This study aims to explore the protective role of Tongfu Pingchuan decoction (TFP) on sepsis. Thirty rats were randomly assigned to Sham, sepsis (cecal ligation and puncture, CLP), and CLP + Tongfu Pingchuan decoction (TFP) groups (n = 10 per group). TFP (1 mL/kg) or PBS was administered by gavage twice daily for 7 days. Cecum tissues were subjected to transcriptome sequencing (n = 6 per group), followed by network pharmacology and WGCNA analyses. Key findings were validated in rat cecum tissues and LPS-stimulated RAW264.7 macrophages. Compared with the Sham group, the Model group showed activation of TNF signaling, complement and coagulation cascades, fatty acid metabolism, and PPAR signaling pathways, along with suppression of cholinergic synapse, ECM–receptor interaction, and vascular smooth muscle contraction pathways. These alterations were largely reversed by TFP treatment. Integrated bioinformatics analyses identified Chrm4 and Pygm as overlapping differentially expressed genes between predicted TFP targets and a key WGCNA module. Chrm4 expression was significantly downregulated in septic rats and restored by TFP administration. Sepsis induced M1 macrophage polarization and suppressed M2 polarization in cecum tissues, whereas TFP reduced M1 markers and enhanced M2 markers. In LPS-stimulated RAW264.7 cells, TFP similarly promoted M2 polarization, reduced IL-6 and TNF-α levels, increased IL-10 expression, and suppressed IL1RN, p-ERK2/ERK2, and p-AKT/AKT signaling. These effects were abolished by Chrm4 silencing or treatment with the PCTR1 inhibitor Boc-2. These findings demonstrate that TFP alleviates sepsis by restoring intestinal Chrm4 expression, promoting macrophage polarization toward a pro-resolving phenotype, and modulating ERK/AKT-associated inflammatory signaling pathways.

Introduction:Colorectal cancer (CRC) is a prevalent malignancy worldwide, often treated with chemotherapy despite its limitations, including adverse effects and resistance. The traditional Chinese medicine (TCM) Jianpi formula has been demonstrated to improve efficacy of chemotherapy, however the underlying mechanisms still need to be explored. In this study, we aim to screen bioactive peptides derived from the blood of CRC patients through peptidomics and explore the molecular mechanisms of the candidate peptides in the inhibition of CRC using multi-omics analysis. Methods:In this study, we recruited 10 patients with CRC who had received either adjuvant chemotherapy or adjuvant chemotherapy combined with the traditional Chinese medicine Jianpi formula after surgery. We collected plasma samples at 2 cycles of adjuvant therapy and performed peptidomic analysis on these samples. The differentially bioactive peptides were screened using a model of HCT116 cells in vitro. To investigate the molecular mechanism underlying YG-22's inhibition of the colorectal cancer cell line HCT116, we performed a multi-omics analysis, including transcriptome, metabolome, chromatin accessibility, H3K4Me3 histone methylation, and NF-κB binding site analyses. Results:Differential peptides were identified in plasma samples from patients treated with adjuvant chemotherapy combined with the Jianpi formula. Among these peptides, YG-22 exhibited the strongest cytotoxic effect on HCT116 cells, reducing cell viability in a dose- and time-dependent manner. Transcriptome analysis highlighted that YG-22 treatment in CRC modulates key pathways associated with lysosome-mediated degradation and apoptosis. Metabolomic profiling further indicated disruptions in tumor-supportive metabolic pathways. Chromatin accessibility and histone modification analyses suggested that YG-22 induces epigenetic reprogramming. Additionally, treatment with YG-22 resulted in significant changes in NF-κB binding and pathway activation. Conclusions:This study demonstrates that combining chemotherapy with TCM Jianpi formula enriches the molecular landscape and generates bioactive peptides with strong antitumor activity. Furthermore, this study also lays the foundation for further development of peptide-based therapies and highlights the value of combining traditional and modern therapeutic strategies for CRC management.

