ABSTRACT
In ancient times, the original plants of Citri Exocarpium Rubrum and Citri Grandis Exocarpium had experienced succession and change, including tangerine(Citrus reticulata), pomelo(C. grandis), and Huazhou pomelo(C. grandis 'Tomentosa'), a specific cultivar of C. grandis produced in Huazhou, Guangdong. Before the Qing Dynasty, tangerine was the main original plant, while Huazhou pomelo came to the fore in the Qing Dynasty. In the 1950 s and 1960 s, the producing area of Huazhou pomelo was destroyed, and thus it had to be supplemented with pomelo. From then on, C. grandis 'Tomentosa' and C. grandis were both listed as the original plants of Citri Grandis Exocarpium in the Chinese Pharmacopoeia. This paper reviewed the historical evolution of the collection, processing, and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium. The research showed that:(1)The harvest time of the original plants of Citri Grandis Exocarpium and Citri Grandis Exocarpium had changed from maturity to immaturity. The collection and processing of Citri Exocarpium Rubrum was first recorded in the Illustrated Classics of Materia Medica in the Song Dynasty. During the Ming and Qing Dynasties, the mesocarp of Citri Exocarpium Rubrum needed to be removed completely, and Citri Grandis Exocarpium from C. grandis 'Tomentosa' was processed into different specifications such as seven-piece, five-piece, and single piece. Furthermore, processed young fruits of Huazhou pomelo appeared.(2)Citri Exocarpium Rubrum and Citri Grandis Exocarpium were processed with carp skin for the first time in the Master Lei's Discourse on Medicinal Processing. It was suggested that carp skin might be helpful for eliminating bones stuck in throat. During the Song, Jin, and Yuan Dynasties, some other processing methods such as ba-king, stir-frying, and salt-processing appeared. Honey, soil, ginger juice, and alum were firstly used as adjuvants for the processing in the Ming and Qing Dynasties. Citri Exocarpium Rubrum was mainly prepared with salt in order to improve the effect of lowering Qi, while it was unnecessary for Citri Grandis Exocarpium from C. grandis 'Tomentosa' because of its obvious effect of lowering Qi and eliminating phlegm. The stir-frying and honey-frying methods helped reduce the strong effect of Citri Grandis Exocarpium from C. grandis 'Tomentosa'.(3)According to the application of Citri Exocarpium Rubrum and Citri Grandis Exocarpium in history, their medicinal use began in Han and Tang Dynasties, developed in Song, Jin, and Yuan Dynasties, and matured in Ming and Qing Dynasties. Citri Grandis Exocarpium from C. grandis 'Tomentosa' was originally applied in Ming and Qing Dynasties, and it still plays an important in role treating COVID-19 nowadays. Moreover, Citri Grandis Exocarpium from C. grandis had cold medicinal property, while Citri Grandis Exocarpium from C. grandis 'Tomentosa' had warm medicinal property, and thus they should not be treated the same. At present, Huazhou pomelo has a certain production scale. Therefore, it is recommended that in the next edition of Chinese Pharmacopoeia, only C. grandis 'Tomentosa' should be included as the original plant of Citri Grandis Exocarpium, and C. grandis should be deleted. The results are conducive to the further development and utilization of Citri Exocarpium Rubrum and Citri Grandis Exocarpium, and support the rational use of Citri Grandis Exocarpium and its processed products.
Subject(s)
Humans , COVID-19 , Citrus , Drugs, Chinese Herbal , Materia Medica , SARS-CoV-2ABSTRACT
Objective:By the method of network pharmacology， the mechanism of Pinelliae Rhizoma and Citri Exocarpium Rubrum in the treatment of metabolic syndrome was explored. Method:Effective components of Pinelliae Rhizoma and Citri Exocarpium Rubrum were retrieved by TCMSP database，and then selected by ADME parameters. TCMID，BATMAN-TCM，SymMap，TCM-MESH database were used to supplement effective components of TCMSP. TCMSP target prediction model was used to predict potential targets of drugs. DRUGBANK，DisGeNET，CTD，GeneCards，OMIM，PharmGkb，KEGG，DiGSeE databases were retrieved to obtain the targets of metabolic syndrome，and the chips were downloaded and analyzed through GEO database No.GSE98895 to screen out the differential genes of normal people and patients with metabolic syndrome，and supplement the target databases of metabolic syndrome. The intersections of Pinelliae Rhizoma-Citri Exocarpium Rubrum and metabolic syndrome disease targets were obtained by Rstudio 3.6.2. The above intersection targets were imported into the Metascape database for module analysis and overall GO（Biological Process），KEGG and Reactome pathway analysis. The core targets were selected from the intersection targets by using the cytohubba plug-in，the core genes were input into the database of BioGPS，Genecards to analyze the tissue distribution and subcellular distribution，and the core targets were assigned by using the database of DisGeNET. Result:A total of 34 active components and 120 targets of Pinelliae Rhizoma and Citri Exocarpium Rubrum were screened out，and 115 targets were obtained after the intersection of Rstudio 3.6.2. The results of Metascape module analysis and whole analysis were mostly the same，mainly involving the biological processes， such as ligand receptor interaction，calcium ion，cGMP-PKG，cholinergic synapse，thyroid hormone，insulin. The cytohubba plug-in was used to screen out 17 targets，involving 17 key genes， such as VEGFA and NOS3. The tissue and subcellular distribution of the core targets mainly included lymphoblasts，CD33+_myeloid cells，amygdala，pineal and cytoplasmic matrix，mitochondria. The main proteins were signal molecules，kinases and nucleic acids. Conclusion:Pinelliae Rhizoma and Citri Exocarpium Rubrum could treat metabolic syndrome through complex biological processes and pathways，such as blood circulation，ligand receptor interaction of nerve activity，cGMP-PKG，interleukin-related action，calcium ion. This indicates that traditional Chinese medicine（TCM） treated diseases through multi-component，multi-target，multi biological processes，multi-channel and other ways（which is also proved by the distribution of core genes in the tissue，subcellular and protein ascription information），indicating the superiority of the holism concept of TCM. Erchetang and its similar prescriptions are suitable for treating metabolic syndrome，which also indicates that the principle of "treating different diseases with the same therapy" of TCM is not only reflected at the theoretical level； and network pharmacology needs to be further proved in the combination with experimental verification.