Fufang Zhenzhu Tiaozhi capsule ameliorates hyperuricemic nephropathy by inhibition of PI3K/AKT/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive serum uric acid (SUA) causes hyperuricemic nephropathy (HN), characterized by inflammatory infiltration and tubulointerstitial fibrosis. Most recently, we demonstrated that Fufang Zhenzhu Tiaozhi (FTZ) capsule attenuated diabetic nephropathy through inhibition of renal inflammation and fibrosis. However, whether FTZ ameliorates HN is still unclear. AIM OF THE STUDY: To determine the protective roles and mechanism of FTZ in mouse renal injury and fibrosis under hyperuricemic condition. MATERIALS AND METHODS: HN mice, induced by potassium oxonate and hypoxanthine, were administrated with 600 and 1200 mg/kg FTZ (intragastrically) daily for three weeks. SUA levels, renal functions and histological changes were analyzed. Western blotting, quantitative real-time PCR (q-PCR) and RNA sequencing were used to identify the roles and underlying mechanism of FTZ in HN mice. RESULTS: We demonstrated that FTZ treatment mitigated renal injury in mice, as evidenced by the decrease in SUA, serum creatinine (SCr) and cystatin C (Cys C) levels, as well as improved renal histology. FTZ markedly attenuates inflammasome activation, collagen deposition and the imbalance of uric acid transporters. RNA-sequencing revealed a key mechanism involved in the protective effects on HN mice was related to PI3K/AKT/NF-κB pathway. Western blot also confirmed that FTZ diminished the phosphorylation of AKT and p65 in HN mice. CONCLUSIONS: FTZ prevents renal injury, inflammation and fibrosis in HN mice via promoting uric acid excretion and inhibiting PI3K/AKT/NF-κB signaling pathway.

Astragaloside IV reverses simvastatin-induced skeletal muscle injury by activating the AMPK-PGC-1α signalling pathway.

In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. High-fat diet-fed apolipoprotein E knockout (ApoE-/- ) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test. Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin-induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin-induced muscle injury without affecting the lipid-lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC-1α, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis.

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility on uric acid metabolism and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in rats with hyperuricemia.

OBJECTIVE: To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility (PR) on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in rats with hyperuricemia. METHODS: Seventy male Sprague Dawley (SD) rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses (3.5, 7, 14 g/kg). Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid (SUA), blood urea nitrogen (BUN) and creatinine (Cr) were determined. In addition, the contents of NGAL and KIM-1 in urine and the mRNA and protein expressions of xanthine oxidase (XOD) in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin (HE) stain method. RESULTS: Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD mRNA and protein in the hyperuricemia rats were increased signifificantly (P<0.01). PR signifificantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the mRNA and protein expressions of hepatic XOD (P<0.05 or P<0.01). In addition, the pathological changes of kidney were signifificantly suppressed by oral administration of PR. CONCLUSIONS: PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

The alleviating pain effect of aqueous extract from tong-xie-yao-fang, on experimental visceral hypersensitivity and its mechanism.

Tong-Xie-Yao-Fang (TXYF) is a prescription in traditional chinese medicine (TCM), used for relieving abdominal pain associated with irritable bowel syndrome. The aim of the present study was to investigate the effects and mechanism of TXYF on experimental visceral hypersensitivity (VH) models. TXYF affected the abdominal withdrawal reflex produced by colonic distention in maternal separation-induced visceral hypersensitivity rats, in a dosage-dependent manner. TXYF significantly decreased serotonin (5-HT) levels in serum and corticotrophin releasing factor (CRF) concentrations in the brain. Moreover, it was found that VH alleviation by TXYF was dependent on the substance P (SP) expression in the colon mucosa. These results suggest that TXYF attenuates behavioral hyperalgesia by regulating substance associated with the brain-gut axis, including decreasing the expression of 5-HT and SP in the periphery and that of CRF in the center.

Electro-acupuncture attenuates stress-induced defecation in rats with chronic visceral hypersensitivity via serotonergic pathway.

Acupuncture has long been used for patients with irritable bowel syndrome. However, it has remained unclear. The aim of this study was to testify the effect of electro-acupuncture(EA) on (1) visceral hypersensitivity induced by the mechanical colorectal irritation during postnatal development of rats, and (2) stress-induced colonic motility changes on rats with chronic visceral hypersensitivity. The abdominal withdrawal reflex (pain threshold and score) for visceral hypersensitivity and fecal pellet output for motor dysfunction were selected as two indexes for measurement. In addition, the effect of EA on 5-HT(4a) receptor and serotonin transporter (SERT) expression in the colon mucosa was analyzed semi-quantitatively through immunohistochemistry and 5-HT concentration in the colon tissue was observed through spectro-photo-fluorimeter detection, respectively. Our results showed that EA significantly elevated pain threshold, decreased the scores and also decreased fecal pellet output during water avoid stress. Furthermore, EA decreased 5-HT concentration in colon in rats with CVH and CVH rats with water avoidance stress, and increased the 5-HT(4a) and SERT expression in rats with CVH. Thus, it can be concluded that EA attenuates behavioral hyperalgesia and stress-induced colonic motor dysfunction in CVH rats via serotonergic pathway.

[Study on anti-tumor effect of medicinal fungi Phellinus igniarius extracts].

OBJECTIVE: To study the inhibiting effect of medicinal fungi Phellinus igniarius extracts on S180 tumor and the immunoregulation effect on the S180-induced tumor mice. METHOD: S180 mice were orally given 100, 200, 400 mg x kg(-1) dosage of P. igniarius extracts, then the inhibition grow effect, spleen index, and thyme index were measured. RESULT: Medicinal fungi P. igniarius extracts can increase the spleen index and thyme index and the inhibiting tumor rate was 31.88%, 46.25%, 53.13%, respectively. Also, medicinal fungi P. igniarius extracts can prolong life in mice. CONCLUSION: The medicinal fungi P. igniarius extracts show obviously anti-tumor effect and immunoregulation effect.