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Laboratory techniques used in this study. A 4–0 suture coated with silicone rubber (a) was used for the MCAO induction. A programmable and motorized running wheel apparatus (b) was employed for the physical exercises post-cerebral ischemia. The design of this study (c). The intragastric administration of BYHWD began 2 h after the MCAO induction and was administered daily from Day 1 to 14 or until euthanasia. The physical exercises began on Day 3 post-ischemia and ended on Day 14 or euthanasia. The analytic modalities (neurobehavioral assessment, immunohistochemistry, and western blot) were performed on Day 3, 7 and 14 after the MCAO induction. Other techniques (TTC and TEM) were performed on Day 3 or 14 after the MCAO induction. BYHWD, Buyang Huanwu decoction; IHC, immunohistochemistry; MCAO, middle cerebral artery occlusion; NBA, neurobehavioral assessment; TEM, transmission electron microscope; TTC, triphenyltetrazolium chloride staining; WB, western-blot
Source publication
Background
Loss of neural function is a critical but unsolved issue after cerebral ischemia insult. Neuronal plasticity and remodeling are crucial for recovery of neural functions after brain injury. Buyang Huanwu decoction, which is a classic formula in traditional Chinese medicine, can positively alter synaptic plasticity. This study assessed the...
Citations
... Previous clinical trials and animal experiments have confirmed that BYHWD can lower blood sugar, significantly improve conduction function, promote the regeneration and repair of neurons, and reduce nerve cell damage. 6,7 However, limited systematic reviews have been conducted. BYHWD is a derivative of vitamin B12, which nourishes and repairs nerves, promotes the synthesis of nucleic acids and proteins, improves the metabolism of neurons and Schwann cells, and restores nerve conduction function. ...
Objective:
To evaluate the efficacy and safety of Buyang Huanwu decoction (BYHWD) in treating diabetic peripheral neuropathy (DPN).
Methods:
Eight electronic databases, including China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, Chinese Biomedical Literature Database, Cochrane Library, Embase, Web of Science, and PubMed, were searched for randomized controlled trials (RCTs) of BYHWD to treat DPN. We identified all RCTs related to BYHWD and those on the treatment of DPN with the combination of mecobalamin. RevMan software was used for the statistical analysis.
Results:
Twentyone RCTs with a total of 1945 patients were included. The methodological quality of the literature included was low. Metaanalysis showed that the efficacy of the treatment group was significantly better than that of the control group in the treatment of DPN with BYHWD [risk ratio () = 0.33, 95% (0.27, 0.40), 11.25, 0.000 01]. The median nerve of median motor nerve conduction velocity (MNCV) [mean difference () = 4.16, 95% (1.35, 6.98)] and median sensory NCV (SNCV) [(= 3.28, 95% (2.35, 4.22)] were improved in the treatment group. The MNCV in the common peroneal nerve [(= 1.63, 95% (0.39, 2.87)] and SNCV [(= 4.56, 95% (3.16, 5.97)] were significantly higher than those in the control group ( 0.01). Plasma viscosity [(= －0.15, 95% (－0.20, －0.09), 5.17, 0.01)], whole blood high shear [(= 0.83, 95% (1.56, －0.11), 2.26, 0.02)]and whole blood low shear [(= 1.61, 95% (2.28, 0.94), 4.68, 0.01)] decreased significantly after treatment. There was no significant difference in fasting blood glucose [(= 0.42, 95% ( 0.89, 0.05), 1.76, 0.08)] between the treatment and control groups; postprandial blood glucose [(= 0.62, 95% ( 1.19, 0.05), 2.12, 0.03)] decreased significantly. No significant difference was found in the blood lipid levels between the treatment and control groups, including triglycerides [(= 0.21, 95% (0.52, 0.10), 1.34, 0.18)] and cholesterol [(= 0.13, 95% ( 0.27, 0.00), 1.92, 0.06)]. Of the 21 RCTs, only five reported adverse reactions, and four studies reported the length of followup. No serious adverse events were reported. None of the studies reported the quality of life and economic conditions.
Conclusions:
Our study suggests that BYHWD has a significant therapeutic effect on DPN. Highquality, largescale RCTs are needed to provide more reliable evidence.
... As previously described, a five-point system was used to assess the neurological deficits of the rats at 48 h after MCAO (Bederson et al., 1986;Pan et al., 2017): 0, no neurological deficits; 1, failure to fully extend right forepaw; 2, circling to the opposite side; 3, falling to contralateral side; 4, not able to walk independently; and 5, died. ...
