Volume 13,Issue 4,2021 Table of Contents

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  • 1  Surging cooperation with ASEAN countries on traditional medicine
    Guo De-an
    2021, 13(4):439-440. DOI: 10.1016/j.chmed.2021.09.007
    [Abstract](327) [HTML](0) [PDF 0.00 Byte](0)
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    In November 4th, 2002, China has signed the landmark agreement with Association of South East Asian Countries (ASEAN), dubbed “Framework Agreement on Comprehensive Economic Cooperation between The Peoples’ Republic of China and the Association of South East Asian Countries”, which signaled the economic and trade cooperation ushering in a brand new historic stage. In the wake of the Framework Agreement, the two sides initiated ensuing pivotal measure to hold the China ASEAN EXPO series which had been practicing for consecutive 18 years as the pragmatic step in a bid to further promote and strengthen the economic and trade development between the two parties. The corresponding effect is obviously remarkable. According to the statistics, the two sides have witnessed bilateral trade rocketing from 8.36 billion U.S. dollars in 1991, the year that China and ASEAN established dialogue relations, to 685.28 billion U.S. dollars in 2020, an increase of over 80 times. Just recently the 18th China-ASEAN Expo and China-ASEAN Business and Investment Summit opened in Nanning, the permanent venue of Expo and capital city of south China's Guangxi Zhuang Autonomous Region with Chinese President Xi Jinping’s congratulatory letter, which indicated the great success from series of operations in enhancing the bilateral ties. Along with the skyrocketing economic and trade development, one has also seen the booming in two sides’ cooperation on traditional medicine and herbal medicine, the area that China and ASEAN have communicated and exchanged with a long history and also reckoned as the significant part in traditional culture exchange between China and ASEAN countries. On top of the increasing concrete project collaborations, China ASEAN Forum on Traditional Medicine has also been annually hosted by the Guangxi local government as important sector of the Expo. Great progress in bilateral operation in the field of traditional and herbal medicines has been reached including the bilateral and multi-lateral collaborative centers of traditional medicine established between China and each member of ASEAN countries. Recently, both sides devoted the cooperation in traditional Chinese medicine (TCM) fighting against Covid-19 by donating TCM products to ASEAN countries and collaborating in screening of traditional medicines and compounds therefrom to fight against Covid-19 infections, which has yielded remarkable research progress from these close collaborations. RCEP is an organization initiated by 10 ASEAN countries in 2012, in which China, Japan, South Korea, Australia, New Zealand and India were invited to participate. There are 16 countries (10 ASEAN+6) for establishing a free trade agreement with a unified market of 16 countries by reducing tariff and non-tariff barriers. RCEP covers about 3.5 billion people, with a total GDP of US$ 23 trillion, accounting for one third of the global total. Because of its special geographical location and climatic conditions, its medicinal plant resources are abundant, and its traditional medicine has obvious advantages. Therefore, it is of far-reaching significance to analyze and study its traditional medicine resources and applications for the benefit of 16 countries. The Editorial Department of CHM organized this special issue according to the "Solvent Contributions Plan of Special Issue RCEP Traditional Medicine Research". Authors from RCEP countries and regions contributed the articles. In this special issue of RCEP Traditional Medicine Research dedicated to unearth the overall picture and progress made related to traditional medicine, 14 review or original research articles were collected to unleash the advancement in the traditional medicine research progress among the countries with same-rooted traditional medicine systems. These articles on basic research and applied development research provided useful information to readers and also will benefit the health of the people in the region and produce beneficial social and economic effects. In his review article, Prof. Chang-xiao Liu, the academician of Chinese Academy of Engineering and the honorary president of Tianjin Pharmaceutical Research Institutes, expounded in detail from five aspects to outline the general situation in traditional medicine development between China and ASEAN countries, including i) development basis of China ASEAN traditional medicine and herbal medicine, ii) development and efficacy of traditional medicine theory system, iii) industry development and regulation management of traditional medicine and herbal medicine products, iv) China-ASEAN traditional medicine exchanges and cooperation to promote traditional medicine cooperation and medicine trade, and v) strengthening academic and industrial cooperation and promoting the healthy development of traditional medicine and herbal medicine, respectively. From the points of geographical adjacency and cultural resemblance between China and ASEAN countries, Prof. Liu indicated that commonly shared culture and similar traditional medical systems formulated the basis for further development in the rising cooperation of traditional medicines. In addition, he also described the formation of each country’s traditional medicine theory system and the traditional and herbal medicine industry development plus the regulatory framework in China and each individual ASEAN country. The similarity, differences and even the restrictions among the theory systems and industrial developments were compared and highlighted. The research and