Metabolic syndrome (MetS) has been widely recognized as a risk factor for lung function. However, the evidence regarding the causal effect of MetS on lung function is limited, and it differs according to multidimensional individual characteristics. This study sought to investigate the causal effects and heterogeneity in the association between MetS and lung function through the development and validation of causal models. This cohort study included adults from the China Health and Retirement Longitudinal Study (CHARLS) aged ≥ 45 years. We applied propensity score overlap weighting to balance baseline characteristics. The CausalForestDML model was used to estimate the causal and heterogeneous treatment effects, and SHapley Additive exPlanations analysis was implemented to explain the importance of features. Model evaluation was conducted using total operating characteristic (TOC) curves and QINI curves, and a heterogeneous analysis placebo test was conducted to verify the robustness of the model. Over the two years, 6,468 participants were included in our analysis, of which 4,498 (69.5

The tumor microenvironment (TME) in gastric cancer (GC) exhibits immunosuppressive features that facilitate tumor advancement and obstruct the effectiveness of immunotherapy. The role of tripartite motif 32 (TRIM32) in the TME has not been extensively studied. GC mouse model was utilized along with flow cytometry analysis, transwell assays, and immunohistochemistry to investigate the impact of TRIM32 on tumor progression and macrophage. To uncover the mechanisms by which TRIM32 operates within the GC microenvironment, various molecular and biochemical methods were utilized, including RNA-sequencing, western blotting, quantitative reverse transcription-polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. TRIM32 originating from tumors was found to be linked to poor prognosis and notably associated with tumor-associated macrophages (TAMs) in. In vitro experiments revealed that TRIM32 induced TAMs recruitment and M2-like polarization. Mechanismly, TRIM32 interacted with Phosphodiesterase 9 A (PDE9A) and activated the downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Additionally, the reprogramming of TAMs by TRIM32 diminished the resistance to anti-PD-1 treatment in GC models. TRIM32/PDE9A axis promotes immune evasion in tumors and hinders the effectiveness of anti-PD-1 treatment by inducing TAMs recruitment and M2-like polarization in GC. This research provides insight into the role of TRIM32 in modulating tumor immunity and suggests that TRIM32 could be a promising target to overcoming resistance to anti-PD-1 therapy in GC.

Colorectal cancer (CRC) is a common digestive tract tumor with a high incidence and a poor prognosis. Traditional chemotherapy drugs are usually accompanied by unpleasant side effects, highlighting the importance of exploring new adjunctive drugs. In this study, we aimed to explore the role of ursolic acid (UA) in CRC cells. Specifically, HT-29 cells were treated with UA at different concentrations (10, 20, 30, and 40 μM), and the expression of miR-140-5p, tumor growth factor-β3 (TGF-β3), β-catenin, and cyclin D1 was determined by real-time quantitative PCR. The cell cycle and apoptosis were checked by flow cytometry, and cell proliferation was detected by Cell Counting Kit-8 assay. The HT-29 cell model was established through overexpression (miR-140-5p mimics) and interference (miR-140-5p inhibitor) of miR-140-5p. Western blot was used to detect the protein expression of TGF-β3. We found that UA could inhibit the proliferation of HT-29 cells, block cells in the G1 phase, and promote cell apoptosis. After UA treatment, the expression of miR-140-5p increased and TGF-β3 decreased. Notably, miR-140-5p downregulated the expression of TGF-β3, while the overexpression of miR-140-5p exerted a similar function to UA in HT-29 cells. Additionally, the messenger RNA expression of TGF-β3, β-catenin, and cyclin D1 was decreased in HT-29 cells after UA treatment. In conclusion, UA inhibited CRC cell proliferation and cell cycle and promoted apoptosis by regulating the miR-140-5p/TGF-β3 axis, which may be related to the inhibition of Wnt/β-catenin signaling pathway.

