Comparative pharmacokinetics, intestinal absorption and urinary excretion of six alkaloids from herb pair Phellodendri Chinensis cortex-Atractylodis Rhizoma.

Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.

Comparative metabolism of the eight main bioactive ingredients of gegen qinlian decoction by the intestinal flora of diarrhoeal and healthy piglets.

Diarrhoeal diseases alter the composition of intestinal flora, thereby affecting the efficacy of herbal medicinal formulations. Gegen Qinlian decoction (GQD), a Chinese traditional herbal formulation, is widely used to treat infectious diarrhoea. However, little is known about the microbial disposition of GQD in the diarrhoeal state. In this study, the comparative metabolism of components of GQD by diarrhoeal and normal intestinal flora was investigated in vitro. UPLC-MS/MS was performed for simultaneous analysis of eight ingredients of GQD in bacterial solution. The type, activities, and sources of microbial enzymes were also investigated. Microbial metabolism of daidzin, genistin and liquiritin (metabolized by ß-glucosidase); baicalin, wogonoside and glycyrrhizin (metabolized by ß-glucuronidase); and berberine and coptisine (metabolized via nitroreductase) was faster in the diarrhoeal group than in the normal group. Moreover, the activities of these enzymes in the diarrhoeal group were higher than those in the normal group. This difference might be associated with the increase in Escherichia spp. Thus, a change in the metabolism of components by diarrhoeal intestinal flora is associated with a preponderance of Escherichia spp., which might improve the efficacy of GQD. These findings have implications for understanding the action mechanism of GQD for diarrhoea treatment in terms of the microbial milieu.

[Study on material basis of Mahuang Fuzi Xixin decoction for anti-inflammation and immune suppression based on combined method of serum pharmacochemistry and serum pharmacology].

To investigate me material basis of Mahuang Fuzi Xixin decoction (MFXD) for anti-inflammation and immune-suppression based on the combined method of serum chemical and serum pharmacological. The LC-MS/MS fingerprints of MFXD, drug-containing serum and blank serum were compared to define the components in plasma. Histamine, ß-hexosaminidase released from RBL-2H3 cell infulenced by drug-containing serum at different time points were measured by ELISA. The effect of drug-containing serum on lipopolysaccharide-induced splenocyte proliferation at different time points were determined by MTT. A correlation analysis was made on components of MFXD and pharmacological indexes based the stepwise regression method. After the intragastrical administration with MFXD, 32 components were discovered in rat serum, including 27 prototype components (10 from Mahuang, 13 from Fuzi and four from Xixin) and five unknown components. Compared with blank serum, drug-containing serum could reduce the release of histamine from RBL-2H3 induced by antigen at different time points (P < 0.05); except the 4-hour drug-containing serum, all of the remaining drug-containing serums could inhibit the RBL-2H3 mastocyte degranulation induced by antigen at different time points (P < 0.05). Drug-containing serum could significantly lipopolysaccharide-induced mouse splenocyte proliferation at 15 and 30 min (P < 0.05). A regression analysis was made on the chemical data of components absorbed into blood and pharmacological indexes, i. e. release rate of histamine, release rate of ß-hexosaminidase and inhibition rate of splenocyte. This suggested the close correlations among methyl pseudo-ephedrine, pseudoephedrine and histamine released from RBL-2H3 induced by antigen; pseudoephedrine, hypaconine, methyl pseudoephedrine and ß-hexosaminidase released from RBL-2H3 induced by antigen; as well as benzoyl hypaconine, benzoylaconine, 14-benzoyl-10-OH-mesaconine, mesaconine and lipopolysaccharide-induced mouse splenocyte proliferation. Methylpseudoephedrine, pseudoephedrine, benzoyl hypaconine, benzoylaconine and mesaconine may be part of material basis of MFXD on anti-inflammation and immune suppression.

[Chemical constituents from the roots of Ilex pubescens].

