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

Wing Lam, Yongshen Ren, Fulan Guan, Zaoli Jiang, William Cheng, Chang-Hua Xu, Shwu-Huey Liu, Yung-Chi Cheng, Wing Lam, Yongshen Ren, Fulan Guan, Zaoli Jiang, William Cheng, Chang-Hua Xu, Shwu-Huey Liu, Yung-Chi Cheng

Abstract

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.

Keywords: Chinese medicine; YIV-906; chemical fingerprint; herbal products; mechanism; quality control.

Figures

FIGURE 1
FIGURE 1
Comparison between in vivo activities among different batches of YIV-906 and HQT which is commercial Huang Qin Tang. (A,B). Effect of YIV-906-10 (A,B) and HQT-F (C,D) on the anti-tumor activity of CPT11 and body weight protection of BDF1 bearing colon 38 tumor. (E) Summary of the effect of YIV-906 and HQT on the anti-tumor activity of CPT11 and body weight protection of BDF1 bearing colon 38 tumor. Details of experimental procedures are given in Section “Materials and Methods.”
FIGURE 2
FIGURE 2
Chemical fingerprint analysis among different batches of YIV-906 and HQT which is commercial Huang Qin Tang. (A) Alignment of chemicals detected in LC-MS for YIV-906 and HQT which is commercial Huang Qin Tang. (B) Correlation analysis of chemical profiles of YIV-906 and HQT where 1 represents exactly the same and 0 is totally different. Details of experimental procedures are given in Section “Materials and Methods.”
FIGURE 3
FIGURE 3
Signal transduction activity response analysis among different batches of YIV-906 and HQT which is commercial Huang Qin Tang. (A) Effect of different batches of YIV-906 and HQT on signal transduction activity response using different luciferase reporter cell lines and enzyme assays. (B) Correlation analysis of the signal transduction activity response for YIV-906 and HQT where 1 represents exactly the same and 0 is totally different. Details of experimental procedures are given in Section “Materials and Methods.”

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Source: PubMed

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