Mechanism Based Quality Control (MBQC) of Herbal Products: A Case Study YIV-906 (PHY906).

YIV-906 (PHY906), a four-herb Chinese medicine formulation, is inspired by an 1800 year-old Chinese formulation called Huang Qin Tang which is traditionally used to treat gastrointestinal (GI) symptoms. In animal studies, it could enhance anti-tumor activity of different classes of anticancer agents and promote faster recovery of the damaged intestines following irinotecan or radiation treatment. Several clinical studies have shown that YIV-906 had the potential to increase the therapeutic index of cancer treatments (chemotherapy, radiation) by prolonging life and improving patient quality of life. Results of animal studies demonstrated five clinical batches of YIV-906 had very similar in vivo activities (protection of body weight loss induced by CPT11 and enhancement of anti-tumor activity of CPT11) while four batches of commercial-made Huang Qin Tang, HQT had no or lower in vivo activities. Two quality control platforms were used to correlate the biological activity between YIV906 and HQT. Chemical profiles (using analysis of 77 peaks intensities) obtained from LC-MS could not be used to differentiate YIV-906 from commercial Huang Qin Tang. A mechanism based quality control (MBQC) platform, comprising 18 luciferase reporter cell lines and two enzymatic assays based on the mechanism action of YIV-906, could be used to differentiate YIV-906 from commercial Huang Qin Tang. Results of MBQC could be matched to their in vivo activities on irinotecan. In conclusion, the quality control of an herbal product should be dependent on its pharmacological usage. For its specific usage appropriate biological assays based on its mechanism action should be developed for QC. Chemical fingerprints comparison approach has limitations unless irrelevant chemicals have been filtered out. Additionally, using a similarity index is only useful when relevant information is used. A MBQC platform should also be applied on other herbal products.

[Study on Dendrobium loddigesii Rolfes from different regions and harvest periods by FTIR].

Infrared Spectroscopy (IR) integrated with two dimensional correlation infrared spectroscopy (2DCOS IR) was employed to rapidly discriminate Dendrobium loddigesii Rolfes (DR) from different regions and harvesting periods. The results showed that the IR peaks around 1 035, 1 051, 1 078, 1 156, 1 500, 1 511 and 1 736 cm-1had perceptible differences among DRs from different regions, indicating that different DRs containing remarkable different compositions and contents of polysaccharides, ketones and esters. 2DCOS IR spectra of DRs from Vietnam, Yunnan, Guangxi, Guizhou each had seven, eight, eight, nine auto peaks, respectively; furthermore, DRs from Guagnxi had the strongest peak in 1 220 cm-1, which was distinguish to those of other DRs (980 cm -1). In the IR spectra of DRs from different harvest seasons, the wave number of key peaks in (1 034 approximately1 023)cm- 1, the wave number of minor peaks in (1 6174)cm-1, as well as the presence of peaks in 1 078(1 076, 1 079)cm-1, showed obvious periodic changes with the seasons, which indicated the accumulation of polysaccharides and ketones from DRs displayed an evident periodic variability discipline. The application of FTIR in DRs could facilitate acquiring their growth conditions, composition and content changes, which would be significant in rational exploitations and utilizations of DR

Unveiling ontogenesis of herbal medicine in plant chemical profiles by infrared macro-fingerprinting.

Given that harvesting time has a great impact on the quality of herbal medicine, knowing the ontogenesis in the chemical profile aspect is essential to determine the optimal harvesting season. A high-throughput and versatile approach (herbal infrared macro-fingerprinting) harmonizing with the character of herbal medicine and providing the whole chemical profile (entirety), group analogues (part), and single compounds (major components) is developed to rapidly disclose the variation rule of the full chemical profile of herbal medicine over a growing season without extraction pretreatments, and thus to determine the optimal harvesting period in respect to groups of chemical compounds using Scutellaria baicalensis as a demonstration. IR macro-fingerprints of Scutellaria baicalensis harvested in the same period have a high similarity (> 0.91) despite small variations, suggesting that IR macro-fingerprinting can faithfully reflect the spectacle of "disordered order" in nature. From Year-1 spring to Year-3 autumn, general contents (%, w/w) of total flavonoids fluctuate up and down with a maximum value in Year-2 spring, and that of saccharides is relatively stable except for the attenuation from Year-2 autumn to Year-3 spring. From Year-1 autumn to Year-2 spring, flavonoid aglycones initially produced in Scutellaria baicalensis are extensively transformed to responding flavonoid glycosides. From Year-2 spring to Year-3 autumn, flavonoid glycosides are converted back to their corresponding aglycones. The best seasons for collecting Scutellaria baicalensis with a high content of flavonoid glycosides and aglycones would be Year-2 spring and Year-3 spring, respectively.

