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Background: Gemcitabine (GEM) is the first-line chemotherapeutic drug used to treat pancreatic ductal adenocarcinoma carcinoma (PDAC), but chemoresistance is often encountered clinically. Nrf2, an oxidative stress responsive transcription factor, is an important contributor to chemoresistance and poor prognosis of PDAC. Brucein D (BD), a naturally occurring quassinoid, has been reported to exert anti-tumor effect in several cancers including PDAC. In this study, we aimed to investigate the efficacy of BD and the role of Nrf2 axes on the chemosensitivity of GEM and elucidate the underlying molecular mechanisms. Methods: Analyses of clinical samples of PDAC and GEPIA database were first conducted to identify the expression of Nrf2 in PDAC. We then established cell lines with stable deletion of Nrf2 through transfecting lentivirus into PDAC cells. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to determine the expression of Nrf2 in these cell lines. The effects of BD and Nrf2 axes on PDAC cell proliferation, colony-formation, tumor growth and chemosensitivity were determined both in vitro and in vivo. Orthotopic xenograft and genetically engineered KPC mouse models of PDAC were used to evaluate the anti-pancreatic cancer effects of BD and GEM. Results: Nrf2 was highly expressed in PDAC in the clinical samples and GEPIA analysis. Gain- and lost-function study demonstrated that Nrf2 affected the chemosensitivity of GEM on PDAC cells both in vitro and in vivo. We further found that BD effectively inhibited PDAC cell proliferation and enhanced the chemosensitivity of GEM. Mechanistic studies revealed that BD sensitized GEM in PDAC cells through the ubiquitin–proteasome-dependent degradation of Nrf2, and downregulating the Nrf2 pathway. Silencing of Nrf2 plus BD treatment resulted in more potent inhibitory effects of GEM. In contrast, Nrf2 activation attenuated the chemosensitivity of GEM, indicating that the action of BD was Nrf2 dependent. Finally, the efficacy of BD alone and in combination with GEM on PDAC was validated on both orthotopic xenograft and genetically engineered KPC mouse models. Conclusions: BD was able to enhance the chemosensitivity of GEM in PDAC through inhibition of the Nrf2 pathway. Our experimental findings indicate that BD, a potent Nrf2 inhibitor, holds promise for further development into a novel adjuvant therapy for PDAC. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The use of African chewing sticks in maintaining oral health is widely practiced in African countries. It has been reported that chewing stick users have a lower rate of dental caries and a better general oral health than non-users. It is generally thought that the beneficial effect of chewing stick is attributed to the mechanical cleansing effect and antimicrobial substances present in the stick. However, the active antimicrobial substances remain uncharacterized. Aim of the study: To provide a scientific basis for the anti-caries effect of African chewing sticks, the authors purify an active antibacterial compound from Garcinia kola Heckel, a Nigerian chewing stick and examined the antibacterial activity of this compound against the cariogenic bacterium Streptococcus mutans. Materials and methods: Methanol extract was prepared from Garcinia kola and was further fractionated by solvent extractions. Silica gel chromatography was used to purify the antibacterial compound from the active fraction. The identity of the purified compound was determined by NMR analysis. The antibacterial activity of the purified compound was examined by standard microbiological assays. Results: The antibacterial activity was found in the ether fraction and the active compound was isolated and determined to be a biflavonoid named GB1. GB1 was active against Streptococcus mutans and other oral bacteria with minimum inhibitory concentration (MIC) values of 32–64μg/ml. The basis for the antibacterial effect of GB1 was investigated using Streptococcus mutans as the target. At 256μg/ml, GB1 exhibited some bacteriocidal activity against Streptococcus mutans and induced the aggregation of Streptococcus mutans. GB1 has no apparent effects on protein synthesis and DNA synthesis but inhibited glucose uptake and utilization by Streptococcus mutans suggesting that GB1 exerts its antibacterial effect by inhibiting metabolism. GB1 also inhibited the formation of water-insoluble glucan by the extracellular glucosyltransferases from Streptococcus mutans in a dose-dependent manner. Streptococcus mutans did not develop resistance to GB1 upon subculturing in the presence of sub-MIC level of the biflavonoid. Conclusion: The antibacterial effect and glucan synthesis-inhibition property of this biflavonoid may account for some of the beneficial effects reported in the chewing stick users. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The use of African chewing sticks in maintaining oral health is widely practiced in African countries. It has been reported that chewing stick users have a lower rate of dental caries and a better general oral health than non-users. It is generally thought that the beneficial effect of chewing stick is attributed to the mechanical cleansing effect and antimicrobial substances present in the stick. However, the active antimicrobial substances remain uncharacterized. Aim of the study: To provide a scientific basis for the anti-caries effect of African chewing sticks, the authors purify an active antibacterial compound from Garcinia kola Heckel, a Nigerian chewing stick and examined the antibacterial activity of this compound against the cariogenic bacterium Streptococcus mutans. Materials and methods: Methanol extract was prepared from Garcinia kola and was further fractionated by solvent extractions. Silica gel chromatography was used to purify the antibacterial compound from the active fraction. The identity of the purified compound was determined by NMR analysis. The antibacterial activity of the purified compound was examined by standard microbiological assays. Results: The antibacterial activity was found in the ether fraction and the active compound was isolated and determined to be a biflavonoid named GB1. GB1 was active against Streptococcus mutans and other oral bacteria with minimum inhibitory concentration (MIC) values of 32–64μg/ml. The basis for the antibacterial effect of GB1 was investigated using Streptococcus mutans as the target. At 256μg/ml, GB1 exhibited some bacteriocidal activity against Streptococcus mutans and induced the aggregation of Streptococcus mutans. GB1 has no apparent effects on protein synthesis and DNA synthesis but inhibited glucose uptake and utilization by Streptococcus mutans suggesting that GB1 exerts its antibacterial effect by inhibiting metabolism. GB1 also inhibited the formation of water-insoluble glucan by the extracellular glucosyltransferases from Streptococcus mutans in a dose-dependent manner. Streptococcus mutans did not develop resistance to GB1 upon subculturing in the presence of sub-MIC level of the biflavonoid. Conclusion: The antibacterial effect and glucan synthesis-inhibition property of this biflavonoid may account for some of the beneficial effects reported in the chewing stick users. [Copyright &y& Elsevier]

