Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes.

BACKGROUND: Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear. AIM: To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes. METHODS: This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments. RESULTS: According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats. CONCLUSION: This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.

Insights into the potential benefits of triphala polyphenols toward the promotion of resilience against stress-induced depression and cognitive impairment.

In response to environmental challenges, stress is a common reaction, but dysregulation of the stress response can lead to neuropsychiatric disorders, including depression and cognitive impairment. Particularly, there is ample evidence that overexposure to mental stress can have lasting detrimental consequences for psychological health, cognitive function, and ultimately well-being. In fact, some individuals are resilient to the same stressor. A major benefit of enhancing stress resilience in at-risk groups is that it may help prevent the onset of stress-induced mental health problems. A potential therapeutic strategy for maintaining a healthy life is to address stress-induced health problems with botanicals or dietary supplements such as polyphenols. Triphala, also known as Zhe Busong decoction in Tibetan, is a well-recognized Ayurvedic polyherbal medicine comprising dried fruits from three different plant species. As a promising food-sourced phytotherapy, triphala polyphenols have been used throughout history to treat a variety of medical conditions, including brain health maintenance. Nevertheless, a comprehensive review is still lacking. Here, the primary objective of this review article is to provide an overview of the classification, safety, and pharmacokinetics of triphala polyphenols, as well as recommendations for the development of triphala polyphenols as a novel therapeutic strategy for promoting resilience in susceptible individuals. Additionally, we summarize recent advances demonstrating that triphala polyphenols are beneficial to cognitive and psychological resilience by regulating 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) receptors, gut microbiota, and antioxidant-related signaling pathways. Overall, scientific exploration of triphala polyphenols is warranted to understand their therapeutic efficacy. In addition to providing novel insights into the mechanisms of triphala polyphenols for promoting stress resilience, blood brain barrier (BBB) permeability and systemic bioavailability of triphala polyphenols also need to be improved by the research community. Moreover, well-designed clinical trials are needed to increase the scientific validity of triphala polyphenols' beneficial effects for preventing and treating cognitive impairment and psychological dysfunction.

Advances in research on the protective mechanisms of traditional Chinese medicine (TCM) in myocardial ischaemia-reperfusion injury.

CONTEXT: Developing effective drugs to treat myocardial ischaemia-reperfusion (MI/R) injury is imperative. Traditional Chinese medicines (TCMs) have had considerable success in the treatment of cardiovascular diseases. Elucidating the mechanisms by which TCMs improve MI/R injury can supplement the literature on MI/R prevention and treatment. OBJECTIVE: To summarise TCMs and their main protective mechanisms against MI/R injury reported over the past 40 years. METHODS: Relevant literature published between 1980 and 2020 in Chinese and English was retrieved from the Web of Science, PubMed, SpringerLink, PubMed Central, Scopus, and Chinese National Knowledge Infrastructure (CNKI) databases. Search terms included 'medicinal plants', 'myocardial ischaemia reperfusion injury', 'Chinese medicine prescriptions', 'mechanisms', 'prevention', 'treatment' and 'protection'. For inclusion in the analysis, medicinal plants had to be searchable in the China Medical Information Platform and Plant Database. RESULTS: We found 71 medicinal species (from 40 families) that have been used to prevent MI/R injury, of which Compositae species (8 species) and Leguminosae species (7 species) made up the majority. Most of the effects associated with these plants are described as antioxidant and anti-inflammatory. Furthermore, we summarised 18 kinds of Chinese compound prescriptions, including the compound Danshen tablet and Baoxin pill, which mainly reduce oxidative stress and regulate mitochondrial energy metabolism. DISCUSSION AND CONCLUSIONS: We summarised TCMs that protect against MI/R injury and their pharmacological mechanisms. This in-depth explanation of the roles of TCMs in MI/R injury protection provides a theoretical basis for the research and development of TCM-based treatment drugs.

Therapeutic effect of a traditional Chinese medicine formulation on experimental choroidal neovascularization in mouse.

