Pancreatitis aguda asociada a cocaína, una complicación inusual. Serie de casos / Cocaine-induced acute pancreatitis, an unusual complication. Case serie / Pancreatite aguda associada à cocaína, uma complicação incomum. Número de casos

La cocaína es una de las sustancias ilegales más consumidas y Colombia no es la ex­cepción. Dentro de las sustancias ilegales es la segunda más consumida después del cannabis. Por su mecanismo mismo de acción, que produce aumento de aminas bióge­nas, se han asociado con la cocaína diferentes riesgos, tanto agudos como crónicos, y dentro de sus complicaciones se han descrito cambios comportamentales, compromiso cardiovascular y neurológico. La coingesta de cocaína y alcohol da lugar a un metabolito conocido como cocaetileno, que lleva a complicaciones cardiovasculares. Poco se ha descrito sobre el riesgo de la cocaína o la coingesta cocaína y alcohol, como un factor sumatorio, para la pancreatitis. Reportamos tres pacientes jóvenes consumidores del alcaloide que desarrollaron pancreatitis aguda, dos de ellos murieron. El objetivo de este reporte es sensibilizar a los trabajadores de la salud sobre otro riesgo para considerar en los pacientes consumidores de cocaína.

Cocaine is one of the most consumed illegal substances and Colombia is no exception. It is the second most consumed among the illegal substances after cannabis. Due to its very mechanism of action, which produces an increase in biogenic amines, different risks, both acute and chronic, have been associated with cocaine, and among its complications, behavioral changes, cardiovascular and neurological compromise have been described. The co-ingestion of cocaine and alcohol gives rise to a metabolite known as cocaethylene, which leads to cardiovascular complications. Little has been described about the risk of cocaine or cocaine and alcohol co-ingestion, as a summative factor, for pancreatitis. We report three young patients consuming the alkaloid who developed acute pancreatitis, two of whom died. The objective of this report is to sensitize health workers about another risk to consider in cocaine-consuming patients.

A cocaína é uma das substâncias ilícitas mais consumidas e a Colômbia não é exceção. Dentro das substâncias ilícitas é a segunda mais consumida depois da maconha. Devido ao seu próprio mecanismo de ação, que produz aumento de aminas biogênicas, diversos riscos, tanto agudos quanto crônicos, têm sido associados à cocaína e, entre suas complicações, têm sido descritas alterações comportamentais, comprometimento cardiovascular e neurológico. A co-ingestão de cocaína e álcool dá origem a um metabólito conhecido como cocaetileno, que leva a complicações cardiovasculares. Pouco tem sido descrito sobre o risco da co-ingestão de cocaína ou cocaína e álcool, como fator somativo, para pancreatite. Relatamos 3 pacientes jovens consumindo o alcalóide que desenvolveram pancreatite aguda, dois dos quais morreram. O objetivo deste relatório é sensibilizar os profissionais de saúde sobre outro risco a ser considerado em pacientes consumidores de cocaína.

An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.

Chemical components of Magnoliae Officinalis Cortex of different origins and with different tree ages before and after being processed with ginger juice:a qualitative and quantitative analysis / 中国中药杂志

This study aimed to investigate the impact of ginger juice on chemical profile of Magnoliae Officinalis Cortex(MOC) when they were processed together. Ultra-high-performance liquid chromatography coupled to quadrupole-orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was used for qualitative analysis of the chemical component of MOC samples before and after being processed with ginger juice. UPLC was performed to observe the content variation of eight main components in processed MOC. A total of 174 compounds were identified or tentatively deduced from processed and unprocessed MOC samples according to MS data obtained in positive and negative ion mode. After MOC was processed with ginger juice, the peak areas of most phenolics increased, while the peak areas of most phenylethanoid glycosides decreased; as for neolignans, oxyneolignans, other lignans and alkaloids, changes in the peak area were variable, and the peak areas of terpenoid-lignans varied little. Additionally, gingerols and diarylheptanoids were only detected in the processed MOC sample. The contents of syringin, magnoloside A, and magnoloside B decreased significantly in the processed MOC sample while no significant difference was observed in the contents of magnoflorine, magnocurarine, honokiol, obovatol, and magnolol. This study comprehensively explored the content variation of chemical components in processed and unprocessed MOC samples derived from different regions and with different tree ages using UPLC and UHPLC-Q-Orbitrap HRMS, and summarized the variation characteristics of various compounds. The results provide a data foundation for further research on pharmacodynamic substances of MOC processed with ginger juice.

