Syndrome differentiation and treatment is the core feature and strength of traditional Chinese medicine (TCM), with syndrome serving as the cornerstone of TCM diagnosis and treatment. However, under the dominance of the modern medical research paradigm, a considerable number of current TCM studies, especially basic experimental research, exhibit a tendency to "emphasize disease while neglecting syndrome," "have disease without syndrome," or even "abandon medical theory while retaining only drugs." This conceptual deviation causes TCM research to lose its distinctive characteristics, and fails to reflect the efficacy evaluation of TCM′s advantages. In the long run, it may further marginalize the core thinking of TCM within the scientific research system, thereby eroding its foundation. Strengthening and promoting the "disease-syndrome combination" research model is the key to resolving this dilemma and achieving the preservation and innovation of TCM. Through over three decades of continuous efforts, our team has explored and put into practice a disease-syndrome combination research model centered on the "Three-Cause Theory" and integrating clinical and basic researches. At the clinical research level, this model integrates macroscopic four-diagnosis information with microscopic physicochemical indicators, utilizes large-sample data and artificial intelligence method, and constructs an objective and quantifiable syndrome diagnosis model. At the basic research level, grounded in the "Three-Cause Theory" (pathogenic factors, genetic constitution, and disease stage), we have established a "Three-Dimensional Model" (macro sign combinations, micro indicator feature combinations, and formula-based counter-evidence) for the preparation and evaluation of disease-syndrome combination animal models, providing a reproducible and verifiable experimental carrier for modern scientific interpretations of TCM theories. Practice has demonstrated that this system can effectively evaluate the efficacy of Chinese herbal formulas in concurrently treating both the disease and syndrome, while also advancing the modern scientific exposition of TCM′s connotation. The establishment of this methodology helps propel syndrome research into a new stage that is modelable, predictable, and verifiable, offering referable pathways and methodological references for the modern interpretation of TCM principles.
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Open Access
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Open Access
Original Article
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To investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).
We explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.
Network pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P < .001), and interleukin-1β (P = .004) mRNAs in vivo.
The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.
Open Access
Original Article
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To evaluate the effect of traditional Chinese medicine (TCM) on anthracycline-induced cardiotoxicity (AIC) in animal models.
Separate systematic searches for preclinical studies were performed in the PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Chinese Scientific Journal Database, and Wanfang Data from inception to August 2019. The primary outcomes were echocardiography, serum assays for myocardial enzymograms, histological assessments, and electrocardiograms. The secondary outcomes mainly included body weight and safety evaluations. The protocol is registered on PROSPERO (CRD42019145819). RevMan (V.5.3) was used for meta-analysis.
We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models. All the included studies reported that, compared with animal model without any intervention, TCM significantly improved ventricular function, cardiac biomarkers, electrocardiograph results, and cardiac fibrosis. Improved survival rates and body mass indices were also observed with TCM. We further pooled the available data from four studies (63 animals) for the meta-analysis and the results showed that, compared with models without any intervention, TCM significantly increased the ejection fraction by 14.13% (95% CI, 9.96–18.29) and fraction shortening by 8.66% (95% CI, 6.05–11.26). Creatine kinase-MB (SMD = −2.49, 95% CI: −3.12 to −1.85) and lactate dehydrogenase (SMD = −2.78, 95% CI: −3.45 to −2.12) were also significantly decreased by TCM.
TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice. Additionally, the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.
Open Access
Original Article
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Longshengzhi capsule (LSZC) is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction (BYHWD), and is approved by the China Food and Drug Administration for treating stroke-induced disability and vascular diseases. Herein, we examined the pharmacodynamics, anti-apoptotic and anti-oxidant actions, and potential mechanisms of action of LSZC following stroke in rats.