Pharmacokinetic comparisons of two different combinations of Shaoyao-Gancao Decoction in rats: competing mechanisms between paeoniflorin and glycyrrhetinic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao-Gancao Decoction (SGD), a well-known traditional Chinese medicine prescription, is a combination of Radix Paeoniae Alba (Paeonia lactiflora Pall, root) and Glycyrrhizae uralensis (Glycyrrhiza uralensis Fisch., root and rhizome, honeyed) for spasmolysis and emergency pain relief. Paeoniflorin (PF) and glycyrrhetinic acid (GA) are two typical active components of SGD for pain relief. AIM OF THE STUDY: To study comparative pharmacokinetics of ten bioactive compounds in SGDs with two different combinations of RP and GU, and therefore to investigate the herb-herb interaction mechanisms of Shaoyao-Gancao Decoction for better spasmolysis and emergency pain relief in rats. MATERIALS AND METHODS: Herbal IR macro-fingerprinting was implemented to provide the full chemical fingerprints of RP, GU and SGD decoctions and to investigate the variation rule of the full chemical profile of SGDs with various combinations of RP and GU. A specifically developed HPLC-MS/MS assay coupled with protein precipitation method was employed to determine the plasma concentrations of the ten analytes. Male Wistar rats were orally administered with SGD1 (RP:GU, 1:1 (w/w)) and SGD2 ((RP:GU, 4:1 (w/w)) equivalent to 9.5 g/kg body weight of GU. RESULTS: Full chemical fingerprints of RP, GU and SGDs with various combinations of RP and GU were provided in the form of IR macro-fingerprints. Except for liquiritin, there were statistically significant differences (p<0.05 or p<0.01) of these analytes between SGD1 and SGD2 in in vivo pharmacokinetic study. Compared with the results when oral administrated with SGD1, six glycosides (PF, albiflorin, oxypaeoniflorin, isoliquiritin, ononin, and glycyrrhizin) exhibited higher systematic exposure levels (AUC0-t) and slower elimination rates (CL) whereas two glycones (GA and isoliquiritigenin) were the reverse when administrated with SGD2. CONCLUSIONS: Increasing the amount of RP attenuated the inhibitory effect of GA via competing being consumed by intestinal bacteria (or ß-glucosidase) to reduce the conversion amount of glycyrrhizin to GA and subsequently to afford significantly higher bioavailability and longer efficacy of PF, glycyrrhizin, albiflorin, oxypaeoniflorin, isoliquiritin, and ononin, leading to better spasmolysis and emergency pain relief.

[Discrimination of eleven genera of Chinese herbs in Geraniaceae by FTIR spectroscopy and clustering analysis].

A fast identification method of eleven genera of Chinese herbs in Geraniaceae was developed by the combination of Fourier transform infrared spectroscopy with clustering analysis. FTIR spectroscopy was employed to identify and analyze eleven genera of Chinese herbs in Geraniaceae. On the basis of a principal component analysis (PCA) model, three genera of Chinese herbs were rapidly classified by using the method of SIMCA clustering analysis. These samples could be successfully classified by SIMCA. Recognition rate and rejection rate reached up to 98%. The accuracy of clustering reached up to 91% during blind sample testing. It is concluded that in combination with clustering analysis, FTIR method provides an effective way to rapidly evaluate Chinese herbs in Geraniaceae.

[Analysis and identification of Geranium by two-dimensional correlation infrared spectroscopy].