cooperation progress in traditional and herbal medicines were individually summarized from each country’s perspective and some of the significant research achievements were exemplified with concrete case studies. He calls for strengthening the academic and industrial cooperation and promoting the healthy development in traditional medicine between China and ASEAN countries from the following respects. Firstly, research and development of traditional medicine products for treatment of Covid-19 should be highly addressed; secondly, research on the resources, medicinal values and application of traditional medicines ought be strengthened; thirdly, scientific research of traditional and herbal medicines should be reinforced and cooperation and sharing system should be established by taking advantage of modern technology like big data and artificial intelligence; fourthly, training of personnel in the areas of new methods and technology, new tools for probing medicinal value of traditional and herbal medicines is also the indispensable aspect. This review article will certainly facilitate the readers to navigate the current situation and future prospect in traditional medicine research between China and ASEAN countries. Other contributions to this special issue cover reviews or original research in the following areas including immuno-metabolism for treatment of rheumatoid arthritis, future development of good agricultural practice, comprehensive analysis of traditional Chinese medicine for treatment and prevention of Covid-19 infections, chemical and pharmacological research progress of some important southeast Asian important medicinal or edible plants, phytochemical analysis and efficacy study of medicinal herbs, and the like, which were contributed by quite diversified authors from Mainland China, Macau China, Japan, Korea, Malaysia, Thailand, Singapore, and Germany. Prof. Liang Liu, also a academician of Chinese Academy of Engineering and former president of Macau University of Science and Technology, together with his team, reviewed the pathological mechanism of rheumatoid arthritis (RA) and strategies to treat RA by applying traditional Chinese medicine and its natural compounds through targeting metabolic reprogramming of immune cells, and project them as a rich resource for providing the new potential paradigm for the treatment of RA. Prof. Jia-gang Deng and his team contributed three review articles with two focusing on the use of traditional Chinese medicine to prevent and treat Covid-19 diseases. In the article entitled “Analysis on Oral Medication Rules of Traditional Chinese Medicine Prescription for the Prevention of COVID-19”, they selected 157 commonly used anti-Covid-19 TCM prescriptions involving a total of 130 TCM herbs for manual screening through Excel and TCM inheritance assistant platform and summarized that the top five TCM herbs with the highest use frequency are Glycyrrhizae Radix et Rhizoma, Astragali Radix, Lonicerae Japonicae Flos, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix respectively. Based the above analysis, they concluded that the anti-Covid-19 TCMs mainly play the role by invigorating and tonifying qi (vital enegy), strengthening spleen, and eliminating dampness and heat according to Chinese medical terms. The contributors to this special issue from Malaysia, Thailand, Singapore, Japan and Korea mainly represented their research outcome dealing with antihypertensive, antioxidant and antiviral activity, anti-allergic contact dermatitis, signaling pathway regulation of local herbal medicines or edible fruit products. It is firmly believed that this special issue will provide valuable information to the readers and related parties on the recent research progress of traditional and herbal medicines among China, and ASEAN and RCEP countries. Due to the inseparable geographic relation and similarly-rooted culture in traditional medicines in the region, there is a nature-endowed advantage to closely cooperate on the research of traditional medicines under the established frameworks of China with ASEAN and RCEP countries. During the process, modern science and technology should be widely embraced to advance the scientific understanding of the theory and action mechanism of traditional medicine. It is anticipated that traditional medicine and herbal medicine would play much more significant role with more scientific understanding of its safety, efficacy, quality and mechanism to maintain and assuring the health of people in the geographical region and even entire mankind at large.
    2  Overview on development of ASEAN traditional and herbal medicines
    Chang-Xiao Liu
    2021, 13(4):441-450. DOI: 10.1016/j.chmed.2021.09.002
    [Abstract](240) [HTML](0) [PDF 0.00 Byte](0)
    Abstract:
    Traditional medicine is an important and often underestimated part of health services. In some countries, it has a long history of use in health maintenance and in disease prevention and treatment, particularly for disease. WHO has always emphasized the important role of traditional, complementary and alternative medicine in human healthcare. In this review article, author provided some information from the following five aspects: (1) Development basis of China ASEAN traditional medicine and herbal medicine; (2) The development and afficacy of traditional medicine theory system; (3) Industry development and regulation management of traditional medicine and herbal medicine products; (4) China-ASEAN traditional medicine exchanges and cooperation to promote traditional medicine cooperation and medicine trade, and (5) Strengthening academic and industrial cooperation and promoting the healthy development of traditional medicine and herbal medicine. It is believed that the information will have certain reference value for readers in studies on traditional and herbal medicines.
