ABSTRACT
Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.
ABSTRACT
Objective: To explore the action mechanism of five Chinese medicines targeting ACE2 for the treatment of COVID-19. Methods: Chinese medicines with human angiotensin converting enzyme II (ACE2) targeting activity were screened through the traditional Chinese medicine (TCM) system pharmacology database and analysis platform (TCMSP), and the TCMSP platform was further utilized to identify the active ingredients of Chinese medicines and their corresponding drug targets. Then, the protein interaction of the above protein targets was analyzed by STRING online database and the relevant data were downloaded. Next, the core sub-network modules in the PPI network system were screened through the MCODE plug-in in CytoScape 3.2.1 software. The functional enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) were carried out, using online enrichment analysis software DAVID v6.8, to predict the pharmacological mechanism of the above five Chinese medicines, and to verify and explore the feasibility of compatibility and clinical application of related herb-pair or formula under the theoretical system of TCM. Results: Five Chinese medicines with potential therapeutic effects on ACE2 were selected through the TCMSP platform, namely Bupleuri Radix, Puerariae Lobatae Radix, Puerariae Lobatae Flos, Cyathulae Radix, and Hemerocallis Radix, which contained 42 active ingredients and 240 drug targets. The results of GO biological function enrichment analysis showed that the above five Chinese medicines could affect the biological processes such as inflammatory response, cell apoptosis and proliferation and etc. The results of KEGG pathway enrichment analysis showed that the pharmacological mechanisms of these Chinese medicines were closely related to PI3K-Akt pathway, TNF pathway, FoxO pathway, MAPK pathway, and so on. In TCM theory, Bupleuri Radix and Puerariae Lobatae Radix is a classic herb-pair for the treatment of infectious and febrile diseases. Chaige Jieji Decoction is widely used in febrile diseases in ancient and modern clinics, and has achieved good clinical effects. The main febrile disease treated by this herb-pair is the triple-yang combination of diseases in the syndrome differentiation of the six meridians, which is in line with the syndrome differentiation of TCM in patients with SARS-CoV-2 infection. It can be used with Cyathulae Radix and Hemerocallis Radix in addition and subtraction. Conclusion: The identified five Chinese medicines have multi-target, multi-function and multi-pathway pharmacological effects on the treatment of COVID-19. According to the theoretical analysis of TCM and previous clinical experience, it is suggested that Chaige Jieji Decoction or Bupleuri Radix and Puerariae Lobatae Radix herb-pair can be used to treat COVID-19.
ABSTRACT
Multi-components compatibility theory of Chinese materia medica (CMM) has been more and more mature and perfect, because of the efforts of many scientific and technological workers for nearly 20 years. Omics, compatibility, and fingerprint are the three key words of the multi-components compatibility theory. Namely in multi-components compatibility theory, modern "omics" and traditional "compatibility" are closely combined through "fingerprint". The modernization of CMM has developed to such a stage that the fingerprint (especially IGD 13C-NMR coupling fingerprint) method could be used to study morden CMM under the guidance of multi-components compatibility theory.
ABSTRACT
The research of modern Chinese herbal components compatibility is a complex systems engineering,based on the academic theories of combination of traditional Chinese medicine(TCM)and modern medicine as a guide,which is the development trend of integration of overall regulation and targeting effect.Angina pectoris is one of the most types of cardiovascular diseases,new drugs created by combination of the effective components of Chinese herbal medicines play an important role in the prevention and treatment of angina pectoris.There are many progresses in the clinical and experimental studies about treatment of angina pectoris through the way of components compatibility.The components compatibility are in the era of modern diseases,sciences and technology,based on the inheritance and innovation of TCM,and towards to found a system science in future.