Abstract: Radix Codonopsis (Dangshen) is a famous traditional Chinese medicine and has long been used for replenishing energy deficiency, strengthening the immune system, lowering blood pressure and improving appetite in China, Japan and Korea. A highly specific quantification method using 1H NMR has been developed for the simultaneous determination of novel quaternary ammonium alkaloids codotubulosine A and B, adenosine and 5-(hydroxymethyl)furfural in Radix Codonopsis materials Codonopsis pilosula, C. pilosula var. modesta, C. tangshen, C. tubulosa, C. subglobosa, C. clematidea, C. lanceolota and Campanumoea javanica collected from different regions of China and Taiwan. A solid-phase extraction with C-18 cartridge followed by elution with water can easily remove sugars the major components that may affect the determination of target constituents. In the 1H NMR spectrum, the signals of N-CH3 of codotubulosine A (δ 2.75) and B (δ 2.83), H-8 of adenosine (δ 8.15), and CHO signal of 5-(hydroxymethyl)furfural (δ 9.49) are well separated from other signals in [2H4]methanol. The quantity of the compounds was calculated by the relative ratio of the integral values of the target peaks of each compound to the known amount of internal standard pyrazine. The described NMR method is found to be relatively simple, specific, precise and accurate for the quality control of Radix Codonopsis herbs and no reference compounds are required for calibration curves, in comparison to conventional HPLC methods, for instance. [Copyright &y& Elsevier]

Abstract: Crude extracts and three purified tannins from Geum japonicum Thunberg (Rosaceae) were examined for relaxant effects in isolated rat thoracic aorta and for hypotensive effects in anesthetized normotensive and hypertensive rats. The acetone extract and the butyl alcohol extract of Geum japonicum at a cumulative concentration of 30μg/ml potently relaxed phenylephrine-precontracted aortic rings by 73±5% and 80±7%, respectively, without affecting the resting tension of these vessels. Removal of the vascular endothelium, inhibition of nitric oxide (NO) synthase with N ω -nitro-l-arginine (l-NA) or inhibition of cGMP biosynthesis with methylene blue all abolished the vasorelaxant effects of the Geum japonicum extracts. Addition of l-arginine, the substrate for NO biosynthesis, reversed the inhibitory effects of l-NA. Similar vasorelaxant effects of 82±10%, 61±8% and 82±14%, were observed with the purified tannins, penta-O-galloyl-β-glucoside, casuariin and 5-desgalloylstachyurin, respectively, at a cumulative concentration of 10μM. Intravenous injection of the butyl alcohol extract of Geum japonicum at a cumulative dose of 2.5mg/kg into both hypertensive and normotensive rats resulted in a marked reduction in the mean arterial blood pressure by 46±6% and 34±7%, respectively, which was abolished by prior injection of l-NA. Therefore, these results suggest that tannins may be responsible for the vasorelaxant and hypotensive effects of Geum japonicum, mediated via endogenous NO and subsequent cGMP formation. The data suggest that extracts of Geum japonicum may have potential use as new anti-hypertensive agents for lowering arterial blood pressure in hypertensive patients. [Copyright &y& Elsevier]

Autophagy plays a complex impact role in tumor initiation and development. It serves as a double-edged sword by supporting cell survival in certain situations while also triggering autophagic cell death in specific cellular contexts. Understanding the intricate functions and mechanisms of autophagy in tumors is crucial for guiding clinical approaches to cancer treatment. Recent studies highlight its significance in various aspects of cancer biology. Autophagy enables cancer cells to adapt to and survive unfavorable conditions by recycling cellular components. However, excessive or prolonged autophagy can lead to the self-destruction of cancer cells via a process known as autophagic cell death. Unraveling the molecular mechanisms underlying autophagy regulation in cancer is crucial for the development of targeted therapeutic interventions. In this review, we seek to present a comprehensive summary of current knowledge regarding autophagy, its impact on cancer cell survival and death, and the molecular mechanisms involved in the modulation of autophagy for cancer therapy. [ABSTRACT FROM AUTHOR]

Garcinia oligantha Merr. is an ethnomedicine plant mainly distributed in Guangdong and Hainan, China. It has the effects of heat-clearing and detoxicating, which has been used by local ethnic minorities to treat a variety of diseases, including inflammation, internal heat, toothache and scald. This review summarizes and discusses the progress of the chemical compounds and biological activities of G. oligantha that have been studied in recent years to provide the direction for the prospective research and applications of G. oligantha. The relevant literature about G. oligantha was accessible from ancient Chinese medical books and records, theses, as well as major scientific databases such as Google Scholar, PubMed, Web of Science, ScienceDirect, SciFinder, Baidu Scholar and China National Knowledge Infrastructure (CNKI). To date, more than 150 chemical compounds were isolated from this plant, including xanthones, volatile oil, fatty acid, benzofurane derivative and biphenyl compounds. Xanthones are the main bioactive compounds that exhibit diverse biological effects, such as antitumor, analgesic, anti-inflammatory, antioxidative, neuroprotective, antimalarial and antibacterial effects, which are consistent with its traditional uses as a folk medicine. Modern pharmacological studies show that these compounds participate in a variety of signaling pathways underlying different pathophysiologies, making them a valuable medicinal resource. G. oligantha is an ethnomedicine with a long history. However, due to regional and cultural constraints, the popularisation and use of ethnomedicine are still limited. Modern pharmacological and chemical research suggest that G. oligantha contains a variety of bioactive compounds and showed diverse biological functions, which is worthy of comprehensive and in-depth research. This review summarizes and discusses the recent progress in studies on G. oligantha , looking forward to promote further research and sustainable development of folk medicinal plants. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-β1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-β1, and α-SMA, and up-regulated OAT1 and E-cadherin. RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis. [Display omitted] • RGE improved metabolic disorders and renal injury induced by obesity and obesity combination with hyperuricemia. • RGE ameliorated obesity-induced lipid accumulation in the kidney. • RGE improved renal inflammation and fibrosis exacerbated by lipotoxicity. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Nineteen unprecedented 7‐methoxylated caged xanthones (1—19) were isolated from the twigs of Garcinia oligantha under the guidance of NMR spectroscopy. Their structures and absolute configurations were demonstrated by extensive spectroscopic data, single‐crystal X‐ray diffraction, electronic circular dichroism (ECD) calculations, and the modified Mosher's method. Compound 1 is a rare scalemic 7‐methoxylated neo‐caged xanthone, which was resolved using HPLC with CD detection on a chiral‐phase AD column, and compounds 2—3 are rare 7‐methoxylated caged xanthones with the hydrogenated Δ8(8a) double bond. Fourteen compounds exhibited promising inhibitory activities against four human cancer cell lines with IC50 values ranging from 1.9 to 14.3 μmol/L. A cell apoptosis analysis using flow cytometry showed that compound 11 could induce apoptosis in a dose dependent manner. Moreover, PARP, caspase‐9, and Bcl‐2 western blotting suggested that compound 11‐induced apoptosis may be involved in caspase‐dependent pathway. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to investigate the underlying mechanism of protease-activated receptor-2 (PAR-2) agonist-induced visceral hyperalgesia. Male Sprague–Dawley rat pups were submitted to colonic injection of PAR-2 agonist for 6 consecutive days. The visceral sensitivity to colorectal distention was evaluated by electromyography. The enterochromaffin (EC) cell number, 5-HT content and tryrptophan hydroxylase (TPH) protein expression were detected with immunohistochemistry, fluorescent measurement and Western blot analysis. PAR-2 agonist induced a significant increase of visceral nociceptive response to colorectal distention and a series of neurochemical changes in rat colon, including proliferation of EC cells, increased 5-HT content and enhanced TPH expression. Expression of PAR-2 in EC cells was reported for the first time. Further, selective 5-HT3 receptor antagonist alosteron significantly inhibited PAR-2-induced visceral hyperalgesia. The enhanced 5-HT signaling is likely responsible for the visceral hyperalgesia induced by PAR-2 agonist. Interruption of this pathway is a possible target for the treatment of visceral hyperalgesia in gastrointestinal diseases. [Copyright &y& Elsevier]

