3-(3,4-Dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide

Identification and quantification of phenolic compounds in Vitex negundo L. var. cannabifolia (Siebold et Zucc.) Hand.-Mazz. using liquid chromatography combined with quadrupole time-of-flight and triple quadrupole mass spectrometers.[Pubmed:25703235]

J Pharm Biomed Anal. 2015 Apr 10;108:11-20.

A high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry method was developed for the identification of phenolic compounds in Vitex negundo L. var. cannabifolia (Siebold et Zucc.) Hand.-Mazz. A total of 31 compounds (10 phenolic acids, 19 flavonoids, and 2 iridoids) were fully or partially identified. Caffeic acid, neochlorogenic acid, cryptochlorogenin acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, schaftoside, isoschaftoside, flavosativaside, vitexin 2"-rhamnoside, and kaempferol 3-(6"-malonylglucoside) were detected for the first time in this plant. In subsequent quantitative analysis, an ultra-performance liquid chromatography combined with triple quadrupole mass spectrometry method was developed for the quantitative analysis of 17 phenolic compounds. All the analytes were detected within 8 min. The limits of detection and quantification were less than 7.251 and 26.454 ng/mL, respectively. The relative standard deviations of intra-day precision, inter-day precision, repeatability, stability, and recovery were less than 2.87%, 3.87%, 4.86%, 4.70%, and 3.61%, respectively. The validated method was applied to assess the quality of different medicinal parts (leaves, seeds, and roots) of V. negundo. The results indicated that chlorogenic acid, agnuside, isochlorogenic acid A, and isochlorogenic acid C might be selected as quantitative markers for the quality control of V. negundo. The contents of the 17 investigated compounds in leaves differed from those in the other parts. Hierarchical cluster analysis suggested that chlorogenic acid, agnuside, vitexin, and schaftoside could be potential chemical markers for the discrimination of different medicinal parts of V. negundo. This qualitative and quantitative analysis of phenolic compounds of V. negundo could provide a new tool for the quality control of this plant or its related remedies.

Low potency homeopathic remedies and allopathic herbal medicines: is there an overlap?[Pubmed:24019954]

PLoS One. 2013 Sep 3;8(9):e74181.

Classical homeopathy is based on the therapeutic application of highly diluted homeopathic stocks. The indications of such medicines are determined by proving, i.e. by applying the remedies in healthy subjects. However, there are several complex homeopathic medicinal products on the market with approved therapeutic indications. The efficacy of these medicines has been assessed in clinical trials on patients. There is no upper limit of dosing for such homeopathic remedies, and these products often contain undiluted mother tincture. The aim of our study was to compare an allopathic herbal medicine and a homeopathic product containing undiluted mother tincture based on the same plant. Two products (an allopathic herbal medicine and a homeopathic product) containing Vitex agnus-castus extract were analyzed by HPLC-DAD for their agnuside and casticin contents. The agnuside content of the allopathic product was approximately four times higher, while the amount of casticin was in the same order of magnitude. Our experiments revealed the presence of active ingredients in allopathic quantity in a homeopathic preparation, highlighting the controversy between the principles of classical and practice of contemporary homeopathy. According to the principles of classical homeopathy these remedies cannot be considered as homeopathic remedies but rather as (allopathic) herbal ones. This phenomenon necessitates a case-by-case approach towards the possible adverse effects and drug interactions of homeopathics in the daily medical practice. Homeopathic products containing active agents in allopathic doses should be treated the same way as allopathic medicines from the point of view of quality assurance and pharmacovigilance.

Chemical Traits of Hemiparasitism in Odontites luteus.[Pubmed:27997755]

Chem Biodivers. 2017 Apr;14(4).

The study of the monoterpene glycosides content of Odontites luteus has shown the presence of a total of fifteen iridoid glucosides. The presence of compounds 1 - 5 and 7 - 10 is perfectly on-line with both the biogenetic pathway for iridoids biosynthesis in Lamiales and the current botanical classification of the species. On the other side, the presence of compounds like agnuside (6), adoxosidic acid (11), monotropein (12), 6,7-dihydromonotropein (13), methyl oleoside (14) and methyl glucooleoside (15) is of high interest because, first of all, they have never been reported before in Lamiales. In second instance, the majority of the last compounds are formally derived from a different biogenetic pathway which involves deoxyloganic acid/loganin and led to the formation of decarboxylated iridoid showing the 8beta-configuration. Furthermore, a second abnormality was found during our study and this regards compounds 14 and 15 which are seco-iriodids and thus not typical for this family. The presence of these unusual compounds, biogenetically not related to species belonging to Lamiales, is a clear evidence of the metabolites transfer from the hosts. In fact, the collection area is also populated by species belonging to Oleaceae and Ericaceae which could be the possible hosts since the biosynthesis of seco-iridoids and or iridoids related to deoxyloganic acid/loganin pathway, with the 8beta-configuration, is well documented in these species.

Validated HPLC method for identification and quantification of p-hydroxy benzoic acid and agnuside in Vitex negundo and Vitex trifolia.[Pubmed:29403861]

J Pharm Anal. 2013 Dec;3(6):500-508.