Tri-step infrared spectroscopy (Fourier transform infrared spectroscopy (FTIR) combined with second derivative spectra and two-dimensional correlation infrared spectroscopy (2D-COS)) was employed to identify and analyze the main components of Heilongjiang (HLJG), Jilin (JLG), Liaoning (LNG) genuine Herba Geranium. The emergence of several characteristic absorption peaks of tannins including 1 730 and 1 337 cm(-1) and peaks around 1 618 and 1 318 cm(-1) belonging to calcium oxalate suggested that Herba Geranii contained tannins and calcium oxalate. Differences near 1 370 and 1 230 cm(-1) were found among the three Herba Geranii. In light of second derivative spectra, four more peaks of tannin components around 1 509, 1 204, 764 and 763 cm(-1) and evident differences around C=O stretching bands (1 750-1 600 cm(-1)) were observed. By 2D-COS spectra with further improved resolution, the three genuine Geraniums were visually distinguished due to their significant differences in auto-peak profile. HLJG has 7 auto peaks with a strongest peak around 1 621 cm(-1), while JLG and LNG both have only 4 auto peaks with a strongest peak around 1 580 and 1 659 cm(-1), respectively. It was demonstrated that the Tri-step infrared spectroscopy was successfully applied to fast analyze and identify genuine Geraniums from different geographical regions and subsequently would be applicable to the study of Chinese medicinal resources and quality standards.

[Study on extracts of active substances from larch bark by FTIR spectroscopy].

The present study is to compare and analyze extracts of active substances from larch bark using ultrasonic wave quickly and undamagedly via Fourier transform infrared spectroscopy, second derivative IR spectroscopy and two dimensional spectroscopy. In the spectra of active substances from larch bark, there are four main components as the structural unit, and (+)-catechin, (-)-epicatechin, gallic acid and vitisinol represented a series of poly polyphenolic compounds. Furthermore the linkage between unit in proanthocyanidins dimmers was confirmed at position C(4)-C(8). Through observing the second derivative IR spectra of active substances from larch bark, the absorption peaks, 1 631, 1 561 and 1 469 cm(-1) of active substances moved to the smaller wave number direction, while 1 606, 1 385, 1 285 and 1 157 cm(-1) of active substances moved to the bigger wave number direction, and the intensity of characteristic peaks can represent the content of corresponding compound. In the two dimensional spectra, the active substances from larch bark have five automatic peaks in 1 345-1 675 cm(-1). The authors developed the new method to analyse and evaluate the active substances from larch bark successfully.

Discrimination of different genuine Danshen and their extracts by Fourier transform infrared spectroscopy combined with two-dimensional correlation infrared spectroscopy.

In this study, six varieties of Danshen from different populations and genuine ("Daodi" in Chinese transliteration) regions were discriminated and identified by a three-step infrared spectroscopy method (Fourier transform-infrared spectroscopy (FT-IR) coupled with second derivative infrared spectroscopy (SD-IR) and two dimensional correlation infrared spectroscopy (2D-IR)). Though only small differences were found among the FT-IR spectra of the six Danshen samples, the positions and intensities of peaks at 3393, 3371, 1613, 1050, and 1,036 cm(-1) could be considered as the key factors to discriminate them. More significant differences were exhibited in their SD-IR, particularly for the peaks around 1080, 1144, 695, 665, 800, 1610, 1510, 1450, 1117 and 1,077 cm(-1). The visual 2D-IR spectra provided dynamic chemical structure information of the six Danshen samples with presenting different particular auto-peak clusters, respectively. Moreover, the contents of salvianolic acid B in all samples were measured quantitatively by a validated ultra performance liquid chromatography (UPLC), which was consistent with the FT-IR findings. This study provides a promising method for characteristics and quality control of the complicated and extremely similar herbal medicine like Danshen, which is more cost effective and time saving.

[Analysis of alcoholic extracts of Cistanche deserticola by tri-step identification of Fourier transform infrared spectroscopy].

Tri-step identification of Fourier transform infrared spectroscopy (FTIR) integrated with second derivative spectroscopy and two dimensional correlation infrared spectroscopy (2D-IR) were applied to analyze and evaluate the alcoholic extracts and corresponding residues of cistanche deserticola from the surface to what lies behind. It was found that active compounds including phenylethanoid glycosides were enriched effectively after alcoholic extraction and the extract by using 70% of alcohol had the highest concentration compared to the others. The technique of the tri-step identification holistically disclosed the profile of active compounds in cistanche deserticola extracted by a series of concentrations of ethanol and validated the rationality of the traditional alcoholic extraction method. It not only could be used in monitoring the process of the alcoholic extraction and the compositions of the extracts and residues, discriminating micro-differences among them, but also could provide a macroscopic guidance for medicinal and pharmacological studies.