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A Nomogram model for the early warning of essential hypertension risks based on the principles of traditional Chinese medicine syndrome elements

ZHUO Zewei ; ZHANG Fei ; YANG Chengwei ; GAO Bizhen ; LI Candong

Digital Chinese Medicine.2023;6(3):245-256.

[Objective] To construct a Nomogram model for the prediction of essential hypertension (EH) risks with the use of traditional Chinese medicine (TCM) syndrome elements principles in conjunction with cutting-edge biochemical detection technologies. [Methods] A case-control study was conducted, involving 301 patients with essential hypertension in the hypertensive group and 314 without in the control group. Comprehensive data, including the information on the four TCM diagnoses, general data, and blood biochemical indicators of participants in both groups, were collected separately for analysis. The differentiation principles of syndrome elements were used to discern the location and nature of hypertension. One-way analysis was carried out to screen for potential risk factors of the disease. Least absolute shrinkage and selection operator (LASSO) regression was used to identify factors that contribute significantly to the model, and eliminate possible collinearity problems. At last, multivariate logistic regression analysis was used to both screen and quantify independent risk factors essential for the prediction model. The “rms” package in the R Studio was used to construct the Nomogram model, creating line segments of varying lengths based on the contribution of each risk factor to aid in the prediction of risks of hypertension. For internal model validation, the Bootstrap program package was utilized to perform 1000 repetitions of sampling and generate calibration curves. [Results] The results of the multivariate logistic regression analysis revealed that the risk factors of EH included age, heart rate (HR), waist-to-hip ratio (WHR), uric acid (UA) levels, family medical history, sleep patterns (early awakening and light sleep), water intake, and psychological traits (depression and anger). Additionally, TCM syndrome elements such as phlegm, Yin deficiency, and Yang hyperactivity contributed to the risk of EH onset as well. TCM syndrome elements liver, spleen, and kidney were also considered the risk factors of EH. Next, the Nomogram model was constructed using the aforementioned 14 risk predictors, with an area under the curve (AUC) of 0.868 and a 95% confidence interval (CI) ranging from 0.840 to 0.895. The diagnostic sensitivity and specificity were found to be 80.7% and 85.0%, respectively. Internal validation confirmed the model’s robust predictive performance, with aconsistency index (C-index) of 0.879, underscoring the model’s strong predictive ability. [Conclusion] By integrating TCM syndrome elements, the Nomogram model has realized the objective, qualitative, and quantitative selection of early warning factors for developing EH, resulting in the creation of a more comprehensive and precise prediction model for EH risks.

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Medication rule and mechanism of traditional Chinese medicine in treating metabolism-associated fatty liver disease based on bioinformatics technology

ZHANG Yunkun ; YAO Rong ; LI Lin ; LI Wenli ; LI Changqing ; PAN Yu ; LI Shunxiang

Digital Chinese Medicine.2023;6(3):257-271. doi:DOI: 10.1016/j.dcmed.2023.10.002

[Objective[ To analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods] Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

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Quality by Design approach for the investigation of critical characteristics of Phyllanthus emblica from different vicinities

Prakash Ramakrishnan ; Priya Masand ; Pooja Dhama ; Anurag ; Sunil Gupta ; Alok Sharma

Digital Chinese Medicine.2023;6(3):272-284. doi:10.1016/j.dcmed.2023.10.003

[Objective] To explore the application of Quality by Design (QbD) tools in assessing geographical variations of Phyllanthus emblica (P. emblica) from five distinct Indian states. [Methods] In the current experiment, the Box-Behnken design with a reduced quartic model and 105 runs was employed with the use of the Design Expert software for randomized response surface mapping. Three different extraction methods (Soxhlet, maceration, and sonication) along with three solventst [distilled water, methanol, and water-methanol mixture (50 : 50 v/v)] were considered in the present study. The anti-oxidant activities, total flavonoid content (TFC), and total phenolic content (TPC) in the P. emblica were determined and analysed by gas chromatography-mass spectrometry (GC-MS) to identify the major components. [Results] The QbD overlay plot showed that the extractive value of the P. emblica was no less than 30% w/w, 2,2-diphenyl-1-picrylhydrazyl (DPPH) no less than 60% mcg/mL (micrograms per millilitre), TFC no less than 75 mg QE/g (milligrams of quercetin equivalents per gram), and TPC no less than 80 mg GAE/g (milligrams of gallic acid equivalents per gram). Moreover, the GC-MS data confirmed the presence of variation in the bioactives of P. emblica extracts. [Conclusion] The model was significant in describing the variation in extractive value, DPPH, TFC, and TPC. The QbD approach may tend to prioritize thoroughness in the extraction process, ultimately resulting in improved quality in the extracted products.