    3  Targeting immunometabolism by active ingredients derived from traditional Chinese medicines for treatment of rheumatoid arthritis
    Yu-fei He Chu-tian Mai Hu-dan Pan Liang Liu Hua Zhou Ying Xie
    2021, 13(4):451-460. DOI: 10.1016/j.chmed.2021.09.005
    [Abstract](663) [HTML](0) [PDF 0.00 Byte](0)
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    Rheumatoid arthritis (RA), the most common inflammatory arthropathy word wild, is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate. Metabolic mis-regulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction, while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA. Recently, natural active compounds from traditional Chinese medicines (TCMs) have potential therapeutic effects on RA and regulating immunometabolism. In this review, in addition to updating the connection between cellular metabolism and cell function in immune cells of RA, we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells, and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.
    4  Chemical constituents and pharmacological effects of durian shell in ASEAN countries: A review
    Yuan-fei Zhana b c d Xiao-tao Houa b c d e Li-li Fan a b c Zheng-cai Dub c d e Ch'ng Soo Eed f Ng Siok Mengg Khamphanh Thepkaysoned h Er-wei Hao b c d e Jia-gang Dengb c d e
    2021, 13(4):461-471. DOI: 10.1016/j.chmed.2021.10.001
    [Abstract](792) [HTML](0) [PDF 0.00 Byte](0)
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    Durio zibethnus is mainly distributed in Southeast Asia. Traditional Chinese medicine believes that durian shells have the effects of clearing heat and purging fire, nourishing yin and moisturizing dryness. Therefore, it is often used as a pharmaceutic food in the Chinese folk to assist treating diseases. At present, the chemical constituents isolated in durian shell include phenolic acids, phenolic glycosides, flavonoids, coumarins, triterpenes, simple glycosides and other compounds. Modern pharmacological studies show that durian shell has many pharmacological activities, such as antioxidant, anti-inflammatory, regulation of glucose and lipid metabolism. The chemical composition and pharmacological effects of durian shells are summarized in order to provide references for the further research and application of durian shell.
    5  Future development of Good Agricultural Practice in China under globalization of traditional herbal medicine trade
    Ru Zhanga Ming-xu Zhanga Yuan Chenf Cong-cong Wanga Chun-hong Zhanga c d Heidi Heubergerb Huan-ting Lia Min-hui Lia c d e f
    2021, 13(4):472-479. DOI: 10.1016/j.chmed.2021.09.010
    [Abstract](492) [HTML](0) [PDF 0.00 Byte](0)
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    Traditional herbal medicine (THM) is an important part of the traditional Chinese medicine culture. Due to its high medicinal potential, it should not only serve for the Chinese people's medical use, but also contribute to the world medicine, THM for the international market must be standardized and large-scale, and produced according to the “Good Agriculture Practice” (GAP). The quality of THM directly affects the patient's treatment status and safety of use. Therefore, the quality assurance of THM runs through the entire process of research and development, production and clinical practice. The standardized production and cultivation of THM is the starting point of the THM industry chain and plays a decisive role in the economic development of the THM industry. This article summarizes the development history, limitations and future development of GAP, and clarifies the opportunities for THM in the rapid development of the international and domestic Chinese medicine industry. In addition, analyzing the deficiencies that were existing in the former GAP implementation process and by suggesting science-based quality measures, it is hoped to stipulate improved GAP guidelines in the future and to lay the foundation for a modern THM international trade.
    6  Dihydrophenanthrenes from medicinal plants of Orchidaceae: A Review
    Jia-xin Qia Di Zhoua Wan-ru Jianga Gang Chena Wei Li b Ning Li a
    2021, 13(4):480-493. DOI: 10.1016/j.chmed.2021.10.004
    [Abstract](639) [HTML](0) [PDF 0.00 Byte](0)
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    The plants of Orchidaceae are widely distributed in the world, 47 species of which have been used as folk medicines with a long history. The tubers and stems of them exhibit diverse efficacy, including clearing heat and resolving toxin, moistening lung and relieving cough and promoting blood circulation. Since dihydrophenanthrenes were responsible for the medical purposes, the characteristic skeletons, pharmacological effects and clinical applications of dihydrophenanthrenes were summarized in this review, so as to provide a theoretical basis for the comprehensive study, development and application of DPs from medicinal plants of Orchidaceae.