Background: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown.Methods: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD).Results: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees.Conclusions: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers. [ABSTRACT FROM AUTHOR]

Prunella vulgaris L. (PVL) is a perennial herb belonging to the Labiate family, first recorded in the "Shen Nong's Classic of the Materia Medica". PVL can enter the liver and gallbladder channel to show its function in clearing the liver fire, dispersing nodules, dissolving swelling, and improving vision. The traditional use of PVL is to protect liver function and has clinical applications in liver diseases therapy. The modern pharmacological studies have been shown to possess potential hepatoprotection, but its underlying mechanisms against alcoholic liver disease (ALD) in mice remains to be elucidated. This study aimed to explore the protective effect and potential mechanism of PVL on alcohol induced liver injury. We used Lieber-DeCarli ethanol liquid diet fed Male C57BL/6 mice for four weeks plus a single binge (NIAAA modified model) to establish an ALD model and explored the protective effects of PVL extract against ALD. Western blot, Flow cytometry and RT-qPCR methods were used to detect lipid metabolism disorders and the inflammatory response induced by macrophages in ALD mice, and the gut microbiota composition changes were detected by 16s rRNA to reveal the potential mechanism of PVL against ALD. In ALD mice, PVL can ameliorate excessive alcohol intake-induced liver injury and lipid metabolism disorders associated with improvement of gut microbiota dysbiosis and intestinal barrier damage. PVL reduced the translocation of endotoxin, which subsequently inhibits hepatic inflammation mediated by the TLR4/MyD88 signaling pathway. These findings demonstrated the protective potential of PVL against gut dysbiosis and endotoxin leakage in ALD mice, which provides a theoretical basis for PVL against liver diseases. [Display omitted] • PVL ameliorated liver injury in ALD mice. • PVL modulated gut dysbiosis in ALD mice. • PVL ameliorated intestinal barrier dysfunction in ALD mice. • PVL alleviated hepatic inflammation in ALD mice. [ABSTRACT FROM AUTHOR]

Mountain-cultivated ginseng (MCG), which is considered the highest quality Panax ginseng C.A. Meyer, is priced higher than cultivated ginseng (CG) due to its longer growth period in the forest. However, accurately determining their age has been a persistent challenge. In this study, we examined the concentration of ginsenoside Rg 1 , Re, Rb 1 , and Rd in MCG and CG by analyzing their terahertz spectroscopic peaks. We found that MCG exhibited significant absorption peaks at 5.11, 8.23, and 9.07 THz in the range of 2–12 THz, while CG showed remarkable peaks at 8.67 and 10.57 THz. By combining the absorption raw data with multivariate statistical analysis OPLS-DA and machine learning, we were able to effectively distinguish MCG from CG with a coefficient of determination (R2) of 97.5 % and a predictive rate (Q2) of 94.5 %. Additionally, using the Multilayer Perceptron (MLP) algorithm, we accurately classified MCG samples aged 5–20 years into three distinct groups with an accuracy of 96.0 %. In contrast, the ginsenoside content analysis using high-performance liquid chromatography only provided broad categories for species and age groups. The terahertz method proved to be a fast and time-saving technique without the need for additional preparation. This method not only enables the differentiation of MCG from CG, but also allows for age-based categorization. [Display omitted] • Terahertz method developed to differentiate mountain-cultivated and cultivated ginseng. • The age identification of mountain cultivated ginseng was investigated. • The method is rapid with microgram samples, without additional extraction. • The results suggests longer growing ginseng possesses more bioactive components. • The method is comparable to the analytical method based on HPLC. [ABSTRACT FROM AUTHOR]

Abstract Fructus Psoraleae (FP) causes cholestatic liver injury; however, its main toxic constituents that are responsible for causing hepatotoxicity remained undetermined in previous studies. In the present study, psoralen and isopsoralen, the two main constituents of FP, were administered orally to rats (80 and 40 mg/kg, respectively) and mice (320 and 160 mg/kg, respectively) for 28 days, followed by biochemical and histopathological examinations to evaluate their hepatotoxicity. The results showed that psoralen and isopsoralen could induce the toxic reactions of liver and other organs in rats, while mice were not sensitive to these two compounds. Furthermore, the corresponding results indicated that administration of psoralen and isopsoralen repressed the expression of CYP7A1, BSEP, MRP2 and SULT2A1 and increased the expression of FXR and MRP3 in the rat liver. In summary, the toxic reactions of psoralen and isopsoralen are different in different species. In this study, multiple organ toxicity, such as cholestatic liver injury, occurs in rats, but not in mice. Psoralen and isopsoralen are the two main toxic constituents of FP. In addition, psoralen and isopsoralen cause liver injury, possibly through inhibiting bile acid excretion in the liver, leading to the accumulation of toxin in hepatocytes. Highlights • Psoralen and isopsoralen cause liver injury in rats but are not sensitive in mice. • Psoralen and isopsoralen cause adrenal, seminal vesicle and prostate damage in rats. • Psoralen and isopsoralen inhibit bile acid excretion in the livers of rats. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Four pairs of new scalemic caged xanthones and twelve known ones were isolated. • The relative configuration of 1 was confirmed by X-ray crystallographic analysis. • Absolute configurations were determined by the comparison of measurements and calculations of ECD spectra and OR values. • HPLC-ECD analysis was a fast and reliable analytical approach for scalemic mixtures. • Compound 4 exhibited a low micromolar activity against four cancer cell lines. Abstract Four pairs of previously undescribed caged xanthones (1 – 4) and twelve known caged xanthones (5 – 16) were isolated from the leaf extract of Garcinia bracteata. Their structures were unambiguously elucidated on the basis of spectroscopic methods. The planar structure and relative configuration of 1 was confirmed by X-ray crystallographic analysis. The enantiomers of compounds 1 , 2 , 4 were further resolved by semi-preparative chiral HPLC, and the absolute configurations of enantiomers of compounds 1 and 4 were determined by measurement and calculation of electronic circular dichroism (ECD) spectra and specific rotations. The inhibitory activities of the isolated compounds against human HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines were assayed, and garcibractatin A (4) showed the most potent inhibitory activities in vitro with IC 50 values from 1.11 to 2.93 μM. A preliminary structure-activity relationship has been discussed, and some helpful conclusions have been drawn. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A four dimensional separation method based on 2D-UHPLC-IM-MS was established. • The dilution effect and long analysis times were avoided by dual trap column mode. • 201 potential ginsenosides were detected from P. ginseng by 2D-UHPLC-IM-MS. • 10 pairs of co-eluting isobaric ginsenosides were resolved using 2D-UHPLC-IM-MS. Abstract Here, time-decoupled comprehensive two-dimensional ultra-high liquid chromatography (UHPLC) coupled with an ion mobility (IM)-high resolution mass spectrometer (HRMS) was established and used to analyze ginsenosides from the main roots of white ginseng (WG) and red ginseng (RG), which enabled the separation of complex samples in four dimensions (2D-LC, ion mobility, and mass spectrometry). The incompatibility of mobile phases, dilution effect, and long analysis time, which are the main shortcomings of traditional comprehensive 2D-LC methods, were largely avoided in this newly established 2D-UHPLC method. The orthogonality of this system was 55%, and the peak capacity was 4392. Under the optimized 2D-UHPLC-IM-MS method, 201 ginsenosides were detected from white and red ginseng samples. Among them, 10 pairs of co-eluting isobaric ginseng saponins that were not resolved by 2D-UHPLC-HRMS were further resolved using 2D-UHPLC-IM-MS. In addition, 24 ginsenoside references were analyzed by UHPLC-IM-MS to obtain their collision cross section (CCS) values and ion mobility characteristics. Finally, the established new method combined with multivariate statistical analysis was successfully applied to differentiate WG and RG, and 9 ginsenosides were found to be the potential biomarkers by S-Plot and the values of max fold change, which could be used for classifying WG and RG samples. Overall, the obtained results demonstrate the applicability and potential of the established time-decoupled online comprehensive 2D-UHPLC-IM-MS system, and it will be extended to the analysis of other targeted or untargeted compounds, especially co-eluting isomers in more herbal extracts. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New spirocyclic PPAPs, hyperhenones G–M (1 – 7), were isolated from the ethyl acetate fraction of Hypericum henryi. • The structures of 1 – 6 shared a common octahydrospiro[cyclohexan-1,5′-indene]-2,4,6-trione core. • Compound 7 possessed a rare 4,5- seco spirocyclic PPAP skeleton. • Compounds 4 and 9 suppressed the metastasis of A549 cell in vitro at 40 μM. Abstract Seven new spirocyclic polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperhenones G–M (1 – 7), were isolated from the ethyl acetate fraction of Hypericum henryi. The structures of 1 – 6 sharing a common octahydrospiro[cyclohexan-1,5′-indene]-2,4,6-trione core and compound 7 possessing a rare 4,5- seco spirocyclic PPAP skeleton, were elucidated on the basis of comprehensive NMR and MS spectroscopic data. The inhibitory activities of all the isolates were examined against three human tumor cell lines, and compound 9 showed week inhibitory activities to A549 and HeLa (IC 50 24.8 and 27.9 μM). In addition, compounds 4 and 9 suppressed the metastasis of A549 cell in vitro at 40 μM. [ABSTRACT FROM AUTHOR]

