The mechanism research of Xiaoyan Lidan formula for the intervention of chronic intrahepatic cholestasis based on metabolomics combined with molecular docking analysis / 药学学报

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

[Effect of heat-reinforcing needling on expression of P2X7R, NLRP3 and Caspase-1 in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis].

OBJECTIVE: To observe the effects of heat-reinforcing needling on the expression of purinergic ligand-gated ion channel 7 receptor(P2X7R)，Nodlike receptor protein 3(NLRP3) and Caspase-1 in synovium tissues of knee joint of rabbits with cold syndrome rheumatoid arthritis(RA)，so as to explore the anti-inflammatory mechanism of heat reinforcing needling in the treatment of RA. METHODS: Thirty male New Zealand white rabbits were randomly divided into normal group, model group, reinforcing-reducing needling group(RRG), heat-reinforcing needling group(HRG), and antagonist group(AG), with 6 rabbits in each group.The model of cold syndrome RA was established by ovalbumin combined with Freund's adjuvant and cryogenic freezing. Rabbits of RRG and HRG were treated with corresponding acupuncture techniques on both sides of "Zusanli"(ST36) for 30 min, once a day for 7 days; Rabbits of the AG was intraperitoneally injected with A438079(2.5 mg/kg), once a day for 7 days. After intervention, color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal.The histomorphological changes of synovial tissues were observed by HE staining. Quantitative real-time PCR method was used to detect the mRNA expression levels of P2X7R, NLRP3, and Caspase-1 in synovial tissues. Western blot was used to detect the protein expression of interleukin(IL)-1ß, IL-6 and tumor necrosis factor(TNF)-α in synovial tissues. RESULTS: Compared with the normal group, the synovial tissues in the model group was thickened, linear and punctate blood flow signals were increased, joint effusion was obvious, synovial coating cells were enlarged, the synovial matrix was severely hyperplasia, inflammatory cells infiltration was obvious.The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1ß, IL-6, TNF-α proteins in synovial tissues were significantly increased(P<0.01). Compared with model group, abnormal blood flow signals, synovial thickness, joint effusion, proliferation of synovial matrix, inflammatory cell infiltration and synovial coating cells in the RRG, HRG and AG were improved. The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1ß, IL-6, TNF-α proteins in synovial tissues were decreased in the RRG, HRG and AG (P<0.05, P<0.01). Compared with the RRG, the above indexes were lower in the HRG and AG (P<0.05, P<0.01).There was no significant difference in all indexes above between the HRG and AG (P<0.01, P<0.05). CONCLUSION: Heat reinforcing needling can improve synovial inflammation of RA, which may be related to regulating the expressions of P2X7R/NLRP3/Caspase-1 signaling pathway.

Effectiveness of Liu-zi-jue exercise on coronavirus disease 2019 in the patients: a randomized controlled trial.

OBJECTIVE: The aim of this study was to examine the effect of Liu-zi-jue exercise on the respiratory symptoms, quality of life, and mental health of patients with mild coronavirus disease 2019 (COVID-19). METHODS: A single-center randomized controlled trial was conducted with 104 patients with mild COVID-19. The patients were randomly assigned to the Liu-zi-jue plus conventional therapy group and conventional therapy group. The outcome measures included Modified Borg Dyspnea Scale (MBDS) score, Patient Health Questionnaire-9 (PHQ-9) score, Fatigue Scale-14 (FS-14), respiratory symptoms, and vital signs. Data were collected on the first and sixth days of hospitalization and on the discharge day. RESULTS: Repeated-measures ANOVA revealed that the whole scales all showed a downward trend in the two groups (all 0.05). The results of single-group effect suggested that the whole scale score in the intervention group was significantly lower than that in the control group at the sixth day of hospitalization. Compared with the control group, only the MBDS, expectoration, and FS-14 scores showed significantly lower scores at the discharge day ( 0.001, 0.011, 0.002). Comparison within the group showed that all the variables were significantly different at the three time points with a decreasing trend ( 0.05), except for the PHQ-9 and expectoration scores ( 0.331, 0.052). All patients' vital signs remained within a stable normal range throughout the hospital stay. CONCLUSION: The results suggested that Liu-zi-jue exercise as a complementary and alternative therapy showed beneficial effects on improving the symptoms (shortness of breath, fatigue, and cough), quality of life, and mental health of patients with mild COVID-19.

