Epigallocatechin-3-gallate promotes wound healing response in diabetic mice by activating keratinocytes and promoting re-epithelialization.

Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol that exhibits anti-inflammatory and anti-oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re-epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re-epithelialization and wound healing in T2D-induced wounds. Murine models of wound healing in T2D were established via feeding high-fat high-fructose diet (HFFD) and the creation of full-thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re-epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch-like ECH-associated protein 1 (KEAP1), thereby inhibiting KEAP1-mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re-epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D.

Babao Dan Alleviates Cancer Cachexia in Mice Via Inhibiting IL-6/STAT3 Signaling Pathway.

BACKGROUND: Cancer cachexia is a common but severe condition that causes muscle wasting, body weight loss, and progressive functional impairment, affecting over 50% of cancer patients. Currently, there are no effective treatments that can alleviate cachexia, and hence the discovery of new therapeutics that can effectively prevent or even reverse cancer cachexia is crucial. Babao Dan (BBD) is a Traditional Chinese Medicine (TCM) formula that has been used clinically in combating various cancers, however, its therapeutic potential in alleviating cancer cachexia remains unexplored. Our current study aims to determine the anti-cachectic effects of BBD treatment in alleviating cancer cachexia, as well as determining the underlying mechanisms involved. METHODS: Mouse models of cancer cachexia were induced via implantation of CT26 colon adenocarcinoma cells, and the anti-cachectic effects and mechanisms of BBD were determined via examinations of body weight and muscle mass, as well as serum and muscle markers of cachexia and muscle atrophy. RESULTS: CT26 tumor implantation reduced in the rapid occurrence of cancer cachexia characterized by marked reductions in body weight and muscle mass, functional decrease in muscle function and accelerated deaths. BBD administration not only demonstrated robust anti-cachectic ability via preventing decreases in body weight, muscle mass, and muscle atrophy, but also markedly prolonged survival. The effects of BBD in alleviating cancer cachexia and its associated adverse effects were due to its ability in preventing the activation of IL-6/STAT3 signaling post-CT26 tumor implantation. CONCLUSION: Our findings demonstrated the robust ability of BBD in preventing cancer cachexia and alleviating the main cachexia-induced symptoms as well as prolonging survival via inhibiting activation of IL-6/STAT3 signaling pathway. Therefore, our study demonstrating the strong anti-cachectic effects of BBD in mice may provide a theoretical basis for the use of BBD as a safe and effective drug in the treatment of cancer cachexia.

Qingda granule prevents obesity-induced hypertension and cardiac dysfunction by inhibiting adverse Akt signaling activation.

Obesity rates have rapidly increased worldwide and obesity-related diseases such as hypertension and cardiovascular diseases have become leading factors for global morbidity and mortality. Currently, there are no effective treatments that can prevent or reverse obesity long-term, and hence the prevention of obesity-related adverse effects such as hypertension is critical. Qingda granule (QDG) is a condensed Traditional Chinese Medicine (TCM) formula that has been used clinically for treating hypertension, however, its effectiveness in obesity-induced hypertension and cardiac dysfunction remains explored. Mouse models of obesity via long-term feeding of high-fat high-fructose diet (HFFD) were established to examine the effect and mechanism of QDG in protecting against obesity-induced hypertension and cardiac dysfunction. C57BL/6 mice were fed with either normal diet or HFFD over a period of 16 weeks and administered with either saline or QDG for assessment of obesity-induced blood pressure and cardiac function. QDG administration demonstrated robust anti-hypertensive effects and significantly attenuated HFFD-induced elevations in blood pressures. Moreover, QDG treatment also demonstrated robust cardioprotective effects during obesity-induced hypertension by markedly improving cardiac function and preventing cardiac hypertrophy. QDG protected against obesity-induced hypertension and cardiac dysfunction was due to its ability to prevent adverse chronic activation of Akt signaling pathway during long-term feeding of HFFD. Long-term usage of QDG treatments exhibited no observable side effects and also completely prevented obesity-induced organ damage, demonstrating the feasibility and safety of prolonged use. Our findings thus elucidated the role of QDG in preventing obesity-induced hypertension and cardiac hypertrophy via inhibiting adverse activation of Akt signaling activation. Therefore, our study provides the theoretical basis for the utilization of QDG as both a safe and effective drug in the therapeutic treatment of metabolic diseases such as obesity-induced hypertension.

Huoxin pill prevents excessive inflammation and cardiac dysfunction following myocardial infarction by inhibiting adverse Wnt/ß­catenin signaling activation.

