[Syndrome Types of Chinese Medicine and Clinical Characteristics of 660 Patients with Diabetic Peripheral Neuropathy].

Objective To summarize the distribution and clinical characteristics of Chinese med- icine (CM) syndrome types in 660 patients with diabetic peripheral neuropathy (DPN). Methods Totally 660 inpatients at Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences were recruited from Jan 2000 to Dec 2014. Their first diagnoses were DNP. The distributions of their syndrome types were observed. Clinical characteristics in patients with different syndrome types were compared. Meanwhile, Logistic regression analysis was performed in independent variable by taking syndrome types of CM as quartering regression variables. Results The ratio of syndrome types was sequenced from high to low as yin deficiency blood stasis syndrome [39.24% (259/660)], yang deficiency blood stasis syndrome [29.39% (194/60)], phlegm stasis in collaterals syndrome [19. 24% (127/660) ] , yin deficiency induced wind stirring syndrome [12. 12% (80/ 660) ]. There was no significant difference in the constituent ratio of CM syndrome patterns among groups with different courses of diabetes (P >0. 05). The ratio of yang deficiency blood stasis syndrome had an increasing trend as the course increased. There was significant difference in HbAlc, fasting C pep- tide (FCP) , systolic blood pressure (SBP) , total cholesterol (TC) , 24 h total urinary protein (24 h UCP) , serum creatinine (SCr), blood urea nitrogen (BUN) among patient groups with different CM syndrome types (P <0. 05). Compared with yang deficiency blood stasis syndrome, HbAlc increased, SBP,SCr,BUN and 24 hUCP decreased in yin deficiency blood stasis syndrome with statistical difference (P = 0. 006, 0. 002,0. 001 ,0. 001, and 0. 007; P <0. 05) ; 24 h UCP also decreased in yin deficiency induced wind stirring syndrome (P =0. 34, P <0. 05). Multiclassified Logistic regression showed that when taking yin deficiency blood stasis syndrome as reference, HbAlc was a protective factor of yang deficiency blood stasis syn- drome, 8 h urinary albumin excretion (UAE) was a risk factor. Both TC and SCr were risk factors for yin deficiency induced wind stirring syndrome. SCr was a risk factor for phlegm stasis in collaterals syndrome. Conclusions Poor control of blood glucose in DPN patients might be related with yin deficiency blood sta- sis syndrome. Patients with yang deficiency blood stasis syndrome might have longer course of disease, and were correlated with poorer control of SBP and renal function. DPN patients complicated diabetic ne- phropathy were more liable to have yang deficiency blood stasis syndrome.

Chrysophanol Inhibits the Progression of Diabetic Nephropathy via Inactivation of TGF-ß Pathway.

BACKGROUND: Diabetic nephropathy (DN) is a common form of diabetic complication which threatens the health of patients with diabetes. It has been reported that chrysophanol (CHR) can alleviate the progression of diabetes; however, the role of CHR in DN remains unclear. METHODS: To mimic DN in vitro, human podocytes (AB8/13 cells) were treated with high glucose (HG). Meanwhile, Western blot was performed to detect protein expressions. CCK-8 assay was used to test cell viability and cell proliferation was detected by Ki-67 staining. In addition, flow cytometry was performed to investigate cell apoptosis and cycle and cell migration was tested by transwell assay. Moreover, in vivo model of DN was established to detect the effect of CHR on DN in vivo. RESULTS: HG-induced AB8/13 cell growth inhibition was significantly rescued by CHR. In addition, HG notably promoted the migration of AB8/13 cells, while this phenomenon was obviously reversed by CHR. Moreover, CHR inhibited the progression of DN via inactivation of TGF-ß/EMT axis. Furthermore, CHR alleviated the symptom of DN in vivo. CONCLUSION: CHR significantly alleviated the progression of DN via inactivation of TGF-ß/EMT signaling in vitro and in vivo. Our findings were helpful to uncover the mechanism by which CHR regulates DN, as well as inspire the development of novel therapy against DN.

[Analysis of Chinese medicine syndrome pattern in patients with type 2 diabetes mellitus and its relationship with diabetic chronic complications].