Background and Purpose: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, and an impaired immune response plays a critical role in IBD. The current drugs and therapies for IBD treatment are of limited use, therefore, there is a need to find novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via a Treg-cell-mediated effect on the immune response.Experimental Approach: Chronic colitis was established in mice using 2% DSS, and cambogin (10 mg·kg-1 , p.o.) was administered for 10 days. Body weight, colon length and colon histology were assessed. Cytokine production was measured using elisa and quantitative real-time PCR. To evaluate the mechanism of cambogin, human CD4+ CD25hi CD127lo Treg cells were isolated from peripheral blood mononuclear cells. Major signalling profiles involved in Treg cell stability were measured.Key Results: Cambogin attenuated diarrhoea, colon shortening and colon histological injury and IL-6, IFN-γ and TNF-α production in DSS-treated mice. Cambogin also up-regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7-mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS-treated cells.Conclusions and Implications: The effect of cambogin on DSS-induced colitis is expedited by a Treg-cell-mediated modification of the immune response, suggesting that cambogin could be applied as a novel agent for treating colitis and other Treg cell-related diseases. [ABSTRACT FROM AUTHOR]

A widely used traditional prescription, Yi-Gan San (YGS) is a remedy for neurodegenerative disorders. The formulation consists of seven Chinese medicinal materials in specific proportions, namely Uncariae Ramulus cum Uncis (Uncaria rhynchophylla (Miq.) Miq. ex Havil.), Bupleuri Radix (Bupleurum chinense DC.), Angelicae Sinensis Radix (Angelica sinensis (Oliv.) Diels), Chuanxiong Rhizoma (Ligusticum wallichii Franch.), Poria (Poria cocos (Schw.) Wolf), Atractylodis Macrocephalae Rhizoma (Atractylodes macrocephala Koidz.) and Glycyrrhizae Radix et Rhizoma (Glycyrrhiza uralensis Fisch.). Using YGS has been shown to alleviate various behavioural and psychological symptoms of dementia (BPSD). The goal of this review is to give up-to-date information about the traditional uses, chemistry, pharmacology and clinical efficacy of YGS based on the scientific literature and to learn the current focus and provide references in the next step. The database search room was accessed using the search terms "Yi-Gan San" and "Yokukansan" to obtain results from resources such as Web of Science, PubMed, Google Scholar and Sci Finder Scholar. We not only consulted the literature of fellow authors for this review but also explored classical medical books. YGS has been used to cure neurosis, sleeplessness, night weeping and restlessness in infants. Its chemical components primarily consist of triterpenes, flavonoids, phenolics, lactones, alkaloids and other types of compounds. These active ingredients displayed diverse pharmacological activities to ameliorate BPSD by regulating serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmission. In addition, YGS showed neuroprotective, antistress, and anti-inflammatory effects. The majority of cases of neurodegenerative disorders are treated with YGS, including Alzheimer's disease and dementia with Lewy bodies. Based on previous studies, YGS has been used as a traditional prescription in East Asia, such as Japan, Korea and China, and it has diverse chemical compounds and multiple pharmacological activities. Nevertheless, few experimental studies have focused on chemical and quantitative YGS studies, suggesting that further comprehensive research on its chemicals and quality assessments is critical for future evaluations of drug efficacy. [Display omitted] • Traditional uses, chemical compounds, pharmacological activities and clinical studies of Yi-Gan San (YGS) were concluded. • The research status about the traditional uses of YGS was presented in this review. • All know chemical constituents isolated from YGS and their chemical structures were proposed in this review. • The research on pharmacological effects and underlying mechanisms of YGS were summarized. • The clinical curative effects of YGS were outlined in detail. [ABSTRACT FROM AUTHOR]

In the present study, a novel polysaccharide, PSP-2B, was isolated from aqueous extracts of Prunellae Spica by direct ultrafiltration membrane separation and gel chromatography purification. PSP-2B is a partially sulphated polysaccharide with a molecular weight of approximately 32 kDa. Its sulfate content is 10.59% by elemental analysis. The major sugars comprising PSP-2B are arabinose, galactose and mannose, in addition to small amounts of glucose and uronic acids. The framework of PSP-2B is speculated to be a branched arabinogalactomannan, and the side chains are terminated primarily by the Ara f residues. PSP-2B also contains 2.98% protein. PSP-2B exhibits activity against herpes simplex virus (HSV), with a half maximal inhibitory concentration (IC 50 ) of approximately 69 μg/mL for HSV-1 and 49 μg/mL for HSV-2. However, PSP-2B demonstrated no cytotoxicity even when its concentration was increased to 1600 μg/mL, suggesting that it has potential as an anti-HSV drug candidate. [ABSTRACT FROM AUTHOR]