Background and purpose
Cerebral ischemia‐reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N‐methyl‐D‐aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury.
Methods
We used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen‐glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR‐ERK/CREB signaling.
Results
Treatment with Ast+Lig, or MK‐801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca²⁺ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5‐triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription‐quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury.
Conclusions
The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B‐ERK/CREB signaling pathway.
... One metaanalysis that assessed 56 studies with 1270 animals indicated a substantial neuroprotective action from BYHW decoction in models of focal cerebral ischemia [48]. The possible mechanism involved anti-inflammation [22], antioxidation [49], regulation of VEGF or angiopoietin-1 expression [50,51], and improvement of synaptic plasticity [52]. Clinical studies have also proved the effectiveness of BYHW decoction on stroke [53][54][55]. ...
Cerebral microinfarcts (CMIs) are characterized by sporadic obstruction of small vessels leading to neurons death. They are associated with increased risk of cognitive impairments and may have different risk factors compared with macroinfarcts. CMIs have a high incidence and result in heavy social burden; thus, it is essential to provide reasonable treatment in clinical practice. However, there are relatively few researches on the mechanism and treatment of CMIs, and the literature is composed almost exclusively of community—or hospital based on autopsy or imageological studies focusing on elderly patients. The Bu Yang Huan Wu (BYHW) decoction, a traditional Chinese herbal formula, has long been used to treat stroke and stroke-related diseases, including cognitive impairments. We applied microsphere-induced CMI model in rats to investigate the behavioral and molecular consequences of CMIs and to determine how they were ameliorated by BYHW decoction treatment. We then used the Morris water maze, quantitative proteomics, immunohistochemistry, and other molecular assays and found that activation of the PKA/CREB pathway by BYHW decoction treatment may reverse mitochondrial dysfunction, inhibit apoptosis of hippocampal neurons, and ameliorate CMI-induced cognitive impairments in rats. Collectively, these findings confirmed the therapeutic potential of the BYHW decoction in treating cognitive impairments induced by CMIs and demonstrated a viable mechanism for its action.
... For example, in the clinical use of BHD, the quality of each medicine in this prescription is adjusted on the basis of the original according to the patient's disease. We have summarized the current animal and clinical doses in Table 3. Buyang Huanwu Decoction 10-40 g/kg in rat (p.o.) 1.0 g/kg in mice (p.o), twice daily raw Astragalus 30 g, angelica 15 g, longan meat 15 g, antler gum 10 g, Salvia miltiorrhiza 10 g, frankincense 10 g, myrrh 10 g, and dried pine 5 g [192][193][194][195] Taohong Siwu decoction 4.5-18 g/kg/d in rat (p.o.) / [196] Danhong injection 0.75-3 mL/kg in rat (i.v.), twice daily 3 mL/kg/d in mice (i.m.) 20-40 mL/d (i.v.) [134,138,197,198] [200][201][202] Shuxuetong injection 6 mL/kg/d in rat (i.v.) 0.27-1.08 mg/kg/d in rat (i.p.) 6-10 mL/d (i.v.) [171,172,203] / Representative did not report. ...
Ischemic stroke (IS) is an acute cerebrovascular disease caused by sudden arterial occlusion, which is characterized by a high morbidity, mortality, and disability rate. It is one of the most important causes of nervous system morbidity and mortality in the world. In recent years, the search for new medicine for the treatment of IS has become an attractive research focus. Due to the extremely limited time window of traditional medicine treatment, some side effects may occur, and accompanied by the occurrence of adverse reactions, the frequency of exploration with natural medicine is significantly increased. Phosphatidylinositol-3-kinase/Protein kinase B (PI3K/Akt) signaling pathway is a classical pathway for cell metabolism, growth, apoptosis, and other physiological activities. There is considerable research on medicine that treats various diseases through this pathway. This review focuses on how natural medicines (including herbs and insects) regulate important pathophysiological processes such as inflammation, oxidative stress, apoptosis, and autophagy through the PI3K/Akt signaling pathway, and the role it plays in improving IS. We found that many kinds of herbal medicine and insect medicine can alleviate the damage caused by IS through the PI3K/Akt signaling pathway. Moreover, the prescription after their combination can also achieve certain results. Therefore, this review provides a new candidate category for medicine development in the treatment of IS.