OBJECTIVE: To study the chemical constituents from the roots of Ilex pubescens. METHODS: The 95% ethanol extract of the plant was separated by silica gel, Sephadex LH-20 and preparative HPLC chromatography. The structures were elucidated based on the physiochemical properties and spectroscopic analysis. RESULTS: Fifteen compounds were isolated and identified as oleuropein(1), oleoside dimethyl ester(2),8 (Z)-nuezhenide(3),3,4-dicaffeoylquinic acid methyl ester(4),3,4,5-tricaffeoylquinic acid methyl ester (5), isovanillic acid(6), syringic acid(7), 3beta-acetyloleanolic acid (8), 3beta-acetylursolic acid(9), uvaol(10), asiatic acid(11), 2alpha-hydroxyursolic acid(12), oleanolic acid (13), ursolic acid (14), stigmasterol-3-O-beta-D-glucopyranoside (15). CONCLUSION: Compounds 2,3,8,9 are obtained from this genus for the first time,compounds 5-7,10-12 are isolated from this plant for the first time.

[GC-MS study on fingerprint of volatile oil from Kadsura heteroclita].

OBJECTIVE: To study the fingerprint of volatile oil from Kadsura heteroclita by GC-MS. METHODS: 10 batches of Kadsura heteroclita were analyzed by GC-MS. TIC profiles were evaluated by" computer aided similarity evaluation system". The characteristic peaks in chromatograms were identified. Hierarchical clustering analysis was performed by SPSS. RESULTS: 23 main peaks was established preliminarily from 10 batches. Resemblance values of 10 batches were a little low. 10 batches were divided into three main clusters based on hierarchical clustering analysis. CONCLUSION: With Good reproducibility, fingerprints established for volatile oil from Kadsura heteroclita provides an effective method for quality control.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of action of Hehuan Yin decoction in polycystic ovary syndrome with insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Hehuan Yin decoction (HHY), first recorded in the Jingyue Quanshu (published in 1624 A.D.), is composed of Albizia julibrissin Durazz. and Ampelopsis japonica (Thunb.) Makino. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of HHY in treating polycystic ovary syndrome with insulin resistance (PCOS-IR). MATERIALS AND METHODS: Network pharmacology and molecular docking were used to predict active compounds, potential targets, and pathways for PCOS-IR treatment using HHY. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) with a high-fat diet to establish a PCOS-IR model. Thereafter, symptoms, ovarian pathology, serum insulin resistance, and sex hormone levels were determined. Western blotting was used to determine the levels of PI3Kp85α, AKT, phospho (p)-AKT, and GSK3ß in the ovaries of rats. RESULTS: Network pharmacology revealed 58 components in HHY and 182 potential targets that were shared between HHY and PCOS-IR. HHY could potentially treat PCOS-IR via the insulin resistance, PI3K/AKT, HIF-1, and steroid hormone biosynthesis pathways. Molecular docking revealed that PI3K, AKT1, GSK3ß, IRS1, and EGFR had high affinities to HHY compounds. In the PCOS-IR rats, HHY significantly normalised the symptoms and ovarian pathology, increased follicle-stimulating hormone (FSH) and oestradiol levels in the serum, and decreased the levels of fasting plasma glucose and fasting insulin, as well as the insulin resistance index. HHY also decreased the luteinising hormone (LH) and testosterone levels and the LH/FSH ratio in the PCOS-IR rats and increased the levels of PI3K, p-AKT, and GSK3ß in ovary tissue, which indicated the activation of the PI3K/AKT pathway. CONCLUSIONS: HHY can improve PCOS-IR symptoms via multiple pharmacological pathways and may be a potential alternative therapy for the treatment of PCOS-IR.