BACKGROUND: Myocardial infarction (MI) is the most common cause of cardiac injury, resulting in widespread and irreversible damage to the heart. The incidence of MI gives rise to the excessive production of inflammatory cytokines that further promotes myocardial dysfunction. Wnt/ß-catenin signaling pathway is adversely activated during MI and plays an important role in the modulation of the inflammatory response following tissue injury. Huoxin pill (HXP) is a Traditional Chinese Medicine formulation that has been long used in the treatment of cardiovascular diseases, however its mechanisms of cardioprotection remain unclear. METHODS: We performed murine models of MI in order to model myocardial ischemic damage and examine the effect and underlying mechanism of HXP in protecting against myocardial ischemic injury. We further constructed conditional cardiomyocyte-specific ß-catenin knockout mice and induced surgical MI in order to better understand the role of Wnt/ß-catenin signaling following myocardial infarction in the adult heart. RESULTS: HXP administration strongly protected against cardiac ischemic injury, improved cardiac function, and markedly decreased the expression of pro-inflammatory cytokines following MI. Nuclear activation of ß­catenin resulted in significantly increased nuclear translocation and activation of NF-κB. In contrast, cardiomyocyte-specific deletion of ß-catenin decreased NF-κB activation and exhibited beneficial effects following ischemic injury. Hence, HXP protected against MI-induced ischemic injury and excessive inflammatory response via inhibiting Wnt/ß­catenin signaling. CONCLUSIONS: Our study elucidated the role of HXP in protecting against ischemic myocardial injury via preventing MI-induced inflammatory response, which was mediated by its ability to inhibit adverse Wnt/ß­catenin signaling activation. Thus, our study provides the basis for the implementation of HXP as an effective therapeutic strategy in protecting against myocardial ischemic diseases.

Huoxin pill prevents acute myocardial ischaemia injury via inhibition of Wnt/ß-catenin signaling.

Myocardial infarction (MI) is one of the leading causes of death worldwide, and due to the widespread and irreversible damage caused, new therapeutic treatments are urgently needed in order to limit the degree of ischaemic damage following MI. Aberrant activation of Wnt/ß-catenin signalling pathway often occurs during cardiovascular diseases including MI, which results in excess production of reactive oxygen species (ROS) and further promotes myocardial dysfunction. Huoxin pill (HXP) is a Traditional Chinese Medicine formula that has been widely used in the treatment of coronary heart disease and angina; however, its mechanisms remain unclear. Here, we performed mouse models of MI and examined the effects and mechanisms of HXP in protecting against MI-induced ischaemic damage. Our study showed that administration with HXP robustly protected against MI-induced cardiac injuries, decreased infarct size and improved cardiac function. Moreover, HXP attenuated ischaemia-induced DNA damage occurrence in vivo and H2 O2 -induced DNA damage occurrence in vitro, via potent inhibition of adverse Wnt/ß-catenin signalling activation. Our study thus elucidated the role and mechanism of HXP in protecting against MI and oxidative stress-induced injuries and suggests new therapeutic strategies in ischaemic heart disease via inhibition of Wnt/ß-catenin signalling pathway.

Network pharmacology-based analysis in determining the mechanisms of Huoxin pill in protecting against myocardial infarction.

CONTEXT: Huoxin pill (HXP) is a commonly used TCM prescription for treatment of cardiovascular diseases. However, its mechanism in protecting against myocardial infarction (MI) remains unknown. OBJECTIVE: We performed a network pharmacology analysis to explore the bioactive ingredients, therapeutic effects, and mechanisms of HXP in protecting against MI. MATERIALS AND METHODS: HPLC was used to identify major bioactive compounds, and overlap with MI target genes were visualised. 10-Week old C57BL/6 mice were randomly assigned as: Sham-operated control, MI + Phosphate buffered saline (PBS), and MI + HXP (3 mg/mL and 9 mg/mL) treatment groups, received oral gavage administration once every two-days starting from 1-week prior to MI, and subsequently MI models were established for one-week before sacrifice. RESULTS: AKT1, VEGFA, TNF and RELA were identified as core target proteins among eighty-five candidate bioactive compounds identified in HXP with overlapping MI-related genes. HXP protection against MI was mainly via regulation of inflammatory pathways, notably TNF signalling pathway. Mouse models of MI and cardiac myoblasts demonstrated that HXP improved MI-induced injury via improving regulation of inflammatory response. DISCUSSION AND CONCLUSION: Stellasterol, deoxycholic acid, kaempferol, and quercetin are important active compounds contained in HXP with anti-inflammatory properties in the therapeutic treatment of MI. Due to the straightforward nature and effectiveness of taking oral HXP medications, our findings provide a theoretical basis for the clinical application of HXP in treating patients with angina or myocardial ischaemia. Future research into the combination of surgical procedures or medications that restore blood flow together with HXP as supportive medication would be worthwhile.