Background and Aim: Xuefu Zhuyu decoction (XZD), a traditional Chinese medicinal formula, was firstly recorded in the Qing dynasty of ancient China and previously demonstrated to ameliorate hepatic steatosis. In the present study, the effects of XZD on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) were evaluated in mice and the hepatic transcriptome was detected to disclose the potential mechanisms of XZD. Experimental procedure: The effects of XZD (low- and high-dosage) on NAFLD induced by HFD for 16 weeks were evaluated. Obeticholic acid was used as control drug. Body weight, food intake and index of homeostatic model assessment for insulin resistance (HOMA-IR) were analyzed. Hepatic histology were observed in haematoxylin and eosin stained sections and quantified with NAFLD activity score (NAS). Lipid in hepatocytes was visualized by Oil red staining. Alanine aminotransferase (ALT) and hepatic triglyceride (TG) was measured. The hepatic transcriptom was detected with RNA-sequencing and validated with real-time polymerase chain reaction, western-blotting and hepatic quantitative metabolomics. Results: XZD ameliorated hepatic histology of NAFLD mice, accompanied with decreasing fasting insulin, HOMA-IR, NAS, ALT and hepatic TG. The hepatic transcriptom of NAFLD was significantly reversed by XZD treatment, especially the genes enriched in the pathways of arachidonic acid metabolism, fatty acid degradation, cytokine-cytokine receptor interaction and extracellular matrix (ECM) -receptor interaction. The hepatic quantitative metabolomics analysis confirmed fatty acid degradation as the key targeting pathway of XZD. Conclusions: XZD ameliorated NAFLD induced by HFD, which probably correlated closely to the pathways of fatty acid degradation.

OBJECTIVE:To evaluate the effects of Sanren Tang (SRT, ) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice and to investigate the hepatic transcriptome regulated by SRT.METHODS:The primary SRT components were identified using ultra-high-performance liquid chromatography-high-resolution accurate mass spectrometry. The SRT-induced pharmacological effects on HFD-induced NAFLD were evaluated in mice for 16 weeks. Obeticholic acid was used as a control drug. Body weight, food intake, and homeostatic model assessment for insulin resistance (HOMA-IR) index were analysed. Hepatic histological changes were observed in haematoxylin and eosin-stained sections and quantified using the NAFLD activity score (NAS). Serum alanine aminotransferase (ALT) and hepatic triglyceride (TG) levels were measured. Lipids in hepatocytes were visualised by Oil red staining. RNA-sequencing was performed to determine the transcriptome profile of the liver tissue. The differentially expressed genes were validated using real-time polymerase chain reaction and Western blotting.RESULTS:Four principal compounds were identified in the SRT: adenosine, amygdalin, luteoloside, and magnolol. SRT ameliorated hepatic histology and lipid deposition in the NAFLD mice, and decreased HOMA-IR, NAS and ALT, and hepatic TG levels. Hepatic transcriptome analysis revealed 232 HFD-regulated genes that were reversed by SRT simultaneously. Retinol metabolism, cytokine-cytokine receptor interaction, and peroxisome proliferator-activated receptor (PPAR) γ signalling were the top three SRT-regulated pathways in NAFLD.CONCLUSIONS:SRT significantly ameliorated HFD-induced NAFLD, which was correlated with the regulation of genes enriched in the retinol metabolism, cytokine-cytokine receptor interaction, and PPARγ signalling pathways.

