COMT Val158Met polymorphism and Parkinson's disease risk: a pooled analysis in different populations.

OBJECTIVE: Many studies have analyzed the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and Parkinson's disease (PD), which yield inconsistent results. This meta-analysis was designed to determine the possible association between the COMT Val158Met polymorphism and the risk of PD in different populations. METHODS: The PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases were used for literature searching up to May 2018. The association between the COMT Val158Met polymorphism and the risk of PD was evaluated by calculating the pooled odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: A total of 27 studies including 10,239 PD patients and 15,538 controls were screened out. In the overall population, COMT Val158Met polymorphism was not significantly associated with the risk of PD. In the subgroup analysis stratified by ethnicity, a significant association between COMT Val158Met polymorphism and PD risk was detected in Japan (LL vs. HH: OR = 1.48, 95% CI = 1.04-2.11; LL vs. HH+HL: OR = 1.54, 95% CI = 1.10-2.15) and India (LL+HL vs. HH: OR = 1.48, 95% CI = 1.14-1.91). CONCLUSION: This study indicated a significantly closer association between COMT Val158Met polymorphism and PD in the Japanese and Indian populations compared with other ethnicities. Ethnicity seems to play an important role in the genetic association of PD.

Sparstolonin B improves neurological outcomes following intracerebral hemorrhage in mice.

Inflammation serves an important role in inducing secondary injury following intracerebral hemorrhage (ICH). It has been demonstrated that sparstolonin B (SsnB) is able to attenuate the lipopolysaccharide-induced inflammatory response in sepsis. Mouse ICH models were used to explore the efficacy of SsnB on the ICH-induced inflammatory response. Mice underwent a working memory version of Morris water maze (MWM) test. They underwent 5 successive days of training consisting of 4 trials each day. The ICH model was established on the last training day. Mice were injected intraperitoneally either with vehicle or SsnB once a day for 3 consecutive days following the establishment of the ICH model. The MWM was used to determine the effect of SsnB on short-term memory following ICH. Neurological deficit scores and brain water content were measured following the MWM. Furthermore, the expression of inflammatory factors and signaling molecules downstream of TLR4 were measured. The results demonstrated that 5 mg/kg SsnB significantly improved the MWM path and time latency (P<0.05). Furthermore, neurological deficit scores were decreased in SsnB-treated mice compared with vehicle-treated mice (P<0.01). Brain water content, levels of inflammatory cytokines and the expression of inflammation-associated proteins were also significantly reduced in the SsnB-treated group (P<0.05). These results indicate that SsnB treatment stimulates short-term neurobehavioral recovery and reduces neurological deficits and this may inhibit the inflammatory response. Therefore, SsnB may attenuate the inflammatory response following ICH.

Madecassoside ameliorates bleomycin-induced pulmonary fibrosis in mice by downregulating collagen deposition.

This study aimed to explore the protective effects of madecassoside (Mad), a triterpenoid saponin isolated from Centella asiatica herbs, on experimental pulmonary fibrosis (PF) and underlying mechanisms. PF model was established in mice by endotracheal instillation with bleomycin (5 mg/kg). Mice were orally administered with Mad (10, 20, 40 mg/kg) and prednisone (5 mg/kg) for 7 or 21 days. Mad (20, 40 mg/kg) significantly improved lung pathological changes and reduced collagen deposition. In the aspect of collagen synthesis, Mad (20, 40 mg/kg) reduced the expressions of α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1), and inhibited the phosphorylations of Smad2 and Smad3 in the lung tissues. However, in vitro, Mad showed little effect on TGF-ß1-induced phosphorylation of either Smad2 or Smad3 in primary mouse lung fibroblasts. Moreover, Mad (20, 40 mg/kg) attenuated oxidative damage and inflammation presented at the early stage of PF, evidenced by reduced total leukocytes in the bronchoalveolar lavage fluid, decreased myeloperoxidase activity and malondialdehyde level, and increased super-oxide dismutase activity and glutathione level in lung tissues. On the other hand, Mad (40 mg/kg) elevated the matrix metalloproteinase 1/tissue inhibitor of metalloproteinase 1 ratio in lung tissues of PF mice mainly by downregulating tissue inhibitor of metalloproteinase 1 expression. The present study demonstrated that Mad can ameliorate PF by preventing the deposition of extracellular matrix, which might be achieved mainly through attenuating inflammation and oxidative stress and consequent TGF-ß1 overexpression.

Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type I collagen.

ETHNOPHARMACOLOGICAL RELEVANCE: In the theory of traditional Chinese medicine, pulmonary fibrosis (PF) belongs to pulmonary arthralgia, which means blood stasis in lung tissue. The roots of Paeonia lactiflora Pall are usually used to relieve the symptoms of this disease by promoting blood circulation and removing blood stasis. Paeoniflorin, the main active ingredient of P. lactiflora, may have anti-PF potential. AIM OF STUDY: This study aimed to investigate the effects and underlying mechanisms of paeoniflorin on bleomycin (BLM)-induced PF in mice. MATERIALS AND METHODS: The PF model was established in mice by an intratracheal instillation of BLM. Paeoniflorin (25, 50, 100mg/kg) and prednisone (6mg/kg), as a positive control, were orally administered for consecutive 21 days. Histopathological changes were evaluated by hematoxylin and eosin stain and Masson's trichrome stain. The content of hydroxyproline was detected by using kits. The contents of type I collagen, TGF-ß1 and IFN-γ were detected by ELISA. The levels of α-SMA, Smad4, Smad7 and the phosphorylations of Smad2/3 were detected by western blot. The mRNA expressions of MMP-1 and TIMP-1 were detected by RT-PCR. RESULTS: In mice treated with BLM, paeoniflorin (50mg/kg) significantly prolonged the survival periods, attenuated infiltration of inflammatory cells, interstitial fibrosis, and deposition of extracellular matrix in lung tissues. It also decreased the contents of hydroxyproline (a marker of collagens), type I collagen and α-SMA (an indicator of myofibroblasts) in lung tissues of mice. Paeoniflorin down-regulated the expressions of TGF-ß1, Smad4 and the phosphorylations of Smad2/3, while up-regulated the expression of Smad7 in lung tissues. Moreover, paeoniflorin increased the content of IFN-γ. But, it only slightly affected mRNA expressions of MMP-1 and TIMP-1 in lung tissues of mice. CONCLUSIONS: Paeoniflorin attenuates PF by suppressing type I collagen synthesis via inhibiting the activation of TGF-ß/Smad pathway and increasing the expression of IFN-γ.