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Protective effects of ginsenosides on macrophages subjected to simulated weightlessness

LI Boye ; CHEN Tian ; JI Enhui ; CHEN Ying ; HU Qin ; LI Qingyan

Digital Chinese Medicine.2023;6(3):285-294. doi:10.1016/j.dcmed.2023.10.004

[Objective] To investigate the evolution of inflammation under conditions and the effects of ginsenosides on macrophages subjected to the simulated weightlessness, with the aim of mitigating the inflammation. [Methods] Initially, genes related to weightlessness, inflammation, and immunity were identified in the GeneCards database. Then, Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) protein network analysis was conducted to determine the core targets involved in the weightlessness-induced inflammation. Subsequently, Label-Free Quantitative (LFQ) proteomics was carried out to discern the distinctive genes within ginsenoside-treated Tohoku Hospital Pediatrics-1 (THP-1) cells. Next, utilizing the outcomes of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the biological processes and signaling pathways in which ginsenosides predominately engaged were scrutinized, and the primary targets of ginsenosides in combating weightlessness-induced inflammation were examined. Finally, enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α from lipopolysaccharide (LPS)-induced THP-1 cells under simulated weightlessness conditions, as well as during the weightlessness recovery period following treatment with ginsenosides. [Results] A total of 2 933 genes associated with inflammation, 425 genes linked to weightlessness, and 4 564 genes connected to immunity were retrieved from the GeneCards database. Protein-protein interaction (PPI) networks were generated to identify pivotal targets associated with weightlessness-induced inflammation such as IL-1β, IL-6, TNF, and albumin (ALB). It was found that ginsenosides primarily participated in the regulation of various inflammationrelated signaling pathways and pathways related to pathogenic microorganism infections. Moreover, it has a significant impact on the expression of proteins such as cluster of differentiation 40 (CD40), IL-1β, and poly ADP-ribose polymerase 1 (PARP1). As revealed in the simulated weightlessness cell test, ginsenosides exhibited a remarkable capacity to attenuate the secretion of inflammatory factors, specifically IL-6 and TNF-α (P < 0.000 1), in THP-1 macrophages following induction by LPS under simulated weightlessness conditions. In addition, it reduced the secretion of IL-1β, IL-6, IL-8, and TNF-α (P < 0.000 1) during the weightlessness recovery phase [Conclusion] Weightlessness can disrupt several inflammation-related signaling pathways, but ginsenosides were shown to mitigate the release of various inflammatory factors in macrophages subjected to simulated weightlessness, thereby exerting a protective role against inflammation. This study has laid a theoretical groundwork for further exploring the potential application of ginsenosides in safeguarding against LPS induced inflammation in a weightlessness environment.

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Croton hirtus attenuating streptozotocin-induced neuroinflammation in rats

Prakash Ramakrishnan ; Jayaram Rajangam ; Binoy Varghese Cherian ; Jose Prakash Dharmian