Eight previously undescribed oleanane-type triterpenoid saponins, clematangoticosides A-H, together with eight known saponins, were isolated from the whole plants of Clematis tangutica (Maxim.) Korsh. Their structures were elucidated by extensive spectroscopic analysis, in combination with chemical methods (acid hydrolysis and mild alkaline hydrolysis). Clematangoticosides D-G were found to be unusual 23, 28-bidesmosidic glycosides. The cytotoxic activities of all of the isolated saponins were evaluated against the four human cancer cell lines SGC-7901, HepG2, HL-60 and U251MG. Clematoside S, sapindoside B, kalopanax saponin A, and koelreuteria saponin A exhibited cytotoxicity against all of the test cancer cell lines with IC 50 values in the range of 1.88–27.20 μM, while clematangoticoside D and F showed selective cytotoxicity against SGC-7901 with IC 50 values of 24.22 and 21.35 μM, respectively. [ABSTRACT FROM AUTHOR]

Leonurus japonicus Houtt., also known as motherwort, is a traditional Chinese medicine that was first identified in Shennong Bencao Jing , the first and essential pharmacy monograph in China. L. japonicus has been regarded as a good gynecological medicine since ancient times. It has been widely used in clinical settings for treatment of gynecological diseases and postnatal rehabilitation with good efficacy and low adverse effects. The main purpose of this study was to determine the angiogenic and wound healing effects of total alkaloid fraction from L. japonicus Houtt. (TALH) in vivo and in vitro. In addition, the main bioactive components of total alkaloids were to be identified and analyzed in this study. First, the UHPLC/Q-TOF-MS method was used to identify and quantify the major components in the TALH extract. The wound healing activity was evaluated in vivo using a rat full-thickness cutaneous wound model. Histological study of wound healing in rat model was performed via immunohistochemistry and immunofluorescence. Cell proliferation was determined by MTT assay. Wound healing and transwell assays were used for detection of cell migration. The effect on tube formation was determined by tube formation assay in HUVECs. Western blot and RT-PCR were used to detect the expressions of relative proteins and genes respectively. Knock-down of SRC by siRNA was done to verify the crucial role of SRC in promotion of angiogenesis induced by TALH. Seven characteristic peaks were recognized in the UHPLC/Q-TOF-MS spectrum, while four of the main components were quantified. The wound model in rats showed that treatment of TALH promoted wound healing by stimulating cellular proliferation and collagen deposition. In vitro experiments showed that co-treatment of TALH and VEGF increased cell proliferation, migration and tube formation in HUVECs. Mechanistic studies suggested that the co-treatment increased gene expressions of SRC, MEK1/2 and ERK1/2, as well as the phosphorylation levels of these proteins. Furthermore, the effect of co-treatment was attenuated after SRC knockdown, suggesting that SRC plays an important role in angiogenesis and wound healing induced by TALH and VEGF co-treatment. Our results showed that TALH was one of the main active components of L. japonicus that promoted angiogenesis and wound healing by regulating the SRC/MEK/ERK pathway. Our study provided scientific basis for better clinical application of L. japonicas. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel multistage MS approach, insource collision-induced dissociation (CID) combined with Time Aligned Parallel (TAP) fragmentation, was established to study the fragmentation behavior of polycyclic polyprenylated acylphloroglucinols (PPAPs), which could provide a more reliable fragmentation relationship between precursor and daughter ions. The diagnostic ions for different subtypes of PPAPs and their fragmentation behaviors have been summarized. Moreover, a new and reliable multidimensional analytical workflow that combines ultrahigh performance liquid chromatography (UHPLC), data-independent mass spectrometry (MS E ), and tandem MS with ion mobility (IM) has been optimized and established for the analysis of PPAPs in the plant Garcinia oblongifolia by diagnostic filtering. Diagnostic fragment ions were used to selectively screen PPAPs from extracts, whereas IM coupled to MS was used to maximize the peak capacity. Under the optimized UHPLC-IM-MS E and UHPLC-IM-MS/MS method, 140 PPAPs were detected from the crude extract of G. oblongifolia , and 10 of them were unambiguously identified by comparing them to the reference compounds. Among those PPAPs, 7 pairs of coeluting isobaric PPAPs that were indistinguishable by conventional UHPLC-HRMS alone, were further resolved using UHPLC-IM-MS. It is anticipated that the proposed method will be extended to the rapid screening and characterization of the other targeted or untargeted compounds, especially these coeluting isomers in complex samples. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed regiodivergent C1 insertion multicomponent reaction involving aryne, CO, and 2-iodoaniline is established to construct the scaffolds of phenanthridinone and acridone alkaloids. Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand-free condition. In comparison, application of the electron-abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed regiodivergent C1 insertion multicomponent reaction involving aryne, CO, and 2-iodoaniline is established to construct the scaffolds of phenanthridinone and acridone alkaloids. Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand-free condition. In comparison, application of the electron-abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method. [ABSTRACT FROM AUTHOR]

An automated headspace solvent free microextraction (HS-SFME) based gas chromatography/mass spectrometry (GC/MS) was developed for discrimination of Radix Angelica sinensis (RAS) from different cultivation regions. The MS data were subjected to principal component analysis (PCA) and hierarchical clustering analysis (HCA) to rapidly find the potential characteristic components of RAS from top-geoherb region and non top-geoherb region. Totally, fifty-one volatile organic compounds (VOCs) were identified, in which β -ocimene, α -pinene, 3-methylbutanal, heptanes, butanal were identified as potential markers for distinguishing RAS from top-geoherb region and non top-geoherb region. Sulphur dioxide was detected in some commercial RAS samples, which implied that sulphur-fumigation might be the main reason for the quality inconsistencies of commercial RAS samples. These results suggested that RAS from top-geoherb region and non-top geoherb region could be discriminated by the method. And characteristic chemical markers found in current study can be used for ensuring consistent quality of top-geoherb of RAS. [ABSTRACT FROM AUTHOR]

Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE’s capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10 g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C 18 column (100 mm × 2.1 mm, 1.7 μm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity ( r 2 > 0.995) over the concentration range from 3.9 to 125.0 ng/mL for emodin, 3.9–500.0 ng/mL for amygdalin, 2.0–4000.0 ng/mL for naringin and hesperidin, 3.9–2000.0 ng/mL for magnolol, 7.8–2000.0 ng/mL for rhein and 3.9–4000.0 ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from −13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0 ng/mL and 7.8 ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future. [ABSTRACT FROM AUTHOR]

