Hypouricaemic and nephroprotective effects of Poria cocos in hyperuricemic mice by up-regulating ATP-binding cassette super-family G member 2.

CONTEXT: Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. OBJECTIVE: To examine hypouricaemic action of Poria coco. MATERIALS AND METHODS: Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. RESULTS: P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 µmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 µmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 µmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. DISCUSSION AND CONCLUSIONS: This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.

Hypouricemic Effects of Armillaria mellea on Hyperuricemic Mice Regulated through OAT1 and CNT2.

Ethanol and water extracts of Armillaria mellea were prepared by directly soaking A. mellea in ethanol (AME) at 65[Formula: see text]C, followed by decocting the remains in water (AMW) at 85[Formula: see text]C. Significantly, AME and AMW at 30, 60 and 120[Formula: see text]mg/kg exhibited excellent hypouricemic actions, causing remarkable declines from hyperuricemic control (351[Formula: see text][Formula: see text]mol/L, [Formula: see text]) to 136, 130 and 115[Formula: see text][Formula: see text]mol/L and 250, 188 and 152[Formula: see text][Formula: see text]mol/L in serum uric acid, correspondingly. In contrast to the evident renal toxicity of allopurinol, these preparations showed little impacts. Moreover, they showed some inhibitory effect on XOD (xanthine oxidase) activity. Compared with hyperuricemic control, protein expressions of OAT1 (organic anion transporter 1) were significantly elevated in AME- and AMW-treated mice. The levels of GLUT9 (glucose transporter 9) expression were significantly decreased by AMW. CNT2 (concentrative nucleoside transporter 2), a key target for purine absorption in gastrointestinal tract was involved in this study, and was verified for its innovative role. Both AME and AMW down-regulated CNT2 proteins in the gastrointestinal tract in hyperuricemic mice. As they exhibited considerable inhibitory effects on XOD, we selected XOD as the target for virtual screening by using molecular docking, and four compounds were hit with high ranks. From the analysis, we concluded that hydrogen bond, Pi-Pi and Pi-sigma interactions might play important roles for their orientations and locations in XOD inhibition.

[Clinical Trials for Treatment of Allergic Rhinitis with Heat Sensitive Moxibustion and Its Regularity of Heat-sensitization Acupoint Distribution].

OBJECTIVE: To observe the clinical effect of heat sensitive moxibustion (HSM) and its regularity of acupoint heat-sensitization in the treatment of allergic rhinitis (AR) patients. METHODS: Seventy patients with AR were randomly divided into HSM and manual acupuncture groups (n＝35/group). For patients of the HSM group, acupoints Yintang (EX-HN 3), bilateral Yingxiang (LI 20), Shangxing (GV 23), Tongtian (BL 7), Feishu (BL 13), Hegu (LI 4), etc. were used, and for patients of the manual acupuncture group, bilateral LI 20 and LI 4, Bitong (EX-HN 8) and EX-HN 3 were needled and stimulated with uniform reinforcing-reducing needling method. The treatment was conducted once every other day, for 20 days, with 3 days' interval between two 10 days. The symptoms of sneezing, running nose, nasal obstruction, and nasal itching were scored as 1, 2 and 3 points according to their severity. The signs of turbinate-nose cavity bottom/nasal septum correlation, morphological state (swelling or not) of inferior nasal concha and color of nasal mucosa, appearance (deviation or polyp) of the middle turbinate and nasal septum were scored as 1, 2 and 3 points according to their severity. The total score equaled to symptom score plus nasal sign score. The distribution of heat sensitization acupoints for effectively improving AR were recorded. RESULTS: The total effective rate of 82.86%(29/35) in the HSM group had no marked difference in comparison with that of 74.29%(26/35) in the manual acupuncture group (P>0.05). After the treatment, the total scores of symptoms and nasal signs of both HSM and manual acupuncture groups were significantly reduced in comparison with their own individual pre-treatment (P<0.01), and those in the HSM group were significantly decrased than those in the manual acupuncture group (P<0.05). In 35 patients of the HSM group, among the detected 57 acupoints, the most frequently sensitive acupoints were LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, Shenque(CV 8), GV 23, Fengchi(GB 20), Die'e and Dazhui (GV 14) in sequence, mainly covering the Governor Vessel, Large Intestine Meridian of Hand-yangming(LI), and Bladder Meridian of Foot-taiyang(BL), and characterized by heat conduction, heat diffusion, diathermancy, non-thermal (mainly itching) sensation, thermal sensation mainly in the deep tissue and in the distant part rather than in the body surface and the local part. CONCLUSIONS: HSM has a positive effect on improvement of AR, when applied, acupoints LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, CV 8, GV 23, GB 20, Die'e and GV 14 are highly recommended.

