an-improved-technique-for-trimethylamine-detection-animal-derived

An Improved Technique for Trimethylamine Detection in Animal-Derived Medicine by Headspace Gas Chromatography-Tandem Quadrupole Mass Spectrometry

Animal-derived medicines have distinctive characteristics and significant curative effects, but most of them have an obvious fishy odor, resulting in the ...

Chengdu University of Traditional Chinese Medicine

 is a famous herbal formula originated in Asia and is popular in America. Due to the high abundance of polyphenols, its oral liquid is unstable and easy to cause precipitate, which results in the loss of activities. However, complex composition and unclear precipitation mechanism hinders the improvement of stability. In this study, the accumulation of precipitation in the storage and its effect on activity were investigated. Then, an integrated chain of evidence was proposed based on the physical phase, chemical profile, and sediment elements. The results showed that antioxidant activity decreased from  115 to 146 μl before and after 90 days of storage, and the anti-fatigue activity decreased from 30.54 to 28.47 min. Turbiscan Lab Expert observed that particle size increased from 106 to 122 nm, and the turbiscan stability index increased from 0 to 14, which indicated that its stability is continuously decreasing. High performance liquid chromatography (HPLC) fingerprint coupled with multivariate statistical analysis identified that these chemical markers changed significantly, such as gallic acid, catechins, and ellagic acid. Loss of catechins tends to be involved in the formation of phlobaphene precipitation. The fact that the new-born ellagic acid in precipitation (0.47 mg/ml) is significantly higher than that reduced in solution (0.25 mg/ml) indicates that it is not only derived from colloid aging. Microscopic observation combined with energy spectrum analysis further confirmed the existence of the multi-precipitates. The crystalline precipitate is ellagic acid, and the other is phlobaphene. In conclusion, based on the evidence chain analysis, this study revealed a systematic change of the whole polyphenol solution system. It provides a novel perspective to understand the sedimentation formation of polyphenol solution, which is an important theoretical contribution to the preparation of polyphenol solutions.

Exploration on the Approaches of Diverse Sedimentations in Polyphenol Solutions: An Integrated Chain of Evidence Based on the Physical Phase, Chemical Profile, and Sediment Elements.

It is a challenging task to suppress the bitterness of liquid preparations, especially for children. Bitter molecules are highly dispersible in liquids, leading to a strong and instant stimulation of the bitter receptors. At present, there is no effective way to correct this issue except for adding sweeteners, resulting in an unsatisfying taste. Based on the three-point contact theory, which is a universally accepted mechanism of bitterness formation, a new idea and application of amphiphilic block copolymers (ABCs) for bitterness suppression was proposed for the first time. We found that ABCs could widely inhibit the bitterness of four typical bitter substances. The mechanism is that ABCs self-assemble to form association colloids, which attract bitter components and reduce their distribution in the molecular form in solution. The bitter components were demonstrated to automatically embed in the spiral hydrophobic cavity of the hydrophobic chain of the ABCs, and their special interaction dispersed the positive electrostatic potential of bitter groups. The combination did not affect the pharmacokinetic parameters and pharmacodynamics of bitter drugs. These findings highlight the novel application of ABCs for the inhibition of bitterness and illuminate the underlying inhibition mechanisms.

Amphiphilic Block Copolymers: A Novel Substance for Bitter-Masking in Aqueous Solutions.

The iterative innovation of processing technology is one of the important tasks in studies on processing of traditional Chinese medicine(TCM). It is also the prerequisite for modern, refined, automatic and intelligent manufacturing of TCM pieces. Microwave processing is a new fire processing technique developed in the recent 30 years, with a unique thermodynamic form, and energy transfer and transformation laws. Moreover, it owns the advantages of a high processing efficiency, good product properties and low production energy consumption, with great application prospects. This paper introduced the study overview of microwave expansion technology in the food industry, reviewed the origin of microwave processing technology of TCM, and expounded the basic concept, principle and main purpose of microwave processing technology used in TCM. Then, the impacts of drug factors and microwave factors on the microwave processing effect were summarized, the industrial equipment that could be used for microwave processing was listed, and the impacts of microwave heating on starch, polysaccharide, protein and other components in Chinese herbal medicines were analyzed. Furthermore, the study advance of microwave processing of 14 herbs was investigated, including Aconiti Lateralis Radix Praeparaia, Galli Gigerii Endothelium Corneum and Asini Corii Colla; and the appearance and components of herbs processed by traditional processing method and microwave processing method were compared, so as to reveal the opportunities and challenges of microwave processing technology in the industrial transformation. We hoped that the systematic study of microwave processing technology could provide new ideas and techniques for the high-quality and high-level development of the TCM pieces industry in the new era, and promote its inheritance, innovation and transformation.

[Study advances of microwave processing technology in traditional Chinese medicine].

Animal medicines have been called &quot;medicine with affinity to flesh and blood&quot; by doctors of all ages, which always act as an important branch of Chinese medicine. They have various types, extensive sources and long application history, with unique cli-nical effects in anti-coagulation, anti-thrombosis, anti-fatigue, immune regulation, anti-tumor, anti-convulsion and so on. Most animal medicines contain proteins, fatty acids, and trimethylamine oxides, which are prone to decomposition and produce substances such as biological amines, aldehydes, ketones, alcohols, trimethylamine and ammonia with unpleasant odors. The stench produced by the combination of various odors can easily cause side effects such as nausea and vomiting, which would probably affect the drug compliance and clinical efficacy in patients, and block the development of high-quality animal medicines. At present, we have insufficient understanding on sources and formation mechanism of the stench of animal medicines, lacking development of taste-masking technology. Therefore, the universality, formation, vomiting mechanism, evaluation methods, and masking technology of stench of animal medicines were summarized in this paper, so as to deepen the recognition of stench, provide references for the development of animal medicines deodorization technology, enhance patients' compliance with animal medicines, and promote animal drugs to better serve public health in the new era.