[Analysis of projects funded by NSFC in field of Chinese medicine toxicology from 2012 to 2021].

This study mainly introduced the research on Chinese medicine toxicology funded by the National Natural Science Foundation of China(NSFC) in 2012-2021 and analyzed the research content. Furthermore, key research topics and characteristic research projects were discussed, such as the toxicity mechanism, relationship between toxicity and efficacy, toxicity-alleviating mechanisms, and new technology and methods. The review suggested that researchers should gain an in-depth understanding of the "toxicity" of Chinese me-dicine, turned to characteristic research topics, and build a toxicological research paradigm suited to the characteristics of Chinese medicine in project application.

Analysis of projects funded by NSFC in field of Chinese medicine toxicology from 2012 to 2021 / 中国中药杂志

This study mainly introduced the research on Chinese medicine toxicology funded by the National Natural Science Foundation of China(NSFC) in 2012-2021 and analyzed the research content. Furthermore, key research topics and characteristic research projects were discussed, such as the toxicity mechanism, relationship between toxicity and efficacy, toxicity-alleviating mechanisms, and new technology and methods. The review suggested that researchers should gain an in-depth understanding of the "toxicity" of Chinese me-dicine, turned to characteristic research topics, and build a toxicological research paradigm suited to the characteristics of Chinese medicine in project application.

[Analysis of research status based on projects in pharmacokinetics of traditional Chinese medicine funded by National Natural Science Foundation of China].

The pharmacokinetics of traditional Chinese medicine is a subject that studies the dynamic changes of the absorption, distribution, metabolism and excretion of complex components of traditional Chinese medicine, which is an important method for elucidating the pharmacodynamic material basis, action characteristics, and compatibility mechanisms of traditional Chinese medicine. However, given on the fact that traditional Chinese medicine is a multi-dimensional and complex system with multiple components, multiple pathways, multiple targets, and an unclear pharmacodynamic material basis, the research on the pharmacokinetics of traditio-nal Chinese medicine has become a scientific and technological problem. Although the pharmacokinetics of traditional Chinese medicine has achieved remarkable development with the emergence of new theories, methods and technologies, there are still some problems in the application of the research direction of the pharmacokinetics of traditional Chinese medicine judging from the current application of the National Natural Science Foundation of China. Therefore, this article discussed the current research status on pharmacokinetics of traditional Chinese medicines by analyzing the projects funded by the National Natural Science Foundation of China in the past 5 years from 2016 to 2020, mainly including the application and funding analysis, main research contents of the projects in pharmacokinetics of traditional Chinese medicines. And the research hotspots, difficulties and deficiencies were focused in order to provide certain reference for researchers engaged in pharmacokinetics of traditional Chinese medicine.

Effectiveness of a telerehabilitation program for COVID-19 survivors (TERECO) on exercise capacity, pulmonary function, lower limb muscle strength, and quality of life: a randomised controlled trial

