Phytochemical Screening and chemical investigation of lipoidal matter of the leaves of Latania verschaffeltii Lem. Family Arecaceae cultivated in Egypt

Abstract This study presents the first preliminary phytochemical screening and investigation of the lipoidal matter of Latania verschaffeltii Lem. leaves, belonging to the Arecaceae family. Gas chromatography coupled with mass spectroscopy (GC/MS) was used to analyze and identify compounds of saponifiable and unsaponifiable content. The preliminary phytochemical screening of total methanolic extract of Latania verschaffeltii Lem. leaves revealed the presence of unsaturated sterols and/or triterpenes, carbohydrates and/or glycosides, flavonoids, tannins, saponins, and phenolic acids in the leaves. However, cardenolides, cyanogenic compounds, alkaloids, and iridoids were not detected. The results of the gas chromatography/mass spectrometry (GC/MS) analysis indicated that the percentage of saturated fatty acids (83.82%) is higher than that of unsaturated fatty acids (9.42%). The predominant methyl ester of a saturated fatty acid detected in the sample was hexadecanoic acid methyl ester, accounting for 41.68% of the total. The composition of the unsaponifiable matter consisted of hydrocarbons (5.66%), fatty alcohols (0.96%), terpenes (85.97%), and sterols (2.18%). The major terpenes observed were phytol (43.62%) and squalene (39.27%).

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.

Research on Anti-inflammatory Targets and Mechanisms of alkaloids in Picrasma quassioides Benn Through Network Pharmacology

Abstract This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma

Development of microparticles and microparticulated tablets containing piperine

Abstract Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.

Excretion of three alkaloids from Simiao Pills in urine, feces, and bile between normal and type 2 diabetic rats / 中国中药杂志

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Differences in chemical components in processing of dried ginger-steamed, sand-fried, and rice swill water-bleached Aconiti Lateralis Radix Praeparata pieces in "Jianchang" faction based on UPLC-MS/MS / 中国中药杂志

This study compared the changes in chemical components during the processing of different types of Aconiti Lateralis Radix Praeparata(ALRP) in "Jianchang" faction, i.e., dried ginger-steamed ALRP pieces(Yin-FP), sand-fried ALRP pieces(Yang-FP), and rice swill water-bleached ALRP pieces(DFP), and provided a scientific basis for the mechanism in toxicity reduction and efficacy enhancement from a compositional perspective. Samples were collected during the processing of the three types of ALRP pieces, yielding raw ALRP pieces, water-bleached Yin-FP, ginger juice-moistened Yin-FP, steamed Yin-FP, water-bleached Yang-FP, sand-fried Yang-FP, water-bleached DFP, rice swill water-bleached DFP, and roasted DFP. Aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, aconine, mesaconine, hypaconine, salsolinol, fuziline, and higenamine in the extracts were determined by UPLC-MS/MS, and then content analysis and cluster heatmap analysis were performed on 11 sets of samples. During the processing of the three types of ALRP pieces, bleaching significantly reduced the content of 12 alkaloids; steaming, stir-frying, and roasting significantly reduced the content of diester-type alkaloids(aconitine, mesaconitine, and hypaconitine) and significantly increased the content of monoester-type alkaloids(benzoylaconine, benzoylmesaconine, and benzoylhypaconine) and aminoalcohol-type alkaloids(aconine, mesaconine, and hypaconine). During the processing of Yin-FP, the diester-type alkaloids continuously decreased, while the monoester-type and aminoalcohol-type alkaloids showed an initial decrease followed by an increase. During the processing of Yin-FP, Yang-FP, and DFP, the diester-type alkaloids continuously decreased, while the monoester-type and aminoalcohol-type alkaloids showed an initial decrease followed by an increase. Steamed Yin-FP showed a higher increase in content than fried Yang-FP and roasted DFP. Comprehensive analysis of content differences in toxic and therapeutic components in three ALRP pieces suggests that the distinctive processing methods in "Jianchang" faction can indeed achieve detoxification and efficacy enhancement on ALRP. This study provides references for understanding the mechanisms of action of the three processing methods.

Chemical constituents of Lindera aggregata and their bioactivities: a review / 中国中药杂志

The medicinal Lindera aggregata(Lindera, Lauraceae) boasts abundant resources, which is widely used in clinical settings. It has been found that the main chemical constituents of this medicinal species are sesquiterpenoids, alkaloids, sesquiterpenoid dimers, flavonoids, and phenolic acids. Some unreported novel structures, including lindenane-type sesquiterpene dimers and trimers, have been discovered from L. aggregata in recent years. The extracts and active components of L. aggregata have anti-tumor, anti-inflammatory, antalgic, liver-protecting, antioxidant, lipid-lowering, and glucose-lowering activities, and their mechanisms of action have been comprehensively investigated. This study summarizes the research on the chemical constituents and bioactivities of L. aggregata over the past decade, which is expected to serve as a reference for the future research and utilization of L. aggregata.

Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis / 中国中药杂志

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-β-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-β-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

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.

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.

Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives / 中国中药杂志

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Research progress of Codonopsis Radix and prediction of its Q-markers / 中国中药杂志

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.

Application of high-speed counter current chromatography in extraction and separation of alkaloids in natural products / 中国中药杂志

Alkaloids, widespread in plants, have a series of pharmacological activities and have been widely used to treat various diseases. Because alkaloids are usually presented in multicomponent mixtures and are deeply low in content, they are very difficult to extract and separate by traditional methods. High-speed counter current chromatography(HSCCC) is a kind of liquid-liquid chromatography without solid support phase, which has the advantages of large injection volume, low cost, and no irreversible adsorption. Compared with the traditional methods of extraction and separation of alkaloids, HSCCC can ensure the separation of many different alkaloids at one time, with a high recovery and large amount. In this paper, the advantages and disadvantages of HSCCC compared with traditional separation methods were discussed and the solvent system and elution mode of HSCCC used to separate alkaloids in recent years were summarized by referring to the relevant literature to provide some references for the separation of alkaloids by HSCCC.

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.

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.