... BYHWD is a traditional Chinese medicine (TCM) used to treat neurological dysfunction and disabilities induced by stroke. Studies have revealed that BYHWD contributes to neuroprotection, neurogenesis [80] and synaptic plasticity post-stroke [81]. Adult male Sprague-Dawley rats involved in a study were divided into three groups, sham, ICH, and BYHWD, in which ICH and BYHWD were given collagenase injection. ...
tRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer’s, epilepsy, Parkinson’s, MELAS, autism, and Huntington’s disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these disorders. Various animal studies are being carried out to decipher their exact role; however, more inputs are required to transform this research knowledge into clinical application. Future investigations also call for high-throughput technologies that could help to bring out the other hidden aspects of these entities. However, studies on tRFs require further research efforts to overcome the challenges posed in quantifying tRFs, their interactions with other molecules, and the exact mechanism of function. In this review, we are abridging the current understanding of tRFs, including their biogenesis, function, relevance in clinical therapies, and potential as diagnostic and prognostic biomarkers of these neurological disorders.
... BHD is the most representative TCM formula for stroke treatment, first documented in Yilin Gaicuo of Wang Qingren in the Qing Dynasty; it includes Astragalus membranaceus, Dang-Gui (Angelica sinensis), Ligusticum chuanxiong, Shao-Yao (Paeonialactiflora), Hong-Hua (Carthamustinctorius), Tao-Ren (seed of Prunus persica), and Di-Long (Lumbricus). BHD attenuates neurological deficits, promotes proliferation (120), neurorehabilitation (121) and the migration of NPCs to ischemic areas (122), and induces synaptic plasticity (121). BHD significantly improves the proliferation and differentiation of NSCs, cerebral infarction, and neuron viability, and decreases cell apoptosis via activation of the PI3K/AKT/Bad and Jak2/Stat3/Cyclin D1 pathways (123). ...
... BHD is the most representative TCM formula for stroke treatment, first documented in Yilin Gaicuo of Wang Qingren in the Qing Dynasty; it includes Astragalus membranaceus, Dang-Gui (Angelica sinensis), Ligusticum chuanxiong, Shao-Yao (Paeonialactiflora), Hong-Hua (Carthamustinctorius), Tao-Ren (seed of Prunus persica), and Di-Long (Lumbricus). BHD attenuates neurological deficits, promotes proliferation (120), neurorehabilitation (121) and the migration of NPCs to ischemic areas (122), and induces synaptic plasticity (121). BHD significantly improves the proliferation and differentiation of NSCs, cerebral infarction, and neuron viability, and decreases cell apoptosis via activation of the PI3K/AKT/Bad and Jak2/Stat3/Cyclin D1 pathways (123). ...
Stroke is associated with a high disability and fatality rate, and adversely affects the quality of life of patients and their families. Traditional Chinese Medicine (TCM) has been used effectively in the treatment of stroke for more than 2000 years in China and surrounding countries and regions, and over the years, this field has gleaned extensive clinical treatment experience. The Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway is important for regulation of cell migration, proliferation, differentiation, and apoptosis, and plays a vital role in vascularization and oxidative stress in stroke. Current Western medicine treatment protocols for stroke include mainly pharmacologic or mechanical thrombectomy to restore blood flow. This review collates recent advances in the past 5 years in the TCM treatment of stroke involving the PI3K/AKT pathway. TCM treatment significantly reduces neuronal damage, inhibits cell apoptosis, and delays progression of stroke via various PI3K/AKT-mediated downstream pathways. In the future, TCM can provide new perspectives and directions for exploring the key factors, and effective activators or inhibitors that affect occurrence and progression of stroke, thereby facilitating treatment.
... Neurological diseases can be caused by damage to the hippocampal CA1 region [13], which is also one of the brain regions most often studied in rodent models of depression [14,15]. Furthermore, there is new evidence suggesting that Chinese herbal medicines may have antidepressant benefits resulting from their ability to upregulate the certain synaptic proteins expression [16][17][18]. Meanwhile, an increasing body of evidence suggests that Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and downstream mammalian target of rapamycin (mTOR) signaling pathways affect the expression of proteins involved in the modulation of synaptic plasticity that may drive the pathophysiology of depression. ...
Background:
Many studies about depression have focused on the dysfunctional synaptic signaling in the hippocampus that drives the pathophysiology of depression. Radix Bupleuri has been used in China for over 2000 years to regulate liver-qi. Extracted from Radix Bupleuri, Saikosaponin D (SSD) is a pharmacologically active substance that has antidepressant effects. However, its underlying mechanism remains unknown.
