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The Official Journal of China Anti-Cancer Association
Editor-in-Chief: XZ Wu, PhD
ISSN 2413-3973
1Traditional Medicine Research (TMR) is a peer-reviewed open access journal managed by TMR Publishing Group. TMR is dedicated to protecting and developing all types of traditional medicines, including traditional Chinese medicine, Persian medicine, Ayurveda, Siddha, minority medicine, etc., using the latest achievements in modern science. TMR emphasizes the historical origin and developmental pipeline of the research objective and encourages authors to analyze the theoretical significance underlying a study and the application of traditional medicine in clinical practice. In addition to editorial, review, article and letter, the following topics are welcome. News column follows important current medical, policy, and archaeological events in the field of traditional medicine, and the comment column discusses the progress of latest and salient research. ... More

Traditional Medical Systems More

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Acupuncture

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Traditional Literatures More

Before 221 B.C. · Shen Nong Ben Cao Jing
Before 221 B.C. · Huang Di Nei Jing
Third century · Shang Han Lun
Third century · Jin Gui Yao Lue
284 A.D.-354 A.D. · Zhou Hou Bei Ji Fang
652 A.D. · Qian Jin Fang
1025 A.D. · The Canon of Medicine
1078 A.D. · Tai Ping Hui Min He Ji Ju Fang
Twelfth century · rGyud bzhi (The Four Tantras)
1740 A.D. · Wai Ke Zheng Zhi Quan Sheng Ji

Current Issue     02 July 2020, Volume 5 Issue 4 Previous Issue   
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News
Treating COVID-19 by traditional Chinese medicine: a charming strategy?
Yu-Liang Zhang, Wan-Ying Zhang, Xin-Zhe Zhao, Jia-Ming Xiong, Guo-Wei Zhang
1Traditional Medicine Research. 2020, 5 (4): 178-181.   https://doi.org/10.12032/TMR20200515179
Abstract ( 308 )   HTML ( 1 )     PDF (558KB) ( 98 )  

On April 14, 2020, the State Council of China announced that “three proprietary Chinese medicines and three decoctions” of effective traditional Chinese medicine (TCM) in the treatment of the novel coronavirus pneumonia have passed clinical practice screenings [1]. Some scholars believe that early TCM intervention of mild and moderate cases and recovery period may reduce the ratio of mild cases progressing into severe and critical cases. Some data have also suggested that the combination of TCM and Western medicine may reduce the mortality rate in severe and critical cases [2, 3]. 

  The “three proprietary Chinese medicines” are Chinese patent drug Jinhua Qinggan granules (approval number of State Food and Drug Administration of China (SFDA) Z20160001), Lianhua Qingwen granules (SFDA approval number Z20100040), and Xuebijing injection (SFDA approval number Z20040033) [4]. In this regard, the National Medical Products Administration of China recently approved the inclusion of the treatment of the novel coronavirus pneumonia as a new indication of the “three proprietary Chinese medicines”, which have become the world’s first batch of drugs suitable for COVID-19 (Table 1) [5]. 

  The “three decoctions” are empirical formula of Chinese medicine Qingfei Paidu decoction, Huashi Baidu decoction, and Xuanfei Baidu decoction (Table 2). Among them, Qingfei Paidu granules and Huashi Baidu granule have been recently approved for clinical trials [5]. 

  Jinhua Qinggan granule is a proprietary Chinese medicine developed during the 2009 H1N1 influenza pandemic. Both Lianhua Qingwen capsule and Xuebijing injection were identified as proprietary Chinese medicines developed and listed during the SARS in 2003 [3–5]. At present, 22 TCM treatment programs have been registered for clinical trials. 

  However, because Lianhua Qingwen capsule contains Houttuynia cordata, Qingfei Paidu decoction contains Belamcandae Rhizoma, and both of them contain aristolochic acid, which can cause kidney injury and liver cancer [6–7]. Xuanfei Baidu decoction and Qingfei Paidu decoction contain Ephedrae Herba, which has cardiovascular toxicity and stimulative effect on central nervous system [8]. Qingfei Paidu decoction contains Alismatis Rhizoma, which may cause kidney injury [9]. Perhaps it is the above toxicity of herb that prohibits the import or clinical application of these six decoctions in Sweden, Singapore, the United States, Canada and other countries [10].

Comment
India’s indigenous idea of herd immunity: the solution for COVID-19?
Ram Shepherd Bheenaveni
1Traditional Medicine Research. 2020, 5 (4): 182-187.   https://doi.org/10.12032/TMR20200519181
Abstract ( 1075 )   HTML ( 8 )     PDF (1020KB) ( 322 )  

Based on folklore and traditional wisdom, when a shepherd purchases a few new sheep from an unknown seller or from a distant place, he keeps them away from his old flock of sheep for a period of 15 days. This, in other words, is a unique practice of herd quarantine. The new flock is permitted to mingle with the old flock only after the completion of the prescribed quarantine period. In case someone tries to violate the principle of herd quarantine, the herd council will impose a rigorous punishment. 

   Whenever traits of virus-causing diseases, like cowpox, sheeppox, and goatpox, appear in cattle herds, shepherds anticipate its inescapability of viral infection and its inevitable outbreak and visualize that herd quarantine may not be a practical solution in the long run. Although shepherds are not exposed to the term “virus,” they have a solid understanding of the very existence of a foreign specie that damages the health of their herds. To mitigate and militate the repulsive repercussions of the virus, they purposively evolve a typical method of treatment named, potthi kattu, known as herd immunity. This can be observed in all remote Indian villages until today. 

   In the modern framework, the idea of herd immunity was first adopted in 1923 to denote the premunity or immunity of a given total population, examining the rate of disease fatality among populace at various degrees of immunity in an experimental research. The study recognized herd immunity as a naturally occurring phenomenon. During the mid-1930s, A.W. Hedrich’s epidemiological study of measles in Baltimore noticed a substantial decline in new infections after several children had been conscientiously exposed and immune to measles. In light of this, mass vaccination is performed to develop premunity among the masses; this process is called herd immunity in our modern medical sciences, as everybody of us naturally develops immunity after a due course of time. 

