Patchouli alcohol against renal fibrosis of spontaneously hypertensive rats via Ras/Raf-1/ERK1/2 signalling pathway.

OBJECTIVES: The present study was designed to obverse the protection of patchouli alcohol (PA) ameliorates hypertensive nephropathy in spontaneously hypertensive rats (SHR) and reveals potential mechanism. METHODS: Briefly, the adult spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats (half male and half female) were intragastric gavaged or not with PA (80, 40 and 20 mg/kg) for 8 weeks. Body weight, blood pressure (BP), renal weight, renal function and renal morphology were measured. Further, western blotting and immunohistochemical analysis were used to study the underlying mechanism. KEY FINDINGS: Compared with the WKY group, plasmatic levels of renin, angiotensin II (Ang-II), transforming growth factor beta 1(TGF-ß1), plasminogen activator inhibitor-1(PAI-1), creatinine (Cr), blood urea nitrogen (BUN), renal index, mRNA levels of ERK1/2 and α-SMA were significantly increased in SHR. Histology results showed that renal tubular injury and tubulointerstitial fibrosis occurred in SHR. After administration, SBP of captopril group decreased at each week after administration, especially at 3, 5, 6 7 and 8 weeks (P < 0.05 or P < 0.01). There is no significant effect was assessed in the olive oil group. Decreased plasma Cr, Renin, Ang-II, TGF-ß1, PAI-1, SCFAs and Renin, TGF-ß1, PAI-1 in renal tissues were observed significantly in captopril (P <0.05 or P < 0.01). Plasma BUN, Ang-II, TGF-ß1 and PAI-1 in renal tissues decreased in the olive oil group significantly (P <0.05 or P < 0.01). PA (80, 40 and 20 mg/kg) lowered BP and plasmatic levels of Renin, Ang-II, TGF-ß1 and PAI-1. Treatment with PA (40, 20 mg/kg) decreased levels of Cr, BUN and suppressed of activation of pro-fibrosis cytokines including TGF-ß1 in kidney. There is no ameliorative change in the olive oil group and the captopril group (P > 0.05) while PA treatment alleviated renal tubular injury and produced dramatic collagen fibre area reductions in mesangial membrane, basement membrane, and renal interstitium obviously (P < 0.05 or P < 0.01). Treatment of SHR with PA-inhibited MFB activation and downregulated mRNA of α-SMA. Treatment with PA suppressed excessive production of the extracellular matrix (ECM) via decreasing Col I, III and FN, downregulating mRNA of tissue inhibitor of TIMP-1 along with upregulating mRNA of MMP-9. The expression of Col III and MMP-9 mRNA-reduced in the captopril group (P < 0.05). In addition, the expression of ERK1/2 and pERK1/2 also reduced in the captopril group significantly (P < 0.05 or P < 0.01). Treatment with PA (20 mg/kg) downregulated proteins expression of Raf-1, ERK1/2 and pERK1/2 and mRNA expression of Ras, Raf-1 and ERK1/2. CONCLUSIONS: Overall, PA restored normal BP, alleviated renal dysfunction and renal fibrosis, possibly by suppressing Ang II and TGF-ß1-mediated Ras/Raf-1/ERK1/2 signalling pathway.

Garlic supplementation for the treatment of chronic liver disease: a meta-analysis of randomized controlled trials.

Introduction: The efficacy of garlic supplementation for chronic liver disease remains controversial. We conduct a meta-analysis to explore the influence of garlic supplementation versus placebo on the treatment of chronic liver disease. Methods: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2021 for randomized controlled trials (RCTs) assessing the efficacy of garlic supplementation versus placebo for chronic liver disease. This meta-analysis is performed using the random-effect model. Results: Four RCTs and 212 patients are included in the meta-analysis. Overall, compared with control group for chronic liver disease, garlic supplementation is associated with significantly reduced alanine aminotransferase (ALT), aspartate-aminotransferase (AST), total cholesterol, low density lipoprotein (LDL) and weight, but demonstrates no substantial impact on the incidence of adverse events. Conclusions: Garlic supplementation is effective to treat chronic liver disease.

Pharmacological Activities and Mechanisms of Hirudin and Its Derivatives - A Review.

Hirudin, an acidic polypeptide secreted by the salivary glands of Hirudo medicinalis (also known as "Shuizhi" in traditional Chinese medicine), is the strongest natural specific inhibitor of thrombin found so far. Hirudin has been demonstrated to possess potent anti-thrombotic effect in previous studies. Recently, increasing researches have focused on the anti-thrombotic activity of the derivatives of hirudin, mainly because these derivatives have stronger antithrombotic activity and lower bleeding risk. Additionally, various bioactivities of hirudin have been reported as well, including wound repair effect, anti-fibrosis effect, effect on diabetic complications, anti-tumor effect, anti-hyperuricemia effect, effect on cerebral hemorrhage, and others. Therefore, by collecting and summarizing publications from the recent two decades, the pharmacological activities, pharmacokinetics, novel preparations and derivatives, as well as toxicity of hirudin were systematically reviewed in this paper. In addition, the clinical application, the underlying mechanisms of pharmacological effects, the dose-effect relationship, and the development potential in new drug research of hirudin were discussed on the purpose of providing new ideas for application of hirudin in treating related diseases.

Pharmacological activities and mechanisms of action of Pogostemon cablin Benth: a review.

Patchouli ("Guanghuoxiang") or scientifically known as Pogostemon cablin Benth, belonging to the family Lamiaceae, has been used in traditional Chinse medicine (TCM) since the time of the Eastern Han dynasty. In TCM theory, patchouli can treat colds, nausea, fever, headache, and diarrhea. Various bioactive compounds have been identified in patchouli, including terpenoids, phytosterols, flavonoids, organic acids, lignins, glycosides, alcohols, pyrone, and aldehydes. Among the numerous compounds, patchouli alcohol, ß-patchoulene, patchoulene epoxide, pogostone, and pachypodol are of great importance. The pharmacological impacts of these compounds include anti-peptic ulcer effect, antimicrobial effect, anti-oxidative effect, anti-inflammatory effect, effect on ischemia/reperfusion injury, analgesic effect, antitumor effect, antidiabetic effect, anti-hypertensive effect, immunoregulatory effect, and others.For this review, we examined publications from the previous five years collected from PubMed, Web of Science, Springer, and the Chinese National Knowledge Infrastructure databases. This review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies focused on clinical applications of this important plant extract.