Stachydrine hydrochloride ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.

Stachydrine hydrochloride (Sta), an activated alkaloid, is isolated from traditional Chinese medicine Yimucao. In previous studies, the cardioprotective effects of Sta were found in our laboratory. However, the underling mechanisms of Sta is not fully elucidated. The aim of this study was to provide a detailed account of the anti-hypertrophic effects of Sta on transcriptional regulation. In vivo, C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were orally treated with Sta. Morphological assessments, echocardiographic parameters, histological analyses and immunofluorescence were used to evaluate cardiac hypertrophy. In vitro, cardiomyocytes were stimulated by phenylephrine (PE), and cell surface and hypertrophy markers were tested by immunofluorescence and real-time polymerase chain reaction (RT-PCR). Moreover, western blotting, RT-PCR and luciferase reporter genes were used to assess the expression of proteins, mRNA and the activity of the CaMKII/HDAC4/MEF2C signal pathway in vivo and in vitro. We found that Sta blocked cardiac hypertrophy induced by pressure overload. We also demonstrated that Sta inhibited nuclear export or promoted nuclear import of HDAC4 through regulation of p-CaMKII, and it further improved the repression of MEF2C. Taken together, our findings demonstrated that Sta ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.

Scutellaria barbata D.Don and Oldenlandia diffusa (Willd.) Roxb crude extracts inhibit hepatitis-B-virus-associated hepatocellular carcinoma growth through regulating circRNA expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata D.Don (SB) and Oldenlandia diffusa (Willd.) Roxb are commonly known as Ban Zhi Lian and Bai Hua She Cao in Chinese herbal medicines, respectively. As a pair of herbs, they have traditionally been used as ethnomedicines for clearing away heat and toxins, removing blood stasis, and promoting blood circulation, diuresis, and detumescence. AIM OF THE STUDY: The aim of the present study was to determine the active ingredients in SB and OD extracts and to investigate whether these extracts can inhibit the growth of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines (HepG2.2.15 and Hep3B) in vitro and in vivo, as well as to explore their mechanisms of action. MATERIALS AND METHODS: We determined the levels of total flavonoids, luteolin, and apigenin in SB and OD extracts via ultraviolet-visible spectrophotometry and high-performance liquid chromatography. The effects of SB and OD extracts on HBV-associated HCC cell growth were assessed by HepG2.2.15 and Hep3B cells phenotype and RNA sequencing of Hep3B cells in vitro, and xenograft models in vivo. RESULTS: The extracts of SB and OD contained total flavonoids. There were active ingredients of luteolin and apigenin in SB, but not in OD. The extracts of SB and OD significantly inhibited HCC growth, migration, invasion, and HBV activity in vitro and in vivo, as well as altered circRNA expression in Hep3B cells. Moreover, we constructed a circRNA-miRNA-mRNA co-expression network. CONCLUSIONS: The extracts of SB and OD may inhibit HCC cell growth and HBV activity in vitro and in vivo through altering circRNA-miRNA-gene expression and that the efficacies of these extracts may be related to the presence of luteolin and apigenin.

Pediatric tuina for the treatment of attention deficit hyperactivity disorder (ADHD) symptoms in preschool children: study protocol for a pilot randomized controlled trial.

BACKGROUND: Medication and behavior therapy are the conventional treatments for attention deficit hyperactivity disorder (ADHD), but they have limitations for preschool children. Evidence suggests that pediatric tuina, which is a modality of traditional Chinese medicine, might have beneficial effects on this condition. OBJECTIVE: To assess the feasibility of conducting an RCT in terms of recruitment, use, and acceptability of the parent-administered pediatric tuina for ADHD symptoms in preschoolers. METHODS: It is a single-center, two-arm, parallel, open-label, pilot randomized controlled trial (RCT). Sixty children with pre-specified ADHD symptoms (hyperactivity, anxiety, and sleep disturbance) together with one of their parents will be recruited and randomized into two groups at a 1:1 ratio. Parents in the parent-administered tuina group (intervention group, n = 30) will attend an online training program to learn pediatric tuina skills for ADHD symptoms and conduct this treatment on their children at home. Parents in the parent-child interaction group (comparison group, n = 30) will attend an online training about progressive muscle relaxation exercise and do this exercise with their children at home. Additional teaching materials will be provided to the participants in both groups. Both interventions should be carried out every other day during a 2-month treatment period, with each time around 20 min. Assessment will be performed at baseline, week 4, and week 8. The primary outcome measure is the Swanson, Nolan, and Pelham parent scale; the secondary outcomes include preschool anxiety scale, children's sleep habits questionnaire, and parental stress scale. A process evaluation embedded within the outcome evaluation will be performed. Differences in the scale scores and test parameters between groups will be examined using a linear mixed-effects model. Qualitative data will be analyzed using thematic content analysis, facilitated by QSR NVivo. DISCUSSION: This study will provide evidence on the acceptability and feasibility of pediatric tuina for ADHD in preschool children. The process evaluation will help to better understand the facilitators and barriers of the intervention functioning. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (Identifier: NCT04237259 ) on 14 February 2020. Protocol version: 2; date, 23 June 2020.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

[Study on somato-type distribution and its correlations with body mass index, blood lipids and hepato-enzymes in 1 163 patients with non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the distribution of somato-types in Chinese medicine and its correlations with body mass index (BMI), blood lipids and hepato-enzymes in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: From January 2008 to December 2008, the somato-types of 1 163 NAFLD patients were categorized, and its correlations with BMI, blood lipids and hepato-enzymes were analyzed. RESULTS: Among the 1 163 patients, 401 were categorized as qi-deficiency type and 371 as phlegm-dampness type, accounting for 66.38%. Levels of BMI, blood lipids (TC, TG, LDL) and hepato-enzymes (ALT, AST, GGT) in patients of phlegm-dampness type were higher than those in patients of other types, the differences were statistically significant (P<0.05). CONCLUSIONS: Qi-deficiency type and phlegm-dampness type are the dominant pathogenetic somsto-types in patients with NAFLD; abnormal BMI, blood lipids and hepato-enzymes may present in those of phlegm-dampness type more frequently.

[Effects of Huatan Xiezhuo Recipe on insulin resistance and leptin in rats with fatty liver].

OBJECTIVE: To observe the effects of Huatan Xiezhuo Recipe (HTXZR) on fatty liver of rats. METHODS: Forty-eight SD rats were randomly divided into five groups: normal control group, untreated group, Dongbao Gantai Tablet (DBGTT)-treated group, low-dose HTXZR-treated group and high-dose HTXZR-treated group. Fatty liver was induced in the rats by hyperlipid diet and intraperitoneal injection of tetracycline. The pathological changes of liver tissues in rats were observed, and the liver function, serum leptin, insulin resistance index, triglyceride (TG) and free fatty acid (FFA) in the liver were detected. RESULTS: The levels of serum leptin, insulin resistance index, FFA and TG in rats of the three treated groups were lower than those of the untreated group (P<0.01), and such effects in the HTXZR-treated groups were more significant than those in the DBGTT-treated group (P<0.05). CONCLUSION: The main action mechanisms of HTXZR in treating fatty liver are probably to promote the lipid metabolism, decrease the leptin and insulin resistance.