Digital Chinese Medicine.2023;6(3):295-306. doi:10.1016/j.dcmed.2023.10.005

Objective: The present study was aimed to investigate the neuroprotective effect of Croton hirtus (CH) extract against streptozotocin (STZ) in rats. Methods: (i) The sub-chronic toxicity consisted of 24 adult rats of either sex weighing from 160 to 200 g were divided into four groups with six rats in each group. Rats in group 1 received Dimethyl sulfoxide (DMSO) mixed with saline; rats in groups 2, 3, and 4 received 100, 200, and 400 mg/kg of methanolic extract of CH (MECH) orally by gavage administration for 28 d, respectively. The functional observation battery and locomotor activity were graded as part of their neurobehavioral activity and the brain regions, including cortex and hippocampus, were analyzed for neuropathological abnormalities. (ii) The main research consisted of 30 adult male Wistar rats weighing from 160 to 200 g, which were divided into five groups and six rats in each group, including control (I), STZ (II), Donepezil (III), MECH (100 mg/kg, IV), and MECH (200 mg/kg, V) groups. Rats in group I received citrate buffer orally and DMSO mixed with saline for 14 d. Rats in group II received STZ via intracerebroventricular injection (3 mg/kg, bilateral ICV-STZ) on days 1 and 3 followed by DMSO mixed with saline for 14 d. Rats in groups III, IV, and V received STZ administration on days 1 and 3 followed by Donepezil [3 mg/(kg·d), p.o.] and MECH [100 and 200 mg/(kg·d), p.o.] for 14 d. Rats were tested for learning and memory parameters such as Morris water maze (MWM) and passive avoidance test (PAT). They were sacrificed after completing behavioural experiments; brains were harvested to estimate the acetylcholinesterase (AChE), lipid peroxidation (LPO), glutathione (GSH), and superoxide dismutase (SOD) by using UV-Visible Spectrophotometer; caspase-3 was evaluated by total fluorescence emission spectra; amyloid β (Aβ) levels were detected using enzyme-linked immuosorbent assay (ELISA); and histopathological examination was conducted in the CA1 region of the hippocampus. Results : (i) The sub-chronic toxicity results revealed that open field test parameters including line crossing, rearing, entering the middle square, defecating, or urinating did not differ significantly in the MECH rats (P > 0.05). The histopathological observation did not show any lesions in the neuronal cells and inflammation in both the regions in MECH rats compared with control rats. (ii) The main study findings demonstrated that STZ-treated rats showed asignificant increase in impairment in learning and memory parameters (P < 0.001), the levels of AChE, caspase-3, Aβ (1-40 and 1-42), and LPO were increased significantly (P < 0.001), and significant decrease was found in the levels of SOD (P < 0.001) and GSH (P < 0.01). Moreover, neuronal damage was found in the hippocampus. In contrast, STZ-induced behavioural and biochemical impairments in rats were considerably decreased by treatment with MECH dose-dependently. Conclusion MECH significantly prevented the memory deficit induced by STZ due to antioxidant action. Restoration of cholinergic functioning may be the cause of behavioural improvement. Therefore, MECH may be able to treat cognitive disorders like Alzheimer's disease (AD).

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Inhibition of photoreceptor apoptosis in mice with retinitis pigmentosa through NF-κB/NLRP3 pathway suppression with Lycium barbarum polysaccharide

Ying WANG ; Ying DENG ; Jing LU ; Jun PENG ; Yasha ZHOU ; Yijing YANG ; Qinghua PENG

Digital Chinese Medicine.2023;6(3):307-316. doi:10.1016/j.dcmed.2023.10.006

Objective: To explore whether Lycium barbarum polysaccharide (LBP) can reduce the apoptosis of retinal photoreceptor cells in retinitis pigmentosa (RP) mice by inhibiting nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling pathway. Methods: (i) In vitro experiments, mouse retinal ganglion cells (661W cells) were divided into normal, model, LBP low-dose (LBP-L, 40 mg/L), LBP middle-dose (LBP-M, 80 mg/L), LBP high-dose (LBP-H, 160 mg/L), and positive drug control (NLRP3 inhibitor, 160 mg/L) groups. And the 661W cells were exposed to varying concentrations of H2O2 ranging from 50 to 400 μmol/L to determine the optimal concentration for inducing apoptosis (200 μmol/L). Then the cell viability was assessed using Cell Counting Kit-8 (CCK-8), while the apoptosis rate was detected by flow cytometry; the expression of NLRP3 was detected by immunofluorescence; and the expression of apoptosis markers was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). (ii) In vivo assays were carried out with the use of C57/BL6 and Rd10 mice. The animal experimental groups were divided into normal, model, LBP-L, LBP-M, LBP-H, and NLRP3 inhibitor groups, in which the normal group was C57/BL6 mice and the other groups were Rd10 mice. Ten mice were included in each group, and the corresponding drugs were administered intragastrically for a duration of four weeks. NF-κB/NLRP3 pathway and the expression of apoptosis markers were observed by electroretinogram, histopathological examination, and WB to assess the effects of LBP on retinal photoreceptor cell apoptosis. Results: (i) In vitro experiments, compared with the normal group, the apoptosis rate of 661W cells in model group was significantly increased (P < 0.01), and the expression levels of key proteins of NF-κB/NLRP pathway, such as NLRP3, NF-κB, p-NF-κB, and pro-apoptotic protein caspase-3, were up-regulated (P < 0.01). The rate of Bax/Bcl-2 was increased (P < 0.01), and the concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly increased (P < 0.01). Compared with the model group, high dose of LBP decreased the apoptosis rate of 661W cells (P < 0.01), and down-regulated the expression levelsof the key proteins of NF-κB/NLRP3 pathway, including NF-κB, NLRP3, p-NF-κB, and caspase-3 (P < 0.01). The rate of Bax/Bcl-2 was decreased (P < 0.01), and the concentrations of IL-1β and TNF-α were decreased (P < 0.01). (ii) In vivo experiments, high dose of LBP significantly increased morphological changes in the outer nuclear layer (ONL) thickness of Rd10 mice, as well as functional changes in the amplitudes of the a-wave and b-wave (P < 0.01), which also down-regulated the expression levels of NF-κB (P < 0.05), NLRP3, p-NF-κB, and caspase-3 (P < 0.01), reduced the Bax/Bcl-2 rate (P < 0.01), and decreased the concentrations of IL-1β (P < 0.01) and TNF-α (P < 0.05). Conclusion LBP could improve both retinal morphology and function, providing protection to photoreceptors from apoptosis through the inhibition of the NF-κB/NLRP3 pathway.