Ethnopharmacological relevance: Qushi Huayu Decoction (QHD) is a traditional Chinese medicine formula con-sisting of five herbs, which has been used for non-alcoholic fatty liver disease (NAFLD) treatment in clinic for decades in China and validated in several NAFLD animal models. The hepatic de novo lipogenesis (DNL) is enhanced greatly to contribute to steatosis in NAFLD. The spliced form of X-box binding protein 1 (XBP1s) initiates DNL independently of sterol regulatory element-binding protein (SREBP) and carbohydrate-responsive element-binding protein (ChREBP). Aim of the study: To disclose the mechanism of inhibition on hepatic DNL by QHD and the responsible compounds. Methods: The effects of QHD on hepatic DNL were evaluated in mice induced by high-fructose diet (HFru). The effects of the serum-absorbed compounds of QHD on XBP1s were evaluated in HepG2 cells induced by tunica-mycin. Hepatic histology, triglyceride (TG) and nonesterified fatty acids were observed. Hepatic apolipoprotein B100 and very low-density lipoprotein were measured to reflect lipid out-transport. The mRNA expression of XBP1s and its target genes were detected by real-time polymerase chain reaction. The protein expression of TG synthetases and DNL enzymes, and inositol requirement enzyme 1 alpha (IRE1 alpha), phosphorylated IRE1 alpha and XBP1s were detected in liver tissue and HepG2 cells by western-blot. The binding activity of SREBP1, protein expression of ChREBP and XBP1s were detected in the nuclear extracts of liver tissue. Results: Dynamical observing suggested feeding with HFru for 2 weeks was sufficient to induce hepatic lipo-genesis and XBP1s. QHD ameliorated liver steatosis without enhancing out-transport of lipids, accompanied with more inhibitory effects on DNL enzymes than TG synthetases. QHD inhibits the nuclear XBP1s without affecting ChREBP and SREBP1. In QHD, chlorogenic acid, geniposide and polydatin inhibit lipogenesis initiated by XPB1s. Conclusion: QHD probably decreases hepatic DNL by inhibiting XBP1s independent of SREBP1 and ChREBP. Chlorogenic acid, geniposide and polydatin are the potential responsible compounds.

ObjectiveTo investigate the effect of Xuefu Zhuyu decoction on nonalcoholic fatty liver disease (NAFLD) and its material basis. MethodsIn experiment 1 for exploring the effect of Xuefu Zhuyu decoction on mice with NAFLD induced by high-fat diet, 50 healthy male C57BL/6J mice were randomly divided into normal group, model group, high- and low-dose Xuefu Zhuyu decoction groups, and obeticholic acid control group, with 10 mice in each group. The mice in the normal group were given control diet, and those in the other groups were given high-fat diet. Gastric administration was started at week 13, and related samples were collected at the end of week 16. Food intake and body weight were recorded, enzyme-linked immunosorbent assay was used to measure the serum level of fasting insulin, fasting blood glucose was measured, and insulin resistance index was calculated. HE staining and NAFLD activity score (NAS) were used to observe liver histopathology in mice, oil red O staining was used to observe lipid deposition, and triglyceride (TG) level in liver tissue and serum alanine aminotransferase (ALT) level were measured. In experiment 2 for exploring the effect of different extracts of Xuefu Zhuyu decoction on mice with NAFLD induced by high-fat diet, the methods of water decocting, water extraction and alcohol precipitation, and petroleum ether extraction were used to obtain the extracts 1, 2, and 3 of Xuefu Zhuyu decoction, and 54 healthy male C57BL/6J mice were randomly divided into normal group, model group, Xuefu Zhuyu decoction extract 1, 2, and 3 groups, and Xuefu Zhuyu decoction control group, with 9 mice in each group. The mice in the normal group were given control diet, and those in the other groups were given high-fat diet. Gastric administration was started at week 13, and related samples were collected at the end of week 16. Food intake and body weight were recorded, and enzyme-linked immunosorbent assay was used to measure the serum level of fasting insulin, fasting blood glucose was measured, and insulin resistance index was calculated. HE and NAS were used to observe liver histopathology in mice, oil red O staining was used to observe lipid deposition, and the levels of TG and gamma-glutamyl transpeptidase (GGT) in liver tissue and the serum level of ALT were measured. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsIn experiment 1, compared with the model group, the high- and low-dose Xuefu Zhuyu decoction groups and the obeticholic acid control group had significant reductions in body weight, insulin resistance index, the distribution of vacuolar lipid droplets in liver tissue, intralobular inflammation, the ballooning degeneration of hepatocytes, NAS score, the level of TG in liver tissue, and the serum level of ALT (all P＜0.05). Compared with obeticholic acid, high- and low-dose Xuefu Zhuyu decoction had a significantly better effect in reducing body weight, insulin resistance index, and total NAS score (all P＜0.05), and low-dose Xuefu Zhuyu decoction had a significantly better effect in improving serum ALT (P＜0.05). In experiment 2, compared with the model group, the Xuefu Zhuyu decoction extract 1, 2, and 3 groups had significant reductions in fasting blood glucose, insulin resistance index, the distribution of lipid droplets in liver tissue, intralobular inflammation lesions, the ballooning degeneration of hepatocytes, total NAS score, and the level of TG in the liver (all P＜0.05). Compared with the model group, the extract 1 group had a significant reduction in body weight (P＜0.05); the extract 2 and 3 groups had a significant reduction in the serum level of ALT (P＜0.05); the extract 2 group had a significant reduction in the level of GGT in liver tissue (P＜0.05). The extract 2 of Xuefu Zhuyu decoction had the closest effect to compound Xuefu Zhuyu decoction. ConclusionXuefu Zhuyu decoction and its extracts can help to achieve varying degrees of improvement in NAFLD induced by high-fat diet in mice, and the extract 2 of Xuefu Zhuyu decoction might be the main material basis for Xuefu Zhuyu decoction.

Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.

Jiaotai Pills is a traditional medical prescription to treat the incompatibility of heart and kidney. It has the distinctive functions of heart and kidney communication, sedation and hypnosis, anti-anxiety and depression, as well as the improvement of insulin resistance. However, this pill is broadly used to cure insomnia, anxiety, depression, and diabetes in the contemporary clinical trials. Based on the article, it illustrates the research progress of the chemical ingredients, pharmacological actions, and clinical applications of Jiaotai Pills. With respect to the &quot;five principles&quot; of Q-marker in Chinese medicine, the Q-marker of Jiaotai Pills is comprehensively predicted and analyzed, noting that berberine, epiberberine, coptisine chloride, palmatine chloride, berberine chloride, berberrubine chloride, ferulic acid, cinnamic acid, cinnamaldehyde, proanthocyanidin B2 can be treated as the Q-marker of Jiaotai Pills. In addition, these components of Q-marker have been selected as indicators to provide a significant reference for the quality control and surveillance research of Jiaotai Pills.

Species of Cinnamomum exhibit excellent economic and medicinal value, and have found use in traditional medicine, are consumed as a spice, as well as being cultivated as landscape plants. Investigations into the pharmacological activities of the genus Cinnamomum revealed that it manifested a wide range of pharmacological properties including antimicrobial, antioxidant, anti-inflammatory and analgesic, antitumor, anti-diabetic and anti-obesity, immunoregulation, insecticidal and acaricidal, cardiovascular protective, cytoprotective, as well as neuroprotective properties both in vivo and in vitro. In the past five years, approximately 306 chemical constituents have been separated and identified from the genus Cinnamomum, covering 111 terpenes, 44 phenylpropanoids, 51 lignans, 17 flavonoids, 53 aromatic compounds, 17 aliphatic compounds, four coumarins, two steroids. This article highlights the traditional uses, phytochemistry and pharmacological properties of the few studied taxa of Cinnamomum through searching for the pieces of literature both at home and abroad, which would provide a reference for the pharmaceutical research and clinical application of this genus.

