The nephroprotective effects and mechanisms of rehmapicrogenin include ROS inhibition via an oestrogen-like pathway both in vivo and in vitro.

BACKGROUND: The root of Rehmannia glutinosa (R. glutinosa) is commonly used in various traditional Chinese herbal formulae to ameliorate nephropathy; however, little is known about its active component(s) and mechanisms. AIM: In the present study, we examined the protective effect and potential mechanism of rehmapicrogenin, a monomeric compound extracted from R. glutinosa, against Adriamycin (ADR)-induced nephropathy (AN) in vivo and in vitro. METHODS: In this study, an ADR-induced kidney injury model was employed to investigate the nephroprotective effects of rehmapicrogenin in mice. In vivo, ELISA kits, flow cytometry, haematoxylin-eosin staining, immunofluorescence techniques, and western blotting were used to evaluate the effect of rehmapicrogenin on kidney injury in mice. In vitro, the effects of rehmapicrogenin on NRK-52E cellular damage induced by ADR were determined using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The mechanism was investigated using ELISA kits, flow cytometry and In-Cell Western™ blotting. RESULTS: In vivo, rehmapicrogenin treatment significantly attenuated the pathological changes in the kidney induced by ADR; rescued weight, serum creatinine (Scr), blood urea nitrogen (BUN) and urine albumin (U-ALB) levels; reduced reactive oxygen species (ROS) accumulation; and decreased oxidative stress, the apoptosis rate, and cell survival in ADR-treated mice. Importantly, both in vivo and in vitro experimental results demonstrated that rehmapicrogenin regulates the Nrf2/ARE signalling pathway, the most important pathway for oxidative stress. Rehmapicrogenin attenuated ADR-induced kidney damage by reducing oxidative stress through the oestrogen receptor pathway. Moreover, after treatment with ICI 182780 (the oestrogen receptor-nonspecific antagonist Faslodex), the improvement induced by rehmapicrogenin was significantly reversed. CONCLUSIONS: In conclusion, rehmapicrogenin attenuates kidney damage by reducing inflammatory factor release through the oestrogen signalling pathway.

[Duzhong Butiansu Capsules for improving fertility in male mice].

OBJECTIVE: To investigate the improving effect of Duzhong Butiansu Capsules (DBC) on the fertility of male mice. METHODS: Forty-eight 4-week-old SPF male Kunming mice weighing 12－16 g were randomly divided into four groups of equal number, distilled water (DW) control, Shengjing Capsules (SJC), low-dose DBC and high-dose DBC, treated intragastrically with distilled water, SJC at 0.8 g/kg/d, DBC at 0.694 g/kg/d and DBC at 1.388 g/kg/d, respectively, all for 3 weeks. After 2 weeks of treatment, the male mice were mated with female ones at a 2∶1 ratio for 1 week. Then, all the male animals were sacrificed for observation of the morphological changes in the testis and epididymis by HE staining, detection of the sperm count and motility, coefficients of different organs and expression of the androgen receptor (AR) in the testis, measurement of the levels of E2, LH, FSH and T by ELISA, and determination of the concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr) and urea nitrogen (BUN) in the serum. At 1 week after mating, the female mice were executed and the number of pregnancies recorded. RESULTS: The pregnancy rate was significantly higher in the low- and high-dose DBC groups (70% and 75%) than in the DW control (54%). The weight-bearing swimming time was markedly longer in the low-dose DBC than in the DW control group (ï¼»394 ± 51ï¼½ vs ï¼»173 ± 17ï¼½ s, P < 0.01) but exhibited no statistically significant difference between the high-dose DBC (ï¼»266 ± 42ï¼½ s) and the latter groups (P > 0.05). Remarkable increases were observed in the low-dose DBC group, compared with the DW control group, in the counts of spermatogonia (77.8 ± 5.0 vs 25.7 ± 5.3, P < 0.01), spermatocytes (132.4 ± 8.9 vs 92.5 ± 10.7, P < 0.01) and mature sperm (734 ± 67 vs 481 ± 56, P < 0.01), as well as in both the low- and high-dose DBC groups in the AR expression (P < 0.01). The AST concentration was markedly higher in the high-dose DBC than in the DW control group (ï¼»44.2 ± 11.0ï¼½ vs ï¼»30.5 ± 13.7ï¼½ U/L, P < 0.05), but there were no statistically significant differences between the DW control and the low- or high-dose DBC groups in the levels of serum T, FSH, LH, E2, Cr and BUN (P > 0.05). CONCLUSIONS: Duzhong Butiansu Capsules could improve the fertility of male mice, which has provided some experimental evidence for the clinical application of the medicine.