   In contrast to modern science, the original idea of herd immunity is not a natural process since inoculation or variolation is a must. This happens when the virulence of the virus is considerably condensed with the help of natural substances, like herbs and plants, and then the attenuated virus will be inoculated into the body of a healthier animal, where the spurious virus enters through the medical intervention of shepherds which will eventually infect the flock one after the other. By this means, the infection becomes mild, unlike the natural attack. The inherent antigens in animals will quickly respond to face the attack of the mild virus by producing awe-inspiring antibodies in order to develop immunity within a stipulated period.

Can Yin-Chai-Xiao-Du decoction be useful of COVID-19? the mechanism research based on network pharmacology
Lu Yang, Ning Li, Hai-Bo Hu, Bin Yin, Guo-Jing Zhao, Feng-Chan Wang, Xu-Hui Wang, Hong-Wu Wang, Xue-Chao Lu, Huan-Tian Cui
1Traditional Medicine Research. 2020, 5 (4): 188-200.   https://doi.org/10.12032/TMR20200601185
Abstract ( 61 )   HTML ( 1 )     PDF (923KB) ( 48 )  

Highlights

Our current study explored the potential mechanisms of Yin-Chai-Xiao-Du decoction, an empirical formula of traditional Chinese medicine derived from the classic ancient prescription Gan-Lu-Xiao-Du decoction, on COVID-19 and found its core herbs.

Traditionality

The empirical formula Yin-Chai-Xiao-Du decoction has evolved based on the classic ancient prescription of Gan-Lu-Xiao-Du decoction, which was first mentioned in Wei Zhixiu’s Xu Mingyi Lei'an (Supplement to Classified Case Records of Celebrated Physicians) in the Qing Dynasty of China that was released in approximately 1770 C.E. Gan-Lu-Xiao-Du decoction could alleviate fever, cough and fatigue, which were the major clinical outcomes of COVID-19. However, the mechanisms of action of Yin-Chai-Xiao-Du decoction in the treatment of COVID-19 remain unclear.

Abstract

Background: In this study, we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology. Methods: The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology; the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases; the COVID-19-related targets were obtained from the online Mendelian inheritance in man, GeneCards, and GeneMANIA databases; the STRING database and Cytoscape were used to build a protein-protein interaction network, and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets; the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function (Gene Oncology) and gene pathway (Kyoto Encyclopedia of Genes and Genomes); the herb-ingredient-target-pathway network diagram was constructed by Cytoscape. Results: The core herbs screened by the network pharmacological analysis were Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the key ingredients were quercetin, kaempferol, isorhamnetin, stigmasterol, beta-sitosterol, and luteolin. Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets, and the key targets were mitogen-activated protein kinase 3, interleukin-6, tumor necrosis factor, vascular endothelial growth factor A, and CC motif ligand 2. Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways, and the key pathways were signaling by interleukins, immune system, cytokine signaling in the immune system, and the signaling pathways of interleukin-17, tumor necrosis factor, and relaxin. Conclusion: The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). The key ingredients are quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol; the critical targets are luteolin, interleukin-6, mitogen-activated protein kinase 3, tumor necrosis factor, and CC motif ligand 2; and the core signaling pathways are those mediated by interleukin-17, tumor necrosis factor, and relaxin.


Traditionality

The empirical formula Yin-Chai-Xiao-Du decoction has evolved based on the classic ancient prescription of Gan-Lu-Xiao-Du decoction, which was first mentioned in Wei Zhixiu’s Xu Mingyi Lei'an (Supplement to Classified Case Records of Celebrated Physicians) in the Qing Dynasty of China that was released in approximately 1770 C.E.

Efficacy of Xuebijing injection for the treatment of coronavirus disease 2019 via network pharmacology
Yu-Liang Zhang, Qian Cui, Dou Zhang, Xin Ma, Guo-Wei Zhang
1Traditional Medicine Research. 2020, 5 (4): 201-215.   https://doi.org/10.12032/TMR20200507178
Abstract ( 383 )   HTML ( 8 )     PDF (4704KB) ( 115 )  

Highlights

The Chinese drug formula Xuebijing (XBJ) injection ameliorated the inflammatory reaction, respiratory distress, and hypoxia caused by coronavirus disease 2019 infection. Its underlying mechanism is via affecting the angiotensin-converting enzyme 2 and signaling pathways of hypoxia inducible factor-1, PI3K-Akt, and NF-κB by regulating the expression of protein kinase 1, VEGF-A, B-cell lymphoma-2, TNF, and other targets.

Traditionality

The prescription of XBJ injection was first introduced in the Xuefu Zhuyu decoction in the medical book Yilin Gaicuo (Correction of Errors in Medical Classics), written by Wang Qingren, a famous Chinese physician in the 1830s of the Qing Dynasty of China. The decoction is composed of such main ingredients as Honghua (Carthami Flos), Chishao (Radix Paeoniae Rubra), Chuanxiong (Chuanxiong Rhizome), Danshen (Radix Salvia) and Danggui (Angelicae Sinensis Radix) with glucose as an auxiliary material that can clear away heat and toxic material (equivalent to an anti-inflammatory effect in Western medicine). XBJ injection has obtained the production approval of the State Food and Drug Administration of China and a new drug certificate for the drug of second class (approval number: Z20040033) in 2004. It has been employed for the clinical treatment of pneumonia for more than ten years, primarily as a treatment for severe pneumonia and severe pneumonia with sepsis, respiratory distress, respiratory failure, and fever with profound effects. It was designated as a severe drug in the Diagnosis and Treatment Protocol for the Novel Coronavirus Pneumonia (trial version 7) and obtained an approval letter of supplementary application by the State Food and Drug Administration of China for use as an additional drug application for new indications including severe pneumonia, critical systemic inflammatory response syndrome, or multiple organ failure from the novel coronavirus.

Abstract

Background: To evaluate the mechanism of Chinese patent drug Xuebijing (XBJ) injection in the treatment of a new coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking technology. Methods: The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection. The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection. Cytoscape was employed to build a network connecting Chinese medicine, compounds, targets, disease, and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets. The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19. Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection. Results: Eight key compounds and 15 key targets were screened and verified by molecular docking; these key compounds included luteolin, quercetin, baicalein, and kaempferol. The key targets included DPP4, AR, ESR1, CALM1, and protein kinase 1. Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology. Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1, VEGF, and PI3K/AKT/NF-κB. Conclusion: The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1, VEGF-A, B-cell lymphoma-2, and TNF, which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1, PI3K-Akt, and NF-κB, which alleviated the inflammation, respiratory distress, and hypoxia caused by COVID-19 infection.