    7  Antiviral medicinal plants found in Lanna traditional medicine
    Jakaphun Julsrigivala b c Panee Sirisa-ardc Sarinya Julsrigivald Nararat Akarchariyac
    2021, 13(4):494-501. DOI: 10.1016/j.chmed.2021.09.006
    [Abstract](722) [HTML](0) [PDF 0.00 Byte](0)
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    Traditional medicine uses a multitude of plants to create medicinal formulations, some of which show antiviral properties that may be of benefit in treating emerging viral diseases, including Covid-19. Lanna, an ancient Kingdom in northern Thailand, with a thriving culture that continues to this day and has a rich history of traditional medicine using local plants that is still practiced today. To find potential antiviral medicinal candidates, we examined ancient manuscripts, interviewed traditional healers practicing today, and inventoried current traditional medicines to catalogue 1400 medicinal formulations used in Lanna traditional medicine. We then narrowed this list to find those traditionally used to treat diseases that in their original use and descriptions most likely map to those we know today to be viral diseases. We identified the plants used in these formulations to create a list of 64 potential antiviral herbal candidates drawn from this ancient Lanna wisdom and matched these to the scientific literature to see which of these plants had already been shown to possess antiviral properties, generating a list of 64 potential antiviral medicinal candidates from Lanna traditional medicine worth further investigation for treating emerging viral diseases.
    8  Analysis on oral medication rules of traditional Chinese medicine prescriptions for prevention of COVID-19
    Dong-yang Wu Zhong-shang Xia Xiao-tao Hou Er-wei Hao Jin-ling Xie Jing-yan Liang Qiu-ming Liang Zheng-cai Du Jia-gang Deng
    2021, 13(4):502-517. DOI: 10.1016/j.chmed.2021.10.007
    [Abstract](435) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: To analyze the medication rules of traditional Chinese medicine (TCM) oral prescriptions for the prevention of COVID-19. Methods: The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, and medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication. Results: The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi-tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional?Chinese?Medicinal?Materials, Traditional?Chinese?Medicinal?Materials for Health Food, and New Resources of Food published by National Health Commission of the People’s Republic of China, there are 35 species belonging to the group of edible traditional?Chinese?medicinal?materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional?Chinese?medicinal?materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic traditional Chinese medicines. Conclusion: We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of "Preventive Treatment of Disease" was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special?attention?should be?paid?to their safety in clinical application.
    9  Analysis on application law of dampness-removing Chinese medicine in treatment of coronavirus disease 2019
    Er-wei Haoa b c Zi-xia Sua b c Yan-ling Gongd Zheng-cai Dua b c Xue Yanga b c Chun-tao Huanga b c Xiao-tao Houa b c Jia-gang Denga b c
    2021, 13(4):518-524. DOI: 10.1016/j.chmed.2021.09.011
    [Abstract](383) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: Coronavirus Disease 2019 (COVID-19) has been diagnosed as an epidemic disease characterized by cold and dampness pathogens in TCM clinic. Due to many Chinese medicines with different functions were used in the treatment of COVID-19, it is very important to find the law of application of damp-removing Chinese medicine with high frequency application, with view to providing a reference for the use and research of Chinese medicine to further control the pandemic. Methods: The publicly released diagnosis and treatment programs issued by the National Health Commission and Health Commission of provinces, autonomous regions and municipalities, and Chinese herbs prescription information in these were collected, a database was established, and Excel and Graphpad 8.0 software were used to analyze the frequency of use of various Chinese medicines, the frequency and property characters including five flavors (bitter, pungent, sweet, sour, and salty) and four qi (warm, hot, cool, and cold) and channel tropisms of Chinese medicine for removing dampness. Results: A total of 137 prescriptions of Chinese medicine for treating COVID-19 were collected, including 178 TCMs showing functions of resolving phlegm, relieving cough and asthma, resolving dampness, clearing damp and inducing dieresis, clearing heat, tonifying deficiency, and relieving exterior syndrome, in which the TCMs with the first four functions that we called the removing-dampness TCMs, accounted for 35.78%. Also a number of TCMs in the rest functions showed removing-dampness. The first four functions were divided into subfunctions including aromatic resolving?dampness, clearing heat and drying dampness, drying dampness and tonifying spleen qi, drying dampness and removing phlegm, inducing diuresis and relieving swelling, inducing diuresis and relieving exterior syndrome. Among them, the most frequently used TCMs was Ephedrae Herba, followed by Citri Reticulatae Pericarpium, Pogostemonis Herba, Pinelliae Rhizoma, Poria, Scutellariae Radix, and Atractylodis Rhizoma. The property character analysis in the removing-dampness TCMs showed that bitter and pungent were largely present and sour and astringent were absent, warm and hot were dominant; And the lung, spleen, stomach, large intestine, bladder were main channel tropisms. Conclusion: This study may provide meaningful and useful information on further research to investigate the effective compounds from the dampness-removing Chinese medicine with high frequency application, and also provide a reference for the clinical treatment of COVID-19 accurately against dampness evil with dampness-removing Chinese medicine.