OBJECTIVE: To investigate the effect of electroacupuncture(EA) at acupoints on the pericardium meridian on the expression of phosphorylated Akt(p-Akt) protein in rat myocardium after ischemia and reperfusion.METHODS: Seventy Wistar rats were evenly randomized into seven groups: the sham operation group(group A), ischemia-reperfusion model Ⅰgroup(group B), ischemia-reperfusion model Ⅱgroup(group C), EA at Neiguan(PC 6) group(group D), EA at Ximen(PC 4) group(group E), EA at Hegu(LI 4) group(group F), and LY294002 + EA at Neiguan(PC 6) group(group G). All processes were monitored by electrocardiography. In group A, the left anterior descending coronary artery was only threaded without ligation for 100 min. In group B,the left anterior descending coronary artery was ligated for 40 min and reperfused for 60 min. The left anterior descending coronary artery in group C was ligated for 40 min and reperfused for 100 min.Groups D, E, and F received EA for 20 min before undergoing ischemia for 40 min, and then received EA for 20 min before undergoing reperfusion for 60 min. Before modeling, group G was injected with LY294002(0.3 mg/kg) into the tail vein, and then underwent the same intervention as the other EA groups. After reperfusion, myocardial tissue from the left cardiac ventricle was collected to enable Western blot analysis of the p-Akt level, and analysis of electrocardiographic changes.RESULTS: In groups B and C, electrocardiography showed obvious elevation of the ST-segment Ⅱlead(ECG-STⅡ), while the ECG-STⅡvalues were significantly lower in groups D, E, and G(P < 0.01). The p-Akt levels in groups D and E were significantly greater than those in groups B and C(P < 0.01).Compared with all other groups, group G showed a significantly different expression of p-Akt(P < 0.01).CONCLUSION: The expression of p-Akt protein in cardiomyocytes was significantly greater in rats that were injected with LY294002 and received EA at Ximen(PC 4) compared with all other groups.This suggests that EA at Ximen(PC 4) resulted in activation of the phosphoinositide 3-kinase/Akt signaling pathway and phosphorylation of Akt.

β‐Carboline alkaloids are the main chemical constituents of the plant Peganum harmala , while they also could be formed endogenously and found in coffee, alcoholic beverages and tobacco. Considering the fact that the possibility of herb–drug interactions has recently received great attention worldwide, the aim of the current study was to assess the potential for the metabolism‐based drug–drug interactions arising from five β‐carboline alkaloids (harmine, harmaline, harmalol, harmol and harmane) from P. harmala in vitro . With microsome incubation assays and UPLC/HPLC methods, the inhibitions on human liver CYP3A4 and CYP2D6 enzymes by those β‐carboline alkaloids were studied kinetically. Harmine, harmol and harmane exhibited noncompetitive inhibition on the activity of CYP3A4 with K i values of 16.76, 5.13 and 1.66 μ m , respectively. These β‐carboline alkaloids were also found to be both substrates and inhibitors for CYP2D6. Harmaline, harmine and harmol showed typical competitive inhibition on the activity of CYP2D6 with K i values of 20.69, 36.48 and 47.11 μ m , respectively. The inhibition of the two major CYP enzymes by those β‐carboline alkaloids suggested that changes in the pharmacokinetics of co‐administered drugs were likely to have occurred. Therefore, caution should be exercised for possible drug interactions of medicinal plants containing those β‐carboline alkaloids and CYP substrates. Copyright © 2011 John Wiley & Sons, Ltd.

Hepatotoxic pyrrolizidine alkaloid (HPA)-containing plants have always been a threat to human and livestock health worldwide. Adonifoline, a main HPA in Senecio, scandens Buch-Ham. ex D. Don Qianli guang), was used officially as an infusion in cases of oral and pharyngeal infections in China. In this study in vivo metabolism of adonifoline was studied for the first time by identifying the metabolites of adonifoline present in bile, urine and feces of rats using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MSn) (ion trap) as well as liquid chromatography/electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS) (quadrupole-time of flight). In total 19 metabolites were identified and, among them, retronecine-N-oxides were confirmed by matching heir fragmentation patterns with their fully characterized synthetic compounds. These metabolites are all involved in both phase I and phase II metabolic processes and the principal in vivo metabolism pathways of adonifoline were proposed. Copyright (C) 2009 John Wiley & Sons, Ltd.