Network pharmacology and pharmacokinetics integrated strategy to investigate the pharmacological mechanism of Xianglian pill on ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with high morbidity, which leads to poor quality of life. The Xianglian pill (XLP) is a classical Chinese patent medicine and has been clinically proven to be an effective treatment for UC. PURPOSE: The pharmacological mechanism of the key bioactive ingredients of XLP for the treatment of UC was investigated by a network pharmacology and pharmacokinetics integrated strategy. STUDY DESIGN AND METHODS: Network pharmacology was used to analyze the treatment effect of nine quantified XLP ingredients on UC. Key pathways were enriched and analyzed by protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses. The effect of XLP on Th17 cell differentiation was validated using a mouse model of UC. The binding of nine compounds with JAk2, STAT3, HIF-1α, and HSP90AB1 was assessed using molecular docking. A simple and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantification of nine ingredients from XLP in plasma and applied to a pharmacokinetic study following oral administration. RESULTS: Nine compounds of XLP, including coptisine, berberine, magnoflorine,berberrubine, jatrorrhizine, palmatine, evodiamine, rutaecarpine, and dehydrocostus lactone, were detected. Network pharmacology revealed 50 crossover genes between the nine compoundsand UC. XLP treats UC mainly by regulating key pathways of the immune system, including Th17 cell differentiation, Jak-Stat, and PI3K-Akt signaling pathways. An in vivo validation in mice found that XLP inhibits Th17 cell differentiation by suppressing the Jak2-Stat3 pathway, which alleviates mucosal inflammation in UC. Molecular docking confirmed that eight compounds are capable of binding with JAk2, HIF-1α, and HSP90AB1, further confirming the inhibitory effect of XLP on the Jak2-Stat3 pathway. Moreover, apharmacokinetic study revealed that the nine ingredients of XLP are exposed in the plasma and colon tissue, which demonstrates its pharmacological effect on UC. CONCLUSION: This study evaluates the clinical treatment efficacy of XLP for UC. The network pharmacology and pharmacokinetics integrated strategy evaluation paradigm is efficient in discovering the key pharmacological mechanism of herbal formulae.

Identification of Active Compounds of Mahuang Fuzi Xixin Decoction and Their Mechanisms of Action by LC-MS/MS and Network Pharmacology.

The decoction is an important dosage form of traditional Chinese medicine (TCM) administration. The Mahuang Fuzi Xixin decoction (MFXD) is widely used to treat allergic rhinitis (AR) in China. However, its active compounds and therapeutic mechanisms are unclear. The aim of this study was to establish an integrative method to identify the bioactive compounds and reveal the mechanisms of action of MFXD. LC-MS/MS was used to identify the compounds in MFXD, followed by screening for oral bioavailability. TCMSP, BindingDB, STRING, DAVID, and KEGG databases and algorithms were used to gather information. Cytoscape was used to visualize the networks. Twenty-four bioactive compounds were identified, and thirty-seven predicted targets of these compounds were associated with AR. DAVID analysis suggested that these compounds exert their therapeutic effects by modulating the Fc epsilon RI, B-cell receptor, Toll-like receptor, TNF, NF-κB, and T-cell receptor signaling pathways. The PI3K/AKT and cAMP signaling pathways were also implicated. Ten of the identified compounds, quercetin, pseudoephedrine, ephedrine, ß-asarone, methylephedrine, α-linolenic acid, cathine, ferulic acid, nardosinone, and higenamine, seemed to account for most of the beneficial effects of MFXD in AR. This study showed that LC-MS/MS followed by network pharmacology analysis is useful to elucidate the complex mechanisms of action of TCM formulas.

Self-Microemulsifying Drug Delivery System for Improved Oral Delivery and Hypnotic Efficacy of Ferulic Acid.

PURPOSE: Ferulic acid (FA) is a natural compound which is used to treat insomnia. However, its use is limited because of its poor oral bioavailability caused by extremely rapid elimination. The current study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral delivery of FA and to enhance its hypnotic efficacy. METHODS: FA-SMEDDS was prepared, and its morphology and storage stability were characterized. The formulation was also subjected to pharmacokinetic and tissue distribution studies in rats. The hypnotic efficacy of FA-SMEDDS was evaluated in p-chlorophenylalanine-induced insomnia mice. RESULTS: FA-loaded SMEDDS exhibited a small droplet size (15.24 nm) and good stability. Oral administration of FA-SMEDDS yielded relative bioavailability of 185.96%. In the kidney, SMEDDS decreased the distribution percentage of FA from 76.1% to 59.4% and significantly reduced its metabolic conversion, indicating a reduction in renal elimination. Interestingly, FA-SMEDDS showed a higher distribution in the brain and enhanced serotonin levels in the brain, which extended the sleep time by 2-fold in insomnia mice. CONCLUSION: This is the first study to show that FA-loaded SMEDDS decreased renal elimination, enhanced oral bioavailability, increased brain distribution, and improved hypnotic efficacy. Thus, we have demonstrated that SMEDDS is a promising carrier which can be employed to improve the oral delivery of FA and facilitate product development for the therapy of insomnia.