Oligosaccharides composition of Descurainiae sophia exerts anti-heart failure by improving heart function and water-liquid metabolism in rats with heart failure.

PURPOSE: To investigate the protective effect of Oligosaccharides composition of Descurainiae sophia on doxorubicin-induced heart failure in rats, and to study its mechanism. METHOD: A rat model of heart failure was established in 180-220 g male Sprague-Dawley rats by low-dose intraperitoneal injection of doxorubicin for 6 weeks. Four weeks after continuous administration, echocardiography was used to detect left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) in each group, and left ventricular short axis shortening rate (LVFS) and ejection fraction (LVEF) were calculated. ELISA method was used to detecte the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), troponin I (cTnI), creatine kinase (CK), angiotensin II (Ang II), aldosterone (ALD), arginine pressurization AVP, Renin, Endothelin (ET-1), Nitric Oxide (NO), AQP2 in urine. 6 h cumulative urine output was measured by metabolic cage method after administration for 3 weeks. The urine osmotic pressure was measured by freezing point method. The expression of AQP2 protein in kidney was detected by Western blot method. The changes of myocardial morphology were observed. RESULTS: Compared with the normal control group, the heart rate of the model group was significantly increased (P < 0.01). LVESD and LVEDD were significantly increased (P < 0.01), LVEF and LVFS were significantly decreased (P < 0.01). The levels of CK, cTnI, NO, ET-1, BNP, ANP, ALD, AngII, Renin, AQP2, AVP and osmotic pressure were significantly increased (P < 0.01). Urine output was significantly decreased (P < 0.01). The heart HE showed obvious lesions. Compared with the model group, the Oligosaccharides composition of Descurainiae sophia significantly reduced the heart rate (P < 0.05), decreased LVESD and LVEDD (P < 0.01 or P < 0.05), and increased LVFS and LVEF values (P < 0.01). Oligosaccharides composition of Descurainiae sophia could significantly improve pathological damage of the heart, decrease the levels of cTnI, BNP, AngII, ALD, Renin, AVP in the serum, osmotic pressure and AQP2in the urine (P < 0.01 or P < 0.05), down-regulate the expression of AQP2 protein in the renal(P < 0.01), increase urine volume (P < 0.05). CONCLUSION: Oligosaccharides composition of Descurainiae sophia can significantly improve cardiac function and the disorder of water metabolism in rats with heart failure. Oligosaccharides composition of Descurainiae sophia exerts anti- heart failure through the RAAS system and the arginine vasopressin system.

Catalpol Ameliorates Podocyte Injury by Stabilizing Cytoskeleton and Enhancing Autophagy in Diabetic Nephropathy.

Catalpol, an iridoid glycoside extracted from Rehmannia glutinosa, has been found to ameliorate diabetic nephropathy (DN), but the mechanism has not been clarified. Podocyte injury play a key role in the pathogenesis of DN. This study mainly investigated the protective effect and potential mechanism of catalpol on podocyte injury of DN in vivo and in vitro. The results indicated that the pathological features of DN in mice were markedly ameliorated after treatment with catalpol. Moreover, podocyte foot process effacement, and down-regulation of nephrin and synaptopodin expression in DN mice were also significantly improved after treatment with catalpol. In vitro, catalpol rescued disrupted cytoskeleton and increased migration ratio in podocytes induced by high glucose, the effect might be attributable to the inhibition of RhoA and Cdc42 activities but not Rac1. Furthermore, the impaired podocyte autophagy in DN mice was significantly enhanced after catalpol treatment. And catalpol also enhanced autophagy and lysosome biogenesis in cultured podocytes under high glucose condition. In addition, we found that catalpol could inhibit mTOR activity and promote TFEB nuclear translocation in vivo and in vitro experiments. Our study demonstrated that catalpol could ameliorate podocyte injury in DN, and the protective effect of catalpol might be attributed to the stabilization of podocyte cytoskeleton and the improvement of impaired podocyte autophagy.