    10  Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer
    Wei Zhou a Min Dong b Hao Wu c Hui-lin Lia Jia-le Xiea Ru-yun Maa Wei-wei Suc Jian-ye Daia
    2021, 13(4):525-533. DOI: 10.1016/j.chmed.2021.08.005
    [Abstract](389) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: “Same treatment for different diseases” is a unique treatment strategy in traditional Chinese medicine. Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease (COPD) and lung cancer. Citrus Grandis Exocarpium (Huajuhong in Chinese, HJH), a famous herbal, is always applied by Chinese medicine practitioners to dispersion the lung toresolve phlegm based on “syndrome differentiation and treatment” theory. However, the common mechanism for HJH’s treatment of COPD and lung cancer is not clear. Methods: In this study, based on network pharmacology and molecular docking technology, the common mechanism of HJH in the treatment of COPD and lung cancer was studied. The active ingredients and related targets of HJH were integrated from TCMSP, BATMAN-TAM, STP, and Pubchem databases. The standard names of these targets were united by UniProt database. Targets of COPD and lung cancer were enriched through GeneCards, NCBI (Gene), Therapeutic Target Database, and DisGeNET (v7.0) databases. Then the intersection targets of HJH and diseases were obtained. The STRING network and the Cytoscape 3.7.2 were used to construct PPI network, the DAVID database was used to perform GO and KEGG analysis. Then Cytoscape 3.6.1 was used to build “ingredient-target-signal pathway” network. Finally, AutoDock 1.5.6 software was used to perform molecular docking of key proteins and molecules. Results: Eleven active ingredients in HJH were obtained by searching the database, corresponding to 184 HJH-COPD-lung cancer targets intersection. The results of biological network analysis showed that naringenin, the active component in HJH, could mainly act on target proteins such as AKT1, EGFR. Then through positive regulation of vasoconstriction and other biological processes, naringenin could regulate estrogen signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer. Conclusion: Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer. And then, the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described. Furthermore, naringenin was proved to strongly bind with AKT1 and EGFR. It may provide the scientific basis for understanding the “Same treatment for different diseases” strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD, lung cancer and other malignant lung diseases.
    11  High water-soluble curcuminoids-rich extract regulates osteogenic differentiation of MC3T3-E1 cells: Involvement of Wnt/β-catenin and BMP signaling pathway
    Yutthana Pengjama Nurul Syazwanib Jakkapong Inchaia Amornkan Numita Thanintorn Yodthongc Thanawat Pitakpornpreechac Pharkphoom Panichayupakaranantb
    2021, 13(4):534-540. DOI: 10.1016/j.chmed.2021.01.003
    [Abstract](134) [HTML](0) [PDF 0.00 Byte](0)
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    Objective The present study aimed to evaluate the effect of a high water-soluble curcuminoids-rich extract (CRE) in a solid dispersion form (CRE-SD) using polyvinylpyrrolidone K30 on osteogenic induction of MC3T3-E1 cells. Methods CRE was pre-purified using a microwave assisted extraction couple with a Diaion? HP-20 column chromatography. The osteoblastic cell proliferation and differentiation potentials of CRE-SD in MC3T3-E1 cells were tested by cell viability, alkaline phosphatase (ALP) activity, and Alizarin red S activity assays. The mRNA expressions of osteoblast-specific genes and underline mechanisms were assessed by a real time PCR and western blot analysis. Results CRE-SD 50 μg/mL increased alkaline phosphatase (ALP) activity, an early differentiation marker of osteoblasts in both MC3T3-E1 cells and non-osteogenic mouse pluripotent cell line, C3H10T1/2, indicating the action of CRE-SD was not cell-type specific. Alizarin red S activity showed a significant amount of calcium deposition in cells treated with CRE-SD. CRE-SD also upregulated the mRNA expression levels of transcription factors that favor osteoblast differentiation including Bmp-2, Runx2 and Collagen 1a, in a dose dependent manner. Western blot analysis revealed that noggin attenuated CRE-SD-promoted expressions of Bmp-2 and Runx2 proteins. siRNA mediated blocking of Wnt/β-catenin signaling pathway also annulled the influence of CRE-SD, indicating Wnt/β-catenin dependent activity. Inhibition of the different signaling pathways abolished the influence of CRE-SD on ALP activity, confirming that CRE-SD induced MC3T3-E1 cells into osteoblasts through Wnt/β-catenin and BMP signaling pathway. Conclusion These results collectively demonstrate that CRE-SD may be a potential therapeutic agent for the treatment of osteoporosis.