Permanent middle cerebral artery occlusion (MCAO) was used as an ischemic stroke model. LSZC was administered intragastrically. We examined the survival rate, bodyweight, and neurological deficits in stroke rats. Brain infarct size was determined by 2, 3, 5-triphenyltetrazolium chloride staining. Brain pathology was examined using hematoxylin and eosin staining, Nissl staining, and TdT-mediated dUTP Nick-End Labeling staining. Malondialdehyde, catalase, superoxide dismutase, and glutathione levels were examined by commercial kits. Expression of Nrf2, heme oxygenase-1, Bax, Bcl-2, cleaved caspase-3, and caspase-3 proteins in brain tissue was measured by Western blot.
LSZC markedly improved the survival rate and bodyweight, and reduced infarct volume and neurological deficit scores, in MCAO stroke rats. LSZC also significantly attenuated oxidative stress, as indicated by decreased expression of malondialdehyde, and upregulation of Nrf2, heme oxygenase-1, catalase, superoxide dismutase, and glutathione. Moreover, LSZC significantly decreased apoptosis, including a decrease in Bax and cleaved caspase-3 expression, and an increase in Bcl-2, as well as a reduction in numbers of apoptotic neurons.
LSZC treatment is neuroprotective against ischemic stroke, potentially via reducing oxidative stress and apoptosis. The Nrf2 and apoptotic signaling pathways may play important roles in the antioxidant and anti-apoptotic actions of LSZC.
Open Access
Original Article
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To investigate the effects of Qishen Yiqi Keli (QSYQ; Astragalus Salvia Granules to Benefit the Qi) on ROS scavenging and inhibition of NADPH oxidase in an effort to identify new natural antioxidants.
A total of 23 representative components in QSYQ were investigated, their effects on hydrogen peroxide induced ROS were assayed by dichlorofluorescein assay. Lucigenin chemiluminescence was adopted to test the effect on NADPH oxidase activity in H9C2 cardiomyocyte cells, and pyrogallol autoxidation was adopted to test the superoxide scavenging capacity.
Nine compounds in QSYQ could significantly inhibited H2O2-induced ROS increase compared with the model group (P < .05), including tanshinone Ⅰ, salvianolic acid A, danshinone ⅡA, and cryptotanshinone from salvia root, luteolin from salvia root, harpagoside, harpagide, and angoroside C from scrophularia root. Nine compounds in QSYQ could significantly inhibited the production of ·O2− in H9C2 cell. Tanshinone Ⅰ showed a lowest IC50 value 0.07 μM, the other including salvianolic acid A, cryptotanshinone, and salvianolic acid B, luteolin, isochlorogenic acid C, astragaloside Ⅳ, and glycyrrhetinic acid. Licochalcone A inhibited the autoxidation of pyrogallol at a low concentration, and tanshinone Ⅰ showed no significant inhibitory effect from 2 μM to 20 μM.
QSYQ had significant effects on ROS scavenging and inhibition of NADPH oxidase. Tanshinone Ⅰ and salvianolic acid A are potential NADPH oxidase inhibitors.
Open Access
Original Article
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To investigate the biological basis of “depression with liver-qi stagnation and spleen deficiency syndrome”.
A digital gene expression profiling method was conducted to explore global changes in the mRNA transcriptome in a rat model of depression with liver-qi stagnation and spleen deficiency syndrome. Real-time quantitative polymerase chain reaction (q-PCR) was performed to verify the five genes most interest based on the Kyoto Encyclopedia of Genes and Genome (KEGG) analysis. Sini San, which disperses stagnated liver qi and strengthens the spleen, was administered to the model rats to observe whether it could reverse these genetic changes in the liver.
Forty-six differentially expressed genes were identified. Three of the five genes of most interest—Hnf4α, Hnf4γ and Cyp1a1—based on KEGG analysis, were confirmed by real-time q-PCR. Sini San reduced the gene expression changes of Hnf4α, Hnf4γ and Cyp1a1 in the rat model.
Hnf4α, Hnf4γ and Cyp1a1 are involved in “depression with liver-qi stagnation and spleen deficiency syndrome”. These findings indicate that depressed rats with liver-qi stagnation and spleen deficiency syndrome are at risk of liver diseases. Furthermore, our results will inform exploration of the etiology of depression and help in the development of effective therapeutic strategies.
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