The activation of RAF- MEK-extracellular signal-regulated kinase ( ERK) mitogen-activated protein kinase cascade by v-raf murine sarcoma viral oncogene homolog B1 ( BRAF)V600E mutation is a key alteration in melanoma. Although BRAF inhibitor ( BRAFi) has achieved remarkable clinical success, the positive response to BRAFi is not sustainable, and the initial clinical benefit is eventually barred by the development of resistance to BRAFi. There is growing evidence to suggest that endoplasmic reticulum ( ER) stress-induced autophagy could be a potential pro-survival mechanism that contributes to genesis of melanoma and to the resistance to BRAFi. ER stress-induced autophagy is an evolutionarily conserved membrane process. By degrading and recycling proteins and organelles via the formation of autophagous vesicles and their fusion with lysosomes, the autophagy plays a key role in homeostasis as well as pathological processes. In this review, we examine the autophagy phenomenon in melanocytic nevus, primary and metastatic melanoma, and its significance in BRAFi-resistant melanoma. [ABSTRACT FROM AUTHOR]

Eleven compounds, including a new compound, methyl 3-phenylpropionate-1-O-glucuronic acid methyl ester (1), four known biflavones 2-5, one known flavone (6), and five other known compounds (7-11) have been isolated from the pericarp of Garcinia yunnanensis. Their structures were elucidated by spectral analysis and by comparison of their spectral data with those in the published literatures. All the compounds were isolated from G. yunnanensis for the first time and screened for their scavenging activity against DPPH radicals. Of all the samples tested, compounds 1-6 showed significant activities with IC50 values of 1.83, 0.87, 0.17, 3.51, 0.75, and 2.21 mM, respectively. [ABSTRACT FROM AUTHOR]

Highlights: [•] A UPLC–PDA–QTOF–MS method was applied to investigate triterpenoids in Poria cocos. [•] Seven triterpenoids were quantified in 40 batches of P. cocos. [•] Ten marker triterpenoids identified and 31 triterpenoids were characterized. [•] This method can be used for bitterness evaluation and quality control of P. cocos. [Copyright &y& Elsevier]

Highlights: [•] HPLC fingerprints of CR herbs and dispensing granules compared to find markers. [•] Major characteristic components identified by LC-PDA-QTOF-MS/MS analysis. [•] Ferulic acid, senkyunolide I, senkyunolide H quantified in CR dispensing granule. [•] Senkyunolide I as quantitative marker for quality control of CR dispensing granule. [ABSTRACT FROM AUTHOR]

Highlights: [•] New method for comparing two dosage forms of herbal drug with complex constituents. [•] Holistic evaluation by UHPLC-Q-ToF and multivariate statistical techniques. [•] Hemp Seed Pills (HSP) and Hemp seed soft gel capsules (HSSGC) were studied. [•] Differentiation between HSP and HSSGC was attributed to Fructus Aurantii Immaturus. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Polygonum chinense Linn., a folk medicine, has long been used for the treatment of diarrhea and enteritis in southwestern China. However, the components responsible for its anti-diarrheal activity are still poorly understood. Aim of the study: To determine anti-diarrheal activities of Polygonum chinense L. and to identify its active components through bioactivity-guided isolation technique. Materials and methods: Animals were orally administered with the extract of Polygonum chinense L. The anti-diarrheal effects of 75% ethanol extract, four fractions with different polarities from 75% ethanol extract, different eluates collected from Diaion HP-20 macroporous resin chromatography, ellagic acid and corilagin, were examined based on mouse models of castor oil- and magnesium sulfate-induced diarrhea. Results: The results showed that the 75% ethanol extract of Polygonum chinense L. exhibited significant anti-diarrheal activities in a dose-dependent manner in two mouse models. Through in vivo bioactivity-guided fractionation processes, n-butanol and aqueous fractions were found to exhibit prominent anti-diarrheal activities, and two major compounds, ellagic acid and corilagin, from these active fractions were found to possess anti-diarrheal effects. Conclusion: Present study provides evidence of the utilization of Polygonum chinense L. for diarrhea, and ellagic acid and corilagin are two components contributing to the anti-diarrheal effect. [Copyright &y& Elsevier]

An approach for rapid optimization of ultra-high-performance supercritical fluid chromatographic (UHPSFC) gradient by response surface methodology was developed for fast separation of complex crude extracts of the leaves of Rosa sericea. The optimization was performed with Box-Behnken designs and the multicriteria response variables were described using Derringer's desirability. Based on factorial design experiments, five factors were selected for Box-Behnken designs to optimize the UHPSFC conditions, which led to 46 experiments being performed within 8 h. An evaporative light-scattering detector (ELSD) was used, and quantitative analysis of main components in R. sericea samples was employed to evaluate the statistical significance of the parameters on UHPSFC-ELSD analytes response. The results indicated that the optimized UHPSFC-ELSD method is very sensitive with LODs and LOQs below 1.19 and 4.55 μg/mL, respectively. The overall intra- and interday variations were less than 3.91 and 6.41%, respectively. The recovery of the method ranged from 95.66 to 104.22%, with RSD < 5.91%. This newly developed UHPSFC-ELSD method was demonstrated to be fast and sensitive in analyzing complex herbal extracts of Traditional Chinese Medicines. [ABSTRACT FROM AUTHOR]

Two-phase solvent system plays crucial role in successful separation of organic compounds using counter-current chromatography ( CCC). An interesting two-phase solvent system, composed of chloroform/ethyl acetate/methanol/water, is reported here, in which both phases contain sufficient organic solvents to balance their dissolving capacities. Adjusting the solvent system to get satisfactory partition coefficients ( K values) for target compounds becomes relatively simple. This solvent system succeeded in sample preparation of aconitine (8.07 mg, 93.69%), hypaconitine (7.74 mg, 93.17%), mesaconitine (1.95 mg, 94.52%) from raw aconite roots (102.24 mg, crude extract), benzoylmesaconine (34.79 mg, 98.67%) from processed aconite roots (400.01 mg, crude extract), and yunaconitine (253.59 mg, 98.65%) from a crude extract of Aconitum forrestii (326.69 mg, crude extract). [ABSTRACT FROM AUTHOR]

Abstract: Two new flavonoids, quercetin-3-O-β-d-xylopyranosyl-(1→2)-α-d-ribopyranoside (1) and kaempferol-3-O-β-d-xylopyranosyl-(1→2)-α-d-ribopyranoside (2), and one new phenolic derivative, gallicin-p-O-(6′-O-caffeoyl)-β-d-glucoside (3), together with twelve known compounds were isolated from the leaves of Rosa sericea (Rosaceae family). The structures of the new compounds were established by means of spectroscopic analysis including one- and two-dimensional NMR spectroscopy. Some of the isolated compounds were tested for the cytotoxicity of a breast cancer cell (MCF-7) line. The results showed that rubanthrone A (4) has moderate cytotoxicity against the MCF-7 cell line. [Copyright &y& Elsevier]