    12  In vitro and in vivo antihypertensive and antioxidant activities of fermented roots of Allium hookeri
    Tao Tonga Yanan Wanga Cheng-Mei Zhangb Seong-Gook Kangc
    2021, 13(4):541-548. DOI: 10.1016/j.chmed.2021.08.003
    [Abstract](356) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: To evaluate antihypertensive and antioxidant activities of Allium hookeri root (AHR) fermented with Lactobacillus plantarum, Leuconostoc mesenteroides, and Weissella cibaria. Methods: The novel fermented AHR products using L. plantarum, L. mesenteroides, and W. cibaria were developed and ACE inhibitory activity, DPPH radical scavenging activity, hydroxyl radical scavenging activity, superoxide anion radical scavenging activity, total phenolic content, and total thiosulfinate content were determined. The antihypertensive and antioxidant effects of fermented AHR were further investigated in spontaneously hypertensive rats (SHRs). Results: Administration of fermented AHR to SHRs had an attenuating effect on both diastolic and systolic blood pressure. The SHRs treated with fermented AHR showed lower plasma ACE activity and higher plasma NO levels. Furthermore, fermented AHR administration led to parallel improvements in plasma oxidative stress biomarkers in SHRs. Conclusion: Our results highlight the potential usefulness of fermented AHR for the prevention of hypertension.
    13  Combined enzymatic hydrolysis and herbal extracts fortification to boost in vitro antioxidant activity of edible bird’s nest solution
    Pei Ling Tanga Hooi Shin Goha Swee Seng Siab
    2021, 13(4):549-555. DOI: 10.1016/j.chmed.2021.10.005
    [Abstract](485) [HTML](0) [PDF 0.00 Byte](0)
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    Objective Edible bird’s nest (EBN) is a popular traditional tonic food in Chinese population for centuries. Malaysia is one of the main EBN suppliers in the world. This study aims to explore the best strategy to boost the antioxidant potential of EBN solution. Methods In this study, the raw EBN (4%, mass to volume ratio) was initially enzymatic hydrolyzed using papain enzyme to produce EBN hydrolysate (EBNH), then spray-dried into powdered form. Next, 4% (mass to volume ratio) of EBNH powder was dissolved in ginger extract (GE), mulberry leaf extract (MLE) and cinnamon twig extract (CTE) to detect the changes of antioxidant activities, respectively. Results Results obtained suggest that enzymatic hydrolysis significantly reduced the viscosity of 4% EBN solution from (68.12 ± 0.69) mPa.s to (7.84 ± 0.31) mPa.s. Besides, the total phenolic content (TPC), total flavonoid content (TFC), total soluble protein, DPPH scavenging activity and ferric reducing antioxidant power (FRAP) were substantially increased following EBN hydrolysis using papain enzyme. In addition, fortification with GE, MLE and CTE had further improved the TPC, TFC, DPPH scavenging activity and FRAP of the EBNH solution. Among the samples, MLE-EBNH solution showed the most superior antioxidant potential at (86.39 ± 1.66)% of DPPH scavenging activity and (19.79 ± 2.96) mmol/L FeSO4 of FRAP. Conclusion This study proved that combined enzymatic hydrolysis and MLE fortification is the best strategy to produce EBN product with prominent in vitro antioxidant potential. This preliminary study provides new insight into the compatibility of EBN with different herbal extracts for future health food production.