[Progress on formation and taste-masking technology of stench of animal medicines].

Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.

[Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA].

Breast cancer is a major chronic disease threatening women's health. It has topped the global cancers as the diagnosed cases outnumbered lung cancer patients in 2020. Internal damage due to the seven emotions is an important cause of breast cancer and the disorders of hypothalamic-pituitary-adrenal(HPA) axis and endocrine system and the abnormal immune defense mechanism in response to psychological stress all affect the occurrence and development of breast cancer. It is noteworthy that the theory of seven emotions in traditional Chinese medicine and the psychological stress theory of modern medicine have something in common in some aspects. Therefore, this study explored the correlation between internal damage due to the seven emotions and psychological stress and analyzed the molecular biological mechanisms of psychological stress influencing breast cancer from the perspective of modern medicine, which is helpful to reasonably prevent breast cancer and other related tumors and improve the prognosis of breast cancer patients through emotion regulation.

[Correlation between internal damage due to seven emotions in traditional Chinese medicine and pathogenesis of breast cancer from perspective of psychological stress].

The American cockroach (Periplaneta americana L.) belongs to the family Blattidae, order Blattodea, and class Insecta. Its medicinal history in China spans thousands of years. In recent years, the anti-tumour activity of American cockroach has gradually attracted the attention of researchers and has a good application prospect in the treatment of tumours. Periplaneta americana has been found to contain proteins, peptides, amino acids and nucleosides. Pharmacological studies have shown that P. americana has anti-tumour, tissue repair, immunoregulatory and other activities. In this study, we investigated the chemical composition and mechanism of action of its active site against hepatocellular carcinoma.

The inhibitory effect of Periplaneta americana L. on hepatocellular carcinoma: Explore the anti-hepatocellular carcinoma active site and its mechanism of action.

Suppressing the bitter taste of traditional Chinese medicine (TCM) largely has been a major clinical challenge due to complex and diverse metabolites and high dispersion of bitter metabolites in liquid preparations. In this work, we developed a novel strategy for recognizing bitter substances, hiding their bitter taste, and elucidated the mechanism of flavor masking in TCM. Huanglian Jie-Du Decoction (HLJDD) with an intense bitter taste was studied as a typical case. UHPLC-MS/MS was used to analyze the chemical components in HLJDD, whereas the bitter substances were identified by pharmacophores. Additionally, the screening results of the pharmacophores were further validated by using experimental assays. The mask formula of HLJDD was effectively screened under the condition of clear bitter substances. Subsequently, computational chemistry, molecular docking, and infrared characterization (IR) techniques were then used to explicate the mechanism of flavor masking. Consequently, neotame, γ-CD, and mPEG-PLLA significantly reduced the bitterness of HLJDD. Specifically, mPEG-PLLA increased the colloid proportion in the decoction system and minimized the distribution of bitter components in the real solution. Sweetener neotame suppressed the perception of bitter taste and inhibited bitter taste receptor activation to eventually reduce the bitter taste. The γ-CD included in the decoction bound the hydrophobic groups of the bitter metabolites in real solution and "packed" all or part of the bitter metabolites into the "cavity". We established a novel approach for screening bitter substances in TCM by integrating virtual screening and experimental assays. Based on this strategy, the bitter taste masking of TCM was performed from three different aspects, namely, changing the drug phase state, component distribution, and interfering with bitter taste signal transduction. Collectively, the methods achieved a significant effect on bitter taste suppression and taste masking. Our findings will provide a novel strategy for masking the taste of TCM liquid preparation/decoction, which will in return help in improving the clinical efficacy of TCM.

New strategies for identifying and masking the bitter taste in traditional herbal medicines: The example of Huanglian Jiedu Decoction.

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.

[Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism].

Despite the distinctive characteristics and remarkable efficacy, animal medicine is stenchy, which decreases the comp-liance of patients. At the moment, the research on the method for deodorizing animal medicines lags behind. To be specific, the components related to the odor and the basic properties transformation of the components are unclear and there is a lack of specific deodorizing method. This study aims to clarify the main components related to the stench of animal medicine, such as aldehydes, amines, trimethylamines and sulfur compounds, and their basic properties, and to explore their metabolism and transformation in vivo and in vitro, which is expected to serve as a reference for the research on deodorization of animal medicine and development of new techniques.

Article	Year
Exploration on the Approaches of Diverse Sedimentations in Polyphenol Solutions: An Integrated Chain of Evidence Based on the Physical Phase, Chemical Profile, and Sediment Elements. Frontiers in pharmacology\| PubMed ID: 31619999	2019
Amphiphilic Block Copolymers: A Novel Substance for Bitter-Masking in Aqueous Solutions. Molecular pharmaceutics\| PubMed ID: 32186879	2020
[Study advances of microwave processing technology in traditional Chinese medicine]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 32495556	2020
[Progress on formation and taste-masking technology of stench of animal medicines]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 32495592	2020
[Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 32726021	2020
[Correlation between internal damage due to seven emotions in traditional Chinese medicine and pathogenesis of breast cancer from perspective of psychological stress]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 34994129	2021
The inhibitory effect of Periplaneta americana L. on hepatocellular carcinoma: Explore the anti-hepatocellular carcinoma active site and its mechanism of action. Journal of ethnopharmacology\| PubMed ID: 34999145	2022
New strategies for identifying and masking the bitter taste in traditional herbal medicines: The example of Huanglian Jiedu Decoction. Frontiers in pharmacology\| PubMed ID: 36060004	2022
[Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 36471956	2022
[Material basis of stench of animal medicine: a review]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 36471959	2022

Hongyan Ma

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