ObjectivesTo investigate superiority of a telerehabilitation program for Covid-19 (TERECO) over no rehabilitation with regard to functional exercise capacity, lower-limb muscle strength (LMS), pulmonary function, health-related quality of life (HRQOL), and perceived dyspnoea. DesignParallel-group randomised controlled-trial with 1:1 block-randomisation. SettingThree major hospitals from Jiangsu and Hubei provinces, China. Participants120 Covid-19 survivors with modified Medical Research Council (mMRC) dyspnoea score of 2-3 who had been discharged from hospital were randomised. 61 were allocated to the control group and 59 to the TERECO group. InterventionThe control group received educational instructions. The TERECO group participated in a 6-week home-based, pulmonary rehabilitation program delivered via smartphone and monitored with chest-worn heart rate telemetry. Exercise types comprised breathing control and thoracic expansion, aerobic exercise, and LMS exercise. OutcomesPrimary outcome was 6-minute walking distance (6MWD) in metres. Secondary outcomes were LMS measured as squat time in seconds; pulmonary function assessed by spirometry with parameters being forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, maximum voluntary ventilation (MVV), and peak expiratory flow; HRQOL measured with SF-12 physical component score (PCS) and mental component score (MCS); and mMRC dyspnoea, favourable outcome (no dyspnoea). Outcomes were assessed at 6 weeks (post-treatment) and 28 weeks (follow-up). Results120 patients were randomised, 15 (12.5%) were lost to follow-up at study endpoint. No serious adverse events occurred. 38 participants in the TERECO group complied with the exercise protocol (64.41% of randomized). The adjusted between-group difference in change in 6MWD from baseline was 65.45 metres (95% CI 43.8-87.1, p<0.001) at post-treatment and 68.62 metres (95% CI 46.39-90.85, p<0.001) at follow-up. Treatment effects for LMS were 20.12 seconds (95% CI 12.34-27.9, p<0.001) post-treatment and 22.23 seconds (95% CI 14.24-30.21, p<0.001) at follow-up. No group differences were found for lung function apart from post-treatment MVV (10.57 litres/minute, 95% CI 0.26-17.88, p=0.005). Increase in SF-12 PCS was greater in the TERECO group with treatment effects estimated as 3.79 (95% CI 1.24-6.35, p=0.004) at post-treatment and 2.69 (95% CI 0.06-5.32, p=0.045) at follow-up. No significant between-group differences were found for improvements in SF-12 MCS. At post-treatment 90.4% endorsed a favourable outcome for mMRC dyspnoea in the TERECO group vs. 61.7% in control (adjusted RR 1.46, 1.17-1.82, p=0.001). ConclusionsThis trial demonstrated superiority of TERECO over no rehabilitation for 6MWD, LMS, and SF-12 PCS. We found no persistent effects on pulmonary function, SF-12 MCS, and perceived dyspnoea. Trial registrationChinese Clinical Trial Registry: ChiCTR2000031834, 11 Apr 2020, URL: http://www.chictr.org.cn/showproj.aspx?proj=52216 KEY POINTSO_ST_ABSWhat is already knownC_ST_ABSMany Covid-19 survivors discharged from hospital have reduced exercise capacity, impaired pulmonary function, muscle weakness, and reduced quality of life, all of which might be addressed with pulmonary rehabilitation. However, evidence on effective pulmonary rehabilitation measures for this population is currently lacking. As delivery of conventional rehabilitation services is furthermore limited due to pandemic control measures, telerehabilitation programs represent a possible alternative. What the study addsWe developed a telerehabilitation program for Covid-19 survivors (TERECO program) that is delivered via smartphone and can be carried out at home. Our study suggests that TERECO was safe and participants of the TERECO program had improved exercise capacity, lower-limb muscle strength, and physical quality of life. No relevant group differences were found for lung function, self-reported breathlessness, and mental quality of life. The TERECO program is inexpensive and could be implemented on a large scale to improve physical health of Covid-19 survivors after discharge from hospital.

Analysis of research status based on projects in pharmacokinetics of traditional Chinese medicine funded by National Natural Science Foundation of China / 中国中药杂志

The pharmacokinetics of traditional Chinese medicine is a subject that studies the dynamic changes of the absorption, distribution, metabolism and excretion of complex components of traditional Chinese medicine, which is an important method for elucidating the pharmacodynamic material basis, action characteristics, and compatibility mechanisms of traditional Chinese medicine. However, given on the fact that traditional Chinese medicine is a multi-dimensional and complex system with multiple components, multiple pathways, multiple targets, and an unclear pharmacodynamic material basis, the research on the pharmacokinetics of traditio-nal Chinese medicine has become a scientific and technological problem. Although the pharmacokinetics of traditional Chinese medicine has achieved remarkable development with the emergence of new theories, methods and technologies, there are still some problems in the application of the research direction of the pharmacokinetics of traditional Chinese medicine judging from the current application of the National Natural Science Foundation of China. Therefore, this article discussed the current research status on pharmacokinetics of traditional Chinese medicines by analyzing the projects funded by the National Natural Science Foundation of China in the past 5 years from 2016 to 2020, mainly including the application and funding analysis, main research contents of the projects in pharmacokinetics of traditional Chinese medicines. And the research hotspots, difficulties and deficiencies were focused in order to provide certain reference for researchers engaged in pharmacokinetics of traditional Chinese medicine.