Traditionality

The prescription of XBJ injection was first introduced in the Xuefu Zhuyu decoction in the medical book Yilin Gaicuo (Correction of Errors in Medical Classics) in the 1830s. XBJ injection has obtained the production approval of the State Food and Drug Administration of China in 2004.

Does Liuzijue Qigong affect anxiety in patients with chronic obstructive pulmonary disease, even during the COVID-19 outbreak? a randomized, controlled trial
Yu-Xuan Zhang, Ying Quan, Ming-Hu Chen, Duo Zhang, Ying Zhang, Zhen-Gang Zhu
1Traditional Medicine Research. 2020, 5 (4): 216-228.   https://doi.org/10.12032/TMR20200528183
Abstract ( 173 )   HTML ( 1 )     PDF (487KB) ( 43 )  

Highlights

Patients with high course of chronic obstructive pulmonary disease (COPD) assessment test scores, self-rating anxiety scale scores, or who live in rural areas, have a higher burden of anxiety and need more attention during the outbreak. As a pulmonary rehabilitation exercise, Liuzijue Qigong (LQG) can relieve anxiety in stable COPD patients, even during the coronavirus disease 2019 outbreak.

Traditionality

LQG has been used as a traditional Chinese Taoism (a Chinese philosophy attributed to Lao Tzu (500 B.C.E.) which contributed to the religion of the people in China) regimen for approximately 1,500 years. The six pronunciations of “Xu, He, Hu, Si, Chui, Xi” in LQG were first recorded as a treatment in the ancient book Yang Xing Yan Ming Lu (Records of Nourishing the Body and Prolonging Life) written by Tao Hongjing in the Southern and Northern Dynasties (420-589 C.E.) of China. It recorded that LQG can regulate the function of internal organs of the body to tend to balance through pronunciation, which was conducive to the health of the body. Until 2007, it became a complete Qigong exercise by General Administration of Sport of China. In recent years, it has been widely used in pulmonary rehabilitation for COPD patients in China.

Abstract

Background: Anxiety is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), but no well-recognized method can provide effective relief. Liuzijue Qigong (LQG) is a traditional Chinese fitness method, based on breath pronunciation. This study aimed to examine the efficacy of LQG to relieve anxiety in COPD patients and to explore the factors that influence anxiety, including whether LQG is effective during the coronavirus disease 2019 (COVID-19) outbreak. Methods: We conducted an open-label, randomized, controlled, clinical trial. A total of 60 patients with stable COPD were randomly assigned to two groups. Both groups were given routine medical treatment, and the patients in the pulmonary rehabilitation (PR) group were given an extra intervention in the form of LQG, performed for 30 minutes each day for 12 weeks. Data collection was performed at baseline and 12 weeks (during the COVID-19 epidemic). The primary outcomes were the self-rating anxiety scale (SAS) scores, and the secondary outcomes were relevant information during the epidemic and analyses of the related factors that influenced SAS scores during the COVID-19 outbreak. Results: Compared with baseline, patients in both groups demonstrated varying degrees of improvements in their SAS scores (all P < 0.01). An analysis of covariance, adjusted for baseline scores, indicated that the SAS scores improved more dramatically in the PR group than in the control group (F = 9.539, P = 0.004). During the outbreak, the SAS scores for sleep disorder were higher than all other factors, reaching 1.38 ± 0.67, and the scores for “I can breathe in and out easily” for the PR group were lower than the scores for the control group (Z = -2.108, P = 0.035). Significant differences were identified between the two groups for the categories “How much has the outbreak affected your life”, “Do you practice LQG during the epidemic” and “Do you practice other exercises during the epidemic” (all P < 0.05). Compared with current reports, LQG had a relatively high adherence rate (80.95%). A multiple linear regression analysis revealed multiple predictors for SAS scores during the outbreak: group (b = -3.907, t = -3.824, P < 0.001), COPD assessment test score (b = 0.309, t = 2.876, P = 0.006), SAS score at baseline (b = 0.189, t = 3.074, P = 0.004), and living in a village (b = 4.886, t = 2.085, P = 0.043). Conclusion: LQG could effectively reduce the risks of anxiety among COPD patients, even during the COVID-19 outbreak. For those COPD patients with high COPD assessment test and high baseline SAS scores or who live in villages, we should reinforce the management and intervention of psychological factors during the epidemic.


Traditionality

The six pronunciations of “Xu, He, Hu, Si, Chui, Xi” in LQG were first recorded as a treatment in the ancient book Yang Xing Yan Ming Lu (Records of Nourishing the Body and Prolonging Life) written by Tao Hongjing in the Southern and Northern Dynasties (420–589 C.E.) of China. Until 2007, it became a complete Qigong exercise by General Administration of Sport of China. In recent years, it has been widely used in pulmonary rehabilitation for COPD patients in China.

Qingfei oral liquid downregulates TRPV1 expression to reduce airway inflammation and mucus hypersecretion injury caused by respiratory syncytial virus infection and asthma in mice
Xiao-Ping Jing, Wu-Ning Yan, Wei-Wei Cheng, Hai-Rong Zeng
1Traditional Medicine Research. 2020, 5 (4): 229-237.   https://doi.org/10.12032/TMR20200128156
Abstract ( 179 )   HTML ( 0 )     PDF (1467KB) ( 56 )  

Highlights

Qingfei oral liquid (QF), an experimental Chinese medicine prescription developed from the ancient prescriptions of traditional Chinese medicine (TCM) Ma Xin Shi Gan and Tingli Dazao Xie Fei decoctions, can inhibit respiratory syncytial virus replication and reduce airway inflammation and mucus hypersecretion injury caused by respiratory syncytial virus infection and asthma, and its mechanism of action may be associated with the downregulation of transient receptor potential vanilloid-1 expression and a decrease in airway mucus hypersecretion injury.