Babao Dan is a robust anti-tumor agent via inhibiting wnt/ß-catenin activation and cancer cell stemness.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown. AIM OF THE STUDY: Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/ß-catenin signaling. Our study aims to elucidate the underlying molecular mechanisms associated with the anti-tumor proliferative effects of Babao Dan (BBD). MATERIALS AND METHODS: We used a hepatoblastoma cell line HepG2 with stem cell-like traits that harbors a constitutively active mutant of ß-catenin in order to study the anti-tumor ability of BBD via targeting Wnt/ß-catenin signaling. RESULTS: BBD robustly attenuated both the intrinsic and extrinsic activation of Wnt/ß-catenin pathway in HepG2 hepatoblastoma cells, as well as Wnt target genes. Moreover, BBD significantly inhibited both the proliferation of well-differentiated cancer cells, as well as the stem-like property of CSCs as evidenced by EpCAM, a Wnt target gene and a novel marker of cancer cell stemness. In addition, mice administered with BBD using HepG2 cell line derived xenograft model had marked reductions in tumor size and weight, as well as significantly decreased expressions of Wnt target genes and cancer cell stemness. CONCLUSION: Our findings elucidated the underlying molecular mechanisms associated with the robust anti-tumor effects of BBD via potent inhibition of Wnt/ß-catenin signaling, and implicate its use in the clinical treatment of cancers.

Effects of midwife-led maternity services on postpartum wellbeing and clinical outcomes in primiparous women under China's one-child policy.

BACKGROUND: The Midwife-led maternity services have been implemented in China in response to the high rates of primiparous women and Caesarean Sections (CS) which may be related to China's one-child policy. However, few studies in China have been reported on the effectiveness of Midwife-led Care at Delivery (MCD) and the Continuity of Midwife-led Care (CMC) on postpartum wellbeing and other clinical outcomes. Therefore, evidence-based clinical validation is needed to develop an optimal maternity service for childbearing women in China. METHODS: A concurrent cohort study design was conducted with 1730 pregnant women recruited from 9 hospitals in Shanghai. Among the 1730 participants at baseline, 1568 participants completed the follow-up questionnaire, with a follow-up rate of 90.6%. RESULTS: Compared with the routine Obstetrician-led Maternity Care (OMC), Midwife-led Care at Delivery (MCD) was associated with CS rate (OR were 0.16; 95%CI: 0.11 to 0.25) and a higher total score of postpartum wellbeing (ßwere 2.70; 95%CI: 0.70 to 4.70) when adjusting for the baseline differences and other confounders during delivery or postpartum period. Moreover, continuity of Midwife-led Care (CMC) was associated with CS rate (OR were 0.30; 95%CI: 0.23 to 0.41), as well as increased rate of breastfeeding within the first 24 h (OR were 2.49; 95% CI: 1.47 to 4.23), higher postpartum satisfaction (ß = 4.52; 95% CI: 1.60 to 12.68), lower anxiety (ßwere 0.66; 95% CI: 0.16 to 1.17), increased self-control (ßwere 0.39; 95% CI: 0.02 to 0.76) and a higher total score of postpartum wellbeing (ßwere 3.14; 95% CI: 1.54 to 4.75). CONCLUSION: CMC is the optimal service for low-risk primiparous women under China's one-child policy, and is worthwhile for a general implementation across China.

Chlorogenic acid prevents isoproterenol-induced hypertrophy in neonatal rat myocytes.

Cardiac hypertrophy is an independent risk factor for cardiovascular disease and its subsequent progression to heart failure represents a major cause of morbidity and mortality in the world. CGA is an important component of Chinese herbal medicine, acting as an antioxidant, scavenging free radicals and preventing inflammation. This study found that with the pre-treatment of chlorogenic acid in Iso-induced neonatal rat myocytes, the levels of the hypertrophic markers, ANP, BNP and ß-MHC decreased. The nuclear translocation of NF-κB was blocked, whereas NF-κBIA, an inhibitor of NF-κB, was upregulated accordingly. And the level of the intracellular ROS was also reduced. These data reveal that chlorogenic acid may inhibit Iso-induced cardiac hypertrophy by attenuating NF-κB signaling pathway and suppressing ROS.