Materials and methods:
A chronic unpredictable mild stress (CUMS) paradigm was used as a rat model of depression. SD rats were randomly assigned to a normal control (NC) group or one exposed to a CUMS paradigm. Of the latter group, rats were assigned to four subgroups: no treatment (CUMS), fluoxetine-treated (FLU), high-dose and low-dose SSD-treated (SSDH and SSDL). SSD was orally administrated of 1.50 mg/kg and 0.75 mg/kg/days for three weeks in the SSDH and SSDL groups, respectively. Fluoxetine was administrated at a dose of 2.0 mg/kg/days. SSD's antidepressant effects were assessed using the open field test, forced swim test, and sucrose preference test. Glutamate levels were quantified by ELISA. Western blot and immunochemical analyses were conducted to quantify proteins in the Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) pathways in the hippocampal CA1 region. To measure related gene expression, RT-qPCR was employed.
Results:
CUMS-exposed rats treated with SSD exhibited increases in food intake, body weight, and improvements in the time spent in the central are and total distance traveled in the OFT, and less pronounced pleasure-deprivation behaviors. SSD also decreased glutamate levels in CA1. In CA1 region of CUMS-exposed rats, SSD treatment increased mGluR5 expression while decreasing Homer1 expression. SSD also increased expressions of postsynaptic density protein 95 (PSD95) and synapsin I (SYP), and the ratios of p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 in the CA1 region in CUMS-exposed rats.
Conclusions:
SSD treatment reduces glutamate levels in the CA1 region and promotes the expression of the synaptic proteins PSD-95 and SYP via the regulation of the Homer1-mGluR5 and downstream mTOR signaling pathways. These findings suggest that SSD could act as a natural neuroprotective agent in the prevention of depression.
... Buyang Huanwu Tang (BHT) is a classic formula that has been used in patients with ischemic stroke for many years. It originates from the old record "Yi Lin Gai Cuo" and was compiled by Qingren Wang, a (Pan et al., 2017). Chen et al. randomly divided 108 SD rats into sham operation, MCAO/R, MCAO/ R + BHT, and MCAO/R + edaravone groups. ...
Cerebral ischemic reperfusion injury (CI/RI) is a critical factor that leads to a poor prognosis in patients with ischemic stroke. It is an extremely complicated pathological process that is clinically characterized by high rates of disability and mortality. Current available treatments for CI/RI, including mechanical and drug therapies, are often accompanied by significant side effects. Therefore, it is necessary to discovery new strategies for treating CI/RI. Many studies confirm that Chinese herbal medicine (CHM) was used as a potential drug for treatment of CI/RI with the advantages of abundant resources, good efficacy, and few side effects. In this paper, we investigate the latest drug discoveries and advancements on CI/RI, make an overview of relevant CHM, and systematically summarize the pathophysiology of CI/RI. In addition, the protective effect and mechanism of related CHM, which includes extraction of single CHM and CHM formulation and preparation, are discussed. Moreover, an outline of the limitations of CHM and the challenges we faced are also presented. This review will be helpful for researchers further propelling the advancement of drugs and supplying more knowledge to support the application of previous discoveries in clinical drug applications against CI/RI.
... Synthetically: "There is substantial evidence …" that such kind of interventions have beneficial effects towards motor control and consequent functionality regain, including with neuroplastic cortical readjustments [166]. More specific: "… the beneficial effects of physical exercise were correlated with the maintenance of pre-and postsynaptic components" [95], including with promoting/enhancing synaptic plasticity, and this may go also for mental exercises and acupuncture (see further a brief comment referring also to this latter type of interventionwith reported beneficial effects upon neurologic impairments consequent to ischemic stroke in rodent experimental models, based on neuroprotective: diminishing of brain edema, and of neurogenesis type: "... proliferation, migration and differentiation of NSCs", actions [167], as well as to on electroacupuncture), respectively [168]. Moreover, together with "... dietary restriction" exercise and EE "... positively modulate neurogenesis ..." [81]. ...
