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.
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.
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.
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.
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.
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.
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 People’s 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.
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.
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.
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.
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.
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.
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