Heterologous biomimetic synthesis of active ingredients in traditional Chinese medicine:a new mode for protection and development of traditional Chinese medicine resources / 中国中药杂志

Heterologous biomimetic synthesis of the active ingredients of traditional Chinese medicine(TCM) is a new mode of resource acquisition and has shown great potential in the protection and development of TCM resources. According to synthetic biology and by constructing biomimetic microbial cells and imitating the synthesis of active ingredients in medicinal plants and animals, the key enzymes obtained from medicinal plants and animals are scientifically designed and systematically reconstructed and optimized to realize the heterologous synthesis of the active ingredients in microorganisms. This method ensures an efficient and green acquisition of target products, and also achieves large-scale industrial production, which is conducive to the production of scarce TCM resources. Additiona-lly, the method playes a role in agricultural industrialization, and provides a new option for promoting the green and sustainable deve-lopment of TCM resources. This review systematically summarized the important progress in the heterologous biomimetic synthesis of TCM active ingredients from three research areas: biosynthesis of terpenoids, flavonoids, phenylpropanoids, alkaloids and other active ingredients, key points and difficulties in heterologous biomimetic synthesis, and biomimetic cells with complex TCM ingredients. This study facilitated the application of new generation of biotechnology and theory to the development of TCM.

In silico screening of Annona Muricata L. Leaf constituents and derivatives towards selected targets of Type 2 Diabetes Mellitus

BACKGROUND@#Type 2 diabetes mellitus, or T2DM, is one of the world's most chronic health problems that is linked to numerous deaths and high health care expenses. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), protein-tyrosine phosphatase 1B (PTP1B) and mono-ADP-ribosyl transferase sirtuin-6 (SIRT6) were among the novel proteins and focus targets of diabetes research. Annona muricata is a commonly used natural remedy for several illnesses, including type 2 diabetes mellitus. However, most of these traditional claims have received few molecular evaluations.@*OBJECTIVES@#This investigated the phytoconstituents and derivatives of the leaves of A. muricata by evaluating their binding profiles towards selected novel T2DM-related protein targets through in silico methods.@*METHODOLOGY@#This study screened the potential lead compounds from the leaves of A. muricata by evaluating the binding energies of the parent compounds and derivatives with the targets compared to the native ligands and known substrates through molecular docking simulations. Additionally, pharmacokinetic, physicochemical properties, and binding interactions were also assessed using several software programs and online databases.@*RESULTS@#Out of the 8 selected parent compounds of Annona muricata, a total of 672 derivatives were designed, tested, and compared against the controls for at least one of the three protein targets. Among these, 280 derivatives exhibited more negative binding energies than controls in each protein target.@*CONCLUSION@#The designed derivatives can be synthesized and further investigated for potential biological effects towards 11β-HSD1, PTP1B, and SIRT6 through in vitro and in vivo experiments.

Alkaloids from fruit of Lycium chinense var. potaninii / 中国中药杂志

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Effect of apigenin in combination with oxymatrine on non-small cell lung cancer and mechanism / 中国中药杂志

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.

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.

Research progress on application of multi-enzyme-catalyzed cascade reactions in enzymatic synthesis of natural products / 中国中药杂志

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.

Screening of housekeeping genes in Gelsemium elegans and expression patterns of genes involved in its alkaloid biosynthesis / 生物工程学报

Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.

Neotuberostemonine and tuberostemonine ameliorate pulmonary fibrosis through suppressing TGF-β and SDF-1 secreted by macrophages and fibroblasts via the PI3K-dependent AKT and ERK pathways / 中国天然药物

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg-1 bleomycin and orally administered with 30 mg·kg-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.

A comprehensive review of natural products with anti-hypoxic activity / 中国天然药物

Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.

Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice / 中国天然药物

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

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.

Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components / 中国中药杂志

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

Two new isoquinoline alkaloids from Corydalis hendersonii / 中国中药杂志

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(β-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 μmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 μmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.

Characterization and identification of alkaloids in Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex based on UHPLC-IM-Q-TOF-MS / 中国中药杂志

A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.

Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats / 中国中药杂志

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina / 中国中药杂志

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 μg·g~(-1)) was higher than that in GFA(0.03-10.41 μg·g~(-1)) and GS(0.04-13.66 μg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.