Traditionality

In children, the finding of an acute asthma attack induced by respiratory syncytial virus infection is in line with the theory of TCM stating that Xiao Zheng (the name of a disease in TCM theory) is caused by exogenous pathogenic factors. The symptoms of Xiao Zheng that recorded in the ancient medical book entitled Huangdi Neijing (Inner Canon of the Yellow Emperor), such as dyspnea, throat phlegm, and thick yellow expectoration, is similar to those of asthma. QF is a compound traditional medicine preparation approved by the Jiangsu Province Food and Drug Administration of China (serial no. Z04000512). It was developed from the clinical experience of Shouchuan Wang, a renowned professor of TCM at the Nanjing University of Chinese Medicine and adapted from the ancient prescriptions of Chinese medicine Ma Xin Shi Gan and Tingli Dazao Xie Fei decoctions. Ma Xin Shi Gan decoction comes from the classic Chinese medicine book Shang Han Lun (Treatise on Cold Damage Diseases); Ting Li Da Zao Xie Fei decoction comes from the well-known Chinese medicine book Jing Gui Yao Lue (Essential Prescriptions from the Golden Cabinet).

Abstract

Objective: Qingfei oral liquid (QF), an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction, has been effectively used since decades to treat patients with viral pneumonia and asthma. In our previous study, we had demonstrated that QF can significantly reduce airway hyperresponsiveness, hyperemia, lung tissue edema, inflammatory lung tissue infiltration in mice, airway mucus secretion, and peripheral airway collagen hyperplasia; however, its mechanism of action is unknown. Methods: Fifty 6-8-week-old male BALB/c mice were equally and randomly divided into five groups: the control, ovalbumin (OVA), OVA + respiratory syncytial virus (RSV), QF, and dexamethasone (Dxms) groups. The QF group was administered QF at 1.17 g·kg-1·d-1, the Dxms group received dexamethasone injections at 0.2 mg·kg-1·d-1, and the remaining groups were administered PBS. Inflammation in the lung tissue was assessed by hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Van Gieson staining. ELISA was used to evaluate the IL-13, IL-25, and IL-33 in the mice. Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1 (TRPV1) and mucin 5AC (MUC5AC) in the lung tissues of mice. Results: Histopathological evaluation revealed that the OVA and OVA + RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining; collagen hyperplasia around the airway was increased in these two groups compared with the control group. The QF group exhibited significantly reduced lung tissue edema, inflammatory lung tissue infiltration, airway secretions, and collagen hyperplasia around the airway compared with the OVA + RSV group. We analyzed the serum levels of IL-13, IL-25, and IL-33 in the mice and found that these levels were higher in the OVA and OVA + RSV groups than in the control group (P < 0.05 in the OVA group, P < 0.01 in the OVA + RSV group). The QF group exhibited significantly decreased serum levels of IL-13, IL-25, and IL-33 compared with the OVA + RSV group (all P < 0.05). The Dxms group also exhibited significant decreases in the serum levels of IL-13 and IL-33 (all P < 0.05) but no significant decrease in the serum levels of IL-25 compared with the RSV + OVA group. Finally, we examined the protein levels of TRPV1 and MUC5AC in the lung tissues of mice using Western blotting. After identifying RSV infection in the mice with asthma, the protein levels of TRPV1 and MUC5AC in the lung tissues of mice were significantly higher than those in the control group (P < 0.05, P < 0.01). We found that compared with RSV + OVA, QF can significantly downregulate the protein level of TRPV1; further, the protein level of MUC5AC was also significantly reduced (all P < 0.001). Conclusion: QF can inhibit RSV replication and reduce airway inflammation and mucus hypersecretion injury caused by RSV infection and asthma, and its mechanism of action may be associated with the downregulation of TRPV1 expression and a decrease in airway mucus hypersecretion injury.


Traditionality

QF is a compound traditional medicine preparation approved by the Jiangsu Province Food and Drug Administration of China (serial no. Z04000512). It was adapted from the ancient prescriptions of Chinese medicine Ma Xin Shi Gan and Tingli Dazao Xie Fei decoctions.

Dissecting the underlying pharmaceutical mechanism of Danggui Buxue decoction acting on idiopathic pulmonary fibrosis with network pharmacology
Cai-Ping Zhao, Hang Li, Xiao-Hong Liu, Shuang Liang, Xue-Lei Liu, Xin-Rong Li, Yi Luo, Mei-Ling Zhu
1Traditional Medicine Research. 2020, 5 (4): 238-251.   https://doi.org/10.12032/TMR20191102146
Abstract ( 302 )   HTML ( 0 )     PDF (1091KB) ( 80 )  

Highlights

Kaempferol and quercetin are found to be the two main compounds of classical prescription of traditional Chinese medicine named Danggui Buxue decoction with the highest network regulation, which can inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of fibrosis markers α-smooth muscle actin, collagen 1, fibronectin.

Traditionality

Danggui Buxue decoction (DBD), a classical prescription in traditional Chinese medicine composed of Huangqi (Radix Astragali) and Danggui (Radix Angelicae Sinensis) in a ratio of 5:1, originates from the Chinese medicine ancient book entitled Neiwai Shangbian Huolun written by the famous medical scientist Li Dongyuan in 1247 C.E. At present, there are many researchers who try to study the biological activity of individual chemical components in DBD and the mechanism of action of whole formula. Some studies have shown that DBD has effect on fibrosis of heart, liver and kidney and has protective effect on bleomycin-induced pulmonary fibrosis in rats by reducing alveolar inflammation and fibrosis.

Abstract

Backgroud: Danggui Buxue decoction (DBD), a classical prescription in traditional Chinese medicine, has been found to have protective effect on bleomycin-induced pulmonary fibrosis in rats by reducing alveolar inflammation and fibrosis. However, the biological activity of individual chemical components and mechanism of action of whole formula are not clear. Methods: Potential targets of active ingredients of DBD were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SymMap database. Target genes related to idiopathic pulmonary fibrosis were obtained from the Online Mendelian Inheritance in Man database, Therapeutic Targets Database and Gkb database. Then, the common targets were obtained by overlapping the potential targets of active ingredients in DBD and diseases related targets. The selected targets were subjected to Kyoto Encyclopedia of Genes and Genomes signaling pathway and Gene Ontology analysis, and the network map of active component-target-pathway was established using Cytoscape 3.7.1 software. The active components of DBD with most targets were selected for fibrosis-related marker verification. The mRNA and protein expression of fibrosis markers, α-smooth muscle actin, collagen 1 and fibronectin, were detected in TGF-β1-induced fibroblast cell line after treatment with the active components. Results: The 14 active ingredients, such as quercetin and kaempferol, were screened from DBD. It acts on 26 targets like estrogen receptor 2 and prostaglandin-endoperoxide synthase 2, and mainly involves 38 signaling pathways such as cell inflammation and autophagy. Kaempferol and quercetin are the two compounds with the highest network regulation, which can inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of fibrosis markers α-smooth muscle actin, collagen 1 and fibronectin. Conclusion: The integration mode of multi-component, multi-target, multi-channel and mechanism of DBD in the treatment of idiopathic pulmonary fibrosis are predicted by means of network pharmacology. Our study could indicate the direction of further anti-fibrotic mechanism research.