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Mechanism of Bugansan Decoction in ameliorating learning and memory impairment in D-galactose-induced aging rats based on AGEs/RAGE/NF-κB pathway

Wei LI ; Shuo WANG ; Jiepeng WANG ; Fang FANG ; Chaoyi FANG

Digital Chinese Medicine.2023;6(3):317-327. doi:10.1016/j.dcmed.2023.10.007

: Objective To investigate the underlying mechanism of the compound Bugansan Decoction (补肝散, BGSD) in intervening learning and memory in D-galactose (D-gal)-induced aging rats. Methods: A total of 40 rats were randomly assigned to four groups: control, model, BGSD [14.06 g/(kg·d)], and piracetam [0.4 g/(kg·d)] groups, with 10 rats in each group. D-gal [400 mg/(kg·d)] was injected intraperitoneally to establish the aging rat model. The rats' body weight, water intake, food intake, and gripping strength were recorded each week. The eightarm maze and step-down test were used to measure the rats' capacity for learning and memory. Liver, thymus, spleen, and brain tissues were weighed to calculate the corresponding organ indices; serum malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Hematoxylin and eosin (HE) staining was adopted to observe the pathological changes of the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the hippocampus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of receptors for advanced glycation end products (RAGE), nuclear factor-κB (NF-κB), TNF-α, IL-6, and IL-1β mRNA in the hippocampus. Western blot (WB) was employed to detect the expression levels of advanced glycation end products (AGEs), RAGE, and NF-κB protein in the hippocampus. Results: In D-gal-induced aging rats, BGSD significantly increased food intake, water intake, body weight, gripping strength, and organ indices (P < 0.05), and significantly decreased working memory error (WME), reference memory error (RME), and total memory errors (TE) in an eight-arm maze (P < 0.05). In the step-down test, step-down latency was prolonged and the frequency of errors dropped (P < 0.05). Additionally, BGSD could lessen the harm done to hippocampus neurons, increase serum SOD activity, lower MDA levels, and down-regulate the expression levels of the pro-inflammatory molecules TNF-α, IL-6, and IL-1β (P < 0.05). Further findings showed that BGSD significantly decreased hippocampal AGEs, RAGE, and NF-κB expression (P < 0.05). Conclusion By blocking the AGEs/RAGE/NF-κB signaling pathway, BGSD may regulate the neuroinflammatory damage in D-gal-induced aging rats, and thus improve learning and memory.

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Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice

Di ZHAO ; Fayyaz Sharmeen ; Ziyang YI ; Zhao LIU ; Yan WANG ; Ping CAI ; Wei HE

Digital Chinese Medicine.2023;6(3):328-340. doi:10.1016/j.dcmed.2023.10.008

Objective: To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). Methods: A total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. Results: Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). Conclusion Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

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Effects of carbonization processing on quality control, chemical compositions, and pharmacological mechanism of Ganjiang (Zingiberis Rhizoma)

