Based on proteomics to explore the mechanism of mecobalamin promoting the repair of injured peripheral nerves.

Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and ßⅢ-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.

Network pharmacology-based research uncovers cold resistance and thermogenesis mechanism of Cinnamomum cassia.

BACKGROUND: Cinnamomum cassia (L.) J.Presl (Cinnamon) was known as a kind of hot herb, improved circulation and warmed the body. However, the active components and mechanisms of dispelling cold remain unknown. METHODS: The effects of several Chinses herbs on thermogenesis were evaluated on body temperature and activation of brown adipose tissue. After confirming the effect, the components of cinnamon were identified using HPLC-Q-TOF/MS and screened with databases. The targets of components were obtained with TCMSP, SymMap, Swiss and STITCH databases. Thermogenesis genes were predicted with DisGeNET and GeneCards databases. The protein-protein interaction network was constructed with Cytoscape 3.7.1 software. GO enrichment analysis was accomplished with STRING databases. KEGG pathway analysis was established with Omicshare tools. The top 20 targets for four compounds were obtained according to the number of edges of PPI network. In addition, the network results were verified with experimental research for the effects of extracts and major compounds. RESULTS: Cinnamon extract significantly upregulated the body temperature during cold exposure.121 components were identified in HPLC-Q-TOF/MS. Among them, 60 compounds were included in the databases. 116 targets were obtained for the compounds, and 41 genes were related to thermogenesis. The network results revealed that 27 active ingredients and 39 target genes. Through the KEGG analysis, the top 3 pathways were PPAR signaling pathway, AMPK signaling pathway, thermogenesis pathway. The thermogenic protein PPARγ, UCP1 and PGC1-α was included in the critical targets of four major compounds. The three major compounds increased the lipid consumption and activated the brown adipocyte. They also upregulated the expression of UCP1, PGC1-α and pHSL, especially 2-methoxycinnamaldehyde was confirmed the effect for the first time. Furthermore, cinnamaldehyde and cinnamon extract activated the expression of TRPA1 on DRG cells. CONCLUSION: The mechanisms of cinnamon on cold resistance were investigated with network pharmacology and experiment validation. This work provided research direction to support the traditional applications of thermogenesis.

Cinnamomum cassia extract promotes thermogenesis during exposure to cold via activation of brown adipose tissue.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia (L.) J.Presl (Lauraceae), a widely used traditional Chinese medicine, is well known to exert hot property. It is recorded as dispelling cold drug in ancient Chinese monographs, such as Synopsis of golden chamber published in Han dynasty. According to Chinese Pharmacopoeia (2015), Cinnamomum cassia (L.) J.Presl (Cinnamon) has the functions of dispersing cold, relieving pain, warming meridians and promoting blood circulation. AIM OF THE STUDY: The aim of this study is to evaluate the effect of Cinnamon extract (CE) on cold endurance and the mechanism of thermogenesis activity. MATERIALS AND METHODS: The improving effect of hypothermia were evaluated with body temperature by infrared camera and multi-thermo thermometer. In vivo, the thermogenic effect was observed with energy metabolism and substrate utilization. The activation of brown adipose tissue (BAT) was evaluated with the histomorphology and expression of thermogenic protein. In vitro, the uncoupling effect on mitochondrial was evaluated with Seahorse and fluorescent staining. The mechanism of thermogenesis was explored in brown adipocyte. RESULTS: The body temperature and energy expenditure were significantly increased by CE administration in cold environment. In morphology, lipid droplets were reduced and the number of mitochondrial was increased. CE significantly increased the non-shivering thermogenesis via upregulating the expression of thermogenic protein. In vitro, the uncoupling effect was obviously along with the decreased mitochondrial membrane potential and ATP production. It was confirmed that the thermogenesis effect was induced via lipolysis and energy metabolism. In addition, CE also alleviated myocardium injury in the morphology in cold environment. Moreover, the major constituent was identified as (1) coumarin, (2) cinnamic acid, (3) cinnamaldehyde and (4) 2-methoxy cinnamaldehyde. CONCLUSIONS: The mechanism of improving cold tolerance was related to lipolysis and activation of BAT. Meanwhile, we provided a kind of potential prevention methods for cold injury.

