Dan Bai Xiao Formula combined with glucocorticoids and cyclophosphamide for pediatric lupus nephritis: A pilot prospective study.

BACKGROUND: Patients with lupus nephritis (LN) typically undergo long-term treatment with glucocorticoids (GCs) and immunosuppressants. There is a growing demand for optimal therapy with better remission results and fewer side effects. Sustained traditional Chinese medicine (TCM) might be quite valuable for multitarget therapy, reducing the total dosage of GCs and minimizing the side effects of immunosuppressants. AIM: To evaluate whether Dan Bai Xiao Formula (DBXF) can reduce the exposure to GCs and cyclophosphamide (CYC) and to assess the efficacy and safety of DBXF for the resolution of proteinuria and hematuria in children with LN. METHODS: A 24-wk pilot study was conducted at Beijing Children's Hospital. Children with active LN were divided into either a TCM group or a control group. Children in the TCM group received DBXF combined with GCs and CYC, and the ones in the control group received GCs and CYC every 4 wk for 24 wk. The primary endpoints of this trial were urinary protein excretion of < 150 mg/d and normal serum albumin concentration and renal function. RESULTS: The trial included 78 children, of whom 38 received GCs and CYC treatment (control group) and the remaining 40 received DBXF combined with GCs and CYC treatment (TCM group). At week 24, the TCM group showed a better rate of complete remission (42.5%); however, there was no significant difference compared with the control group (31.5%, P > 0.05). The urine red blood cell count and urine protein level were significantly lower in the TCM group than in the control group at weeks 4, 12, and 24 (P < 0.05). Furthermore, patients in the TCM group had a lower proportion of methylprednisolone pulses than those in the control group (1.30 ± 1.41 vs 3.05 ± 2.02, P < 0.0001). The ending GC dose was significantly lower in the TCM group than in the control group (P < 0.001). Moreover, more hepatic function damage, gastrointestinal adverse effects, and hypertension were observed in the control group than in the TCM group (P < 0.05). CONCLUSION: The findings suggest that DBXF treatment is effective and safe as a supplementary therapy for LN and is superior to routine GC and CYC therapy. DBXF containing combination treatment possibly results in a faster resolution of proteinuria and hematuria, smoother GC reduction, fewer methylprednisolone pulses, and fewer adverse events.

Effect of animal protein diet on the prognosis of children with Henoch-Schönlein purpura. / 动物蛋白饮食对过敏性紫癜患儿预后的影响分析.

OBJECTIVES: To study the association of animal protein diet with the recurrence of Henoch-Schönlein purpura (HSP)/skin rash and the risk factors for recurrence of HSP. METHODS: A prospective analysis was performed for 121 children with HSP who were admitted to the Beijing Children's Hospital from October to December 2020. The children were given the doctor's advice of the same diet (animal protein diet could be added after 1 week without new-onset skin rash). Follow-up was performed at the outpatient service for half a year. According to the presence or absence of animal protein intake, the children were divided into an observation group with 65 children and a control group with 56 children. The times of skin rash recurrence, the incidence of HSP recurrence, and the incidence of kidney injury were compared between the two groups. According to the presence or absence of recurrence, the children were divided into a recurrence group with 32 children and a non-recurrence group with 89 children. A questionnaire on food frequency was used to record the daily intake of animal protein in the two groups. A multivariate logistic regression analysis was used to identify the risk factors for recurrence of HSP in children. RESULTS: There was no significant difference between the observation and control groups in the times of skin rash recurrence, the incidence rate of HSP recurrence, and the incidence rate of kidney injury (P>0.05). There was no significant difference in the daily intake of animal protein between the recurrence and non-recurrence groups (P>0.05). The multivariate logistic regression analysis showed that presence of kidney injury at initial onset, respiratory infection after cure for the first time, and lack of exercise control after cure for the first time were independent risk factors for the recurrence of HSP in children (P<0.05). CONCLUSIONS: There is no significant association between animal protein diet and the recurrence of HSP or skin rash. Timely treatment of kidney injury, avoidance of infection after cure, and limitation of strenuous exercise may help to reduce the recurrence rate of HSP in children. Citation.