Yiqun ZHOU ; Ping WU ; Yu TANG ; Wenlong LIU ; Jilian SHI ; Fuyuan HE

Digital Chinese Medicine.2023;6(3):341-356. doi:10.1016/j.dcmed.2023.10.009

Ganjiang (Zingiberis Rhizoma, ZR) and Jiangtan (Carbonized Zingiberis Rhizoma, CZR) have long been used in traditional Chinese medicine (TCM) with a rich history in the treatment of various ailments. While ZR and CZR obviously stem from the same botanical source, their attributes, chemical compositions, pharmacological behaviors, and clinical applications are different owing to variations in the extent of drying and processing they undergo. In this paper, data pertaining to ZR and CZR were retrieved from databases including China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Google Scholar. These sources were scrutinized to elucidate the distinctions between ZR and CZR arising from carbonization processing in terms of their ethnopharmacology, quality control, chemical compositions, biological activities, pharmacological mechanisms, and clinical uses. In this study, a total of 56 chemical constituents were identified and isolated from ZR and CZR, which primarily encompassed volatile oils, gingerols, and diphenylheptane compounds. CZR's pharmacological effects include hemostatic, anti-oxidant, analgesic, antibacterial, anti-cancer, and other biological activities. ZR has pungent and warm properties. It is a Yang-supplementing herbal medicine for ailments exacerbated by cold or damp climatic influences. CZR is a product of ZR after undergoing high temperature, with diminished intensity of its pungent and warm attributes. This change leads to a more gradual treatment efficacy, renowned hemostatic effects and its ability to gently invigorate the spleen and effectively alleviate diarrhea. Currently, research on the pharmacological mechanism of CZR is mainly focused on the effects of CZR on coagulation and fibrinolysis. Although the healing effect of CZR has long been known, and some correlation has been found between the changing composition and the changing color of the decoctions, people still lack relatively clear processing mechanisms to reflect the characteristics and specific quality standards of the ingredients of CZR's hemostatic effect. This review provides a systematic summary on quality control, chemical composition, ethnopharmacology, and pharmacology of CZR, offering novel perspectives for advancing the exploration of additional carbonized herbal medicine and fostering their application in clinical settings

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Patents research and development prospects of spleen-invigorating health food with the homology of medicine and food from 2000 to 2022: a bibliometric analysis

Ping LIU ; Rui FANG ; Jiawei HE ; Ze LI ; Yue ZHOU ; Yong YANG ; CHENG Shaowu

Digital Chinese Medicine.2023;6(3):357-368. doi:10.1016/j.dcmed.2023.10.010

: ,Objective To analyze the current status and development trends of the patents of spleen-invigorating health food with the homology of medicine and food in China, and to provide ideas and references for the research and development of traditional Chinese medicine (TCM) spleen-invigorating health food with the homology of medicine and food. Methods: The State Administration for Market Regulation website’s “Special Food Information Query Platform” and the incoPat global patent database were searched in this study. Based on the methods of bibliometrics, the registered health food and patents related to spleen-invigorating health food with the homology of medicine and food in China were sorted out. Furthermore, the research and development numbers, provinces, institutions, technology and efficacy classification, major drugs, active ingredients and others of invigorating spleen health food in China were analyzed, and filtered patent data were visualized and analyzed by R programming language and CytoScape software. Results: A total of 285 patents of health food with the homology of medicine and food for invigorating spleen were included and analyzed. From 2012, the patent registration numbers of these spleen-invigorating health food with the homology of medicine and food increased significantly in China. Over the past 20 years, the top five provinces in terms of patent disclosures were Guangdong, Anhui, Jiangsu, Shandong, and Guangxi. It was found that the technical efficacy of over 20 patents was described as “immune enhancement” “digestion” “disease prevention”, etc. Patent applications were mainly aimed at the research and development of the preservation of food or ingredients, the specific therapeutic activity of compounds, and pharmaceutical preparations, which were led by corporation research and development registrations, and supplemented by applications from research institutions and individuals. Among the 285 patents, the top 10 raw materials of spleen-invigorating health food with the homology of medicine and food were Shanyao (Dioscoreae Rhizoma), Fuling (Poria), Shanzha (Crataegi Fructus), Baizhu (Atractylodis Macrocephalae Rhizoma), Chenpi (Citri Reticulatae Pericarpium), Dazao (Jujubae Fructus), Gancao (Glycyrrhizae Radix et Rhizoma), Fengmi (Mel), Maiya (Hordei Fructus Germinatus), and Dangshen (Salviae Miltiorrhizae Radix et Rhizoma). The main functions were to nourish spleen and replenish Qi, invigorate spleen and benefit lungs, nourish blood and promote fluid production, and nourish spleen and stomach. Conclusion The main drug composition and functional components of spleen-invigorating health food with the homology of medicine and food are relatively clear, and the technical effects of invigorating the spleen and stomach, eliminating accumulation of food, and enhancing immunity are highly targeted. This paper provides evidence for the research and development, mechanism research, and process improvement of spleen-invigorating health food with the homology of medicine and food in the future.

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