Abstract: Hepatocellular carcinoma (HCC) is a global public health problem which causes approximately 500,000 deaths annually. Considering that the limited therapeutic options for HCC, novel therapeutic targets and drugs are urgently needed. In this study, we discovered that 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP), isolated from the traditional Chinese medicinal herb, Garcinia oblongifolia, effectively inhibited cell growth and induced the caspase-dependent mitochondrial apoptosis in HCC. A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were performed to find the molecular targets of TDP in HCC cells. Eighteen proteins were identified as differently expressed, with Hsp27 protein being one of the most significantly down-regulated proteins induced by TDP. In addition, the following gain- and loss-of-function studies indicated that Hsp27 mediates mitochondrial apoptosis induced by TDP. Furthermore, a nude mice model also demonstrated the suppressive effect of TDP on HCC. Our study suggests that TDP plays apoptosis-inducing roles by strongly suppressing the Hsp27 expression that is specifically associated with the mitochondrial death of the caspase-dependent pathway. In conclusion, TDP may be a potential anti-cancer drug candidate, especially to cancers with an abnormally high expression of Hsp27. [Copyright &y& Elsevier]

Abstract: Sulfur-fumigation may induce chemical transformation of medicinal herbs. Development of rapid method to reveal potential sulfur-fumigation induced chemical transformation of herbs is a very important issue for efficacy and safety of herb application. In present study, a new strategy was proposed to rapidly reveal chemical transformation of sulfur-fumigated herbs by ultra-high-performance liquid chromatography–quadrupole/time of flight mass spectrometry (UHPLC–QTOF-MS/MS) based chemical profiling approach. The non-fumigated herb was water-wetted and further treated with burning sulfur to get sulfur-fumigated herb. Then the chemical fingerprints of both non-fumigated and sulfur-fumigated samples were compared by UHPLC–QTOF-MS/MS analysis. The identities of all detected peaks, in particular those newly generated in sulfur-fumigated samples were confirmed by comparing the mass spectra and retention times of peaks with that of reference compounds, and/or tentatively assigned by matching empirical molecular formula with that of published compounds, and/or elucidating quasi-molecular ions and fragment ions referring to available literature information. The identification could be rationalized through deducing possible reactions involved in the generation of these newly detected compounds. The proposed strategy was extensively investigated in the case of white ginseng. Total 82 components were detected in non-fumigated and sulfur-fumigated white ginseng samples, among them 35 sulfur-containing compounds detected only in sulfur-fumigated white ginseng and its decoction were assigned to be sulfate or sulfite derivatives of original ginsenosides, and were deduced to be generated via reactions of esterification, addition, hydrolysis and dehydration during sulfur-fumigation and decocting of white ginseng. The established approach was applied to discriminate sulfur-fumigated white ginseng among commercial samples from America, Canada, and Hong Kong SAR, Macau SAR and Mainland of China, which indicated that the proposed approach is rapid and specific, and should also be useful for investigation of potential chemical transformation of other sulfur-fumigated medicinal herbs. [Copyright &y& Elsevier]

Abstract: Papers published in the last two years concerning quantitative analysis of medicinal herbs were searched from Scopus database and viewed to critically discuss reliability of spike recovery for evaluating the accuracy of analytical methods for medicinal herbs without testing extraction efficiencies of analytes. This issue was raised regarding different strategies of analytical method development, i.e., with or without testing extraction efficiencies, employed in these papers, and experimentally verified on an example of determining three major bioactive components aloe-emodin, rhein and emodin of rhubarb by high performance liquid chromatography. The simple experiment was particularly designed to compare the difference between the recoveries of spiked analytes and the extraction efficiencies of native analytes in the sample with the same extraction durations. The results showed that the overall extraction efficiencies of three native analytes with extraction duration of 3, 5, 10 and 20min was unacceptable from about 73% to 94%, whereas the spike recovery values with the same extraction durations found to be acceptable from nearly 97% to 103%, indicating that spike recovery may not always reflect the true value of the analytical accuracy, and that the spike recovery may be unreliable for accuracy evaluation of analytical methods for medicinal herbs when the extraction efficiencies of analytes were not properly tested. Extraction efficiencies of analytes should always be tested in method development, so that spike recovery can really represent the accuracy of analytical methods for medicinal herbs. [Copyright &y& Elsevier]

Abstract: In traditional Chinese medicine practice, white ginseng (WG) and red ginseng (RG) have traditionally been used for different purposes. In the present study, an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was developed to evaluate the holistic qualities and to explore characteristic chemical components of commercial WG and RG. Through unsupervised principal component analysis (PCA) and supervised orthogonal partial least squared discrimination analysis (OPLS-DA) of the data from UPLC-QTOF-MS/MS, holistic quality inconsistencies of commercial WG and RG were identified, and the possible reasons involved were deduced by further elucidating the characteristic components of the groups. Heat treating and sulfur-fumigation were likely the main reasons for the quality differences in WG, and non-standardized processing procedures might have caused the inconsistent quality of RG. Together with ginsenoside Rg3, a nitrogen-containing component and ginsenoside 20(R)-Rh1 were detected as characteristic components of RG, whereas malonyl ginsenoside Rb1/isomer and malonyl ginsenoside Rg1/isomer were found to be characteristic components of WG. It was suggested that post-harvest handling procedures for WG and processing procedures for RG should be standardized using the identified characteristic components as chemical markers to ensure the consistent quality and consequently the efficacy of WG and RG. [Copyright &y& Elsevier]

Abstract: Four new compounds, oliganthins A–D (1–4), and one known caged xanthone gaudichaudione H (5) were isolated from the stems of Garcinia oligantha. The structures of the new compounds were elucidated by spectroscopic evidences. All of the five compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. All of them induced cell apoptosis at 10μM or lower concentrations. The apoptotic activity of oliganthins A, B and gaudichaudione H were further confirmed by detecting the cleavage of PARP, which is the substrate of activated caspase-3, in these compounds-treated cells using the method of Western blot. Moreover, the values of IC50 were measured for all five compounds on HeLa cells using the MTT assay. Among them, gaudichaudione H had the lowest IC50 value of 0.90μM, while the other four new compounds had IC50 values of 1.58, 1.52, 4.15, and 7.82μM, respectively. These results show that gaudichaudione H has the strongest apoptosis-inducing effect and cell growth inhibition effect among these xanthones and it may have the potential to be developed into a new anticancer agent. [Copyright &y& Elsevier]