Mahuang Fuzi Xixin Decoction Ameliorates Allergic Rhinitis in Rats by Regulating the Gut Microbiota and Th17/Treg Balance.

Mahuang Fuzi Xixin Decoction (MFXD), a Chinese traditional herbal formulation, has been used to treat allergic rhinitis (AR) in China for centuries. However, the mechanism underlying its effect on AR is unclear. This study investigated the mechanism underlying the therapeutic effects of MFXD on AR. Ovalbumin-induced AR rat models were established, which were then treated with MFXD for 14 days. Symptom scores of AR were calculated. The structure of the gut microbiota was analyzed by 16S rRNA gene sequencing and qPCR. Short-chain fatty acid (SCFA) content in rat stool and serum was determined by GC-MS. Inflammatory and immunological responses were assessed by histopathology, ELISA, flow cytometry, and western blotting. Our study demonstrated that MFXD reduced the symptom scores of AR and serum IgE and histamine levels. MFXD treatment restored the diversity of the gut microbiota: it increased the abundance of Firmicutes and Bacteroidetes and decreased the abundance of Proteobacteria and Cyanobacteria. MFXD treatment also increased SCFA content, including that of acetate, propionate, and butyrate. Additionally, MFXD administration downregulated the number of Th17 cells and the levels of the Th17-related cytokines IL-17 and RORγt. By contrast, there was an increase in the number of Treg cells and the levels of the Treg-related cytokines IL-10 and Foxp3. MFXD and butyrate increased the levels of ZO-1 in the colon. This study indicated MFXD exerts therapeutic effects against AR, possibly by regulating the gut microbial composition and Th17/Treg balance.

Gegen Qinlian Decoction Treats Diarrhea in Piglets by Modulating Gut Microbiota and Short-Chain Fatty Acids.

Gut microbiota and its metabolites, short-chain fatty acids (SCFAs), play important roles in diarrheal diseases. Gegen Qinlian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries. However, little is known about the mechanism underlying its efficacy and whether it is mediated by gut microbiota and SCFAs. In this study, the composition of gut microbiota from bacterial diarrheal piglets was assessed using 16S rRNA analysis. The concentrations of fecal SCFAs were determined using a gas chromatography-mass spectrometer (GC-MS). The expression of mucosal pro-inflammatory cytokines in the colon was ascertained. Results showed that GQD reverses the reduction in the richness of gut microbiota, changes its structure, and significantly increases the relative abundances of SCFA-producing bacteria, including Akkermansia, Bacteroides, Clostridium, Ruminococcus, and Phascolarctobacterium. Moreover, GQD increased the levels of fecal SCFAs, including acetic acid, propionic acid, and butyric acid. GQD thus attenuates diarrhea in piglets. Further, our results suggest that the SCFAs could help to attenuate mucosal pro-inflammatory responses following GQD treatment by inhibiting histone deacetylase and the NF-κB pathway. We thus suggseted that gut microbiota play an important role during diarrhea treatment, an effect may be promoted by the GQD-induced structural changes of the gut microbial community and production of SCFAs. The increased levels of SCFAs probably provide further help to attenuate mucosal inflammation and diarrhea. In conclusion, our study might provide evidence that GQD treats diarrhea maybe involved in modulating gut microbiota and increasing SCFA levels.

Comparative pharmacokinetics of major bioactive components from Puerariae Radix-Gastrodiae Rhizome extracts and their intestinal absorption in rats.