AIM: To investigate therapeutic effects of traditional Chinese medicine formulations, Hexuemingmu (HXMM) on laser-induced choroidal neovascularization (CNV) and follow-up effect in mice. METHODS: C57BL/6 mice of 8-week-old were used and CNV was induced with 577 nm laser photocoagulation. Animals were randomly divided into groups and different doses of HXMM were administered daily. One, four, and eight weeks after the intervention, the electroretinogram (ERG), fundus fluorescence angiography, choroidal flat mount and immunofluorescence staining were preformed to evaluate the function and CNV formation. The expression levels of angiogenic proteins were determined by Western blotting and immunofluorescence staining. An analysis of variance and Kruskal-Wallis test were used to test the differences among the groups. RESULTS: The results showed that HXMM effectively increased amplitude of ERG of mice (P<0.05), alleviated fundus CNV leakage (P<0.05), and reduced the area of neovascularization and the expression of angiogenic proteins (P<0.05) after laser-induced CNV. CONCLUSION: HXMM can protect the retinal function of mice after laser-induced CNV, and inhibit the CNV development.

Fushiming Capsule Attenuates Diabetic Rat Retina Damage via Antioxidation and Anti-Inflammation.

AIMS: Diabetic retinopathy (DR) remains one of the leading causes of acquired blindness. Fushiming capsule (FSM), a compound traditional Chinese medicine, is clinically used for DR treatment in China. The present study was to investigate the effect of FSM on retinal alterations, inflammatory response, and oxidative stress triggered by diabetes. MAIN METHODS: Diabetic rat model was induced by 6-week high-fat and high-sugar diet combined with 35 mg/kg streptozotocin (STZ). 30 days after successful establishment of diabetic rat model, full field electroretinography (ffERG) and optical coherence tomography (OCT) were performed to detect retinal pathological alterations. Then, FSM was administered to diabetic rats at different dosages for 42-day treatment and diabetic rats treated with Calcium dobesilate (CaD) capsule served as the positive group. Retinal function and structure were observed, and retinal vascular endothelial growth factor-α (VEGF-α), glial fibrillary acidic (GFAP), and vascular cell adhesion protein-1 (VCAM-1) expressions were measured both on mRNA and protein levels, and a series of blood metabolic indicators were also assessed. KEY FINDINGS: In DR rats, FSM (1.0 g/kg and 0.5 g/kg) treatment significantly restored retinal function (a higher amplitude of b-wave in dark-adaptation 3.0 and OPs2 wave) and prevented the decrease of retinal thickness including inner nuclear layer (INL), outer nuclear layer (ONL), and entire retina. Additionally, FSM dramatically decreased VEGF-α, GFAP, and VCAM-1 expressions in retinal tissues. Moreover, FSM notably improved serum antioxidative enzymes glutathione peroxidase, superoxide dismutase, and catalase activities, whereas it reduced serum advanced glycation end products, methane dicarboxylic aldehyde, nitric oxide, and total cholesterol and triglycerides levels. SIGNIFICANCE: FSM could ameliorate diabetic rat retina damage possibly via inhibiting inflammation and improving antioxidation.

Therapeutic Effect of Traditional Chinese Medicine on a Rat Model of Branch Retinal Vein Occlusion.

Branch retinal vein occlusion (BRVO) is a common retinal vascular disorder leading to visual impairment. Currently, the general strategies for BRVO are symptomatic therapies. Cardiovascular aspects are essential risk factors for BRVO. The traditional Chinese medicine hexuemingmu (HXMM), consisting of tanshinol and baicalin, dilates the vasculature and accelerates microcirculation. Therefore, the aim of this study was to determine the efficacy and possible mechanism of HXMM in a BRVO rat model established by laser photocoagulation. Successful BRVO rat models were treated with different doses of HXMM. Fundus photography and fluorescein fundus angiography (FFA) of the animals were applied. The retinal layers were measured by optical coherence tomography (OCT). Full-field electroretinography (ffERG) was applied to evaluate the retinal function. The ear vein flow velocity was measured via a microcirculation detector. The expression of the vascular endothelial growth factor (VEGF-α) was measured via western blotting and immunofluorescent staining. Our study found that retinal edema predominantly occurred in the inner nuclear layer (INL) and outer nuclear layer (ONL). The retinal edema of the treated groups was significantly relieved in the early stage of BRVO as visualized via OCT detection and HE staining. The amplitudes of the b wave and oscillatory potentials (OPs) waves of ffERG in the treated groups were increased compared with those of the control group at several detection points (3, 5, 7, 10, 14, and 21 d postocclusion). The expression of VEGF-α was reduced in the treated groups at an early stage of BRVO. Furthermore, the ear vein flow velocity of the HXMM treatment groups was faster than that of the control group. Thus, our study indicates that the traditional Chinese medicine HXMM could ameliorate retinal edema and rescue the retinal structure and function in BRVO models through promoting occluded vein recanalization, improving microcirculation, and regulating the expression of VEGF-α.