characteristic processing of Tianxiong only handed down in Sichuan province and Lingnan area, which can be discriminated by the last step. The efficacies of Tianxiong can be directly understood from its literal name, including dispersing wind, dissipating cold, and replenishing fire to assist yang. Nowadays, Tianxiong is mostly used to strengthen yang.

Selection of optimal qRT-PCR reference genes for Aconitum vilmorinianum / 中国中药杂志

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.

A systematic review of pharmacological activities, toxicological mechanisms and pharmacokinetic studies on Aconitum alkaloids / 中国天然药物

The tubers and roots of Aconitum (Ranunculaceae) are widely used as heart medicine or analgesic agents for the treatment of coronary heart disease, chronic heart failure, rheumatoid arthritis and neuropathic pain since ancient times. As a type of natural products mainly extracted from Aconitum plants, Aconitum alkaloids have complex chemical structures and exert remarkable biological activity, which are mainly responsible for significant effects of Aconitum plants. The present review is to summarize the progress of the pharmacological, toxicological, and pharmacokinetic studies of Aconitum alkaloids, so as to provide evidence for better clinical application. Research data concerning pharmacological, toxicological and pharmacokinetic studies of Aconitum alkaloids were collected from different scientific databases (PubMed, CNKI, Google Scholar, Baidu Scholar, and Web of Science) using the phrase Aconitum alkaloids, as well as generic synonyms. Aconitum alkaloids are both bioactive compounds and toxic ingredients in Aconitum plants. They produce a wide range of pharmacological activities, including protecting the cardiovascular system, nervous system, and immune system and anti-cancer effects. Notably, Aconitum alkaloids also exert strong cardiac toxicity, neurotoxicity and liver toxicity, which are supported by clinical studies. Finally, pharmacokinetic studies indicated that cytochrome P450 proteins (CYPs) and efflux transporters (ETs) are closely related to the low bioavailability of Aconitum alkaloids and play an important role in their metabolism and detoxification in vivo.

Diterpenoid alkaloids from roots of Aconitum kongboense / 中国中药杂志

The chemical constituents from the roots of Aconitum kongboense were studied. Twenty-five diterpenoid alkaloids were isolated from the 95% methanol extract of the roots of A. kongboense by silica gel, reverse-phase silica gel and basic alumina column chromatography. They included a new aconitine-type diterpenoid alkaloid, named as kongboensenine(1), and twenty-four known ones(2-25), i.e., acotarine F(2), acotarine G(3), 14-acetyltalatisamine(4), talatisamine(5), indaconitine(6), yunaconitine(7), chasmanine(8), 6-epi-foresticine(9), homochasmanine(10), 8-deacetyl-yunaconitine(11), chasmaconitine(12), ajaconine(13), franchetine(14), ezochasmanine(15), crassicautine(16), 14-O-deacylcrassicausine(17), genicunine A(18), falconeridine(19), sachaconitine(20), liljestrandisine(21), 8-methyl-14-acetyltalatisamine(22), kongboendine(23), 14-benzoylchasmanine(24) and pseudaconine(25). Their structures were elucidated by common spectroscopic methods including high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) and nuclear magnetic resonance(NMR) techniques. Compounds 2-4, 10, 13, 15-19 and 21-22 were isolated from this plant for the first time. Experimental results showed that all compounds did not have a significant inhibitory activity against acetylcholinesterase(AChE).

Evolution of Sichuan Dao-di herbs recorded in ancient works of materia medica of different historical periods / 中国中药杂志

Sichuan province is very famous for its abundant resources of traditional Chinese medicine(TCM).However, within the scope of administrative division of Sichuan province, the origin records of Dao-di herbs in different historical periods show a dynamic distribution process. On the basis of carefully sorting out the geographical scope of Sichuan province in different historical periods, this article focuses on the textual research of the Dao-di herbs in Sichuan province recorded in the seven mainstream ancient works of materia medica.The results showed that, according to the records of Mingyi bielu and Bencaojing Jizhu, the main distribution areas of Dao-di herbs were mainly in the central and eastern regions of Sichuan province, mainly including Moschus, Coptidis Rhizoma, Zingiberis Rhizoma, Aconiti Lateralis Radix Praeparata and most of the rest materia medica had become unused in the historical process. Qianjin Yifang records that the distribution areas of Dao-di herbs were mainly in the middle and eastern part of Sichuan province.Aconiti Radix, Lateralis Radix Praeparata, Zingiberis Rhizoma, Notopterygii Rhizoma et Radix are still the Dao-di herbs of Sichuan province. According to the book of Bencao Tujing,the main distribution areas of Dao-di herbs are Chengdu Plain, Yibin and Santai, While Toosendan Fructus, Chuanxiong Rhizoma, Zanthoxyli Pericarpium, Aconiti Radix are still the Dao-di herbs of Sichuan province. Ben Cao Gang Mu records the place of origin as Sichuan.Coptidis Rhizoma, Toosendan Fructus, Cyathulae Radix are still the Dao-di herbs of Sichuan pro-vince. Yaowu Chuchanbian and Zengding Weiyao Tiaobian records the place of origin as Sichuan, as well as Kangding, Songpan, Dujiang-yan, Jiangyou, Nanchong, Ya'an, etc. Moschus, Coptidis Rhizoma, Eucommiae Cortex, Phellodendri Chinensis Cortex are still the Dao-di herbs of Sichuan province. The results of this article provide a new understanding of the history and distribution changes of Dao-di herbs in Sichuan province, and can help to further understand the formation connotation of Sichuan Dao-di herbs.