Hypouricemic Effects of Ganoderma applanatum in Hyperuricemia Mice through OAT1 and GLUT9.

Ganoderma applanatum (G. applanatum) dispels wind to eliminate dampness and exhibited nephron- and liver-protective effects as noted in Chinese herbal classic literature; it might also affect hyperuricemia. Therefore, we examined the hypouricemia effects and mechanisms underlying G. applanatum on chemical-induced hyperuricemia in mice. Ethanol (GAE) and water (GAW) extracts were prepared by extracting G. applanatum in ethanol (GAE), followed by bathing the remains in water to yield GAW. GAE and GAW were administered orally at different doses to hyperuricemia mice, while allopurinol and benzbromarone served as positive controls. Both GAE and GAW showed remarkable hypouricemia activities, rendering a substantial decline in the SUA (serum uric acid) level in hyperuricemia control (P < 0.01). Moreover, the urine uric acid (UUA) levels were enhanced by GAE and GAW. In contrast to the evident renal toxicity of allopurinol, GAE and GAW did not show a distinct renal toxicity. Almost no suppressing effect was observed on the XOD activities. However, compared to the hyperuricemia control, OAT1 was elevated remarkably in mice drugged with GAE and GAW, while GLUT9 was significantly decreased. Similar to benzbromarone, GAE decreased the URAT1 protein levels significantly (P < 0.01), while GAW did not display a similar effect. GAE and GAW downregulated the level of CNT2 proteins in the gastrointestinal tract of hyperuricemia mice. Thus, G. applanatum produced outstanding hypouricemic effects, mediated by renal OAT1, GLUT9, and URAT1 and gastrointestinal CNT2 that might elevate urine uric secretions and decline in the absorption of purine in the gastrointestinal tracts. G. applanatum showed little negative influence on inner organs. By docking screening, four top-ranked compounds were identified that necessitated further investigation. Compounds: potassium oxonate, hypoxanthine, allopurinol, benzbromarone.

[Effects of Ruanmailing Oral Liquid on spatial learning and memory ability and expression of APE/Ref-1 in hippocampal CA1 region in rats with experimental vascular dementia].

OBJECTIVE: To study the effects of Ruanmailing Oral Liquid, a compound traditional Chinese herbal medicine, on spatial learning and memory ability and expression of apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) in hippocampal CA1 region in rats with experimental vascular dementia (VaD). METHODS: VaD was induced in rats by permanent occlusion of bilateral common carotid arteries. Forty-five VaD rats were randomly divided into untreated group, nimodipine group, low-dose Ruanmailing group and high-dose Ruanmailing group. Another 15 rats underwent a sham operation consisting of similar skin incision and manipulation but without occlusion of carotid arteries. From the next day after occlusion, the rats were intragastrically administered with normal saline, nimodipine suspension or Ruanmailing Oral Liquid respectively for 30 days. Morris water maze experiment was adopted to test learning and memory of rats in each group. Expression of APE/Ref-1 protein in the hippocampal CA1 region was measured by immunohistochemical method. RESULTS: Escape latency was significantly shortened and number of entries in the target area of rats was significantly increased in the high-dose Ruanmailing group as compared with those in the untreated group (P<0.01). Compared with the untreated group, count of APE/Ref-1 positive cells was significantly increased in the hippocampal CA1 region in the high- and low-dose Ruanmailing groups (P<0.01). Compared with the low-dose group and the nimodipine group, the count of APE/Ref-1 positive cells was remarkably increased in the hippocampal CA1 region in rats of the high-dose Ruanmailing group (P<0.01). There was no statistical difference between the low-dose Ruanmailing group and the nimodipine group. CONCLUSION: Ruanmailing Oral Liquid can improve the learning and memory ability and enhance the lowered expression level of APE/Ref-1 in the hippocampal CA1 region of rats with VaD.