Traditionality

Danggui Buxue decoction (DBD), a classical prescription in traditional Chinese medicine composed of Huangqi (Radix Astragali) and Danggui (Radix Angelicae Sinensis) in a ratio of 5:1, originates from the Chinese medicine ancient book entitled Neiwai Shangbian Huolun written by the famous medical scientist Li Dongyuan in 1247 C.E. 

Marine natural products with anti-inflammation effects
Mei-Mei Zhao, Ke-Wu Zeng
1Traditional Medicine Research. 2020, 5 (4): 252-260.   https://doi.org/10.12032/TMR20200417173
Abstract ( 129 )   HTML ( 5 )     PDF (693KB) ( 86 )  

Highlights

The present review reviewed the research progress of marine-derived anti-inflammation compounds including terpenes, polypeptides, polysaccharides, sterols, etc. and the relative anti-inflammatory mechanisms, to bring a new insight into inflammation therapies with multifarious sources and minimal side effects.

Traditionality

China has a long history of marine natural products application. The earliest Chinese pharmacopoeia, Shennongbencaojing (Shengnog’s Classic of Materia Medica; Eastern Han dynasty of China, 200 C.E.), reported 12 kinds of marine medicines, including Haizao (seaweed; Sargassum), Haige (sea clams; Cyclina sinensis Gmelin), Muli (animal shell; Ostreae concha) and Wuzeigu (cuttlefish bone; Cleistocactus sepium). Moreover, more than 100 traditional Chinese medicines contained in Bencaogangmu (Compendium of Materia Medica; Ming dynasty of China, 1578 C.E.) were derived from marine. Recently, increasing numbers of marine-derived products have been reported, including 144 kinds of marine medicines collected in Dictionary of Traditional Chinese Medicine (1977) and more than 600 kinds of marine medical products collected in Chinese Materia Medica (1988). Haizao (seaweed; Sargassum) is a traditional Chinese medicine. In the ancient literature Shanhaijing (Xia and Shang dynasties of China, 1,600 B.C.E.), Haizao (seaweed; Sargassum) was reported to prevent tumorigenesis like thyrophyma. With the development of modern medicine, the novel mannose oligosaccharide diacid derived from brown algae, a kind of seaweed, namely GV-971, has been conditionally approved for market in China, for the treatment of mild to moderate Alzheimer's disease.

Abstract

The ocean possesses a complex setting with high pressure, high salinity, oligotrophy, low temperature and weak illumination conditions. To survive and evolve in such harsh surroundings, marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition. During recent decades, the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases. Correspondingly, a myriad of marine bioactive molecules including terpenes, polypeptides, polysaccharides, sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects. And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases. Herein, the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed, to provide a basis for the research and development of anti-inflammatory marine drugs.


Traditionality

China has a long history of marine natural products application. The earliest Chinese pharmacopoeia, Shennongbencaojing (Shengnog’s Classic of Materia Medica; Eastern Han dynasty of China, 200 C.E.), reported 12 kinds of marine medicines. Moreover, more than 100 traditional Chinese medicines contained in Bencaogangmu (Compendium of Materia Medica; Ming dynasty of China, 1578 C.E.) were derived from marine. 

The advances of traditional Chinese medicine in the treatment of liver diseases in 2019
Min Cao, Jing Miao, Li Wang, Hai-Zhao Liu, Huan-Tian Cui, Yu-Hong Bian
1Traditional Medicine Research. 2020, 5 (4): 261-271.   https://doi.org/10.12032/TMR20200520182
Abstract ( 98 )   HTML ( 0 )     PDF (924KB) ( 48 )  

Highlights

This article focuses on introducing the mechanism and application prospect of the active ingredients and formulas of traditional Chinese medicine in the treatment of liver diseases in 2019. Metabolomics, transcriptomics, network pharmacology, 16S rRNA gene sequencing, and other omic analyses have been widely used in many studies in the past year.

Traditionality

This annual review summarizes the hot research mechanisms of traditional Chinese medicine in the treatment of liver disease, especially hepatitis, liver injury, non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma in 2019, which can provide a comprehensive description of the hot spots and ongoing research areas.

Abstract

Background: Currently, the treatment of liver diseases remains an unsolved problem due to its complicated etiology and pathogenesis. Traditional Chinese medicine (TCM) has been used for liver disease treatment for thousands of years. Disease treatment using TCM compounds conforms to the concept of “holism”, which coincides with the complicated pathogenic mechanisms of liver diseases. However, the mechanisms have not been clearly explained due to the complex components and multi-targets, which is a big obstacle TCM’s popularity and application. In recent years, studying the mechanisms and identifying the novel ingredients in herbal medicines are becoming a hot spot for many researchers. Therefore, we obtained literature in PubMed and summarized the progress of TCM’s active ingredients and formulas in treating various liver diseases in 2019. Based on the literature, flavonoids, polysaccharides, saponins, and alkaloids, as well as Chinese medicine formulas, such as Ba-Bao pill and Yin-Chen-Hao decoction, have attracted much attention. In addition, we also focused on the application of new omics analysis techniques, such as metabolomics, network pharmacology, and other omics analyses in the study of TCM formulas.


Traditionality

This annual review summarizes the hot research mechanisms of traditional Chinese medicine in the treatment of liver disease, especially hepatitis, liver injury, non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma in 2019, which can provide a comprehensive description of the hot spots and ongoing research areas.

The selection rules of acupoints and meridians of traditional acupuncture for postoperative nausea and vomiting: a data mining-based literature study
Li-Sha Liu, Jian Huo, Xiu-Li Yuan, Yi Lan, Jing-Yuan Zhang, Hong-Mei Zhong, Yu Wang, Yun-Sheng He
1Traditional Medicine Research. 2020, 5 (4): 272-281.   https://doi.org/10.12032/TMR20200114154
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Highlights

The present study collected the clinical researches regarding acupuncture for postoperative nausea and vomiting in the recent decade and explored the selection rules based on data mining technology, to give scientific guide and evidence to clinical researchers.

