[Research progress on traditional Chinese medicine in treatment of neurodegenerative diseases by delaying neurovascular unit aging].

Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

[Meta-analysis and GRADE evaluation of Shuxuetong Injection in treatment of stroke in progressive].

This study aims to systematically evaluate the efficacy and safety of Shuxuetong Injection in the treatment of stroke in progressive. Randomized controlled trials of Shuxuetong Injection in the treatment of stroke in progressive were searched from CNKI, Wanfang, VIP, CMB, PubMed and EMbase. After strict literature screening, data extraction and quality evaluation, a total of 22 articles were included for analysis by RevMan 5.3. The Meta-analysis showed that Shuxuetong Injection combined with conventional treatment was superior to the conventional treatment alone in the major outcome indicators including effective rate(RR=1.27, 95%CI[1.20, 1.33], Z=9.18, P<0.000 01), deterioration rate(RR=0.38, 95%CI[0.22, 0.68], Z=3.31, P=0.000 9), NIHSS scores(MD=-3.89, 95%CI[-4.34,-3.43], Z=16.83, P<0.000 01), CSS scores(MD=-5.59, 95%CI[-6.42,-4.76], Z=13.20, P<0.000 01) and activity of daily living scores(MD=12.02, 95%CI[10.31, 13.72], Z=13.83, P<0.000 01), mortality during treatment was not increased(RR=0.40, 95%CI[0.13, 1.26], Z=1.56, P=0.12). Moreover, Shuxuetong Injection combined with conventional treatment further reduced the secondary outcome indicators including fibrinogen(MD=-0.35, 95%CI[-0.58,-0.13], Z=3.09, P=0.002), triglyceride(MD=-0.38, 95%CI[-0.67,-0.10], Z=2.65, P=0.008), low density lipoprotein cholesterol(MD=-0.72, 95%CI[-0.83,-0.61], Z=12.64, P<0.000 01), serum hypersensitive C-reactive protein(MD=-4.41, 95%CI[-6.96,-1.86], Z=3.38, P=0.000 7), and interleukin-6(MD=-5.43, 95%CI[-6.91,-3.96], Z=7.22, P<0.000 01). GRADE evaluation results showed that the major outcome indicators had low quality of evidence. Shuxuetong Injection in the treatment of stroke in progressive can improve the clinical effective rate, reduce the deterioration rate, improve the neurological function and activity of daily living, down-regulate the levels of fibrinogen, triglyceride, low density lipoprotein cholesterol and alleviate the inflammatory response. Although most studies have reported no adverse reactions, there are selective reports. The safety of Shuxuetong Injection needs to be further verified by more high-quality randomized controlled trial.

Effects of buyang huanwu tang combined with bone marrow mesenchymal stem cell transplantation on the expression of VEGF and Ki-67 in the brain tissue of the cerebral ischemia-reperfusion model rat.

OBJECTIVE: To explore the mechanism of Buyang Huanwu Tang (Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. METHODS: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. RESULTS: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P < 0.05), and with the most strongest effect in the combination group. CONCLUSION: Buyang Huanwu Tang combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.

Effect of tiaozhi yanggan decoction in treating patients with non-alcoholic fatty liver.

OBJECTIVE: To observe the clinical efficacy and safety of Tiaozhi Yanggan Decoction (TZYGD) in treating non-alcoholic fatty liver. METHODS: One hundred and thirty-eight patients were enrolled and randomized into two groups according to the random number table in a ratio of 3:1, with 8 cases eventually dropping out. The symptoms, signs, liver function markers, blood lipids, iconographic indices and clinical comprehensive efficacy after a 12-week treatment course were assessed in 101 patients treated with TZYGD in the treated group and 29 patients treated with Thiola in the control group. RESULTS: The total effective rate in the treated group and the control group was 81.19% and 68.97%, respectively, showing a significant difference between the two groups with the former being significantly higher than the latter (P<0.05). Moreover, the improvements in the symptoms, signs, liver function, blood lipids and iconographic indices in the treated group were favorable with no serious adverse reactions. CONCLUSION: TZYGD is effective and highly safe in treating non-alcoholic fatty liver.