    14  Qualitative and quantitative analysis of Arnebiae Radix and Dictamni Cortex and efficacy study of herbal extracts on allergic contact dermatitis using 3D human reconstructed epidermis
    Huan Lia Esther Lima Gladys Anga Zhi-qing Lima Martin Hui Caia Jo-anne Loha b Celine Nga Peijia Seetoha Edmund Tiana Lay Beng Goha b
    2021, 13(4):556-564. DOI: 10.1016/j.chmed.2021.10.006
    [Abstract](530) [HTML](0) [PDF 0.00 Byte](0)
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    Objective: To evaluate the quality of Arnebiae Radix (AR) and Dictamni Cortex (DC) and study the efficacy of herbal extracts of these two herbs on the treatment of allergic contact dermatitis (ACD). Methods: Qualitative and quantitative analysis of effective components was performed using High Performance Thin Layer Chromatography (HPTLC), High Performance Liquid Chromatography (HPLC), and HPLC-Quadrupole Time of Flight-Mass Spectrometry (HPLC-QTOF-MS). In vitro allergic ACD 3D model was established by incubating 3D reconstructed human epidermis (RHE) with skin sensitizer, potassium dichromate. A total of 65 gene expression that were associated with ACD, which included 24 antioxidant responsive element (ARE) and 41 SENS-IS genes were quantified by qRT-PCR. More than or equal to 10 ARE genes and 18 SENN-IS genes were induced by 1.3-fold, demonstrating the successful establishment of in vitro ACD model. Oil extracts of AR and DC were applied on the in vitro ACD model to study the efficacy. Results: Batch 3 of AR and batch 2 of DC showed presence of all active ingredients with the highest concentrations. Active ingredients of the herbs were extracted using a special oil and formulated into herbal oil extracts. The herbal oil extracts were able to down regulate the induced genes in the in-vitro ACD skin model, bringing the tissue back to homeostatic status. Conclusion: The oil extracts showed the potent efficacy of using AR and DC in ACD treatment. The combination study will be done to optimize the formulation ratio which will be developed into a topical cream.
    15  Submerged fermentation improves bioactivity of mulberry fruits and leaves
    Hui Qian Chuah Pei Ling Tang Ni Jing Ang Hui Yin Tan
    2021, 13(4):565-572. DOI: 10.1016/j.chmed.2021.09.003
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    Abstract:
    Objective Mulberry (Morus spp.) fruits and leaves have been proven to possess nutraceutical properties. Due to its fast and easy growing characteristics, mulberry fruits (MF) and leaves (ML) potentially emerge as a great source of functional foods. This study aims to enhance bioactivities (antioxidant, anti-inflammation, and hypoglycemic activity) of MF and ML via submerged fermentation using bacteria (Lactobacillus plantarum TAR 4), yeast (Baker’s yeast and red yeast) and fungi (Tempeh and Tapai starter). Methods In this study, 25% (mass to volume ratio) of MF and ML were fermented (48 h) with 1% (mass to volume ratio) of different microbial cultures, respectively. Effects of different fermentations on MF and ML were determined based on the changes of total phenolics (TPC), flavonoids (TFC), anthocyanins, total sugar, DPPH activity, ferric reducing antioxidant power (FRAP), albumin denaturation inhibition activity (ADI), anti-lipoxygenase activity and α-amylase inhibition activity (AI). Results Generally, ML had higher AI than MF. However, MF exhibited higher DPPH, FRAP and anti-lipoxygenase activity than ML. After all forms of fermentation, DPPH and AI activity of MF and ML were increased significantly (P < 0.05). However, the effects of fermentation on TPC, FRAP, ADI and anti-lipoxygenase activity of MF were in contrast with ML. TPC, FRAP and anti-lipoxygenase activity of ML were enhanced, but reduced in MF after fermentation. Although the effects exerted by different microorganisms in MF and ML fermentation were different, the bioactivities of MF and ML were generally improved after fermentation. Fermentation by Tempeh starter enhanced TPC (by 2-fold), FRAP (by 2.3-fold), AI (at 10% increment) and anti-lipoxygenase activity (by 5-fold) of ML, whereas Tapai fermentation effectively enhanced the DPPH (at 17% increment) and ADI (by 2-fold) activity of MF. Conclusion Findings of this study provide an insight into the future process design of MF and ML processing into novel functional foods.

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