Notopterygium incisum extract (NRE) rescues cognitive deficits in APP/PS1 Alzhneimer's disease mice by attenuating amyloid-beta, tau, and neuroinflammation pathology.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and "deficiency" is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum (Qiang huo) is beneficial to bladder, liver, and kidneys. It is used to treat liver and kidney deficiency, language difficulties, and mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. AIM OF THE STUDY: This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aß cascade, tau pathology and inflammatory pathology of AD. MATERIALS AND METHODS: In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aß. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3ß and triggering hyperphosphorylation of tau. The Aß levels and the expression of phosphorylated tau were detected by ELISA and Western blot. The cognitive ability of NRE on APP/PS1 mice was detected using a Morris water maze (MWM) assay and Aß contents were also evaluated. RESULTS: In HEK APPswe293T cells, NRE (10, 20, 40 µg/mL) significantly inhibited the secretion and production of Aß in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1 mice, and the contents of Aß, IL-1ß and TNF-α were significantly depressed in hippocampus and cortex. CONCLUSION: In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aß cascade, tau pathology and neuroinflammation in vitro and in vivo.

Jiang Gui Fang activated interscapular brown adipose tissue and induced epididymal white adipose tissue browning through the PPARγ/SIRT1-PGC1α pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gui Zhi Tang, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, has been widely used to treat exogenous cold for thousands of years. Recent studies have shown that Gui Zhi Tang has the effect of regulating the body temperature. Because of its effect on heat production, protecting vital organs of the body and avoiding damage from the cold environment, Jiang Gui Fang (JG) was obtained from the Department of Traditional Chinese Medicine at the General Hospital of Northern Theatre Command where it has been used clinically for many years and has exhibited favourable efficacy. Based on research on Gui Zhi Tang, the principles of traditional Chinese medicine and survey of a large number of studies, this empirical formula was developed. The composition of JG included Dried ginger, Cassia twig, and Liquorice in Gui Zhi Tang, which play a major role in the treatment of exogenous cold, and combined these components with other Chinese medicines, such as Pueraria, Spatholobus, Acanthopanacis cortex, Evodiae fructus, and Codonopsis pilosula. AIM OF THE STUDY: To promote the core body temperature and prevent invasion of the major organs from the cold environment, we studied the effect of JG on the core body temperature of mice and then explored its regulation of interscapular brown adipose tissue (iBAT) and epididymal white adipose tissue (eWAT) and the possible mechanism. Finally, we determined the phytochemical composition of JG that plays a role in heat production. MATERIALS AND METHODS: In vivo study, we performed a 4-week treatment of JG in acute cold environment at -20 °C and chronic cold exposure at 4 °C. The core temperature, adipose tissue weight, serum parameters, and morphological observation of adipocytes, liver and kidney were measured. Then we investigated the expression levels of adipogenic factors, thermogenic factors and lipoprotein. In vitro, we determined the lipid droplet content, ATP content, and the maximum oxygen consumption of mitochondria. RESULTS: JG treatment promoted core temperature, inhibited eWAT weight, protected liver, and reduced glucose and lipids in Kunming (KM) mice. JG also increased the expression of BAT-associated thermogenic factors, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α). The levels of the lipogenic factor peroxisome proliferate-activator receptor gamma (PPARγ) and the lipolytic protein hormone-sensitive triglyceride lipase (HSL) in eWAT were elevated. The results of H&E and immunohistochemistry showed that JG significantly reduced the size of iBAT and eWAT and increased the content of UCP1. In vitro, JG reduced the content of lipid droplets and ATP in brown fat cells. The maximum oxygen consumption capacity of mitochondria and the expression levels of UCP1, PGC1α and silent mating type information regulation 2 homologue 1 (SIRT1) were enhanced after JG treatment. CONCLUSIONS: In vivo and in vitro studies, the results demonstrated that JG obviously increased the core temperature of mice by activating iBAT and inducing eWAT browning, which proved the mechanism is closely related to the PPARγ/SIRT1- PGC1α pathway. In this paper, we will provide a reference for further study of iBAT activation and eWAT browning.