Abstract: Furocoumarins are a group of natural products with many biological activities. Clinical evidences have demonstrated the important contribution of furocoumarins to the toxicity of some foods and herbs. In order to assess liver and kidney toxicity of furocoumarins, male mice were orally administrated with psoralen, isopsoralen, imperatorin, isoimperatorin and xanthotoxin at 20 and 40mg/kg once daily for 28 days, respectively. No changes of food or water intake were observed in furocoumarins-treated mice. Only 40mg/kg isopsoralen reduced body weight. 40mg/kg furocoumarins altered serum activities of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and/or levels of albumin, showing hepatotoxicity. Furthermore, furocoumarins increased activity and protein expression of hepatic microsomal cytochrome P450 (CYP450) 3A11. CYP 2E1 activity and protein expression were suppressed by psoralen and isopsoralen and increased by xanthotoxin. Renal protein levels of organic cation/carnitine transporters (OCT1, OCT2 and OCTN2) and organic anion transporter 3 were increased by most furocoumarins. Renal urate transporter 1, glucose transporter 9 and multidrug resistance protein 4 were influenced by furocoumarins. These findings suggest that furocoumarins may interfere in metabolism, excretion and bioavailability of endogenous and exogenous compounds to impair liver and kidney functions mediated by affecting hepatic CYP450 and renal organic ion transport system. [Copyright &y& Elsevier]

Abstract: An ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (QTOF-MS) procedure is designed for the first simultaneous analysis of nortriterpenoids and lignans in Schisandra samples. The method consists of three individual mass spectrometric experiments, including the full scan MS, MS/MS experiment and in-source collision induced dissociation (CID) MS/MS, which enable the identification of diagnostic fragmentation pathways of nortriterpenoids and lignans. As such, a total of 6 nortriterpenoids and 10 lignans were unequivocally identified, and one nortriterpenoid and 20 lignans were tentatively identified from different Schisandra samples within 12.5min. In addition, 6 nortriterpenoids and 10 lignans were quantified in 48 samples of S. chinensis and S. sphenanthera using an extract ion chromatogram (XIC) of the full scan MS experiment. Dataset obtained from UPLC–MS was processed with principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) to compare the difference between the two Schisandra species. [Copyright &y& Elsevier]

Background & Aims: One major cause of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of pyrrolizidine alkaloid (PA)-containing products. Over 8000 PA-induced HSOS cases have been reported worldwide and at least 51 among them were suspected to be attributed to exposure to the Chinese medicine ‘Tusanqi’. PA-induced hepatotoxicity involves cytochrome P450-mediated metabolic activation of PAs to electrophilic pyrrolic metabolites which react with macromolecules, such as proteins. However, no studies have found such protein adduction in HSOS patients. We report one HSOS case confirmed by liver biopsy, where the patient claimed taking ‘Tusanqi’ as self-medication. Methods: The herb was analyzed by HPLC–MS, and its induced hepatotoxicity in rats was assessed by monitoring the alteration of serum ALT level and liver morphology. Blood pyrrole–protein adducts were determined by UPLC–MS. Results: The herb the patient consumed was identified as Gynura segetum, an erroneous substitute of non-PA-containing Sedum aizoon, called ‘Tusanqi’. Hepatotoxic PAs senecionine and seneciphylline were detected in G. segetum. In the PA-exposed patient, serum pyrrole–protein adducts were detected by a newly developed analytical approach. The animal study showed a good correlation of liver injury with the ingestion of G. segetum. Conclusions: For the first time, serum pyrrole–protein adducts were unequivocally detected in a PA-induced HSOS patient, and such adducts show a potential to be developed as a biomarker for the assessment of PA-induced HSOS. Similar to the well-known case of aristolochic acid-poisoning, the observed HSOS was confirmed to arise from the consumption of PA-containing G. segetum, an erroneous substitute of non-PA-containing S. aizoon. [ABSTRACT FROM AUTHOR]

ims: Post-infectious irritable bowel syndrome (PI-IBS) is a subset of IBS which occurs after an episode of acute gastrointestinal infections. The mechanisms of PI-IBS are not fully understood. Currently, numerous animal models have been used in the study of PI-IBS. This article reviews the strengths and weaknesses of these models. Methods: All relevant articles were identified by searching in Ovid SP from 1962, the year the term PI-IBS was coined, up to December 31, 2009. The types of model were categorized as either post-infectious or post-inflammatory, and the characteristics of each kind of model were listed. Results: Based on our literature search, 268 articles were identified. Of those articles, 50 were included in this review. The existing PI-IBS models include infection with bacteria (e.g., Campylobacter jejuni, Salmonella enterica, and Campylobacter rodentium), and infection with parasites (e.g., Trichinella spiralis, Nippostrongylus brasiliensis, and Cryptosporidium parvum). The post-inflammatory IBS models are commonly induced with chemical agents, such as acetic acid, deoxycholic acid, dextran sulfate sodium, mustard oil, zymosan, and trinitrobenzene sulfonic acid (TNBS). TNBS is the most commonly used agent for post-inflammatory IBS models, but the experimental protocol varies. These models have one or more aspects similar to IBS patients. Conclusions: Different methods have been used for the development of post-infectious or post-inflammatory IBS models. Each model has its weaknesses and strengths. More studies are needed to establish post-infection IBS models using more common pathogens. A standard protocol in developing TNBS-induced post-inflammatory IBS model is needed. [ABSTRACT FROM AUTHOR]

Abstract: An UPLC–Q-TOF-MS/MS based chemical profiling method was developed to evaluate decocting-induced chemical transformations in Du–Shen–Tang, the decoction of the root of Panax ginseng. Under the optimized UPLC and Q-TOF-MS/MS conditions, over 50 peaks were separated and detected in Du–Shen–Tang within 18min. The components were identified by comparing the mass spectra and retention time with that of reference compounds, and/or tentatively assigned by elucidating low energy CID fragment ions as well as matching empirical molecular formula with that of the published known compounds. Totally 45 major ginsenosides were identified in Du–Shen–Tang, 21 of which were determined to be newly generated during the decoction of ginseng. The mechanisms involved were further deduced to be hydrolysis, dehydration, decarboxylation and addition reactions of the original ginsenosides in white ginseng through analyzing mimic decoctions of 13 pure reference ginsenosides. Significant difference in chemical profiles between decoctions of two batches of white ginseng suggested that storage duration or other factors significantly influenced the quality consistency of not only the crude drug but also the decoction (Du–Shen–Tang) of white ginseng. [ABSTRACT FROM AUTHOR]

Abstract: A rapid, but sensitive and selective method for simultaneous screening and quantification of toxic pyrrolizidine alkaloids (PAs) by ultra performance liquid-chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) on a tandem quadrupole mass spectrometer (TQ-MS) is described. This was accomplished by incorporating the precursor ion scan (PIS) acquisition and multiple reaction monitoring (MRM) acquisition in the same UPLC–MS/MS run. Notably, the developed PIS approach for detecting two pairs of characteristic product ions at m/z 120/138 or 168/150, allowed specific identification of toxic retronecine and otonecine types PAs. This PIS method is highly sensitive with over 10-fold sensitivity improvement upon previously published LC–MS method. Moreover, this new approach is suitable for high sample throughput and was applied to the screening and quantifying toxic PAs in 22 samples collected from seven Parasenecio species and four Senecio species. In addition, coupling the MRM with PIS approach generated quantitative results equivalent to those obtained by conventional MRM-only approach. This coupled MRM with PIS approach could provide both qualitative and quantitative results without the need of repetitive analyses. [ABSTRACT FROM AUTHOR]