Traditionality

The acupoints selection principles for nausea and vomiting was initially documented in the book Huangdi Neijing (Yellow Emperor's Canon of Internal Classic) (221 B.C.E.-220 C.E.), valuably inspiring doctors of later generations. As revealed from the book Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion) of Mi Huangpu in 282 C.E., nausea and vomiting displayed associations with the Zangfu (the general name of human internal organs in traditional Chinese medicine theory) and 18 core acupoints to treat nausea and vomiting were developed. In the 1950s, JF Xu adopted acupuncture at Neiguan (PC 6), Tianshu (ST 25) and chewed ginger to achieve nausea and vomiting treatment. In 1997, National Institutes of Health confirmed the role of acupuncture to treat nausea and vomiting. The mechanism of acupuncture may display associations with the enhancing effect on gastric motility and suppressing effect on temporary lower esophageal sphincter relaxation. The acupoints selection refers to the fundamental step of the effect, whereas the selection rules for postoperative nausea and vomiting remain unclear.

Abstract

Background: Postoperative nausea and vomiting (PONV) refers to a problem commonly occurring after surgery. Acupuncture is considered a critical complementary alternative therapy for PONV. The acupoints selection critically determines the efficacy of acupuncture, whereas the selection rules remain unclear. The objective of the present study was to delve into the principles of acupoints selection for PONV using data mining technology. Methods: The clinical trials assessing the acupuncture effect for PONV were searched with the use of computer in PubMed, China National Knowledge Infrastructure, and Chinese Biomedical Database; the time span was confined as 2009-2019. The database of acupuncture prescriptions for PONV was built using Excel 2016; the description and association were analyzed by IBM SPSS modeler 18. Result: Eighty-three relevant literatures were screened out. The number of specific acupoints took up 72.5% of all acupoints; specific acupoints exhibited the frequency taking up 91.30% of the total frequency. As revealed from the result, Neiguan (PC 6), Zusanli (ST 36), Hegu (LI 4), and Zhongwan (CV 12) were most frequently applied, suggesting the tightest associations. Most acupoints were taken from the stomach meridian and pericardium meridian. The common acupoints were concentrated in the lower limbs, chest, as well as abdomen. Conclusion: Data mining acts as a feasible method to identify acupoints selection and compatibility characteristics. As suggested from our study, the acupoints selection for PONV prioritizes specific acupoints and related meridians. The selection and combination of acupoints comply with the theory of traditional Chinese medicine.


Traditionality

The acupoints selection principles for nausea and vomiting was initially documented in the book Huangdi Neijing (Yellow Emperor's Canon of Internal Classic) (221 B.C.E.–220 C.E.). As revealed from the book Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion) of Mi Huangpu in 282 C.E., 18 core acupoints to treat nausea and vomiting were developed. In 1997, National Institutes of Health confirmed the role of acupuncture to treat nausea and vomiting. 

Acupuncture and/or moxibustion for the treatment of lumbar disc herniation: quality assessment of systematic reviews
Zi-Han Yin, Chao-Xi Zhu, Gui-Xing Xu, Cheng Ying, Ai-Ling Huang, Ya-Nan Fu, Jiao Chen, Ling Zhao, Fan-Rong Liang
1Traditional Medicine Research. 2020, 5 (4): 282-294.   https://doi.org/10.12032/TMR20190930137
Abstract ( 336 )   HTML ( 2 )     PDF (677KB) ( 172 )  

Highlights

In the current systematic review on acupuncture and/or moxibustion for lumbar disc herniation (LDH), the methodology and quality of evidence and reports were evaluated via AMSTAR list, GRADE system and PRISMA statement and conclusion is that acupuncture and/or moxibustion have some advantages in terms of efficacy and safety with regard to LDH treatment.

Traditionality

LDH belongs to the category of low back pain (LBP) in Chinese medicine theory. LBP was recorded in the earliest Chinese medical classic Huangdi Neijing published in Qinhan period of China (the time of writing is unknown). Subsequently, evidence on the use acupuncture for the treatment of LBP by a large number of scholars of Ming dynasty of China was recorded in Jingyue Quanshu, Zhenjiu Dacheng, and other ancient books on acupuncture. With the development of modern medicine, National Institute for Health and Clinical Excellence guidelines published in 2012 highlighted the need for a treatment course of acupuncture of up to 10 sessions over 12 weeks for patients with LBP.

Abstract

Objective: In the current systematic review on acupuncture and/or moxibustion for lumbar disc herniation (LDH), we evaluated the methodology and quality of evidence and reports to provide necessary information for accurate clinical decision-making regarding acupuncture and/or moxibustion for LDH. Methods: From databases such as CBM (Chinese biomedical literature database), VIP (China science and technology journal database), CNKI (China national knowledge infrastructure), WF (Wanfang database), Web of Science, Embase, Medline, and Cochrane Library, systematic reviews on acupuncture and/or moxibustion for LDH were retrieved, and the methodological quality of the literature was evaluated according to the assessment of multiple systematic reviews (AMSTAR) list. Furthermore, the grading of recommendations assessment, development and evaluation (GRADE) system was used to grade the quality of evidence and the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement to evaluate the quality of the report. Results: A total of 18 systematic reviews were included, and the conclusion is that acupuncture and/or moxibustion have some advantages in terms of efficacy and safety with regard to LDH treatment. According to the AMSTAR score, there were 4 high-quality studies, 13 moderate-quality studies, and 1 low-quality study. GRADE showed that quality of evidence such as total effective rate of LDH and VAS was low and that of other forms of evidence was lower. The PRISMA statement showed that 8 articles were in line with 20 or more of the 27 items, and 10 articles were in line with 10-19 of the 27 items. Conclusion: At present, acupuncture and/or moxibustion for LDH has a good curative effect. More importantly, its methodological quality was of moderate level and the report quality was generally good and relatively complete. However, the poor quality of the original research results was reflected in the quality of evidence. More studies are needed to make sure whether acupuncture is more effective than other treatment methods.


Traditionality  

Low back pain was recorded in the earliest Chinese medical classic Huangdi Neijing. Subsequently, evidence on the use acupuncture for the treatment of low back pain by a large number of scholars of Ming dynasty of China was recorded in Jingyue QuanshuZhenjiu Dacheng, and other ancient books.