[Acupuncture technique of Jingou Diaoyu combined with speech rehabilitation training for post-stroke motor aphasia].

OBJECTIVE: To compare the clinical efficacy of the acupuncture technique of Jingou Diaoyu combined with speech rehabilitation training and speech rehabilitation training alone for post-stroke motor aphasia. METHODS: A total of 70 patients with post-stroke motor aphasia were randomly divided into an observation group and a control group, 35 cases in each group. The patients in the control group were treated with basic treatment and speech rehabilitation training; on the basis of the control group, the patients in the observation group were treated with the acupuncture technique of Jingou Diaoyu at Yamen (GV 15), Jinjin (EX-HN 12), Yuye (EX-HN 13), and Hegu (LI 4) etc., once a day, 6 days per week, for a total of 4 weeks. The speech function score, aphasia grade, daily life speech ability score of the two groups before and after treatment were observed, and the clinical efficacy was evaluated. RESULTS: The total effective rate was 94.3% (33/35) in the observation group, which was superior to 80.0% (28/35) in the control group (P<0.05). In addition to listening comprehension, each score of speech function in the two groups was significantly increased after treatment (P<0.05), and the increasing in the observation group was greater than that in the control group (P<0.05). After treatment, the aphasia grade of the two groups were improved (P<0.05), and the aphasia grade in the observation group was significantly better than that in the control group (P<0.05). After treatment, the scores of daily life speech ability in the two groups were significantly improved (P<0.05), and the increasing in the observation group was greater than that in the control group (P<0.05). CONCLUSION: The acupuncture technique of Jingou Diaoyu combined with speech rehabilitation training could improve the speech function of patients with post-stroke motor aphasia, and its curative effect is superior to the speech rehabilitation training alone.

[Analysis of projects funded by NSFC in field of pharmacology of traditional Chinese medicine in 2019].

The projects which supported by National Natural Science Foundation of China(NSFC) including General Program, Young Scientist Fund, and Fund for Less Developed Regions, in field of pharmacology of traditional Chinese medicine in 2019 were reviewed. Based on these research items, the main contents and characteristics, as well as the main problems from academic and non-academic point of view, were summarized for reference.

Analysis of projects funded by NSFC in field of Chinese materia medica quality evaluation in recent five years / 中草药

The paper reviewed the funding situation of Chinese materia medica quality evaluation projects in Medical Science Department, National Natural Science Foundation of China in recent five years. The research progress and achievements of some funded projects were summarized from the perspectives of research approach, new technique and innovation of Chinese materia medica quality evaluation. The types of projects funded and supportive organizations were analyzed, and the problems of the applications have been also summarized so as to provide the reference for the subsequent applicants.

Analysis of projects funded by NSFC in field of pharmacology of traditional Chinese medicine in 2019 / 中国中药杂志

The projects which supported by National Natural Science Foundation of China(NSFC) including General Program, Young Scientist Fund, and Fund for Less Developed Regions, in field of pharmacology of traditional Chinese medicine in 2019 were reviewed. Based on these research items, the main contents and characteristics, as well as the main problems from academic and non-academic point of view, were summarized for reference.

New amide alkaloids from Delphinium brunonianum.

Five new amide alkaloids, named delamide A-E (1-5), along with five known ones, methyl-N-(3-carboxy-2-methylpropanoyl) anthranilate (6), benzoic acid, 2-[(1-oxodecyl) amino]-methylester (7), puberline (8), benzoic acid, 2-[(4-methoxy-2-methyl-1, 4-dioxobutyl) amino]-methylester (9) and benzoic acid, 2-[(4-methoxy-3-methyl-1, 4-dioxobutyl) amino]-methylester (10) were isolated from the extract of Delphinium brunonianum. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). 1-10 were also evaluated for their acetylcholinesterase (AChE) inhibiting activity by the Ellman's method. Delamide A (1) showed highly selective AChE inhibition activity. The kinetic analysis revealed that 1 was a mixed-type reversible inhibitor of AChE.

The Effect of Sensor Dimensions on the Performance of Flexible Hot Film Shear Stress Sensors.