Considering its marked life-threatening and (not seldom: severe and/or permanent) disabling, potential, plus the overall medico-psycho-socio-economic tough burden it represents for the affected persons, their families and the community, the cerebrovascular accident (CVA)-including with the, by far more frequent, ischemic type-is subject to considerable scientific research efforts that aim (if possible) at eliminating the stroke induced lesions, and consist, as well, in ambitious-but still poorly transferable into medical practice-goals such as brain neuroregeneration and/or repair, within related corollary/upshot of neurorestoration. We have conducted, in this respect, a systematic and synthetic literature review, following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" concept. Accordingly, we have interrogated five internationally renowned medical data bases: Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science (the last one to check whether the initially identified articles are published in ISI indexed journals), based on a large (details in the body text) number of most appropriate, to our knowledge, key word combinations/"syntaxes"-used contextually-and subsequently fulfilling the related, on five steps, filtering/selection methodology. We have thereby selected 114 fully eligible (of which contributive: 83-see further) papers; at the same time, additionally, we have enhanced our documentation-basically, but not exclusively, for the introductive part of this work (see further)-with bibliographic resources, overall connected to our subject, identified in the literature within a non-standardized search. It appears that the opportunity window for morph-functional recovery after stroke is larger than previously thought, actually being considered that brain neurorestoration/repair could occur, and therefore be expected, in later stages than in earlier ones, although, in this context, the number of cases possibly benefitting (for instance after physical and/or cognitive rehabilitation-including with magnetic or direct current transcranial stimulation) is quite small and with more or less conflicting, related outcomes, in the literature. Moreover, applying especially high intense, solicitating, rehabilitation interventions, in early stages post (including ischemic) stroke could even worsen the functional evolution. Accordingly, for clarifications and validation of more unitary points of view, continuing and boosting research efforts in this complex, interdisciplinary domain, is necessary. Until finding (if ever) effective modalities to cure the lesions of the central nervous system (CNS)-including post ischemic stroke-it is reasonable and recommendable-based on rigorous methodologies-the avail of combined ways: physiatric, pharmacologic, possibly also bio-technologic. On a different note, but however connected to our subject: periodic related systematic, synthetic literature reviews reappraisals are warranted and welcome.
... Besides, the chronic inflammatory response intensity also parallels the degree of renal damage in diabetes; with higher urinary protein levels, the inflammatory response in patients is more severe. It follows that the increased levels of inflammatory factors in serum of DN patients are the important factor for the development of diabetic microangiopathy, and thus, anti-inflammatory therapy will also be a novel strategy for preventing, monitoring, and treating type II diabetes and its complications [18,19]. Based on relevant TCM studies, it seems that the occurrence of DN may be due to the deficiencies of qi and yin caused by the disease with the symptom of frequent ; the numbers of ineffective cases, effective cases, and marked effective cases in the control group were 11, 34, and 30, respectively, and the number of total effective cases was 64; the numbers of ineffective cases, effective cases, and marked effective cases in the experimental group were 3, 29, and 43, respectively, and the number of total effective cases was 72; * indicates a significant between-group difference in the marked effective rate of treatment (X 2 � 4.510, P � 0.034), and * * indicates a significant between-group difference in the total effective rate of treatment (X 2 � 5.042, P � 0.025). ...
Objective:
To study the efficacy of restricting dietary protein intake combined with Buyang Huanwu decoction in treating diabetic nephropathy (DN) and its effect on patients' inflammatory factor levels.
Methods:
The medical data of 150 DN patients treated in Wuhan No.1 Hospital (June 2018-May 2021) were retrospectively analyzed. All patients received regular therapy, those who received the intervention of restricting dietary protein intake were included in the control group (n = 75), and on this basis, those treated with Buyang Huanwu decoction were included in the experimental group (n = 75), so as to scientifically evaluate their efficacy and inflammatory factor levels after treatment.
Results:
The patients' general information was not statistically different between the two groups (P > 0.05); after treatment, the experimental group gained remarkably higher marked effective rate and total effective rate of treatment than the control group (P < 0.05); the inflammatory factor levels of all patients were obviously better than before (P < 0.05), and the levels of TNF-α, IL-2, IL-8, IL-4, and IL-10 were obviously lower in the experimental group than in the control group (P < 0.05); the levels of fasting blood glucose, 2 h postprandial blood glucose, and glycosylated hemoglobin of all patients were remarkably lower than before (P < 0.05), but with no significant between-group difference (P > 0.05); the renal function indexes of all patients were better than before, and between the two groups, the levels of 24 h microalbuminuria, 24 h urine protein excretion, and serum creatinine were obviously lower and the glomerular filtration rate was significantly higher in the experimental group (P all <0.05), and the patients' traditional Chinese medicine (TCM) symptom scores were remarkably lower in the experimental group (P < 0.05).
Conclusion:
Jointly applying Buyang Huanwu decoction on the basis of restricting dietary protein intake can effectively promote the clinical efficacy of DN, which is conducive to adjusting the inflammatory factor levels, promoting the patients' renal function, and alleviating the clinical symptoms.