Stachydrine hydrochloride alleviates pressure overload-induced heart failure and calcium mishandling on mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far. AIM OF THE STUDY: The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action. MATERIALS AND METHODS: In vivo, transverse aorta constriction was carried out in C57BL/6J mice, and thereafter, 7.2 mg/kg telmisartan (a selective AT1R antagonist as positive control) and 12 mg/kg stachydrine hydrochloride was administered daily intragastrically for 4 weeks. Cardiac function was evaluated by assessing morphological changes as well as echocardiographic and haemodynamic parameters. In vitro, neonatal rat cardiomyocytes or adult mice cardiomyocytes were treated with stachydrine hydrochloride and challenged with phenylephrine (α-AR agonist). Ventricular myocytes were isolated from the hearts of C57BL/6J mice by Langendorff crossflow perfusion system. Intracellular calcium was measured by an ion imaging system. The length and movement of sarcomere were traced to evaluate the systolic and diastolic function of single myocardial cells. RESULTS: Stachydrine hydrochloride improved the cardiac function and calcium transient amplitudes, and inhibited the SR leakage and the amount of sparks in cardiac myocytes isolated from TAC mice. We also demonstrated that stachydrine hydrochloride could ameliorated phenylephrine-induced enhance in sarcomere contraction, calcium transients and calcium sparks. Moreover, our data shown that stachydrine hydrochloride blocked the hyper-phosphorylation of CaMKII, RyR2, PLN, and prevented the disassociation of FKBP12.6 from RyR2. CONCLUSION: Our results suggest that stachydrine hydrochloride exerts beneficial therapeutic effects against heart failure. These cardioprotective effects may be associated with the regulation of calcium handling by stachydrine hydrochloride through inhibiting the hyper-phosphorylation of CaMKII.

Stachydrine Protects Against Pressure Overload-Induced Cardiac Hypertrophy by Suppressing Autophagy.

BACKGROUND: Autophagy is required for the maintenance of cardiomyocyte homeostasis. However, excessive autophagy plays a maladaptive role in pressure overload-induced heart failure. To identify mechanisms by which Stachydrine inhibits pressure overload-induced cardiac hypertrophy, we determined inhibitory activities against activation of NADPH oxidase, reactive oxygen species(ROS) production and excessive activation of autophagy. METHODS: Stachydrine was administered intragastrically to Wistar rats after Transverse aortic constriction(TAC) and H9c2 cells were treated with Stachydrine after Angiotension II stimulation. The activation of NADPH oxidase2 required the membrane translocation of p47phox and p67phox. Cell membrane fraction was isolated by ultracentrifuge in sucrose. The expression of p67phox, p47phox, gp91phox subunit in the cell membrane were determined by western blot. The combination of p67phox and gp91 phox subunit was detected by immunofluorescence staining. The expression of phosphorylated p47phox subunit was determined by western blot. The intracellular ROS were measured with DCF-DA fluoresence. The autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. Reuslts: We report here that stachydrine, a major constituent of Leonurus heterophyllus Sweet, inhibited AngII-induced excessive autophagy within H9c2 cells. Stachydrine blocked the over phosphorylation of the p47phox subunit, decreased the translocation of p47phox and p67phox to the membrane, inhibited the activity of NOX2, and reduced the generation of ROS. We also demonstrated that stachydrine ameliorated TAC-induced cardiac hypertrophy, dysfunction and excessive autophagy in vivo. CONCLUSIONS: Our study highlights the importance of regulating NOX2 when autophagy is obviously activated. By inhibiting NOX2, Stachydrine inhibits ROS production, thus exerting a remarkable activity of inhibiting hypertrophy, which could have considerable effect on clinical practice.

Shengmai San Ameliorates Myocardial Dysfunction and Fibrosis in Diabetic db/db Mice.

In this study, we mainly investigated the effects of Shengmai San (SMS) on diabetic cardiomyopathy (DCM) in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24-week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF-ß dependent pathway.