This paper presents a study to determine the effect of sensor dimensions (length, width, and thickness) on the performance of flexible hot film shear stress sensors. The sensing component of a hot film sensor is nickel thermistor, and the flexible substrate material is polyimide. Several groups of flexible hot film shear stress sensors with different lengths, widths, and thicknesses were studied. The temperature coefficient of resistance (TCR) was measured. The TCR increased slightly with increasing thickness. The frequency response (time constant) of the flexible hot film shear stress sensor was obtained by the square wave, while the sensitivity was tested in a wind tunnel. The study found that as the sensor length was shortened, the frequency response increased, and the sensitivity decreased.

Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS.

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites-rhamnocitrin 3-O-ß-glc and rhamnocitrin-in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites-rhamnocitrin-was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

Qualitative and Quantitative Analysis of the Major Constituents in WLJ Herbal Tea Using Multiple Chromatographic Techniques.

Quality control of Chinese herbal tea remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling and famous brand of beverage in China, Wanglaoji Herbal Tea (WLJHT), via a full component quantitative analysis. In this paper, a total of thirty-two representative constituents were identified or tentatively characterized using ultra-high performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Moreover, the quantitative analyses of fourteen constituents were performed by high performance liquid chromatography with a triple quadruple tandem mass spectrometry (HPLC-MS/MS) method and saccharide compositions of WLJHT were also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on a Hilic column, separately. Using multiple chromatographic techniques presented a good precision, sensitivity, repeatability and stability, and was successfully applied to analyze 16 batches of WLJHT samples. Therefore, it would be a reliable and useful approach for the quality control of WLJHT.

[Interaction of phenylethanoid glycosides and calf thymus DNA].

In physiological condition, the interaction of acteoside and forsythoside B with calf thymus DNA using neutral red (NR) as a fluorescence probe were investigated by fluorescence, UV-visible spectrophotometry, viscosity, DNA melting techniques, and molecular docking. It is observed that acteoside and forsythoside B can react with DNA. The major mode of recognition between drug and DNA is groove binding by hydrogen bonds, and the interaction of acteoside with DNA is stronger than that of forsythoside B.

A new diterpenoid alkaloid isolated from Delphinium caeruleum.

The present study was designed to determine the chemical constituents of Delphinium caeruleum Jacq. ex Camb.. The chemical constituents were isolated and purified by column chromatography with silica gel, ODS, and Sephadex LH-20. Their structures were elucidated by IR, MS, and NMR. Ten compounds were obtained and identified as caerudelphinine A (1), lycoctonine (2), talitine B (3), talitine A (4), talitine C (5), tatsienine-V (6), d-magnoflorine (7), 2-trimethyl-ammonio-3-(3-indolyl) propionate (8), vakhmatine (9), and delatisine (10). Compound 1 was a new lycoctonine-type C19-diterpenoid alkaloid, and compounds 4-10 were isolated from this plant for the first time.

Interaction of phenylethanoid glycosides and calf thymus DNA / 中国中药杂志

In physiological condition, the interaction of acteoside and forsythoside B with calf thymus DNA using neutral red (NR) as a fluorescence probe were investigated by fluorescence, UV-visible spectrophotometry, viscosity, DNA melting techniques, and molecular docking. It is observed that acteoside and forsythoside B can react with DNA. The major mode of recognition between drug and DNA is groove binding by hydrogen bonds, and the interaction of acteoside with DNA is stronger than that of forsythoside B.

A new diterpenoid alkaloid isolated from Delphinium caeruleum / 中国天然药物

The present study was designed to determine the chemical constituents of Delphinium caeruleum Jacq. ex Camb.. The chemical constituents were isolated and purified by column chromatography with silica gel, ODS, and Sephadex LH-20. Their structures were elucidated by IR, MS, and NMR. Ten compounds were obtained and identified as caerudelphinine A (1), lycoctonine (2), talitine B (3), talitine A (4), talitine C (5), tatsienine-V (6), d-magnoflorine (7), 2-trimethyl-ammonio-3-(3-indolyl) propionate (8), vakhmatine (9), and delatisine (10). Compound 1 was a new lycoctonine-type C19-diterpenoid alkaloid, and compounds 4-10 were isolated from this plant for the first time.