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  • From religious manual to herbal pharmacopoeia: a textual study of the formation and transformation of Shennong’s Classic of Materia Medica 
    ...

    Highlights

    This paper reviews the formation and transformation process of the earliest Ben Cao (i.e., materia medica) book: the Shen Nong Ben Cao Jing (Shennong’s Classic of Materia Medica; 25 C.E.–220 C.E.), which appeared during the Han Dynasty period (202 B.C.E.–220 C.E.). A close relationship was found between traditional Chinese medicine and the local religions Fang Xian Dao and Daoism in ancient China.

     

    Traditionality

    Although the early records of pharmacology in traditional Chinese medicine can be traced back to the Pre-Qin period (–221 B.C.E.), the term “Ben Cao” first appeared in the book Han Shu (History of the Han Dynasty; 105 C.E.). The term of “Ben Cao” was used to refer to a group of religious people called Fang Xian Daoists who specialized in the study of alchemy and herbology in Han Shu. Since then, there appeared a series of Ben Cao Jing (Classics of Materia Medica; 25 C.E.–220 C.E.), which recorded a type of mixed knowledge involving medicine and religion. Tao Hongjing (456 C.E.–536 C.E.), a famous doctor and Daoist of the Liang Dynasty (502 C.E.–557 C.E.), compiled the Ben Cao Jing Ji Zhu (Variorum of Classics of Materia Medica; 456 C.E.–536 C.E.). In this book, he claimed that the Shen Nong Ben Cao Jing (Shennong’s Classic of Materia Medica; 25 C.E.–220 C.E.) was the only orthodox Ben Cao Jing written by the legendary sage sovereign Shennong.


    Abstract

    The earliest Ben Cao Jing (Classics of Materia Medica; 25 C.E.–220 C.E.) appeared during the reign of the Han Dynasty (202 B.C.E.–220 C.E.); their origins are traceable to the religious group called Fang Xian Dao. In addition to their use as a medical reference, the Ben Cao Jing works were also used for religious purposes. Tao Hongjing (456 C.E.–536 C.E.), a famous doctor and Daoist (one member of the Chinese local religion, Daoism) of the Liang Dynasty (502 C.E.–557 C.E.), compiled the Ben Cao Jing Ji Zhu (Variorum of Classics of Materia Medica; 456 C.E.–536 C.E.) based on the Shen Nong Ben Cao Jing (Shennong’s Classic of Materia Medica; 25 C.E.–220 C.E.). During the compilation of this book, Tao made a radical medical revision to the Shen Nong Ben Cao Jing, by reducing its religious contents while complementing its medical contents. After such revisions, the ancient Ben Cao Jing was transformed from a religious manual into an herbal pharmacopoeia.

    ...
    Bi-Sheng Peng, Min Lu
  • A new strategy of enhancing absorptivity and safety for evodiamine: polyamidoamine derivatives modified by polyethylene glycol chain 
    ...

    Highlights

    This study confirmed that polyamidoamine-co-polyethylene glycol with molecular weight of 2000 could be used as a potentially safe and efficient oral absorption promoter for evodiamine, one of the major alkaloids found in the traditional Chinese medicine Wu Zhu Yu (Fructus Evodiae) with low solubility and permeability.

     

    Traditionality

    Traditional Chinese medicine Wu Zhu Yu (Fructus Evodiae) is comprised of the dried, nearly ripe fruit of the following plants, Evodia rutaecarpa (Juss.) Benth, Evodia rutaecarpa (Juss.Benth. var. bodinieri (Dode) Huang, or Evodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang in the family Rutaceae. This herbal drug was originally documented in the Li Shizhen’s Bencao Gangmu (Compendium of Materia Medica; 1518 C.E.–1593 C.E.), which is the first complete medical book ever written in the history of traditional Chinese medicine. Wu Zhu Yu (Fructus Evodiae) is bitter, hot, and possesses mildly toxic properties. Moreover, it is the principle drug used in the preparation of the ancient prescriptions Zuo Jin pill and Wu Zhu Yu decoction. Wu Zhu Yu (Fructus Evodiae) is clinically indicated for headaches, vertigo, abdominal pain, diarrhea, vomiting, and other diseases. Evodiamine is one of the major alkaloids in this herbal medicine and is also the active ingredient attributed to the clinical action.


    Abstract

    Background: Traditional Chinese medicine involves complex ingredients and mixtures of ingredients that often exhibit low bioavailability, and excipients are often lacking to increase the absorption-enhancing effects. This study modified the generation 4 polyamidoamine dendrimer with polyethylene glycol of different molecular weights (5000, 2000, 1000) to form a series of polyamidoamine-co-polyethylene glycol (PAMAM-co-PEG) as a novel class of oral absorption enhancers. Evodiamine, the major alkaloid found in the traditional Chinese medicine Wu Zhu Yu (Fructus Evodiae), was used as a model drug to verify the absorption-enhancing effects and the safety of this alkaloid. Methods: This study utilized the solubility determination method documented in the Pharmacopoeia of the Peoples Republic of China (2015 edition) and the D0 values recommended in the US FDA guidelines to comprehensively evaluate the solubility of evodiamine. The permeability of evodiamine was assessed using the apparent permeability coefficient in experiments based on in vitro cell models. Multiple aspects of the biological safety of PAMAM-co-PEG were explored using the MTT assay, LDH assay, and total protein release of the rat intestinal tract. Moreover, the absorption-enhancing effects of PAMAM-co-PEG at different molecular weights on evodiamine were verified via the use of in vitro cell models and in vivo intestinal loop circulation experiments with rats. Results: Evodiamine exhibited low solubility and permeability and was classified into class IV compounds using the biopharmaceutical classification system. PAMAM-co-PEG 2000 demonstrated improvement in the biosafety and absorption-enhancement effect of evodiamine at a specific concentration. This study showed that 0.05% (w/v) of PAMAM-co-PEG 2000 increased the cumulative penetration of evodiamine via cell transport by 1.32 times, and 0.10% (w/v) of PAMAM-co-PEG 2000 increased the area under curve value of evodiamine by 1.31 times. Conclusion: Evodiamine possesses low solubility and permeability and leads to poor oral bioavailability and a certain degree of cytotoxicity. PAMAM-co-PEG 2000 was found to be a potentially safe and efficient oral absorption enhancer. The results of this study might create a foundation for the development of novel excipients suitable for the complex active ingredients of traditional Chinese medicine.