OBJECTIVE: To analyze the Chinese medicine (CM) syndrome pattern of patients with type 2 diabetes mellitus (DM2) and the relationship of CM patterns with the different blood glucose levels controlled and the incidences of diabetic chronic complications. METHODS: CM syndromes in 557 DM2 patients were sorted into 7 patterns, A: the Fei-Wei yin-deficiency with exuberant heat pattern; B: the Pi-qi deficiency pattern; C: the Shen-qi deficiency pattern; D: the Pi-Shen qi-deficiency pattern; E: the Gan-Shen yin-deficiency pattern; F: the both qi-yin deficiency pattern; and G: the both yin-yang deficiency pattern, the concurrent or accompanied excessive syndromes were not taken as the indication for sorting. The blood glucose level, duration of illness and incidence of diabetic chronic complications in patients of different patterns were compared. RESULTS: The CM syndrome patterns commonly encountered in mostly of the 557 patients was pattern F (in 264 patients, accounting for 47.4%); the next was pattern C (95 patients, 17.1%) and E (92 patients, 16.5%). The concurrent syndromes appeared in most patients was blood stasis (501 patients, 89.9%), Gan-qi stagnation was the second (225 patients, 40.4%), and the portion of damp-heat syndrome was also rather large (180 patients, 32.3%). The duration of diabetes mellitus for patients with various patterns was significantly different (P < 0.01), the longest appeared in patients of pattern G, followed by pattern D, C, F, and E in sequence, and patients of pattern A and B had a rather shorter duration. Level of fasting blood glucose was rather higher in patients of pattern A, C, D, F, and G than in those of pattern B and E. Level of glycosylated hemoglobin in patients of pattern G was the highest and in pattern A the second, while in pattern B and E was rather lower. Incidences of diabetic chronic complications, including diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, cerebral infarction, and atherosclerosis in patients of pattern A and B were lower than in those of other 5 patterns (P < 0.05); but the highest incidence of multiple chronic complications revealed in pattern D and G, and that of coronary heart disease revealed in pattern C and G, all showed significant different as compared with other patterns (P < 0.01). CONCLUSION: The most commonly encountered CM syndrome patterns in DM2 patients of early stage are pattern A and B; and those of middle stage are pattern C, D, E and F, various diabetic chronic complications may reveal in this stage; pattern G could be found in patients accompanied with multiple chronic complications and with uncontrolled blood glucose for a long time.

Mechanism underlying treatment of diabetic kidney disease using Traditional Chinese Medicine based on theory of Yin and Yang balance.

The pathogenic mechanism of diabetic kidney disease (DKD) is complex. The development of DKD cannot be fully explained by a single mechanism. Traditional Chinese Medicine (TCM) has been applied extensively for the treatment of DKD in China. However, studying the mechanism of DKD using theories and methods that are appropriate for TCM characteristics and searching for theoretical bases for TCM clinical application are topics that still need to be explored and researched. Activation of the transforming growth factor (TGF)-¦Â1/Smad and PI3K/Akt/mTOR signaling pathways functions as a self-protection mechanism against renal microinflammation in DKD. However, the persistent abnormal overactivation of reactions causes secondary cell dysfunction, cell apoptosis, increased extracellular matrix (ECM) secretion, and eventually renal fibrosis. During this process, the dysregulation of self-balance among a variety of signaling pathways and the loss of self-feedback regulatory mechanisms downstream of these signaling pathways are critical causes of the occurrence and development of DKD. TCM may both inhibit the expression or activation of ""hyperactive"" signaling pathways (NF-B, Smad3, and PI3K/Akt/mTOR) and increase the expression or activation of ""deficient"" signaling pathways (Smad7 and PTEN) to restore balance to cells with an abnormal pathophysiological status and achieve the goal of DKD treatment.

Jinmaitong decreases sciatic nerve DNA oxidative damage and apoptosis in a streptozotocin-induced diabetic rat model.

Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes. Jinmaitong (JMT), a Traditional Chinese Medicine, improves certain symptoms of DPN, such as limb pain and numbness. The aim of the present study was to investigate the effects of JMT on DNA oxidative damage and apoptosis in the sciatic nerve of diabetic rats. The rats were divided into a normal and a diabetic group. Diabetes was induced using streptozotocin (60 mg/kg). The diabetic model (DM) rats received vitamin C (0.05 g/kg/day) or JMT [low-dosage (L), 0.44 g/kg/day; medium-dosage (M), 0.88 g/kg/day or high-dosage (H), 1.75 g/kg/day]. After 16 weeks, the mechanical pain threshold of the rats was evaluated. The expression of 8-hydroxy-deoxyguanosine (8-OHdG), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox, B-cell lymphoma 2 (Bcl-2), caspase 3 and cleaved-poly(ADP-ribose) polymerase 1 (PARP-1) in the sciatic nerve tissues was measured using the reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. JMT had no effect on body weight and fasting blood glucose levels. Following treatment, the rats in the JMT groups had an improved pain threshold compared with the DM controls (JMT-L, 52.9±6.5 g; JMT-M, 74.7±9.3 g; and JMT-H, 61.7±2.0 g vs. DM control, 35.32±12.06 g; all P<0.01), while the threshold in the JMT-M rats was similar to that of normal controls (P>0.05). 8-OHdG and NADPH oxidase p22phox expression was significantly decreased in the three JMT groups compared with that in the DM controls (all P<0.05). Following JMT treatment, Bcl-2 levels were increased, while caspase 3 and cleaved-PARP-1 levels were decreased compared with those in the DM controls (all P<0.01). In conclusion, JMT may reduce DNA oxidative damage to the sciatic nerve in diabetic rats, as well as regulate genes involved in peripheral neuronal cell apoptosis, suggesting that JMT could be used to prevent or treat DPN in diabetic patients.

[Phenotypic modulation of mesangial cells in diabetic rats and effect of tujian mixture].

OBJECTIVE: To explore whether there is phenotypic modulation of mesangial cells in streptozotocin (STZ) induced diabetic rats and study the effect of Tujian Mixture (TJM) on it. METHODS: SD rats were divided into the normal control group (NC group, n = 8), the unilateral nephrectomized control group (QC group, n = 8), the STZ induced diabetes mellitus with unilateral nephrectomy model group (DM group, n = 8), the Valsartan treated group (VT group, n = 8) and the TJM treated group (ZY group, n = 9), rats in the latter two groups were modeled as in the DM group and treated with Valsartan (20 mg/kg.d) and TJM (20 g/kg.d) respectively for 12 weeks. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta 1 (TGF-beta 1) in rats glomeruli were observed by immunohistochemistry assay, and the ratio of alpha-SMA and TGF-beta 1 positive area/total glomerule tuft area (SMA/GT and TGF/GT) were analyzed using computer-assisted image analysis software. RESULTS: In the NC and the QC groups, only trace of alpha-SMA positive staining was found. But there was prominant alpha-SMA positive staining in glomeruli of the DM group, with SMA/GT and TGF/GT increased significantly (P < 0.01), and marked increase of 24 hrs proteinuria excretion (P < 0.01). As compared with the DM group, the three indexes were all significantly lower in the VT and ZY groups (P < 0.01), and the lowering of proteinuria was more significant in the ZY group than that in the VT group (P < 0.01). CONCLUSION: The expression of alpha-SMA in glomeruli in STZ induced diabetic rats with unilateral nephrectomy is pronounced, indicating that phenotypic modulation of mesangial cells involvement in the pathogenesis of diabetic nephropathy. TJM and Valsartan can reduce 24 hrs proteinuria excretion, inhibit the phenotypic modulation of mesangial cells and the expression of TGF-beta 1 in glomeruli of diabetic rats, and the effect of TJM is more potent than that of Valsartan in lowering urinary protein excretion.

[Effect of Tujian decoction on protein kinase C activity in renal cortex in diabetic rat].

OBJECTIVE: To investigate influence of administration of Tujian decoction (Chinese herbal medicine) on protein kinase C (PKC) activity, renal function and structure in diabetic rat kidney. METHOD: Experimental diabetic nephropathy model was induced by nephrectomy combined with streptozotocin (STZ) injection in sprague-dawley rat. Tujian decoction (20 g x kg(-1) x d(-1)) and Valsartan (20 mg x kg(-1) x d(-1)) were orally administrated respectively for 12 weeks. PKC activity was measured by [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) binding assay. 24 h urine protein excretion (Upro) and renal pathological changes were observed. RESULT: In 12th week, diabetic nephrectomized rats developed proteinuria, glomerulosclerosis, increased membrane PKC activity (mPKC), decreased cytosol PKC (cPKC), and increased ratio of mPKC and cPKC (M/C). Administration of Tujian decoction or Valsartan led to a reduction in proteinuria, structural injury, mPKC and M/C, and a recovery in cPKC. CONCLUSION: Tujian decoction possesses a renoprotective effect on diabetic nephrectomized rat, at least partially via the inhibition of PKC activation in renal cortex.