Puerariae Radix (PR) and Gastrodiae Rhizome (GR) is frequently used in traditional herbal formulas to treat cardio-cerebral vascular diseases due to their synergistic effects. In this study, to elucidate the action mechanism of PR-GR in vivo, a simple and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of nine bioactive ingredients from PR-GR in plasma was developed and applied to a comparative pharmacokinetic study following oral administration of PR, GR, and PR-GR aqueous extracts in rats. The effect of GR on the absorption of components of PR was also investigated by single-pass intestinal perfusion study. Results showed that comparing to the single herbs, PR-GR extract significantly increased the systemic exposure of puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, 6″-O-xylosylpuerarin, daidzin, genistein, and gastrodin. Moreover, the intestinal absorption of puerarin and daidzin could be improved by GR extract and inhibitors of P-glycoprotein and multidrug resistanceassociated protein 2, respectively. These results indicate that the combination of PR and GR increases the levels of their bioactive ingredients exposed in the blood, and GR increases the absorption of ingredients of PR may by inhibition of the efflux mediated by P-glycoprotein and multidrug resistanceassociated protein 2. This is the first report for the pharmacokinetics and intestinal absorption of PR-GR, which may explain their synergetic effects in the treatment of circulatory systematic diseases and provide a meaningful insight for their clinical applications.

Comparative pharmacokinetics of three phenylpropanoids in rat plasma after oral administration of Ramulus Cinnamomi and Ramulus Cinnamomi-Ephedrae Herba herb-couple extract.

OBJECTIVE: To investigate the pharmacokinetic characteristics of three phenylpropanoids (cinnamic acid, cinnamic alcohol and coumarin) in Ramulus Cinnamomi (GZ) and Ramulus Cinnamomi-Ephedrae Herba (MH) herb-couple (GZMH). METHODS: Twelve male Sprague-Dawley rats were randomly and equally divided into the GZ and GZMH herb-couple groups. Blood samples were collected at 0, 0.08, 0.25, 0.5, 0.75, 1.5, 3, 4, 6, 8, 12, 24, 36 and 48 h after oral administration. The three phenylpropanoids in rat plasma were quantified using an ultra-performance liquid-chromatography with tandem mass spectrometry (UPLC-MS/MS) method for pharmacokinetic study. RESULTS: In GZMH group, the area under the curve (AUC), mean retention time (MRT) of cinnamic acid and coumarin were increased significantly (P<0.01, respectively), and biological half-life (t1/2z) was obviously shorter (P<0.05) compared with the GZ group. There were no significant differences in the mean retention time from 0 to ∞ (MRT0-∞), the peak concentration (Cmax), the time to peak (Tmax) and t1/2z, except for AUC and MRT0-t (the mean retention time from 0 to t) of cinnamic alcohol in the GZMH group by comparison to the GZ group (P<0.01, respectively). The AUC, MRT (both P<0.01) and t1/2z (P<0.05) of coumarin were increased significantly, while Cmax, and Tmax were decreased slightly by comparison to the GZ group (P>0.05). CONCLUSIONS: There were statistically significant differences in some pharmacokinetic parameters of the three compounds between GZ and GZMH groups, which meant that MH could affect the absorption and elimination of the three compounds.

[Isolation and identification of hetisine-type alkaloids from Aconitum coreanum by high speed countercurrent chromatography].

AIM: To search for more bioactive compounds from the roots of Aconitum coreanum (Lèvl.) Rapaics. METHODS: High speed countercurrent chromatography was successfully applied to the separation of alkaloids from Aconitum coreanum. The structures were elucidated by their physicochemical properties and spectroscopic analysis. RESULTS: Two-phase solvent system composed of CHCl3-CH3OH-0.2 mol x L(-1) HCl (10:3:3, volume ratio) was used in this experiment, eight alkaloids were obtained from the roots of Aconitum coreanum, which were identified as: 2alpha-propionyl-11alpha,13beta-diacetyl-14-hydroxyhetisine (I), Guanfu base P (II), Guanfu base G (III), Guanfu base F (IV), Guanfu base Z (V), Guanfu base O (VI), Guanfu base A (VII), Guanfu base B (VIII). CONCLUSION: Compound I is a new alkaloid, named Guanfu base R.

Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs, Ephedra and Gypsum.

OBJECTIVE: Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine (CM). In the present study, we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum. METHODS: The antipyretic effects of Ephedra-Gypsum were evaluated in yeast-induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5 groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum groups of different doses (6, 12, 24 g/kg). Ephedra-Gypsum extract and asprin were administered orally 6 h after the injection of yeast solution and body temperature was measured every 1 h for 8 h. The antiasthmatic effects of Ephedra-Gypsum were evaluated using an ovalbumin (OVA)-induced asthmatic rat model. Thirty-six male SD rats were randomly divided into 6 groups. Rats were alternately sensitized and OVA+Al(OH) challenged by exposure to mists of ovalbumin. Ephedra-Gypsum extracts (6, 12, 24 g/kg) or dexamethasone were administered 45 min prior to the allergen challenge for 8 days. Latent period and the weight of wet to dry ratio of lung were determined. In addition, the eosinophils in blood and white blood cell (WBC) were counted by an YZ-Hemavet Analyzer. RESULTS: The Ephedra-Gypsum extracts at test dose (6, 12, 24 g/kg) significantly and dose-dependently attenuated yeast-induced fever in rats. The Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced increases in eosinophils and WBC, and decreased the wet and dry weight ratio of the lungs in the anti-asthmatic test. CONCLUSIONS: These findings indicate that the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence, the results support additional scientific evidence in prescriptions.

A new cytotoxic biflavonoid from the rhizome of Wikstroemia indica.

One new chalcone-flavone biflavonoid, 3'-hydroxydaphnodorin A (1), together with 12 known biflavonoids (2-13), was isolated from the rhizome of Wikstroemia indica. Their structures were established on the basis of extensive spectroscopic methods. Eight isolated compounds 1-3, 6, 7, 9, 12 and 13 were evaluated for their cytotoxic activities against cancer-derived cell lines Hep3B, HepG2 and CNE2, and 1 was found to possess moderate cytotoxicity against HepG2 and CNE2 cell lines, with IC50 values of 65.5 ± 11.4 and 53.6 ± 10.1 µM, respectively.

[A new hetisine-type alkaloid from the stems and leaves of Aconitum coreanum].

AIM: To study the chemical constituents of the stems and leaves of Aconitum coreanum (Lèvl.) Rapaics. METHODS: The constituents of Aconitum coreanum were isolated by using various kinds of modern chromatographic methods. The new alkaloid was identified on the basis of spectral analysis. RESULTS: Two compounds were isolated and identified as: 13-dehydro-1beta-acetyl-2alpha,6beta-dihydroxyhetisine (I) and Guanfu base G (II). CONCLUSION: Compound I is a new alkaloid.

New diterpenoid alkaloids from Aconitum coreanum and their anti-arrhythmic effects on cardiac sodium current.

Two new diterpenoid alkaloids, Guan-Fu base J (GFJ, 1) and Guan-Fu base N (GFN, 2) along with nineteen known alkaloids (3-21) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics, which is the raw material of a new approval anti-arrhythmia drug "Acehytisine Hydrochloride". The structures of isolated compounds were established by means of 1D, 2D NMR spectroscopic and chemical methods. All isolates obtained in the present study were evaluated for their inhibitory effects on blocking the ventricular specific sodium current using a whole-cell patch voltage-clamp technique. Among these 21 compounds, Guan-Fu base S (GFS, 3) showed the strongest inhibitory effect with an IC50 value of 3.48 µM, and only hetisine-type C20 diterpenoid alkaloids showed promising IC50 values for further development.

Guadial A and psiguadials C and D, three unusual meroterpenoids from Psidium guajava.

The first monoterpene-based meroterpenoid (1) and two novel sesquiterpene-based ones (2 and 3) with unprecedented skeletons were isolated from the leaves of Psidium guajava. Their structures with absolute configuration were elucidated by extensive spectroscopic studies. A plausible biosynthetic pathway for all meroterpenoids from the title plant is also proposed. Compounds 2 and 3 showed significant cytotoxicity toward HepG2 and HepG2/ADM cells.