    ...
    Yao-Chun Gao, Yuan-Sheng Lao, Meng-Xue Zhang, Nan Li, Chen-Yang Wu, Zheng-Qi Dong
  • Molecular mechanism prediction analysis of compound Kushen injection in the treatment of COVID-19 based on network pharmacology and molecular docking 
    ...

    Highlights

    The alkaloids in compound Kushen injection (CKI) can blocking viral replication and its binding to severe acute respiratory syndrome coronavirus 2 3CL hydrolase and angiotensin-converting enzyme 2 receptors. They regulate the interleukin-6-mediated signaling pathway, tumor necrosis factor signaling pathway, and steroid hormone biosynthesis, thereby initiating therapeutic responses against coronavirus disease 2019.

     

    Traditionality

    The traditional Chinese medicine CKI was launched in China in 1995 with the approval number of State Food and Drug Administration of China Z14021230, which is composed of Kushen (Sophorae Flavescentis Radix) and Baituling (Rhizoma Heterosmilacis Japonicae). It can effectively clear damp heat, and cool and detoxify blood, which is similar to the anti-inflammatory effects of Western medicine. Kushen (Sophorae Flavescentis Radix) was first recorded in the ancient Chinese medicine record Shen Nong Ben Cao Jing (Shennong’s Classic of Materia Medica, unknown author, written in the Han Dynasty), and Baituling (Rhizoma Heterosmilacis Japonicae) was recorded in Ben Cao Gang Mu (Compendium of Materia Medica) by the famous medical scientist Li Shizhen (written in 1552–1578 C.E.). CKI, one of the eight effective Chinese medicines for treating atypical pneumonia, played an important role in combating severe acute respiratory syndrome coronavirus-induced pneumonia in China in 2003. The study found that CKI has the effect of inhibiting inflammation, and its main chemical ingredients, namely matrine and oxymatrine, promotes Th cells to recognize and eliminate viruses. CKI is now used in the clinical treatment of coronavirus disease 2019, but its molecular mechanism remains unclear and warrants further investigation.


    Abstract

    Background: As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia, compound Kushen injection (CKI) played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003. CKI is known to inhibit inflammation, and its main chemical components, namely matrine and oxymatrine, can promote Th cells to recognize and eliminate viruses. In this study, network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients. The “ingredient-target” network was constructed using the Cytoscape software. The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets. Results: Sophocarpine, sophoridine, matrine, (+)-allomatrine, AIDS211310, and sophranol were the six active ingredients. After docking the active ingredients with severe acute respiratory syndrome coronavirus 2 3CL hydrolase and angiotensin-converting enzyme 2 (ACE2), they displayed suitable affinity, which could block viral replication and its binding to ACE2. The key targets mainly involved inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway. The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway. Conclusion: The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors. They regulate the IL-6-mediated signaling pathway, TNF signaling pathway, and steroid hormone biosynthesis, thereby initiating therapeutic responses against coronavirus disease 2019.

    ...
    Wan-Ying Zhang, Ying Chen, Miao-Miao Zhang, Guo-Wei Zhang
  • Brucea javanica oil inhibits proliferation of hepatocellular carcinoma cells and induces apoptosis via the PI3K/AKT pathway 
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    Highlights

    Brucea javanica oil, extracted from traditional Chinese medicine Ya-dan-zi (Brucea javanica (L.) Merr.), inhibits proliferation of hepatocellular carcinoma cells and induces apoptosis through the PI3K/AKT pathway by upregulating C-caspase3, C-caspase9, Bax, and adenosine monophosphate-activated protein kinase, and downregulating Bcl-2 and mechanistic target of rapamycin.

    Traditionality

    Ya-dan-zi (Brucea javanica (L.) Merr.), a dry fruit widely distributed in Southeast Asia, has been recorded in the ancient book of Chinese medicine, Bencao Gangmu Shiyi (A Supplement to Compendium of Materia Medica), written by the famous medical scientist named Zhao Xuemin in 1765 C.E. (Qing Dynasty of China). Brucea javanica oil, extracted from its mature seeds, has proven effective at treating hepatocellular carcinoma by promoting apoptosis, although the underlying mechanism remains to be determined.

    Abstract

    Background: Brucea javanica oil (BJO), distributed primarily in Southeast Asia, has long been utilized as a therapeutic agent for treating malignancies. However, its anticancer mechanisms are not clearly understood. The objective of this study was to examine the mechanisms underlying its treatment of hepatocellular carcinoma cells. Methods: CCK8 assay was used to evaluate cell viability. Hoechst33342 staining and flow cytometry analyses were used to examine apoptosis. Mito-Tracker Red CMXRos kit was used to measure the membrane potential of mitochondria. ATP assay kit was used to evaluate ATP levels. Western blots were used to assess the presence of AKT, adenosine monophosphate-activated protein kinase, Caspase3, Caspase9, Bax, and Bcl-2. Results: BJO inhibited the proliferation of hepatocellular carcinoma cells HepG2 in a time- and dose-dependent manner. It induced apoptosis, with the percentage of cells treated with 50-150 μg/mL BJO increasing from 8.01% to 28.02% in a concentration-dependent manner (P < 0.05, when 50 μg/mL of BJO group compared with the control group; P < 0.001, when 100 or 150 μg/mL of BJO group compared with the control group). After exposed to BJO, the expression of C-caspase3, C-caspase9 and Bax upregulated while that of Bcl-2 downregulated. BJO suppressed the PI3K/AKT pathway and promoted phosphorylation of adenosine monophosphate-activated protein kinase, while repressing the phosphorylation of mechanistic target of rapamycin. Compared with treatment by BJO alone, the PI3K/AKT agonist 740Y-P increased the survival rate of HepG2 cells (P < 0.01) and attenuated the inhibitory effect of BJO on cell apoptosis (P < 0.05). Conclusion: BJO is capable of inhibiting proliferation of HepG2 cells and inducing apoptosis via the PI3K/AKT pathway.

    ...
    Yan-Peng , Zhan Ye, Zhao-Jun Zheng, You-Dong Li, Jing Chen, Farah Zaaboul, Yong-Jiang Xu, Yuan-Fa Liu

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