Dracorhodin Perchlorate Accelerates Cutaneous Wound Healing in Wistar Rats.

Dracorhodin perchlorate (DP) is extracted from Dragon's blood, which is widely used in traditional Chinese medicine, especially in wound healing. The aim of this paper is to investigate the influence of DP ointment, which contained DP dissolved in DMSO and mixed with Vaseline, on cutaneous wound healing in Wistar rats. Forty Wistar rats were divided into two groups: control and DP groups. The skin on the back of each rat was punched with two full-thickness wounds and then treated with the corresponding drug. After 3, 7, 10, 14, and 21 days, four rats were sacrificed for immunological, biochemical, and histological analyses. Compared with the control treatment, DP could significantly promote wound closure. Histological and biochemical analyses of the skin biopsies also showed that DP regulated the expression of inflammatory responses by TNF-α and IL-ß and by supporting wound tissue growth and collagen deposition. Western blot revealed that DP could also facilitate the expression of EGF and VEGF proteins. In conclusion, DP promotes wound healing.

Efficacy of salvianolic acid B combined with triamcinolone acetonide in the treatment of oral submucous fibrosis.

OBJECTIVE: The aim of this study was to investigate the effectiveness of triamcinolone acetonide (TA) and salvianolic acid B (SA-B) intralesional combined injection in the treatment of oral submucous fibrosis (OSF). MATERIAL AND METHODS: A randomized clinical trial was performed. TA, SA-B, and TA combined with SA-B were consecutively applied intralesionally weekly for 20 weeks. Mouth opening and burning sensation improvement as determined by a 100-mm visual analog scale were evaluated at weeks 10, 20, and 44. RESULTS: Forty-two subjects fulfilled the study without obvious adverse reactions. The net gain in mouth opening was 2.00 ± 1.21 mm in the TA group, 3.48 ± 2.23 mm in the SA-B group, and 5.50 ± 1.80 mm in the TA + SA-B group at week 44. The burning sensation improved by 3.05 ± 0.76 in the TA group, 4.96 ± 0.97 in the SA-B group, and 6.11 ± 0.93 in the TA + SA-B group by the end of the study. CONCLUSIONS: TA + SA-B intralesional injections improved mouth open and burning sensation in these OSF patients.

Effects of berberine gelatin on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial in a Chinese cohort.

OBJECTIVE: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease, yet effective therapeutic approaches are lacking. This study aimed to determine the effects of application of berberine gelatin in the treatment of minor RAS (MiRAS). METHODS: A randomized, double-blind, placebo-controlled, clinical trial was performed. The gelatin containing berberine (5 mg/g) or vehicle only was applied 4 times per day for 5 days. Clinical evaluation included pain level, size, erythema, and exudation of certain ulcers on days 1, 2, 4, and 6. RESULTS: A total of 84 subjects fulfilled the study without obvious side effects. Berberine gelatin treatment reduced the ulcer pain score compared with placebo gelatin (P < 0.05). Ulcer size was significantly reduced (P < 0.05) and lower erythema (P < 0.05) and exudation (P < 0.05) levels were associated with berberine treatment. CONCLUSIONS: Berberine gelatin may be a safe and effective treatment for MiRAS.

A new therapeutic candidate for oral aphthous ulcer: Allicin.

Recurrent aphthous ulcer (RAU) is the most common ulcer of oral non-keratinized mucosa, but the treatment is always limited at present. Considering the multifactorial etiology of RAU, a novel therapeutic agent with multi-bioactivties should be presented. Garlic has been recognized as a favorable natural medicine against a large number of pathologic conditions. The major component of garlic is allicin, which could effectively decrease inflammatory factors secretion, reduce the migration of neutrophils, inhibit bacterium and virus, antagonize oxidation and regulate immunity. By these bioactivities of anti-inflammation, anti-microbial activity, anti-oxidation and immunomodulation, the allicin may be an effective therapeutic candidate to control the pain, promote ulcer healing and prevent the recurrence of RAU.