Chemical variation in Aconti Kusnezoffii Radix before and after processing based on UPLC-Orbitrap-MS / 中国中药杂志

Some Chinese herbal medicine needs to be processed before it can be used as medicine, especially toxic Chinese medicine. Highly toxic Aconti Kusnezoffii Radix(Caowu in Chinese) is widely used in traditional Chinese medicine and Mongolian medicine. In traditional Chinese medicine, Caowu is usually processed by boiling with water(CW) until no white part inside and being tasted without tongue-numbing. In Mongolian medicine, it is usually soaked in Chebulae Fructus(Hezi in Chinese) decoction for several days(CH). Both methods could reduce toxicity according to reports. The biggest difference between CW and CH is that CW needs to be heated for 4-6 h, while CH needs Hezi as processing adjuvants. To explore the toxicity reduction mechanism of CW and CH, we studied the contents of various compounds in Caowu processed by two methods by UPLC-Orbitrap-MS. The results indicated that CW had 14 new ingredients, such as 14-O-anisoylneoline and dehydro-mesaconitine, while N-demethyl-mesaconitine and aconitine disappeared. At the same time, it could significantly decrease the content of diester diterpenoid alkaloids and increase the contents of monoester diterpenoid alkaloids and amine-diterpenoid alkaloids. CH had 9 new ingredients from Hezi, like gallic acid, chebulic acid and shikimic acid. Neither the kinds nor the contents of compositions from Caowu in CH changed little. This suggested that the processing mechanism of CW reduced highly toxic components(diester diterpenoid alkaloids) and increased the content of lowly toxic components(monoester diterpenoid alkaloids and amine-diterpenoid alkaloids). Attenuated principle of CH may be related to the components of Hezi. In this experiment, the conclusion shows that the chemical constituents of CW and CH are essentially different, and the two methods have different toxicity reduction principles.

Detoxification mechanism of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix based on metabolic enzymes in liver / 中国中药杂志

The enzymes CYP1 A2 and CYP3 A4 were measured by building a "Cocktail" probe drug and the incubation system of liver microsomes. The compatibility of Aconiti Lateralis Radix Praeparata combined with dried Rehmanniae Radix on CYP450 enzyme protein and gene expression was explored from the level of protein and molecular biology. It explored the molecular mechanism of compatibility detoxication of Aconiti Lateralis Radix Praeparata to provide scientific support for clinical safe and effective application of Aconiti Lateralis Radix Praeparata. The CYP450 enzyme activity was determined by using "Cocktail" probe drugs. The content of CYP450 enzyme was measured by CO reduction of differential spectrum method. The mRNA expression of CYP1 A2 and CYP3 A4 enzyme was detected by RT-PCR technology. Compared with the blank group, the CYP1 A2 and CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group with significant differences(P<0.05), while the CYP3 A4 enzyme activity and mRNA expression were no influence in the Aconiti Lateralis Radix Praeparata group. The CYP3 A4 enzyme activity and mRNA expression were increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The content of CYP450 enzyme was decreased in the Aconiti Lateralis Radix Praeparata group, contributed to extremely significant difference(P<0.01). The content of CYP450 enzyme was increased in the dried Rehmanniae Radix and the dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata group, and there were significant differences(P<0.05). The CYP1 A2 and CYP3 A4 enzyme activity and gene expression were enhanced after dried Rehmanniae Radix combined with Aconiti Lateralis Radix Praeparata. The metabolism of toxic ingredients of Aconiti Lateralis Radix Praeparata was accelerated to reach an effect of detoxication. The detoxication mechanism of compatibility of Aconiti Lateralis Radix Praeparata was verified from the viewpoint of liver metabolic enzymes.

Research progress of natural alkaloids with analgesic activity / 中国中药杂志

Pain is a protective defense response of the body to harmful stimuli. Long-term pain not only seriously affects the body of the patient and brings great pain to the patient, but also brings huge economic burden to the patient's family and society. It has become one of the most serious problems affecting human health. At present, opioids and non-steroidal anti-inflammatory drugs(NSAIDs) are commonly used as painkillers, but they tend to cause a variety of adverse reactions or risk of addiction. To find and develop new analgesic drugs, which are safer and more effective, has become the hot spot and difficulty in medical research. A variety of alkaloids derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical analgesic medicines. Various alkaloids have been proved to have good analgesic effects, such as morphine and the related to opioids, the main analgesic active components from Corydalis Rhizoma and Aconiti Lateralis Radix Praeparata. Here we summarized the research progress of natural alkaloids with analgesic activity, in order to provide reference for the research and development of analgesic drugs based on natural products.