A high performance liquid chromatography coupled with photodiode array detection method was developed for the identification and quantification of p-hydroxy benzoic acid and agnuside in the extracts of Vitex negundo and Vitex trifolia. The separation was achieved using acetonitrile and O-phosphoric acid-water (0.5%, v/v) as the mobile phase in an isocratic elution mode. Mean retention times of standard p-hydroxy benzoic acid and agnuside were 6.14 and 11.90 min respectively. The developed method was validated as per the ICH guidelines for limit of detection, limit of quantification, linearity, accuracy and precision. Good linearity (r(2)>/=0.999) was observed for both the compounds in wide concentration range. Relative standard deviation values for intra-day and inter-day precision studies were less than 2%. The analytical recoveries of p-hydroxy benzoic acid and agnuside by the developed HPLC method were 93.07% and 106.11% respectively. Two compounds were identified and quantified in leaves and bar extracts of V. negundo and V. trifolia using the developed HPLC method.

Synthesis of novel lipidated iridoid glycosides as vaccine adjuvants: 6-O-palmitoyl Agnuside elicit strong Th1 and Th2 response to ovalbumin in mice.[Pubmed:23954198]

Int Immunopharmacol. 2013 Nov;17(3):593-600.

Novel lipidated analogs of iridoids viz., Agnuside and Negundoside with different chain length were synthesized and tested for immune adjuvant activity in the presence of weak antigen ovalbumin. Based on in vitro assay, 6-O-palmitoyl Agnuside (AG-3) was further taken up for detailed in vivo activity and found to significantly enhance the production of anti OVA IgG titer, neutralizing antibody (IgG1 and IgG2a) titer as well as soluble mediators of a Th1 (IL-2, IFN-gamma)/Th2 response (IL-4) and proliferation of T lymphocyte subsets (CD4/CD8) and co stimulatory molecules CD80/CD86. Furthermore, the SAR studies revealed that presence of acyl group at aglycon moiety of these iridoid glycosides is crucial for immune adjuvant activity.

Quality evaluation of medicinal products and health foods containing chaste berry (Vitex agnus-castus) in Japanese, European and American markets.[Pubmed:24695348]

Chem Pharm Bull (Tokyo). 2014;62(4):379-85.

The aim of present study was to evaluate the qualities of chaste berry (fruit of Vitex agnus-castus L.) preparations using HPLC fingerprint analysis. Seven medicinal products 1 from Japan and 6 from Europe, and 17 health foods, 6 from Japan and 11 from the United States were analyzed. HPLC profile and 26 authentic peaks were compared medicinal products and health foods. Whereas medicinal products had similar HPLC profiles, health foods had various profiles and each peak was also greatly different. The measured amounts of two markers in 5 traditional medicinal products, agnuside and casticin specified in the European Pharmacopoeia (EP), the U.S. Pharmacopoeia (USP) or the WHO monographs of chaste berry, were much lower than those in 2 medicinal products defined as "well-established use" by the European Medicines Agency. The amounts of two markers for 17 health foods differed in a great deal from 14-5054% and 3-1272%, respectively. Furthermore the amount ratios of two markers, agnuside/casticin, in about half of the health foods were remarkably larger than the standard crude drug and the ratios were closer to one of the related Chinese herbs, Vitex negundo L. It is concluded that a combination of HPLC fingerprints and the amount ratios of the marker compounds of chaste berry preparations serves as a useful tool to evaluate the qualities of these preparations.

Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure-activity relationship.[Pubmed:26560048]

Eur J Med Chem. 2016 Jan 1;107:1-11.

The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, reserpine, seseberecine and fascaplysin as P-gp inducers. Fascaplysin (6a), a marine-derived bis-indole alkaloid, was the most potent among all of them, showing induction of P-gp with EC50 value of 25 nM. P-gp induction is one of the recently targeted strategy to increase amyloid-beta clearance from Alzheimer brains. Thus, we pursued a medicinal chemistry of fascaplysin to establish its structure-activity relationship for P-gp induction activity. Four series of analogs viz. substituted quaternary fascaplysin analogs, D-ring opened quaternary analogs, D-ring opened non-quaternary analogs, and beta-carbolinium analogs were synthesized and screened for P-gp induction activity. Among the total of 48 analogs screened, only quaternary nitrogen containing analogs 6a-g and 10a, 10h-l displayed promising P-gp induction activity; whereas non-planar non-quaternary analogs 9a-m, 13a-n, 15a-h were devoid of this activity. The P-gp induction activity of best compounds was then confirmed by western-blot analysis, which indicated that fascaplysin (6a) along with 4,5-difluoro analog of fascaplysin 6f and D-ring opened analog 10j displayed 4-8 fold increase in P-gp expression in LS-180 cells at 1 muM. Additionally, compounds 6a and 6f also showed inhibition of acetylcholinestease (AChE), an enzyme responsible for neuronal loss in Alzheimer's disease. Thus, fascaplysin and its analogs showing promising P-gp induction along with AChE inhibition at 1 muM, with good safety window (LS-180: IC50 > 10 muM, hGF: 4 muM), clearly indicates their promise for development as an anti-Alzheimer agent.